AReA 3 - IDIBAPS
Transcription
AReA 3 - IDIBAPS
Roselló, 149-153 08036 Barcelona www.idibaps.org Your gateway to IDIBAPS. A portal open to medical professionals, scientists and biomedicine enthusiasts where you will find information about the institution and its activities Annual Scientific Report Rosselló, 149-153 08036 Barcelona www.idibaps.org Hospital Clínic – Fundació Clínic University of Barcelona – Faculty of Medicine CSIC – Institut d’Investigacions Biomèdiques de Barcelona Generalitat de Catalunya – Departament d’Economia i Coneixement Published by: IDIBAPS Rosselló, 149-153 – 08036 Barcelona Editorial Board: Dr. Ramon Gomis, Director of IDIBAPS Dr. Joan Rodés, Director of IIS IDIBAPS - Hospital Clínic Dr. Pastora Martínez, Managing Director of IDIBAPS Dr. Albert Barberà, IDIBAPS Scientific Manager Mrs. Teresa Peña, Fundació Clínic Research Management Office Mrs. Sandra Vidal, Fundació Clínic Technical Office Mr. Àlex Argemí, IDIBAPS Communication Officer Production and design: BPMO Edigrup C/ Guitard, 43, 1ª planta 08014 Barcelona Tel.: 933 637 840 www.bpmoedigrup.com Legal Deposit: B-47.798-2005 Centres de recerca de Catalunya This centre has been cofinanced by the European Union through the European Regional Development Fund (ERDF) IDIBAPS is accredited as a Health Care Research Institute by the Carlos III Health Institute INDEX Foreword IDIBAPS • Introduction.................................................................................................................................................................................... 7 • Presentation..................................................................................................................................................................................... 8 • Organisation chart....................................................................................................................................................................... 10 • IDIBAPS Research and Innovation.............................................................................................................................................. 13 • Platforms.......................................................................................................................................................................................... 35 • Networking...................................................................................................................................................................................... 50 • International projection............................................................................................................................................................ 61 • Biotrack............................................................................................................................................................................................. 63 • Training............................................................................................................................................................................................. 64 • IDIBAPS and society......................................................................................................................................................................... 68 1 AREA 1 Biological aggression and response mechanism ............................................................................................. 70 2 AREA 2 Respiratory, cardiovascular, renal and pathobiology bioengineering ..................................................... 102 3 AREA 3 Liver, digestive system and metabolism ............................................................................................................... 142 4 AREA 4 Clinical and experimental neuroscience .............................................................................................................. 196 5 AREA 5 Oncology and haematology ..................................................................................................................................... 246 Transversal research groups ...................................................................................................................................... 294 Index • TEAM LEADER INDEX........................................................................................................................................................................... 308 INTRODUCTION Josep Maria Martorell i Rodon Director General of Research of the Generalitat de Catalunya and President of the Steering Committee of IDIBAPS The Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), a secure mark of value related to research conducted in Catalonia, works with renewed energy to maintain its excellence in the midst of a complex international scenario. Therefore it gives me great satisfaction to be in charge of introducing this Annual Report, which reflects a year of advances made by a large team of professionals with the highest scientific standards. IDIBAPS is the flagship of biomedical research conducted in Catalonia, focused on the patient and destined to improve public health. Since its creation in 1996, many successful projects have served to define IDIBAPS as the most productive biomedical research centre in Catalonia and in the rest of Spain, as its scientific publications demonstrate. The past, present and future of IDIBAPS speak of this excellence. The Institute honours the reputed Catalan physician, August Pi i Sunyer, who contributed to establishing Medicine as we know it today in Catalonia. The present IDIBAPS is founded upon initiatives merging both public and private efforts –such as the Esther Koplowitz centre–, to ensure sustainability of the research work. Based on solid foundations, this Institute looks to the future with enthusiasm, with projects such as the creation of the new Cellex Biomedical Research Centre - the future headquarters of IDIBAPS. This enormous potential for capturing resources and their conversion into results applicable to clinical practice constitute the best guarantee for securing the future of the Centre. As Director General of Research of the Generalitat de Catalunya and President of the Steering Committee of this Institute, I will strive to consolidate research in our country, and the ascending trajectory of centres such as IDIBAPS. This demands reorganization of the research system in Catalonia and firm efforts to consolidate and extrapolate those initiatives which offer added value, such as the ICREA - a key tool for the recruitment and preservation of talent. We must strive to ensure that the research centres in Catalonia continue to serve as a model of excellence and the capture of competitive funding. It is essential to intensify the scientific and technological capacities of Catalonia and its unique facilities that allow it to compete at top international level. It is advisable to shorten the interval between the generation of new knowledge and its application - this likewises represents a key objective for IDIBAPS. I invite you to learn further about the achievements of our professionals, through the pages of this Report. Josep Maria Martorell i Rodon Director General of Research of the Generalitat de Catalunya and President of the Steering Committee of IDIBAPS 7 Presentation IDIBAPS Foreword Introduction We are very pleased to present the Scientific Memorandum of the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), one of the first Health Care Research Institutes accredited by the Carlos III Health Institute in 2009. The research activities of the centre are divided into five different areas, which group around 55 top-level research teams. This Memorandum offers a summary of the objectives and configuration of each of these research teams, together with an exhaustive presentation of the data relating to their scientific production. The objective of this document is to underscore the enormous potential of the investigators of the IDIBAPS and to reflect the numerous financing entities and collaborators that make it all possible. In addition to the information on the different areas, we have also included the research made by three transversal groups: Primary Care, Clinical Pharmacology and Nursing – these groups are very important to ensure top-quality research and enhance the valorisation and transfer of the knowledge gained to the patient. Moreover, a summary of the research made by the Barcelona Centre for International Health Research (CRESIB) has also been included due to the tight collaboration between the two CERCA institutes, since CRESIB was created from the IDIBAPS’ area 6 of International Health. A good indicator of the good health of IDIBAPS is the number of publications made by its investigators. In 2010, IDIBAPS published a total of 846 original articles in international journals, with a global impact factor of 4.176,72. This means an average of 4,94 impact factor points per article – an important figure that adequately reflects the quality of our research which has significantly increased from 2009. All considered, we have nothing but admiration for the professionals who allow the Institute to advance, allowing us to view the future with optimism. In this Memorandum you will find interesting lines of research and front-line initiatives. We have achieved many things, but we can most certainly achieve many more. We have human potential, institutional and economical support, and the desire to continue moving forward. Management Report IDIBAPS FUNDING FINANTIAL YEAR 2010 1. Funding of IDIBAPS. The funding of IDIBAPS during 2010 totalled 18.339.000 Euros. Twenty three percent of this amount corresponds to the contribution of the Department of Innovation, Universities and Enterprise (Departament d’Innovació, Universitats i Empresa) of the Catalan government (Generalitat de Catalunya). The rest of the funding received by IDIBAPS during 2010 corresponds to calls for research funding (71%), as well as contracts and cooperation agreements with private entities (5%), and financial income sources (1%). 2. Resource volume generated by the IDIBAPS researchers. A significant aspect is the resource volume generated by the IDIBAPS research groups. In this context, the resources executed by researchers of the IDIBAPS during the financial year corresponding to 2010 totalled 43.319.435 Euros. These resources have been managed by different institutions: IDIBAPS itself (12.622.559 Euro) and the Fundació Clínic per a la Recerca Biomèdica (30.696.876 Euro). It is important to mention that 63% of the resources executed by investigators of IDIBAPS during 2010 (more than 27 MEuro) correspond to competitive research projects and grant basis (calls for funding). The remaining 37% is distributed as follows: 19% contracts with private entities, 5% clinical trials managed by the Fundació Clínic, 10% donations, and 4% teaching contracts. 8 COMPETITIVE PROJECTS (CALLS FOR FUNDING) 13.031.000 € PRIVATE FUNDING 948.000 € FINANCIAL INCOME 174.000 € DIUE CONTRIBUTION 4.186.000 € RESOURCES GENERATED BY THE IDIBAPS INVESTIGATORS IN 2010 COMPATITIVE PROJECTS 27.098.759 € 63% PRIVATE FUNDING 8.380.685 € 19% CLINICAL TRIALS 2.011.198 € 5% DONATIONS 4.205.317 € 10% TEACHING 1.623.475 € 4% Enhancing the Impact of Research and Innovation at IDIBAPS Enhancing the Impact of Research and Innovation at IDIBAPS For many years IDIBAPS has been one of the leading institutions in Spain and a major player in Europe in terms of the scientific impact of its biomedical and clinical research. This is thanks to the scientific excellence of its partners that work together in order to ensure fruitful cooperation between basic biomedical research and patient driven clinical research. A few years ago, the governing bodies of IDIBAPS decided to move several steps ahead and start fostering and measuring additional outcomes closely related with the impact of the job done by IDIBAPS researchers beyond the scientific impact factor, specifically the impact on clinical guidelines and the ability of the institution to partner and to create new opportunities in the biotech and medtech sectors. It is remarkable to see that the scientific output of IDIBAPS has kept its growing trend in 2010, but even more remarkable is the fact that this biomedical and clinical research output has influenced as many as 23 clinical guidelines. In terms of patenting and transferring activity, it is worth mentioning that 3 additional patents have been extended internationally and that 6 technologies developed at IDIBAPS have already been transferred or were in an advanced stage to be transferred to industry partners in 2010. A new spin-off, Immunovative Developments, was created in February 2010 aimed at developing new biological therapies for the prevention and treatment of immunological disorders. Immunovative Developments, as well as the other two start – up companies created from IDIBAPS research, has been able to raise enough capital to move forward in spite of the difficult economical environment. The opening of the new Esther Koplowitz Center has been another remarkable achievement in 2010, that will provide additional competitive capacities to keep on pursuing our objective of striving to advance medical knowledge that is actually applied to patients, and that has the potential of making an impact on healthcare and on society overall. Idibaps and the Health University of Barcelona Campus (HUBc) In 2010 the University of Barcelona obtained the accolade ‘excellence of research in health’. This recognition was called Health Universitat de Barcelona Campus (HUBc). IDIBAPS is an active member of the HUBc project. It participated in the design of the new Campus and is one of the key players for the success of its research strategy. The HUBc project has its origins in the Faculty of Medicine of the University of Barcelona, one of the constituent institutions of IDIBAPS. The faculty is the main hub for the various connections that make up the campus, from top hospitals and research centres committed to training and medical research, to business sectors closely linked to technological development and the progress of innovation. The main strength of HUBc is its high level of specialization in the field of health, which is the reason for the strategic alliance to promote excellence, the ability to attract talent, internationalization and the power to transform the local environment. The HUBc project aims to take the opportunity to accelerate the positive factors driving this circle shaped by teaching, research and healthcare. At the same time, because it is a complex project involving multiple participants, HUBc also has the opportunity to become a means of forging relationships with the production sector, of creating new wealth and transforming the local urban environment. For further information: http://hub.ub.edu 9 Organisation chart Governing Board 2010 Scientific council Chairman Joan Roca i Acín, Director General of Research, Catalan Government (Generalitat de Catalunya) Jesús Ávila, Severo Ochoa Molecular Biology Centre, Madrid José A. Berciano, Neurology Department, Hospital Universitario Marqués de Valdecilla, Santander Lisardo Bosca, Biochemical Institute, Universidad Complutense, Madrid Jesús Florez, Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, Santander Roberto Gallego, Neuroscience Institute, Universidad Miguel Hernández, Alicante Francisco Javier García-Sancho, Biology and Molecular Genetics Institute, School of Medicine, Valladolid Roberto Groszmann, Hepatic Hemodinamic Lab. Yale University School of Medicine, West Haven José López Barneo, Department of Medical Physiology and Biophysics, School of Medicine, Seville Carlos López Otín, Department of Biochemistry and Molecular Biology, University of Oviedo José M. Mato, Cooperative Bioscience Research Centre (CIC bioGUNE), Biscay Federico Mayor, Severo Ochoa Molecular Biology Centre, Madrid Ginés Morata, Severo Ochoa Molecular Biology Centre, Madrid Miguel Ángel del Pozo, Integrin Signalling Laboratory, National Cardiovascular Research Centre (CNIC), Madrid Ciril Rozman, Haematology Department, Hospital Clínic de Barcelona, University of Barcelona Margarita Salas, Severo Ochoa Molecular Biology Centre, Madrid Jesús San Miguel, Haematology Department, Hospital Clínico de Salamanca Francisco Sánchez-Madrid, Immunology Department, Hospital La Princesa, Madrid Eugenio Santos, Cancer Research Centre, Salamanca Vice-Chairman Cristina Suñol, Director of Barcelona Biomedical Research Institute (IIBB-CSIC) Board members Jordi Alberch, Research Vice-Dean of University of Barcelona Josep Maria Piqué, General Manager of Hospital Clínic of Barcelona Joan Bigorra, Innovation Director of Hospital Clínic of Barcelona Lluís Calvo i Calvo, Institutional Coordinator of the CSIC in Catalonia Francesc Cardellach, Dean of the University of Barcelona School of Medicine Miquel Gómez, Secretari d’Estratègia i Coordinació - Catalan Government (Generalitat de Catalunya) Ramon Gomis, Director of IDIBAPS Secretary Pastora Martínez, Managing Director of IDIBAPS 10 Director’s Advisory Committee Management Committee Ramon Gomis, Director of IDIBAPS and of the Fundació Clínic for Biomedical Research Cristina Suñol, Director of Barcelona Biomedical Research Institute Francesc Cardellach, Dean of the UB School of Medicine Persons representing the Institutions Xavier Bosch, Hospital Clínic de Barcelona Doctors’ Representatives Guadalupe Mengod, Researcher at IIBB-CSIC Persons representing the Areas Area 1 Jordi Vila Estapé, Coordinator Ana Angulo, Representative Area 2 Ramón Farré, Coordinator Joan Albert Barberà, Representative Area 3 Julià Panés, Coordinator Jorge Ferrer, Representative Area 4 Anna Planas, Coordinator Pablo Villoslada, Representative Area 5 Dolors Colomer, Coordinator Cristina Nadal, Representative Neus Agell, School of Medicine (UB) Guest members Joan Rodés, Director of IDIBAPS Health Research Institute Hospital Clínic Antonio Sisó, CAPSE-GESCLINIC Research Coordinator Joan Bigorra, Hospital Clínic Innovation Director Jaume Bosch CIBERehd Scientific Director Josep M. Gatell, National Coordinator of the RETIC on AIDS Secretary Albert Barberà, Scientific coordinator of IDIBAPS Teaching Coordinator 11 INNOVATION IDIBAPS Organisation chart The IDIBAPS organisation chart is shown below. With a view to ensuring smooth functioning, the research structure of IDIBAPS is supported by the Management and Administration Departments offered by the Fundació Clínic. Governing Board Ethical Committee in Clinical Research Scientific Council Ethical Committee in Animal Experimentation Director Director’s Consultant Council Research Areas Biological aggression and response mechanisnms Respiratory, Cardiovascular and Kidney Bioengineering and Biopathology Liver, Digestive System and Metabolism Clinical and Experimental Neurosciences Oncology and Hematology Scientific Manager Scientific Platforms Biobank Managing Director Scientific Management Laboratories Management Flow Cytometry and cell separation Knowledge Management Functional Genomics Biosecurity Medical Imaging Bioinformatics Administration Units Research Management Office Innovation Management Office International Cooperation Office Accounting & Finance Human Resources Purchases & General Services 12 IDIBAPS Research and Innovation Scientific production Since its creation in 1996, IDIBAPS has shown constant growth of the principal quality indicators of a research centre: The number of scientific publications, theimpact factor, the economic resources, and the contracting of qualified personnel. This section aims to show the evolution of these indicators and other success factors over time, in a graphic and comprehensible manner. Scientific production The number of publications and their impact factor represent one of the most reliable indicators of the competitiveness of a research centre. Both parameters show a clear rising trend in IDIBAPS, and in the year 2010 there have been 846 original publications in scientific journals with an important impact factor. An original paper is taken to be an article contributing new knowledge as a result of experiments performed by investigators of the Institute. In order to be counted as such, the article must have among its signing authors at least one member of the IDIBAPS pertaining to one of the research teams reflected in this Report, with specific mention of IDIBAPS or of the entities with which agreements have been signed. ORIGINALS 2002-2010 850 840 750 736 700 686 650 600 1.Biological aggression and response mechanisms 2.Respiratory, cardiovascular and renal pathobiology and bioengineering 3.Liver, digestive system and metabolism 4.Clinical and experimental neuroscience 5. Oncology and haematology 531 537 500 475 450 452 400 2006 197 210 ORIGINALS 2008-2010 2008 2009 2008 2010 163 168 162 156 138 160 2010 2009 187 200 2007 161 2005 163 2004 221 2003 232 2002 144 Below is a list of the reported areas, with a graphic representation of the scientific production of each of them - once again considering only the number of original papers. 577 550 135 A good part of the Area of International Health comprises the activity carried out within the setting of the Research Centre in International Health in Barcelona (Centre de Recerca en Salut Internacional de Barcelona) (CRESIB), a centre which thanks to the support of the Catalan government (Generalitat de Catalunya) and other sources of funding has been consolidated due to its solid foundations established over time in IDIBAPS. This implies that the level of growth in number of publications has been attenuated due to the fact that this year it has not been possible to assume as proprietary of IDIBAPS the activities of the mentioned centre, which now takes its own course. Nevertheless, close scientific and administrative ties are maintained with the setting of the IDIBAPS. 846 800 212 The investigators of the IDIBAPS, originating from the different institutions that conform it, are distributed into 5 fields of activity. Each area is divided into different teams that combine in-house research conducted with their own lines of research or in cooperation with other teams. It should be commented that in this Report, and apart from the 5 areas of the IDIBAPS, there is a specific section dedicated to research in Primary Care, Nursing, Pharmacology and Clinical Trials, which also play a very important role in translational research. 900 120 80 40 0 Area 1 Area 2 Area 3 Area 4 Area 5 13 It should be mentioned that the sum of the articles per area is higher than the institutional total. This is because publications resulting from collaboration between teams in two different areas have been counted once for each area. The representation shows that production in all the areas has been of a very high level, and collaboration among areas has increased notoriously compared with the previous year. The impact factor (IF) of the journals in which publication is made constitutes a measure or marker of the influence of the research carried out in a given centre. This comprises statistical data measured based on the number of times the articles published in a certain journal are cited. Even though there are probably many factors that are just as important or even more important for analysing the work carried out by our researchers, the IF is an objective piece of information that serves as a guide. The progression of the total IF for IDIBAPS publications in recent years is shown in the following figure. In 2010, the 846 articles published by investigators of IDIBAPS have reached a total of 4.176,72 IF points. This means that the mean IF points per article published by IDIBAPS during 2010 is 4,94 - a figure that implies an important increase with respect to the 4,62 points recorded in 2009. Added to this, close to 60% of these original papers, have appeared in journals pertaining to the upper quartile of impact in their field. Thus, while the number of publications increases yearly, their quality does not decrease. It should be commented that the number of editorials (72) and reviews (102) has also been outstanding. This reflects the role as opinion leaders of the members of IDIBAPS. On the other hand, the present Report documents 47 multicentre studies, in which the professionals of IDIBAPS have participated actively, but without being the main signing authors of the studies. These authors are specifically mentioned in some section or annex of the article, forming part of the work group. It should be mentioned that for the first time, the 23 clinical guides published in 2010 in high impact factor journals have been contemplated as an independent category. This has reduced the number of original papers and reviews that would have been registered if the methodology of the preceding year had been followed. Nevertheless, this decision allows us to underscore the importance of these documents through which the members of the IDIBAPS leave their mark upon international clinical practice. 14 IMPACT FACTOR 2002-2010 4200 4100 4000 3900 3800 3700 3600 3500 3400 3300 3200 3100 3000 2900 2800 2700 2600 2500 2400 2300 2200 2100 2000 1900 1800 2002 2003 2004 846 originals 2005 2006 2007 2008 2009 2010 IF: 4.176,72 Mean: 4,94 102 reviews 463,24 4,54 72 editorials 441,07 6,13 23 guies 128,17 5,57 47 multicentrics studies 452,82 9,63 Since the impact factor (IF) refers to the journals and not to the specifically published articles, a figure is presented below, indicating the number of citations received by the studies published by the investigators of the IDIBAPS (data calculated through the ISI Web of Knowledge): CITATIONS 45000 40000 35000 30000 38267 39236 2009 2010 35978 29032 25000 20000 15000 10000 5000 0 2007 2008 The total is 142.513 citations received by IDIBAPS studies in the last four years. This figure confirms the international projection of the work carried out by this Institute. Another important aspect to be taken into account is the type of research reflected in the original works published by our investigators. Of note is the fact that over 15% of the original publications listed in this Report have been carried out in collaboration between two or more IDIBAPS teams, while 26,5% of the publications have received the collaboration of two or more teams of the IDIBAPS. In the collaborative projects, the joining of efforts between basic and clinical research teams accounted for 30% of the studies carried out among different IDIBAPS teams. It also should be noted that 23% of the originals have been developed in collaboration with other Spanish institutions, corresponding to all the Autonomous Communities, and that 28% of the original publications have been made in collaboration with leading foreign institutions. 15 Research resources The funding obtained from public institutions is one of the main driving forces of research. The table below shows the large number of projects granted in 2010 by different entities that make the excellence of the IDIBAPS possible: Public funding (competitive calls for funding) Funding Institutions Number of Projects Ministry of Science and Innovation (MICINN) / National Plan I+D+i 22 Carlos III Hralth Institute (MICINN) 50 CDTI (MICINN 4 Ministerio de Sanidad, Política Social e Igualdad 11 Autonomus Communities – Generalitat de Catalunya (Catalan Government) 1 Agencia d’Avaluació de Tecnologies i Recerca Mèdica 3 European Comission 16 National Institute of Health (NIH) 1 Private funding (competitive calls for funding) Funding Institutions Number of Projects Asociación Española contra el Cancer 1 Fundació Marató TV3 4 FIPSE 3 Fundació Caja Navarra 5 Fundació Mutua Madrileña 2 Fundació Olga Torres 1 RECERCAIXA 2 High Q Foundation 2 In the area of Human Resources, it should be mentioned that many of the professionals of IDIBAPS come from the different institutions that make up the latter. The table below shows the origin of the 416 accredited investigators: 16 Hospital Clínic and University of Barcelona 161 Hospital Clínic de Barcelona 135 CSIC 32 University of Barcelona 35 IDIBAPS 36 Fundació Clínic 13 ICREA 4 TOTAL: 416 In order to carry out their work, these investigators are supported by the contributions of investigating and research support personnel contracted through the Clinical Foundation for Biomedical Research (Fundació Clínic per a la Recerca Biomèdica) (472 contracts) and the IDIBAPS itself (290 contracts). Also of great importance is funding from public calls for research aids, allowing us to expand our number of top-line investigators: HUMAN RESOURCES Funding Institutions 1. Public funding (competitive calls for funding) Number Aids (Grants and contracts) Number of Projects Ministry of Science and Innovation (MICINN) a) Ramon y Cajal 6 b) Juan de la Cierva 2 c) Research Personnel Training (FPI) 7 d) Supporting Technicians 2 Carlos III Health Institute (MICINN) a) Miguel Servet 2 b) Post-doctorate training (CD) 4 c) Río Hortega (Post-medical residency) 5 d) Research Personnel training (FI) 5 e) Supporting Technicians 3 Ministry of Education a) University Professor Training (FPU) 1 Autonomous Communities – Generalitat de Catalunya (Catalan Goverment) a) Beatriu de Pinós scholarships 2 b) Research Personnel Training (FI-DGR) 3 a) Pre-doctorate 18 b) Post-doctorate 4 2. IDIBAPS’ calls 17 Institució Catalana de Recerca i Estudis Avançats (ICREA) The Catalan Institute for Research and Advanced Studies (Institució Catalana de Recerca i Estudis Avançats, ICREA) is a foundation that is supported by both the Catalan Government through the Catalan Ministry of Innovation, Universities and Enterprise (Departament d’Innovació, Universitats i Empresa, DIUiE), and the Catalan Foundation for Research and Innovation (Fundació Catalana per a la Recerca i la Innovació, FCRI). Through its programme for contracting of senior investigators, ICREA reinforces the principal Catalan research institutions. The IDIBAPS has four ICREA investigators that contribute knowledge, experience and leadership for the teams to which they have been incorporated: Dr. Josep M. Llovet Translational research group in liver oncology The Translation research group in liver oncology was created in 2006 by Dr. Josep M. Llovet, ICREA Research Professor of the DIBAPS-Hospital Clínic and Professor of Medicine of the Mount Sinai School of Medicine. The group is composed of 8 people from the IDIBAPS and leads an international consortium on genomic research in liver cancer, the HCC Genomic Consortium, with about 30 investigators. In 2009 it received the AACR-Landon International Innovator Award, and was acknowledged as a Singular Research Group by the Catalan Government. In 2010 the group received a European Project, FP-7-HEALTH (HEPTROMIC), involving the coordination of 6 academic centres and two companies, with the purpose of identifying new oncogenes and treatment targets. The fundamental contributions of the group during these years have been the following: • Definition of a molecular classification of hepatocellular carcinoma (Chang, Can Res, 2008; Hoshida, Cancer Res 2009). • Identification of key oncogenes in hepatocarcinogenesis, such as miRNA Let-7 (Viswanathan, Nature Genetics 2009), EGF and c-MET (Keng, Nature Biotech 2009), AEG-1 (Yoo, J Clin Invest, 2009) and the signalling pathway of IGFR1 (Tovar, J Hepatol 2010). Dr. Albert Pol Cell proliferation and signalling The aim of our project is to characterize - in health and in illness - the cellular processes that are regulated or altered due to lipid accumulation within the cells. All prokaryote and eukaryote cells maintain the evolutive competence of accumulating lipids in organelles known as intracellular lipid bodies. In healthy cells, a small population of lipid bodies is present at all times, though these organelles become abundant in response to different physiopathological conditions such as obesity, diabetes, fatty liver disease (steatosis), liver cirrhosis, viral hepatitis, arteriosclerosis and even cancer. Globally, these disorders affect over half of the population in western countries. Recent advances in the cellular biology of lipid bodies have shown the latter to be multifunctional organelles that are metabolically very active and thus constitute key elements in the complex system of lipids and proteins in constant movement within the cells. Dr. Antonio Postigo Transcriptional regulation of genic expression laboratory The laboratory investigates mechanisms involved in the regulation of genic expression during cell differentiation and in cancer, using as models the ZEB transcription factors. The ZEB1 and ZEB2 proteins regulate key events during embryonic development, the truncal maintenance of normal stem cells and cancer cells, the differentiation of many tissues, tumour invasion, and metastasis. 18 The main lines of research being developed are the following: • Study of the mechanisms by which ZEB1 and ZEB2 regulate E-cadherin and epithelial-mesenchymal transition (EMT) during tumour invasion and carcinoma metastasis. • Role of ZEB1 and ZEB2 in genic regulation during normal haematopoietic differentiation and its malignant transformation. Dr. Maria V. Sánchez-Vives Cortical networks and EVENT Lab (Virtual Environments in Neuroscience and Technology) Dr. Sánchez-Vives joined the IDIBAPS in 2008 and is the head of the Systems Neurosciences Group of the IDIBABS, acknowledged by the AGAUR as a Consolidated Research Group. Understanding how the brain processes information and how brain activity is generated and modulated in neuronal networks is crucial for intervening in cerebral function when the latter has been altered. Neuron connectivity and the cellular and synaptic properties conform brain activity, and the latter at the same time has effects upon the network. The objective of the group is to determine how these processes take place, particularly as regards the generation of brain rhythms: how information is generated, synchronized or encoded. These activity patterns are altered under pathological conditions, and their restoration may contribute to recover function. The models of diseases in genetically modified mice allow us to carry out such studies. Another line of research of the group is referred to the integration of information in the brain cortex, resulting in body representation. We use virtual reality and brain-computer interfaces with a view to understanding and acting upon these processes. At present, and within the setting of a project integrated in the European Union, we are studying the usefulness of body representation in virtual reality for the treatment of pain and the restoration of motor function. Dr. Josep Dalmau Autoimmunity against synaptic antigens The Autoimmunity Against Synaptic Antigens team is led by Dr. Josep Dalmau i Obrador, ICREA Research Professor of the DIBAPS-Hospital Clínic and Professor of Neurology at the University of Pennsylvania in Philadelphia. Dr. Dalmau is a clinical neuro-oncologist trained and working as Associate Professor of Neurology in the Memorial Sloan-Kettering Cancer Center in New York. His research focuses on a group of diseases located at the intercrossing of autoimmunity, cancer and synaptic proteins. This includes the description of new syndromes, the associated immune mechanisms, isolation of the target antigens, and the development of diagnostic tests and treatment strategies. These studies have identified 17 autoantigens and have led to diagnostic tests - some of which are used all over the world. In the last 5 years we have discovered a new category of autoimmune processes resulting in alterations of memory, behaviour and cognition, and which may cause psychosis. These processes are associated with autoimmune responses characterized by antibodies targeted to synaptic proteins and receptors such as for example the glutamate receptors (NMDA, AMPA) or the GABA(B) receptors, or to synaptic proteins related with epilepsy (LGI1, Caspr2), among others. Once the antigens have been identified, our studies focus on the cellular and molecular mechanisms whereby the antibodies alter the function of the synaptic proteins and receptors and produce the symptoms. The results of these studies have had an impact on many medical disciplines and on neuroscience, since they offer a link between immune processes and synaptic activity related to memory, behaviour, psychosis, epilepsy and neuron degeneration. 19 Innovation and transference With the aim of improving people’s health, the IDIBAPS is firmly committed to innovation in the healthcare sector. Above and beyond evaluating research and protecting knowledge, IDIBAPS is concerned with promoting the use of new medical technologies that will improve patients’ state of health, their quality of life and the efficiency of healthcare processes. Taking innovation into consideration is not a complementary task in the routine work of researchers, but a philosophy that is present in all the activities they carry out. It is important for researchers, for patients and for the Institute. A list is provided below of the patents that have evolved during 2010. Patents applied for: Official code P201031183 EP10382224 B333810 Inventors Assignees Title Tipology Farré Ventura, Ramon Navajas Navarro, Daniel Montserrat Canal, Josep Mº Universitat de Barcelona Hospital Clínic de Barcelona Ciber de enfermedades respiratorias Institut d’investigacions Biomèdiques August Pi i Sunyer Dispositivo para regenerar una obstrucción de las vías respiratorias superiores en animales Medical Device Sánchez Fueyo, Alberto Hospital Clínic de Barcelona Method and Kit for the diagnosis LOZANO, Juan José Centro de Investigación Biomédica and prognosis of tolerance in liver Martínez Llordella, Marc Diagnostics en Red de Enfermedades Hepáticas transplantation employing liver Rimola Castella, Antoni y Digestivas (CIBEREHD) tissue Bohne, Felix Berruezo Sanchez, Universitat de Barcelona Hospital Antonio Clínic de Barcelona Tissue characterization tool kit ICT Silvia García, Etelvino Fundacio Clinic per la recerca Andreu Caballero, David biomedica Gabriel Alvarado; Francesc Artigas; Analía Bortolozzi; Andrés Montefeltro; Miquel Vila nLife Therapeutics, S.L. Compositions and methods for selective delivery of oligonucleotide molecules to specific neuron types Treatment Inventors Assignees Title Tipology PCT/ES2010/070710 Morales Funciños, Miguel; Gasull Casanova, Xavier; Acebes Vindel, Ángel; Ferrús Gamero, Alberto; Pintor Just, Jesús Universitat de Barcelona Consejo Superior de Investigaciones Científicas (CSIC) Universidad Complutense de Madrid Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Fundación Rioja Salud Péptidos para el tratamiento de la hipertensión ocular y/o el glaucoma Treatment PCT/ES2010/070531 Campo Güerri, Elías; Salamero García, Olga; Fernàndez Pascual, Verònica; Jares Gerboles, Pedro; López Guillermo, Armando Hospital Clínic de Barcelona Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Fundació Clínic per a la Recerca Biomèdica Universitat de Barcelona Método y kit para el pronóstico de linfoma de células del manto Diagnostics PCT/EP2010/001239 Chamorro Sánchez, Àngel Hospital Clínic de Barcelona Pharmaceutical composition for neuroprotective treatment in patients with ictus Treatment PCT/IB2010/002351 Moreno, Beatriz; Villoslada, Pablo; Navarro, Gloria; Messeguer, Joaquín; Messeguer, Àngel Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Consejo Superior de Investigaciones Científicas (CSIC) Peptoid agonists of nerve growth factor and their use as medicaments Treatment PCT/IB2010/002340 Moreno, Beatriz; Villoslada, Pablo; Messeguer, Joaquín; Navarro, Gloria; Messeguer, Àngel Institut d’Investigacions Biomèdiques August Pi i Sunyer 3 -Oxopiperazinium derivatives as (IDIBAPS) agonists of nerve growth factor Consejo Superior de Investigaciones and their use as medicaments Científicas (CSIC) 61/325,515 - United States Patent Gabriel Alvarado, Francesc Artigas, Analía Bortolozzi, Andrés Montefeltro, Miquel Vila 10382087.4 - 1216 European Patent Office Patent Cooperation Treaty (PCTs): PCT 20 nLife Therapeutics, S.L Compositions and methods for selective delivery of oligonucleotide molecules to specific neuron types Treatment Treatment Patents in course of transference: Official code WO2009141470 Inventors Assignees Universitat de Barcelona Carmen Peralta Institut d’Investigacions (IDIBAPS); Joan Roselló Biomèdiques August Pi i Sunyer (CSIC); Ismail Ben (IDIBAPS) (CSIC); Ramón Bartrons Consejo Superior de Investigaciones (UB) Científicas (CSIC) Hospital Clínic de Barcelona Fundació Clínic per a la Recerca Biomèdica Universitat de Barcelona Title Licensed to Aqueous solution for the preservation of tissues and organs Janus Developments CD5 pharmaceutical compositions for the treatment of infectious and inflammatory processes of fungal origin Immunovative Developments Protein product for the treatment of infectious diseases and related inflammatory processes Immunovative Developments WO2009153336 López Soto, Francisco; Vera Fernández, Jorge WO2008119851 López Soto, Francisco; Sarrias, Maria Rosa WO2010066827 Gratacós Solsona, Eduard; Amat Roldán, Iván Fundació Clínic per a la Recerca Biomèdica Hospital Clínic de Barcelona Universitat de Barcelona Equipment for infrared vision of anatomical srtuctures and signal processing methods thereof Transmural Biotech WO2011024079 Moreno, Beatriz; Villoslada, Pablo; Navarro, Gloria; Messeguer, Joaquín; Messeguer, Àngel Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Consejo Superior de Investigaciones Científicas (CSIC) Peptoid agonists of nerve growth factor and their use as medicaments Bionure Farma WO2011024078 Moreno, Beatriz; Villoslada, Pablo; Messeguer, Joaquín; Navarro, Gloria; Messeguer, Àngel Institut d’Investigacions 3 -Oxopiperazinium derivatives Biomèdiques August Pi i Sunyer as agonists of nerve growth (IDIBAPS) factor and their use as Consejo Superior de Investigaciones medicaments Científicas (CSIC) Bionure Farma WO2009138446 Fondevila, Constantino; Ruíz, Ángel; GarcíaValdecasas, Juan Carlos Universitat de Barcelona Fundació Clínic per a la Recerca Biomèdica Devide for the preservation of a hepatic graft in normothermia Grífols 21 Spin-off companies The knowledge dealt with from the IDIBAPS usually completes its cycle when transferred to the industry. In other cases the link with the centre is maintained through the creation of spin-off companies. A new company has been created in the course of 2010: ImmunNovative Developments S.L. (IND). This spin-off company was created in February 2010, based on the transference of two patents pertaining to the University of Barcelona, the Hospital Clínic de Barcelona, and the Fundació Clínic per a la Recerca Biomèdica. The activity of IND focuses on the development of new biological therapies for the prevention and treatment of inflammatory disorders with an immune basis. For further information: www.immunnovative.com Other spin-off companies in the setting of the IDIBAPS are: Bionure (2009). Spin-off of Hospital Clínic/IDIBAPS and CSIC for the development of new neuroprotective drugs for the treatment of multiple sclerosis and other neurological diseases. For further information: www.bionure.com Transmural Biotech (2009). Spin-off of the Hospital Clínic and the UB, for the development and commercialization of different diagnostic devices in the gynecology field. For further information: www.transmuralbiotech.com Health Services (2009). Linkcare HS administers a Patient-Centric, Case Management oriented Open Health Care model that has been designed as a joined effort of several leading medical care research centers in Europe leaded by Hospital Clínic. Linkcare’s Open Source platform links clinical data from different systems such as Primary Care Information (PCIS), Hospital Information (HIS), Electronic Health Record (EHR) and Enterprise Resource Programming (ERP) Systems with a library of customized patient profile protocols. Linkcare application main areas are: Chronicity, Fragility, End of life care, Reproduction and perinatology, Wellness and Clinical Research. For further information: info@linkcare.es Neurotec Pharma (2006). A R&D company which centres its activity on the development of new diagnostic and therapeutic tools for acute and chronic central nervous system diseases that occur with inflammation and/or neurodegeneration such as Stroke, Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Parkinson (PD) and Alzheimer disease (AD), among others. For further information: www.neurotec-pharma.com 22 IDIBAPS Research and Innovation Clinical trials approved by the CREC The IDIBAPS constitutes the ideal setting for completing a number of the crucial steps in the development of new medicinal products. Basic biomedical research and applied clinical research, together with quality specialized healthcare practice, are aspects of IDIBAPS that may be very useful for the development of drugs. The table below summarizes the number of clinical trials approved by the Clinical Research Ethics Committee (CREC) in the past years. Of note is the large number of clinical trials designed and promoted by the investigators of the IDIBAPS setting themselves: Clinical trial type Approved in 2010 Single centre trial 10 22 Multicentre (reference ethics committee) 32 254 21 Medical devices 9 2002 286 17 Multicentre (concerned ethics committee) 154 2003 293 17 Observational/non-comparative phase IV study 11 2004 266 13 Other 3 2005 270 13 Total 219 2006 214 5 2007 288 17 2008 248 7 2009 230 14 2010 219 ? Clinical trials presented to the CREC Clinical trials promoted by investigators of the IDIBAPS 2000 244 2001 CLINICAL TRIALS PRESENTED TO THE CREC 350 286 300 250 244 254 288 293 266 270 248 200 214 230 219 150 100 50 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 23 Impact upon clinical practice The fundamental objective of IDIBAPS is to combine clinical research of proven quality with high-level basic research. It can thereby achieve a more effective transfer of scientific advances in the prevention and treatment of the most common health problems. As a measure of such transference, the list below reflects the participation of investigators of the IDIBAPS in clinical guides published in international journals subject to peer review. In addition to contributing new data for improving patient treatment, the influence of the investigators of the IDIBAPS places them at the head of expert committees that establish the new tendencies to be followed in medical practice. The names of the investigators of the IDIBAPS are reflected in capital letters under the section Authors: Title Diagnosis and treatment of melanoma: European consensusbased interdisciplinary guideline 24 Associated Journal Short Text IF Authors Text EUR J CANCER 2010; 46:270-283 4,121 Garbe C, Peris K, Hauschild A, Saiag P, Middleton M, Spatz A, Grob JJ, MALVEHY J, Newton-Bishop J, Stratigos A, Pehamberger H, Eggermont A 3,703 Natale A, Raviele A, Al-Ahmad A, Alfieri O, Aliot E, Almendral J, Breithardt G, BRUGADA J, Calkins H, Callans D, Cappato R, Camm JA, DellaBella P, Guiraudon GM, Haissaguerre M, Hindricks G, Ho SY, Kuck KH, Marchlinski F, Packer DL, Prystowsky EN, Reddy VY, Ruskin JN, Scanavacca M, Shivkumar K, Soejima K, Stevenson WJ, Themistoclakis S, Verma A, Wilber D Venice Chart International Consensus Document on Ventricular Tachycardia/ Ventricular Fibrillation Ablation J CARDIOVASC ELECTR 2010; 21:339-379 Guidelines for the use of bisphosphonates in multiple myeloma: Recommendations of the expert committee of the Spanish Myeloma Group from the PETHEMA group MED CLINBARCELONA 2010; 134:268-278 1,231 Garcia-Sanz R, Alegre A, Capote FJ, Hernandez JM, Rosinol L, DeLaRubia J, Sureda A, DeArriba F, Bargay J, Mediavilla JD, Garcia-Larana J, Lahuerta JJ, Mateos MV, Prosper F, Miguel JS, BLADE J The second European evidencebased Consensus on the diagnosis and management of Crohn’s disease: Definitions and diagnosis J CROHNS COLITIS 2010; 4:7-27 1,729 VanAssche G, Dignass A, PANES J, Beaugerie L, Karagiannis J, Allez M, Ochsenkuhn T, Orchard T, Rogler G, Louis E, Kupcinskas L, Mantzaris G, Travis S, Stange E Hepatocellular Carcinoma (HCC) A Global Perspective J CLIN GASTROENTEROL 2010; 44:239-245 2,207 Ferenci P, Fried M, Labrecque D, BRUIX J, Sherman M, Omata M, Heathcote J, Piratsivuth T, Kew M, Otegbayo JA, Zheng SS, Sarin S, Hamid SS, Modawi SB, Fleig W, Fedail S, Thomson A, Khan A, Malfertheiner P, Lau G, Carillo FJ, Krabshuis J, LeMair A Recommendations for diagnosis, staging and treatment of pancreatic cancer (Part I). Grupo Español de Consenso en Cáncer de Páncreas MED CLINBARCELONA 2010; 134:643-655 1,231 NAVARRO S, Vaquero E, MAUREL J, BOMBI JA, DeJuan C, Feliu J, Cruz LF, GINES A, Girela E, Rodriguez R, Sabater L Recommendations for diagnosis, staging and treatment of pancreatic cancer (Part II) MED CLINBARCELONA 2010; 134:692-702 1,231 NAVARRO S, Vaquero E, MAUREL J, BOMBI JA, DeJuan C, Feliu J, Cruz LF, GINES A, Girela E, Rodriguez R, Sabater L Associated Journal Short Text IF Authors Text Consensus guidelines for the optimal management of adverse events in newly diagnosed, transplant-ineligible patients receiving melphalan and prednisone in combination with thalidomide (MPT) for the treatment of multiple myeloma ANN HEMATOL 2010; 89:803-811 2,919 Palumbo A, Davies F, Kropff M, BLADE J, Delforge M, DaCosta FL, Sanz RG, Schey S, Facon T, Morgan G, Moreau P Familial colorectal cancer risk: ESMO Clinical Practice Guidelines ANN ONCOL 2010; 21:v78-v81 5,647 Balmana J, CASTELLS A, Cervantes A Antiretroviral Treatment of Adult HIV Infection 2010 Recommendations of the International AIDS Society-USA Panel JAMA-J AM MED ASSOC 2010; 304:321-333 28,899 Thompson MA, Aberg JA, Cahn P, Montaner JSG, Rizzardini G, Telenti A, GATELL JM, Gunthard HF, Hammer SM, Hirsch MS, Jacobsen DM, Reiss P, Richman DD, Volberding PA, Yeni P, Schooley RT 8,111 Mosca M, Tani C, Aringer M, Bombardieri S, Boumpas D, Brey R, CERVERA R, Doria A, Jayne D, Khamashta MA, Kuhn A, Gordon C, Petri M, Rekvig OP, Schneider M, Sherer Y, Shoenfeld Y, Smolen JS, Talarico R, Tincani A, VanVollenhoven RF, Ward MM, Werth VP, Carmona L 6,38 Bousquet J, Schunemann HJ, Zuberbier T, Bachert C, Baena-Cagnani CE, Bousquet PJ, Brozek J, Canonica GW, Casale TB, Demoly P, GerthVanWijk R, Ohta K, Bateman ED, Calderon M, Cruz AA, Dolen WK, Haughney J, Lockey RF, Lotvall J, O’byrne P, Spranger O, Togias A, Bonini S, Boulet LP, Camargos P, Carlsen KH, Chavannes NH, Delgado L, Durham SR, Fokkens WJ, Fonseca J, Haahtela T, Kalayci O, Kowalski ML, Larenas-Linnemann D, Li J, Mohammad Y, MULLOL J, et al. Title European League Against Rheumatism recommendations for monitoring patients with systemic lupus erythematosus in clinical practice and in observational studies Development and implementation of guidelines in allergic rhinitis - an ARIAGA2LEN paper ANN RHEUM DIS 2010; 69:1269-1274 ALLERGY 2010; 65:1212-1221 25 Title Associated Journal Short Text EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis ANN RHEUM DIS 2010; 69:1744-1750 Guidelines on acute pulmonary embolism from the European Society of Cardiology: reflections from the perspective of the emergency physician EMERGENCIAS 2010; 3,08 22:61-67 Community Acquired Pneumonia. New Guidelines of the Spanish Society of Chest Diseases and Thoracic Surgery (SEPAR) ARCH BRONCONEUMOL 2010; 46:543-558 EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric ANN RHEUM DIS manifestations: report of a task force 2010; 69:2074-2082 of the EULAR standing committee for clinical affairs 26 IF 8,111 Authors Text Basu N, Watts R, Bajema I, Baslund B, Bley T, Boers M, Brogan P, Calabrese L, CID MC, Cohen-Tervaert JW, Flores-Suarez LF, Fujimoto S, DeGroot K, Guillevin L, Hatemi G, Hauser T, Jayne D, Jennette C, Kallenberg CGM, Kobayashi S, Little MA, Mahr A, Mclaren J, Merkel PA, Ozen S, Puechal X, Rasmussen N, Salama A, Salvarani C, Savage C, Scott DGI, Segelmark M, Specks U, Sunderkoetter C, Suzuki K, Tesar V, Wiik A, Yazici H, Luqmani R JIMENEZ S 2,166 Menendez R, TORRES A, Aspa J, Capelastegui A, Prat C, DeCastro FR 8,111 Bertsias GK, Ioannidis JPA, Aringer M, Bollen E, Bombardieri S, Bruce IN, CERVERA R, Dalakas M, Doria A, Hanly JG, Huizinga TWJ, Isenberg D, Kallenberg C, Piette JC, Schneider M, Scolding N, Smolen J, Stara A, Tassiulas I, Tektonidou M, Tincani A, VanBuchem MA, VanVollenhoven R, Ward M, Gordon C, Boumpas DT Colorectal Cancer OncoGuia: surgical pathology report guidelines CLIN TRANSL ONCOL 2010; 12:211- 1,146 213 Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 Revision J ALLERGY CLIN IMMUN 2010; 126:466-476 9,165 Sanjuan X, SALAS A, Lloreta J, Walsh PM Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB, VanWijk RG, Ohta K, Zuberbier T, Schunemann HJ (MULLOL J) Title Guidelines on myocardial revascularization The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Guidelines on myocardial revascularization The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Associated Journal Short Text EUR HEART J 2010; 313:2501-2555 EUR J CARDIOTHORAC 2010; 38:S1-S52 EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and J HEPATOL 2010; hepatorenal syndrome in cirrhosis 53:397-417 European Association for the Study of the Liver IF Authors Text 9,8 Wijns W, Kolh P 2,397 Kolh P, Wijns W, Danchin N, DiMario C, Falk V, Folliguet T, Garg S, Huber K, James S, Knuuti J, Lopez-Sendon J, Marco J, Menicanti L, Ostojic M, Piepoli MF, Pirlet C, POMAR JL, Reifart N, Ribichini FL, Schalij MJ, Sergeant P, Serruys PW, Silber S, Uva MS, Taggart D 7,818 GINES P, Angeli P, Lenz K, Møller S, Moore K, Moreau R, Merkel C, Ring-Larsen H, Bernardi M, Garcia-Tsao G, Hayers P Colorectal Cancer OncoGuia CLIN TRANSL ONCOL 2010; 12:188210 1,146 ManchonWalsh P, Borras JM, Ferro T, Espinas JA (CASTELLS A) EASL Clinical Practice Guidelines: Management of chronic hepatitis B J HEPATOL 2010; 50:227-242 7,818 FORNS X, et. Al. 27 IDIBAPS IN FIGURES Surgical innovations Another way of exerting an impact upon patient care through research is surgical innovation. It is also possible to improve the processes that take place in the operating room through experimental surgical facilities and the daily experience of many of the investigators of the IDIBAPS – Hospital Clínic, as well as collaboration with pioneering companies. Some of the advances made during 2010 by different IDIBAPS teams are: Area 3 Gynaecological endocrinology and human reproduction The use of minimally invasive surgical techniques is one of the options for improving the medical care of our patients. This makes it essential to investigate surgical innovations with a view to expanding procedures of this kind. Minimally invasive surgery is a surgical innovation representing a clear quality marker for the benefit of patients. Our group was the first to introduce such minimally invasive techniques in both benign and malignant gynaecological diseases. In this context, we have extensive experience in the conservative management of fertility in cervical cancer patients (Pahisa J, Int J Gynecol Cancer 2010); have been the first to describe the learning curve associated with the conservative treatment of severe deep endometriosis via laparoscopy (Carmona F, Fertil Steril 2009); and have gained extensive experience in the detection of the sentinel node in laparoscopically treated gynaecological cancers - with the description of a specific technique for detecting the mentioned node in endometrial cancer (Torné A, Rev Esp Med Nuc 2009). Our recent research activity has focused on demonstrating that the inflammatory response and haemodynamic effects of a type of ultra-minimally invasive surgery known as LESS (Laparoendoscopic Single-site Surgery) in experimental animals (Yorkshire pigs) are similar to those found in conventional laparoscopic surgery. On the other hand, we have introduced a new technique for improving the intraoperative search for sentinel nodes in difficult locations, based on the use of a portable gamma camera (Vidal S, J Nucl Med 2010). Area 3 Gastrointestinal and pancreatic oncology Innovation and minimum invasiveness in surgery The experimental research conducted by IDIBAPS-Hospital Clínic, as well as close participation of the industrial sector, have allowed the development of surgical innovation, paving a new way towards the obtainment of improved results in patient care. The development of a technological application through new experimental procedures aims to offer a practical demonstration of the feasibility and safety of a new technical resource for transfer to the operating room and to the patient - avoiding its inherent risks and taking advantage of its benefits, with the objective of minimizing tissue damage, reducing pain, and shortening the time to healing and recovery. 28 Through its investigators, the Department of Gastrointestinal Surgery of the IDIBAPS - Hospital Clínic de Barcelona offers some examples of innovation in surgery. The Department, and particularly its Director, Dr. Antonio Lacy, represent a pioneering effort in Spain and throughout the world in technological advances for the development of surgical procedures in the treatment of benign and malignant gastrointestinal diseases, as well as in the management of morbid obesity and metabolic syndrome. The Department is a leader in innovation in minimally invasive techniques. It has been the first to develop laparoscopic surgery technology in digestive cancer treatment, with excellent oncological results. It has also been the first to publish a randomized study demonstrating the safety and reliability of this new approach compared with conventional open surgery. The Department is also regularly called upon for reviews in important topics in laparoscopy. Revision surgery after sleeve gastrectomy. Lacy AM, Ibarzabal A, Pando E, Adelsdorfer C, Delitala A, Corcelles R, Delgado S, Vidal J. Surg Laparosc Endosc Percutan Tech, 2010; 20 (6): 428-33. Some examples of the main contributions to surgical innovation are the following: NOTES surgery NOTES (Natural Orifices Transluminal Endoscopic Surgery) is the combination of two imaging guided surgical approaches - flexible endoscopy and laparoscopy - in which access to the abdominal cavity is gained through the human body’s orifices: the mouth (transgastric route), vagina, urethra and anus (transrectal route) - lessening surgical aggression by reducing or eliminating abdominal wall incisions; minimizing pain and disability; and improving the aesthetic component, with avoidance of the complications associated with conventional surgery. This technique started in 2008 with the extraction of a gallbladder, followed by the caecal appendix via the transgastric approach. Following technological improvements and the adoption of experimental protocols to evaluate safety and feasibility of use, the complexity of the procedures has increased with very successful results in the extraction of gastric and colorectal tumours via the vaginal, transgastric and transanal routes. Rectal resection through NOTES, using TEM (Transanal Endoscopic Microsurgery), in the management of rectal cancer; the first case in the world of transrectal low anterior resection was performed by this group. Prior experience had been limited to experiments in animals. NOTES transanal rectal cancer resection using transanal endoscopic microsurgery and laparoscopic assistance. Sylla P, Rattner DW, Delgado S, Lacy AM. Surg Endosc, 2010 May; 24 (5): 1205-1210. MA-NOS (Mini-laparoscopic Assisted Natural Orifices Surgery) is a hybrid procedure combining mini-laparoscopic surgery (instruments measuring 2-3 mm in diameter) with transvaginal natural orifices surgery. This technique has been used for the extraction of colorectal tumours in over 30 patients, as well as for the resection of a gastric tumour (GIST) measuring 9 cm in diameter. Hybrid vaginal MA-NOS sleeve gastrectomy: technical note on the procedure in a patient. Lacy AM, Delgado S, Rojas OA, Ibarzabal A, Fernandez-Esparrach G, Taura P. Surg Endosc, 2009 May; 23 (5): 1130-1137. MA-NOS radical sigmoidectomy: report of a transvaginal resection in the human. Lacy AM, Delgado S, Rojas OA, Almenara R, Blasi A, Llach J. Surg Endosc, 2008; 22: 1717-1723. 29 Study of experimental surgery in large animals (Yorkshire pigs). The results of the research done in these animals has shown that the effects of NOTES upon the microcirculation of the intraabdominal organs is not altered compared with the situation found in conventional laparoscopic surgery. Effects of pneumoperitoneum on intra-abdominal organs perfusion during natural orifice transluminal endoscopic surgery: the role of NAC and hypertonic saline pre-treatment. Euro NOTES 2010. Research Fund Project Grant Winners. Single-port surgery Surgery with the same objectives as NOTES as regards to the minimization of surgical invasion, involving a single peri-umbilical port using the same instrumentation as in conventional laparoscopic surgery. We have used this technique to perform sleeve gastrectomy in 30 morbidly obese individuals, with long-term results that warrant its use. Area 5 Diagnosis and therapy in oncology This team has promoted innovations such as the three-dimensional reconstruction of SPECT/CT images with volume rendering to assess the sentinel node in surgical patients. 30 IDIBAPS ReSeARch AnD InnovAtIon jouRnAl InDex This list reflects all the journals with an impact factor over 5 in which the investigators of the IDIBAPS have published original articles during 2010. The publications with an impact factor over 10 points are highlighted. Original Articles Published in 2010 Impact Factor (IF) Quartiles AIDS 7 5,632 1 ALLERGY 4 5,334 1 AM J CLIN NUTR 1 6,562 1 AM J GASTROENTEROL 5 5,608 1 AM J PATHOL 4 5,917 1 AM J RESP CRIT CARE 8 9,091 1 AM J TRANSPLANT 6 6,843 1 ANN INTERN MED 2 14,78 1 ANN NEUROL 1 8,051 1 ANN ONCOL 4 5,179 1 ANN RHEUM DIS 5 5,767 1 ANNU REV MED 1 13,237 1 ARCH INTERN MED 1 7,92 1 ARCH NEUROL-CHICAGO 2 5,204 1 ARTERIOSCL THROM VAS 1 6,883 1 ARTHRITIS RHEUM-US 3 7,332 1 BIOL PSYCHIAT 1 7,154 1 BIOMATERIALS 1 5,196 1 BLOOD 12 10,37 1 BRAIN 2 7,617 1 BRAIN PATHOL 1 5,274 1 BRIT MED J 1 9,245 1 CANCER CELL 2 24,077 1 CANCER RES 3 7,656 1 Abreviated Journal Name 31 32 Abreviated Journal Name Original Articles Published in 2010 Impact Factor (IF) Quartiles CANCER-AM CANCER SOC 1 5,418 1 CARDIOVASC RES 2 5,826 1 CELL 1 29,194 1 CELL DEATH DIFFER 1 7,463 1 CEREB CORTEX 1 6,368 1 CIRCULATION 4 10,94 1 CLIN CANCER RES 5 6,177 1 CLIN CHEM 1 5,454 1 CLIN INFECT DIS 2 6,186 1 CNS NEUROL DISORD-DR 1 14,75 1 CURR PHARM DESIGN 2 5,27 1 DIABETES CARE 2 7,912 1 DIABETOLOGIA 2 5,247 1 EMBO REP 1 8,175 1 ENDOCRINOLOGY 1 5,236 1 EUR HEART J 4 7,286 1 EUR RESPIR J 12 5,076 1 GASTROENTEROLOGY 12 12,457 1 GENOME RES 1 10.256 1 GUT 8 9,002 1 HAEMATOL-HEMATOL J 8 5,032 1 HEPATOLOGY 19 10,446 1 HUM MUTAT 1 6,473 1 HYPERTENSION 1 6,007 1 INT J NEUROPSYCHOPH 3 5,184 1 J ALLERGY CLIN IMMUN 1 8,829 1 Original Articles Published in 2010 Impact Factor (IF) Quartiles J AM CHEM SOC 1 7,696 1 J AM SOC NEPHROL 1 7,371 1 J BIOL CHEM 4 5,808 1 J CELL SCI 1 6,427 1 J CLIN ENDOCR METAB 1 5,799 1 J CLIN ONCOL 5 13,598 1 J CLIN PSYCHIAT 11 5,533 1 J HEPATOL 16 6,073 1 J IMMUNOL 2 6,293 1 J MED CHEM 1 5,115 1 J NATL CANCER I 1 15,271 1 J NEUROSCI 3 7,453 1 J PATHOL 1 5,759 1 J PROTEOME RES 2 5,151 1 J VIROL 2 5,341 1 JAMA-J AM MED ASSOC 2 23,175 1 LANCET 2 25,8 1 LANCET INFECT DIS 1 11,808 1 LANCET NEUROL 5 9,479 1 LANCET ONCOL 3 10,119 1 LEUKEMIA 1 6,146 1 MEDICINE 3 5,167 1 NANOMED-NANOTECHNOL 1 5,44 1 NAT GENET 6 24,176 1 NAT MED 2 28,588 1 NATURE 1 26,681 1 Abreviated Journal Name 33 Original Articles Published in 2010 Impact Factor (IF) Quartiles NEUROBIOL AGING 1 5,599 1 NEUROIMAGE 2 5,559 1 NEUROLOGY 2 5,69 1 NEUROPSYCHOPHARMACOL 2 5,889 1 NEW ENGL J MED 5 51,296 1 ONCOGENE 3 6,582 1 ONCOLOGIST 1 5,206 1 P NATL ACAD SCI USA 1 9,643 1 PEDIATRICS 2 5,012 1 PHARMACOL THERAPEUT 1 8,657 1 PLOS GENET 1 7,671 1 PROTEOMICS 2 5,735 1 SEMIN LIVER DIS 4 5,302 1 THORAX 2 6,064 1 TRAFFIC 1 6,612 1 Abreviated Journal Name 34 Platforms Scientific Platforms and Services High-level biomedical research requires the use of high-cost techniques and equipment. In addition, the high competitiveness of many of these techniques requires the dedication of specialized personnel. In many cases a given technique is applied by different research teams without any of them requiring an exclusive and permanent use of the methodology. IDIBAPS promotes the constitution of common service platforms to support research for use by all researchers, with the purpose of improving the performance and profitability of investments and efficiency in the use of available resources. The IDIBAPS has 5 scientific platforms of its own: • Biobank of Hospital Clínic – IDIBAPS (Page 36) • Bioinformatics (Page 39) • Cytometry and cell sorting (Page 40) • Functional genomics (Page 42) • Medical imaging (Page 43) In turn, other services are shared with the entities with which agreements have been established: • Proteomics Unit (IDIBAPS-UB-PCB platform) (Page 44) • Animal housing facilities (UB) (Page 45) • DNA unit (Hospital Clínic) (Page 46) • Confocal microscopy unit (UB) (Page 47) • Electronic microscopy unit (UB) (Page 48) 35 INTRODUCTION IDIBAPS Platforms Biobank of Hospital Clínic-IDIBAPS www.clinicbiobanc.org The Biobank is a centralised institutional support platform for coordinating the collection, processing, storage and transfer of biological samples to promote biomedical research of the highest standard. When it was first set up, the Biobank had a dual mission: • To provide the scientific community with standard, well characterised biological samples with high added value, in order to promote, foster and develop biomedical research in accordance with current legislation. • To standardise all the Institute’s research sample collections (in accordance with article 67 of Law 14/2007, relating to Biomedical Research Act). The bank’s catalogue of samples is divided into three broad categories which are available for scientific purposes for the consolidation of personalized medicine: 1) Neurological Tissue Biobank A nervous tissue repository (brain and spinal cord) created from donations from cadavers with or without neurological conditions, helping to facilitate research into neurological illnesses in order to improve diagnoses and enhance patient assistance. 2) Tumour Biobank and Anatomical Pathologies Collections A Repository of tumorous tissue and samples from cancer patients. This biobank also manages an extensive collection of other disease-related tissue provided by the Department of Anatomical Pathology at the Hospital Clínic from excess samples used in their diagnoses. This material is essential to providing current large-scale tissue research projects with the samples they require. 3) Blood and Fluid Biobank This repository contains samples of metabolic, inflammatory bowel, hepatic, digestive and maternal and foetal diseases, among others. It houses a large range of samples of scientific interest, primarily DNA, serum and plasma, which are provided by doctors’ surgeries and laboratories where blood and fluid are taken for lab tests and blood and fluid donation. Services The Biobank of Hospital Clínic – IDIBAPS offers a wide range of samples and services. The scientific community may make full use of the bank’s equipment and professional staff to achieve their most ambitious goals. The work of the biobank goes beyond simply providing samples; they offer support to researchers during the various stages of projects requiring the use of biological samples. Sample providing • Nerve tissue from cadaveric donors affected by neurologic diseases • Frozen biological samples and paraffin-embedded tissue blocks representing the most common tumours • DNA, serum, plasma and PBMCs from different diseases as well as from control donors Technical and scientific advice • Creation and management of new collections • Methodology (technical guidance) • Experimental design with human and animal tissue samples • Design and interpretation of immunohistochemical studies • Quality management programmes • Harmonization of quality procedures for the handling of DNA samples • Technical assessment for the manipulation of the Biobank equipment (microdissector and morphometre) 36 Private collections management • Collection management of multicentre studies • Storage of pre-existing collections Histological techniques • Processing of frozen and paraffin embedded tissues (macroscopy, cryopreservation, paraffin blocks) • Lasser microdissection • Tissue microarrays (TMA) • Histological staining • Definitive neuropathological diagnosis of neurological diseases Cellular techniques • Purification and cryopreservation of mononuclear cells • Immortalization of B lymphocytes • Explant obtaining Molecular techniques • DNA extraction from peripheral blood • DNA/RNA/protein extraction from tissue (frozen and paraffin embedded) •WGA • Serum and plasma isolation Equipment • -20ºC, -80ºC and -150ºC freezers with safety systems • Vapour phase liquid Nitrogen tanks Neurological tissue bank • Cubicles for obtaining the material in sterile conditions • Instruments for preparing samples for the microscope • Filing cabinets for collecting paraffined samples • Gas filtration cabinet • Automated immunostaining appliance • Combination refrigerator and -40ºC freezer for preserving fungibles • Autoclave for sterilising surgical material Tumour bank • Equipment for preparing tissue microarrays • Tissue microdissection microscope with laser • Microtome and cryostat Blood and Fluid Biobank • Programmable freezer with a controlled freezing ramp • “Chemagic MSM1®” automated device for obtaining DNA from large volumes of blood • “Tecan EVO150®” automated station for the aliquoting of samples • “CoulterZ1®” cells and particles counter • Cabinets for isolating cells in sterile conditions • Cell immortalisation platform • Computer systems for managing samples and related data 37 People Scientific coordinator(s): Director Dr. Joan Albert Barberà HCB jbarbera@clinic.ub.es Scientific coordinator Dr. Anna Bosch Comas IDIBAPS abosch1@clinic.ub.es Managing assistant Ms. Meritxell Rufet Fundació Clínic mrufet@clinic.ub.es Informed Consent Manager Ms. Ángela Martín Fundació Clínic martin3@clinic.ub.es Lab Manager Ms. Regina A. Cañaveras Fundació Clínic rcanaver@clinic.ub.es • Neurological tissue bank Dr. Francesc Graus (HC-UB) fgraus@clinic.ub.es • Tumour bank Dr. Pedro L. Fernández HC plfernan@clinic.ub.es • Blood and Fluid Biobank Dra. Anna Bosch Comas IDIBAPS abosch1@clinic.ub.es Staff: • Neurological tissue bank Dr. Maria Jesús Rey Neuropathologist. Senior technician – I (UB) Dr. Ellen Gelpí Neurologist. Senior Technician I (UB) Ms. Carina Antiga Secretary (IDIBAPS) Ms. Sara Charif Laboratory technician (IDIBAPS) Ms. Rosa Rivera Specialised technician – III (UB) Ms. Verónica Santiago Laboratory technician (CIBERNED) Mr. Abel Muñoz Autopsy Assistant (Fundació Clínic) Ms. Leyre Etxarri Autopsy Assistant (Fundació Clínic) • Tumour bank Laura Gelabert Laboratory technician (Fundació Clínic) Mónica Marín Laboratory technician (Hospital Clínic) Eva Fernández López Laboratory technician (Hospital Clínic) Raquel Bermudo Gascón Bank Manager (Fundació Clínic) • Blood and Fluid Biobank Albert Davins Laboratory technician (CIBERDEM) Roser Mas Laboratory technician and quality supervisor (IDIBAPS) Anna Morales Laboratory technician (IDIBAPS) Laura Tugores Nurse (IDIBAPS) Location: • Neurological tissue bank Faculty of Medicine UB. South wing, floor 0 (~140 sq m) • Tumour bank, Blood and Fluid Biobank C/ Roselló 149-153, -1 Floor 38 IDIBAPS Research and Innovation Bioinformatics The Bioinformatics Unit is mainly devoted to the analysis and support in the interpretation of data coming from OMICS disciplines. The integration of data coming from the Genomics, Proteomics, or Metabolomics fields requires huge efforts in the development of common languages, tools, and specific databases. Differential expression or classification studies in every OMICS field usually face two big challenges: the high dimensionality and the small sample size. Furthermore, clinical research is frequently aimed at understanding very complex biological problems for the discovery of specific biomarkers for diagnosis. It is then necessary to use sophisticated tools with complex statistical methodologies to derive information in the usual conditions of high-throughput experiments. At this current moment, the emerging field of Systems Biology is aimed at analyzing and integrating data from the entire OMICS field to ultimately create working models of entire biological systems. Services Bioinformatic support in different areas of biomedical research, particularly in OMICS technologies; development of new tools and diffusion: • Consultancy: counselling in experimental design; low-level and quality control analyses; orientation on biostatistical resources; assistance in tool utilisation; intensive analysis of OMICS technology data in collaborative settings; interpretation of results. • Bioinformatic resources development and administration: software processing; access to computer resources via proprietary Linux services; development of customised tools and databases, particularly in web settings. Equipment • IBM eServer BladeCenter HS21 server. 1 Intel (R) Xeon (R) E5345 @ 2.33 Ghz CPU. 64 Bit. RAM: 16 GB. H.D: 465 GB (Raid 5) OS: Suse Linux Enterprise Server 10 • Intel Dual Xeon 3.0 GHz Server. 32 Bit. RAM 3 GB. HD 120 GB. OS Linux Red Hat 9 • Intel Dual Xeon 3.0 GHz Server. 32 Bit. RAM 3 GB. HD 120 GB. OS Windows 2003 OS • HP XW4200 Server. Pentium IV 3.5 GHz. HD 120 GB. RAM 2 GB. OS Windows XP • 2 PC Intel Core 2 Duo® E8400 @3.0GHz. Arq. 32 Bits, Memoria RAM 3.5GB, HD: 250 GB. OS: Windows XP Scientific coordinator: • Dr. Susana Kalko (IDIBAPS) skalko@clinic.ub.es Staff: • Dr. Nuria Queralt Rosinach Technician (IDIBAPS) • Sr. Joan Protasio Technician (IDIBAPS) Location: • Bioinformatics Platform CEK C/ Roselló, 149-153, -1 Floor 39 Cytometry and cell sorting www.idibaps.ub.edu/citomica Flow cytometry measures and analyzes the characteristics of single particles, normally cells, as they move in a stream and are passed through a laser. Thousands of cells can be analyzed by a flow cytometer in a single second. It is possible to mark the particles with one or more fluorescent substances that then makes it possible to measure physical characteristics such as cell size, shape, internal complexity and any cell component or function that can be detected by a fluorescent compound. The applications of flow cytometry are numerous, and this has led to the widespread use of these instruments in the biological and medical fields. The facility is subdivided into four groups: FACS analysis, data analysis, cell sorting and high resolution images of each cell directly in flow. 1.Analysis of population of interest (Up to 18 colors) • FACSCalibur (Up to 4 colors) • FACSCantoI (Up to 6 colors) • FACSCantoII (Up to 8 colors) • LSRFortessa SORP HTS 4 LASER (Up to 16 colors) • LSRFortessa SORP 5 LASER (Up to 18 colors) 2.Apoptosi •FACSCalibur •FACSCantoI •FACSCantoII • LSRFortessa SORP HTS 4 LASER • LSRFortessa SORP 5 LASER 3.Cell cycles •FACSCalibur •FACSCantoI •FACSCantoII • LSRFortessa SORP HTS 4 LASER • LSRFortessa SORP 5 LASER 4.Functional Analysis •FACSCalibur •FACSCantoI •FACSCantoII • LSRFortessa SORP HTS 4 LASER • LSRFortessa SORP 5 LASER 5.Stem Cells • LSRFortessa SORP 5 LASER 6.Viability •FACSCalibur •FACSCantoI •FACSCantoII • LSRFortessa SORP HTS 4 LASER • LSRFortessa SORP 5 LASER 40 7.Multiparameter quantitative trials on soluble molecules and phosphoproteins (CBA and CBA Flex Set) •FACSCalibur •FACSCantoI •FACSCantoII • LSRFortessa SORP HTS 4 LASER • LSRFortessa SORP 5 LASER 8.Cell sorting • autoMACS (magnetic sorter) • FACSAria II (Up to 9 colors) • FACSAria SORP 5 LASER (Up to 18 colors) 9.High resolution microscopy in flow (Cell Signaling and molecular translocation, Internalization, Co-localization, Cellcell Interaction, Morphology Analysis, Cell Death and Autophagy, Cell Cycle and Mitosi, DNA damage and repair) • ImageStreamX : 2 cameras, 4 LASER (AMNIS Corporation) Equipment • FACSCalibur cytofluorimeter (IDIBAPS) • FACSCantoll cytofluorimeter (IDIBAPS) • Vantage SE FACS cell sorter (IDIBAPS) • FACSAriaII cell sorter (IDIBAPS) Scientific coordinator(s): • Scientific advisor Dr. Pablo Engel UB pengel@ub.edu • Department head Isabel Crespo Specialist technician (IDIBAPS) icrespo@clinic.ub.es Staff: • Cristina López Technician (IDIBAPS) Location: • Cytomics Platform CEK C/ Roselló 149-153, -1 Floor 41 SOCIETY Functional Genomics The Genomic Unit of IDIBAPS provides access to different genome wide protocols. We manage samples for genomic projects starting from quantitative and qualitative analysis of nucleic acids up to genome wide gene expression, genotyping and gene dose analysis using different platforms including real-time PCR and microarrays. Recently we have incorporated a next generation sequencer in our facility. Services • Quantification of nucleic acids • Qualitative analysis of nucleic acids • Expression analysis by Real-time PCR • Genotyping analysis by Real-time PCR • Digital PCR • Genome Wide Expression analysis (Affymetrix microarrays) • Genome Wide Genotyping analysis (Affymetrix microarrays) • High thought put expression analysis (GeneTitan Affymetrix) • High thought put Genotyping analysis (GeneTitan Affymetrix) • CGH-Arrays (Agilent) • Scanner Axon 4000B • Next generation sequencing (Illumina) In addition to these services, the Platform offers advice on experimental design for transcriptomic studies, on extracting RNA and on analysis of microarray data. Equipment •NanoDrop •Sinergy2 • Bioanalyzer 2100 (Agilent) • Viia7 (Applied Biosystems) • Fluidigim (BioMark) • GeneChip Affymetrix genetic analysis system • GeneTitan Affymetrix genetic analysis system • Agilent platform • Axon 4000B scanner • GenomeAnalyzer IIx (Illumina) Scientific director: • Dr. Elías Campo HC-UB ecampo@clinic.ub.es Scientific coordinator: • Dr. Pedro Jares HC-UB pjares@clinic.ub.es 42 Unit manager: • Dra. Magda Pinyol mpinyolm@clinic.ub.es Staff: • Montse Sánchez Technician (IDIBAPS) • Laura Plà Technician (IDIBAPS) • Helena Suárez Technician (IDIBAPS) • Dra. Anna Enjuanes Technician (IDIBAPS) Location: • Genomics Platform CEK C/ Roselló 149-153, -1 Floor IDIBAPS Research and Innovation Medical Imaging Main objectives • To provide services related to medical imaging techniques for researchers from IDIBAPS and other institutions, and to industries connected with health. • To perform first-rate basic and clinical research into medical imaging using structural and functional magnetic resonance, resonance spectroscopy, molecular imaging, image processing and other types of medical imaging. • Researcher training in techniques and basic research to enable them to conduct experimental and clinical studies, thereby allowing them to explore the advantages of translational research. Departments and equipment Clinical Imaging Research (3T MRI Unit) • RM 3T- Siemens 3T TRIO, B17 software • 32 phased-array head coil • 8 phased-array head coil • Body coil • Others phase array coil Experimental Imaging Research (7T MRI Unit) • Bruker BioSpec 70/30 (gradient system of 400 mT/m) • Imaging volume coils for mice, rat and small cats or rabbits • Surface coil for rat and mouse brain imaging • Surface coil for rat heart imaging (with CINE acquisition sequence) • Volume coils for 1H/13C, 1H/31P and 1H/19F spectroscopy • Surface coil for 1H/13C spectroscopy • Electric stimulator for fMRI • Inhalation anaesthetic system including animal monitoring • 4 PC for imaging post-processing and analysis Post-processing Imaging Lab • 3 dedicated workstations (1 Mac, 2 linux) and 7 high performance PC (5 dual windows-linux, 2 windows) for image postprocessing • 10 standard PC • Software licenses: 10 Matlab, 2 LcModel, 1 AnalyzeDirect Scientific coordinator(s): • Clinical Imaging Research (3T MRI Unit) Dr. Núria Bargalló Alabart Hospital Clinic bargallo@clinic.ub.es • Experimental Imaging Research (7T MRI Unit) Dra. Guadalupe Soria Rodríguez IDIBAPS gsoriar@clinic.ub.es Dr. Raúl Tudela (CIBER-BBN, GIB-UB) • Post-processing Imaging Lab Dr. Carles Falcón Falcón IDIBAPS cfalcon@clinic.ub.es Location: • 3T MRI Unit 7T MRI Unit Hospital Clinic de Barcelona, floor 0, 3a stairs • Post-processing Imaging Lab C/ Roselló 149-153, -1 Floor Imaging Lab, CEK 43 INTRODUCTION Shared Platforms Proteomics Unit (IDIBAPS-UB-PCB Platform) Services • Separation of peptides and proteins • Characterisation and sequencing of peptides and proteins • Analysis of complex protein samples • Quantitative analysis of complex protein samples (DIGE, ITRAQ, LABEL-FREE LC-MS) • Whole protein analysis (top-down proteomics) Equipment • Strips Protean IPG Bio-Rad system for sorting of proteins by pl (IDIBAPS) • SDS-PAGE system for sorting of Protean Dodecacell Bio-Rad gels (IDIBAPS) • SDS-PAGE system for sorting of Mini Protean Dodecacell Bio-Rad gels (IDIBAPS) • PDQUEST Bio-Rad analysis software for 2-dimensional gels (IDIBAPS) • Scanner for digitising G-810 Bio-Rad gels (IDIBAPS) • Fluro-S Bio-Rad analyser (IDIBAPS) • Solution automatic genomic digester (IDIBAPS) • Espectròmetre de masses: MALDI-TOF-TOF 4800 (Applied Biosystems) • MALDITOF Voyager DE Prespective (IDIBAPS) • Thermo Finnigan NanoESI-Ion Trap LCQ DECA XP (IDIBAPS) • VELOS ORBITRAP-ETD NanoESI LTQ Linear Ion Trap (UB) • PROXEON LC nanoEASY (IDIBAPS) • Thermo Finnigan MicroHPLC Surveyor (IDIBAPS) • Typhoon (GE HealthCare) for quantitative analysis of proteins (UB) • Decyder; computer analysis of differential studies (UB) • Peptide and protein analytical software (SEQUEST, PROTEOME DISCOVERER, PEAKS, etc.) Scientific coordinator(s): • Dr. Oriol Bachs UB obachs@ub.edu Staff: • Dr. Josep Maria Estanyol Unit supervisor (SCT-UB) jmestanyol@ub.edu • Dr. M. José Fidalgo UB. Masses supervising technician • Dr. Eva Olmedo IDIBAPS. Technician • Mr. Juan Martínez Heredia IDIBAPS. Technician Location: • UB School of Medicine 5th floor, South Wing, Casanova, 143 44 IDIBAPS Research and Innovation Animal housing facilities (UB) Services • To comply with the applicable legislation on protecting animals used for experiments and for other scientific purposes: - Curing and maintenance of the housed species - Accreditation control of the personnel implicated in the handling of animals, according to legislation - Control of the procedures approved by the Catalan Environmental Departament. Generalitat de Catalunya • Forming part of the Animal Experimentation Ethics Committee (CEEA-UB) • Crossbreeding and maintenance of colonies of transgenic breeds, knock-out and special breeds of rat • Technical and veterinary counselling. Veterinary control • Supervision of reception and the shipment of animals to other centres Equipment • Stabling drawers and racks (FC + UB) • Ventilated racks (UB) • Extractors (UB + FC) • Biological safety chamber (UB) • Siemens X-ray equipment (FC) • Experimental large animal operating theatre (UB + FC) • Surgical lenses (UB) • Ventilators (UB + FC) • Anaesthesia equipment (UB) • Autoclaves (UB) • Equipment washer and bottle washer (UB) • SAS (UB) Scientific coordinator(s): • Dr. Jordi Alberch UB alberch@ub.edu • Dr. Jaume Bosch HC jbosch@clinic.ub.es • Dr. Josep Mª Tusell CSIC jmtnqi@iibb.csic.es Staff: • Dr. Amèrica Giménez Animal housing facilities supervisor. Senior technician (UB) agimenez@ub.edu • Mr. Josep Ma Marimon Cryopreservation and embyonic transference supervisor. Senior technician (UB) • Ms. Leire Barguín Veterinarian (UB) • Mr. David Almató Experimenter. Category III stabling technician (UB) • Ms. Dolores Ruiz Experimenter. Category III stabling technician (UB) • Ms. Blanca Caballero Keeper. Stabling assistant (FC) • Sr. David López Keeper. Stabling assistant (FC) • Mr. Ivan Ortega Experimenter. Category III stabling technician • Mr. Raul Ramírez Experimenter. Category III stabling technician • Mr. Robert Fortea Experimenter. Category III stabling technician • Cleaning personnel 1FC and 3UB Location: • 6th floor, School of Medicine (~600 sq m) 45 SOCIETY DNA Unit (Hospital Clínic) Services • DNA extraction • DNA sequencing • Genotyping (Analysis of DNA fragments, microsatellites, SNPs, MLPA, etc.) Equipment • One DNA capillary sequencer (IDIBAPS) • One ultra-deep sequencing system (HC) • Two genetic analyzers (HC/IDIBAPS) • Two automatic DNA extraction systems (HC) Scientific coordinator(s): • Dr. Joan Clària HC jclaria@clinic.ub.es Staff: • Ms. Montserrat Bernat Specialist technician (HC) • Ms. Anabel Martínez Specialist technician (IDIBAPS) Location: • Hospital Clinic’s Biological Diagnosis Centre Stairway 7, 5th floor. HC (~20 sq m) 46 IDIBAPS Research and Innovation Confocal microscopy unit (SCT-UB) Services Equipment Light microscopy • Confocal laser microscopy • Two-photon excitation microscope (multiphoton) • Wide-field microscopy • Multiphoton and high-velocity spectral confocal microscope (Leica TCS-SP5) • Spectral confocal microscope (Leica TCS-SL) • Confocal microscope (Leica TCS-NT) • Microinjector (Leica AS TP) • Wide-field fluorescence microscope (Leica DMI6000 B) (Faculty of Medicine) • General laboratory • Culture room • Imaging analysis workstations Scientific coordinator(s): • Dr. Carles Enrich Department of Cellular Biology, UB enrich@ub.edu Light microscopy applications • Fluorescent, reflection and transmitted light, multi-channel and multidimensional (xyztλ) images. Mosaic and multi-position images • Live cell microscopy • Molecular proximity analysis: FRET (Fluorescence resonance energy transfer) • Molecular dynamics analysis by photobleaching and photolabelling techniques: - FRAP (Fluorescence recovery after photo-bleaching) - Inversed FRAP - FLIP (Fluorescence loss in photo-bleaching) - Photo-activation, photo-conversion • Intravital Microscopy (live animal): - Confocal, multi-photon - Resonant scan (high speed) • Two photon excitation microscopy (Multi-photon): -Fluorescence - Second Harmonic Generation Cell culture and micromanipulation • Maintenance of cell lines for microscopy experiments •Microinjection • Molecular and cellular dyes (transfection, staining) Staff: • Dr. Maria Calvo Senior technician and head of the Confocal Microscopy Unit, IDIBAPS mcalvo@sct.ub.es • Anna Bosch Specialised technician, IDIBAPS abosch@sct.ub.es Location: • Faculty of Medecine, South Wing, 5 floor (c/ Casanova, 143, 08036, Barcelona) Image processing and analysis • Technical assistance in image processing and analysis (3D reconstruction, quantification, co-localization, FRET analysis, molecular dynamics analysis, particle tracking) • Development of custom instructions macros • Training days of image processing and analysis User support and innovation • Assistance in planning, preparation, performance and analysis of light microscopy experiments • Training in the use of equipment • Development of new methodologies 47 SOCIETY Electronic Microscopy Unit (UB) Services Transmission electron microscopy (TEM) • Ultrastructure studies of tissues and cell cultures (on different subtrates) • Studies of suspensions ( bacteria, virus, flagella, lipid vesicles...) • Studies of cellular organelles extraction (reticulum, mitochondria, exosomes...) • Molecular localization and colocalization of proteins, glucidic residues,... • Molecular localization of DNA or RNA sequences by “in situ” hybridation • Cytochemical studies (enzymatic activity, enzymatic digestions...) • Correlative techniques (optical, confocal and electron microscope) • Preparing of samples for TEM-based microanalysis • Studies of viruses, organules and proteins by negative staining Scanning electron microscopy (SEM) • Microstructural analysis of surface cell cultures on different substrates (glass, thermanox, aclar,...) • Surface characterization of tissues or organs • Studies of cellular suspensions(bacteira • Studies of surfaces: bony, teeth, cornea, skin,... • Characterization of biofilms and their formation • Morphological studies of small organisms and micro-organisms • Surface molecular localization • Characterization of biomaterials, implants... • Study, analysis and assessment of the images Examples of applications • Biomedical characterization of any kind of cell culture or tissues by SEM or TEM • Studies of markers incorporation (colloidal gold, quantum-dots..) inside the tissues or cell culture (ex. Inhalation of nanogold and their localisation by light and transmissionn electron microscopy) • Sperm cell study by TEM and SEM for diagnosis • Studies of biofilms on water filters, tracheal tubes, historical monuments... • Characterization of protein aggregates for example in Alzheimer’s disease • Biopsies in pathology • Calcium microanalysis detection Sample preparation types • Cryomethods preparation (cryofixation) - High pressure cryofixation, cryosubstitution, cryo embedding in epoxy resins ( for ultrastructural studies) - High pressure cryofixation, cryosubstitution, cryo embedding in acrylic resins at low temperatures (molecular location studies: immunolocalization, “in situ” hybridization, etc.) - High pressure cryofixation, cryosubstitution, critical point process (3-D studies using scanning electron microscopy) • Standard preparation method (chemical fixation) - Chemical fixation, dehydration and embedding in epoxy resins for ultrastructural studies - Ultramicrotomy at room temperature - Negative staining (viruses, flagella, proteins, etc.) - Cytochemical techniques (detection of enzymes, glycoproteins, sugars, etc.) - Chemical fixation, dehydration, critical point (scanning electron microscopy) 48 • Mixed preparation: combination of standard methods and cryomethods - Chemical fixation, cryoprotection, cryosubstitution and embedding in epoxy resins (ultrastructural study) - Chemical fixation, cryofixation and embedding in epoxy resins (ultrastructural study) - Chemical fixation, cryoprotection, cryosubstitution and embedding at low temperatures (molecular localization studies: immunolocalization, “in situ” hybridization, etc.) - Chemical fixation, cryoprotection, cryofixation and cryoultramicrotomy (molecular location studies: immunolocalization, “in situ” hybridization, etc.) - Chemical fixation, cryofixation, cryosubstitution, critical point process (for scanning electron microscopy) • Molecular localization - Proteins, sugar residues,... - Markers: nanogold, silver enhancement, colloidal gold, quantum-dots, lectins,.. • Correlative techniques - To observe the “same” cell (for example a dynamic process) by light microscopy (at low resolution) and by transmission electron microscopy (higher resolution) using cryofixtion or chemical fixation Equipment • Jeol EM 1010 transmission electronic microscope • Zeiss DSM 940A scanning electron microscope • EM PACT cryofixation system (Leica) • Cryosubstitution systems - AFS (Leica) - AFS2 (Leica) •Ultramicrotomes - Ultracut (Reichert-Jung) - Ultracut E (Reichert-Jung) - Ultracut UCT (Leica) + FCS Cryoultramicrotomy Unit (Leica) • VGMicrotech CPD 7501 critical point system • Fisons Instrument FC510 Sputtering System • Optical microscopes - Leica DMLS - Olympus CX41 RF + Olympus DP 70 digital camera Scientific coordinator(s): • Dr Núria Cortadellas Unit Head nuriac@ccit.ub.es Tel. 93 403 44 07 - 93 403 98 59 Staff: • Ms Almudena Garcia Ultramicrotomy Section Manager • Ms Ana Ribera Laboratory technician • Ms Eva Fernández IDIBAPS technician – research support contract Location: • UB Faculty of Medicine, North Wing, 6th floor 49 NETWORKING Spanish excellence networks (CIBERS, RETICS and CAIBER) The Ministry of Science and Innovation promotes health research through the Carlos III Health Institute. In the last few years much of its economical effort has focused on the consolidation of the Spanish National Research Networks. The Networked Biomedical Research Centres (Centros de Investigación Biomédica en Red, CIBERs), Health Cooperative Research Topic Networks (Redes Temáticas de Investigación Cooperativa en Salud, RETICs), and the Networked Biomedical Research Support Consortium - Spanish Clinical Trials Platform (Consorcio de Apoyo a la Investigación Biomédica en Red – Plataforma Española de Ensayos Clínicos, CAIBER), represent a new way of understanding cooperative biomedical research that has given excellent results during recent years. The IDIBAPS participates in most of these virtual research structures and leads some of them. Investigators of the IDIBAPS direct the following networks: • Networked Biomedical Research Centre for Hepatic and Digestive Diseases (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd) • Networked Biomedical Research Centre for Diabetes and Associated Metabolic Diseases (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM) • CIBER for Respiratory Diseases (CIBERES) • AIDS Research Network (RIS) • Spanish Multiple Sclerosis Network (REEM) 50 Networked Biomedical Research Centre for Hepatic and Digestive Diseases (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd) www.ciberehd.org CIBERehd was created on 29 November 2006, and is presently composed of 49 groups (one of them on an associated basis), corresponding to 28 centres in 10 Autonomous Communities throughout Spain. It is headed by a Scientific Director, Dr. Jaume Bosch, and its activities are supervised by an external Steering Committee and Scientific Committee. Its central facilities are located in calle Córcega 180, in Barcelona. Director: Dr. Jaume Bosch The objectives of the CIBER for Liver and Digestive Diseases are the following: • To promote top level research in liver and digestive diseases, in an international context, promoting interaction among the best Spanish groups. • Preferentially focusing on translation research, favouring the obtainment of results that can be transferred to clinical practice and to biotechnological applications. • Activity as a promoting and facilitating agent in the national setting, and serving as a reference in international cooperation. The scientific activity of the CIBERehd fundamentally focuses on its research programs and strategic actions, and is complemented by the training programme, the platforms and common resources. The CIBERehd has its own platforms in genomics, transcriptomics, proteomics, metabolomics, genic silencing and bioinformatics, as well as a biobank (integrated within the IDIBAPS biobank), a steatosic liver bank and telemedicine platforms for diagnostic and therapeutic support in liver cancer, and genetic counselling in colorectal cancer. The CIBERehd has 6 major research programs: • Portal hypertension and mechanisms of transition to cirrhosis • Hepatitis viruses • Cholestasis and metabolic disorders • Liver immunology, cell therapy and transplantation • Liver and digestive cancer • Gastrointestinal inflammation and motility Its budget, totalling 6,3 million euros in 2010, covers the salaries of the investigators that work in the different groups, the scientific infrastructure, training programmes and strategies actions - involving the implementation of large research projects that can only be addressed through firm cooperative action. The activity of the CIBERehd is reflected in its annual report, with the publication of over 200 articles a year in journals pertaining to the upper quartile of the SCI, and numerous clinical guides, as well as the conduction of over 50 clinical trials. In the last year, the CIBERehd has obtained two large projects of the INPACTO programme and the CDTI, and moreover participates in many European consortiums. 51 Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM) www.ciberdem.org www.investigaladiabetes.org The CIBER in Diabetes and Associated Metabolic Disorders is a public state consortium established by the Carlos III Health Institute-Ministry of Science and Innovation. Constituted by 32 elite research groups in 19 associate institutions, it represents the biggest network of scientific diabetes research in Spain. Its objectives are to lead highest standards of research practice and to accelerate the translation of scientific results into clinical application. Director: Dr. Ramon Gomis CIBERDEM began its activity over three years ago and it is now time to take stock of its achievements. Some are already evident and among these is the qualitative leap forward as regards the number and excellence of publications. To this success we should add others such as the ability of groups to work together, especially in the case of clinical and basic research groups, which is a clear indication of our strong commitment to translational research, as well as an obvious demonstration that these associations between groups are advantageous when it comes to obtaining funding. With the objective of achieving pioneering biomedical advances, CIBERDEM fosters the development of projects in collaboration with other national and international institutes, and it counts on its own two technological platforms: the Biobank, which with more than 10.000 samples provides characterised human DNA and other types of biological samples to the scientific community; and the Metabolomics Platform which offers high performance technology for the profiling and identification of metabolites. The consortium looks to involve not only the scientific community but also the business sector in R&D investment. It offers companies the possibility of working together on research projects, scientific consultancy, organisation of scientific events and socially responsible corporate actions. Furthermore, it diffuses and divulges its scientific work through multiple actions such as the periodic organisation of scientific seminars and its annual Science Open Day always with the active collaboration of patient associations. In its mision to promote diabetes research CIBERDEM has created «Investiga la diabetes», an initiative which seeks to increase awareness of the diabetes problem in Spain. Its objective is to generate active participation from society and business with the aim of collecting funds which will enable the continued promotion and financing of scientific activity to find new means of preventing, diagnosing, treating and curing diabetes. 52 CIBER for Respiratory Diseases (CIBERES) www.ciberes.org The CIBER for respiratory diseases (CIBERES) is a networked, multidisciplinary and multicentre research institution integrating basic, clinical and populational research in respiratory illnesses. CIBERES is composed of 34 research groups, of which 60% belong to hospitals and 40% to universities and research centres. The Scientific director of CIBERES is Dr. Alvar Agustí (Chest Institute, Hospital Clinic). The administrative centre of CIBERES is in the Fundació Caubet-Cimera in Mallorca. Director: Dr. Àlvar Agustí The research activity of CIBERES is structured upon the basis of Corporate Research Programmes (Programes Corporatius de Investigació) (PCI). Each PCI comprises a series of projects that in a cooperative and integrated manner address a relevant healthcare problem in the field of respiratory disease. At present, CIBERES has 10 active PCIs: • Refractory asthma • Pulmonary fibrosis • Chronic obstructive pulmonary disease (COPD) • Thoracic cancer • Acute lung injuries • Sleep apnoea syndrome •Tuberculosis • Respiratory infections and sepsis • New therapeutic targets • H1N1 influenza In parallel to these PCIs, CIBERES has organized a series of research support platforms, such as: (1) Pulmonary biobank; (2) Technological development and transference; (3) Training program; and (4) Communications Department. CIBERES organizes annual scientific sessions and different monographic research seminars. 53 AIDS Research Network (RIS) www.retic-ris.net The AIDS Research Network (Red de Investigación en SIDA) (RIS) was created in 2003, and established the bases for driving vanguard research in the field of AIDS. In its second call (2007-2010), the Network has become consolidated and has centred its activity on the creation of common platforms (Cohorts, Laboratories and Resistances) that generate data and biological samples on which the research strategies are founded (clinico-epidemiological, clinico-therapeutic, immunopathogenesis and vaccines). Priority has focused on those projects that require a network in order to function, and on those subjects which are specific to our country, or in which we are able to make high-level original contributions. Director: Dr. Josep M. Gatell The AIDS network aims to address original problems through novel technological approaches. A series of large scale projects have been defined. The strategies used to reach the established objectives are based on references which can only be addressed through network-based effort and the creation of different platforms. A numerous cohort has been defined, corresponding to different groups of patients of homogeneous characteristics which allows us to evaluate the efficacy of new treatment protocols and intervention strategies, and to carry out studies on toxicity, resistances and pathogenesis. The particular characteristics of the HIV epidemic in our country allows the study of certain pathologies associated to HIV infection, such as hepatitis C. The AIDS network is composed of 19 research groups, 17 clinical healthcare groups and three associated groups, and includes groups with different experience in virology, immunology, and cellular and molecular biology that contribute complementary points of view and techniques to globally address complex problems in relation to the pathogenesis of HIV infection, such as immune reconstitution, virus-host interaction and the mechanisms underlying cell damage. 54 Spanish Multiple Sclerosis Network (REEM) www.reem.es The Spanish Multiple Sclerosis Network (Red Española de Esclerosis Múltiple) (REEM) is composed of basic and clinical investigators at national level, interested in the aetiopathogenesis of multiple sclerosis and in the development of new diagnostic and treatment methods with which to combat the disease. The Director of the institution is Dr. Pablo Villoslada, Head of the IDIBAPS Neuroimmunology team. Approved by the Instituto de Salud Carlos III in 2008, it is coordinated through the IDIBAPS by Dr. Pablo Villoslada and his management team, composed of a project manager and an assistant. Director: Dr. Pablo Villoslada The REEM has three objectives: • Development of a cooperative research programme on the aetiology, diagnosis and treatment of multiple sclerosis. • Promotion of the creation of shared resources among the different centres participating in the REEM, such as biobanks or clinical databases. • Training of young investigators in the knowledge of multiple sclerosis, based on courses, conferences and stays in other laboratories. Multiple sclerosis presently affects over two million people throughout the world, and our greatest challenge is to improve the quality of life of the affected patients. 55 Networked Biomedical Research Support Consortium (Consorcio de Apoyo a la Investigación Biomédica en Red) Spanish Clinical Trials Platform (Plataforma Española de Ensayos Clínicos, CAIBER) The CAIBER is composed of 40 Central Units of Clinical Research in Clinical Trials (Unidades Centrales de Investigación Clínica en Ensayos Clínicos, UCICEC), distributed in centres with research excellence in 16 Spanish Autonomous Communities, coordinated by the Central Unit of the CAIBER (UCCA), located in the central or core facilities of the CAIBER in the Instituto de Salud Carlos III. Different clinical investigators of the IDIBAPS form part of the UCICEC. The aim of the CAIBER is to promote the development of clinical research programs and clinical trials generated internally and conducted on a networked basis, particularly those lacking commercial interest, together with preventive, diagnostic, therapeutic and services studies, in the subject areas reflected in the Strategic Action in Health, as most relevant groups of social and healthcare interest. The idea is to facilitate and promote the conduction of multicentre clinical trials that are safe, rigorous, controlled and with guarantees for preserving quality of the study, patient safety and data reliability. 56 INTRODUCTION CIBERs and RETICs in which IDIBAPS takes part The IDIBAPS also actively participates in the rest of CIBER and RETIC research networks, through its research teams: Networked Biomedical Research Centres (CIBERs) CIBER IDIBAPS Team Principal investigator CIBERdem - Diabetes y enfermedades metabolicas Diabetes: metabolic and molecular networks Anna Maria Novials Sardà CIBERdem - Diabetes y enfermedades metabólicas Genomic Programming of Beta Cells and Diabetes Jorge Pedro Ferrer Marrades CIBERdem - Diabetes y enfermedades metabólicas Diabetes: metabolic and molecular networks Ramon Gomis Barbarà CIBERehd - Enfermedades hepáticas y digestivas Physiopathology and treatment of ascites and altered renal function in liver cirrhosis Vicente Arroyo Pérez CIBERehd - Enfermedades hepáticas y digestivas Liver hemodynamics and portal hypertension. Digestive bleeding secondary to ruptured esophageal varicose veins Jaime Bosch Genover CIBERehd - Enfermedades hepáticas y digestivas Hepatic oncology Jordi Bruix Tudó CIBERehd - Enfermedades hepáticas y digestivas Gastrointestinal and pancreatic oncology Antoni Castells Garangou CIBERehd - Enfermedades hepáticas y digestivas Viral hepatitis in the immune competent host and in liver transplant patients Xavier Forns Bernhardt CIBERehd - Enfermedades hepáticas y digestivas Inflammatory bowel disease (IBD) Julián Panés Díaz CIBERehd - Enfermedades hepáticas y digestivas Cholestasis and bone pathology Albert Parés Darnaculleta CIBERehd - Enfermedades hepáticas y digestivas Liver transplantation and graft viability Antonio Rimola Castellà CIBERehd - Enfermedades hepáticas y digestivas Mitochondrial regulation of cell death and steatohepatitis José Carlos Fernández-Checa CIBERned - Enfermedades neurodegenerativas Neurodegenerative diseases: Clinical and experimental research Eduard Tolosa Sarró CIBERned - Enfermedades neurodegenerativas Neuropharmacology and experimental neuropathology. Guadalupe Mengod CIBERned - Enfermedades neurodegenerativas Cellular biology of pathological processes Jordi Alberch CIBERned - Enfermedades neurodegenerativas Neurobiology Unit Ramon Trullas Oliva CIBERned - Enfermedades neurodegenerativas Neuropharmacology and experimental neuropathology. Eduard Rodríguez Farré CIBERer - Enfermedades raras Secondary lesions due to chronic alcohol ingestion, muscle pathology Francesc Cardellach López CIBERer - Enfermedades raras Fetal and perinatal medicine Eduard Gratacós Solsona CIBERer - Enfermedades raras Genetics Montserrat Milà Recasens CIBERer - Enfermedades raras Hereditary metabolic diseases Maria Antònia Ribes Rubio CIBERes - Enfermedades respiratorias Physiopathological mechanisms of respiratory illnesses Joan Albert Barberà Mir CIBERes - Enfermedades respiratorias Applied research in infectious respiratory diseases, critically ill patients and lung cancer José María Montserrat Canal CIBERes - Enfermedades respiratorias Clinical and Experimental Respiratory Immunoallergy (IRCE) César Picado Vallés CIBERes - Enfermedades respiratorias Applied research in infectious respiratory diseases, critically ill patients and lung cancer Antoni Torres Martí 57 CIBER IDIBAPS Team Principal investigator CIBERes - Enfermedades respiratorias Respiratory biophysics and bioengineering Ramón Farré CIBERobn - Fisiopatología de la obesidad y nutrición Hypertension, lipids and cardiovascular risk Emili Ros Rahola CIBERobn - Fisiotatología de la obesidad y nutrición Secondary lesions due to chronic alcohol ingestion, muscle pathology Ramon Estruch Riba CIBERsam - Salud Mental Biological bases of psychiatric disorders and nuclear psychiatry Miguel Bernardo Arroyo CIBERsam - Salud Mental Biological bases of psychiatric disorders and nuclear psychiatry Eduard Vieta Pascual CIBERsam - Salud Mental Neuropharmacology and experimental neuropathology Francesc Artigas CIBER-BBN - Bioingeniería, Biomateriales y Nanomedicina (Grupo Asociado) Respiratory biophysics and bioengineering Ramón Farré CIBER-BBN - Bioingeniería, Biomateriales y Nanomedicina Respiratory biophysics and bioengineering Javer Pavia Cooperative Health Research Thematic Networks (RETICs) 58 RETIC IDIBAPS Team Principal investigator REDINSCOR - Red de Investigación en Insuficiencia Cardíaca en España Arrhythmias, resynchronization and cardiac imaging Josep Brugada Terradellas RIS - Red Española de Investigación en SIDA Infectious diseases and AIDS Josep Maria Gatell Artigas REIPI - Red española de investigación en patología infecciosa (REIPI) Immune receptors of the innate and adaptive system Francisco Lozano Soto HERACLES - Determinantes Genéticos y Ambientales de la Disfunción Vascular en la Hipertensión y Cardiopatía Isquémica Atherosclerosis and coronary disease Maria Magdalena Heras Fortuny HERACLES - Determinantes genéticos y ambientales de la disfunción vascular Hemotherapy - hemostasis Ginés Escolar Albaladejo Red de Terapia Celular Cellular biology of pathological processes Josep Mª Canals Coll RETICEF - Red temática de investigación cooperativa en envejecimiento y fragilidad Neuropharmacology and experimental neuropathology Coral Sanfeliu Pujol RECAVA - Factores de Riesgo, Evolución y Tratamiento de las Enfermedades Cardiovasculares y sus Mecanismos Diagnosis and therapy in oncology Maria Àfrica Muxí Pradas REDINREN - Red de Investigación en Enfermedades Renales Nephro-urological diseases and kidney transplantation Esteban Poch López de Briñas REDINREN - Red de Investigación en Enfermedades Renales Nephro-urological diseases and kidney transplantation Josep Maria Campistol Plana RED DE CANCER - Red temática de investigación cooperativa de cáncer Hematological oncology Francisco Cervantes Requena RED DE CANCER - Red temática de investigación cooperativa de cáncer Hematological oncology Juan Bladé Creixenti RED DE CANCER - Red temática de investigación cooperativa de cáncer Cell proliferation and signaling Oriol Bachs Valldeneu RED DE CANCER - Red temática de investigación cooperativa de cáncer Hematopoietic progenitor cell transplantation Álvaro Urbano Ispizúa RED DE CANCER - Red temática de investigación cooperativa de cáncer Physiopathology and molecular bases in hematology Dolors Colomer Pujol RED DE CANCER - Red temática de investigación cooperativa de cáncer Diagnosis and therapy in oncology Francisca Eugenia Pons Pons RETIC IDIBAPS Team Principal investigator RED DE CANCER - Red temática de investigación cooperativa de cáncer Human and experimental functional oncomorphology Elias Campo Guerri RED DE CANCER - Red temática de investigación cooperativa de cáncer Hematological oncology Emili Montserrat Costa RED DE CANCER - Red tematica de investigación cooperativa de cancer. Molecular and translational oncology Pedro Gascón Vilaplana RED DE CANCER - Red tematica de investigación cooperativa de cancer Cell proliferation and signaling Carles Enrich REEM - Red Española de Esclerosis Múltiple Clinical and experimental neuroimmunology Pablo Villoslada Díaz REEM - Red Española de Esclerosis Múltiple Clinical and experimental neuroimmunology Francesc Graus Ribas RIRAAF - Red de Investigación de Reacciones Adversas a Alérgenos y Fármacos Clinical and Experimental Respiratory Immunoallergy (IRCE) Joan Bartra Tomàs RIER - Red de investigación en inflamación y enfermedades reumáticas Inflammatory joint diseases (IJDs) Juan de Dios Cañete Crespillo RETIC de Biobancos Physiopathological mechanisms of respiratory illnesses Joan Albert Barberà Mir / Anna Bosch RETICS INNOVACIÓN - RETICS de Innovación en Tecnologías Médicas y Sanitarias Direction of Innovation, Hospital Clínic of Barcelona Juan Bigorra Llosas OFTARED - RETIC en Oftalmología Neurophysiology and functional studies of the nervous system Arcadi Gual 59 CENITS AND CONSOLIDERS CENITs and CONSOLIDERs In addition to the necessary traditional research projects, where a point line of investigation is financed, there are more ambitious long-term options. In effect, more important funding is possible for developing projects aimed at transference and the definition of settings for broad scientific collaboration. In this context, the Spanish Ministry of Science and Innovation promotes major initiatives within the setting of the Inventiveness Programme (Programa Ingenio). CONSOLIDER is a strategic line focusing on research excellence, with the formation of large cooperative research groups. The increase in critical mass and research excellence through this programme makes it possible to improve the competitiveness of the Spanish research groups. The CENIT programme (National Strategic Consortiums for Technological Research) (Consorcios Estratégicos Nacionales de Investigación Tecnológica) aims to stimulate cooperation in R&D+I among companies, universities public research organisms and centres, scientific and technological institutions and technological centres. In this way cooperation between the public and private sectors is reinforced. The IDIBAPS has again formed part of the Consolider and CENIT programmes with new projects in the calls for 2010: • CONSOLIDER: BRAINAGE - Brain dysfunction in ageing: relevance to Alzheimer’s disease A program headed by the Severo Ochoa Molecular Biology Centre (CBM) of the CSIC, with very active participation on the part of the IDIBAPS team, Neurodegenerative diseases. Its planned duration is until 2015, and the programme will make it possible to define the molecular and cellular mechanisms responsible for functional deterioration of the brain in ageing, and particularly in Alzheimer’s disease (AD) - validating this knowledge in primary diagnosis of the disease, its evolution and/or treatment. • CENIT: Projects evaluated and approved by the Industrial Technological Development Centre (Centro de Desarrollo Tecnológico Industrial, CDTI) - DENDRIA - Innovative Solutions Aimed at Accelerating Novel Drug Discovery and Development for Nervous System Pathologies. DENDRIA Consortium is composed of 12 specialized biopharmaceutical companies: Noscira, S.A. (leader company of the consortium), Faes Farma, S.A., Palau Pharma, S.A., Sylentis, S.A.U., Instituto Biomar, S.A., Biocross, S.L., Brainco Biopharma, S.L., Protein Alternatives, S.L., One Way Liver Genomics, S.L., Neurosciences Technologies, S.L., nLife Therapeutics, S.L. and Oryzon Genomics, S.A. The project also includes 24 state biomedical research centers, including three IDIBAPS teams: Respiratory biophysics and bioengineering, Systems neuropharmacology and Neurophysiology. - AMIT: Advanced Molecular Imaging Technologies. The AMIT consortium is composed of 10 companies and 13 public research organisms that have joined their efforts to overcome technological barriers in the field of molecular imaging technology, in benefit of Medicine and Biomedicine. This discipline offers important biological information in clinical medicine and biomedicine, and promises exponential expansion of its applications. However, in practice the development of its full potential is hampered by limiting factors, identified during the CDTEAM project; the solution of these problems would represent an important step forward, with technological, scientific and medical implications. The Respiratory Biophysics and Bioengineering team of the IDIBAPS participates in this project in reference to definition of the system, simulations and design, biomarkers and animal models, and in the integration and evaluations of the demonstrators. 60 INTERNATIONAL PROJECTION European projects and international networks International projection is one of the strategic objectives of IDIBAPS, with a view both to establishing collaborative ties with reference entities in other countries and to gain access to international calls for research funding. The presence of investigators of this Institute in major international projects is a growing reality. A good example is offered by the increasing presence of investigators of the IDIBAPS in research projects financed by the European Commission. At present we are participating in 86 projects financed by the European Commission (FPVI and FPVII). Of these projects we coordinate a total of 17; in 64 we participate as partners; and we have 5 monocontract Marie Curie projects. Of note is the fact that this year we have received coordination of the HEPTROMIC project (Genomic predictors and oncogenic drivers in hepatocellular carcinoma), headed by an ICREA investigator (Dr. Josep M. Llovet). This project aims to establish a new approach to the fight against hepatocellular carcinoma (www.heptromic.eu). We also wish to mention that in July 2010, the IDIBAPS - together with the CDTI - organized a Spanish-French Partnering Session involving Catalan and French investigators, with a view to establishing new collaborations. The collaborative projects in which the IDIBABPS participates are not limited to Europe. In the year 2010 we also participated in 8 projects financed by the United States National Institutes of Health, with the following working teams: Mitochondrial regulation of cell death and steatohepatitis; Genomic programming of beta-cells and diabetes; Human and experimental functional oncomorphology; Liver transplantation and graft viability; Damage secondary to chronic alcohol consumption; Muscle disease; and Biological bases of psychic disorders and nuclear psychiatry. Some of the international networks in which the IDIBAPS participates with its investigators of greatest projection are presented below: European Clinical Research Infrastructures Network and biotherapy facilities: Preparation Phase for the Infrastructure (ECRIN-PPI) Coordinating centre: INSERM - DRCT Institut Thématique Santé Publique Coordinator of the Spanish node: Xavier Carné PI IDIBAPS: Xavier Carné 2008 - 2011 Funding source: European Commission Official code: 211738 NoE - Diagnostic Molecular Imaging (DiMI) Coordinating centre: Klinikum Der Universität München PI IDIBAPS: Anna Planas-Obradors 2005 - 2010 Funding source: European Commission Official code: LSHB-CT-2005-512146 NoE-Strengthen and develop scientific and technological excellence in research and therapy of leukemia (CML,AML,ALL,CLL,MDS,CMPD) by integration of the leading national leukemia networks and their interdisciplinary partner groups in Europe (EUROPEAN LEUKEMIANET) Coordinating centre: Ruprecht-Karls-Universität Heidelberg PI IDIBAPS: Emili Montserrat 2004 - 2010 Funding source: European Commission Official code: LSHC-CT-2004-503216 61 NoE - Genetic and environmental risk factors for melanoma: translation into behavioural change (GenoMel) Coordinating centre: University of Leeds PI IDIBAPS: Susana Puig 2005 - 2010 Funding source: European Commission Official code: LSHM-CT-2006-018702 NoE - Integrated Genomics, Clinical Research and Care in Hypertension (InGenious Hypercare) Coordinating centre: ISCCS Instituto Auxologico Italiano PI IDIBAPS: Antonio Coca 2006 - 2010 Funding source: European Commission Official code: LHSM-CT-2006-037093 NoE - European AIDS Treatment Network (NEAT) Coordinating centre: Instituto Nazionale per le Malattie Infettive PI IDIBAPS: Josep Maria Gatell 2007 - 2012 Funding source: European Commission Official code: LSHP-CT-2006-037570 Estudio de la genómica de Leucemia Linfática Crónica (International Cancer Genome Consortium) Coordinating centre: Hospital Clínic de Barcelona - Fundació Clínic Coordinator of the Spanish node: Elías Campo PI IDIBAPS: Elías Campo 2009 - 2012 Funding source: MICINN - ISCIII (Spanish part) Hepatocellular carcinoma (HCC) Genomic Consortium (HCC Genomic Consortium - AARC) Coordinating centre: IDIBAPS LLOVET-BAYER, Josep M. PI IDIBAPS: Josep Maria Llovet 2009 - 2011 Funding source: American Association for Cancer Research 62 BIOTRACK BIOTRACK is a co-funded project by the Marie Curie Actions of the 7th Framework Program of the European Commission and the IDIBAPS consortium for the Professional Training and Career Development in Biomedicine. With this programme, IDIBAPS creates new positions and helps researchers in their further development and expertise, to keep being part of the most productive Biomedical Research Consortium in Southern Europe. For more information visit: www.idibaps.org/biotrack 63 TRAINING Research seminars The research seminars of the Biomedical Research Institute August Pi i Sunyer (IDIBAPS) reflect clear teaching dedication, as well as being orientated towards the creation of networks. The speakers participating in the seminars organized by this Institute always offer added value that can contribute to the knowledge of our investigators. The goal is to share knowledge as it becomes available, with the consolidation of alliances all over the world in order to secure better research. The institutional seminars organized by the management of IDIBAPS during the year 2010 have been the following: • Neurocritical care of stroke Stephan A. Mayer Professor of Neurology and Neurological Surgery, Columbia University College of Physicians & Surgeons; Director, Neurological Intensive Care Unit, New York Presbyterian Hospital/Columbia • The chemical environment and the neurodevelopment Jordi Sunyer Centre for Research on Environmental Epidemiology (CREAL), Barcelona • Cortex and Memory: Emergence of a New Paradigm Joaquin M. Fuster Professor of Psychiatry and Cognitive Neuroscience, University of California Los Angeles • Seeing and hearing actions: Phenomenology and neural correlates Salvatore M Aglioti Cognitive and Social Neuroscience Laboratory Sapienza University of Rome (Italy) • Pattern recognition proteins containing fibrinogen-related domains: The case of FIBCD1, a new acetyl-group binding molecule with a possible role as a chitin-receptor Uffe Holmskov Head of Institute of Molecular Medicine Winsløwparken, Odense (Denmark) • From Molecules to Nutritional Interventions for Healthy Aging Rafael de Cabo Ph.D., Investigator; Aging, Metabolism, and Nutrition Unit; National Institutes of Aging (NIA-NIH), Bethesda, USA • TAM receptor regulation of the innate immune response Greg Lemke Molecular Neurobiology Laboratory, Immunobiology and Microbial Pathogenesis Laboratory, The Salk Institute (La Jolla) • Identification of drivers through sequencing in cancer Jessica Zucman-Rossi Head of Inserm unit U674, Génomique Fonctionnelle des tumeurs solides • Harnessing autoregulatory T-Cell memory for the treatment of autoimmune disease Pere Santamaria Department of Microbiology & Infectious Diseases Chair, Julia Mc Farlane Diabetes Research Centre (Calgary) Apart from the institutional seminars, the setting of IDIBAPS offers numerous scientific sessions and seminars from the other institutions in the consortium: the Hospital Clínic de Barcelona, the University of Barcelona School of Medicine, and the Barcelona Biomedical Research Institute of the CSIC. In the year 2010 alone, under the communications coordination of the IDIBAPS, over 100 activities were registered in the IDIBAPS website, related to its research activities, and over 200 scientific seminars were announced in the weekly sessions calendar. 64 BIOTRACK Doctoral theses The training dedication of the IDIBAPS is also reflected by the large number of doctoral theses that are driven and supported by the IDIBAPS integrated members. A list is provided below of the 69 doctoral theses directed by investigators from this centre during 2010: Author Title Doctorate thesis reader Morales, Emma M. Anàlisis de prevalença, despesa sanitària i morbimortalitat cardiovascular del dolor crònic no-oncológic a l’atenció primària Siso A Sara de Mateo López, Universitat de Barcelona Proteomic and molecular characterization of human spermatozoa in infertile patients and controls Oliva R Anna Serra-Pérez Efecte de la glucosa en un model d’isquèmia in vitro: modulació del factor Santalucia T, Planas A induït per hipòxia i de la mort cel·lular programada Ana Celia Adet Caldelari Neoplasias quísticas del páncreas: Análisis descriptivo y factores predictivos de malignidad Elena Alcover Bloch Seguimiento del desarrollo psicomotor de prematuros extremos mediante la Escala del Desarrollo Infantil de Kent(EDIK) cumplimnetada por los Figueras-Aloy J padres y situación neuroevolutiva a los 2 y 5 años Jordi Altirriba Gutierrez Bases Moleculares del efecto del tungstato de sodio sobre la plasticidad pancreática y Tmem27 Gomis R Blanca Alvarez Moya Regulación de la funcionalidad de K-Ras4B por unión A Cam y fosforilación de la Ser 181 Agell N Marta Amigo Correig Efecte Hipotalàmic del tungstat de sodi i la seva relació amb la via de la leptina: una possible teràpia antiobesitat Carmona MC, Gomis R Maria del mar Bennasar Sans Aplicación de la ecografia 4D-STIC(Spatio temporal image correlation) en el diagnóstico prenatal de las cardiopatías Martinez JM, Puerto B Carolina Berga Cullere Acontecimientos adversos producidos por medicamentos en pacientes hospitalizados: Influencia de las estrategias de actuación en su detección Codina C y prevención Guillem Bori Tuneu Utilitat de la histologia en el diagnòstic de la infecció de l’ artroplàstia de maluc Beatriz Bosch Capdevila Influencia de la reserva cognitiva en la estructura y funcionalidad cerebral Bartres D, Molinuevo JL en el envejecimiento sano y patologico David Calatayud Mizrahi La perfusión normotérmica “Ex - Situ” como continuación de la “ Recirculación Normotérmica” en la obtención de injertos hepáticos procedentes de donantes a corazón parado. Fondevila C, GarciaValdecasas JC Joaquim Carreras Esteban Factors pronòstics en neoplàsies limfoides B de cèl·lula petita Campo E Alba Carreras Palou Activation of bone Marrow Mesenchymal Stem Cells in a rat model of obstructive sleep apnea Farre R Jose Antonio Carrion Rodriguez Tratamiento de la hepatitis crónica C antes y despues del trasplante Hepático(TH) y diagnóstico no invasivo de su recurrencia tras el TH Forns X Carlos Cervera Alvarez Influencia de los poliformismos de los genes de la inmunidad innata en el desarrollo y evolución de las infecciones tras un trasplante de órgano sólido Lozano F, Moreno A Laura Conde del Campo Mecanismos moleculares implicados en el desarrollo del carcinoma escamoso de laringe Nadal A Desamparats Crespo March Caracterizacion de los factores de transcripcion de la familia Ikaros durante el desarrollo estriatal Canals JM Nuria Cruz Culebra Diagnostic specifiers of the onset, course and outcome of bipolar disorder Colom F, Vieta E Rogelio Cruz Martinez Cerebral and cardiac doppler parameters in the identification of fetuses with late-onset intrauterine growth restriction at risk of adverse perinatal and neurobehavioral outcome Gratacos E Sara de Mateo Lopez Proteomic and molecular characterization of human spermatozoa in infertile patients and control Oliva R Castells A, Navarro S Garcia S, Soriano A 65 Author 66 Title Doctorate thesis reader Emilio Fernandez Egea Diferencias en la respuesta a pruebas de reconocimiento facial de las emociones entre pacientes esquizofrénicos deficitarios versus esquizofrénicos no deficitarios Parellada E, Bernardo M Davinia Fernández Espejo The vegetative and the minimally conscious state: brain function, connectivity and structural abnormalities Junque C Alejandro Forner Gonzalez Actitud a seguir ante la detección de una lesión focal inferior o igual a 2 cm de tamaño en un paciente con cirrosis hepática. Bruix J Miguel Angel Galicia Paredes Aportaciones a al epidemiologia y a las manisfestaciones clínicas de las sobredosis causadas por la cocaina y las nuevas drogas de diseño Miro O, Nogue S Ana García Martínez Consecuencias clínicas de la persistencia de actividad inflamatoria en la arteritis de células gigantes. Estudio de factores implicados. Cid MC Yoelvis Garcia Mesa El ejercicio físico voluntario como terapia para la enfermedad de Alzheimer. Estudio en ratones tripletransgénicos 3xTg-AD Sanfeliu C Ellen Gelpi Mantius Fatal Human Tick-Borne Encephalitis: Immunohistochemical characterisation of viral distribution and inflammatory reaction Ribalta T Eva Giné Soca Estudi del fenomen de la transformació histològica en síndromes limfoproliferatives indolents Bosch F Albert Giralt Torroella Estudio de los procesos activadores de la patologia en la enfermedad de Huntington: Alteraciones en la plasticidad sinaptica y perspectivas terapeuticas Alberch J Marta Gomez Nuñez Vacunas con células dendríticas y pépticos en el tratamiento de las enfermedades neoplásicas Cervantes F Jose Maria Guilemany Toste Asociación de bronquiectasias pulmonares y patologia nasosinusal. Estudio de los aspectos epidemiológicos etiológicos, de diagnóstico y tratamiento Mullol J Eva Guisantes Pintos Injertos de tejido adiposo autólogo en la lipoatrofia facial de pacientes VIH+: Comparación de dos estrategias de tratamiento y utilidad de la tomografia computerizado en la evaluación de su durabilidad. Martinez-Chamorro E Raquel Horrillo Saura Paper de la ciclooxigenasa-2 i la 5-lipooxigenasa en la inflamació hepàtica i Claria J del teixit adipós. Laura Izquierdo Reyes Factores pronóstico moleculares en el carcinoma urotelial de tracto urinario superior Vincenzo La Mura Valor pronóstico de nuevos parámetros hemodinámicos en el tratamiento Bosch J de la hipertensión portal Laia Lladó Pelfort Paper del receptor 5HT 1A en el mecanisme d’ acció de psicofàrmacs Ingrid Lopez Lerma Estudio de moléculas de adhesión en procesos dermatológicos malignos(Micosis fungoide-síndrome de Sézary) y benignos mediados por Estrach MT células T Luis Mº Lozano Lizarraga Artroplastia total de rodilla en pacientes obesos graves y mórbidas Victor Angel Macias Hernandez Radioterapia hipofraccionada acelerada como tratamiento curativo del cáncer de próstata localizado: Análisis prospectivo de la toxicidad aguda y Biete A de la toxicidad tardía Marc Mejias Hernandez Implicació de l’ angiogènesi en al patofisiologia de la hipertensió portal Bosch J, Fernandez M Pedro Melgar Lesmes Fisiopatologia del edema y de la formacion de ascitis en la cirrosis hepática experimental Jimenez W Jose Maria Mora Guix Nuevo protocolo de lectura de imágenes y sistemas de clasificacion de las Suso S fracturas del humero proximal(FHP) Montserrat Moreno Sanchez Investigación de nuevas estrategias terapeúticas para la inflamación y la fibrosis hepática. Alcaraz A Artigas F, Celada MP Macule F, Segur JM, Suso S Bataller R Author Title Doctorate thesis reader Susagna Padrissa Altes Noves dianes terapèutiques en el trasplantament de fetge amb empelt de Peralta C, Rosello-Catafau J mida reduïda Nuria Palau Balaña Plasticitat de la cèlula Beta en l’ obesitat Gomis R Daniel Orós López Perinatal and neurodevelopmental outcome of late-onset growth restricted fetuses Figueras F Paola Paoletti Rubia Estudio de las vías de supervivencia y muerte neuronal en modelos de la nefermedad de Huntington Gines S Marta Perez de Lis Novo Impacto de la enfermedad cardiovascular en el síndrome de Sjögren primario Coca A, Ramos M Isabel Puig-pey Comas Phenotypic and transcriptional biomarkets in organ transplantation Sanchez-Fueyo A Santseharay Ramirez Almeida Estudio de la evolución genética y la compartimentalización del virus de la Forns X hepatitis C Mariana Rickmann Ashwell Estudio de los tocotrienoles como inductores de muerte programada en las células estrelladas del páncreas Vaquero E Francisco Rodriguez Moranta Prevención del cáncer colorrectal: Nuevas estrategias de cribado, vigilancia y quimioprofilaxis Castells A, Pique JM Ignasi Salaet Madorran Paper de P27kip1 en la respiració cel·lular Bachs O Jacobo Sellares Torres Fisiopatología y papel de la ventilación no invasiva en el fracaso del weaning Ferrer M, Torres A Juan Turnes Vazquez Implicaciones pronósticas de la reducción farmacologica de la presión portal en pacientes con cirrosis hepatica.Mecanismos fisiopatologicos de Bosch J, Garcia-Pagan JC no respuesta a los betabloqueantes y nuevas estrategias terapeuticas Xabier Urra Nuin Implicaciones Clínicas y pronósticas del síndrome de inmunodepresión mediado por el ictus agudo Chamorro A, Planas A Nasiruddin Khan Interaction between cocoa polyphenols and inflammatory biomarkers of atherosclerosis in high-risk subjects for cardiovascular disease Andres-Lacueva C, Estruch R, Monagas M Raquel Bermudo Gascón Perfiles transcripcionales del cáncer de próstata Fernandez PL Benito Herreros Gilarte Repercusiones Cardiovasculares de la Anorexia Nerviosa Mont L Gemma Gay Jordi Efecto del ejercicio crónico en el desarrollo de fibrosis cardíaca: mecanismos implicados Mont L, Serrano-Mollar A Gelabert Arbiol E. Depresión posparto y rasgos de la personalidad Martin-Santos R Marta Díez Cuñado Mecanismos implicados en la diferenciación de las células progenitoras endoteliales durante el remodelado vascular pulmonar Peinado V, Barbera JA María Umpiérrez Impact of aging and physical exercise on transcriptional and epigenetic profiles (brain and cardiac studies) Kaliman P María Jesús Álvarez López Estudio epigenético y transcripcional de un modelo murino de envejecimiento acelerado (estudio en linfocitos) Kaliman P Julita de la Vega Arias Real time analysis of hippocampal activity for the control of external devices. Sanchez-Vives MV Rosario Jesús Perea Palazón Utilidad de la resonancia magnética en pacientes con fibrilación auricular tributarios de tratamiento con ablación percutánea de las venas pulmonares Brugada J, DeCaralt MT Lluís González de Paz, Universitt de Barcelona. Vigència de la Carta de Drets i Deures dels ciutadans en relació a la Salut i l’Atenció Sanitària entre els usuaris dels serveis d’Atenció Primària de Salut Siso A, Navarro D 67 IDIBAPS and society This research centre does not wish to conclude its work with new biomedical discoveries. The idea is to inform society of the advances, of the basic and healthcare novelties, and the principal research lines being pursued. The responsibility of informing society is based upon the principle that a well informed person is a healthier person. A key aspect is the relationship with the communication and news media, where IDIBAPS and its professionals have a very important presence. But this is not the only way to reach society. Thanks to the involvement of many investigators, under communications coordination of the IDIBAPS, each year numerous informative activities are promoted or shared with the contribution of the Institute. Some noteworthy examples are the following: • School visits to the laboratories of the IDIBAPS. Each year different centres visit the scientific facilities of the IDIBAPS, where they can interact with professionals in different fields. Some of these visits are set within the ESCOLAB project, promoted and propelled by the Barcelona city authorities. • Virtual Laboratory divulgating project. Thanks to initial funding by the Generalitat de Catalunya through the ACDC aids, and posteriorly with the implication of the Foundation “La Caixa”, the IDIBAPS coordinates informative activities targeted at school children. The generation of contents linked to the teaching programmes of the secondary school students is carried out in collaboration with many specialists and with the company Ambientech, dedicated to the creation and presentation of contents of this kind. • World Brain Week. This is an initiative promoted by the Dana Foundation and organized by the Centre de Regulació Genòmica (CRG) and the Institut d’Educació de Barcelona, in the setting of the programme Barcelona Ciència 2010. The World Brain Week was held in the month of March simultaneously in 76 countries with over 2200 collaborating centres, with the aim of informing about the efforts being made in the study of the human brain. In Catalonia over 30 groups participated, including the IDIBAPS team in Brain ischemia: Clinical and experimental studies, with Dr. Anna M. Planas and Dr. Guadalupe Soria of the IIBB-CSIC-IDIBAPS as leading experts. • Cell therapy, the Medicine of the future. Cell therapy is one of the treatment alternatives of the future, and aims to restore the function of organs and tissues damaged as a result of trauma or chronic degenerative illnesses. In order to make this therapy known, Dr. Josep M. Canals, of the IDIBAPS team Cellular biology of disease processes, and a Professor of the Faculty of Medicine of the University of Barcelona, has developed and directed the informative video: “Cell therapy, the Medicine of the future”. This documentary has been produced by the Audiovisual Department of the University of Barcelona, and has been coordinated by the Cell Therapy Network of the Instituto de Salud Carlos III. 68 69 Inflammatory joint diseases 72 Systemic autoimmune diseases 73 Infectious diseases and AIDS 79 Immune receptors of the innate and adaptive system 89 Musculoskeletal repair and plasticity 92 Immunogenetics of the autoinflammatory response 95 Emergencies: Processes and pathologies 97 Molecular and cellular bases of inflammation. Structural and biological mass spectrometry 100 AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Team envolved in: Red de Investigación en Inflamación y Enfermedades Reumáticas (RIER) Inflammatory joint diseases Group Members TEAM LEADER Raimon Sanmartí (Hospital Clínic) Tel.: 93 227 54 00 (Ext.: 2236/2604) E-mail: sanmarti@clinic.ub.es IDIBAPS MEMBERS: Juan D. Cañete (Hospital Clínic) Postdoctoral fellows: Raquel Celis (Fundació Clínic) Maria Victoria Hernández (Fundació Clínic) Research Fellows: Virginia Ruiz-Esquide (Fundació Clínic) Collaborators: Guadalupe Ercilla (Hospital Clínic) Jaume Pomés (Hospital Clínic) Xavier Tomas (Hospital Clínic) Odette Viñas (Hospital Clínic) J.A. Gómez-Puerta (Fundació Clínic) Strategic Objectives PUBLICATIONS Promotion of research into the most prevalent chronic forms of arthritis: rheumatoid arthritis (RA) and spondyloarthritis, including psoriatic arthritis. Originals I.F.: 10,06 Main Lines of Research 1. Prognostic factors in initial arthritis a.Prognostic factors (clinical and immunogenetic) in patients with initial rheumatoid arthritis. b.Production of new synthetic citrullinated peptides for the design of immunoassays with diagnostic and prognostic value in recent-onset rheumatoid arthritis. 2. Immunopathology of synovitis in chronic arthritis a.Utility in differential diagnosis and prognosis. Immunopathological changes related to biological treatments. Synovial response biomarkers. 3. Role of synovial fibroblasts in arthritis refractory to antirheumatic treatment 4. Role of autoinflammatory genes in the pathogenesis of chronic arthritis a. MEFV gene mutations in intermittent arthritis. 1 Alonso A, Julia A, Tortosa R, Canaleta C, Canete JD, Ballina J, Balsa A, Tornero J, Marsal S. CNstream: A method for the identification and genotyping of copy number polymorphisms using Illumina microarrays. BMC BIOINFORMATICS, 2010. 11:-. I.F.:3,43. 2 Graell E, Arostegui JI, Sanmarti R, Blanco FJ, Yague J, Pinto JA, Plaza S, FernandezSueiro JL, Gonzalez A, Canete JD. Possible association between NOD2 variants and joint surgery in psoriatic arthritis. CLIN EXP RHEUMATOL, 2010. 28:30-34. I.F.:2,40. 3 Balsa A, DelAmo J, Blanco F, Caliz R, Silva L, Sanmarti R, Martinez FG, Tejedor D, Artieda M, Pascual-Salcedo D, Oreiro N, Collado MD, Andreu JL, Graell E, Simon L, Martinez A, Mulero J. Prediction of functional impairment and remission in rheumatoid arthritis patients by biochemical variables and genetic polymorphisms. RHEUMATOLOGY, 2010. 49:458-466. I.F.:4,24. Editorials I.F.: 8,11 1 Canete JD, Celis R, Hernandez V, Pablos JL, Sanmarti R. Synovial immunopathological changes associated with successful abatacept therapy in a case of severe refractory psoriatic arthritis. ANN RHEUM DIS, 2010. 69:935-U195. I.F.:8,11. Multicentrics I.F.: 8,11 1 Garcia-Doval I, Perez-Zafrilla B, Descalzo MA, Rosello R, Hernandez MV, GomezReino JJ, Carmona L. Incidence and risk of hospitalisation due to shingles and chickenpox in patients with rheumatic diseases treated with TNF antagonists. ANN RHEUM DIS, 2010. 69:1751-1755. I.F.:8,11. 72 AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Systemic autoimmune diseases Strategic Objectives Group Members TEAM LEADER Dr. Ricard Cervera Segura (Hospital Clínic) Tel.: 93 227 57 74 Fax: 93 227 17 07 E-mail: rcervera@clinic.ub.es IDIBAPS MEMBERS: Gerard Espinosa Garriga (Hospital Clínic) Miguel Ingelmo Morín (Hospital Clínic) Manuel Ramos Casals (Hospital Clínic) Alfredo Adán (Hospital Clínic) Albert Bové (Facultat de Medicina) Ricardo P. Casaroli (Hospital Clínic) Maria Cinta Cid (Hospital Clínic) José Hernández Rodríguez (Hospital Clínic) Elena Millá (Hospital Clínic) Research Fellows: Joan Plaza Nicolau (Hospital Clínic) Ana García Martínez (Hospital Clínic) Sergio Prieto (Hospital Clínic) Georgina Espígol (IDIBAPS) Marc Corbera (IDIBAPS) Montserrat Butjosa (Hospital Clínic) Miguel Angel Plasín (Hospital Clínic) Guillermo Pons-Estel (IDIBAPS) Juan Carlos Mejía (Hospital Clínic) Cándido Díaz-Lagares (Hospital Clínic) Ester Planas (IDIBAPS) Administrative Staff: Isabel Chaves (Hospital Clínic) Collaborators: Silvia Bucciarelli (Hospital Clínic) Xavier Bosch Aparici (Hospital Clínic) María Teresa Sainz de la Maza (Hospital Clínic) Antoni Sisó (GESCLINIC) Visiting Scientists: María Kourilovitch (Cuenca, Ecuador) Marta Pérez de Lis (Vigo) Roberto Pérez-Alvarez (Vigo) Rafael Belenguer (València) Miriam Akasbi (Madrid) Miriam Gandía (Cádiz) The Systemic Autoimmune Diseases research group promotes basic, clinical and translational research in these diseases in a multidisciplinary manner, with the participation of members of the following Departments: Autoimmune Diseases, Ophthalmology, Internal Medicine, Nephrology, Immunology, Hemostasis, Hepatology, Obstetrics and Dermatology, among others. These activities are carried out in close collaboration with different international work groups, of which the team members are national and/or international coordinators: European Working Party on Systemic Lupus Erythematosus (EWPSLE), European Forum on Antiphospholipid Antibodies (EFAPL), Catastrophic Antiphospholipid Syndrome (CAPS) Registry Project Group, International Pediatric Register of Antiphospholipid Syndrome (Ped-APS Register), Systemic Lupus International Collaborative Centers (SLICC), Sjögren’s Syndrome-Hepatitis C Virus (SS-HCV) Heart valve damage in a patient with primary antiphospholipid syndrome requiring valve replacement surgery. 73 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Systemic autoimmune diseases Study Group, HISPAMEC Study Group, Systemic Autoimmune Disease Study Group – Use of Biological Therapies (BIOGEAS), Spanish Sjögren’s Syndrome Multicenter Study Group (GEMESS), European Vasculitis Study Group (EUVAS), European League Against Rheumatism (EULAR) Systemic Vasculitis Task Force, EULAR Standing Committee for International Clinical Studies Including Therapeutics, and the American College of Rheumatology (ACR) Work Group for Development of Classification Criteria for Rheumatic Polymyalgia, among others. Main Lines of Research 1. Systemic lupus erythematosus and antiphospholipid syndrome: • Epidemiological multicenter studies on the clinical manifestations and long-term evolution of these diseases. • Clinical trials in new biological therapies. • Study of genetic polymorphisms as risk factors of the different clinical manifestations of these diseases. • Study of the cardiovascular and endothelial damage risk factors found in these diseases. • Basic research in animal models on the mechanism of action of antiphospholipid antibodies. 2. Sjögren’s syndrome and autoimmune manifestations of hepatitis C virus infection: • Epidemiological multicenter studies on the clinical manifestations and longterm evolution of these diseases. • Study of lymphomas associated with Sjögren’s syndrome. • Study of the cardiovascular and endothelial damage risk factors found in this syndrome. • Clinical and basic studies in mixed Cryoglobulinemia. Emergent Group Autoimmune ophthalmopathy Group Leader: Alfredo Manuel Adan (Hospital Clínic) This group studies the clinical, diagnostic and therapeutic aspects of autoimmune eye diseases. The scientific contribution of this line of research is very competitive and is internationally renowned. The group also studies the genetic polymorphisms of uveitis as risk factors for the different clinical manifestations of the disease, and participates in different clinical trials involving novel biological treatments. research Group Systemic vasculitis Group Leader: Maria Cinta Cid (Hospital Clínic) This group studies the clinical, diagnostic and therapeutic aspects of systemic vasculitic disorders, as well as the mechanisms producing vascular damage in these diseases. The scientific contribution of this line of research is very competitive and is internationally renowned. Clinical studies are also made of the systemic vascular lesions characterizing giant cell arteritis, exploring the mechanisms that produce these vascular lesions in this disease, and participating in different clinical trials involving new biological treatments. The group also coordinates the Spanish registries of vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA) and Behçet’s disease. 74 • International registry of treatments with biological drugs for systemic autoimmune disorders (BIOGEAS). 3. Systemic vasculitis: • Investigation of the mechanisms involved and the clinical consequences of the persistence of vascular inflammation in giant cell arteritis. Identification of new therapeutic targets. • Study of the mechanisms involved in the development of abnormal vascular remodelling (occlusion or dilatation) and its clinical consequences. • Development of an organ culture model for studying the factors implicated in the perpetuation of inflammation and in vascular remodelling. • Study of the prevalence of large vessel inflammatory involvement at the start and during the course of giant cell arteritis. • Clinical trials promoted fundamentally for investigating new biological therapies in the management of systemic vasculitis. • Spanish systemic vasculitis registry. • Spanish Behçet’s disease registry. 4. Autoimmune ophthalmopathy: • Clinical trials in new biological therapies. • Study of genetic polymorphisms in uveitis as risk factors of the different clinical manifestations of such ophthalmological disorders. • Treatment with anti-Vascular Endothelial Growth Factor (VEGF) drugs for choroid neovascularization and cystic macular edema secondary to uveitis. AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Systemic autoimmune diseases PUBLICATIONS Originals I.F.: 173,60 1 Houssiau FA, D’cruz D, Sangle S, Remy P, Vasconcelos C, Petrovic R, Fiehn C, Garrido ED, Gilboe IM, Tektonidou M, Blockmans D, Ravelingien I, LeGuern V, Depresseux G, Guillevin L, Cervera R. Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. ANN RHEUM DIS., 2010. 69:2083-2089. I.F.:8,11. 2 Espinosa C, Cervera R. Belimumab, a blys-specific inhibitor for the treatment of systemic lupus erythematosus. DRUG TODAY, 2010. 46:891-899. I.F.:1,59. 3 Soto-Cardenas MJ, Perez-De-Lis M, Bove A, Navarro C, Brito-Zeron P, Diaz-Lagares C, Gandia M, Akasbi M, Siso A, Ballester E, Torres A, RamosCasals M. Bronchiectasis in primary Sjogren’s syndrome: prevalence and clinical significance. CLIN EXP RHEUMATOL, 2010. 28:647-653. I.F.:2,40. 4 Perez-De-Lis M, Akasbi M, Siso A, Diez-Cascon P, Brito-Zeron P, DiazLagares C, Ortiz J, Perez-Alvarez R, Ramos-Casals M, Coca A. Cardiovascular risk factors in primary Sjogren’s syndrome: a case-control study in 624 patients. LUPUS, 2010. 19:941948. I.F.:2,59. 5 Pinazo MJ, Espinosa G, Gallego M, Lopez-Chejade PL, Urbina JA, Gascon J. Case Report: Successful Treatment with Posaconazole of a Patient with Chronic Chagas Disease and Systemic Lupus Erythematosus. AM J TROP MED HYG, 2010. 82:583587. I.F.:2,80. 6 Ramos-Casals M, Brito-Zeron P, Perez-De-Lis M, Diaz-Lagares C, Bove A, Soto MJ, Jimenez I, Belenguer R, Siso A, Muxi A, Pons F. Clinical and Prognostic Significance of Parotid Scintigraphy in 405 Patients with Primary Sjogren’s Syndrome. J RHEUMATOL, 2010. 37:585-590. I.F.:3,85. 308 patients stratified by gender. CLIN EXP DERMATOL, 2010. 35:729-735. I.F.:1,55. 12 Adan A, Serra-Grabulosa JM. Effects of caffeine and glucose, alone and combined, on cognitive performance. HUM PSYCHOPHARM CLIN, 2010. 25:310-317. I.F.:2,50. 7 Ruiz-Irastorza G, Ramos-Casals M, 13 Mendoza-Pinto C, Garcia- Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. ANN RHEUM DIS, 2010. 69:20-28. I.F.:8,11. Carrasco M, Jimenez-Hernandez M, Hernandez CJ, Riebeling-Navarro C, Zavala AN, Recabarren MV, Espinosa G, Quezada JJ, Cervera R. Etiopathogenesis of Behcet’s disease. AUTOIMMUN REV, 2010. 9:241-245. I.F.:6,37. 8 Martinez-Zamora MA, Tassies D, Carmona F, Espinosa G, Cerverac R, Reverter JC, Balasch J. Clot lysis time and thrombin activatable fibrinolysis inhibitor in severe preeclampsia with or without associated antiphospholipid antibodies. J REPROD IMMUNOL, 2010. 86:133140. I.F.:2,52. 14 Rojas-Villarraga A, Toro CE, Espinosa G, Rodriguez-Velosa Y, DuarteRey C, Mantilla RD, Iglesias-Gamarra A, Cervera R, Anaya JM. Factors influencing polyautoimmunity in systemic lupus erythematosus. AUTOIMMUN REV, 2010. 9:229-232. I.F.:6,37. 9 Vera-Recabarren MA, Garcia-Car- 15 Pisoni CN, Brucato A, Ruffatti rasco M, Ramos-Casals M, Herrero C. Comparative analysis of subacute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus: clinical and immunological study of 270 patients. BRIT J DERMATOL, 2010. 162:91-101. I.F.:4,26. A, Espinosa G, Cervera R, BelmonteSerrano M, Sanchez-Roman J, GarciaHernandez FG, Tincani A, Bertero MT, Doria A, Hughes GRV, Khamashta MA. Failure of Intravenous Immunoglobulin to Prevent Congenital Heart Block Findings of a Multicenter, Prospective, Observational Study. ARTHRITIS RHEUM-US, 2010. 62:1147-1152. I.F.:7,33. 10 Luceno F, Castilla JA, GomezPalomares JL, Cabello Y, Hernandez J, Marqueta J, Herrero J, Vidal E, Fernandez-Shaw S, Coroleu B. Comparison of IVF cycles reported in a voluntary ART registry with a mandatory registry in Spain. HUM REPROD, 2010. 25:30663071. I.F.:3,86. 11 Vera-Recabarren MA, GarciaCarrasco M, Ramos-Casals M, Herrero C. Cutaneous lupus erythematosus: clinical and immunological study of 16 Smithson A, Perello R, Aibar J, Espinosa G, Tassies D, Freire C, Castro P, Suarez B, Lozano F, Nicolas JM. Genotypes Coding for Low Serum Levels of Mannose-Binding Lectin Are Underrepresented among Individuals Suffering from Noninfectious Systemic Inflammatory Response Syndrome. CLIN VACCINE IMMUNOL, 2010. 17:447-453. I.F.:2,37. 75 AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Systemic autoimmune diseases 17 Serra-Grabulosa JM, Adan A, 22 Praprotnik S, Agmon-Levin N, Falcon C, Bargallo N. Glucose and caffeine effects on sustained attention: an exploratory fMRI study. HUM PSYCHOPHARM CLIN, 2010. 25:543552. I.F.:2,50. Porat-Katz BS, Blank M, Meroni PL, Cervera R, Miesbach W, Stojanovich L, Szyper-Kravitz M, Rozman B, Tomsic M, Shoenfeld Y. Prolactin’s role in the pathogenesis of the antiphospholipid syndrome. LUPUS, 2010. 19:1515-1519. I.F.:2,59. 18 Colli A, Mestres CA, Espinosa G, Plasin MA, Pomar JL, Font J, Cervera R. Heart valve surgery in patients with the antiphospholipid syndrome: analysis of a series of nine cases. EUR J CARDIO-THORAC, 2010. 37:154-158. I.F.:2,40. Bellalta M, Garcia-Martinez A, Espigol-Frigole G, Pla-Campo A, Hernandez-Rodriguez J, Cid MC. Increased expression of the endothelin system in arterial lesions from patients with giant-cell arteritis: association between elevated plasma endothelin levels and the development of ischaemic events. ANN RHEUM DIS, 2010. 69:434442. I.F.:8,11. L, Bae SC, Gordon C, Wallace DJ, Clarke A, Bernatsky S, Isenberg D, Rahman A, Alarcon GS, Gladman DD, Fortin PR, Sanchez-Guerrero J, Romero-Diaz J, Merrill JT, Ginzler E, Bruce IN, Steinsson K, Khamashta M, Petri M, Manzi S, Dooley MA, Ramsey-Goldman R, VanVollenhoven R, Nived O, Sturfelt G, Aranow C, Kalunian K, Ramos-Casals M, Zoma A, Douglas J, Thompson K, Farewell V. Prospective analysis of neuropsychiatric events in an international disease inception cohort of patients with systemic lupus erythematosus. ANN RHEUM DIS, 2010. 69:529-535. I.F.:8,11. 20 Ramos-Casals M, Garcia- 24 Quintana G, Coral-Alvarado P, Hernandez FJ, DeRamon E, Callejas JL, Martinez-Berriotxoa A, Pallares L, Caminal-Montero L, SelvaO’callaghan A, Oristrell J, Hidalgo C, Perez-Alvarez R, Mico ML, Medrano F, Gomez-De-La-Torre R, Diaz-Lagares C, Camps M, Ortego N, SanchezRoman J. Off-label use of rituximab in 196 patients with severe, refractory systemic autoimmune diseases. CLIN EXP RHEUMATOL, 2010. 28:468-476. I.F.:2,40. Aroca G, Patarroyo PM, Chalem P, Iglesias-Gamarra A, Ruiz AI, Cervera R. Single anti-P ribosomal antibodies are not associated with lupus nephritis in patients suffering from active systemic lupus erythematosus. AUTOIMMUN REV, 2010. 9:750-755. I.F.:6,37. 19 Lozano E, Segarra M, Corbera- 21 Siso A, Ramos-Casals M, Bove A, Brito-Zeron P, Soria N, Nardi N, Testi A, Perez-De-Lis M, Diaz-Lagares C, Darnell A, Sentis J, Coca A. Outcomes in Biopsy-Proven Lupus Nephritis Evaluation of 190 White Patients From a Single Center. MEDICINE, 2010. 89:300-307. I.F.:5,05. 76 23 Hanly JG, Urowitz MB, Su 25 Ramos-Casals M, Brito-Zeron P, Perez-De-Lis M, Jimenez I, Blanco MJ, Bove A, Soto MJ, Akasbi M, Diaz C, Sentis J, Siso A. Sjogren Syndrome or Sjogren Disease? The Histological and Immunological Bias Caused by the 2002 Criteria. CLIN REV ALLERG IMMU, 2010. 38:178185. I.F.:2,60. 26 O’neill S, Cervera R. Systemic lupus erythematosus. BEST PRACT RES CL RH, 2010. 24:841-855. I.F.:2,90. 27 Segarra M, Lozano E, CorberaBellalta M, Vilardell C, Cibeira MT, Esparza J, Izco N, Blade J, Cid MC. Thalidomide decreases gelatinase production by malignant B lymphoid cell lines through disruption of multiple integrin-mediated signaling pathways. HAEMATOL-HEMATOL J, 2010. 95:456-463. I.F.:6,42. 28 Houssiau FA, Vasconcelos C, D’cruz D, Sebastiani GD, Garrido ED, Danieli MG, Abramovicz D, Blockmans D, Cauli A, Direskeneli H, Galeazzi M, Gul A, Levy Y, Petera P, Popovic R, Petrovic R, Sinico RA, Cattaneo R, Font J, Depresseux G, Cosyns JP, Cervera R. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. ANN RHEUM DIS, 2010. 69:61-64. I.F.:8,11. 29 Galarza-Maldonado C, Kourilovitch MR, Molineros JE, Cardiel MH, Zurita L, Soroka NF, Yagur VY, Doukh N, Cervera R. The administration of low doses of rituximab followed by hydroxychloroquine, prednisone and low doses of mycophenolate mofetil is an effective therapy in Latin American patients with active systemic lupus erythematosus. AUTOIMMUN REV, 2010. 10:108-111. I.F.:6,37. 30 Espinosa G, Mendizabal A, Minguez S, Ramo-Tello C, Capellades J, Olive A, Cervera R. Transverse Myelitis Affecting More Than 4 Spinal Segments Associated with Systemic Lupus Erythematosus: Clinical, Immunological, and Radiological Characteristics of 22 Patients. SEMIN ARTHRITIS RHEU, 2010. 39:246-256. I.F.:4,72. AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Systemic autoimmune diseases 31 Ramos-Casals M, Tzioufas 3 Cervera R. Catastrophic antiphos- AG, Stone JH, Siso A, Bosch X. Treatment of Primary Sjogren Syndrome A Systematic Review. JAMA-J AM MED ASSOC, 2010. 304:452460. I.F.:28,90. pholipid syndrome (CAPS): update from the ‘CAPS Registry’. LUPUS, 2010. 19:412-418. I.F.:2,59. 32 Garcia-Martinez A, HernandezRodriguez J, Espigol-Frigole G, PrietoGonzalez S, Butjosa M, Segarra M, Lozano E, Cid MC. Clinical Relevance of Persistently Elevated Circulating Cytokines (Tumor Necrosis Factor alpha and Interleukin-6) in the LongTerm Followup of Patients With Giant Cell Arteritis. ARTHRIT CARE RES. 62 (6): 835-841. I.F.: 4,75 33 Urowitz MB, Gladman D, Ibanez D, Bae SC, Sanchez-Guerrero J, Gordon C, Clarke A, Bernatsky S, Fortin PR, Hanly JG, Wallace DJ, Isenberg D, Rahman A, Alarcon GS, Merrill JT, Ginzler E, Khamashta M, Nived O, Sturfelt G, Bruce IN, Steinsson K, Manzi S, Ramsey-Goldman R, Dooley MA, Zoma A, Kalunian K, RAMOS M, van Vollenhoven RF, Aranow C, Stoll T, Petri M, Maddison P. Atherosclerotic Vascular Events in a Multinational Inception Cohort of Systemic Lupus Erythematosus . ARTHRIT CARE RES. 62 (6): 881-887. I.F.: 4,75 Reviews I.F.: 25,341 1 Ramos-Casals M, ROBERTOPEREZ-ALVAREZ, Diaz-Lagares C, Cuadrado MJ, Khamashta MA. Autoimmune diseases induced by biological agents A double-edged sword?. AUTOIMMUN REV, 2010. 9:188-193. I.F.:6,37. 2 Cervera R, Balasch J. Autoimmunity and Recurrent Pregnancy Losses. CLIN REV ALLERG IMMU, 2010. 39:148-152. I.F.:2,60. 4 Erkan D, Espinosa G, Cervera R. Catastrophic antiphospholipid syndrome: Updated diagnostic algorithms. AUTOIMMUN REV, 2010. 10:74-79. I.F.:6,37. 5 Serra-Grabulosa JM, Adan A, Perez-Pamies M, Lachica J, Membrives S. Neural bases of numerical processing and calculation. REV NEUROLOGIA, 2010. 50:39-46. I.F.:1,23. 6 Espinosa G, Cervera R. RECENT TRENDS IN THE MANAGEMENT OF ANTIPHOSPHOLIPID SYNDROME (HUGHES SYNDROME). DRUG TODAY, 2010. 46:39-47. I.F.:1,59. 7 Hernandez-Rodriguez J, Hoffman GS, Koening CL. Surgical interventions and local therapy for Wegener’s granulomatosis. CURR OPIN RHEUMATOL, 2010. 22:2936. I.F.:4,60. Editorials I.F.: 3,713 1 Cervera R, Espinosa G. Antiphospholipid syndrome: long-time research on pathogenic mechanisms has finally lead to new therapeutic strategies. EXPERT OPIN THER TAR, 2010. 14:1279-1282. I.F.:3,71. Clinical Guidelines I.F.: 24,33 Y, Shoenfeld Y, Smolen JS, Talarico R, Tincani A, VanVollenhoven RF, Ward MM, Werth VP, Carmona L. European League Against Rheumatism recommendations for monitoring patients with systemic lupus erythematosus in clinical practice and in observational studies. ANN RHEUM DIS, 2010. 69:1269-1274. I.F.:8,11. 2 Basu N, Watts R, Bajema I, Baslund B, Bley T, Boers M, Brogan P, Calabrese L, Cid MC, Cohen-Tervaert JW, Flores-Suarez LF, Fujimoto S, DeGroot K, Guillevin L, Hatemi G, Hauser T, Jayne D, Jennette C, Kallenberg CGM, Kobayashi S, Little MA, Mahr A, Mclaren J, Merkel PA, Ozen S, Puechal X, Rasmussen N, Salama A, Salvarani C, Savage C, Scott DGI, Segelmark M, Specks U, Sunderkoetter C, Suzuki K, Tesar V, Wiik A, Yazici H, Luqmani R. EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis. ANN RHEUM DIS, 2010. 69:1744-1750. I.F.:8,11. 3 Bertsias GK, Ioannidis JPA, Aringer M, Bollen E, Bombardieri S, Bruce IN, Cervera R, Dalakas M, Doria A, Hanly JG, Huizinga TWJ, Isenberg D, Kallenberg C, Piette JC, Schneider M, Scolding N, Smolen J, Stara A, Tassiulas I, Tektonidou M, Tincani A, VanBuchem MA, VanVollenhoven R, Ward M, Gordon C, Boumpas DT. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. ANN RHEUM DIS, 2010. 69:2074-2082. I.F.:8,11. 1 Mosca M, Tani C, Aringer M, Bombardieri S, Boumpas D, Brey R, Cervera R, Doria A, Jayne D, Khamashta MA, Kuhn A, Gordon C, Petri M, Rekvig OP, Schneider M, Sherer 77 AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS LOGOS Systemic autoimmune diseases Multicentrics I.F.: 12,08 1 Ginzler EM, Wofsy D, Isenberg D, Gordon C, Lisk L, Dooley MA. Nonrenal Disease Activity Following Mycophenolate Mofetil or Intravenous Cyclophosphamide as Induction Treatment for Lupus Nephritis. ARTHRITIS RHEUM-US, 2010. 62:211-221. I.F.:7,33. 2 Seror R; Mariette X; Bowman S; Baron G; Gottenberg JE; Boostma H; Theander E; Tzioufas A; Vitali C; Ravaud P . Accurate Detection of Changes in Disease Activity in Primary Sjogren’s Syndrome by the European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index4,152. ARTHRIT CARE RES. 62 (4): 551-558. I.F.: 4,75 Grants for research in progress 78 Identificación de dianas terapéuticas. Sponsored by: Ministerio de Ciencia e Innovación (Plan Nacional I+D), SAF 08/04328. Amount: 232.320,00 euros. Duration: 01/01/2009-31/12/2011. Ramos M. Alteraciones genéticas del sistema inmunitario innato y estado protrombótico como factores predisponentes de arteriosclerosis subclínica y enfermedad cardiovascular en pacientes con síndrome de Sjögren primario. Sponsored by: FIS, PI040154. Amount: 68.000,00 euros. Duration: 01/01/2009-31/12/2011. Casaroli R. Análisis celular y molecular de las células progenitoras mesenquimales estromales de la medula ósea humana y su potencial en la en la terapia celular para la superficie ocular. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/0992. Amount: 102.074,40 euros. Duration: 01/01/2010-31/12/2012. Cid MC. Mechanisms involved in the development of neurologic ischemic complications in giant-cell arteritis. Sponsored by: Fundació Marató TV3, 60710. Amount: 170.375,00 euros. Duration: 06/02/2007-05/02/2010. Ramos M. Multilingual Organic Information Management in the Medical Domain. Sponsored by: European Comission, Coordinador: Kentro Erevnon Notioanatolikis Evropis Astiki Mi Kerdoskopiki, 250534. Amount: 83.250,00 euros. Duration: 01/03/2010-31/08/2012. Adan AM. Estudio aleatorizado y abierto de la eficacia, seguridad y tolerabilidad de dosis repetidas de bevacizumab intravítreo en pacientes con edema macular uveítico refractario. Sponsored by: Fondo de Investigaciones Sanitarias, EC08/00096. Amount: 218.405,00 euros. Duration: 01/01/200831/12/2011. Ramos M. Susceptibilitat immunogenètica i alteracions metabòliques com a factors etiopatogènics de dolor crònic en pacients amb síndrome de Sjögren en comparació amb pacients atesos a l’àmbit de l’atenció primària. Sponsored by: FUNDACIÓ LA MARATÓ DE TV3, 071810. Amount: 180.525,00 euros. Duration: 13/02/2008-12/08/2012. Cid MC. Mecanismos implicados y consecuencias clínicas de la persistencia de la inflamación vascular en la arteritis de células gigantes. Casaroli R. Medicina Regenerativa en la Superfície Ocular: Aplicación de terapia celular para la reparación de la superficie oculr mediante amplifica- ción ex vivo de éclulas progenitoras autólogas del limbo esclerocorneal sobre membrana amniótica. Sponsored by: MINISTERIO DE SANIDAD, POLÍTICA SOCIAL E IGUALDAD, TRA-072. Amount: 110.160,00 euros. Duration: 01/01/2010-31/12/2011. Thesis Cid MC. Consecuencias clínicas de la persistencia de actividad inflamatoria en la arteritis de células gigantes. Estudio de factores implicados. PhD student: Ana García Martínez Coca A, Ramos M. Impacto de la enfermedad cardiovascular en el síndrome de Sjögren primario. PhD student: Marta Pérez de Lis Novo AREA 1 Team envolved in: BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Infectious diseases and AIDS Group Members TEAM LEADER Josep M. Gatell (Hospital Clínic) Tel.: 93 227 54 30 Fax: 93 451 54 38 E-mail: jmgatell@clinic.ub.es Idibaps members: Mireia Arnedo (IDIBAPS) Miguel Caballero (Hospital Clínic) Felipe García (Hospital Clínic) Montserrat Laguno (Fundació Clínic) Josep Mallolas (Hospital Clínic) Esteban Martínez (Hospital Clínic) José Antonio Martínez (Hospital Clínic) José Mensa (Hospital Clínic) José M. Miró (Hospital Clínic) Asunción Moreno (Hospital Clínic) Montserrat Plana (IDIBAPS) Alex Soriano (Hospital Clínic) M. Eloisa Yuste (IDIBAPS) Research Fellows: Victor Casanova (Facultat de Farmàcia) Maria Lopez-Dieguez (Fundació Clínic) Christian Manzardo (Fundació Clínic) Hodei Arneras (Fundació Clínic) Nicolas Boulanger (IDIBAPS) Laura Linares (IDIBAPS) Gemma Sanclemente (Hospital Clínic) Irma Hoyo (UB) Carolina Ferreira (IDIBAPS) Technicians: Pilar Callau (Fundació Clínic) Tuixent Escriba (IDIBAPS) Ana García (Fundació Clínic) Maria Teresa García (Fundació Clínic) Carmen Hurtado (Fundació Clínic) M. José Maleno (Fundació Clínic) Laia Miralles (IDIBAPS) Sara Nieto (IDIBAPS) Yolanda Armero (Fundació Clínic) Alberto Crespo (IDIBAPS) Manuel Enric Bargalló (IDIBAPS) Carmen Álvarez (Fundació Clínic) Cristina Rovira (Fundació Clínic) Alberto Merino (IDIBAPS) Nursing Staff: Emmanuela Fernandez (Fundació Clínic) Administrative Staff: Carmen Mensa (IDIBAPS) Irene Ruíz (Fundació Clínic) Staticians: Jose Ignacio Pérez (Fundació Clínic) Collaborators: José Luis Blanco (Hospital Clínic) Marta Calvo (Fundació Clinic) Carlos Cervera (Hospital Clínic) Nuria Climent (IDIBAPS) Ana del Rio (Fundació Clínic) Teresa Gallart (Hospital Clínic) Cristina Gil (IDIBAPS) Joan Joseph (Fundació Clínic) Elisa de Lazzari (Fundació Clínic) Agathe León (Fundació Clínic) Montserrat Loncà (Fundació Clínic) Sonsoles Sánchez-Palomino (Fundació Clínic) Narcís Saubí (IDIBAPS) Sara Varea (Fundació Clínic) Laura Zamora (Fundació Clínic) María Martínez (IDIBAPS) Víctor Sánchez-Merino (Fundació Clínic) Cristina García de la María (Fundació Clínic) Ana Muñoz (Fundació Clínic) Ana Gonzalez (Fundació Clínic) Florencia Etcheverry (Fundació Clínic) Luisa Benito Serrano (GESCLINIC) Zoe Herreras Pérez (CAPSE) Ignacio Menacho Pascual (GESCLINIC) Ethel Sequeira Aymar (CAPSE) Olga Barba (CAPSE) Mª Angeles Moreno Ubiedo (CAPSE) Marta Catalán (CAPSE) Valentín Araunde (CAPSE) Ana Picas (GESCLINIC) Jordi Hoyo (GESCLINIC) Mª José Giner (GESCLINIC) Dani Cararach (GESCLINIC) Eloisa Molés (GESCLINIC) Mª Luisa Moro (GESCLINIC) Pilar Arrabal (GESCLINIC) Visiting Scientists: Sebastien Lyonnais (IDIBAPS) Gilles Mirambeau (UB) 79 AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Infectious diseases and AIDS Strategic Objectives 1. In the AIDS field: • Immunotherapy of the disease and natural and acquired defense mechanisms, including the development of therapeutic and preventive vaccines. • Efficacy and resistance and tolerance mechanisms of new antiretrovirals. • Immunopathogenesis, treatment response and resistance mechanisms of certain opportunistic infections, including tuberculosis, pneumocystis carinii pneumonia (PCP) and toxoplasmosis. 2. In the general infections field: • Prevention and treatment support in endocarditis due to multiresistant germs, including animal models. • Infection in solid-organ transplant recipients. • Interactions between nosocomial infections and antibiotic use. Main Lines of Research 1. In the AIDS field: • The most important line focuses on the peripheral (blood) and central response (lymphatic tissue and cerebrospinal fluid) to different antiretroviral therapies when administered in very early evolutive stages (CD4 > 500 mm3). We have developed ultrasensitive techniques for the determination of viral load in plasma and tissues, as well as techniques for the determination of genotypic resistance and for immunophenotyping and the evaluation of CD4+ lymphocyte proliferation in response to antigens of the HIV virus. Techniques for the determination of drug levels have also been developed in collaboration with the clinical pharmacology group. Having ruled out the possibility of eradicating the HIV virus, the working hypothesis is to see whether it is possible to almost completely suppress HIV replication over the long term, recover the host immune system and quantify the degree of such recovery. The interruption of treatment leads to a rapid disease rebound effect. RESEARCH GROUP Endocarditis. Cardiovascular infections. Experimental model Group Leader: Josep Maria Miro (Hospital Clínic) Levels of a-defensins 1-3 produced by imMDDC from HIV-infected individuals. (A) Comparison between the secreted levels of a-defensins 1-3 by imMDDC from HIV-controllers (elite controllers and viremic controllers; n = 19) and HIV non-controllers (viremic non-controllers and patients with HAART; n = 20). (B) Secreted levels of a-defensins 1-3 by imMDDC from healthy non-infected (NI; n = 15), elite controllers (ELITE; n = 4), viremic controllers (VC; n = 15), viremic non-controllers (VNC; n = 11) and patients receiving HAART (HAART; n = 9). Dots indicate each patient, and lines represent median 6 interquartile ranges (Rodriguez-Garcia M, et al. PloS ONE 2010;5:1-10). 80 This group studies the epidemiological, clinical, diagnostic, preventive and therapeutic aspects of infectious endocarditis. This is done based on studies of local, national or international cohorts (ICE) that have revealed an increase in endocarditis produced by methicillin-sensitive and -resistant Staphylococcus aureus (MSSA and MRSA, respectively). Studies using the experimental model of endocarditis due to MRSA and glycopeptide intermediate-resistant Staphylococcus aureus (GISA) have evaluated the activity of new antibiotic combinations (phosphomycin and imipenem), or new antibiotics such as daptomycin and telavancin. AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Infectious diseases and AIDS •The mechanism by which the virus is able to escape the cytotoxic immune response is subject to study, and could correspond to the selection of quasispecies different from the reservoirs (immunological resistance). For this reason we have started a research line aimed at developing techniques for stimulating the immune system, with a view to associating them with antiretroviral therapy. Cyclic interruption of the treatment can induce recovery of the specific immune response to HIV antigens, associated with a spontaneous decrease in viral load, which is correlated to the degree of proliferative and specific cytotoxic response against HIV-1 in a small percentage of patients. • We have also developed an immunotherapeutic technique based on the administration of autologous dendritic cells stimulated ex vivo with the virus of the patient. The first phase I study in patients has already been completed and published. The second study, using higher viral concentrations to induce the ex vivo stimulation of the autologous dendritic cells, has now practically been completed. • We are developing different immunogens which may be potential candidates for therapeutic or preventive vaccines. 2. In the general infections field: • Clinical and experimental endocarditis, including endocarditis in illegal drug abusers (Dr. J.M. Miró). RESEARCH GROUP Infections in solid-organ transplant recipients Group Leader: Asunción Moreno (Hospital Clínic) In the last year, this group has studied the clinical and evolutive characteristics of bacteremias in patients subjected to different solid organ transplants (kidney, liver, heart and renal-pancreatic). We have shown that mannose binding to lectin polymorphisms (MBL) condition an increase in the prevalence of cytomegalovirus (CMV) disease, and have analyzed the mortality risk factors of pneumonia in transplant patients. Studies have been made of the prevalence of other viruses of the herpes group (HHV-6 and -7) in the transplant population, as well as their pathogenic role in the post-transplantation period. These studies have been made jointly with investigators specialized in Microbiology and Immunology, and with the different Transplantation Units (Institutes of Digestive, Renal and Thoracic Diseases). • Infections in transplant recipients. Microbiological diagnosis and prognostic markers (Dr. A. Moreno). • Predictive factors and markers of treatment response in nosocomial infections (Dr. J. Mensa). • Response to treatment, resistance and transmission of tuberculosis. • Prognostic factors of communityacquired and nosocomial respiratory infections in both immunocompetent and immune depressed individuals. • The genetic fundaments of host susceptibility and the biochemical, molecular and replicative capacity bases of the resistant strains. For further information: www.idibaps.org/aidsresearch RESEARCH GROUP AIDS and HIV infection Group Leader: Josep Maria Gatell (Hospital Clínic) This group studies the clinical, diagnostic, therapeutic and preventive aspects of HIV infection. The scientific contribution of this line of research is very competitive and is internationally renowned. This group of investigators focuses on exploration of the potential for eradicating HIV infection and on reconstruction of the immune system, including the development of preventive and therapeutic vaccines. Since its start in 2002, Dr. Gatell has coordinated the Spanish network of research groups in AIDS (RIS), funded by the FIS, and since 2007 has coordinated the HIVACAT project on research into vaccines against HIV infection. Emergent Group Nosocomial infection study group Group Leader: Álex Soriano (Hospital Clínic) This group studies the clinical, diagnostic, therapeutic and preventive aspects of nosocomial (in-hospital) infections. The scientific contribution is particularly notorious in the treatment and management of bacteremia, infections in Intensive Care Units, and infections related to orthopedic implants. Its components are members of the REIPI (Spanish Research Network in Infectious Disease), and participate actively in multicenter projects financed by the FIS. 81 AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Infectious diseases and AIDS PUBLICATIONS Originals I.F.: 207,37 1 Martinez E, Larrousse M, Podzamczer D, Perez I, Gutierrez F, Lonca M, Barragan P, Deulofeu R, Casamitjana R, Mallolas J, Pich J, Gatell JM. Abacavir-based therapy does not affect biological mechanisms associated with cardiovascular dysfunction. AIDS, 2010. 24:F1-F9. I.F.:4,91. 2 Lujan B, Hakim S, Moyano S, Nadal A, Caballero M, Diaz A, Valera A, Carrera M, Cardesa A, Alos L. Activation of the EGFR/ERK pathway in highgrade mucoepidermoid carcinomas of the salivary glands. BRIT J CANCER, 2010. 103:510-516. I.F.:4,35. 3 Lalani T, Cabell CH, Benjamin DK, Lasca O, Naber C, Fowler VG, Corey GR, Chu VH, Fenely M, Pachirat O, Tan RS, Watkin R, Ionac A, Moreno A, Mestres CA, Casabe J, Chipigina N, Eisen DP, Spelman D, Delahaye F, Peterson G, Olaison L, Wang A. Analysis of the Impact of Early Surgery on In-Hospital Mortality of Native Valve Endocarditis Use of Propensity Score and Instrumental Variable Methods to Adjust for Treatment-Selection Bias. CIRCULATION, 2010. 121:1005-1013. I.F.:14,82. JAIDS-J ACQ IMM DEF, 2010. 55:582589. I.F.:4,21. 7 12 Puisac B, Arnedo M, Casale Fernandez-Ruiz M, Cervera C, Pitart C, Perez G, DelRio A, Miro JM, Marco F, Moreno A. Community-Acquired Methicillin-Resistant Staphylococcus aureus Meningitis Complicated by Cerebral Infarction. Role of Antibiotic Combination of Linezolid Plus Levofloxacin. INTERNAL MED, 2010. 49:1971-1974. I.F.:1,04. 8 Kanafani Z, Boucher H, Fowler V, Cabell C, Hoen B, Miro JM, Lalani T, Vigliani G, Campion M, Corey R, Levine D. Daptomycin compared to standard therapy for the treatment of native valve endocarditis. ENFERM INFEC MICR CL, 2010. 28:498-503. I.F.:1,39. 9 Garcia-De-La-Maria C, Marco F, Armero Y, Soy D, Moreno A, DelRio A, Almela M, Cervera C, Ninot S, Falces C, Mestres CA, Gatell JM, DeAnta MTJ, Miro JM. Daptomycin Is Effective for Treatment of Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus epidermidis. ANTIMICROB AGENTS CH, 2010. 54:27812786. I.F.:4,80. CH, Ribate MP, Castiella T, Ramos FJ, Ribes A, Perez-Cerda C, Casals N, Hegardt FG, Pie J. Differential HMG-CoA lyase expression in human tissues provides clues about 3-hydroxy-3-methylglutaric aciduria. J INHERIT METAB DIS, 2010. 33:405410. I.F.:3,60. 13 Poveda E, Anta L, Blanco JL, Casado JL, Gutierrez F, Garcia F, Gomez-Sirvent JL, Iribarren JA, Soriano V, DeMendoza C. Drug Resistance Mutations in HIV-Infected Patients in the Spanish Drug Resistance Database Failing Tipranavir and Darunavir Therapy. ANTIMICROB AGENTS CH, 2010. 54:3018-3020. I.F.:4,80. 14 Herrera E, Tenckhoff S, Gomara MJ, Galatola R, Bleda MJ, Gil C, Ercilla G, Gatell JM, Tillmann HL, Haro I. Effect of Synthetic Peptides Belonging to E2 Envelope Protein of GB Virus C on Human Immunodeficiency Virus Type 1 Infection. J MED CHEM, 2010. 53:6054-6063. I.F.:4,80. 15 Veloso S, Olona M, Garcia F, 4 Ortega M, Marco F, Soriano A, Al- 10 Lifson AR, Belloso WH, Davey mela M, Martinez JA, Pitart C, Mensa J. Candida spp. bloodstream infection: influence of antifungal treatment on outcome. J ANTIMICROB CHEMOTH, 2010. 65:562-568. I.F.:4,35. RT, Duprez D, Gatell JM, Hoy JF, Krum EA, Nelson R, Pedersen C, Perez G, Price RW, Prineas RJ, Rhame FS, Sampson JH, Worley J. Development of Diagnostic Criteria for Serious Non-AIDS Events in HIV Clinical Trials. HIV CLIN TRIALS, 2010. 11:205-219. I.F.:1,63. Domingo P, Alonso-Villaverde C, Broch M, Peraire J, Vilades C, Plana M, Pedrol E, Lopez-Dupla M, Aguilar C, Gutierrez M, Leon A, Tasias M, Gatell JM, Richart C, Vidal F. Effect of TNF-a genetic variants and CCR5 Delta 32 on the vulnerability to HIV-1 infection and disease progression in Caucasian Spaniards. BMC MED GENET, 2010. 11:63-63. I.F.:2,84. 11 Trullas JC, Mocroft A, Cofan F, 16 Gonzalez R, Castro P, Garcia Tourret J, Moreno A, Bagnis CI, Fux CA, Katlama C, Reiss P, Lundgren J, Gatell JM, Kirk O, Miro JM. Dialysis and Renal Transplantation in HIVInfected Patients: a European Survey. F, Plana M, Bayas JM, Lafuente S, Serrano B, Mora B, Argelich R, Gatell JM, Vilella A. Effects of highly active antiretroviral therapy on vaccine-induced humoral immunity in HIV-infected 5 Tuset M, Lopez-Sune E, Cervera C, Moreno A, Miro JM. Characteristics of antiviral drugs, excluding antiretroviral agents: Update 2009. ENFERM INFEC MICR CL, 2010. 28:199-199. I.F.:1,39. 6 Lopez-Sune E, Tuset M, Laguno M, Moreno A, Miro JM. Characteristics of hepatitis and influenza antivi- 82 rals: update 2009. ENFERM INFEC MICR CL, 2010. 28:253-253. I.F.:1,39. AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Infectious diseases and AIDS adults. HIV MED, 2010. 11:535-539. I.F.:2,88. Antiretroviral Therapy. J CLIN DENSITOM, 2010. 13:197-203. I.F.:2,39. 17 Cobos-Trigueros N, Pitart C, 23 Buzon MJ, Massanella M, Llibre Marco F, Martinez JA, Almela M, Lopez J, Ortega M, Soriano A, Mensa J. Epidemiology and clinical presentation of Panton-Valentine leukocidin positive methicillin-resistant Staphylococcus aureus. REV ESP QUIM, 2010. 23:9399. I.F.:0,73. JM, Esteve A, Dahl V, Puertas MC, Gatell JM, Domingo P, Paredes R, Sharkey M, Palmer S, Stevenson M, Clotet B, Blanco J, Martinez-Picado J. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. NAT MED, 2010. 16:460U143. I.F.:27,14. 18 Hoyo I, Linares L, Cervera C, Almela M, Marcos MA, Sanclemente G, Cofan F, Ricart MJ, Moreno A. Epidemiology of Pneumonia in Kidney Transplantation. TRANSPL P, 2010. 42:2938-2940. I.F.:0,99. 19 Mocroft A, Kirk O, Reiss P, DeWit S, Sedlacek D, Beniowski M, Gatell J, Phillips AN, Ledergerber B, Lundgren JD. Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients. AIDS, 2010. 24:16671678. I.F.:4,91. 20 Poveda E, Anta L, Blanco JL, Perez-Elias MJ, Garcia F, Leal M, Ribera E, Gutierrez F, Soriano V, DeMendoza C. Etravirine resistance associated mutations in HIV-infected patients failing efavirenz or nevirapine in the Spanish antiretroviral resistance database. AIDS, 2010. 24:469-471. I.F.:4,91. 21 Diaz A, Alos L, Leon A, Mozos A, Caballero M, Martinez A, Plana M, Gallart T, Gil C, Leal M, Gatell JM, Garcia F. Factors associated with collagen deposition in lymphoid tissue in longterm treated HIV-infected patients. AIDS, 2010. 24:2029-2039. I.F.:4,91. 22 Freitas P, Santos AC, Carvalho D, Pereira J, Marques R, Martinez E, Sarmento A, Medina JL. Fat Mass Ratio: An Objective Tool to Define Lipodystrophy in HIV-Infected Patients Under 24 Miro JM, Manzardo C, Pich J, Domingo P, Ferrer E, Arribas JR, Ribera E, Arrizabalaga J, Lonca M, Cruceta A, DeLazzari E, Fuster M, Podzamczer D, Plana M, Gatell JM. Immune Reconstitution in Severely Immunosuppressed AntiretroviralNaive HIV Type 1-Infected Patients Using a Nonnucleoside Reverse Transcriptase Inhibitor-Based or a Boosted Protease Inhibitor-Based Antiretroviral Regimen: Three-Year Results. AIDS RES HUM RETROV, 2010. 26:747757. I.F.:2,18. 25 Fortun J, Martin-Davila P, Pascual J, Cervera C, Moreno A, Gavalda J, Aguado JM, Pereira P, Gurgui M, Carratala J, Fogueda M, Montejo M, Blasco F, Bou G, Torre-Cisneros J. Immunosuppressive therapy and infection after kidney transplantation. TRANSPL INFECT DIS, 2010. 12:397405. I.F.:2,06. 26 Rodriguez-Garcia M, Climent N, Oliva H, Casanova V, Franco R, Leon A, Gatell JM, Garcia F, Gallart T. Increased alpha-Defensins 1-3 Production by Dendritic Cells in HIV-Infected Individuals Is Associated with Slower Disease Progression. PLOS ONE, 2010. 5:-. I.F.:4,35. 27 Martinez JA, Cobos-Trigueros N, Soriano A, Almela M, Ortega M, Marco F, Pitart C, Sterzik H, Lopez J, Mensa J. Influence of Empiric Therapy with a beta-Lactam Alone or Combined with an Aminoglycoside on Prognosis of Bacteremia Due to Gram-Negative Microorganisms. ANTIMICROB AGENTS CH, 2010. 54:3590-3596. I.F.:4,80. 28 Linares L, Cervera C, Hoyo I, Sanclemente G, Marco F, Cofan F, Ricart MJ, Navasa M, Moreno A. Klebsiella pneumoniae Infection in Solid Organ Transplant Recipients: Epidemiology and Antibiotic Resistance. TRANSPL P, 2010. 42:2941-2943. I.F.:0,99. 29 Steigbigel RT, Cooper DA, Teppler H, Eron JJ, Gatell JM, Kumar PN, Rockstroh JK, Schechter M, Katlama C, Markowitz M, Yeni P, Loutfy MR, Lazzarin A, Lennox JL, Clotet B, Zhao J, Wan H, Rhodes RR, Strohmaier KM, Barnard RJ, Isaacs RD, Nguyen BYT. Long-Term Efficacy and Safety of Raltegravir Combined with Optimized Background Therapy in Treatment-Experienced Patients with Drug-Resistant HIV Infection: Week 96 Results of the BENCHMRK 1 and 2 Phase III Trials. CLIN INFECT DIS, 2010. 50:605-612. I.F.:8,20. 30 Gatell JM, Katlama C, Grinsztejn B, Eron JJ, Lazzarin A, Vittecoq D, Gonzalez CJ, Danovich RM, Wan H, Zhao J, Meibohm AR, Strohmaier KM, Harvey CM, Isaacs RD, Nguyen BYT. Long-Term Efficacy and Safety of the HIV Integrase Inhibitor Raltegravir in Patients With Limited Treatment Options in a Phase II Study. JAIDS-J ACQ IMM DEF, 2010. 53:456-463. I.F.:4,21. 31 Joseph J, Fernandez-Lloris R, Pezzat E, Saubi N, Cardona PJ, Mothe B, Gatell JM. Molecular Characterization of Heterologous HIV1gp120 Gene Expression Disruption 83 AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Infectious diseases and AIDS in Mycobacterium bovis BCG Host Strain: A Critical Issue for Engineering Mycobacterial Based-Vaccine Vectors. J BIOMED BIOTECHNOL, 2010. :-. I.F.:1,75. 32 Polverino E, Dambrava P, Cilloniz C, Balasso V, Marcos MA, Esquinas C, Mensa J, Ewig S, Torres A. Nursing home-acquired pneumonia: a 10 year single-centre experience. THORAX, 2010. 65:354-359. I.F.:7,04. 33 Moreno A, Sanchez F, Nelson J, Miro JM, Cayla JA. On the way to shortening tuberculosis treatments: clinical trials of the Unitat d’ Investagacio en Tuberculosi de Barcelona supported by the Centers for Disease Control and Prevention. GAC SANIT, 2010. 24:171-171. I.F.:1,17. 34 Pion M, Serramia MJ, Diaz L, Bryszewska M, Gallart T, Garcia F, Gomez R, DeLaMata FJ, Munoz-Fernandez MA. Phenotype and functional analysis of human monocytes-derived dendritic cells loaded with a carbosilane dendrimer. BIOMATERIALS, 2010. 31:8749-8758. I.F.:7,37. 35 Etcheverry MF, DeLazzari E, Fuchs JD, Merono M, Sierra E, DelRomero J, Evans JL, Mendez-Arancibia E, Jacques C, Rojas D, Segu M, Gatell JM, Joseph J. Pilot Study Assessing HIV Vaccine Trial Readiness Among Female Sex Workers, Injection and Non-injection Drug Users, and Men Who Have Sex with Men in Spain. AIDS BEHAV, 2010. 14:607-617. I.F.:3,04. 36 Perello R, Miro O, Marcos MA, Almela M, Bragulat E, Sanchez M, Agusti C, Miro JM, Moreno A. Predicting bacteremic pneumonia in HIV1-infected patients consulting the ED. AM J EMERG MED, 2010. 28:454459. I.F.:1,54. 84 37 Rodriguez D, Almirante B, 42 Mocroft A, Reiss P, Gasiorowski Cuenca-Estrella M, Rodriguez-Tudela JL, Mensa J, Ayats J, Sanchez F, Pahissa A. Predictors of candidaemia caused by non-albicans Candida species: results of a population-based surveillance in Barcelona, Spain. CLIN MICROBIOL INFEC, 2010. 16:16761682. I.F.:4,01. J, Ledergerber B, Kowalska J, Chiesi A, Gatell J, Rakhmanova A, Johnson M, Kirk O, Lundgren J. Serious Fatal and Nonfatal Non-AIDS-Defining Illnesses in Europe. JAIDS-J ACQ IMM DEF, 2010. 55:262-270. I.F.:4,21. 38 Letang E, Almeida JM, Miro JM, Ayala E, White IE, Carrilho C, Bastos R, Nhampossa T, Menendez C, Campbell TB, Alonso PL, Naniche D. Predictors of Immune Reconstitution Inflammatory SyndromeAssociated With Kaposi Sarcoma in Mozambique: A Prospective Study. JAIDS-J ACQ IMM DEF, 2010. 53:589-597. I.F.:4,21. 39 Alvarez-Martinez MJ, Miro JM, Valls ME, Mas J, DeLaBellacasa JP, Sued O, Sole M, Rivas PV, DeLazzari E, Benito N, Garcia F, Agusti C, Wilson PE, Gatell JM, DeAnta MTJ, Meshnick SR, Moreno A. Prevalence of dihydropteroate synthase genotypes before and after the introduction of combined antiretroviral therapy and their influence on the outcome of Pneumocystis pneumonia in HIV-1-infected patients. DIAGN MICR INFEC DIS, 2010. 68:60-65. I.F.:2,45. 43 Martinez E, Larrousse M, Llibre JM, Gutierrez F, Saumoy M, Antela A, Knobel H, Murillas J, Berenguer J, Pich J, Perez I, Gatell JM. Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study. AIDS, 2010. 24:1697-1707. I.F.:4,91. 44 Martinez E, Visnegarwala F, Grund B, Thomas A, Gibert C, Shlay J, Drummond F, Pearce D, Edwards S, Reiss P, El-Sadr W, Carr A. The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters. AIDS, 2010. 24:353-363. I.F.:4,91. 45 Montes AH, Valle-Garay E, Suarez-Zarracina T, Melon S, Martinez E, Carton JA, Collazos J, Asensi V. The MMP1 (-16071G/2G) single nucleotide polymorphism associates with the HAART-related lipodystrophic syndrome. AIDS, 2010. 24:2495-2502. I.F.:4,91. 40 Telli M, Guiral E, Martinez JA, 46 Ferrer M, Liapikou A, Valencia Almela M, Bosch J, Vila J, Soto SM. Prevalence of enterotoxins among Escherichia coli isolates causing bacteraemia. FEMS MICROBIOL LETT, 2010. 306:117-121. I.F.:2,20. M, Esperatti M, Theessen A, Martinez JA, Mensa J, Torres A. Validation of the American Thoracic SocietyInfectious Diseases Society of America Guidelines for Hospital-Acquired Pneumonia in the Intensive Care Unit. CLIN INFECT DIS, 2010. 50:945-952. I.F.:8,20. 41 Guerra S, Gonzalez JM, Climent N, Reyburn H, Lopez-Fernandez LA, Najera JL, Gomez CE, Garcia F, Gatell JM, Gallart T, Esteban M. Selective Induction of Host Genes by MVA-B, a Candidate Vaccine against HIV/ AIDS. J VIROL, 2010. 84:8141-8152. I.F.:5,15. 47 Gatell JM. When and why to start antiretroviral therapy?. J ANTIMICROB CHEMOTH, 2010. 65:383-385. I.F.:4,35. AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Infectious diseases and AIDS Reviews I.F.: 4,34 1 DeLaCamara R, Mensa J, Carreras E, Estrella MC, Rodriguez JAG, Gobernado M, Picazo J, Aguado JM, Sanz MA. Antifungal prophylaxis in oncohematologic patients: Literature review and recommendations. MED CLIN-BARCELONA, 2010. 134:222233. I.F.:1,23. 2 Candel FJ, Martinez-Sagasti F, Borges M, Maseda E, Herrera-Gutierrez M, Garnacho-Montero J, Maynar FJ, Zaragoza R, Mensa J, Azanza JR. Endotoxin adsortion as adjuvant therapy in gramnegative severe sepsis. REV ESP QUIM, 2010. 23:115-121. I.F.:0,73. 3 Llibre JM, Antela A, Arribas JR, Domingo P, Gatell JM, Lopez-Aldeguer J, Lozano F, Miralles C, Molto J, Moreno S, Ortega E, Riera M, Rivero A, Villalonga C, Clotet B. Role of fixeddose combinations of antiretrovirals in HIV-1 therapy. ENFERM INFEC MICR CL, 2010. 28:615-620. I.F.:1,39. 4 Miro JM, Ricart MJ, Trullas JC, Cofan F, Cervera C, Brunet M, Tuset M, Manzardo C, Oppenheimer F, Moreno A. Simultaneous PancreasKidney Transplantation in HIV-infected Patients: A Case Report and Literature Review. TRANSPL P, 2010. 42:38873891. I.F.:0,99. Editorials I.F.: 3,08 1 Gatell JM, Zulaica D, DelRomero J, Robledo T. How to promote and facilitate the early diagnosis of HIV-1 infection: the emergency department’s role. EMERGENCIAS, 2010. 22:230232. I.F.:3,08. Clinical Guidelines I.F.: 28,90 1 Thompson MA, Aberg JA, Cahn P, Montaner JSG, Rizzardini G, Telenti A, Gatell JM, Gunthard HF, Hammer SM, Hirsch MS, Jacobsen DM, Reiss P, Richman DD, Volberding PA, Yeni P, Schooley RT. Antiretroviral Treatment of Adult HIV Infection 2010 Recommendations of the International AIDS Society-USA Panel. JAMA-J AM MED ASSOC, 2010. 304:321-333. I.F.:28,90. Multicentrics I.F.: 118,83 1 Fryer HR, Frater J, Duda A, Roberts MG, Phillips RE, Mclean AR. Modelling the Evolution and Spread of HIV Immune Escape Mutants. PLOS PATHOG, 2010. 6:-. I.F.:8,98. 2 Trevino A, Soriano V. Current situation of human immunodeficiency virus type 2 and Human T lymphotropic virus in Spain. ENFERM INFEC MICR CL, 2010. 28:442-445. I.F.:1,39. 3 Friis-Moller N, Thiebaut R, Reiss P, Weber R, Monforte AD, DeWit S, El-Sadr W, Fontas E, Worm S, Kirk O, Phillips A, Sabin CA, Lundgren JD, Law MG. Predicting the risk of cardiovascular disease in HIV-infected patients: the Data collection on Adverse Effects of Anti-HIV Drugs Study. EUR J CARDIOV PREV R, 2010. 17:491501. I.F.:2,51. 4 Nahid P, Bliven EE, Kim EY, MacKenzie WR, Stout JE, Diem L, Johnson JL, Gagneux S, Hopewell PC, Kato-Maeda M. Influence of M. tuberculosis Lineage Variability within a Clinical Trial for Pulmonary Tuberculosis. PLOS ONE, 2010. 5:-. I.F.:4,35. 5 Lodwick R, Costagliola D, Reiss P, Torti C, Teira R, Dorrucci M, Ledergerber B, Mocroft A, Podzamczer D, Cozzi-Lepri A, Obel N, Masquelier B, Staszewski S, Garcia F, DeWit S, Castagna A, Antinori A, Judd A, Ghosn J, Touloumi G, Mussini C, Duval X, Ramos J, Meyer L, Warsawski J, Thorne C, Masip J, Perez-Hoyos S, Pillay D, VanSighem A, LoCaputo S, Gunthard H, Paredes R, DeLuca A, Paraskevis D, Fabre-Colin C, Kjaer J, Chene G, Lundgren JD, Phillips AN. Triple-Class Virologic Failure in HIV-Infected Patients Undergoing Antiretroviral Therapy for Up to 10 Years. ARCH INTERN MED, 2010. 170:410-419. I.F.:9,81. 6 Caro-Murillo AM, Luciano AG, Rubio GN, Noval ML, Ramos JRB. HIV infection in different age groups: Potential implications for prevention. CoRIS Cohort, Spain, 2004-2008. MED CLIN-BARCELONA, 2010. 134:521527. I.F.:1,23. 7 Soriano V, Mocroft A, Peters L, Rockstroh J, Antunes F, Kirkby N, DeWit S, Monforte AD, Flisiak R, Lundgren J. Predictors of hepatitis B virus genotype and viraemia in HIV-infected patients with chronic hepatitis B in Europe. J ANTIMICROB CHEMOTH, 2010. 65:548-555. I.F.:4,35. 8 Marshall V, Martro E, Labo N, Ray A, Wang DA, Mbisa G, Bagni RK, Volfovsky N, Casabona J, Whitby D. Kaposi Sarcoma (KS)-Associated Herpesvirus MicroRNA Sequence Analysis and KS Risk in a European AIDS-KS Case Control Study. J INFECT DIS, 2010. 202:1126-1135. I.F.:5,87. 9 Tavel JA. Effects of Intermittent IL-2 Alone or with Peri-Cycle Antiretroviral Therapy in Early HIV Infection: The STALWART Study. PLOS ONE, 2010. 5:-. I.F.:4,35. 85 AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Infectious diseases and AIDS 10 Dore GJ, Soriano V, Rockstroh J, 14 Worm SW, Friis-Moller N, Bru- Kupfer B, Tedaldi E, Peters L, Neuhaus J, Puoti M, Klein MB, Mocroft A, Clotet B, Lundgren JD. Frequent hepatitis B virus rebound among HIV-hepatitis B virus-coinfected patients following antiretroviral therapy interruption. AIDS, 2010. 24:857-865. I.F.:4,91. yand M, Monforte AD, Rickenbach M, Reiss P, El-Sadr W, Phillips A, Lundgren J, Sabin C. High prevalence of the metabolic syndrome in HIVinfected patients: impact of different definitions of the metabolic syndrome. AIDS, 2010. 24:427-435. I.F.:4,91. Touloumi G, Carrieri P, Guest JL, Brockmeyer NH, Phillips AN. Death rates in HIV-positive antiretroviralnaive patients with CD4 count greater than 350 cells per mu L in Europe and North America: a pooled cohort observational study. LANCET, 2010. 376:340-345. I.F.:30,76. 11 Ray M, Logan R, Sterne JAC, 15 Aldeguer JL, Et AL. AIDS Study 20 Weber R, Sabin C, Reiss P, Hernandez-Diaz S, Robins JM, Sabin C, Bansi L, VanSighem A, DeWolf F, Costagliola D, Lanoy E, Bucher HC, VonWyl V, Esteve A, Casabona J, DelAmo J, Moreno S, Justice A, Gouler J, Lodi S, Phillips A, Seng R, Meyer L, Perez-Hoyos S, DeOlalla PG, Herman MA, Phillips AN, Gilson R, Easterbrook P, Fisher M, Gazzard B, Johnson M, Walsh J, Leen C, Orkin C, Anderson J, Pillay D, Delpech V, Schwenk A, Dunn D, Gompels M, Hill T, Porter K, Babiker A. The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals. AIDS, 2010. 24:123-137. I.F.:4,91. Group/Spanish AIDS Plan consensus document on antiretroviral therapy in adults with human immunodeficiency virus infection (updated January 2010). ENFERM INFEC MICR CL, 2010. 28:-. I.F.:1,39. DeWit S, Worm SW, Law M, Dabis F, Monforte AD, Fontas E, El-Sadr W, Kirk O, Rickenbach M, Phillips A, Ledergerber B, Lundgren J. HBV or HCV coinfections and risk of myocardial infarction in HIV-infected individuals: the D:A:D Cohort Study. ANTIVIR THER, 2010. 15:1077-1086. I.F.:4,32. 12 Smith C, Sabin CA, Lundgren JD, Thiebaut R, Weber R, Law M, Monforte AD, Kirk O, Friis-Moller N, Phillips A, Reiss P, El-Sadr W, Pradier C, Worm SW. Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D study The Data Collection on Adverse Events of AntiHIV drugs (D:A:D) Study Group. AIDS, 2010. 24:1537-1548. I.F.:4,91. 13 Worm SW, Sabin C, Weber R, Reiss P, El-Sadr W, Dabis F, DeWit S, Law M, Monforte AD, Friis-Moller N, Kirk O, Fontas E, Weller I, Phillips A, Lundgren J. Risk of Myocardial Infarction in Patients with HIV Infection Exposed to Specific Individual Antiretroviral Drugs from the 3 Major Drug Classes: The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study. J INFECT DIS, 2010. 201:318-330. I.F.:5,87. 86 16 Gutierrez F, Et AL. Diagnosis, treatment and prevention of renal diseases in HIV infected patients. Recommendations of the Spanish AIDS Study Group/National AIDS Plan28(8):520.e1-22. ENFERM INFEC MICR CL, 2010. 28:-. I.F.:1,39. 17 Reekie J, Kosa C, Engsig F, Monforte AD, Wiercinska-Drapalo A, Domingo P, Antunes F, Clumeck N, Kirk O, Lundgren JD, Mocroft A. Relationship Between Current Level of Immunodeficiency and Non-Acquired Immunodeficiency Syndrome-Defining Malignancies. CANCER-AM CANCER SOC, 2010. 116:5306-5315. I.F.:5,42. 18 Reekie J, Mocroft A, Ledergerber B, Beniowski M, Clotet B, VanLunzen J, Chiesi A, Pradier C, Machala L, Lundgren JD. History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change*. HIV MED, 2010. 11:469-478. I.F.:2,88. 19 Lodwick RK, Sabin CA, Porter K, Ledergerber B, VanSighem A, CozziLepri A, Khaykin P, Mocroft A, Jacobson L, DeWit S, Obel N, Castagna A, Wasmuth JC, Gill J, Klein MB, Gange S, Riera M, Mussini C, Gutierrez F, 21 Mocroft A, Phillips AN, Ledergerber B, Smith C, Bogner JR, Lacombe K, Wiercinska-Drapalos A, Reiss P, Kirk O, Lundgren JD. Estimated average annual rate of change of CD4(+) Tcell counts in patients on combination antiretroviral therapy. ANTIVIR THER, 2010. 15:563-570. I.F.:4,32. Grants for research in progress Gatell JM. CA - The EuroSIDA Network 2005-2009. Clinical and Virological outcome of patients with HIV under care in Europe. Sponsored by: European Comission, LSHPCT-2006-018632. Amount: 11.578,00 euros. Duration: 01/03/200628/02/2010. Gatell JM. NoE - European AIDS Treatment Network. Sponsored by: European Commission, LSHPCT-2006-037570. Amount: 45.000,00 euros. Duration: 01/02/200731/01/2012. AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Infectious diseases and AIDS Mallolas J. Cohorte de GESIDA de pacientes coinfectados por VIH y virus de hepatitis C que reciben tratamiento para la hepatitis C (20082010). Sponsored by: Fundación para la Investigación y la Prevención del Sida en España, 36702/07. Amount: 3.300,00 euros. Duration: 19/11/2007-18/11/2010. Martinez JA. Eficacia y seguridad del tratamiento de infecciones nosocomiales graves causadas por Acinetobacter Baumannii multiresistente con rifampicina más imipenem. Sponsored by: Ministerio Sanidad y Consumo, EC07/90565. Amount: 3.533,20 euros. Duration: 29/10/2007-30/12/2010. Miro JM. Tratamiento antiretroviral una vez al dia en pacientes con infecciones por el VIH-1 no tratados previamente y con cifras de linfocitos CD4+ inferiores a 100 céls/MM3. Estudio prospectivo aleatorizado, multicéntrico y abierto. Estudio advanz-3. Sponsored by: Ministerio Sanidad y Consumo, EC07/90642. Amount: 219.615,00 euros. Duration: 29/10/2007-30/12/2010. Plana M. Caracterización Ex Vivo de la respuesta inmunitaria celular frente al VIH-1 mediante vectores virales. Sponsored by: Ministerio Sanidad y Consumo, PI070291. Amount: 119.790,00 euros. Duration: 26/11/2007-30/12/2010. Caballero M. Desarrollo de un modelo experimental en cobaya de enfermedad de vías aéreas superiores por exposición al humo de tabaco. Estudio de los cambios anatomopatológicos y de los marcadores de inflamación. Sponsored by: Ministerio Sanidad y Consumo, PI070434. Amount: 40.777,00 euros. Duration: 26/11/2007-30/12/2010. Gatell JM. Red de SIDA. Sponsored by: Ministerio Sanidad y Consumo, RD06/0006/0000. Amount: 1.426.015,20 euros. Duration: 01/01/2007-31/12/2010. Arnedo M. Factores genéticos implicados en el desarrollo de dislipemia en pacientes infectados por VIH-1 que inician tratamiento antiretroviral de gran actividad. Sponsored by: FIPSE-FUNDACION PARA INVESTIGACIÓN Y PREVENCIÓN DEL SIDA EN ESPAÑA, PS09/00396. Amount: 124.480,00 euros. Duration: 30/10/2008-29/10/2011. Miro JM. Optimización farmacocinética/farmacodinámica del tratamiento con vancomicina de la endocarditis experimental por Staphylococcus aureus resistente o no a la meticilina causada por cepas con una CMI a la vancomicina de 0.5, 1 o 2 mcg/mL. Sponsored by: FIS, PI080268. Amount: 81.675,00 euros. Duration: 01/01/200931/12/2011. Miro JM. Proyecto de constitución y organización del banco de muestras biológicas de pacientes coinfectados vih-VHC y/o VHB de la cohorte de trasplante hepático (TOH). Sponsored by: FIPSE, BB-TOH/VIH-07. Amount: 49.821,00 euros. Duration: 01/01/2008-31/12/2010. Miro JM. Estudio FIPSE de trasplante hepático en pacientes infectados por el VIH en España. Sponsored by: FIPSE, TOH/VIH-08. Amount: 600.000,00 euros. Duration: 01/01/2009-31/12/2011. Miro JM. Supervivencia de los pacientes con infección por el VIH en terapia renal sustitutiva o trasplante renal en España. Sponsored by: FIPSE, 24-0858-09. Amount: 133.925,00 euros. Duration: 01/01/2010-31/12/2011. Garcia F. Desarrollo de una vacuna frente a VIH: Estudio de los cambios de la biología de células dendríticas humanas tras interacción con distintos inmunógenos. Sponsored by: Instituto de Salud Carlos III, PS09/01297. Amount: 219.615,00 euros. Duration: 01/01/201031/12/2013. Arnedo M. Factores genéticos implicados en el desarrollo de dislipemia en pacientes infectados por VIH-1 que inician tratamiento antiretroviral de gran actividad. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/0396. Amount: 80.465,00 euros. Duration: 01/01/2010-31/12/2012. Eloisa Yuste. Desarrollo de una vacuna frente al VIH: aislamiento y caracterización de nuevos anticuerpos neutralizantes de amplio espectro. Diseño de inmunógenos capaces de generar dichos anticuerpos. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1459. Amount: 116.765,00 euros. Duration: 01/01/2010-31/12/2012. Gatell JM. Evaluación del impacto de nuevos sistemas de información en el cuidado de pacientes VIH crónicos. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/90897. Amount: 49.610,00 euros. Duration: 01/01/2010-31/12/2012. Miro JM. Supervivencia de los pacientes con infección por el VIH en terapia renal sustitutiva o trasplante renal en España. Sponsored by: FIPSE-FUNDACIÓN PARA INVESTIGACIÓN Y PREVENCIÓN DEL SIDA EN ESPAÑA, 24-0858-09. Amount: 28.600,00 euros. Duration: 04/01/2010-03/01/2012. 87 AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Infectious diseases and AIDS Joseph J. Inclusión social, sanitaria y laboral de personas vulnerables que se encuentran en riesgo de exclusión social y pobreza: mujeres que ejercen la prostitución en la calle, usuarios de drogas y/o población inmigrante con bajos recursos económicos. Sponsored by: FUNDACIO “LA CAIXA”, ES100192. Amount: 24.000,00 euros. Duration: 09/07/2010-30/09/2011. Garcia F. Estudio en fase I abierto para evaluar la seguridad e inmunogenicidad de la vacuna frente a VIH-1 MVA-B en pacientes infectados por VIH crónicos en tratamiento antirretroviral (RISVAC03). Sponsored by: MINISTERIO DE SANIDAD, POLÍTICA SOCIAL E IGUALDAD, TRA-094. Amount: 411.906,60 euros. Duration: 01/01/2010-31/12/2011. Moreno A. Evaluar la eficacia y la seguridad de la cambinación de fosfomicina (F) e imipenem (I) para el tratamiento de la endocarditis (EI) sobre la válvula nativa o protésica por S.aureus resistente a meticilina (MRSA). Sponsored by: INSTITUTO DE SALUD CARLOS III, EC08/00190. Amount: 339.634,90 euros. Duration: 01/01/2009-30/12/2011. 88 Thesis Lozano F, Moreno A. Influencia de los poliformismos de los genes de la inmunidad innata en el desarrollo y evolución de las infecciones tras un trasplante de órgano sólido. PhD student: Carlos Cervera Alvarez. Martinez-Chamorro E. Injertos de tejido adiposo autólogo en la lipoatrofia facial de pacientes VIH+: Comparación de dos estrategias de tratamiento y utilidad de la tomografia computerizado en la evaluación de su durabilidad. PhD student: Eva Guisantes Pintos. AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Team envolved in: Red Española de Investigación en Patología Infecciosa (REIPI) Immune receptors of the innate and adaptive system Group Members TEAM LEADER Francisco Lozano (Hospital Clínic/UB) Tel.: 93 227 54 00 (Ext.: 4217/4546) Fax: 93 451 80 38 E-mail: flozano@clinic.ub.es Idibaps members: Ana Angulo (IDIBAPS) Pablo Engel (Facultat de Medicina UB) Carles Serra (Hospital Clínic) Ricardo Bastos (IDIBAPS) Postdoctoral fellows: Esther Carrasco Miguel (Fundació Clínic) Mario Martínez Florensa (UB-FBG) Vanesa G. Martínez (Fundació Clínic) Research Fellows: Lyzette Bonet (Fundació Clínic) Rafael Fenutría (Fundació Clínic) Elena Isern (IDIBAPS) Jordi Sintes (UB) Antonio Guilabert Vidal (FIS-FSE) Cristina Miró (MEC/FPU) Cristina Escoda (MEC/FPI) Natalia Pérez Carmona (UB) Jessica Matesanz (IDIBAPS) Jose de Salort (UB) M. Carmen Diaz-Ramos (IDIBAPS) Technicians: Adriana Lázaro (Fundació Clínic) Laia Llinas (Fundació Clínic) Noelia Armiger Borràs (IDIBAPS) Strategic Objectives Main Lines of Research 1. Genetic and molecular characterization of receptors of both the innate and adaptive immune system. 2. Functional characterization of the ligand- receptor interactions responsible for intercellular communication between the innate and adaptive immune system components. 3. Molecular characterization of pathogenhost interactions. 4. Molecular characterization of the biology, pathogenesis and immunology of cytomegalovirus (CMV). 1. Study of the structure and function of the SLAM (Signaling Lymphocytic Activation Molecule) and SAP (SLAM-Associated Protein) leukocyte molecule families. 2. Identification and characterization of leukocyte receptors and intracellular ligands of the 3BP2 adaptor molecule. Molecular dissection of the 3BP2 signaling pathways in lymphocytes. 3. Study of the molecules that intervene in leukocyte adhesion and inflammation. 4. Immunogenetics of receptors and molecules implicated in the regulation of innate and adaptive immune responses. 5. Study of the role of the CD5 and CD6 receptors in lymphocyte activation and differentiation. 6. Molecular and functional characterization of nonlymphoid members of the superfamily of receptors with extracellular domains rich in cysteine (SRCR, Scavenger Receptor Cysteine-Rich) residues. 7. Characterization of the genic regulation mechanisms of CMV and identification of functions encoded for by CMV. 8. Study of CMV mediated modulation of immune response and immune evasion strategies. Immunohistochemical staining of a normal tonsil specimen exhibiting secondary folicles. Brown, CD279/PD-1 (Programmed death-1) positive cells (activated T and B lymphocytes). Red, CD23 positive cells (activated B cells and Follicular Dendritic Cells). Emergent Group Molecular mechanisms of the pathogenesis of CMV disease Group Leader: Ana Angulo (IDIBAPS) Cytomegalovirus (CMV) is an ubiquitous pathogen that establishes latent infections for life – with serious consequences for immune-compromised individuals. The group studies different aspects of the interactions between CMV and the host, with special emphasis on the mechanisms that regulate viral genic expression, the determination of new functions encoded by the virus, and the identification of processes of interference with the immune system. 89 AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Immune receptors of the innate and adaptive system PUBLICATIONS originals I.F.: 55,45 1 Smithson A, Perello R, Aibar J, Espinosa G, Tassies D, Freire C, Castro P, Suarez B, Lozano F, Nicolas JM. Genotypes Coding for Low Serum Levels of Mannose-Binding Lectin Are Underrepresented among Individuals Suffering from Noninfectious Systemic Inflammatory Response Syndrome. CLIN VACCINE IMMUNOL, 2010. 17:447-453. I.F.:2,37. 2 Herrero-Gonzalez JE, Iranzo P, Benitez D, Lozano F, Herrero C, Mascaro JM. Correlation of Immunological Profile with Phenotype and Disease Outcome in Pemphigus. ACTA DERM-VENEREOL, 2010. 90:401-405. I.F.:3,01. 3 Wang NH, Calpe S, Westcott J, Castro W, Ma CY, Engel P, Schatzle JD, Terhorst C. Cutting Edge: The Adapters EAT-2A and -2B Are Positive Regulators of CD244- and CD84Dependent NK Cell Functions in the C57BL/6 Mouse. J IMMUNOL, 2010. 185:5683-5687. I.F.:5,65. 4 Fink DR, Holm D, Schlosser A, Nielsen O, Latta M, Lozano F, Holmskov U. Elevated numbers of SCART1(+) gamma delta T cells in skin inflammation and inflammatory bowel disease. MOL IMMUNOL, 2010. 47:1710-1718. I.F.:3,20. 5 Podlech J, Pintea R, Kropp KA, Fink A, Lemmermann NAW, Erlach KC, Isern E, Angulo A, Ghazal P, Reddehase MJ. Enhancerless Cytomegalovirus Is Capable of Establishing a Low-Level Maintenance Infection in Severely Immunodeficient Host Tissues but Fails in Exponential Growth. J VIROL, 2010. 84:6254-6261. I.F.:5,15. 90 6 Cervera A, Planas AM, Justicia C, Urra X, Jensenius JC, Torres F, Lozano F, Chamorro A. Genetically-Defined Deficiency of Mannose-Binding Lectin Is Associated with Protection after Experimental Stroke in Mice and Outcome in Human Stroke. PLoS ONE. 5:-. I.F.:4,35. 7 Muntasell A, Magri G, Pende D, Angulo A, Lopez-Botet M. Inhibition of NKG2D expression in NK cells by cytokines secreted in response to human cytomegalovirus infection. BLOOD, 2010. 115:5170-5179. I.F.:10,56. Grants for research in progress Lozano F. Estudio de las propiedades inmunomoduladoras de miembros linfoides y no linfoides de la superfamilia de receptores SRCR (Scavenger Receptor Cysteine-Rich). Sponsored by: Ministerio Educación y Ciencia, SAF2007-62197. Amount: 376.310,00 euros. Duration: 01/12/200730/11/2010. 8 Angulo A. Regulación transcripcional y funciones de los genes principales inmediatamente tempranos: implicaciones en la patogénesis viral. Sponsored by: MINISTERIO DE EDUCACIÓN Y CIENCIA, SAF2008-00382. Amount: 121.000,00 euros. Duration: 01/01/2008-31/12/2011. 9 Lozano F. Red Española de Investigación en Patología Infecciosa (REIPI). Sponsored by: Instituto de Salud Carlos III, RD06/0008. Amount: 60.000,00 euros. Duration: 01/01/200831/12/2010. Sintes J, Romero X, DeSalort J, Terhorst C, Engel P. Mouse CD84 is a pan-leukocyte cell-surface molecule that modulates LPS-induced cytokine secretion by macrophages. J LEUKOCYTE BIOL, 2010. 88:687-697. I.F.:4,40. Valles X, Roca A, Lozano F, Morais L, Suarez B, Casals F, Mandomando I, Sigauque B, Nhalungo D, Esquinas C, Quinto L, Alonso PL, Torres A. Serotype-specific pneumococcal disease may be influenced by mannosebinding lectin deficiency. EUR RESPIR J, 2010. 36:856-863. I.F.:5,53. 10 Guilabert A, Lozano F, Iranzo P, Julia M, Suarez-Casasus B, Moreno N, Herrero-Gonzalez J, Mascaro JM. The role of Fc gamma receptors polymorphisms in bullous pemphigoid. J AM ACAD DERMATOL, 2010. 63:161-163. I.F.:4,11. 11 Sanchez-Tillo E, Lazaro A, Torrent R, Cuatrecasas M, Vaquero EC, Castells A, Engel P, Postigo A. ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1. ONCOGENE, 2010. 29:3490-3500. I.F.:7,14. Lozano F. Nova bioteràpia en sepsis fùngica i polimicrobiana. Sponsored by: Centre d’Innovació i Desenvolupament Empresarial (CIDEM), VALTEC08-2-0034. Amount: 62.998,11 euros. Duration: 01/01/200831/12/2010. Lozano F. Immunoreceptores del Sistema Inmunitario Innato y Adaptativo. Sponsored by: Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR), 2009/SGR/00252. Amount: 68.640,00 euros. Duration: 01/01/2009-31/12/2012. Lozano F. Papel modulador de receptroes linfocitarios tipo scavenger (CD5 y CD6) en la patofisiología de la infección por el virus de la inmunodeficiencia humana 1 (VIH-1). Spon- AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Immune receptors of the innate and adaptive system sored by: FIPSE-FUNDACION PARA INVESTIGACIÓN Y PREVENCIÓN DEL SIDA EN ESPAÑA, 36-0773-09. Amount: 159.665,00 euros. Duration: 04/01/2010-03/01/2013. Engel P. Estudio de las moléculas CD150/SLAM en la función efectora de los linfocitos B de “tipo innato”. Sponsored by: Ministerio de Ciencia e Innovación, SAF2009-07071. Amount: 219.900,00 euros. Duration: 01/01/2009-31/12/2010. Thesis Lozano F, Moreno A. Influencia de los poliformismos de los genes de la inmunidad innata en el desarrollo y evolución de las infecciones tras un trasplante de órgano sólido. PhD student: Carlos Cervera Alvarez. 91 AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Musculoskeletal repair and plasticity Strategic Objectives Group Members TEAM LEADER Joaquim Forés i Viñeta (Hospital Clínic) Tel.: 93 227 93 14 E-mail: jfores@clinic.ub.es Idibaps members: Jesús Benito (Hospital Clínic) Andrés Combalía (Hospital Clínic) Francisco Maculé (Hospital Clínic) Montserrat Nuñez (Hospital Clínic) Jaume Pomés (Hospital Clínic) Josep M. Segur (Hospital Clínic) Sebastián García (Hospital Clínic) Sergi Sastre (Hospital Clínic) Santiago Suso (Hospital Clínic) Administrative Staff: Antònia Bayo (Hospital Clínic) Collaborators: Alex Soriano (Hospital Clínic) M.ª Teresa Anglada (Hospital Clínic) Jordi Asunción (Hospital Clínic) Misericordia Basora (Hospital Clínic) Guillem Bori (Hospital Clínic) Xavier Carné (Hospital Clínic) Ana Carreño (Hospital Clínic) Adela Faulí (Hospital Clínic) 92 Jenaro A. Fernández-Valencia (Hospital Clínic) Joan Xavier Fontdevila (Hospital Clínic) Salvador Fuster (Hospital Clínic) Xavier Gallart (Hospital Clínic) Eloy M. García Díez Ruben García Elvira Raquel García Tarriño Anna López Gutiérrez Felipe Orient (Hospital Clínic) Lluis Peidro (Hospital Clínic Daniel Poggio (Hospital Clínic) Dragos Popescu (Hospital Clínic) Salvi Prat (Hospital Clínic) Josep Riba (Hospital Clínic) Moisés Rios (Hospital Clínic) Xavier Sala (Hospital Clínic) Isabel Sañudo (Hospital Clínic) Xavier Tomás (Hospital Clínic) Pere Torner (Hospital Clínic) Antoni Trilla (Hospital Clínic) Raquel Vilarrasa (Hospital Clínic) Josep M. Serra (Hospital Clínic) Our research group, which was incorporated to the IDIBAPS in 2007, aims to agglutinate and generate synergies among specialists in different disciplines that work in the field of the locomotor system. This is a field with a growing social and technological demand, but with scant incidence in the research setting of this institution. There are many aspects of new knowledge related to the musculoskeletal system: cellular, genic and pharmacological therapies; new materials and implants; robotics; top-level surgical and anesthetic technology; and sophisticated imaging techniques. The lack of clinical scientific evidence relating to much of the new knowledge, and the great volume of patients in our setting, with limited resources, represent an important source of work from which to derive intellectual benefit. Working with humbleness but “thinking big” seems to us to be the best strategy for reaching the objective of being a reference group in our setting. Navigation and robotics applied to skeletal grafts. AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS MUSCULOSKELETAL REPAIR AND PLASTICITY Main Lines of Research 1. Bone physiopathology, pathological variation with age, evaluation of fracture setting techniques and bone substitutes. 2. Cartilage, degeneration and repair through tissue engineering. 3. Evaluation and design of new prosthetic implants. 4. Minimally invasive surgery with new technology and instruments. 5. Infections of the locomotor apparatus, their prevention and treatment. 6. Acute postoperative pain and chronic musculoskeletal pain. 7. Functional re-adaptation, prevalence and evaluation of health results in degenerative arthropathies. 8. Biology of autologous adipose tissue grafts. 9. Musculoskeletal system tissue bank. 10.Imaging diagnosis, new technologies in diagnosis and follow-up. 11.Collaboration in joint projects with the UASP. 12.Acute-phase response in open fractures. Use of IL-6, C-reactive protein and CK in predicting results, and correlation with the Gustilo classification. 13.Vascular anatomy of the upper extremity applied to reconstructive procedures. 14.Surgical management of facial lipoatrophy based on the injection of autologous adipose tissue in HIVinfected patients. 15.Nervous system: • Tubulization repair of peripheral nervous system damage. • Experimental reimplantation of nerve root preganglionic avulsions. PUBLICATIONS originals I.F.: 27,313 1 Ortega M, Marco F, Soriano A, Almela M, Martinez JA, Pitart C, Mensa J. Candida spp. bloodstream infection: influence of antifungal treatment on outcome. J ANTIMICROB CHEMOTH, 2010. 65:562-568. I.F.:4,35. 2 Martinez JA, Cobos-Trigueros N, Soriano A, Almela M, Ortega M, Marco F, Pitart C, Sterzik H, Lopez J, Mensa J. Influence of Empiric Therapy with a beta-Lactam Alone or Combined with an Aminoglycoside on Prognosis of Bacteremia Due to Gram-Negative Microorganisms. ANTIMICROB AGENTS CH, 2010. 54:3590-3596. I.F.:4,80. 3 Basora M, Pereira A, Soriano A, Martinez-Pastor JC, Sanchez-Etayo G, Tio M, Salazar F. Allogeneic blood transfusion does not increase the risk of wound infection in total knee arthroplasty. VOX SANG, 2010. 98:124-129. I.F.:2,59. 4 Martinez-Pastor JC, Vilchez F, Pitart C, Sierra JM, Soriano A. Antibiotic resistance in orthopaedic surgery: acute knee prosthetic joint infections due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. EUR J CLIN MICROBIOL, 2010. 29:1039-1041. I.F.:2,61. 5 Font-Vizcarra L, Garcia S, MartinezPastor JC, Sierra JM, Soriano A. Blood Culture Flasks for Culturing Synovial Fluid in Prosthetic Joint Infections. CLIN ORTHOP RELAT R, 2010. 468:22382243. I.F.:2,07. 6 Sastre S, Popescu D, Nunez M, Pomes J, Tomas X, Peidro L. Doublebundle versus single-bundle ACL reconstruction using the horizontal femoral position: a prospective, randomized study. KNEE SURG SPORT TR A, 2010. 18:32-36. I.F.:1,67. 7 Ruiz-Gaspa S, Guanabens N, Enjuanes A, Peris P, Martinez-Ferrer A, DeOsaba MJM, Gonzalez B, Alvarez L, Monegal A, Combalia A, Pares A. Lithocholic acid downregulates vitamin D effects in human osteoblasts. EUR J CLIN INVEST, 2010. 40:25-34. I.F.:2,64. 8 Popescu D, Sastre S, Caballero M, Lee JWK, Claret I, Nunez M, Lozano L. Meniscal repair using the FasT-Fix device in patients with chronic meniscal lesions. KNEE SURG SPORT TR A, 2010. 18:546-550. I.F.:1,67. 9 Jansa M, Hernandez C, Vidal M, Nunez M, Bertran MJ, Sanz S, Castell C, Sanz G. Multidimensional analysis of treatment adherence in patients with multiple chronic conditions. A cross-sectional study in a tertiary hospital. PATIENT EDUC COUNS, 2010. 81:161-168. I.F.:1,98. 10 Rodriguez-Blanco T, FernandezSan-Martin I, Balague-Corbella M, Berenguera A, Moix J, Montiel-Morillo E, Nunez-Juarez E, Gonzalez-Moneo MJ, Pie-Oncins M, Martin-Penacoba R, Roura-Olivan M, Nunez-Juarez M, Pujol-Ribera E. Study protocol of effectiveness of a biopsychosocial multidisciplinary intervention in the evolution of non-speficic sub-acute low back pain in the working population: cluster randomised trial. BMC HEALTH SERV RES, 2010. 10:-. I.F.:1,66. 11 Enjuanes A, Ruiz-Gaspa S, Peris P, Ozalla D, Alvarez L, Combalia A, DeOsaba MJM, Monegal A, Pares A, Guanabens N. The effect of the alendronate on OPG/RANKL system in differentiated primary human osteoblasts. ENDOCRINE, 2010. 37:180186. I.F.:1,28. 93 AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS MUSCULOSKELETAL REPAIR AND PLASTICITY Grants for research in progress Soriano A. Estudio aleatorizado y doble ciego para establecer el momento más apropiado de la administración de la proxilaxis antibiótica en la artroplastia total de rodilla cuando se realiza bajo isquemia. Sponsored by: Ministerio Sanidad y Consumo, EC07/90330. Amount: 147.741,00 euros. Duration: 29/10/2007-30/12/2010. Fores J. Taller sobre el dolor per pacients i familiars (Chronic pain workshop for patients and relatives). Sponsored by: Fundació Marató TV3, 72810. Amount: 198.468,76 euros. Duration: 22/01/2008-21/01/2011. Nuñez M. Calidad de vida relacionada con la salud, dependencia física y costes en pacientes con artrosis después de artroplastia total de rodilla. Estudio prospectivo. Sponsored by: Fondo de Investigacion Sanitaria (FIS) Instituto de Salud Carlos III, PS09/01148. Amount: 35.695,00 euros. Duration: 01/01/201031/12/2012. Nuñez M. Efectivitat d’una intervenció multidisciplinària en l’evolució de la lumbàlgia subaguda inespecífica en població activa. Sponsored by: Patronat de la Fundació de la Marató de TV3, TV3 071610. Amount: 177.425,00 euros. Duration: 01/01/2008-31/12/2010. Fores J. Eficacia del tratamiento con condroitin sulfato en la rizartrosis. Medicion con test sensoriales y funcionales cuantitativos y analisis de concordancia con escalas subjetivas de dolor. Sponsored by: INSTITUTO DE SALUD CARLOS III, EC08/00079. Amount: 77.198,00 euros. Duration: 01/01/200930/12/2011. Garcia S. Estudio aleatorizado y abierto para determinar si la administración de 94 un antibiótico puede reducir la incidencia de infección en pacientes con cultivos positivos durante una artroplastia de cadera. Sponsored by: INSTITUTO DE SALUD CARLOS III, EC08/00182. Amount: 46.464,00 euros. Duration: 01/01/2009-30/12/2011. Soriano A. Estudio comparativo de la eficacia de pautas “cortas” y “largas” de la combinación rifampicina-levofloxacino en la infección estafilocócica postquirúrgica precoz y hematógena de prótesis articular.. Sponsored by: INSTITUTO DE SALUD CARLOS III, EC08/00189. Amount: 6.050,00 euros. Duration: 01/01/2009-30/12/2011. Thesis Garcia S, Soriano A. Utilitat de la histologia en el diagnòstic de la infecció de l’ artroplàstia de maluc. PhD student: Guillem Bori Tuneu. Macule F, Segur JM, Suso S. Artroplastia total de rodilla en pacientes obesos graves y mórbidas. PhD student: Luis Mª Lozano Lizarraga. Suso S. Nuevo protocolo de lectura de imágenes y sistemas de clasificacion de las fracturas del humero proximal (FHP). PhD student: Jose Maria Mora Guix. AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Immunogenetics of the autoinflammatory response Strategic Objectives Group Members TEAM LEADER Jordi Yagüe (Hospital Clínic) Tel.: 93 227 54 00 (Ext: 2155) Fax: 93 451 80 38 E-mail: jyague@clinic.ub.es Idibaps members: Juan Ignacio Aróstegui (Hospital Clínic) Manel Juan (Hospital Clínic) In the field of autoinflammatory diseases: Promotion of basic, clinical and translation research in the physiopathology of autoinflammatory diseases as a model for gaining in-depth knowledge of the regulation of the normal inflammatory response, its dysfunctions, and its repercussions upon the immune response. In the field of immune response: Determination of the components of normal and pathological inflammatory response is essential for modulating the specific recognition phenomena of the immune response. Main Lines of Research Research Fellows: Emma Garcia Melchor (Agaur) Collaborators: Laura Carretero (IDIBAPS) Mariona Pascal (Hospital Clínic) Eva Gonzalez Roca (Hospital Clínic) In the field of autoinflammatory diseases: • Determination of the genetic and molecular bases of the autoinflammatory process. • Characterization of the regulatory mechanisms of the inflammasome and its dysfunction. • Characterization of the specific transcriptional profiles of autoinflammatory diseases. • Isolation of new genes responsible for hereditary autoinflammatory diseases and identification of genetic susceptibility factors for the development of polygenic autoinflammatory processes. • Definition of new therapeutic targets for the treatment of autoinflammatory diseases. PUBLICATIONS originals I.F.: 19,96 1 Graell E, Arostegui JI, Sanmarti R, Blanco FJ, Yague J, Pinto JA, Plaza S, Fernandez-Sueiro JL, Gonzalez A, Canete JD. Possible association between NOD2 variants and joint surgery in psoriatic arthritis. CLIN EXP RHEUMATOL, 2010. 28:30-34. I.F.:2,40. 2 Arostegui JI, Saldana MDL, Pascal M, Clemente D, Aymerich M, Balaguer F, Goel A, DelCastillo CF, Rius J, Plaza S, Robledillo JCL, Juan M, Ibanez M, Yague J. A Somatic NLRP3 Mutation as a Cause of a Sporadic Case of Chronic Infantile Neurologic, Cutaneous, Articular Syndrome/Neonatal-Onset Multisystem Inflammatory Disease Novel Evidence of the Role of Low-Level Mosaicism as the Pathophysiologic Mechanism Under. ARTHRITIS RHEUM-US, 2010. 62:1158-1166. I.F.:7,33. 3 Picard C, VonBernuth H, Ghandil P, Chrabieh M, Levy O, Arkwright PD, Mcdonald D, Geha RS, Takada H, Krause JC, Creech CB, Ku CL, Ehl S, Marodi L, Al-Muhsen S, Al-Hajjar S, Al-Ghonaium A, Day-Good NK, Holland SM, Gallin JI, Chapel H, Speert DP, Rodriguez-Gallego C, Colino E, Garty BZ, Roifman C, Hara T, Yoshikawa H, Nonoyama S, Domachowske J, Issekutz AC, Tang M, Smart J, Zitnik SE, Hoarau C, Kumararatne DS, Thrasher AJ, Davies EG, Bethune C, Sirvent N, DeRicaud D, Camcioglu Y, Vasconcelos J, Guedes M, Vitor AB, Rodrigo C, Almazan F, Mendez M, Arostegui JI, Alsina L, Fortuny C, Reichenbach J, Verbsky JW, Bossuyt X, Doffinger R, Abel L, Puel A, Casanova JL. Clinical Features and Outcome of Patients With IRAK-4 and MyD88 Deficiency. MEDICINE, 2010. 89:403-425. I.F.:5,05. 95 AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS Immunogenetics of the autoinflammatory response 4 Faner R, James E, Huston L, PujolBorrel R, Kwok WW, Juan M. Reassessing the role of HLA-DRB3 T-cell responses: Evidence for significant expression and complementary antigen presentation. EUR J IMMUNOL, 2010. 40:91-102. I.F.:5,18. Reviews I.F.: 3,01 1 Colobran R, Pedrosa E, CarreteroIglesia L, Juan M. Copy number variation in chemokine superfamily: the complex scene of CCL3L-CCL4L genes in health and disease. CLIN EXP IMMUNOL, 2010. 162:41-52. I.F.:3,01. Grants for research in progress Juan M. Variantes de CCL4 (MIP-1beta) y linfocitos T intratiroideos: modelo de la implicación de las quimiocinas en el reconocimiento de los linfocitos T CD4+ autorreactivos. Sponsored by: Instituto de Salud Carlos III, PI070329. Amount: 116.160,00 euros. Duration: 23/01/2008-30/12/2010. Yagüe J. Análisis de las vías de señalización TOLL/IL-1 receptor (TIR), NODLIKE receptor (NLR) y NF-kB en las formas hereditarias y no hereditarias de las enfermedades autoinflamatorias. Sponsored by: FIS, PS09/01182. Amount: 161.535,00 euros. Duration: 01/01/2010-30/12/2012. Lozano F. Nova bioteràpia en sepsis fùngica i polimicrobiana. Sponsored by: Centre d’Innovació i Desenvolupament Empresarial (CIDEM), VALTEC08-2-0034. Amount: 62.998,11 euros. Duration: 01/01/200831/12/2010. 96 Yagüe J. Análisis de las vías de señalización TOLL/IL-1 receptor (TIR), NODLIKE receptor (NLR) y NF-kB en las formas hereditarias y no hereditarias de las enfermedades autoinflamatorias. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1182. Amount: 161.535,00 euros. Duration: 01/01/2010-31/12/2012. AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS EMERGENCIES: PROCESSES AND PATHOLOGIES Strategic Objectives Group Members TEAM LEADER Oscar Miró Andreu (Hospital Clínic) Tel.: 93 227 54 00 (Ext.: 3153) E-mail: omiro@clinic.ub.es Idibaps members: Santiago Nogué Xarau (Hospital Clínic) Miguel Sánchez Sánchez (Hospital Clínic) Blanca Coll-Vinent Puig (Hospital Clínic) Sònia Jiménez Hernández (Hospital Clínic) Research Fellows: Emilio Salgado García (Hospital Clínic) Beatriz López Barbeito (Hospital Clínic) Albert Antolín Santaliestra (Hospital Clínic) María Torres Oliveros (Hospital Clínic) Núria Corominas García (Hospital Clínic) María Teresa Ruiz (Hospital Clínic) Victor Gil Espinosa (Hospital Clínic) Sira Aguiló Mir (Hospital Clínic) Rafel Perelló Carbonell (Hospital Clínic) Rosa Escoda Turón (Hospital Clínic) Francesc Xavier Escalada Roig (SEM) Núria Díaz Miranda (Pedagoga, Escola Molina, Barcelona) Alba Riesgo (Facultat de Medicina) Maria Luisa Benito (CAP Les Corts) Nursing Staff: Montserrat Amigó Tadín (Hospital Clínic) Eva Gómez Rodríguez (Hospital Clínic) Collaborators: Elisenda Gómez Angelats (Hospital Clínic) Josep Ramon Alonso Viladot (Hospital Clínic) Miguel Galicia Paredes (Hospital Clínic) Francesc Xavier Jiménez Fábrega (SEM) Mar Ortega Romero (Hospital Clínic) The group has a general interest in the study of all processes and pathologies inherent to the emergency setting - in all cases adopting a patient – centered approach and focusing on the acute process leading to emergency consultation. This approach is absolutely unique in Catalonia and in Spain, in view of the topic involved and the perspective from which it is addressed. The processes seen in the Emergency Department are exclusive and unique, and improvement in their knowledge leads to healthcare and organizational implications with considerable scope and repercussion. While the transverse characteristics of emergency disease conditions cause them to be dealt with by other disciplines, in the first few hours of their presentation they are exclusively addressed by the Emergency Department, where clinical research has not classically been considered. As a result, the possibilities for gaining in-depth and new knowledge on the part of the group are immense. Main Lines of Research 1. Functional aspects of Hospital Emergency Departments. Since 1997, the group has dedicated an important part of its research effort to exploring the fundamental functional mechanisms of a Hospital Emergency Department. In a series of studies, the group has demonstrated that the most important limiting element regarding the efficacy, effectiveness and quality of the Emergency Department is fundamented upon extrinsic rather than upon intrinsic factors (service demand). Among the intrinsic factors, those dependent upon the Hospital rather than on the Emergency Department as such are the most decisive in determining the functionality of a given Emergency Department. 2. Clinical aspects of intoxicated patients. This is a line of long tradition and history in our research group. The Clinic Hospital is a reference centre in Catalonia for healthcare and research in relation to intoxications of all kinds. It is a member of the SEMES-TOX group, which is the toxicology working group of the Spanish Society of Emergency Care Medicine and Urgencies, and of the STC-AETOX group of the Spanish Association of Toxicology. 3. Treatment of arrhythmias in the emergency room. For over 10 years the group has participated in a coordinated manner with the cardiologists of the center, with primary care physicians working in clinics in their corresponding reference areas, and with other investigators in Spain who work in Emergency Departments (the group forms part of the arrhythmias chapter of the Spanish Society of Emergency Care Medicine and Urgencies), in the investigation of disorders of this kind. The most relevant contributions of the group in this setting have been in reference to ATRIAL FIBRILLATION. 4. Evaluation of chest pain in the Emergency Department. The group coordinates and conducts important research work in the only structural chest pain unit currently operating in Spain, which began its activities in 2002. From the start, the group has centered its efforts on taking advantage of this fact to investigate the medical care of these patients, and to further knowledge of a subgroup of these subjects who had not been diagnosed at the time with acute coronary disease, and had therefore not been sufficiently investigated. 5. Diffusion of the teaching of cardiopulmonary resuscitation maneuvers among the general population. This is an interdisciplinary line of work which, from its start in the year 2000, has involved different professionals (physicians and nurses in both out- 97 AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS EMERGENCIES: PROCESSES AND PATHOLOGIES PUBLICATIONS and in-hospital emergency services, with pedagogical support). Its main objective is to explore all the possibilities and difficulties for diffusing knowledge of cardiopulmonary resuscitation maneuvers among the general population. The setting in which the research activity has been most intense is among students in secondary education (14-16 years of age), where the approach is made through a specific program, the PROCES (Programa de Reanimació cardiopulmonar Orientat a Centres d’Ensenyament Secundari, or cardiopulmonary resuscitation program oriented towards secondary education centres) designed exclusively for application in the current Catalan educational model, which has been fully developed by members of the group (Òscar Miró i Andreu, Miquel SánchezSánchez, and Núria Díaz-Miranda). 6. Emergency medical care for problems caused by drug abuse. Originally conceived as a toxicological variant, the importance and specificity of research in this field made it possible in 2001 to create this line of research. The advantages derived as a result of research from the emergency care perspective has made it possible to clearly improve our knowledge of this group of disorders. At present, the group works in collaboration with other groups in Spain and in other countries. 7. Acute heart failure. This more recently created research line focuses on the differential aspects (both clinical and epidemiological) of acute decompensated heart failure. Investigation of this syndrome – highly prevalent in Emergency Departments – is carried out in combination with other Emergency Departments throughout Spain, within the context of the acute heart failure working group of the Spanish Society of Emergency Care Medicine and Urgencies. 98 originals I.F.: 40,833 1 Perello R, Miro O, Marcos MA, Almela M, Bragulat E, Sanchez M, Agusti C, Miro JM, Moreno A. Predicting bacteremic pneumonia in HIV-1-infected patients consulting the ED. AM J EMERG MED, 2010. 28:454-459. I.F.:1,54. 2 Miro O, Martin-Sanchez FJ, BurilloPutze G, Julian A, Tomas S, Pacheco A, Sanchez M. Bibliometric and publication quality markers of Emergencias from 2005 to 2009 and comparison with emergency medicine journals included in Journal Citation Reports. EMERGENCIAS, 2010. 22:165-174. I.F.:3,08. 3 Noguera A, Moren C, Rovira N, Sanchez E, Garrabou G, Nicolas M, Munoz-Almagro C, Cardellach F, Miro O, Fortuny C. Evolution of Mitochondrial DNA Content After Planned Interruption of HAART in HIV-Infected Pediatric Patients. AIDS RES HUM RETROV, 2010. 26:1015-1018. I.F.:2,18. 4 Miro O, Galicia M, Sanchez M, Nogue S. Factors related to emergency department revisits after cocaine use. EMERGENCIAS, 2010. 22:408-414. I.F.:3,08. 5 Miro O, Burillo-Putze G, Plunkett PK, Brown AFT. Female representation on emergency medicine editorial teams. EUR J EMERG MED, 2010. 17:84-88. I.F.:0,73. 6 Duenas-Laita A, Putze GB, Alonso JR, Bajo A, Climent B, Corral E, Felices F, Ferrer A, Frutos MDH, Nogue S, Puiguriguer J. Fundamentals in the clinical management of intoxication due to smoke inhalation. EMERGENCIAS, 2010. 22:384-394. I.F.:3,08. 7 Antolin A, Ambros A, Mangiron P, Alves D, Sanchez M, Miro O. Grade of knowledge about the advance directive document by the chronic patient who comes to the emergency department. REV CLIN ESP, 2010. 210:379-388. I.F.:0,58. 8 Riesgo A, Herrero P, Llorens P, Jacob J, Martin-Sanchez FJ, Bragulat E, Miro O. Influence of patient’s sex in the form of presentation and the management of acute heart failure in Spanish emergency rooms. MED CLIN-BARCELONA, 2010. 134:671-677. I.F.:1,23. 9 Coll-Vinent B, Sanchez M, Nogue R, Miro O. Instruction in emergency medicine at university schools of medicine: the current situation in Spain. EMERGENCIAS, 2010. 22:21-27. I.F.:3,08. 10 Antolin A, Sanchez M, Llorens P, Sanchez FJM, Gonzalez-Armengol JJ, Ituno JP, Carbajosa JF, FernandezCanadas JM, DelCastillo JG, Miro O. Knowledge About Disease Course and Living Wills Among Patients With Heart Failure. REV ESP CARDIOL, 2010. 63:1410-1418. I.F.:2,75. 11 Coll-Vinent B, Torres S, Sanchez A, Miro N, Sanchez M, Miro O. Medical students’ predisposition to specialize in emergency medicine. EMERGENCIAS, 2010. 22:15-20. I.F.:3,08. 12 Negredo E, Romeu J, RodriguezSantiago B, Miro O, Garrabou G, Puig J, Perez-Alvarez N, Moren C, Ruiz L, Bellido R, Miranda C, Clotet B. Mild Improvement in Mitochondrial Function After a 3-Year Antiretroviral Treatment Interruption Despite Persistent Impairment of Mitochondrial DNA Content. CURR HIV RES, 2010. 8:379-385. I.F.:1,98. 13 Xarau SN, Romay MA, Martinez JMM, Clanchet JD, Prat ER, Sola JF. Multiple chemical sensitivity: Epidemiological, clinical and prognostic differences between occupational and non-occupational cases. MED CLIN-BARCELONA, 2010. 135:52-58. I.F.:1,23. AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS EMERGENCIES: PROCESSES AND PATHOLOGIES 14 Miro O, Llorens P, Martin-Sanchez FJ, Herrero P, Jacob J, PerezDura MJ, Gonzalez C, Alonso H, Gil V, Alvarez AB, Perello R, GonzalezArmengol JJ. Predicting the risk of reattendance for acute heart failure patients discharged from Spanish Emergency Department observation units. EUR J EMERG MED, 2010. 17:197-202. I.F.:0,73. 15 Bosch X, Loma-Osorio P, Guasch E, Nogue S, Ortiz JT, Sanchez M. Prevalence, Clinical Characteristics and Risk of Myocardial Infarction in Patients With CocaineRelated Chest Pain. REV ESP CARDIOL, 2010. 63:1028-1034. I.F.:2,75. 16 Jimenez S, Aguilo S, Gil V, Antolin A, Prieto S, Bragulat E, Coll-Vinent B, Miro O, Sanchez M. Psychosocial factors determine patients’ acceptance of emergency department discharge directly to hospital-at-home care. GAC SANIT, 2010. 24:303-308. I.F.:1,17. 17 Fonseca M, Sanclemente G, Hernandez C, Visiedo C, Bragulat E, Miro O. Residents, duties and burnout syndrome. REV CLIN ESP, 2010. 210:209-215. I.F.:0,58. 18 Nogue S, Ramos A, Portillo Sitges M, Pare C, Bosch X, Bragulat E, Sanchez M. Utility of coronary computed tomography to rule out acute coronary syndrome in the emergency department: a pilot study. EMERGENCIAS, 2010. 22:101-108. I.F.:3,08. 21 Galicia M, Nogue S, Sanjurjo E, Miro O. Visits to the emergency department due to ecstasy (MDMA) and amphetamine derivative consumption: Epidemiological, clinical and evolutional profile. REV CLIN ESP, 2010. 210:371378. I.F.:0,58. Reviews I.F.: 3,08 1 Oliu G, Nogue S, Miro O. Carbon monoxide poisoning: pathophysiologic principles underlying good treatment. EMERGENCIAS, 2010. 22:451-459. I.F.:3,08. Editorials I.F.: 12,32 1 Ferrando JP, Martin BB, Puig TC, Xarau SN. Assessing risk of liver toxicity in acute paracetamol intoxication when basing treatment on a RumackMatthew toxicity nomogram is not feasible. EMERGENCIAS, 2010. 22:365-368. I.F.:3,08. M, Bohils M. Triage and assignment of responsibility for care in cases of acute intoxication in the emergency department. EMERGENCIAS, 2010. 22:338-344. I.F.:3,08. 2 Miro O. Nenikekamen We have 19 3 Miro O. Project EMEGER: A bonis Amigo M, Nogue S, Miro O. Use of activated charcoal in acute poisonings: Clinical safety and factors associated with adverse reactions in 575 cases. MED CLIN-BARCELONA, 2010. 135:243-249. I.F.:1,23. 20 Miro O, Ortiz-Perez JT, Leon R, Lopez B, Perea R, DeCaralt TM, prevailed!. EMERGENCIAS, 2010. 22:401-403. I.F.:3,08. ad meliora. EMERGENCIAS, 2010. 22:1-2. I.F.:3,08. 4 Miro O. Specialization in emergency medicine: a residency program that is needed and in demand. EMERGENCIAS, 2010. 22:321-322. I.F.:3,08. Clinical Guidelines I.F.: 3,08 1 Jimenez S. Guidelines on acute pulmonary embolism from the European Society of Cardiology: reflections from the perspective of the emergency physician. EMERGENCIAS, 2010. 22:61-67. I.F.:3,08. Grants for research in progress Coll-Vinent B. Utilidad de la detección precoz de la fibrilación auricular. Sponsored by: Fondo de Investigaciones Sanitarias, PI070278. Amount: 99.220,00 euros. Duration: 01/01/2008-30/12/2010. Miro O. Grup de recerca consolidat. Sponsored by: Generalitat de Catalunya, SGR 2009-1385. Amount: 45.760,00 euros. Duration: 01/01/2009-31/12/2013. Miro O, Gomez E, Bragulat E, Nogue S, Sanchez M. Prevalencia, perfil demográfico, social y clínico, y pronóstico de los pacientes consumidores de cocaína que acuden a urgencias por dolor torácico. Sponsored by: Fondo de Investigaciones Sanitarias, PI07/0089. Amount: 32.500,00 euros. Duration: 01/01/2008-31/12/2010. Miro O. “Comparación de dos metodologías diferentes para la difusión de la enseñanza de la reanimación cardiopulmonar básica durante la escolarización obligatoria”. Sponsored by: Fondo de Investigación Sanitaria (FIS), PI 07/0073. Amount: 33.456,00 euros. Duration: 01/01/200831/12/2010. Thesis Miro O, Nogue S. Aportaciones a al epidemiologia y a las manisfestaciones clínicas de las sobredosis causadas por la cocaina y las nuevas drogas de diseño. PhD student: Miguel Angel Galicia Paredes. 99 AREA 1 BIOLOGICAL BIOLOGICAL AGGRESSION AGGRESSION AND AND RESPONSE RESPONSE MECHANISMS MECHANISMS Molecular and cellular bases of inflammation. EMERGENCIES: PROCESSES AND PATHOLOGIES Structural and biological mass spectrometry Strategic Objectives Group Members TEAM LEADER Daniel Closa (IIBB-CSIC) Tel.: 93 363 83 43 Fax: 93 363 83 01 E-mail: daniel.closa@iibb.csic.es 1.Molecular and cellular bases of inflammation: Study of inflammatory response in general. 1.Structural and biological mass spectrometry: Development of techniques for solving problems in proteomics and in the analysis of biomolecules in general. Application to the study of antigen presentation in autoimmune diseases and to the investigation of therapeutic targets and markers of the disease. Main Lines of Research 1. Molecular and cellular bases of inflammation: • Mechanisms involved in the development of systemic inflammatory processes. • New therapies for idiopathic pulmonary fibrosis. • Study of the protein associated with pancreatitis. Idibaps members: Oriol Bulbena (IIBB-CSIC) Emili Gelpí (IIBB-CSIC) Joaquín Abián (IIBB-CSIC-UAB) Montserrat Carrascal (IIBB-CSIC) Emma Folch (IBB-CSIC) Research Fellows: Gemma Gay S. Gea (TS) C. Lebrero (GENAME) R. Guillamat (CIBERES) 100 Technicians: L. Ignacio Sanchez V. Sirenko (IDIBAPS) Edita Bueno (JAE-TEC) Joan Villanueva (Proteored) Ana González (Proteored) D. Ovelleiro (Proteored) V. Casas (TS- MICINN) Collaborators: F. Pí (IIBB-CSIC) A. Salas (RC) A. Serrano (IIBB-CSIC) M. Gay (JAE-DOC) N. Franco (CIBEREHD) 2. Structural and biological mass spectrometry: • Phosphoproteomics of the human T lymphocyte. • Diagnostic and prognostic markers in cancer and other diseases. • External scientific-technical services. Proteomics Services and Coordination of Proteored Network. AREA 1 BIOLOGICAL AGGRESSION AND RESPONSE MECHANISMS MOLECULAR AND CELLULAR BASES OF INFLAMMATION. STRUCTURAL AND BIOLOGICAL MASS SPECTROMETRY PUBLICATIONS originals I.F.: 51,15 1 Gay M, Carrascal M, Gorga M, Pares A, Abian J. Characterization of peptides and proteins in commercial HSA solutions. PROTEOMICS, 2010. 10:172-181. I.F.:4,43. 2 Carrascal M, Gay M, Ovelleiro D, Casas V, Gelpi E, Abian J. Characterization of the Human Plasma Phosphoproteome Using Linear Ion Trap Mass Spectrometry and Multiple Search Engines. J PROTEOME RES, 2010. 9:876-884. I.F.:5,13. 7 Franco-Pons N, Gea-Sorli S, Closa D. Release of inflammatory mediators by adipose tissue during acute pancreatitis. J PATHOL, 2010. 221:175-182. I.F.:6,47. 8 Ponce J, Brea D, Carrascal M, Guirao V, Degregorio-Rocasolano N, Sobrino T, Castillo J, Davalos A, Gasull T. The effect of simvastatin on the proteome of detergent-resistant membrane domains: Decreases of specific proteins previously related to cytoskeleton regulation, calcium homeostasis and cell fate. PROTEOMICS, 2010. 10:19541965. I.F.:4,43. 3 Rodriguez-Trigo G, Zock JP, Pozo- 9 Banon-Maneus E, Diekmann F, Rodriguez F, Gomez FP, Monyarch G, Bouso L, Coll MD, Verea H, Anto JM, Fuster C, Barbera JA. Health Changes in Fishermen 2 Years After Clean-up of the Prestige Oil Spill. ANN INTERN MED, 2010. 153:489W176. I.F.:16,23. 4 Gutierrez P, Closae D, Piner R, Bulbena O, Menendez R, Torres A. Macrophage activation in exacerbated COPD with and without communityacquired pneumonia. EUR RESPIR J, 2010. 36:285-291. I.F.:5,53. 5 Vendrell I, Carrascal M, Campos F, Abian J, Suñol C. Methylmercury disrupts the balance between phosphorylated and non-phosphorylated cofilin in primary cultures of mice cerebellar granule cells A proteomic study. TOXICOL APPL PHARM, 2010. 242:109-118. I.F.:3,36. Carrascal M, Quintana LF, Moya-Rull D, Bescos M, Ramirez-Bajo MJ, Rovira J, Gutierrez-Dalmau A, Sole-Gonzalez A, Abian J, Campistol JM. Two-Dimensional Difference Gel Electrophoresis Urinary Proteomic Profile in the Search of Nonimmune Chronic Allograft Dysfunction Biomarkers. TRANSPLANTATION, 2010. 89:548-558. I.F.:3,50. Grants for research in progress Closa D. Caracterización de la activación de macrófagos intersticiales y alveolares en patologías respiratorias no infecciosas. Sponsored by: SEPAR, 2009-841. Amount: 12.000,00 euros. Duration: 01/01/2009-31/12/2010. 6 Lopez-Font I, Gea-Sorli S, De- Abian J. ProteoRed (Instituto Nacional de Proteómica). Sponsored by: Genoma España, 0000. Amount: 432.829,00 euros. Duration: 01/06/2005-01/06/2010. Madaria E, Gutierrez LM, PerezMateo M, Closa D. Pancreatic and pulmonary mast cells activation during experimental acute pancreatitis. WORLD J GASTROENTERO, 2010. 16:3411-3417. I.F.:2,09. Abian J. GENAME: Defining targets for therapeutics in spinal muscular atrophy. Sponsored by: Genoma España, 0000. Amount: 205.775,00 euros. Duration: 01/03/2007-31/05/2010. Abian J. Análisis proteómico de marcadores de enfermedad en suero humano. Sponsored by: Ministerio de Industria, Turismo y Comercio, CENIT/ ONCNOSIS. Amount: 499.903,00 euros. Duration: 18/01/2006-18/01/2010. Abian J. La activación linfocitaria a través del análisis del fosfoproteoma. Determinación de perfiles de fosforilación in vivo. Sponsored by: MICINN, BIO2009-11735. Amount: 147.000,00 euros. Duration: 01/01/201031/12/2012. Closa D. Trasplante de macrófagos reprogramados ex vivo como terapia para la pancreatitis aguda experimental. Sponsored by: Ministerio Ciencia e Innovación, SAF2009-07605. Amount: 80.000,00 euros. Duration: 01/01/201031/12/2011. Closa D. Derivados lipídicos como agentes moduladores de la respuesta hiperinflamatoria sistémica. Sponsored by: Ministerio Ciencia e Innovación, 201022002. Amount: 18.000,00 euros. Duration: 01/06/2010-01/06/2011. Bulbena O. Trasplante de células alveolares tipo II, derivadas de células madre adultas, para el tratamiento de la fibrosis pulmonar idiopática. Sponsored by: FIS, 201022002. Amount: 169.400,00 euros. Duration: 01/01/201031/12/2013. Thesis Mont L, Serrano-Mollar A. Efecto del ejercicio crónico en el desarrollo de fibrosis cardíaca: mecanismos implicados. PhD student: Gemma Gay Jordi 101 2 2 Respiratory, cardiovascular, renal AND pathobiology bioengineering Atherosclerosis and coronary disease 104 Arrhythmias, resynchronization and cardiac imaging 109 Nephro-urological diseases and kidney transplantation 114 Hypertension, lipids and cardiovascular risk 118 Respiratory biophysics and bioengineering 122 Applied research in infectious respiratory diseases, critically ill patients and lung cancer 125 Physiopathological mechanisms of respiratory illnesses 131 Clinical and Experimental Respiratory Immunoallergy (IRCE) 134 Inflammation and repair in respiratory illnesses 138 Urological genetics and tumors 140 AREA 2 Team envolved in: Respiratory, cardiovascular, renal pathobiology and bioengineering Determinantes genéticos y ambientales de la disfunción vascular en la hipertensión y cardiopatía isquémica (Red HERACLES) Atherosclerosis and coronary disease Strategic Objectives GROUP Members TEAM LEADER Manel Sabaté (Hospital Clínic) Tel.: 93 227 93 05 Fax: 93 227 93 05 E-mail: masabate@clinic.ub.es Idibaps members: Magda Heras Fortuny (Hospital Clínic) Amadeu Betriu (Hospital Clínic) Xavier Bosch (Hospital Clínic) Ana Paula Dantas (IDIBAPS) Carles Paré (Hospital Clínic) Félix Pérez Villa (Hospital Clínic) José Luis Pomar (Hospital Clínic) Montserrat Rigol (IDIBAPS) Mercè Roqué (Hospital Clínic) Research Fellows: Luis Álvarez Contreras Technicians: Nadia Castillo (Fundació Clínic) Nursing Staff: Anna Barrabés (Fundació Clínic) Elisabet de Mingo (IDIBAPS) 104 Administrative Staff: Montserrat Vázquez González (FCRB) Mª Ángeles Álvarez (Hospital Clínic) Collaborators: Montserrat Batlle (IDIBAPS) Mònica Masotti (Hospital Clínic) África Muxí (Hospital Clínic) Núria Solanes (FCRB) José Ortiz Pérez (Hospital Clínic) Alessandro Sionis (Hospital Clínic) Laura Novensà (IDIBAPS) Rut Andrea (Hospital Clínic) Manel Azqueta (Hospital Clínic) Montserrat Cardona (Hospital Clínic) Carles Falces (Hospital Clínic) Victoria Martín Yuste (Hospital Clínic) Sussanna Prat (Hospital Clínic) Mª José Pulgarín (IDIBAPS) 1. Physiopathology and improvement in the diagnosis and treatment of acute coronary syndrome. Role of the vascular inflammation mechanisms and thrombosis. a.Identification of different clinical signs and biomarkers of inflammation, necrosis and hemodynamic stress allowing improved diagnostic evaluation and risk stratification of patients with chest pain and negative troponin findings. b.Evaluation of the role of different inflammatory biomarkers and thrombosis in the physiopathology and course of patients with myocardial infarction. 2. Prevention of ventricular dysfunction in patients subjected to chemotherapy. A randomized study evaluating different drugs in the prevention of ventricular dysfunction in oncological patients subjected to high-dose chemotherapy with drugs of known cardiotoxicity. 3. Control mechanisms of post-vascular lesion intimal hyperplasia and regulation of vascular tone: a.Porcine model with femoral artery transplantation. b.Graft vasculopathy model with aortic transplantation in the rat. c.Model of femoral artery damage in the mouse. d.Porcine model of intimal hyperplasia of the coronary arteries. 4. Post-infarction myocardial regeneration. Study of the mechanisms of implantation, differentiation and regeneration of pluripotent stem cells in a porcine model of acute myocardial infarction. 5. Determination of the mechanisms involved in the regulation of nitric oxide and superoxide anion systems through steroid receptors, and their role in regulating the development of cardiovascular diseases such as atherosclerosis, hypertension, diabetes and metabolic syndrome. AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Atherosclerosis and coronary disease 6. Clinical evaluation of new devices for the treatment of ischemic and structural heart disease. 7. Evaluation of the efficacy of cellular therapy in patients with refractory angina. Main Lines of Research 1. Physiopathology and improvement in the diagnosis and treatment of acute coronary syndrome. Role of the vascular inflammation mechanisms and thrombosis. Evaluation of circulating endothelial cells and precursor endothelial cells. 2. Prevention of ventricular dysfunction in patients subjected to chemotherapy. 3. Study of the impact of gender difference upon ischemic heart disease. Evaluation of the characteristics of cardiovascular diseases in women and the different factors influencing their prognosis. 4. Vascular biology. Study of the mechanisms underlying post-revascularization procedure intimal hyperplasia. Within this line of work we have different projects involving different vascular lesion models in both large animals (such as pigs) and in small mammals (rats and mice). Specifically, in the experimental cardiology laboratory we have a model of angioplasty and stent placement in pigs, a model of intimal hyperplasia development in mice - with which studies in genetically modified animals are made – and two vascular transplant models in pigs and rats. 5. Study of neurohormonal activation and the fibrotic process associated with ventricular remodelling in heart failure in idiopathic or ischemic dilatory myocardiopathies. We use molecular biological and immunohistochemical techniques in myocardial tissue and serum neurohormonal determinations. This line will allow us to gain in-depth knowledge of the physiopathological mechanisms and evolutive course of heart failure. 6. Study of neurohormonal activation and the fibrotic process associated with ventricular remodelling in heart failure in idiopathic or ischemic dilatory myocardiopathies. This line will allow us to gain in-depth knowledge of the physiopathological mechanisms and evolutive course of heart failure. 7. Investigation of the mechanisms by which aging and menopause affect the signaling pathways of the nitric oxide and superoxide anion systems, and their role in regulating cardiovascular function in both healthy individuals and in patients with pre-existing cardiovascular diseases. 8.Clinical studies for evaluating the efficacy and safety of intracoronary devices (stents). 9.Chronic total coronary artery occlusion in humans: from physiopathology to the clinical implications of successful recanalization via percutaneous coronary intervention. 10. Cellular therapy in patients with refractory angina not amenable to recanalization. 11. Structural heart disease: study of quality of life in patients subjected to TAVI. 12. Mechanical circulatory assist devices. Ventricular assist as a bridge to transplantation. The role of estrogens upon oxidative stress in vivo. Representative images at left show mesenteric arterioles under visible light, and at right under fluorescent light, nuclei stained with ethidium bromide, 60 minutes after starting the hydroethidine perfusion. A)arterioles of a spontaneously hypertensive female rat (SHR) with physiological stress (OE); B) arterioles of an ovariectomized SHR (OVX); C) arterioles of an ovariectomized SHR treated with estrogen (OVX + E2). 105 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Atherosclerosis and coronary disease Team Members PUBLICATIONS Originals I.F.: 131,29 Colli A, Mestres CA, Espinosa G, Plasin MA, Pomar JL, Font J, Cervera R. Heart valve surgery in patients with the antiphospholipid syndrome: analysis of a series of nine cases. EUR J CARDIOTHORAC, 2010. 37:154-158. I.F.:2,40. 2 Garcia-De-La-Maria C, Marco F, 7 Ortiz-Perez JT, Betriu A, Lee DC, Armero Y, Soy D, Moreno A, DelRio A, Almela M, Cervera C, Ninot S, Falces C, Mestres CA, Gatell JM, DeAnta MTJ, Miro JM. Daptomycin Is Effective for Treatment of Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus epidermidis. ANTIMICROB AGENTS CH, 2010. 54:2781-2786. I.F.:4,80. DeCaralt TM, Meyers SN, Davidson CJ, Perea RJ, Sitges M, Bosch X, Bonow RO, Masotti M, Brugada J, Wu E. Angiographic and Magnetic Resonance Imaging Evaluation of In-Hospital Delay in Primary Percutaneous Intervention Delivery on Myocardial Salvage. AM J CARDIOL, 2010. 106:924-930. I.F.:3,58. 1 3 Bosch X, Loma-Osorio P, Guasch E, Nogue S, Ortiz JT, Sanchez M. Prevalence, Clinical Characteristics and Risk of Myocardial Infarction in Patients With Cocaine-Related Chest Pain. REV ESP CARDIOL, 2010. 63:1028-1034. I.F.:2,75. 4 Miro O, Ortiz-Perez JT, Leon R, Lopez B, Perea R, DeCaralt TM, Sitges M, Pare C, Bosch X, Bragulat E, Sanchez M. Utility of coronary computed tomography to rule out acute coronary syndrome in the emergency department: a pilot study. EMERGENCIAS, 2010. 22:101-108. I.F.:3,08. 5 Abu-Assi E, Ferreira-Gonzalez I, Ribera A, Marsal JR, Cascant P, Heras M, Bueno H, Sanchez PL, Aros F, Marrugat J, Garcia-Dorado D, Pena-Gil C, Gonzalez-Juanatey JR, PermanyerMiralda G. “Do GRACE (Global Registry of Acute Coronary events) risk scores still maintain their performance for predicting mortality in the era of contemporary management of acute coronary syndromes?”. AM HEART J, 2010. 160:826-U73. I.F.:4,36. 106 6 Martinez-Olondris P, Sibila O, Agusti C, Rigol M, Soy D, Esquinas C, Piner R, Luque N, Guerrero L, Quera MA, Marco F, DeLaBellacasa JP, Ramirez J, Torres A. An experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus in ventilated piglets. EUR RESPIR J, 2010. 36:901906. I.F.:5,53. 8 Garcia-Alvarez A, Sitges M, GarciaAlbeniz X, Sionis A, Loma-Osorio P, Bosch X. Atypical cardiac manifestation of hypereosinophilic syndrome and reversible cardiotoxicity to imatinib. INT J CARDIOL, 2010. 139:E29-E31. I.F.:3,47. 9 Ferreira-Gonzalez I, Marsal JR, Ribera A, Permanyer-Miralda G, GarciaDelBlanco B, Marti G, Cascant P, Martin-Yuste V, Brugaletta S, Sabate M, Alfonso F, Capote ML, DeLaTorre JM, Ruiz-Lera M, Sanmiguel D, Cardenas M, Pujol B, Baz JA, Iniguez A, Trillo R, Gonzalez-Bejar O, Casanova J, SanchezGila J, Garcia-Dorado D. Background, Incidence, and Predictors of Antiplatelet Therapy Discontinuation During the First Year After Drug-Eluting Stent Implantation. CIRCULATION, 2010. 122:1017U122. I.F.:14,82. 10 Miguel-Velado E, Perez-Carretero FD, Colinas O, Cidad P, Heras M, Lopez-Lopez JR, Perez-Garcia MT. Cell cycle-dependent expression of Kv3.4 channels modulates proliferation of human uterine artery smooth muscle cells. CARDIOVASC RES, 2010. 86:383391. I.F.:5,80. 11 Garcia-Alvarez A, Sitges M, Pinazo MJ, Regueiro-Cueva A, Posada E, Poyatos S, Ortiz-Peerez JT, Heras M, Azqueta M, Gascon J, Sanz G. Chagas Cardiomiopathy: The Potential of Diastolic Dysfunction and Brain Natriuretic Peptide in the Early Identification of Cardiac Damage. PLOS NEGLECT TROP D, 2010. 4:-. I.F.:4,69. 12 Cidad P, Moreno-Dominguez A, Novensa L, Roque M, Barquin L, Heras M, Perez-Garcia MT, Lopez-Lopez JR. Characterization of Ion Channels Involved in the Proliferative Response of Femoral Artery Smooth Muscle Cells. ARTERIOSCL THROM VAS, 2010. 30:1203-U297. I.F.:7,24. 13 Rodriguez-Guardado A, Miquel R, Perez F, Fresno M, Corachan M. Colonic polyposis due to Schistosoma intercalatum. T ROY SOC TROP MED H, 2010. 104:443-445. I.F.:2,55. 14 Guerrero L, Martinez-Olondris P, Rigol M, Esperatti M, Esquinas C, Luque N, Piner R, Torres A, Soy D. Development and validation of a high performance liquid chromatography method to determine linezolid concentrations in pig pulmonary tissue. CLIN CHEM LAB MED, 2010. 48:391-398. I.F.:1,89. 15 Sanchez MA, Jimenez-Navarro M, Crespo M, Alonso-Pulpon L, DeTeresa E, Castro-Beiras A, Roig E, Artigas R, Zapata A, DeUlibarri IL, Muniz J. Effect of a Training Program for Primary Care Physicians on the Optimization of BetaBlocker Treatment in Elderly Patients With Heart Failure. REV ESP CARDIOL, 2010. 63:677-685. I.F.:2,75. 16 Rigol M, Solanes N, Farre J, Roura S, Roque M, Berruezo A, Bellera N, Novensa L, Beng DT, Prat-Vidal C, Huzman MA, Batlle M, Hoefsloot M, Sitges M, Ramirez J, Dantas AP, Merino A, Sanz G, Brugada J, Bayes-Genis A, Heras M. Effects of Adipose Tissue-Derived Stem AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Atherosclerosis and coronary disease 27 Cell Therapy After Myocardial Infarction: Impact of the Route of Administration. J CARD FAIL, 2010. 16:357-366. I.F.:3,25. predictor of poor response to cardiac resynchronization therapy. EUR J HEART FAIL, 2010. 12:492-498. I.F.:3,71. 17 Novensa L, Selent J, Pastor 23 Diaz-Ricart M, Brunso L, Pino M, M, Sandberg K, Heras M, Dantas AP. Equine Estrogens Impair Nitric Oxide Production and Endothelial Nitric Oxide Synthase Transcription in Human Endothelial Cells Compared With the Natural 17 beta-Estradiol. HYPERTENSION, 2010. 56:405-U140. I.F.:6,61. Navalon F, Jou JM, Heras M, White JG, Escolar G. Preanalytical treatment of EDTA-anticoagulated blood to ensure stabilization of the mean platelet volume and component measured with the ADVIA counters. THROMB RES, 2010. 126:E30-E35. I.F.:2,41. 18 Novella S, Dantas AP, Segarra G, 24 Crespo-Leiro MG, Delgado JF, Pania- 28 Sionis A, Garcia-Alvarez A, Castel Novensa L, Bueno C, Heras M, Hermenegildo C, Medina P. Gathering of aging and estrogen withdrawal in vascular dysfunction of senescent accelerated mice. EXP GERONTOL, 2010. 45:868-874. I.F.:3,34. gua MJ, DePrada JAV, Fernandez-Yanez J, Almenar L, Diaz-Molina B, Roig E, Arizon JM, Alonso-Pulpon L, Garrido IP, Sanz ML, DeLaFuente L, Mirabet S, Manito N, Muniz J. Prevalence and severity of renal dysfunction among 1062 heart transplant patients according to criteria based on serum creatinine and estimated glomerular filtration rate: results from the CAPRI study. CLIN TRANSPLANT, 2010. 24:E88-E93. I.F.:2,00. 19 Molina BD, Leiro MGC, Pulpon LA, Mirabet S, Yanez JF, Bonet LA, Vilchez FG, Delgado JF, Manito N, Rabago G, Arizon JM, Romero N, Roig E, Blasco T, Pascual D, DeLaFuente L, Muniz J. Incidence and Risk Factors for Nonmelanoma Skin Cancer After Heart Transplantation. TRANSPL P, 2010. 42:3001-3005. I.F.:0,99. 20 Colli A, D’amico R, Mestres CA, Pomar JL, Camara ML, Ruyra X, Mulet J. Is Early Antithrombotic Therapy Necessary after Tissue Mitral Valve Replacement?. J HEART VALVE DIS, 2010. 19:405-411. I.F.:1,03. 21 Bellera MN, Ortiz JT, Caralt MT, Perez-Rodon J, Mercader J, FernandezGomez C, Pare C, Heras M. Magnetic resonance reveals long-term sequelae of apical ballooning syndrome. INT J CARDIOL, 2010. 139:25-31. I.F.:3,47. 22 Tolosana JM, Mont L, Sitges M, Berruezo A, Delgado V, Vidal B, Tamborero D, Morales M, Batlle M, Roig E, Castel MA, Perez-Villa F, Godoy M, Brugada J. Plasma tissue inhibitor of matrix metalloproteinase-1 (TIMP-1): an independent 25 Sanchis J, Bosch X, Bodi V, Nunez J, Doltra A, Heras M, Mainar L, Santas E, Bragulat E, Garcia-Alvarez A, Carratala A, Llacer A. Randomized comparison between clinical evaluation plus N-terminal pro-B-type natriuretic peptide versus exercise testing for decision making in acute chest pain of uncertain origin. AM HEART J, 2010. 159:-. I.F.:4,36. 26 Widimsky P, Wijns W, Fajadet J, DeBelder M, Knot J, Aaberge L, Andrikopoulos G, Baz JA, Betriu A, Claeys M, Danchin N, Djambazov S, Erne P, Hartikainen J, Huber K, Kala P, Klinceva M, Kristensen SD, Ludman P, Ferre JM, Merkely B, Milicic D, Morais J, Noc M, Opolski G, Ostojic M, Radovanovic D, DeServi S, Stenestrand U, Studencan M, Tubaro M, Vasiljevic Z, Weidinger F, Witkowski A, Zeymer U. Reperfusion therapy for ST elevation acute myocardial infarction in Europe: description of the current situation in 30 countries. EUR HEART J, 2010. 31:943-957. I.F.:9,80. Delgado JF, Crespo-Leiro MG, Gomez-Sanchez MA, Paniagua MJ, Gonzalez-Vilchez F, DePrada JAV, Fernandez-Yanez J, Pascual D, Almenar L, Martinez-Dolz L, Diaz B, Roig E, Segovia J, Arizon JM, Garrido I, Blasco T, Lopez J, Brossa V, Manito N, Muniz J. Risk factors associated with moderate-to-severe renal dysfunction among heart transplant patients: results from the CAPRI study. CLIN TRANSPLANT, 2010. 24:E194-E200. I.F.:2,00. MA, Cordero M, Josa M, Perez-Villa F, Roig E. Severe aortic regurgitation and reduced left ventricular ejection fraction: Outcomes after isolated aortic valve replacement and combined surgery. J HEART LUNG TRANSPL, 2010. 29:445448. I.F.:3,54. 29 Sola R, Bruckert E, Valls RM, Narejos S, Luque X, Castro-Cabezas M, Domenech G, Torres F, Heras M, Farres X, Vaquer JV, Martinez JM, Almaraz MC, Anguera A. Soluble fibre (Plantago ovata husk) reduces plasma low-density lipoprotein (LDL) cholesterol, triglycerides, insulin, oxidised LDL and systolic blood pressure in hypercholesterolaemic patients: A randomised trial. ATHEROSCLEROSIS, 2010. 211:630-637. I.F.:4,52. 30 Portillo K, Santos S, Madrigal I, Blanco I, Pare C, Borderias L, Peinado VI, Roca J, Mila M, Barbera JA. Study of the BMPR2 Gene in Patients with Pulmonary Arterial Hypertension. ARCH BRONCONEUMOL, 2010. 46:129-134. I.F.:2,17. 31 Castel A, Magnani S, Mont L, Roig E, Tamborero D, Mendez-Zurita F, Femenia JF, Tolosana JM, Perez-Villa F, Brugada J. Survival in New York Heart Association class IV heart failure patients treated with cardiac resynchronization therapy compared with patients on optimal pharmacological treatment. EUROPACE, 2010. 12:1136-1140. I.F.:1,87. 107 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Atherosclerosis and coronary disease 32 Gonzalez-Vilchez F, Almenar L, Arizon JM, Mirabet S, Delgado JF, DeMolina BD, Gomez M, Paniagua MJ, Perez-Villa F, Roig E, DePrada JAV. Temporal Trends in the Use of Proliferation Signal Inhibitors in Maintenance Heart Transplantation: A Spanish Multicenter Study. TRANSPL P, 2010. 42:2997-3000. I.F.:0,99. 33 Martinez-Olondris P, Rigol M, Torres A. What lessons have been learnt from animal models of MRSA in the lung?. EUR RESPIR J, 2010. 35:198-201. I.F.:5,53. Reviews I.F.: 8,40 1 Bosch X, Marrugat J, Sanchis J. Platelet glycoprotein IIb/IIIa blockers during percutaneous coronary intervention and as the initial medical treatment of non-ST segment elevation acute coronary syndromes. COCHRANE DB SYST REV, 2010. :-. I.F.:5,65. 2 Segovia J, Bermejo J, Alfonso F, Heras M. The Right Heart and Pulmonary Circulation. Is It Really a Minor Circulation?. REV ESP CARDIOL, 2010. 63:77-80. I.F.:2,75. Editorials I.F.: 6,91 1 Bosch X. Safeguarding good scientific practice in Europe The increasingly global reach of science requires the harmonization of standards. EMBO REP, 2010, 2010. 11:252-257. I.F.:6,91. Clinical Guidelines I.F.: 12,20 1 Wijns W, Kolh P. Guidelines on myocardial revascularization The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) 108 and the European Association for CardioThoracic Surgery (EACTS). EUR HEART J, 2010. 31:2501-2555. I.F.:9,80. 2 Kolh P, Wijns W, Danchin N, DiMario C, Falk V, Folliguet T, Garg S, Huber K, James S, Knuuti J, Lopez-Sendon J, Marco J, Menicanti L, Ostojic M, Piepoli MF, Pirlet C, Pomar JL, Reifart N, Ribichini FL, Schalij MJ, Sergeant P, Serruys PW, Silber S, Uva MS, Taggart D. Guidelines on myocardial revascularization The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). EUR J CARDIO-THORAC, 2010. 38:S1-S52. I.F.:2,40. Multicentrics I.F.: 61,87 1 Gerstein HC, Ratner RE, Cannon CP, Serruys PW, Garcia-Garcia HM, VanEs GA, Kolatkar NS, Kravitz BG, Miller DM, Huang C, Fitzgerald PJ, Nesto RW. Effect of Rosiglitazone on Progression of Coronary Atherosclerosis in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease. CIRCULATION, 2010. 121:1176-1187. I.F.:14,82. 2 Mehta SR, Bassand JP, Chrolavicius S, Diaz R, Eikelboom JW, Fox KAA, Granger CB, Jolly S, Joyner CD, Rupprecht HJ, Widimsky P, Afzal R, Pogue J, Yusuf S. Dose Comparisons of Clopidogrel and Aspirin in Acute Coronary Syndromes. NEW ENGL J MED, 2010. 363:930-942. I.F.:47,05. Grants for research in progress Heras M. HERACLES - Determinantes Genéticos y Ambientales de la Disfunción Vascular en la Hipertensión y Cardiopatía Isquémica. Sponsored by: Ministerio Sanidad y Consumo, RD06/0009/0008. Amount: 204.018,22 euros. Duration: 01/01/2007-31/12/2010. Batlle M. Análisis del papel del péptido Ang1-7 del Sistema Renina Angiotensina en el desarrollo del remodelado ventricular en la Insuficiencia Cardíaca. Sponsored by: Sociedad Española de Cardiología, IP004486. Amount: 12.000,00 euros. Duration: 01/01/200931/12/2010. Dantas AP. Regulación hormonal del perfil proteómico y la función vascular durante el envejecimiento y la evolución de enfermedades cardiovasculares. Sponsored by: FIS, PI040171. Amount: 104.302,00 euros. Duration: 01/01/2009-31/12/2011. Heras M. Células endoteliales circulantes y células progenitoras endoteliales en la enfermedad cardiovascular aguda. Correlación con la función endotelial y la evolución clínica. Sponsored by: FIS, PI080272. Amount: 68.002,00 euros. Duration: 01/01/2008-31/12/2011. Bosch X. Prevención de la disfunción ventricular con enalapril y carvedilol en pacientes sometidos a quimioterapia intensiva para el tratamiento de hemopatías malignas. Sponsored by: Instituto de Salud Carlos III, EC07/90211. Amount: 289.825,25 euros. Duration: 01/01/2008-31/12/2010. Roque M, Heras M, Novensà L, Rigol M, Solanes N. Prevenció i tractament de la hiperplàsia de l’íntima mitjançant l’ús de bloquejants del canal Kv1.3. Sponsored by: Generalitat de Catalunya (VALTEC), PI040823. Amount: 80.000,00 euros. Duration: 01/01/200931/12/2011. Sabate M. Chronic total occlusions of human coronary arteries: from pathophysiology to long-term clinical implications of successful recanalization by means of percutaneous coronary intervention. Sponsored by: FUNDACIÓ LA MARATÓ DE TV3, 082130. Amount: 95.200,72 euros. Duration: 29/04/201004/03/2012. AREA 2 Respiratory, cardiovascular and renal pathobiology and bioengineering Team envolved in: Red de Investigación en Insuficiencia Cardiaca en España (REDINSCOR) Arrhythmias, resynchronization and cardiac imaging Strategic Objectives Group Members TEAM LEADER Josep Brugada (Hospital Clínic) Tel.: 93 227 55 51 E-mail: jbrugada@clinic.ub.es Idibaps members: Lluis Mont (Hospital Clínic) Marta Sitges (Hospital Clínic) Teresa M. de Caralt (Hospital Clínic) Vidal, Bárbara (Hospital Clínic) José Tomás Ortiz (Hospital Clínic) Postdoctoral fellows: Gemma Gay-Jordi (FIS) Montserrat Batlle (Fundació Clínic) Montserrat Rigor (Fundació Clínic) Núria Solanes (Fundació Clínic) Research Fellows: Etel Silva (Fundació Clínic - cvREMOD) Paola Berne (CNIC) Eduard Guasch (Rio OrtegaIDIBAPS-ISC III) David Andreu (Fundació Clínic) Silvia Montserrat (Hospital Clínic- Fundació Clínic) Juan Fernández-Armenta (Fundacio Clínic - cvREMOD) Ada Doltra (Fundació Clínic cvREMOD) Naiara Calvo (Hospital Clínic - Premi fi de residència, 3 anys) Pablo Ramos (Premi fi de residència HCP, 1 any) Esther Guiu (Fundació Clínic) Technicians: Cira Rubies (Fundació Cinic HERACLES) Nursing Staff: Mariona Matas (Hospital Clínic) Silvia Poyatos (Fundació Clínic) Anna Barrabes (Fundació Clínic) Silvia Vidorreta (Fundació Clínic iCARDEA) Sara Hevia (Fundació Clínic REDINSCOR) Administrative Staff: Neus Portella (Fundació Clínic) Staticians: Roger Borras (Fundació Clínic) Collaborators: Antonio Berruezo (Hospital Clínic) Mª Àngels Castel (Hospital Clínic) José Mª Tolosana (Hospital Clínic) Rosario J Perea (Hospital Clínic) Visiting Scientists: Csaba Herczku (Beca EHRA, European Heart Rhythm Association) Hervoika M Zeljo (Beca EHRA, European Heart Rhythm Association) Edi Belu (Beca EHRA, European Heart Rhythm Association) Freddy E. Diaz (Fellow Venezuela) Damian Azocar (Beca Fundación Carolina, Argentina) The aims for the coming year are fundamentally to continue developing the five main research lines of the group: genetic cardiovascular diseases, atrial fibrillation, cardiac resynchronization, ventricular tachycardias, and experimental models of etiological factors in atrial fibrillation. A new research line may be added in sports cardiology, taking advantage of our previous experience in arrhythmias and cardiac imaging, and in the previous development of a murine experimental model of chronic training. Another strategic aim of the group is to consolidate the Cardiac Imaging Subgroup, which collaborates with all the group research lines, applying cardiac imaging techniques to the study of the physiopathology of arrhythmias and their mechanics. Furthermore, we wish to continue promoting prospective multicenter projects allowing the obtainment of transcendental clinical results, without abandoning practical clinical research, with a view to improving patient care. Main Lines of Research 1. Cardiovascular genetic diseases: •This year patients continue to be included in the multicenter study ‘Sudden cardiac death: Translating basic science into clinical care’, in collaboration with Dr. Ramon Brugada of the Cardiovascular Genetics Center UdG-IDIBGI, in Girona. 2. Experimental models for the study of etiological factors in atrial fibrillation: •We wish to continue analyzing the mechanisms conditioning the appearance of atrial and ventricular fibrosis in the rat model of resistance exercise. •We are continuing collaboration with the Pneumology Sleep Unit and the Department of Physical Medicine of the Faculty of Medicine of Barcelona 109 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Arrhythmias, resynchronization and cardiac imaging University, with the purpose of studying the repercussions of obstructive apnea upon the heart, using an experimental model in rats. 3. Atrial fibrillation (AF): •On one hand we are continuing the study of etiological factors in primary atrial fibrillation, specifically with the FUTURE study, which analyzes the role of undetected hypertension and physical exercise. •Recruitment is continuing in the SARA study (Spanish Atrial Fibrillation vs Antiarrhythmic Drugs). Comparative multicenter study of the efficacy of ablation versus drug treatment. •Recruitment has been completed in two randomized, prospective studies designed to compare different ablation techniques. 4. Ventricular tachycardia (VT): •Multicenter study of antiarrhythmic drugs versus ablation in ischemic patients with automated implantable defibrillators. •A prospective study evaluating the ejection fraction following ventricular extrasystolia ablation in patients with ventricular extrasystoles and structural heart disease. •Different prospective studies are being conducted, evaluating the clinical usefulness of epicardial ablation in different substrates. •Software has been developed to delimit the slow conduction zones within myocardial scars by means of magnetic resonance studies and their fusion with images obtained from three-dimensional navigation sysems. •Siemens has has sponsored a prospective study to evaluate remodelling and sudden death risk predictive capacity with MRI and biomarker levels in patients with structural heart disease. 5. Sports cardiology: •We are continuing work on the murine experimental model of cardiac adaptation to chronic training, developed for the study of atrial fibrillation physiopathology, focusing research mainly on right ventricle adaptation. •We have incorporated the human clinical model thanks to collaboration of the group with elite sports entities (FC Barcelona and the Consell Català de la Salut), performing cardiac imaging studies of all the athletes, and again focusing on cardiac adaptation to chronic training. (A) Map of atrial fibrillation: Atrial fibrillation ablation procedure. We see the ablation scheme and integration of the 3D reconstruction of a CAT scan within the navigator. This system allows real time catheter localization within the heart of the patient. (B) Map of ventricular tachycardia: Ventricular tachycardia ablation procedure. In this case we see an epicardial map of the left ventricle in a patient with structural heart disease (right). The 3D reconstruction derived from an MRI scan with gadolinium contrast injection allows noninvasive characterization of the tissue and planning of the intervention (left). RESEARCH GROUP Cardiac resynchronization Group Leader: Lluis Mont (Hospital Clínic) Our group focuses its research on the applications and results of cardiac resynchronization techniques. At present we are carrying out a number of studies:- We are continuing recruitment in two studies to evaluate the effect of optimization in the success of cardiac resynchronization. BEST study.- Inclusion is continuing in the ECHO-CRT study on the efficacy of cardiac resynchronization therapy (CRT) in patients with narrow QRS waves.- Inclusion has ended in the multicenter SEPTAL-CRT trial, designed to evaluate the efficacy of 110 septal versus right ventricle apical stimulation.- We have started the CRT CAT project, which is a multicenter prospective study in Catalonia, designed to evaluate the efficacy, cost and complications of cardiac resynchronization in our setting.- We have started the multicenter SPARE III study, designed to evaluate the efficacy of CRT in atrial fibrillation. - The cvREMOD study is ongoing, financed by the CENIT (CDTI). This project has allowed us to develop a porcine experimental model of mechanical dyssynchrony, with the purpose of producing the tools necessary for further exploring the mechanisms of action of CRT. AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Arrhythmias, resynchronization and cardiac imaging PUBLICATIONS Originals I.F.: 93,71 1 Diastolic Dysfunction and Brain Natriuretic Peptide in the Early Identification of Cardiac Damage. PLOS NEGLECT TROP D, 2010. 4:-. I.F.:4,69. encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. HEART RHYTHM, 2010. 7:33-46. I.F.:4,56. 6 10 Partemi S, Berne PM, Batlle M, 2 Miro O, Ortiz-Perez JT, Leon R, Rigol M, Solanes N, Farre J, Roura S, Roque M, Berruezo A, Bellera N, Novensa L, Beng DT, Prat-Vidal C, Huzman MA, Batlle M, Hoefsloot M, Sitges M, Ramirez J, Dantas AP, Merino A, Sanz G, Brugada J, Bayes-Genis A, Heras M. Effects of Adipose Tissue-Derived Stem Cell Therapy After Myocardial Infarction: Impact of the Route of Administration. J CARD FAIL, 2010. 16:357-366. I.F.:3,25. Garcia-De-La-Maria C, Marco F, Armero Y, Soy D, Moreno A, Del Rio A, Almela M, Cervera C, Ninot S, Falces C, Mestres CA, Gatell JM, DeAnta MTJ, Miro JM. Daptomycin Is Effective for Treatment of Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus epidermidis. ANTIMICROB AGENTS CH, 2010. 54:2781-2786. I.F.:4,80. Lopez B, Perea R, DeCaralt TM, Sitges M, Pare C, Bosch X, Bragulat E, Sanchez M. Utility of coronary computed tomography to rule out acute coronary syndrome in the emergency department: a pilot study. EMERGENCIAS, 2010. 22:101-108. I.F.:3,08. 3 Ortiz-Perez JT, Betriu A, Lee DC, DeCaralt TM, Meyers SN, Davidson CJ, Perea RJ, Sitges M, Bosch X, Bonow RO, Masotti M, Brugada J, Wu E. Angiographic and Magnetic Resonance Imaging Evaluation of In-Hospital Delay in Primary Percutaneous Intervention Delivery on Myocardial Salvage. AM J CARDIOL, 2010. 106:924-930. I.F.:3,58. 4 Garcia-Alvarez A, Sitges M, Garcia-Albeniz X, Sionis A, LomaOsorio P, Bosch X. Atypical cardiac manifestation of hypereosinophilic syndrome and reversible cardiotoxicity to imatinib. INT J CARDIOL, 2010. 139:E29-E31. I.F.:3,47. 5 Garcia-Alvarez A, Sitges M, Pinazo MJ, Regueiro-Cueva A, Posada E, Poyatos S, Ortiz-Peerez JT, Heras M, Azqueta M, Gascon J, Sanz G. Chagas Cardiomiopathy: The Potential of 7 Tolosana JM, Mont L, Sitges M, Berruezo A, Delgado V, Vidal B, Tamborero D, Morales M, Batlle M, Roig E, Castel MA, Perez-Villa F, Godoy M, Brugada J. Plasma tissue inhibitor of matrix metalloproteinase-1 (TIMP-1): an independent predictor of poor response to cardiac resynchronization therapy. EUR J HEART FAIL, 2010. 12:492-498. I.F.:3,71. 8 Castel A, Magnani S, Mont L, Roig E, Tamborero D, Mendez-Zurita F, Femenia JF, Tolosana JM, Perez-Villa F, Brugada J. Survival in New York Heart Association class IV heart failure patients treated with cardiac resynchronization therapy compared with patients on optimal pharmacological treatment. EUROPACE, 2010. 12:1136-1140. I.F.:1,87. 9 Kapplinger JD, Tester DJ, Alders M, Benito B, Berthet M, Brugada J, Brugada P, Fressart V, Guerchicoff A, HarrisKerr C, Kamakura S, Kyndt F, Koopmann TT, Miyamoto Y, Pfeiffer R, Pollevick GD, Probst V, Zumhagen S, Vatta M, Towbin JA, Shimizu W, Schulze-Bahr E, Antzelevitch C, Salisbury BA, Guicheney P, Wilde AAM, Brugada R, Schott JJ, Ackerman MJ. An international compendium of mutations in the SCN5A- Berruezo A, Mont L, Riuro H, Ortiz JT, Roig E, Pascali VL, Brugada R, Brugada J, Oliva A. Analysis of mRNA from human heart tissue and putative applications in forensic molecular pathology. FORENSIC SCI INT, 2010. 203:99-105. I.F.:2,10. 11 Silva E, Sitges M, Doltra A, Mont L, Vidal B, Castel MA, Tolosana JM, Berruezo A, Juanatey JRG, Brugada J. Analysis of temporal delay in myocardial deformation throughout the cardiac cycle: Utility for selecting candidates for cardiac resynchronization therapy. HEART RHYTHM, 2010. 7:1580-1586. I.F.:4,56. 12 Auricchio A, Brugada J, Ellenbogen KA, Gold MR, Leyva F. Assessment of a novel device-based diagnostic algorithm to monitor patient status in moderate-to-severe heart failure: rationale and design of the CLEPSYDRA study. EUR J HEART FAIL, 2010. 12:1363-1371. I.F.:3,71. 13 Tamborero D, Mont L, Berruezo A, Guasch E, Rios J, Nadal M, Matiello M, Andreu D, Sitges M, Brugada J. Circumferential pulmonary vein ablation: Does use of a circular mapping catheter improve results? A prospective randomized study. HEART RHYTHM, 2010. 7:612-618. I.F.:4,56. 14 Vidal B, Delgado V, Mont L, Poyatos S, Silva E, Castel MA, Tolosana JM, Berruezo A, Brugada J, Sitges M. Decreased likelihood of response to cardiac resynchronization in patients with severe heart failure. EUR J HEART FAIL, 2010. 12:283-287. I.F.:3,71. 111 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Arrhythmias, resynchronization and cardiac imaging 15 Berruezo A, Zeljko HM, Bartrons J, Mayol J, Prada F, Brugada J. Defibrillation threshold decrease with the supradiaphragmatic extracardiac implantable cardioverter-defibrillator implantation technique. EUROPACE, 2010. 12:1649-1651. I.F.:1,87. 16 Calvo N, Mont L, Tamborero D, Berruezo A, Viola G, Guasch E, Nadal M, Andreu D, Vidal B, Sitges M, Brugada J. Efficacy of circumferential pulmonary vein ablation of atrial fibrillation in endurance athletes. EUROPACE, 2010. 12:30-36. I.F.:1,87. 17 Wu J, Shimizu W, Ding WG, Ohno S, Toyoda F, Itoh H, Zang WJ, Miyamoto Y, Kamakura S, Matsuura H, Nademanee K, Brugada J, Brugada P, Brugada R, Vatta M, Towbin JA, Antzelevitch C, Horie M. KCNE2 modulation of Kv4.3 current and its potential role in fatal rhythm disorders. HEART RHYTHM, 2010. 7:199-205. I.F.:4,56. 18 DePotter T, Berruezo A, Mont L, Matiello M, Tamborero D, Santibanez C, Benito B, Zamorano N, Brugada J. Left ventricular systolic dysfunction by itself does not influence outcome of atrial fibrillation ablation. EUROPACE, 2010. 12:24-29. I.F.:1,87. 22 Criado E, Sanchez M, Ramirez J, Arguis P, DeCaralt TM, Perea RJ, Xaubet A. Pulmonary Sarcoidosis: Typical and Atypical Manifestations at High-Resolution CT with Pathologic Correlation. RADIOGRAPHICS, 2010. 30:1567-U155. I.F.:2,75. 23 Pepi M, Evangelista A, Nihoyannopoulos P, Flachskampe FA, Athanassopoulos G, Colonna P, Habib G, Ringelstein EB, Sicari R, Zamorano JL, Sitges M. Recommendations for echocardiography use in the diagnosis and management of cardiac sources of embolism. EUR J ECHOCARDIOGR, 2010. 11:461-476. I.F.:1,48. 24 Pava LF, Perafan P, Badiel M, Arango JJ, Mont L, Morillo CA, Brugada J. R-wave peak time at DII: A new criterion for differentiating between wide complex QRS tachycardias. HEART RHYTHM, 2010. 7:922-926. I.F.:4,56. 25 Moreno J, Quintanilla JG, Lopez- D, Berruezo A, Montserrat J, Embid C, Rios J, Villacastin J, Brugada J, Mont L. Low efficacy of atrial fibrillation ablation in severe obstructive sleep apnoea patients. EUROPACE, 2010. 12:1084-1089. I.F.:1,87. Farre A, Archondo T, Cervigon R, Aragoncillo P, Usandizaga E, Silva J, Rodriguez-Bobada C, Rojo JL, PerezCastellano N, Mironov S, Mont L, DePrada TP, Macaya C, Perez-Villacastin J. Skeletal myoblast implants induce minor propagation delays, but do not promote arrhythmias in the normal swine heart. EUROPACE, 2010. 12:1637-1644. I.F.:1,87. 20 Herrera-Mundo N, Sitges M. 26 Prystowsky EN, Camm J, Lip Mechanisms underlying striatal vulnerability to 3-nitropropionic acid. J NEUROCHEM, 2010. 114:597-605. I.F.:4,00. GYH, Allessie M, Bergmann JF, Breithardt G, Brugada J, Crijns H, Ellinor PT, Mark D, Naccarelli G, Packer D, Tamargo J. The Impact of New and Emerging Clinical Data on Treatment Strategies for Atrial Fibrillation. J CARDIOVASC ELECTR, 2010. 21:946-958. I.F.:3,70. 19 Matiello M, Nadal M, Tamborero 21 Richter S, Sarkozy A, Paparella G, Henkens S, Boussy T, Chierchia GB, Brugada R, Brugada J, Brugada 112 P. Number of electrocardiogram leads displaying the diagnostic coved-type pattern in Brugada syndrome: a diagnostic consensus criterion to be revised. EUR HEART J, 2010. 31:1357-1364. I.F.:9,80. 27 Merkely B, Roka A, Kutyifa V, Boersma L, Leenhardt A, Lubinski A, Oto A, Proclemer A, Brugada J, Vardas PE, Wolpert C. Tracing the European course of cardiac resynchronization therapy from 2006 to 2008. EUROPACE, 2010. 12:692-701. I.F.:1,87. Reviews I.F.: 10,65 1 Capulzini L, Brugada P, Brugada J, Brugada R. Arrhythmia and Right Heart Disease: From Genetic Basis to Clinical Practice. REV ESP CARDIOL, 2010. 63:963-983. I.F.:2,75. 2 Mont L. Arrhythmias and sport practice. HEART, 2010. 96:398-405. I.F.:5,39. 3 Giada F, Biffi A, Cannom DS, Cappato R, Capucci A, Corrado D, Delise P, Drezner JA, El-Sherif N, Estes M, Furlanello F, Heidbuchel H, Inama G, Lindsay BD, Maron BJ, Maron MS, Mont L, Olshansky B, Pelliccia A, Thiene G, Viskin S, Zeppilli P, Natale A, Raviele A. Sports and arrhythmias: a report of the International Workshop Venice Arrhythmias 2009. EUR J CARDIOV PREV R, 2010. 17:607-612. I.F.:2,51. Editorials I.F.: 9,80 1 Auer J, Brugada J. Restoration of sinus rhythm in patients undergoing surgery for rheumatic valvular heart disease: is it worth the effort?. EUR HEART J, 2010. 31:2572-2574. I.F.:9,80. AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Arrhythmias, resynchronization and cardiac imaging Clinical Guidelines I.F.: 3,70 1 Grants for research in progress Natale A, Raviele A, Al-Ahmad A, Alfieri O, Aliot E, Almendral J, Breithardt G, Brugada J, Calkins H, Callans D, Cappato R, Camm JA, DellaBella P, Guiraudon GM, Haissaguerre M, Hindricks G, Ho SY, Kuck KH, Marchlinski F, Packer DL, Prystowsky EN, Reddy VY, Ruskin JN, Scanavacca M, Shivkumar K, Soejima K, Stevenson WJ, Themistoclakis S, Verma A, Wilber D. Venice Chart International Consensus Document on Ventricular Tachycardia/Ventricular Fibrillation Ablation. J CARDIOVASC ELECTR. 21:339-379. I.F.:3,70. Brugada J. Integración de las diferentes técnicas de imagen médica en una única imagen multimodal. Desarrollo de distintos modelos de aplicación. Estudios electrofisiológicos y de imagen cardiaca. Sponsored by: Ministerio de Industria Turismo y Comercio, CDTEAM1. Amount: 500.000,00 euros. Duration: 11/01/2006-11/01/2010. Multicentrics I.F.: 5,94 Mont L. Estudi de la terapia de resincronització a Catalunya (TRC-CAT). Sponsored by: AATRM (Agencia d’Avaluació de Tecnología i Recerca Mèdiques, 0000. Amount: 76.800,00 euros. Duration: 01/01/200931/12/2012. 1 Ruiter JH, Mulder E, Schuchert A, Burri H, Stuhlinger MC, Hartikainen J, Sermasi S, Vlasinova J, Mairesse GH, Bub E, Lewalter T. The Feasibility of Fully Automated Pacemaker Advise in Treating Atrial Tachyarrhythmias. PACE. 33:605-614. I.F.:1,58. 2 Boriani G, Kranig W, Donal E, Calo L, Casella M, Delarche N, Lozano IF, Ansalone G, Biffi M, Boulogne E, Leclercq C. A randomized double-blind comparison of biventricular versus left ventricular stimulation for cardiac resynchronization therapy: The Biventricular versus Left Univentricular Pacing with ICD Back-up in Heart Failure Patients (B-LEFT HF) trial. AM HEART J. 159:1052-U12. I.F.:4,36. Brugada J. REDISCOR - Red de Investigación en Insuficiencia Cardíaca en España. Sponsored by: Ministerio Sanidad y Consumo, RD06/0003/0008. Amount: 346.785,30 euros. Duration: 01/01/2007-31/12/2010. Brugada J. Mecanismos y reversibilidad de la fibrosis miocàrdica asociada al ejercicio. Sponsored by: Ministerio de Ciencia e Innovación, DEP2009-12455. Amount: 42.350,00 euros. Duration: 01/01/2010-31/12/2012. Brugada J. Arítmies i Estimulació Cardíaca. Sponsored by: Agència de Gestió d’Ajuts Universitaris i de Recerca, 2009 SGR 1104. Amount: 43.680,00 euros. Duration: 01/01/200931/12/2013. Brugada J. Mecanismos y Reversibilidad de la Fibrosis Miocárdica Asociada al Ejercicio. Sponsored by: MINISTERIO DE EDUCACIÓN, DEP2009_12455. Amount: 42.350,01 euros. Duration: 01/01/2010-31/12/2012. Ortiz JT. Utilidad de la angiografía coronaria no invasiva mediante tomografía computerizada multidetector en el diagnóstico del síndrome coronario agudo en urgencias. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/90513. Amount: 48.400,00 euros. Duration: 01/01/2010-31/12/2011. Brugada J. An Intelligent Platform for Personalized Remote Monitoring of the Cardiac Patients with Electronic Implant Devices. Sponsored by: SRDC YAZILIM ARASTIRMA VE GELISTIRME VE DANISMANLIK TICARET, 248240. Amount: 219.400,00 euros. Duration: 01/02/201031/01/2013. Thesis Mont L. Repercusiones Cardiovasculares de la Anorexia Nerviosa. PhD student: Benito Herreros Gilarte. Mont L, Serrano-Mollar A. Efecto del ejercicio crónico en el desarrollo de fibrosis cardíaca: mecanismos implicados. PhD student: Gemma Gay Jordi. Brugada J, De Caralt MT. Utilidad de la resonancia magnética en pacientes con fibrilación auricular tributarios de tratamiento con ablación percutánea de las venas pulmonares. PhD student: Rosario Jesús Perea Palazón. Brugada J. iCARDEA. Sponsored by: European Comission, PI040847. Amount: 219.400,00 euros. Duration: 01/02/2010-31/01/2013. 113 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Team envolved in: Red de Investigación en Enfermedades Renales (REDINRED) Nephro-urological diseases and kidney transplantation Strategic Objectives GROUP Members TEAM LEADER Josep Mª Campistol (Hospital Clínic) Tel.: 93 227 54 00 (Ext.: 9346) E-mail: jmcampis@clinic.ub.es Idibaps members: Pilar Arrizabalaga (Hospital Clínic) Albert Botey (Hospital Clínic) Aleix Cases (Hospital Clínic) Guadalupe Ercilla (Hospital Clínic) Georgina Hotter (IIBB-CSIC) Jaume Martorell (Hospital Clínic) Eduard Mirapeix (Hospital Clínic) Federico Oppenheimer (Hospital Clínic) Esteban Poch (Hospital Clínic) Research Fellows: Joan Nistal (Fundació Clínic) Michaela Jung (IIBB-CSIC) Marina Ventayol (IIBB-CSIC) Chrysa Mastora (IIBB-CSIC) 114 Technicians: Maite del Hierro (IIBB-CSIC) Collaborators: Celia Bádenas (Fundació Clínic) Pablo Carretero (Hospital Clínic) Federico Cofán (Hospital Clínic) Elisabeth Coll (Hospital Clínic) Marta Crespo (Hospital Clínic) Nuria Esforzado (Hospital Clínic) V. Fortuna (Hospital Clínic) J. Jiménez (Hospital Clínic) O. Millán (Fundació Clínic) Vicenç Torregrosa (Hospital Clínic) Anna Sola (IIBB-CSIC) José Luis Viñas (IIBB-CSIC) Eugenia Vinuesa (IIBB-CSIC) The general objectives of this research team are to gain in-depth knowledge of the physiopathology and treatment of diseases of the kidneys, urinary tract and male genital apparatus, as well as of the medical complications derived from renal replacement therapy in the form of dialysis or transplantation. The objectives include particularly the study of immunosuppression in aspects relating to pharmacokinetics and pharmacodynamics. On the other hand, with the incorporation of a team specialized in transplant immunology, our objectives also include the improvement of allograft and xenograft tolerance, and minimization of the need for immunosuppressors. Another new challenge is to gain in-depth knowledge of the degree of immune depression achieved in patients in accordance with their needs: pharmacokinetic/pharmacodynamic (PK/PD) relationship. AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering nephro-urological diseases and kidney transplantation Main Lines of Research 1. Hereditary renal diseases, especially renal polycystosis, Alport syndrome and benign familial hematuria. 2. Amyloidosis associated with dialysis or beta-2-microglobulin, and other types of hereditary and nonhereditary amyloidosis with renal involvement. 3. Diabetic nephropathy and antiproteinuric effect of ARA II drugs. 4. Anemia of renal origin, and erythropoiesis-stimulating proteins in uremia. 5. Uremic myopathy. 6. Renal osteodystrophy and calciumphosphorus metabolism. 7. Cardiovascular risk and accelerated arteriosclerosis in the renal patient. 8. Hepatitis C virus infection in patients on dialysis and renal transplantation. 9. Endothelial dysfunction and effect of the uremic medium upon the endothelial cells. 10. Chronic rejection and role of TGFbeta. 11. Dyslipidemia and cardiovascular risk in renal transplantation, and apolipoprotein polymorphisms. 12. Immunosuppressor drug pharmacokinetics and pharmacodynamics: Calcineurin inhibitors, sirolimus, rapamycin and MMF. 13. Renal-pancreatic transplantation and metabolic control. 14. Neoplasms of the urinary system (kidney, prostate and bladder). 15. Erectile dysfunction and the use of sildenafil in kidney transplantation. 16. Experimental kidney transplantation. 17. Definition of the molecular bases of the mechanisms regulating clonal anergy or deletion in a model of allogenic or xenogenic presentation, thus determining transplant antigen tolerance. 18. Definition of the pharmacokinetic and pharmacodynamic parameters allowing the minimization of immune depression to meet the needs of each individual organ recipient. 19. Identification of strategies allowing the replacement of cell, organ or tissue functions with minimization of immune depressor use. Our investigators also have lines of research shared with other teams of the IDIBAPS, very particularly in the fields of arterial hypertension, endothelial dysfunction and systemic autoimmune diseases with renal involvement. PUBLICATIONS Originals I.F.: 117,61 1 Herrera E, Tenckhoff S, Gomara MJ, Galatola R, Bleda MJ, Gil C, Ercilla G, Gatell JM, Tillmann HL, Haro I. Effect of Synthetic Peptides Belonging to E2 Envelope Protein of GB Virus C on Human Immunodeficiency Virus Type 1 Infection. J MED CHEM, 2010. 53:60546063. I.F.:4,80. 2 Banon-Maneus E, Diekmann F, Carrascal M, Quintana LF, Moya-Rull D, Bescos M, Ramirez-Bajo MJ, Rovira J, Gutierrez-Dalmau A, Sole-Gonzalez A, Abian J, Campistol JM. Two-Dimensional Difference Gel Electrophoresis Urinary Proteomic Profile in the Search of Nonimmune Chronic Allograft Dysfunction Biomarkers. TRANSPLANTATION, 2010. 89:548-558. I.F.:3,50. 3 Durrbach A, Pestana JM, Pearson T, Vincenti F, Garcia VD, Campistol J, Rial MD, Florman S, Block A, DiRusso G, Xing J, Garg P, Grinyo J. A Phase III Study of Belatacept Versus Cyclosporine in Kidney Transplants from Extended Criteria Donors (BENEFIT-EXT Study). AM J TRANSPLANT, 2010. 10:547-557. I.F.:6,43. 4 Oppenheimer F, Revuelta I, Serra N, Lozano M, Gutierrez-Dalmau A, Esforzado N, Cofan F, Ricart MJ, Torregrosa JV, Crespo M, Paredes D, Martorell J, Alcaraz A, Campistol JM. ABO incompatible living donor kidney transplantation: a dream come true. Experience of Hospital Clinic of Barcelona. NEFROLOGIA, 2010. 30:54-63. I.F.:0,53. 5 Gomara MJ, Fernandez L, Perez T, Ercilla G, Haro I. Assessment of synthetic chimeric multiple antigenic peptides for diagnosis of GB virus C infection. ANAL BIOCHEM, 2010. 396:51-58. I.F.:3,29. 115 BIOLOGICAL AGGRESSION AND RESPOBNSE MECHANISMS Nephro-urological diseases and kidney transplantation Team Members 6 Larsen CP, Grinyo J, MedinaPestana J, Vanrenterghem Y, Vincenti F, Breshahan B, Campistol JM, Florman S, Rial MD, Kamar N, Block A, DiRusso G, Lin CS, Garg P, Charpentier B. Belatacept-Based Regimens Versus a Cyclosporine A-Based Regimen in Kidney Transplant Recipients: 2-Year Results From the BENEFIT and BENEFIT-EXT Studies. TRANSPLANTATION, 2010. 90:1528-1535. I.F.:3,50. py. AM J TRANSPLANT, 2010. 10:26042614. I.F.:6,43. 7 12 Duran CE, Torregrosa JV, Almaden Go T, Jungebluth P, Baiguero S, Asnaghi A, Martorell J, Ostertag H, Mantero S, Birchall M, Bader A, Macchiarini P. Both epithelial cells and mesenchymal stem cell-derived chondrocytes contribute to the survival of tissue-engineered airway transplants in pigs. J THORAC CARDIOV SUR, 2010. 139:437-443. I.F.:3,06. 8 Puig-Pey I, Bohne F, Benitez C, Lopez M, Martinez-Llordella M, Oppenheimer F, Lozano JJ, GonzalezAbraldes J, Tisone G, Rimola A, Sanchez-Fueyo A. Characterization of gamma delta T cell subsets in organ transplantation. TRANSPL INT, 2010. 23:1045-1055. I.F.:3,25. 9 Baccaro ME, Pepin MN, Guevara M, Colmenero J, Torregrosa JV, Martin-Llahi M, Sola E, Esforzado N, Fuster J, Campistol JM, Arroyo V, Navasa M, Garcia-Valdecasas J, Gines P. Combined liver-kidney transplantation in patients with cirrhosis and chronic kidney disease. NEPHROL DIAL TRANSPL, 2010. 25:2356-2363. I.F.:3,31. 10 Brouard S, Puig-Pey I, Lozano JJ, Pallier A, Braud C, Giral M, Guillet M, Londono MC, Oppenheimer F, Campistol JM, Soulillou JP, SanchezFueyo A. Comparative Transcriptional and Phenotypic Peripheral Blood Analysis of Kidney Recipients Under Cyclosporin A or Sirolimus Monothera- 116 11 Gutierrez-Dalmau A, Revuelta I, Ferrer B, Mascaro JM, Oppenheimer F, Albanell J, Campistol JM. Distinct Immunohistochemical Phenotype of Nonmelanoma Skin Cancers Between Renal Transplant and Immunocompetent Populations. TRANSPLANTATION, 2010. 90:986-992. I.F.:3,50. Y, Canalejo A, Campistol JM, Rodriguez M. Dynamics of calcium-regulated PTH secretion in secondary hyperparathyroidism: comparison between “in vivo” vs. “in vitro” responses. NEFROLOGIA, 2010. 30:73-77. I.F.:0,53. 13 Gomez-Alamillo C, FernandezFresnedo G, Ortega F, Campistol JM, Gentil MA, Arias M. Erythropoietin Resistance as Surrogate Marker of Graft and Patient Survival in Renal Transplantation: 3-Year Prospective Multicenter Study. TRANSPL P, 2010. 42:2935-2937. I.F.:0,99. 14 Clemente PA. Feminisation and nephrology. NEFROLOGIA, 2010. 30:110-113. I.F.:0,53. 15 Hor H, Kutalik Z, Dauvilliers Y, Valsesia A, Lammers GJ, Donjacour CEHM, Iranzo A, Santamaria J, Adrados RP, Vicario JL, Overeem S, Arnulf I, Theodorou I, Jennum P, Knudsen S, Bassetti C, Mathis J, Lecendreux M, Mayer G, Geisler P, Beneto A, Petit B, Pfister C, Burki JV, Didelot G, Billiard M, Ercilla G, Verduijn W, Claas FHJ, Vollenwider P, Waeber G, Waterworth DM, Mooser V, Heinzer R, Beckmann JS, Bergmann S, Tafti M. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. NAT GENET, 2010. 42:786-U80. I.F.:34,28. 16 Maduell F, Arias M, Garro J, Vera M, Fontsere N, Barros X, Masso E, Mar- tina MN, Sentis A, Duran C, Bergada E, Cases A, Campistol JM. Guidelines for Automated Manual Infusion: A Practical Way of Prescribing Postdilution On-line Haemodiafiltration. NEFROLOGIA, 2010. 30:349-353. I.F.:0,53. 17 Duran CE, Torregrosa JV, Canalejo A, Almaden Y, Campistol JM, Portillo MR. In vitro dynamics of parathyroid hormone secretion regulated by calcium and effects on the cell cycle: parathyroid hyperplasia versus adenoma. NEFROLOGIA, 2010. 30:413-419. I.F.:0,53. 18 Morales JM, Campistol JM, Dominguez-Gil B, Andres A, Esforzado N, Oppenheimer F, Castellano G, Fuertes A, Bruguera M, Praga M. Long-Term Experience With Kidney Transplantation From Hepatitis C-Positive Donors Into Hepatitis C-Positive Recipients. AM J TRANSPLANT, 2010. 10:2453-2462. I.F.:6,43. 19 Campistol JM. Long-Term Maintenance Therapy With Calcineurin Inhibitors: An Update. TRANSPL P, 2010. 42:S21-S24. I.F.:0,99. 20 Campistol JM, DeFijter JW, Flechner SM, Langone A, Morelon E, Stockfleth E. mTOR inhibitor-associated dermatologic and mucosal problems. CLIN TRANSPLANT, 2010. 24:149-156. I.F.:2,00. 21 Musquera M, Peri LL, Alvarez-Vijande R, Oppenheimer F, Gil-Vernet JM, Alcaraz A. Orthotopic Kidney Transplantation: An Alternative Surgical Technique in Selected Patients. EUR UROL, 2010. 58:927-933. I.F.:7,67. 22 Collado S, Coll E, Deulofeu R, Guerrero L, Pons M, Cruzado JM, DeLaTorre B, Vera M, Azqueta M, Nicolau C, Cases A. Prevalence of cardiovascular disease in uraemia and relevance of cardiovascular risk factors. NEFROLOGIA, 2010. 30:342-348. I.F.:0,53. AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering nephro-urological diseases and kidney transplantation 23 Fons C, Arias A, Sempere A, 28 Izquierdo L, Peri L, Piqueras M, Poo P, Pineda M, Mas A, LopezSala A, Garcia-Villoria J, Vilaseca MA, Ozaez L, Lluch M, Artuch R, Campistol J, Ribes A. Response to creatine analogs in fibroblasts and patients with creatine transporter deficiency. MOL GENET METAB, 2010. 99:296299. I.F.:2,90. Revuelta I, Alvarez-Vijande R, Musquera M, Oppenheimer F, Alcaraz A. Third and Fourth Kidney Transplant: Still a Reasonable Option. TRANSPL P, 2010. 42:2498-2502. I.F.:0,99. 24 Marti J, Fuster J, Hotter G, Sola AM, Deulofeu R, Modolo MM, Loera MA, Ferrer J, Fondevila C, GarciaValdecasas JC. Serum neutrophil gelatinase-associated lipocalin in patients with colorectal liver metastases: preliminary results of an exploratory prospective study. INT J BIOL MARKER, 2010. 25:21-26. I.F.:1,42. 25 Pinto JR, Torres EMA, Franco A, Morales JM, Ruiz JC, Diekmann F, Alperovich G, Campistol JM. Sirolimus monotherapy as maintenance immunosuppression: a multicenter experience. TRANSPL INT, 2010. 23:307-312. I.F.:3,25. 26 Polanco N, Gutierrez E, Covarsi A, Ariza F, Carreno A, Vigil A, Baltar J, Fernandez-Fresnedo G, Martin C, Pons S, Lorenzo D, Bernis C, Arrizabalaga P, Fernandez-Juarez G, Barrio V, Sierra M, Castellanos I, Espinosa M, Rivera F, Oliet A, Fernandez-Vega F, Praga M. Spontaneous Remission of Nephrotic Syndrome in Idiopathic Membranous Nephropathy. J AM SOC NEPHROL, 2010. 21:697-704. I.F.:7,69. 27 Cabanas NS, Freiria XB, Martinez JG, Pelicano MB, Canals FM, Rabasa AT, DeBrinas EPL. The monitoring of dialysis dose by ionic dialysance-based Kt reveals less dialysis adequacy than the Kt/V-UREA-based measurement in critically ill patients with acute renal failure. NEFROLOGIA, 2010. 30:232-235. I.F.:0,53. 29 Oliveras A, Armario P, Hernandez-DelRey R, Arroyo JA, Poch E, Larrousse M, Roca-Cusachs A, DeLaSierra A. Urinary albumin excretion is associated with true resistant hypertension. J HUM HYPERTENS, 2010. 24:27-33. I.F.:2,29. 30 Maduell F, Arias M, Fontsere N, Vera M, Masso E, Garro J, Barros X, Martina MN, Elena M, Bergada E, Cases A, Bedini JL, Campistol JM. What Infusion Flow Should Be Used for MidDilution Hemodiafiltration?. BLOOD PURIFICAT, 2010. 30:25-33. I.F.:1,89. Reviews I.F.: 0,99 1 Miro JM, Ricart MJ, Trullas JC, Cofan F, Cervera C, Brunet M, Tuset M, Manzardo C, Oppenheimer F, Moreno A. Simultaneous PancreasKidney Transplantation in HIV-infected Patients: A Case Report and Literature Review. TRANSPL P, 2010. 42:38873891. I.F.:0,99. Editorials I.F.: 0,99 1 Campistol JM. Conclusions From the Symposium. TRANSPL P, 2010. 42:S47-S48. I.F.:0,99. Grants for research in progress de vejiga mediante marcadores moleculares y utilización de éstos para pronosticar la evolución clínica de la enfermedad. Sponsored by: Ministerio Sanidad y Consumo, PI070040. Amount: 61.468,00 euros. Duration: 26/11/2007-30/12/2010. Poch E. REDINREN - Red de Investigación en Enfermedades Renales. Sponsored by: Ministerio Sanidad y Consumo, RD06/0016/0015. Amount: 60.242,42 euros. Duration: 01/01/2007-31/12/2010. Alcaraz A. Red de Investigación de Reacciones Adversas a Alérgenos y Fármacos (RIRAAF). Sponsored by: Instituto de Salud Carlos III, RD07/0064/0006. Amount: 6.000,00 euros. Duration: 29/02/200831/12/2011. Martorell J, Rimola A, Millan O, Ruiz A. Valor predictivo de parámetros inmológicos pre-trasplante del receptor y de donante en el desarrollo de rechazo e infección en el trasplante hepático. Sponsored by: FIS, PS09/00418. Amount: 92.565,00 euros. Duration: 01/01/2010-31/12/2012. Poch E. Análisis de biomarcadores predictores de insuficiencia renal aguda post cirugía cardíaca. Sponsored by: Instituto de Salud Carlos III, PI08/0140. Amount: 178.475,00 euros. Duration: 01/01/2009-30/12/2011. Campistol JM. Análisis de biomarcadores urinarios en la disfunción crónica del injerto: estudio de validación e implicación de la vía WNT/BETACATENINA. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/0281. Amount: 305.525,00 euros. Duration: 01/01/2010-31/12/2012. Alcaraz A. Determinación de la diseminación linfática del carcinoma urotelial 117 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Team envolved in: CIBER en Fisiología de la obesidad y nutrición (CIBERobn) Hypertension, lipids and cardiovascular risk Strategic Objectives GROUP Members TEAM LEADER Emili Ros (Hospital Clínic) Tel.: 93 227 93 83 E-mail: eros@clinic.ub.es Idibaps members: Antonio Coca (Hospital Clínic) Daniel Zambón (Hospital Clínic) Cristina Sierra (Hospital Clínic) Postdoctoral fellows: Montserrat Cofán (ISCIII) Aleix Sala-Vila (ISCIII) Research Fellows: Verònica Escurriol (AGAUR) Cinta Valls (ISCIII) Nursing Staff: Anna López (ISCIII) Dietists: Ana Mª Pérez-Heras (Fundació Clínic) Mercè Serra (ISCIII) Staticians: Emili Corbella (IDIBELL) Collaborators: Núria Bargalló (Hospital Clínic) Maria Teresa de Caralt (Hospital Clínic) Mònica Doménech (Fundació Clínic) Ramón Estruch (Hospital Clínic) Rosa Gilabert (Hospital Clínic) Isabel Núñez (Hospital Clínic) Visiting Scientists: Nagila R. Teixeira Damasceno (University of Sao Paulo) Ana Paula de Queiroz Mello (University of Sao Paulo) Patricia Casas Agustench (URV) The general aim of our group is to gain in-depth knowledge of the epidemiology, pathogenesis, diagnosis, treatment and prevention of arterial hypertension, dyslipidemia and associated cardiovascular risk. The research lines we wish to continue consolidating are the following: 1. Mechanisms and consequences of silent lesions in target organs of hypertension. 2. Interaction of environmental determinants in cardiovascular disease, such as salt intake and the salt sensitivity phenomenon. 3. Candidate genes of hypertension and its complications. 4. Characterization of genetic dyslipidemias. 5. Detection of preclinical atherosclerosis. 6. Study of the intestinal absorption of cholesterol. 7. Phytosterolemia as a cardiovascular risk factor. 8. Determination of the fatty acids profile in phospholipids and blood cell membranes, and their associations with diet, metabolic syndrome, cardiovascular risk phenotype and preclinical arteriosclerosis. 9. Study of the cardiovascular functionality of foods, including the effects of foods rich in omega-3 fatty acids upon carotid atheroma plaque characteristics. 10. Effects of the Mediterraenan diet upon carotid atheroma plaque vulnerability evaluated by MRI. 11. Identification of genetic variants associated with different responses to foods and nutrients (nutrition genetics). Main Lines of Research 1. External arterial ultrasound applied to femoral and carotid arteries, coronary CAT and carotid plaque MRI. Relationship between preclinical atherosclerosis and conventional and emergent risk 118 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering hypertension, lipids and cArdiovascular risk An updated scheme of the cardiovascular continuum. Abbreviations: BNP, brain natriuretic peptide; CHF, chronic heart failure; CV, cardiovascular; GFR, glomerular filtration rate; HF-PEF, heart failure with preserved ejection fraction; hsCRP, high-sensitivity C-reactive protein; LAD, left atrial dilatation; LVH, left ventricular hypertrophy; MI, myocardial infarction; PAD, peripheral arterial disease; UAE, urinary albumin excretion. factors and biomarkers of the usual diet, including unsaturated fatty acids and phospholipids in plasma, circulating vitamins and phytosterols. Influence of diet upon carotid atheroma plaque vulnerability evaluated by sequential MRI. Correlation of plaque composition by MRI with histology. 2. Circadian patterns, arterial pressure variability and target organ damage. Sensitivity to salt in arterial hypertension. Inflammation in hypertension. Hypertension and atrial fibrillation as manifestation of hypertension-induced cardiac damage. 3. Candidate genes for cerebrovascular stroke risk in hypertensive patients. Candidate genes for the development of left ventricular hypertrophy and heart failure in hypertensive patients. 4. Functionality of the dietary standards and complete foods: influence upon arterial pressure evaluated by ambulatory and home monitoring, insulin resistance, biological markers of cholesterol absorption and vascular risk, dietary biomarkers (unsaturated fatty acids in whole blood, carotenes and vitamin E in plasma, polyphenols in urine) and physicochemical properties of the low-density lipoproteins (LDLs) and high-density lipoproteins (HDLs). 5. Mild age-associated cognitive impairment in participants in the PREDIMED study after two years of intervention with Mediterranean diets or low-fat diets. 6. Effect of hypercholesterolemia of different origins and severity upon cognitive function as assessed by neuropsychological tests and functional brain MRI. 7. Cholesterol absorption and synthesis evaluated by the determination of plasma non- cholesterol sterol levels using gas chromatography: measurement, genetic conditioning factors, influence upon cardiovascular risk and relationship with lipid response to phytosterols, ezetimibe and statins. 8. Influence of polyunsaturated long-chain fatty acids (plant and marine omega-3) upon preclinical atherosclerosis of the carotid arteries, evaluated by high-resolution ultrasound with microbubble contrast and with MRI. 9. Associations of the fatty acids profile in whole plasma, whole blood and a circulating phospholipid fraction with SCD1 activity; cardiometabolic risk factors and non-alcoholic liver steatosis; dietary determinants of the omega-3 index in whole blood; fatty acids composition of the “lipid rafts”; and effect upon cell signaling. 119 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Hypertension, lipids and cardiovascular risk Team Members PUBLICATIONS Originals I.F.: 97,91 1 Perez-De-Lis M, Akasbi M, Siso A, Diez-Cascon P, Brito-Zeron P, Diaz-Lagares C, Ortiz J, PerezAlvarez R, Ramos-Casals M, Coca A. Cardiovascular risk factors in primary Sjogren’s syndrome: a case-control study in 624 patients. LUPUS, 2010. 19:941-948. I.F.:2,59. 2 Siso A, Ramos-Casals M, Bove A, Brito-Zeron P, Soria N, Nardi N, Testi A, Perez-De-Lis M, DiazLagares C, Darnell A, Sentis J, Coca A. Outcomes in Biopsy-Proven Lupus Nephritis Evaluation of 190 White Patients From a Single Center. MEDICINE, 2010. 89:300-307. I.F.:5,05. 3 Martin B, Solanas-Barca M, Garcia-Otin AL, Pampin S, Cofan M, Ros E, Rodriguez-Rey JC, Pocovi M, Civeira F. An NPC1L1 gene promoter variant is associated with autosomal dominant hypercholesterolemia. NUTR METAB CARDIOVAS, 2010. 20:236-242. I.F.:3,52. 7 Tovillas-Moran FJ, Vilaplana-Cosculluela M, Dalfo-Pibernat A, ZabaletaDel-Olmo E, Galceran JM, Coca A, Dalfo-Baque A. Decreased glomerular filtration rate using the CockgroftGaultand MDRD formulas does not always predict cardiovascular morbidity and mortality in hypertensive primary care patients. NEFROLOGIA, 2010. 30:653-660. I.F.:0,53. 8 4 Lohse B, Psota T, Estruch R, Zazpe I, Sorli JV, Salas-Salvado J, Serra M, Krall JS, Marquez F, Ros E. Eating Competence of Elderly Spanish Adults Is Associated with a Healthy Diet and a Favorable Cardiovascular Disease Risk Profile. J NUTR. 140:1322-1327, 2010. I.F.:4,09. 5 Tovillas-Moran FJ, Vilaplana- Llorente-Cortes V, Estruch R, Mena MP, Ros E, Gonzalez MAM, Fito M, Lamuela-Raventos RM, Badimon L. Effect of Mediterranean diet on the expression of pro-atherogenic genes in a population at high cardiovascular risk. ATHEROSCLEROSIS, 2010. 208:442-450. I.F.:4,52. Guillen D, Cofan F, Ros E, Millan O, Cofan M, Brunet M. Biomarker Assessment of the Immunomodulator Effect of Atorvastatin in Stable Renal Transplant Recipients and Hypercholesterolemic Patients. MOL DIAGN THER, 2010. 14:357-366. I.F.:2,17. Cosculluela M, Zabaleta-Del-Olmo E, Dalfo-Baque A, Galceran JM, Coca A. Cardiovascular morbidity and mortality and electrocardiographic criteria of left ventricular hypertrophia in hypertensive patients treated in primary care. MED CLIN-BARCELONA, 2010. 135:397-401. I.F.:1,23. 120 6 Corella D, Carrasco P, Amiano P, Arriola L, Chirlaque MD, Huerta JM, Martinez C, Martinez-Camblor P, Molina E, Navarro C, Quiros JR, Rodriguez L, Sanchez MJ, Ortega-Azorin C, Ros E, Sala N, Gonzalez CA, Moreno C. Common cholesteryl ester transfer protein gene variation related to highdensity lipoprotein cholesterol is not associated with decreased coronary heart disease risk after a 10-year follow-up in a Mediterranean cohort: Modulation by alcohol consumption. ATHEROSCLEROSIS, 2010. 211:531538. I.F.:4,52. 9 10 Prieto RM, Fiol M, Perello J, Estruch R, Ros E, Sanchis P, Grases F. Effects of Mediterranean diets with low and high proportions of phytaterich foods on the urinary phytate excretion. EUR J NUTR, 2010. 49:321326. I.F.:2,87. 11 Cabre A, Lazaro I, Cofan M, Jarauta E, Plana N, Garcia-Otin AL, Ascaso JF, Ferre R, Civeira F, Ros E, Masana L. FABP4 plasma levels are increased in familial combined hyperlipidemia. J LIPID RES, 2010. 51:11731178. I.F.:4,92. 12 Redon J, Coca A, Lazaro P, Aguilar MD, Cabanas M, Gil N, SanchezZamorano MA, Aranda P. Factors associated with therapeutic inertia in hypertension: validation of a predictive model. J HYPERTENS, 2010. 28:17701777. I.F.:4,99. 13 Sala-Vila A, Cofan M, PerezHeras A, Nunez I, Gilabert R, Junyent M, Mateo-Gallego R, Cenarro A, Civeira F, Ros E. Fatty acids in serum phospholipids and carotid intimamedia thickness in Spanish subjects with primary dyslipidemia. AM J CLIN NUTR, 2010. 92:186-193. I.F.:6,31. 14 Corella D, Carrasco P, Fito M, Martinez-Gonzalez MA, SalasSalvado J, Aros F, Lapetra J, Guillen M, Ortega-Azorin C, Warnberg J, Fiol M, Ruiz-Gutierrez V, Serra-Majem L, Martinez JA, Ros E, Estruch R. Geneenvironment interactions of CETP gene variation in a high cardiovascular risk Mediterranean population. J LIPID RES, 2010. 51:2798-2807. I.F.:4,92. 15 Zambon D, Quintana M, Mata P, Alonso R, Benavent J, Cruz-Sanchez F, Gich J, Pocovi M, Civeira F, Capurro S, Bachman D, Sambamurti K, Nicholas J, Pappolla MA. Higher Incidence of Mild Cognitive Impairment in Familial Hypercholesterolemia. AM J MED, 2010. 123:267-274. I.F.:4,47. 16 Junyent M, Gilabert R, Jarauta E, Nunez I, Cofan M, Civeira F, Pocovi AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering hypertension, lipids and cArdiovascular risk M, Mallen M, Zambon D, Almagro F, Vega J, Tejedor D, Ros E. Impact of low-density lipoprotein receptor mutational class on carotid atherosclerosis in patients with familial hypercholesterolemia. ATHEROSCLEROSIS, 2010. 208:437-441. I.F.:4,52. 17 Pladevall M, Brotons C, Gabriel R, Arnau A, Suarez C, DeLaFiguera M, Marquez E, Coca A, Sobrino J, Divine G, Heisler M, Williams LK. Multicenter Cluster-Randomized Trial of a Multifactorial Intervention to Improve Antihypertensive Medication Adherence and Blood Pressure Control Among Patients at High Cardiovascular Risk (The COM99 Study). CIRCULATION, 2010. 122:1183-U81. I.F.:14,82. 18 Sabate J, Oda K, Ros E. Nut Consumption and Blood Lipid Levels A Pooled Analysis of 25 Intervention Trials. ARCH INTERN MED, 2010. 170:821-827. I.F.:9,81. 19 Escurriol V, Cofan M, MorenoIribas C, Larranaga N, Martinez C, Navarro C, Rodriguez L, Gonzalez CA, Corella D, Ros E. Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort. J LIPID RES, 2010. 51:618624. I.F.:4,92. 20 Zazpe I, Estruch R, Toledo E, Sanchez-Tainta A, Corella D, Bullo M, Fiol M, Iglesias P, Gomez-Gracia E, Aros F, Ros E, Schroder H, SerraMajem L, Pinto X, Lamuela-Raventos R, Ruiz-Gutierrez V, Martinez-Gonzalez MA. Predictors of adherence to a Mediterranean-type diet in the PREDIMED trial. EUR J NUTR, 2010. 49:9199. I.F.:2,87. 21 Perona JS, Covas MI, Fito M, Cabello-Moruno R, Aros F, Corella D, Ros E, Garcia M, Estruch R, Martinez-Gonzalez MA, Ruiz-Gutierrez V. Reduction in systemic and VLDL triacylglycerol concentration after a 3-month Mediterranean-style diet in high-cardiovascularrisk subjects. J NUTR BIOCHEM, 2010. 21:892-898. I.F.:4,29. Reviews I.F.: 3,52 1 Lopez-Miranda J, Perez-Jimenez F, Ros E, DeCaterina R, Badimon L, Covas MI, Escrich E, Ordovas JM, Soriguer F, Abia R, DeLaLastra CA, Battino M, Corella D, Chamorro-Quiros J, Delgado-Lista J, Giugliano D, Esposito K, Estruch R, Fernandez-Real JM, Gaforio JJ, LaVecchia C, Lairon D, Lopez-Segura F, Mata P, Menendez JA, Muriana FJ, Osada J, Panagiotakos DB, Paniagua JA, Perez-Martinez P, Perona J, Peinado MA, Pineda-Priego M, Poulsen HE, Quiles JL, RamirezTortosa MC, Ruano J, Serra-Majem L, Sola R, Solanas M, Solfrizzi V, DeLaTorre-Fornell R, Trichopoulou A, Uceda M, Villalba-Montoro JM, Villar-Ortiz JR, Visioli F, Yiannakouris N. Olive oil and health: Summary of the II international conference on olive oil and health consensus report, Jaen and Cordoba (Spain) 2008. NUTR METAB CARDIOVAS, 2010. 20:284-294. I.F.:3,52. Editorials I.F.: 5,75 1 Camafort M, Coca A. Hypertension and Analgesic Intake: Light and Shade on an Old Problem. REV ESP CARDIOL, 2010. 63:265-267. I.F.:2,75. 3 Volpe M, Camm J, Coca A, Unger T. The cardiovascular continuum refined: A hypothesis. BLOOD PRESSURE, 2010. 19:273-277. I.F.:1,77. Grants in research in progress Coca A. NoE - Integrated Genomics, Clinical Research and Care in Hypertension. Sponsored by: European Commission, INGENIOUS HYPERCARE, LHSM-CT-2006-037093. Amount: 136.281,00 euros. Duration: 01/11/2006-31/10/2010. Ros E. Projecte d’investigació postdoctoral: Ácidos grasos omega-3 y aterosclerosis carotídea evaluada mediante técnicas de bioimagen. Sponsored by: FIS, CD07/00083. Amount: 36.500,00 euros. Duration: 01/01/2008-31/12/2011. Ros E. Contribución de la variabilidad en el promotor del gen del receptor LDL a la hipercolesterolemia poligénica. Subproyecto 5: Análisis de biomarcadores de absorción y síntesis de colesterol. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1292. Amount: 68.365,00 euros. Duration: 01/01/2010-31/12/2012. Thesis Coca A, Ramos M. Impacto de la enfermedad cardiovascular en el síndrome de Sjögren primario. PhD student: Marta Perez de Lis Novo. 2 Salinas AM, Coca A. Obesity, physical activity and cardiovascular risk: ergoanthropometric classification, pharmacological variables, biomarkers and “obesity paradox”. MED CLINBARCELONA, 2010. 134:492-498. I.F.:1,23. 121 AREA 2 Respiratory, cardiovascular and renal pathobiology and bioengineering Team envolved in: & Bioingeniería, Biomateriales y Nanomedicina (CIBER-bbn) Respiratory biophysics and bioengineering GRUOP Members TEAM LEADER Ramon Farré (Universitat de Barcelona) Tel.: 93 402 45 15 Fax: 93 403 52 78 E-mail: rfarre@ub.edu Idibaps members: Javier Pavía (Hospital Clínic) Domènec Ros (Facultat de Medicina UB) Mar Rotger (Facultat de Medicina UB) Strategic Objectives Main Lines of Research The general objectives of the group are the study of the biophysical mechanisms determining respiratory function, and the development of models and methods for the processing of biomedical images and signals. The work of the group is based on an interdisciplinary approach, with integration between basic and clinical research. In parallel to the scientific objectives, our group promotes transfer to the industrial setting of the technological advances derived from the research work. 1.Respiratory mechanics. The aim of research in respiratory mechanics is to investigate the viscoelastic properties of the airways and lung tissues. At present, the work fundamentally focuses on the study of upper airway collapsibility in obstructive apnea-hypopnea during sleep and in the monitoring of noninvasive mechanical ventilation during respiratory failure. The clinical aim of this research is to obtain improved noninvasive diagnostic techniques, and to optimize the treatment methods based on ventilation assist measures. Postdoctoral fellows: Theodora Tsapikouni (CIBERES) Elena Garreta (Marie Curie - IDIBAPS) Laura Chimenti (Marie Curie - European Respiratory Society) Research Fellows: Irene Acerbi (MEC) Alba Carreras (MEC) Núria Roé (IDIBAPS) Berta Martí (CIBER-BBN) Esther Melo (MEC) Valentina Isetta (UE) Foteini Popota (IDIBAPS) Technicians: Miguel Rodríguez (UB) Rocío Nieto (CIBERES) Collaborators: Carles Falcón (IDIBAPS) Raúl Tudela (CIBER-BBN) Albert Cot (UB-CIBER-BBN) Jordi Alcaraz (UB) Xavier Trepat (UB-IBEC) Daniel Navajas (UB-IBEC) 122 De-cellularized rat lung. AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Respiratory biophysics and bioengineering 2.Molecular and cellular nanomechanics. The introduction of nanotechnologies allowing the manipulation of materials on the nanometric and picoNewton scale has opened up new perspectives for the investigation of individual biomolecules and cells. Our group uses atomic force microscopy, magnetic microspheres and traction force microscopy to study cell adhesion and the mechanical properties of lung cells and leukocytes. Studies are also made of the mechanical properties of embryonic and adult stem cells during the differentiation process, and of the way in which mechanical stimuli can enhance differentiation towards the alveolar epithelial phenotype. One of our projects in this setting focuses on organ regeneration. Specifically, work is done on the bioartificial production of functional rat lungs by means of the re-cellularization of the extracellular matrix of the organ with stem cells, and recreation of the mechanical pulmonary micronano environment, to optimize cell differentiation. 3.Biomedical imaging analysis. Research in imaging analysis currently focuses on the processing of photon emission tomography (SPECT) and positron emission tomography (PET) images, with the purpose of securing more precise quantification of gammagraphic (scintigraphic) studies. With this objective in mind, iterative algorithms are being developed for the three-dimensional reconstruction of images and for the fusion of SPECT and magnetic resonance imaging (MRI) images. For further information: www.ub.edu/biofisica PUBLICATIONS Originals I.F.: 48,63 6 1 Iranzo A, Isetta V, Molinuevo JL, Serradell M, Navajas D, Farre R, Santamaria J. Electroencephalographic slowing heralds mild cognitive impairment in idiopathic REM sleep behavior disorder. SLEEP MED, 2010. 11:534-539. I.F.:3,70. 2 Aguiar P, Rafecas M, Ortuno JE, Kontaxakis G, Santos A, Pavia J, Ros D. Geometrical and Monte Carlo projectors in 3D PET reconstruction. MED PHYS, 2010. 37:5691-5702. I.F.:2,70. Fernandez-Egea E, Parellada E, Lomena F, Falcon C, Pavia J, Mane A, Horga G, Bernardo M. (18)FDG PET study of amygdalar activity during facial emotion recognition in schizophrenia. EUR ARCH PSY CLIN N, 2010. 260:69-76. I.F.:2,75. Lage E, Villena JL, Tapias G, Martinez NP, Soto-Montenegro ML, Abella M, Sisniega A, Pino F, Ros D, Pavia J, Desco M, Vaquero JJ. A SPECT Scanner for Rodent Imaging Based on Small-Area Gamma Cameras. IEEE T NUCL SCI, 2010. 57:2524-2531. I.F.:1,59. 3 Almendros I, Montserrat JM, Torres M, Gonzalez C, Navajas D, Farre R. Changes in oxygen partial pressure of brain tissue in an animal model of obstructive apnea. RESP RES, 2010. 11:-. I.F.:3,13. 4 Iranzo A, Lomena F, Stockner H, Valldeoriola F, Vilaseca I, Salamero M, Molinuevo JL, Serradell M, Duch J, Pavia J, Gallego J, Seppi K, Hogl B, Tolosa E, Poewe W, Santamaria J. Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapideye-movement sleep behaviour disorder: a prospective study. LANCET NEUROL, 2010. 9:1070-1077. I.F.:18,13. 5 Martinez-Vidal B, Farre R, Montserrat JM, Torres M, Almendros I, Aguilar F, Embid C, Vilaseca I. Effects of heated humidification on nasal inflammation in a CPAP rat model. SLEEP MED, 2010. 11:413416. I.F.:3,70. 7 8 Bullich S, Cot A, Gallego J, Gunn RN, Suarez M, Pavia J, Ros D, Laruelle M, Catafau AM. Impact of scatter correction on D-2 receptor occupancy measurements using I-123-IBZM SPECT: Comparison to C-11-Raclopride PET. NEUROIMAGE, 2010. 50:1511-1518. I.F.:5,74. 9 Carreras A, Almendros I, Montserrat JM, Navajas D, Farre R. Mesenchymal stem cells reduce inflammation in a rat model of obstructive sleep apnea. RESP PHYSIOL NEUROBI, 2010. 172:210-212. I.F.:2,14. 10 Carreras A, Rojas M, Tsapikouni T, Montserrat JM, Navajas D, Farre R. Obstructive apneas induce early activation of mesenchymal stem cells and enhancement of endothelial wound healing. RESP RES, 2010. 11:-. I.F.:3,13. 11 Guerrero A, Embid C, Farre R, Navajas D, Masa JF, Duran J, Montserrat JM. Sleep Breathing Flow Characteristics as a Sign for the Detection of Wakefulness in Patients with Sleep Apnea. RESPIRATION, 2010. 80:495-499. I.F.:1,94. 123 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Respiratory biophysics and bioengineering Team Members Grants for research in progress Farré R. Efecto de los estímulos mecánicos en la diferenciación de células madres hacia el fenotipo epitelial alveolar. Sponsored by: Ministerio de Ciencia e Innovación, SAF2008-02991. Amount: 133.100,00 euros. Duration: 01/01/2009-31/12/2011. Ros D. Desarrollo del proyecto “Tecnologías de Imagen Molecular Avanzada (AMIT)”. Sponsored by: CDTI - CETIR, CENTRE MEDIC, S.A., 10/192. Amount: 50.000,00 euros. Duration: 01/01/2010-01/01/2013. Ros D. Cuantificación de estudios de SPECT cerebral utilizando ligandos del transportador de dopamina en modelos animales y en diagnóstico clínico. Sponsored by: Ministerio de Ciencia e Innovación, SAF200908076. Amount: 36.300,00 euros. Duration: 01/01/2010-31/12/2012. Farré R. Michromechanics of airway smooth muscle in culture. Sponsored by: NIHE - National Institutes of Health (USA), 2RO1-HL65960-06. Amount: 3.360.362,00 euros. Duration: 01/01/2005-31/12/2010. Farré R. An open, ubiquitous and adptive chronic disease management platform fr COPD and renal insufficiency (CHRONIOUS). 7COICT - COOPERATION. ICT. 7è Programa Marc. Information and Communication Technologies (Tecnologies de la Informació i la Comunicació). Sponsored by: European Commission, FP7-ICT-2007-1#216461. Amount: 189.844,75 euros. Duration: 01/01/2007-31/12/2010. 124 Pavia J, Ros D. Caracterización de gammacámaras: estandarización de estudios para SPECT cerebral. Sponsored by: GEHE - GE HEALTHCARE BIO-SCIENCES,S.A, 09/484. Amount: 17.000,00 euros. Duration: 01/01/2009-31/12/2011. Thesis Farre R. Activation of bone Marrow Mesenchymal Stem Cells in a rat model of obstructive sleep apnea. PhD student: Alba Carreras Palou. Estrach MT. Estudio de moléculas de adhesión en procesos dermatológicos malignos(Micosis fungoide-síndrome de Sézary) y benignos mediados por células T. PhD student: Ingrid Lopez Lerma. AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Team envolved in: Applied research in infectious respiratory diseases, critically ill patients and lung cancer Strategic Objectives GROUP Members TEAM LEADER Antoni Torres (Hospital Clínic) Tel.: 93 227 55 49 Fax: 93 227 55 49 E-mail: atorres@clinic.ub.es Idibaps members: Carles Agustí (Hospital Clínic) Joan Ramon Badia (Hospital Clínic) Miquel Ferrer (Hospital Clínic) Ramon Marrades (Hospital Clínic) Néstor Soler (Hospital Clínic) Dolors Soy (Hospital Clínic) Josep Mª Montserrat Marc Miravitlles (Fundació Clínic) Postdoctoral fellows: Gianluigi Li Bassi (IDIBAPS) Laura Guerrero (IDIBAPS) Isaac Almendros (CIBERes) Research Fellows: Mariano Esperatti (FIS) Arnoldo Guerrero (Hospital Clínic) Arturo Huerta (FIS) Catia Cillóniz (SGR) Gema Tirado (SEPAR) Laia Fernàndez (CIBERes) Hugo Loureiro (Hospital Clínic) Carmen Lucena (Hospital Clínic) Zinka Matkovic (ERS) Lina María Saucedo (Fundació Clínic) Marta Torres (CIBERes) Nursing Staff: Patrícia Fernández (FIS) Encarnación Moreno (Fundació Clínic) Alicia San José (CIBERes) Isabel Martín (Fundació Clínic) Rebeca Domingo (FIS) Administrative Staff: Elisabet Sancho (CIBERes) Staticians: Albert Gabarrús Barri (CIBERes) Physiotherapists: Joan Daniel Martí (Fundació Clínic) Beatriz Herrero (Fundació Clínic) Collaborators: Núria Sànchez (CAPSE) Jacobo Sellarés (Hospital Clínic) Pilar Martínez (Hospital Clínic) Eva Polverino (Hospital Clínic) Montserrat Rigol (IDIBAPS) 1. Study of community-acquired respiratory infections, nosocomial infections and infections in immune depressed patients. 2. Study of invasive and noninasive mechanical ventilation in acute respiratory failure, particularly in weaning from artificial ventilation. 3. Study of the exacerbation of chronic obstructive pulmonary disease (COPD) and the implication of bacterial, viral and fungal infectious agents. 4. Physiopathological and treatment studies in an animal model of ventilation associated pneumonia. 5. Human and animal model research in sleep apnea syndrome. 6. Multicenter studies in relation to sleep respiratory pathology and cardiovascular disease. 7. Epidemiology, diagnosis and treatment of adult bronchiectasia not associated with cystic fibrosis: Study of inflammatory response, new treatment modalities and immunoglobulin replacement therapy. Main Lines of Research 1. Epidemiology, prevention, diagnosis and new treatments of pneumonias associated with artificial ventilation. Resistances of microorganisms. Study of biofilms in endotracheal tubes. 2. Epidemiology and diagnosis of community-acquired pneumonia. Multicenter studies in the setting of community-acquired pneumonia. New treatments. Resistances of microorganisms. 3. Study of the risk factors, microbiology and prognosis of Health Care Associated Pneumonia (HCAP). 4. Etiopathogenesis, bronchial infection and inflammation in the patient with chronic obstructive pulmonary disease (COPD). Role of infections in exacerbation of the disease. Study of bronchial and associated systemic 125 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Applied research in infectious respiratory diseases, critically ill patients and lung cancer 5. 6. 7. 8. 9. response. Analysis of the risk and prognostic factors in acute episodes. Smoking. Epidemiology and diagnosis of alpha-1-antitrypsin deficiency. Chronic pulmonary infections: bronchiectasia not associated with cystic fibrosis, immune deficiencies and cystic fibrosis in the adult. Control of bronchial colonization. Study of bronchial inflammatory and associated systemic response. New treatment modalities (nebulizer antibiotic treatment). Replacement therapy with immunoglobulins. Infectious lung complications in immune depressed patients. Evaluation of the etiological factors. Optimization of the diagnostic techniques. Study of bronchial inflammatory and associated systemic response. Analysis of prognostic factors. Invasive and noninvasive mechanical ventilation: epidemiology, cost-effectiveness and physiopathology. New techniques. Weaning from mechanical ventilation: role of the inflammatory response and respiratory failure following extubation. Study of the pharmacokinetics of antibiotics and other drugs in the ventilated and non-ventilated patient. Porcine model of acute pulmonary damage due to P. aeruginosa and methicillin-resistant S. aureus: study of new coadjuvant drugs in the treatment of pneumonia, study of new antibiotics, prevention of ventila- Noninvasive ventilation after extubation significantly improves patient survival in relation to conventional treatment with oxygen therapy (Lancet; 374: 1082–88). tor-associated pneumonia (VAP), and new forms of mechanical ventilation. 10. Chronic sleep apnea models. 11. European studies of respiratory infections. Participation in the GRACE, MOSAR and THERAEDGE projects, which respectively investigate community-acquired respiratory infections, in-hospital respiratory infections and new diagnostic methods. For further information: www.idibapsrespiratoryresearch.org RESEARCH GROUP Breathing disturbances in sleep Group Leader: Josep M. Montserrat (Hospital Clínic) The main research line of this group is the analysis of respiratory disturbances in sleep. Specifically, the two most important lines are the following: the study of diagnostic methods and effects of treatment in a population of apneic patients in which the indication is not clear; and the study of animal models for exploring the mechanisms underlying the origin and consequences of the disorder. Both lines are carried out in the context of national multicenter clinical trials. 126 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Applied research in infectious respiratory diseases, critically ill patients and lung cancer PUBLICATIONS Originals I.F.: 197,85 fected patients. DIAGN MICR INFEC DIS, 2010. 68:60-65. I.F.:2,45. 1 Soto-Cardenas MJ, Perez-De-Lis 6 Ferrer M, Liapikou A, Valencia M, M, Bove A, Navarro C, Brito-Zeron P, Diaz-Lagares C, Gandia M, Akasbi M, Siso A, Ballester E, Torres A, RamosCasals M. Bronchiectasis in primary Sjogren’s syndrome: prevalence and clinical significance. CLIN EXP RHEUMATOL, 2010. 28:647-653. I.F.:2,40. Esperatti M, Theessen A, Martinez JA, Mensa J, Torres A. Validation of the American Thoracic Society-Infectious Diseases Society of America Guidelines for Hospital-Acquired Pneumonia in the Intensive Care Unit. CLIN INFECT DIS, 2010. 50:945-952. I.F.:8,20. 2 Garcia-De-La-Maria C, Marco F, 7 Valles X, Roca A, Lozano F, Morais Armero Y, Soy D, Moreno A, DelRio A, Almela M, Cervera C, Ninot S, Falces C, Mestres CA, Gatell JM, DeAnta MTJ, Miro JM. Daptomycin Is Effective for Treatment of Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus epidermidis. ANTIMICROB AGENTS CH, 2010. 54:2781-2786. I.F.:4,80. L, Suarez B, Casals F, Mandomando I, Sigauque B, Nhalungo D, Esquinas C, Quinto L, Alonso PL, Torres A. Serotype-specific pneumococcal disease may be influenced by mannosebinding lectin deficiency. EUR RESPIR J, 2010. 36:856-863. I.F.:5,53. 3 Polverino E, Dambrava P, Cilloniz C, Balasso V, Marcos MA, Esquinas C, Mensa J, Ewig S, Torres A. Nursing home-acquired pneumonia: a 10 year single-centre experience. THORAX, 2010. 65:354-359. I.F.:7,04. 4 Perello R, Miro O, Marcos MA, Almela M, Bragulat E, Sanchez M, Agusti C, Miro JM, Moreno A. Predicting bacteremic pneumonia in HIV-1-infected patients consulting the ED. AM J EMERG MED, 2010. 28:454-459. I.F.:1,54. 5 Alvarez-Martinez MJ, Miro JM, Valls ME, Mas J, DeLaBellacasa JP, Sued O, Sole M, Rivas PV, DeLazzari E, Benito N, Garcia F, Agusti C, Wilson PE, Gatell JM, DeAnta MTJ, Meshnick SR, Moreno A. Prevalence of dihydropteroate synthase genotypes before and after the introduction of combined antiretroviral therapy and their influence on the outcome of Pneumocystis pneumonia in HIV-1-in- 8 Gutierrez P, Closae D, Piner R, Bulbena O, Menendez R, Torres A. Macrophage activation in exacerbated COPD with and without communityacquired pneumonia. EUR RESPIR J, 2010. 36:285-291. I.F.:5,53. 9 Martinez-Olondris P, Sibila O, Agusti C, Rigol M, Soy D, Esquinas C, Piner R, Luque N, Guerrero L, Quera MA, Marco F, DeLaBellacasa JP, Ramirez J, Torres A. An experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus in ventilated piglets. EUR RESPIR J, 2010. 36:901-906. I.F.:5,53. 10 Guerrero L, Martinez-Olondris P, Rigol M, Esperatti M, Esquinas C, Luque N, Piner R, Torres A, Soy D. Development and validation of a high performance liquid chromatography method to determine linezolid concentrations in pig pulmonary tissue. CLIN CHEM LAB MED, 2010. 48:391-398. I.F.:1,89. 11 Martinez-Olondris P, Rigol M, Torres A. What lessons have been learnt from animal models of MRSA in the lung?. EUR RESPIR J, 2010. 35:198-201. I.F.:5,53. 12 Almendros I, Montserrat JM, Torres M, Gonzalez C, Navajas D, Farre R. Changes in oxygen partial pressure of brain tissue in an animal model of obstructive apnea. RESP RES, 2010. 11:-. I.F.:3,13. 13 Martinez-Vidal B, Farre R, Montserrat JM, Torres M, Almendros I, Aguilar F, Embid C, Vilaseca I. Effects of heated humidification on nasal inflammation in a CPAP rat model. SLEEP MED, 2010. 11:413-416. I.F.:3,70. 14 Carreras A, Almendros I, Montserrat JM, Navajas D, Farre R. Mesenchymal stem cells reduce inflammation in a rat model of obstructive sleep apnea. RESP PHYSIOL NEUROBI, 2010. 172:210-212. I.F.:2,14. 15 Carreras A, Rojas M, Tsapikouni T, Montserrat JM, Navajas D, Farre R. Obstructive apneas induce early activation of mesenchymal stem cells and enhancement of endothelial wound healing. RESP RES, 2010. 11:-. I.F.:3,13. 16 Guerrero A, Embid C, Farre R, Navajas D, Masa JF, Duran J, Montserrat JM. Sleep Breathing Flow Characteristics as a Sign for the Detection of Wakefulness in Patients with Sleep Apnea. RESPIRATION, 2010. 80:495499. I.F.:1,94. 17 Soler N, Ballester E, Martin A, Gobartt E, Miravitlles M, Torres A. Changes in management of chronic obstructive pulmonary disease (COPD) in primary care: EMMEPOC study. RESP MED, 2010. 104:67-75. I.F.:2,33. 127 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Applied research in infectious respiratory diseases, critically ill patients and lung cancer Team Members 18 Malinis M, Myers J, Bordon J, Peyrani P, Kapoor R, Nakamatzu R, Lopardo G, Torres A, Feldman C, Allen M, Arnold F, Ramirez J. Clinical outcomes of HIV-infected patients hospitalized with bacterial communityacquired pneumonia. INT J INFECT DIS, 2010. 14:E22-E27. I.F.:2,17. Pineiro L, Sanchez G, Serra J, SolerCataluna JJ, Torres A, Viejo JL, Sobradillo-Pena V, Ancochea J. Geographical Variations in the Prevalence of COPD in Spain: Relationship to Smoking, Death Rates and other Determining Factors. ARCH BRONCONEUMOL, 2010. 46:522-530. I.F.:2,17. 19 Miravitlles M, Marin A, Monso 24 Almirall J, Bolibar I, Serra-Prat E, Vila S, DeLaRoza C, Hervas R, Esquinas C, Garcia M, Millares L, Morera J, Torres A. Colour of sputum is a marker for bacterial colonisation in chronic obstructive pulmonary disease airway. RESP RES, 2010. 11:-. I.F.:3,13. M, Palomera E, Roig J, Hospital I, Carandell E, Agusti M, Ayuso P, Estela A, Torres A. Inhaled drugs as risk factors for community-acquired pneumonia. EUR RESPIR J, 2010. 36:1080-1087. I.F.:5,53. 20 Pino-Yanes M, Corrales A, Casula M, Blanco J, Muriel A, Espinosa E, Garcia-Bello M, Torres A, Ferrer M, Zavala E, Villar J, Flores C. Common Variants of TLR1 Associate with Organ Dysfunction and Sustained Pro-Inflammatory Responses during Sepsis. PLOS ONE, 2010. 5:-. I.F.:4,35. 21 Duran-Cantolla J, Aizpuru F, Montserrat JM, Ballester E, TeranSantos J, Aguirregomoscorta JI, Gonzalez M, Lloberes P, Masa JF, De La Pena M, Carrizo S, Mayos M, Barbe F. Continuous positive airway pressure as treatment for systemic hypertension in people with obstructive sleep apnoea: randomised controlled trial. BRIT MED J, 2010. 341:-. I.F.:13,66. 22 Partridge MR, Miravitlles M, Stahl E, Karlsson N, Svensson K, Welte T. Development and validation of the Capacity of Daily Living during the Morning questionnaire and the Global Chest Symptoms Questionnaire in COPD. EUR RESPIR J, 2010. 36:96-104. I.F.:5,53. 23 Soriano JB, Miravitlles M, Borderias L, Duran-Tauleria E, Rio FG, Martinez J, Montemayor T, Munoz L, 128 25 Miravitlles M, Herr C, Ferrarotti I, Jardi R, Rodriguez-Frias F, Luisetti M, Bals R. Laboratory testing of individuals with severe alpha(1)-antitrypsin deficiency in three European centres. EUR RESPIR J, 2010. 35:960968. I.F.:5,53. 26 Barbe F, Duran-Cantolla J, Capote F, DeLaPena M, Chiner E, Masa JF, Gonzalez M, Marin JM, Garcia-Rio F, DeAtauri JD, Teran J, Mayos M, Monasterio C, DelCampo F, Gomez S, DeLaTorre MS, Martinez M, Montserrat JM. Long-term Effect of Continuous Positive Airway Pressure in Hypertensive Patients with Sleep Apnea. AM J RESP CRIT CARE, 2010. 181:718-726. I.F.:10,69. 27 Esperatti M, Ferrer M, Theessen A, Liapikou A, Valencia M, Saucedo LM, Zavala E, Welte T, Torres A. Nosocomial Pneumonia in the Intensive Care Unit Acquired by Mechanically Ventilated versus Nonventilated Patients. AM J RESP CRIT CARE, 2010. 182:1533-1539. I.F.:10,69. 28 Polverino E, Nava S, Ferrer M, Ceriana P, Clini E, Spada E, Zanotti E, Trianni L, Barbano L, Fracchia C, Balbi B, Vitacca M. Patients’ charac- terization, hospital course and clinical outcomes in five Italian respiratory intensive care units. INTENS CARE MED, 2010. 36:137-142. I.F.:5,17. 29 Arnold FW, Brock GN, Peyrani P, Rodriguez EL, Diaz AA, Rossi P, Ramirez JA. Predictive accuracy of the pneumonia severity index vs CRB-65 for time to clinical stability: Results from the CommunityAcquired Pneumonia Organization (CAPO) International Cohort Study. RESP MED, 2010. 104:1736-1743. I.F.:2,33. 30 Diez-Padrisa N, Bassat Q, Machevo S, Quinto L, Morais L, Nhampossa T, O’callaghan-Gordo C, Torres A, Alonso PL, Roca A. Procalcitonin and C-Reactive Protein for Invasive Bacterial Pneumonia Diagnosis among Children in Mozambique, a Malaria-Endemic Area. PLOS ONE, 2010. 5:-. I.F.:4,35. 31 Sethi S, Jones PW, Theron MS, Miravitlles M, Rubinstein E, Wedzicha JA, Wilson R. Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. RESP RES, 2010. 11:-. I.F.:3,13. 32 Soriano JB, Ancochea J, Miravitlles M, Garcia-Rio F, Duran-Tauleria E, Munoz L, Jimenez-Ruiz CA, Masa JF, Viejo JL, Villasante C, FernandezFau L, Sanchez G, Sobradillo-Pena V. Recent trends in COPD prevalence in Spain: a repeated cross-sectional survey 1997-2007. EUR RESPIR J, 2010. 36:758-765. I.F.:5,53. 33 Ewig S, Welte T, Chastre J, Torres A. Rethinking the concepts of community-acquired and healthcare-associated pneumonia. LANCET INFECT DIS, 2010. 10:279-287. I.F.:15,58. AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Applied research in infectious respiratory diseases, critically ill patients and lung cancer 34 Garcia-Rio F, Miravitlles M, Soriano JB, Munoz L, Duran-Tauleria E, Sanchez G, Sobradillo V, Ancochea J. Systemic inflammation in chronic obstructive pulmonary disease: a population-based study. RESP RES, 2010. 11:-. I.F.:3,13. 35 Miravitlles M, Ferrara G, Lange C, Dimopoulos G, Rohde G, Blasi F, Migliori GB. TB or not TB: update from the ERS Respiratory Infection Assembly 10. EUR RESPIR J, 2010. 36:665-670. I.F.:5,53. 36 Pinazo MJ, Munoz J, Posada E, Lopez-Chejade P, Gallego M, Ayala E, DelCacho E, Soy D, Gascon J. Tolerance of Benznidazole in Treatment of Chagas’ Disease in Adults. ANTIMICROB AGENTS CH, 2010. 54:48964899. I.F.:4,80. 37 Butler CC, Hood K, Kelly MJ, Goossens H, Verheij T, Little P, Melbye H, Torres A, Molstad S, GodyckiCwirko M, Almirall J, Blasi F, Schaberg T, Edwards P, Rautakorpi UM, Hupkova H, Wood J, Nuttall J, Coenen S. Treatment of acute cough/lower respiratory tract infection by antibiotic class and associated outcomes: a 13 European country observational study in primary care. J ANTIMICROB CHEMOTH, 2010. 65:2472-2478. I.F.:4,35. 38 Torres A, Rello J. Update in Community-acquired and Nosocomial Pneumonia 2009. AM J RESP CRIT CARE, 2010. 181:782-787. I.F.:10,69. 39 Espana PP, Capelastegui A, Quintana JM, Bilbao A, Diez R, Pascual S, Esteban C, Zalacain R, Menendez R, Torres A. Validation and comparison of SCAP as a predictive score for identifying low-risk patients in communityacquired pneumonia. J INFECTION, 2010. 60:106-113. I.F.:3,06. Reviews I.F.: 13,55 1 Bassi GL, Ferrer M, Saucedo LM, Torres A. Do guidelines change outcomes in ventilator-associated pneumonia?. CURR OPIN INFECT DIS, 2010. 23:171-177. I.F.:4,72. 2 Gomez-Caro A, Badia JR, Ausin P. Extracorporeal Lung Assist in Severe Respiratory Failure and ARDS. Current Situation and Clinical Applications. ARCH BRONCONEUMOL, 2010. 46:531-537. I.F.:2,17. 3 Anzueto A, Miravitlles M. Shortcourse fluoroquinolone therapy in exacerbations of chronic bronchitis and COPD. RESP MED, 2010. 104:13961403. I.F.:2,33. 4 Martinez-Garcia MA, Duran-Cantolla J, Montserrat JM. Sleep ApneaHypopnea Syndrome in the Elderly. ARCH BRONCONEUMOL, 2010. 46:479-488. I.F.:2,17. 5 Sevilla-Sanchez D, Soy-Muner D, Soler-Porcar N. Usefulness of Macrolides as Anti-Inflammatories in Respiratory Diseases. ARCH BRONCONEUMOL, 2010. 46:244-254. I.F.:2,17. Editorials I.F.: 16,35 1 Torres A, Menendez R. Enterobacteriaceae and Pseudomonas aeruginosa in community-acquired pneumonia: the reality after a decade of uncertainty?. EUR RESPIR J, 2010. 35:473-474. I.F.:5,53. 2 Ferrer M. Non-Invasive Mechanical Ventilation and the Prognosis in Chronic Obstructive Pulmonary Disease. ARCH BRONCONEUMOL, 2010. 46:399-401. I.F.:2,17. 3 Ewig S, Torres A. Severity scores for CAP. ‘Much workload for the next bias’. THORAX, 2010. 65:853-855. I.F.:7,04. 4 Polverino E, Ferrer M. VAP surveillance: role of non-quantitative culture of endotracheal aspirates (NQC-ETA). MINERVA ANESTESIOL, 2010. 76:572-574. I.F.:1,61. Clinical Guidelines I.F.: 2,17 1 Menendez R, Torres A, Aspa J, Capelastegui A, Prat C, DeCastro FR. Community Acquired Pneumonia. New Guidelines of the Spanish Society of Chest Diseases and Thoracic Surgery (SEPAR). ARCH BRONCONEUMOL. 46:543-558. I.F.:2,17. Multicentrics I.F.: 47,05 1 Sciurba FC, Ernst A, Herth FJF, Strange C, Criner GJ, Marquette CH, Kovitz KL, Chiacchierini RP, Goldin J, Mclennan G. A Randomized Study of Endobronchial Valves for Advanced Emphysema. NEW ENGL J MED. 363:1233-1244. I.F.:47,05. Grants for research in progress Ferrer M. Eficacia de los glucocorticoides en la neumonía asociada a la ventilación mecánica estudio clínico aleatorizado. Sponsored by: Ministerio Sanidad y Consumo, EC07/90390. Amount: 34.418,45 euros. Duration: 29/10/2007-30/12/2010. Soy D. Eficacia del tratamiento con Linezolid comparado con vancomicina en la neumonia asociada a la venti- 129 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Applied research in infectious respiratory diseases, critically ill patients and lung cancer Team Members lación mecánica (NAVM) por Staphylococcus Aureus Meticilin-resistente. Estudio en un modelo porcino. Sponsored by: Ministerio Sanidad y Consumo, PI070419. Amount: 87.107,90 euros. Duration: 26/11/200730/12/2010. Soler N. Evalución prospectiva de la purulencia del esputo y la procalcitonina como marcadores de infección respiratoria discal en la agudización de la enfermedad pulmonar obstructiva crónica (EPOC). Sponsored by: Ministerio Sanidad y Consumo, PI070472. Amount: 43.560,00 euros. Duration: 26/11/2007-30/12/2010. Torres A. GENOMICS TO COMBAT RESISTANCE AGAINST ANTIBIOTICS IN COMMUNITY-ACQUIRED LRTI IN EUROPE. Sponsored by: Universiteit Antwerpen, LSHM-CT-2005-518226. Amount: 151.700,00 euros. Duration: 01/03/2007-28/02/2011. Torres A. An integrated platform enabling Theranostic applications at the Point of Primary Care. Sponsored by: NTE, S.A., 216027. Amount: 99.999,75 euros. Duration: 01/03/2008-29/02/2012. Torres A. Health Care Associated Pneumonia (HCAP). Sponsored by: Fondo de Investigación Sanitaria, PI080240. Amount: 127.292,00 euros. Duration: 01/01/2009-31/12/2012. Torres A. Coordinador de equipo del Grup de Recerca de Qualitat . Sponsored by: Generalitat de Catalunya, SGR/911. Amount: 58.240,00 euros. Duration: 01/01/2009-31/12/2013. Ferrer M. Papel de la respuesta inflamatoria y el estrés oxidativo sistémico en la retirada de la ven- 130 tilación mecánica invasiva. Sponsored by: Fondo de Investigación Sanitaria, PI080232. Amount: 61.962,00 euros. Duration: 01/01/2008-31/12/2010. Marrades R. Expresión y cuantificación de micrornas en sangre periférica, tejido tumoral y tejido normal en pacientes con cáncer de pulmón: relaciones terapéuticas y pronósticas. Sponsored by: Fondo de Investigación Sanitaria, PI080135. Amount: 61.962,00 euros. Duration: 01/01/2008-31/12/2010. Soler N. Utilidad del tratamiento antibiótico en las agudizaciones de la enfermedad pulmonar obstructiva crónica (EPOC) sin purulencia en el esputo: ensayo clínico aleatorizado, controlado y doble ciego de eficacia y seguridad. Sponsored by: Fondo de Investigación Sanitaria, EC08/00061. Amount: 109.505,00 euros. Duration: 01/01/2008-31/12/2010. Torres A. Mastering of Hospital Antimicrobial Resistance (MOSAR) Surgical WP4. Sponsored by: European Comisión, CP040280. Amount: 75.877,00 euros. Duration: 01/01/2008-31/12/2010. Torres A. Mastering of Hospital Antimicrobial Resistance (MOSAR) ICU WP3. Sponsored by: European Comisión, CP040280. Amount: 69.102,00 euros. Duration: 01/01/2008-31/12/2010. Torres A, Polverino E. Fracaso del tratamiento en la neumonía adquirida en la comunidad. Factores de riesgo de exceso de inflamación y su impacto en el pronóstico. Sponsored by: Fondo de Investigación Sanitaria (FIS), PI080472. Amount: 27.346,00 euros. Duration: 01/01/200831/12/2010. Torres A. Efectos de los flujos insipartorio-respiratorio y la presión positiva al final de la espiración en el aclaramiento de secreciones y la neumonía asociada al ventilador. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1249. Amount: 38.115,00 euros. Duration: 01/01/2010-31/12/2012. Montserrat JM. Efectos sistémicos del síndrome de las apneas durante el sueño. Análisis mediante modelos animales y estudios cognitivos en humanos.. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI08/0277. Amount: 98.252,00 euros. Duration: 31/12/2008-30/12/2011. Thesis Ferrer M, Torres A. Fisiopatología y papel de la ventilación no invasiva en el fracaso del weaning. PhD student: Jacobo Sellares Torres. AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Team envolved in: & RETICS de Biobancos Physiopathological mechanisms of respiratory illnesses GROUP Members Strategic Objectives TEAM LEADER Joan Albert Barberà (Hospital Clínic) Tel.: 93 227 57 47 Fax: 93 227 54 55 E-mail: jbarbera@clinic.ub.es Idibaps members: Josep Roca (Hospital Clínic) Robert Rodríguez-Roisín (Hospital Clínic) Elizabeth Zavala (Hospital Clínic) Postdoctoral fellows: Melina Musri (IDIBAPS) Research Fellows: Marta Díez (FIS) Elisabeth Ferrer (FIS) Diego Rodríguez (ERS-SEPAR) Karina Portillo (Fundació Clínic) Ebymar Arismendi (Fundació Clínic) Jéssica Garcia (Fundació Clínic) David Domínguez (Fundació Clínic) Borja Lobo (Fundació Clínic) Technicians: Raquel Puig-Pey (IDIBAPS) Núria Coll (Fundació Clínic) Nursing Staff: Conchi Gistau (Hospital Clínic) Yolanda Torralba (CIBERES) Maite Simó (Hospital Clínic) Maria Palomo (Fundació Clínic) Xavier Alsina (Hospital Clínic) Beatriz Valeiro (Fundació Clínic) Administrative Staff: Mirjam Hillenius (Fundació Clínic) Julio Más (Fundació Clínic CIBERES) Physiotherapists: Anael Barberan (Fundació Clínic) Ane Arbillaga (Fundació Clínic) Collaborators: Albert Alonso (Fundació Clínic) Isabel Blanco (Hospital Clínic) Felip Burgos (Hospital Clínic) Federico Gómez (Universitat de Barcelona) Carme Hernández (Hospital Clínic) Graciela Martínez-Pallí (Hospital Clínic) Victor I. Peinado (CIBERES) Sandra Pizarro (Hospital Clínic) Jordi Vilaró (Fundació Clínic) Elena Gimeno (IDIBAPS) 1. Investigation of the molecular and cellular bases of chronic respiratory diseases, with special emphasis on pulmonary circulatory disorders and systemic manifestations. 2. Study of the physiopathological and pathogenic mechanisms related to acute and chronic respiratory failure, focusing on chronic obstructive diseases, hepatopulmonary disorders and obesity. 3. Evaluation of the potential of cell therapy and tissue engineering applied to respiratory diseases. 4. Development of artificial and bioartificial lung models for the support of patients with acute and chronic respiratory failure. 5. Study of the determining factors of the clinical course and healthcare resource utilization in chronic respiratory diseases. Main Lines of Research 1. Biopathology and physiopathology of pulmonary circulation disorders. 2. Physical activity, cell bioenergetics and systemic effects of chronic obstructive pulmonary disease (COPD). 3. Physiopathological mechanisms underlying gas exchange alterations in airway obstructive diseases. 4. Interaction between systemic and pulmonary inflammation in COPD and morbid obesity. 5. Tissue engineering and bioartificial lung models. 6. Prognostic and determining factors of healthcare resource utilization in chronic respiratory disease. 7. Analysis of inflammation and oxidative stress biomarkers in exhaled air in the study of respiratory diseases. View of two precursor vascular cells with interdifferential technology. One of the cells maintains the precursor phenotype, while the other has acquired a smooth muscle cell phenotype. 131 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Physiopathological mechanisms of respiratory illnesses Team Members PUBLICATIONS Originals I.F.: 121,18 1 Rodriguez-Trigo G, Zock JP, PozoRodriguez F, Gomez FP, Monyarch G, Bouso L, Coll MD, Verea H, Anto JM, Fuster C, Barbera JA. Health Changes in Fishermen 2 Years After Clean-up of the Prestige Oil Spill. ANN INTERN MED, 2010. 153:489-W176. I.F.:16,23. 2 Portillo K, Santos S, Madrigal I, Blanco I, Pare C, Borderias L, Peinado VI, Roca J, Mila M, Barbera JA. Study of the BMPR2 Gene in Patients with Pulmonary Arterial Hypertension. ARCH BRONCONEUMOL, 2010. 46:129-134. I.F.:2,17. 3 Go T, Jungebluth P, Baiguero S, Asnaghi A, Martorell J, Ostertag H, Mantero S, Birchall M, Bader A, Macchiarini P. Both epithelial cells and mesenchymal stem cell-derived chondrocytes contribute to the survival of tissue-engineered airway transplants in pigs. J THORAC CARDIOV SUR, 2010. 139:437-443. I.F.:3,06. 4 Pino-Yanes M, Corrales A, Casula M, Blanco J, Muriel A, Espinosa E, Garcia-Bello M, Torres A, Ferrer M, Zavala E, Villar J, Flores C. Common Variants of TLR1 Associate with Organ Dysfunction and Sustained Pro-Inflammatory Responses during Sepsis. PLOS ONE, 2010. 5:-. I.F.:4,35. 5 Esperatti M, Ferrer M, Theessen A, Liapikou A, Valencia M, Saucedo LM, Zavala E, Welte T, Torres A. Nosocomial Pneumonia in the Intensive Care Unit Acquired by Mechanically Ventilated versus Nonventilated Patients. AM J RESP CRIT CARE, 2010. 182:1533-1539. I.F.:10,69. 6 Melgosa MT, Ricci GL, GarciaPagan JC, Blanco I, Escribano P, Abraldes JG, Roca J, Bosch J, Barbera 132 JA. Acute and Long-Term Effects of Inhaled Iloprost in Portopulmonary Hypertension. LIVER TRANSPLANT, 2010. 16:348-356. I.F.:3,72. 7 Haq I, Chappell S, Johnson SR, Lotya J, Daly L, Morgan K, GuettaBaranes T, Roca J, Rabinovich R, Millar AB, Donnelly SC, Keatings V, Macnee W, Stolk J, Hiemstra PS, Miniati M, Monti S, O’connor CM, Kalsheker N. Association of MMP-12 polymorphisms with severe and very severe COPD: A case control study of MMPs - 1, 9 and 12 in a European population. BMC MED GENET, 2010. 11:-. I.F.:2,84. 8 Macchiarini P, Rovira I, Ferrarello S. Awake Upper Airway Surgery. ANN THORAC SURG, 2010. 89:387-390. I.F.:3,64. 9 Barreiro E, Peinado VI, Galdiz JB, Ferrer E, Mann-Corral J, Sanchez F, Gea J, Barbera JA. Cigarette Smokeinduced Oxidative Stress A Role in Chronic Obstructive Pulmonary Disease Skeletal Muscle Dysfunction. AM J RESP CRIT CARE, 2010. 182:477-488. I.F.:10,69. 10 Azzalini L, Ferrer E, Ramalho LN, Moreno M, Dominguez M, Colmenero J, Peinado VI, Barbera JA, Arroyo V, Gines P, Caballeria J, Bataller R. Cigarette Smoking Exacerbates Nonalcoholic Fatty Liver Disease in Obese Rats. HEPATOLOGY, 2010. 51:15671576. I.F.:10,84. 11 Mascia L, Pasero D, Slutsky AS, Arguis MJ, Berardino M, Grasso S, Munari M, Boifava S, Cornara G, DellaCorte F, Vivaldi N, Malacarne P, DelGaudio P, Livigni S, Zavala E, Filippini C, Martin EL, Donadio PP, Mastromauro I, Ranieri VM. Effect of a Lung Protective Strategy for Organ Donors on Eligibility and Availability of Lungs for Transplantation A Randomized Controlled Trial. JAMA-J AM MED ASSOC, 2010. 304:2620-2627. I.F.:28,90. 12 Diez M, Musri MM, Ferrer E, Barbera JA, Peinado VI. Endothelial progenitor cells undergo an endothelial-to-mesenchymal transition-like process mediated by TGF beta RI. CARDIOVASC RES, 2010. 88:502-511. I.F.:5,80. 13 Vilaro J, Ramirez-Sarmiento A, Martinez-Llorens JM, Mendoza T, Alvarez M, Sanchez-Cayado N, Vega A, Gimeno E, Coronell C, Gea J, Roca J, Orozco-Levi M. Global muscle dysfunction as a risk factor of readmission to hospital due to COPD exacerbations. RESP MED, 2010. 104:1896-1902. I.F.:2,33. 14 Blanco I, Gimeno E, Munoz PA, Pizarro S, Gistau C, Rodriguez-Roisin R, Roca J, Barbera JA. Hemodynamic and Gas Exchange Effects of Sildenafil in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension. AM J RESP CRIT CARE, 2010. 181:270-278. I.F.:10,69. 15 Blanco I, Villaquiran C, Valera JL, Molina-Molina M, Xaubet A, Rodriguez-Roisin R, Barbera JA, Roca J. Peak Oxygen Uptake During the Sixminute Walk Test in Diffuse Interstitial Lung Disease and Pulmonary Hypertension. ARCH BRONCONEUMOL, 2010. 46:122-128. I.F.:2,17. 16 Sanchez-Lorente D, Go T, Jungebluth P, Rovira I, Mata M, Ayats MC, Macchiarini P. Single double-lumen venous-venous pump-driven extracorporeal lung membrane support. J THORAC CARDIOV SUR, 2010. 140:558-U105. I.F.:3,06. AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Physiopathological mechanisms of respiratory illnesses Reviews I.F.: 2,75 1 Subias PE, Mir JAB, Suberviola V. Current Diagnostic and Prognostic Assessment of Pulmonary Hypertension. REV ESP CARDIOL, 2010. 63:583596. I.F.:2,75. Multicentrics I.F.: 50,08 1 Sciurba FC, Ernst A, Herth FJF, Strange C, Criner GJ, Marquette CH, Kovitz KL, Chiacchierini RP, Goldin J, Mclennan G. A Randomized Study of Endobronchial Valves for Advanced Emphysema. NEW ENGL J MED, 2010. 363:1233-1244. I.F.:47,05. 2 Leidy NK, Wilcox TK, Jones PW, Murray L, Winnette R, Howard K, Petrillo J, Powers J, Sethi S. Development of the EXAcerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT): A Patient-Reported Outcome (PRO) Measure. VALUE HEALTH, 2010. 13:965-975. I.F.:3,03. Grants for research in progress Roca J. Indicators for Monitoring COPD and Asthma in the Eu - IMCA 11. Sponsored by: FUNDACIO IMIMPARC DE RECERCA BIOMÈDICA, 2005121. Amount: 240.115,00 euros. Duration: 15/12/2006-30/06/2010. Roca J. IP - Healthcare by Biosensor Measurements And Networking. Sponsored by: European Commision, NMP4-CT-2006-017333. Amount: 203.670,00 euros. Duration: 01/11/2005-31/10/2010. Barbera JA. Estudio de los efectos de sildenafilo sobre el intercambio gaseoso, la hemodinámica pulmonar y la tolerancia al esfuerzo en pacientes con hipertensión pulmonar asociada a la enfermedad pulmonar obstructiva crónica. Sponsored by: Fondo de Investigación Sanitaria (FIS), EC0790049. Amount: 332.750,00 euros. Duration: 01/01/200831/12/2011. Thesis Peinado V, Barbera JA. Mecanismos implicados en la diferenciación de las células progenitoras endoteliales durante el remodelado vascular pulmonar. PhD student: Marta Díez Cuñado. Roca J. Healthier and Independent Living for Chronic Patients and Elderly - NEXES». Sponsored by: Unión Europea, FP7 (CIP-ICT) 225025. Amount: 484.280,00 euros. Duration: 01/01/200831/12/2011. Peinado V. Mecanismos moleculares de la diferenciación de células progenitoras endoteliales durante la reparación del endotelio en la hipertensión pulmonar. Sponsored by: Fundació Marató TV3, 08/1310. Amount: 195.725,63 euros. Duration: 01/01/2009-31/12/2011. Barbera JA. Estudio de nuevas dianas terapéuticas en el tratamiento de la hipertensión pulmonar asociada a la enfermedad pulmonar obstructiva crónica. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/0536. Amount: 328.515,00 euros. Duration: 01/01/201031/12/2013. Roca J. Servicios innovadores de atención integrada para pacientes crónicos. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/90634. Amount: 167.585,00 euros. Duration: 01/01/201031/12/2012. Rodriguez R. Obesidad mórbida e inflamación sistématica y pulmonar. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI08/0311. Amount: 92.202,00 euros. Duration: 31/12/200830/12/2011. 133 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Clinical and Experimental Respiratory Immunoallergy (IRCE) Team envolved in: & Red de Investigación de Reacciones Adversas a Alérgenos y Fármacos (RIRAAF) Team Members Strategic Objectives TEAM LEADER César Picado (Hospital Clínic, Universitat de Barcelona) Tel.: 93 227 26 34 Fax: 93 227 98 13 E-mail: cpicado@clinic.ub.es Idibaps members: Joaquim Mullol (IDIBAPS) Antoni Xaubet (Hospital Clínic) Joan Bartra (Hospital Clínic) Antonio Valero (Hospital Clínic) Laura Pujols Tarrés (Fundació Clínic) Isam Alobid (Hospital Clínic) Postdoctoral fellows: Josep Maria Guilemany (FIS - SEORL) Jordi Roca-Ferrer (UB) Research Fellows: Rosa Maria Muñoz-Cano (FIS) Francisco Garcia Garcia (FIS) Laura Fernández-Bertolin (IDIBAPS) Francisco de Borja Callejas (FIS) Marta Gabasa (CIBERES) Suha Jabr (Ministeri d’Afers Exteriors i Cooperació) Jaume Sánchez López (Fundació Clínic) Maria Rueda (Fundació Clínic) Liliana Carbalho (Erasmus Portugal) Franklin Mariño Sánchez (Hospital Clínic) Erola Ainsua Enrich (FPI) Esteban Cano (Hospital Clínic) 134 Technicians: Mireia Fuentes Prado (Fundació Clínic) María Pérez Gonzalez (Fundació Clínic) Nursing Staff: Sílvia Centellas (Hospital Clínic) Sarai Sánchez Fuentes (Fundació Clínic) Administrative Staff: Elena Arrufat (Fundació Clínic) Collaborators: Assumpció Martínez-Antón (CCMD NIH) Yvonne Torres (Ministeri d’Educació, Govern de Panamà) Rosa Torres (FIS) María del Carmen Vennera (CIBERes) Joaquim Ensenyat Nora (Hospital Clínic) Margarita Martin Andorrà (Fundació Clínic) Damiana Alvarez Errico (Juan de la Cierva) 1. Investigation of the mechanisms regulating inflammatory response and remodelling in bronchial asthma, rhinosinusitis and pulmonary interstitial diseases. 2. Investigation of the mechanisms underlying food allergies. 3. Investigation of the mechanisms involved in anaphylaxis of complex etiopathogenesis. 4. Investigation of the mechanisms involved in loss of smell. Main Lines of Research 1. Molecular and cellular bases of the inflammatory response in asthma, rhinosinusitis and pulmonary interstitial diseases. 2. Role of the MUC genes in the modulation of mucosal secretion in respiratory diseases, and glucocorticoid regulation. 3. Role of arachidonic acid metabolites (prostaglandins and leukotrienes) in the etiopathogenesis of asthma, rhinosinusitis and pulmonary interstitial diseases. 4. Role of the angiotensin system in lung fibrosis. 5. Study of the mechanisms regulating the response to glucocorticoid treatment in inflammatory respiratory diseases. 6. Study of the mechanisms involved in severe asthma and relationship with alterations in glucocorticoid receptor function. 7. Study of the relationship between upper airway disorders (nasal and sinuses) and alterations of the lower airway (asthma, bronchiectasia, chronic obstructive pulmonary disease). 8. Study of the mechanisms regulating the response to food allergens and relationship with nonsteroidal antiinflammatory drugs and arachidonic acid metabolism. AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Clinical and Experimental Respiratory Immunoallergy (IRCE) PUBLICATIONS 9. New therapeutic modalities (endothelin, proteosome and COX-2 inhibitors; prostaglandin E2 receptor 3 agonists) in asthma, rhinosinusitis and pulmonary interstitial diseases based on in vitro models and animal models of asthma and pulmonary fibrosis. 10. Study of the mechanisms of anaphylactic reactions of multiple origin (indolent mastocytosis, predisposing genetic alterations). 11. Study of quality of life in nasosinusal pathology. 12. Loss of smell: role of nasosinusal inflammation, Parkinson’s disease and congenital alterations. Originals I.F.: 58,14 1 Criado E, Sanchez M, Ramirez J, Arguis P, DeCaralt TM, Perea RJ, Xaubet A. Pulmonary Sarcoidosis: Typical and Atypical Manifestations at High-Resolution CT with Pathologic Correlation. RADIOGRAPHICS, 2010. 30:1567-U155. I.F.:2,75. Immunohistochemical study showing the presence of mucin 5C in the epithelial goblet cells of a nasal polyp. 2 Blanco I, Villaquiran C, Valera JL, Molina-Molina M, Xaubet A, Rodriguez-Roisin R, Barbera JA, Roca J. Peak Oxygen Uptake During the Six-minute Walk Test in Diffuse Interstitial Lung Disease and Pulmonary Hypertension. ARCH BRONCONEUMOL, 2010. 46:122-128. I.F.:2,17. 3 Xaubet A, Fu WJ, Li M, SerranoMollar A, Ancochea J, Molina-Molina M, Rodriguez-Becerra E, Morell F, Rodriguez-Arias JM, Pereda J, Casanova A, Molins L, Picado C. A haplotype of cyclooxygenase-2 gene is associated with idiopathic pulmonary fibrosis. SARCOIDOSIS VASC DIF, 2010. 27:121-130. I.F.:1,06. RESEARCH GROUP Nasosinusal Inflammatory and Olfactory Research Group (INGENIO) Group Leader: Joaquim Mullol (IDIBAPS) In this group we investigate different aspects of inflammatory nasosinusal disorders (allergic and non-allergic rhinitis, chronic rhinosinusitis, nasal polyposis): • We explore the physiopathological mechanisms of nasosinusal mucosal hypersecretion and the regulation of mucins and MUC genes. • We analyze the physiopathological and clinical association of nasosinusal disorders with asthma, atopy, NSAID intolerance and bronchiectasia, and their impact upon patient quality of life. • We evaluate olfactory alterations and their mechanisms of action as diagnostic and severity markers. We have validated a proprietary olfactometric test (BAST24), and have carried out an epidemiological study (OLFACAT) on olfactory function in the Catalan population. • We use an eosinophil and epithelial cell culture model for testing and comparing the antiinflammatory action of different drugs employed in situations of respiratory inflammation, such as corticosteroids, antihistamines and antileukotrienes. 4 Munoz-Cano R, Salvador R, Valero A, Berenguer J, Alobid I, Bartra J, Guilemany JM, Mullol J, Picado C. Accuracy of acoustic rhinometry versus computed tomography in the evaluation of nasal cavity in patients with nasal polyposis. RHINOLOGY, 2010. 48:224-227. I.F.:2,18. 5 Palacin A, Bartra J, Munoz R, Diaz-Perales A, Valero A, Salcedo G. Anaphylaxis to Wheat Flour-Derived Foodstuffs and the Lipid Transfer Protein Syndrome: A Potential Role of Wheat Lipid Transfer Protein Tri a 14. INT ARCH ALLERGY IMM, 2010. 152:178-183. I.F.:2,54. 6 Romero ADB, Nora JE, Topczewski TE, DeAguiar PHP, Alobid I, Rodriguez EF. Cerebrospinal fluid 135 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Clinical and Experimental Respiratory Immunoallergy (IRCE) fistula after endoscopic transsphenoidal surgery Experience in a spanish center. ARQ NEURO-PSIQUIAT, 2010. 68:414-417. I.F.:0,55. 7 Sastre J, Olaguibel J, Vega JM, DelPozo V, Picado C, Vina AL. Cut-off points for defining asthma control in three versions of the Asthma Control Questionnaire. J ASTHMA, 2010. 47:865-870. I.F.:1,37. 8 Valero A, Ferrer M, Baro E, Sastre J, Navarro AM, Marti-Guadano E, Davila I, DelCuvillo A, Colas C, Antepara I, Alonso J, Mola O, Izquierdo I, Mullol J. Discrimination between moderate and severe disease may be used in patients with either treated or untreated allergic rhinitis. ALLERGY, 2010. 65:1609-1613. I.F.:6,38. 9 Bousquet J, Bachert C, Canonica GW, Mullol J, VanCauwenberge P, Jensen CB, Fokkens WJ, Ring J, Keith P, Gopalan G, Lorber R, Zuberbier T. Efficacy of Desloratadine in Persistent Allergic Rhinitis - A GA(2) LEN Study. INT ARCH ALLERGY IMM, 2010. 153:395-402. I.F.:2,54. 10 Ebbens FA, Toppila-Salmi SK, Renkonen JA, Renkonen RLO, Mullol J, VanDrunen CM, Fokkens WJ. Endothelial L-selectin ligand expression in nasal polyps. ALLERGY, 2010. 65:95-102. I.F.:6,38. 11 Serrano C, Torrego A, Loosli A, Valero A, Picado C. Hypersensitivity Pneumonitis after Exposure to Candida spp. ARCH BRONCONEUMOL, 2010. 46:275-277. I.F.:2,17. 12 Zoccatelli G, Pokoj S, Foetisch K, Bartra J, Valero A, SanMiguelMoncin MD, Vieths S, Scheurer S. Identification and characterization of the major allergen of green bean (Phaseolus vulgaris) as a non-specific lipid transfer protein (Pha v 3). MOL 136 IMMUNOL, 2010. 47:1561-1568. I.F.:3,20. 13 Sastre J, Olaguibel JM, Vina AL, Vega JM, DelPozo V, Picado C. Increased Body Mass Index Does Not Lead to a Worsening of Asthma Control in a Large Adult Asthmatic Population in Spain. J INVEST ALLERG CLIN, 2010. 20:551-555. I.F.:1,19. 14 Bellido-Casado J, Plaza V, Perpina M, Picado C, Bardagi S, Martinez-Bru C, Torrejon M. Inflammatory Response of Rapid Onset Asthma Exacerbation. ARCH BRONCONEUMOL, 2010. 46:587-593. I.F.:2,17. 15 Mullol J, Callejas FB, Mendez-Arancibia E, Fuentes M, Alobid I, Martinez-Anton A, Valero A, Picado C, Roca-Ferrer J. Montelukast reduces eosinophilic inflammation by inhibiting both epithelial cell cytokine secretion (GM-CSF, IL-6, IL-8) and eosinophil survival. J BIOL REG HOMEOS AG, 2010. 24:403-411. I.F.:3,17. 16 Castillo JA, Molina J, Valero A, Mullol J. Prevalence and characteristics of rhinitis in asthmatic patients attending primary care in Spain (the RINOASMAIR study). RHINOLOGY, 2010. 48:35-40. I.F.:2,18. 17 Ibanez MD, Navarro A, Sanchez MC, Rondon C, Montoro J, Mateu V, Lluch-Bernal M, Fernandez-Parra B, Dordal MT, Davila I, Conde J, Anton E, Colas C, Valero A. Rhinitis and its Association With Asthma in Patients Under 14 Years of Age Treated in Allergy Departments in Spain. J INVEST ALLERG CLIN, 2010. 20:402-406. I.F.:1,19. 19 Iniguez-Cuadra R, Alobid I, BoresDomenech A, Menendez-Colino LM, Caballero-Borrego M, Bernal-Sprekelsen M. Type III Tympanoplasty With Titanium Total Ossicular Replacement Prosthesis: Anatomic and Functional Results. OTOL NEUROTOL, 2010. 31:409-414. I.F.:1,44. 20 Bousquet PJ, Bachert C, Canonica GW, Casale TB, Mullol J, Klossek JM, Zuberbier T, Bousquet J. Uncontrolled allergic rhinitis during treatment and its impact on quality of life: A cluster randomized trial. J ALLERGY CLIN IMMUN, 2010. 126:666-668. I.F.:9,17. 21 DelCuvillo A, Montoro J, Bartra J, Valero A, Ferrer M, Jauregui I, Davila I, Sastre J, Mullol J. Validation of ARIA duration and severity classifications in Spanish allergic rhinitis patients - The ADRIAL cohort Study. RHINOLOGY, 2010. 48:201-205. I.F.:2,18. Reviews I.F.: 7,47 1 Pujols L, Mullol J, Picado C. Importance of glucocorticoid receptors in upper and lower airways. FRONT BIOSCI, 2010. 15:789-800. I.F.:3,74. 2 Pujols L, Mullol J, Picado C. mportance of glucocorticoid receptors in upper and lower airways. FRONT BIOSCI, 2010. 15:789-800. I.F.:3,74. Editorials I.F.: 14,94 18 Marino-Sanchez FS, Alobid I, 1 Sanchez-Lopez J, Munoz-Cano R, Centellas S, Alberca C, Guilemany JM, Canals JM, DeHaro J, Mullol J. Smell training increases cognitive smell skills of wine tasters compared to the general healthy population. The WINECAT Study. RHINOLOGY, 2010. 48:273-276. I.F.:2,18. Bartra J, Valero A, Picado C. Desensitization to clopidogrel: a growing need. ALLERGY, 2010. 65:279-280. I.F.:6,38. 2 Alobid I. Nasal polyposis, sense of smell, and surgery. RHINOLOGY, 2010. 48:377-378. I.F.:2,18. AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Clinical and Experimental Respiratory Immunoallergy (IRCE) 3 Munoz-Cano R, Sanchez-Lopez J, Bartra J, Valero A. Yellow fever vaccine and egg allergy: really a problem?. ALLERGY, 2010. 65:533-534. I.F.:6,38. Clinical Guidelines I.F.: 15,55 1 Bousquet J, Schunemann HJ, Zuberbier T, Bachert C, Baena-Cagnani CE, et al. Development and implementation of guidelines in allergic rhinitis - an ARIAGA2LEN paper. ALLERGY, 2010. 65:12121221. I.F.:6,38. 2 Brozek JL, Bousquet J, Baena-Cag- Mullol J. Estudio del papel de la inflamación neurógenano alérgica en la expresión de mucinas y el proceso de remodelado de la mucosa respiratoria nasosinusal. Sponsored by: Ministerio Sanidad y Consumo, PI080188. Amount: 140.844,00 euros. Duration: 01/01/2009-30/12/2011. Picado C. Estudio de la regulación epigenética del gen de la COX-2 en el asama con intolerancia a los antiinflamatorios no esteroideos. Sponsored by: Ministerio Sanidad y Consumo, PI080249. Amount: 139.150,00 euros. Duration: 01/01/2009-30/12/2011. nani CE, Bonini S, Canonica GW, Casale TB, VanWijk RG, Ohta K, Zuberbier T, Schunemann HJ. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 Revision. J ALLERGY CLIN IMMUN, 2010. 126:466-476. I.F.:9,17. Xaubet A. Implicación del sistema de la angiotensina en la etiopatogenia de la fibrosis pulmonar idiopática. Sponsored by: Ministerio Sanidad y Consumo, PI0900672. Amount: 209.171,49 euros. Duration: 01/01/201030/12/2012. Grants for research in progress Valero AL. Efecto clínico e inflamatorio nasal tras la aplicación frl factor de agregación plaquetaria (PAF). Sponsored by: Ministerio Sanidad y Consumo, PI0901202. Amount: 55.660,00 euros. Duration: 01/01/2010-30/12/2012. Mullol J. Global Allergy and Asthma European Network. Sponsored by: Universiteit Gent Directie Financiën, FOOD-CT-2004-506378. Amount: 40.000,00 euros. Duration: 01/08/200831/01/2010. Valero AL. Inhibición del efecto de la administración nasal del Factor de Activación Plaquetaria (PAF) tras la administración de Rupatadina (NARUPAF). Sponsored by: Beca Grupo Uriach Pharma , DC/03/RUP/I/08. Amount: 119.231,00 euros. Duration: 01/09/200831/03/2010. Pujols L. Papel de la prostaglandina E2 en la determinación de la sensibilidad de los glucocorticoides en enfermedades respiratorias de origen inflamatorio. Sponsored by: Ministerio Sanidad y Consumo, PI080419. Amount: 91.718,00 euros. Duration: 01/01/2009-30/12/2011. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI08/0419. Amount: 91.718,00 euros. Duration: 01/01/200930/12/2011. Xaubet A. Trasplante de células alveolares tipoII para el tratamiento de la fibrosis pulmonar idiopática. Sponsored by: Ministerio de Sanidad y Política Social, CP09/00233. Amount: 240.000,00 euros. Duration: 01/01/2010-31/12/2012. Thesis Mullol J. Asociación de bronquiectasias pulmonares y patología nasosinusal. Estudio de los aspectos epidemiológicos etiológicos, de diagnóstico y tratamiento. PhD student: Jose Maria Guilemany Toste. Valero AL. Efecto clínico e inflamatorio nasal tras la aplicación del factor de agregación plaquetaria (PAF). Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1202. Amount: 55.660,00 euros. Duration: 01/01/2010-31/12/2012. Xaubet A. Implicación del sistema de la angiotensina en la etiopatogenia de la fibrosis pulmonar idiopática. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/0672. Amount: 209.172,71 euros. Duration: 01/01/2010-31/12/2012. Pujols L. Papel de la prostsglandina E2 en la determinación de la sensibilidad a los glucocorticoides en enfermedades respiratorias de origen inflamatorio. 137 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Inflammation and repair in respiratory illnesses Strategic Objectives GROUP Members TEAM LEADER Alvar Agustí (Hospital Clínic) Tel.: 93 227 54 00 (1701) Fax: 93 227 98 68 E-mail: alvar.agusti@clinic.ub.es Idibaps members: Eugeni Ballester (Hospital Clínic) Collaborators: Dra. Patricia Sobradillo (CIBERes) Dra. Rosa Faner (CIBERes) Sra. Gemma Sunyer (CIBERes) Nuria Gonzalez (CIBERes) (A) Healthy lung, (B) Unstructured lung of a COPD patient. 138 The general objective of the group is to investigate the inflammatory and tissue repair mechanisms in chronic obstructive pulmonary disease (COPD), their clinicalfunctional correlation, the diagnostic, prognostic and therapeutic implications of such knowledge, and particularly their relevance in relation to pulmonary oncogenesis. COPD is presently the fourth most common cause of death in the world, and will rank third within a decade. Lung cancer is the most common malignant tumor in males (and soon also will be the most common malignancy in females), and involves one of the poorest prognosis with the currently available treatment options. Main Lines of Research 1. Mechanisms of autoimmunity and autoinflammation that may contribute to the pathogenesis of acute outbreaks of the disease (in collaboration with the group headed by Dr. J. Yagüe, of the Department of Immunology of the Clinic Hospital). 2. Mechanisms of abnormal katabasis (resolution of the inflammation) that perpetuate the inflammatory response even after smoking cessation (a necessary yet insufficient treatment measure) (in collaboration with Dr. J. Clària, of the Clinic Hospital Biomedical Diagnostic Center). 3. Mechanisms of oncogenesis in COPD (in collaboration with investigators of the Fundació Caubet-Cimera in Mallorca and the CIBER of respiratory diseases (CIBERES): SINECAN project). 4. Application of the methodology of systems biology (“omic” platforms and bioinformatics) to COPT, with a view to integrating the cellular and molecular alterations with clinical data. This line is developed in the setting of the CIBER of respiratory diseases (www.ciberes. org), involving a strategic alliance with the Institute for Systems Biology (Seattle, USA), Harvard University (USA) and the pharmaceutical industry with an interest in COPD. PUBLICATIONS Originals I.F.: 99,55 1 Soto-Cardenas MJ, Perez-DeLis M, Bove A, Navarro C, BritoZeron P, Diaz-Lagares C, Gandia M, Akasbi M, Siso A, Ballester E, Torres A, Ramos-Casals M. Bronchiectasis in primary Sjogren’s syndrome: prevalence and clinical significance. CLIN EXP RHEUMATOL, 2010. 28:647-653. I.F.:2,40. 2 Soler N, Ballester E, Martin A, Gobartt E, Miravitlles M, Torres A. Changes in management of chronic obstructive pulmonary disease (COPD) in primary care: EMMEPOC study. RESP MED, 2010. 104:67-75. I.F.:2,33. 3 Duran-Cantolla J, Aizpuru F, Montserrat JM, Ballester E, Teran-Santos J, Aguirregomoscorta JI, Gonzalez M, Lloberes P, Masa JF, DeLaPena M, Carrizo S, Mayos M, Barbe F. Continuous positive airway pressure as treatment for systemic hypertension in people with obstructive sleep apnoea: randomised controlled trial. BRIT MED J, 2010. 341:-. I.F.:13,66. 4 Sala E, Villena C, Balaguer C, Rios A, Fernandez-Palomeque C, Cosio BG, Garcia J, Noguera A, Agusti A. Abnormal Levels of Circulating Endothelial Progenitor Cells During Exacerbations of COPD. LUNG, 2010. 188:331338. I.F.:1,58. 5 Sorheim IC, Bakke P, Gulsvik A, Pillai SC, Johannessen A, Gaarder PI, Campbell EJ, Agusti A, Calverley PMA, Donner CF, Make BJ, Rennard SI, Vestbo J, Wouters EFM, Pare PD, Levy RD, AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Inflammation and repair in respiratory illnesses Coxson HO, Lomas DA, Hersh CP, Silverman EK. alpha(1)-Antitrypsin Protease Inhibitor MZ Heterozygosity Is Associated With Airflow Obstruction in Two Large Cohorts. CHEST, 2010. 138:1125-1132. I.F.:6,36. 6 Agusti A, Calverley PMA, Celli B, Coxson HO, Edwards LD, Lomas DA, Macnee W, Miller BE, Rennard S, Silverman EK, Tal-Singer R, Wouters E, Yates JC, Vestbo J. Characterisation of COPD heterogeneity in the ECLIPSE cohort. RESP RES, 2010. 11:-. I.F.:3,13. 7 Pozo-Rodriguez F, Alvarez CJ, Castro-Acosta A, Moreno CM, Capelastegui A, Esteban C, Carcereny CH, Lopez-Campos JL, Alonso JLI, Quilez AL, Agusti A. Clinical Audit of Patients Admitted to Hospital in Spain due to Exacerbation of COPD (AUDIPOC Study): Method and Organisation. ARCH BRONCONEUMOL, 2010. 46:349-357. I.F.:2,17. 8 Soriano JB, Rigo F, Guerrero D, Yanez A, Forteza JE, Frontera G, Togores B, Agusti A. High Prevalence of Undiagnosed Airflow Limitation in Patients With Cardiovascular Disease. CHEST, 2010. 137:333-340. I.F.:6,36. 9 Gomez-Caro A, Garcia S, Reguart N, Arguis P, Sanchez M, Gimferrer JM, Marrades R, Lomena F. Incidence of occult mediastinal node involvement in cNO non-small-cell lung cancer patients after negative uptake of positron emission tomography/computer tomography scan. EUR J CARDIO-THORAC, 2010. 37:1168-1174. I.F.:2,40. 10 Sala E, Balaguer C, Villena C, Rios A, Noguera A, Nunez B, Agusti A. Low Erythropoietin Plasma Levels during Exacerbations of COPD. RESPIRATION, 2010. 80:190-197. I.F.:1,94. 11 Renom F, Yanez A, Garau M, Rubi M, Centeno MJ, Gorriz MT, Medinas M, Ramis F, Soriano JB, Agusti A. Prognosis of COPD patients requiring frequent hospitalization: Role of airway infection. RESP MED, 2010. 104:840-848. I.F.:2,33. 12 Hurst JR, Vestbo J, Anzueto A, Locantore N, Mullerova H, Tal-Singer R, Miller B, Lomas DA, Agusti A, Macnee W, Calverley P, Rennard S, Wouters EFM, Wedzicha JA. Susceptibility to Exacerbation in Chronic Obstructive Pulmonary Disease.. NEW ENGL J MED, 2010. 363:11281138. I.F.:47,05. 13 Barcelo A, Pierola J, LopezEscribano H, DeLaPena M, Soriano JB, Alonso-Fernandez A, Ladaria A, Agusti A. Telomere shortening in sleep apnea syndrome. RESP MED, 2010. 104:1225-1229. I.F.:2,33. 14 Marin A, Monso E, Garcia-Nunez M, Sauleda J, Noguera A, Pons J, Agusti A, Morera J. Variability and effects of bronchial colonisation In patients with moderate COPD. EUR RESPIR J, 2010. 35:295-302. I.F.:5,53. nary Disease Phenotypes The Future of COPD. AM J RESP CRIT CARE, 2010. 182:598-604. I.F.:10,69. 2 Cosio BG, Agusti A. Update in Chronic Obstructive Pulmonary Disease 2009. AM J RESP CRIT CARE, 2010. 181:655-660. I.F.:10,69. 3 Agusti A, Barnes PJ. What the Journal Would Like to Publish on Chronic Obstructive Pulmonary Disease. AM J RESP CRIT CARE, 2010. 182:1-2. I.F.:10,69. Multicentrics I.F.: 47,05 1 Sciurba FC, Ernst A, Herth FJF, Strange C, Criner GJ, Marquette CH, Kovitz KL, Chiacchierini RP, Goldin J, Mclennan G. A Randomized Study of Endobronchial Valves for Advanced Emphysema. NEW ENGL J MED, 2010. 363:1233-1244. I.F.:47,05. Grants for research in progress Agusti A. Cohorte Española de Pacientes con EPOC Avanzada (CEPA): Inflamosoma, comorbilidad y curso clínico. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/0629. Amount: 145.200,00 euros. Duration: 01/01/2010-31/12/2012. Editorials I.F.: 32,07 1 Han MK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, Fabbri LM, Goldin JG, Jones PW, Macnee W, Make BJ, Rabe KF, Rennard SI, Sciurba FC, Silverman EK, Vestbo J, Washko GR, Wouters EFM, Martinez FJ. Chronic Obstructive Pulmo- 139 AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Team involved in: Urological genetics and tumours Strategic Objectives GROUP Members TEAM LEADER Antonio Alcaraz (Hospital Clínic) Tel.: 93 227 55 45 Fax: 93 227 55 45 E-mail: aalcaraz@clinic.ub.es Idibaps members: Maria José Ribal (Hospital Clínic) Mireia Musquera (Hospital Clínic) Postdoctoral fellows: Lourdes Mengual (Fundació Clínic) Research Fellows: Cristina Gázquez (IDIBAPS) Technicians: Mercedes Ingelmo-Torres (IDIBAPS) Administrative Staff: Maite Dalet (Fundació Clínic) Collaborators: Laura Izquierdo (Hospital Clínic) 140 At present, the research group in urological oncology is conducting two main lines of research, based on the two most frequent urological tumors: urothelial and prostate cancer. The objectives are summarized below: 1. Identification of molecular markers in the urine of bladder cancer patients, for the non-invasive diagnosis of the disease. 2. Identification of molecular markers for the noninvasive diagnosis of prostate cancer. 3. Identification of molecular markers for the prognosis of muscle invading bladder cancer. 4. Study of the prognostic factors of upper urinary tract tumors. Main Lines of Research 1. Microchips for the diagnosis and prognosis of bladder tumors. 2. Identification of micro-RNA for the noninvasive diagnosis of bladder tumors. 3. Determination of disseminated tumor disease in patients with muscle invading bladder cancer, based on evaluation of the genic expression of bladder-specific markers in lymph nodes and peripheral blood. 4. Determination of the genic expression profile associated with treatment response to neoadjuvant chemotherapy with cisplatin and gemcitabine in patients with muscle invading bladder cancer. 5. Study of the prognostic factors of upper urinary tract tumors based on immunohistochemistry and quantitative PCR. 6. Microchips for the diagnosis and prognosis of prostate tumors. 7. Identification of micro-RNA for the noninvasive diagnosis of prostate tumors. PUBLICATIONS Originals I.F.: 42,53 1 Oppenheimer F, Revuelta I, Serra N, Lozano M, Gutierrez-Dalmau A, Esforzado N, Cofan F, Ricart MJ, Torregrosa JV, Crespo M, Paredes D, Martorell J, Alcaraz A, Campistol JM. ABO incompatible living donor kidney transplantation: a dream come true. Experience of Hospital Clinic of Barcelona. NEFROLOGIA, 2010. 30:5463. I.F.:0,53. 2 Musquera M, Peri LL, AlvarezVijande R, Oppenheimer F, Gil-Vernet JM, Alcaraz A. Orthotopic Kidney Transplantation: An Alternative Surgical Technique in Selected Patients. EUR UROL, 2010. 58:927-933. I.F.:7,67. 3 Izquierdo L, Peri L, Piqueras M, Revuelta I, Alvarez-Vijande R, Musquera M, Oppenheimer F, Alcaraz A. Third and Fourth Kidney Transplant: Still a Reasonable Option. TRANSPL P, 2010. 42:2498-2502. I.F.:0,99. 4 Izquierdo L, Peri L, Alvarez-Vijande R, Alcaraz A. Audit of an Initial 100 Cases of Laparoscopic Live Donor Nephrectomy. TRANSPL P, 2010. 42:3437-3439. I.F.:0,99. 5 Alcaraz A, Peri L, Molina A, Goicoechea I, Garcia E, Izquierdo L, Ribal MJ. Feasibility of Transvaginal NOTES-Assisted Laparoscopic Nephrectomy. EUR UROL, 2010. 57:233-237. I.F.:7,67. 6 Mengual L, Burset M, Ribal MJ, Ars E, Marin-Aguilera M, Fernandez M, Ingelmo-Torres M, Villavicencio H, Alcaraz A. Gene Expression Signature in Urine for Diagnosing and Assessing Aggressiveness of Bladder Urothelial Carcinoma. CLIN CANCER RES, 2010. 16:2624-2633. I.F.:6,75. AREA 2 Respiratory, cardiovascular, renal pathobiology and bioengineering Urological genetics and tumours 7 14 Fourcade RO, Benedict A, 8 Black LK, Stokes ME, Alcaraz A, Castro R. Treatment costs of prostate cancer in the first year after diagnosis: a short-term cost of illness study for France, Germany, Italy, Spain and the UK. BJU INT, 2010. 105:49-56. I.F.:2,87. Izquierdo L, Truan D, Mengual L, Mallofre C, Alcaraz A. HER-2/AKT Expression in Upper Urinary Tract Urothelial Carcinoma: Prognostic Implications. ANTICANCER RES, 2010. 30:2439-2445. I.F.:1,43. Garcia-Cruz E, Vera-Rivera M, Molina JMC, Mallafre-Sala JM, Alcaraz A. Laparoscopic placement of peritoneal dialysis catheter: description and results of a two-port technique. NEFROLOGIA, 2010. 30:354-359. I.F.:0,53. 9 Izquierdo L, Mengual L, Gazquez C, Ingelmo-Torres M, Alcaraz A. Molecular characterization of upper urinary tract tumours. BJU INT, 2010. 106:868-872. I.F.:2,87. 10 Siddiqui K, Chopra R, Vedula S, Sugar L, Haider M, Boyes A, Musquera M, Bronskill M, Klotz L. MRI-guided Transurethral Ultrasound Therapy of the Prostate Gland Using Real-time Thermal Mapping: Initial Studies. UROLOGY, 2010. 76:15061511. I.F.:2,37. 11 Sebastia C, Peri L, Salvador R, Bunesch L, Revuelta I, Alcaraz A, Nicolau C. Multidetector CT of Living Renal Donors: Lessons Learned from Surgeons. RADIOGRAPHICS, 2010. 30:1875-1890. I.F.:2,75. 12 Alcover J, Filella X, Luque P, Molina R, Izquierdo L, Auge JM, Alcaraz A. Prognostic Value of IL-6 in Localized Prostatic Cancer. ANTICANCER RES, 2010. 30:4369-4372. I.F.:1,43. 13 Hou M, Venier N, Sugar L, Musquera M, Pollak M, Kiss A, Fleshner N, Klotz L, Venkateswaran V. Protective effect of metformin in CD1 mice placed on a high carbohydrate-high fat diet. BIOCHEM BIOPH RES CO, 2010. 397:537-542. I.F.:2,55. 15 Casas F, Borras JM, Ferrer F, Guanyabens N, Gutierrez R, Leon C, Lopez J, Mellado B, Morote J, Puig J, Ribal J, Serra A, Valls V, Zapatero A. Evidence-based consensus recommendations to improve the quality of life in prostate cancer treatment. CLIN TRANSL ONCOL, 2010. 12(5):346355. I.F.:1,15. Alcaraz A. Determinación de la disem inación linfática del carcinoma urotelial de vejiga mediante marcadores moleculares y utilización de estos para pronosticar la evolución clínica de la enfermedad. Sponsored by: Fondo de Investigaciones Sanitarias (FIS), PI070040. Amount: 61.468,00 euros. Duration: 01/01/200831/12/2010. Thesis Alcaraz A. Factores pronóstico moleculares en el carcinoma urotelial de tracto urinario superior. PhD student: Laura Izquierdo Reyes. Reviews I.F.: 7,67 1 Greco F, Hoda MR, Alcaraz A, Bachmann A, Hakenberg OW, Fornara P. Laparoscopic Living-Donor Nephrectomy: Analysis of the Existing Literature. EUR UROL, 2010. 58:498-509. I.F.:7,67. Editorials I.F.: 7,67 1 Alcaraz A. Nephron-Sparing Surgery: Some Considerations Regarding an Underused Standard of Care. EUR UROL, 2010. 58:346-348. I.F.:7,67. Grants for research in progress Alcaraz A. Estudio de validación prospectivo de método no invasivo para el diagnóstico del cáncer de próstata. Sponsored by: Beca “Pedro Cifuentes Díaz”, Fundación de Investigación en Urología (FIU), 0000. Amount: 35.000,00 euros. Duration: 01/01/2010-31/12/2012. 141 3 3 Liver, digestive system AND metabolism Gynecological endocrinology and human reproduction 144 Fetal and perinatal medicine 148 Metabolic regulation and molecular pathology 153 Viral hepatitis in the immune competent host and in liver transplant patients 154 Physiopathology and treatment of ascites and altered renal function in liver cirrhosis 157 Hepatic oncology 161 Liver hemodynamics and portal hypertension. Digestive bleeding secondary to ruptured esophageal varicose veins 164 Inflammatory bowel disease (IBD) 169 Cholestasis and bone pathology 172 Mitochondrial regulation of cell death and steatohepatitis 175 Liver transplantation and graft viability 178 Gastrointestinal and pancreatic oncology 182 Hereditary metabolic diseases 186 Genomic Programming of Beta Cells and Diabetes 189 Diabetes: metabolic and molecular networks 191 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM Gynecological endocrinology and human reproduction Group Members TEAM LEADER Juan Balasch (Hospital Clínic) Tel.: 93 227 54 36 Fax: 93 227 93 25 E-mail: jbalasch@ub.edu IDIBAPS Members: Francisco Carmona (Hospital Clínic) Camil Castelo-Branco (Hospital Clínic) Montserrat Creus (Hospital Clínic) Dolors Manau Trullás (Fundació Clínic) Jaume Ordi (Hospital Clínic) Bienvenido Puerto (Hospital Clínic) Francisco Fábregues (Hospital Clínic) Jaume Pahisa (Hospital Clínic) Aureli Torné (Hospital Clínic) Strategic Objectives Main Lines of Research The global aim of this research group for the coming years is to advance in the knowledge of different aspects relating to the physiopathology of human reproduction: from endocrinological considerations to the most important benign and malignant pathological processes of the female reproductive system, as well as the investigation and treatment of human reproduction failure. 1. Reproductive failure markers. Analysis of the possible role of new markers of hemostasis alterations as a new pathogenic mechanism of thrombotic disease in early and advanced pregnancy, in patients with or without antiphospholipid syndrome. Study is also made of the usefulness of immunohistochemical and quantitative and qualitative proteomic parameters in the human endometrium as markers of endometrial receptiveness. In-depth research of the pathogenic mechanisms involved in the block of pre-implantation embryonic development in vitro. 2. Ovarian dysfunction and stimulation/hyperstimulation. Investigation of the possibilities of ultrasound, hormonal, endocrinemetabolic and genetic markers in relation to the prediction of ovarian response. Study of the role of LH and the androgens as ovarian sensitizing factors in relation to ulterior stimulation with FSH. Investigation of the possible role of the ovarian follicular cells (granulosum, macrophages) in More specifically, the main objectives of our research group are to advance in the existing lines of work, with the purpose of: 1. Determining the most relevant mechanisms in the pathogenesis of reproductive failure (sterility, repeated miscarriages, repeated implant failure after in vitro fertilization) and of the principal female reproductive disease processes (endometriosis, uterine myoma, genital cancer). 2. Optimizing and innovating as far as possible the preventive or therapeutic potential in the aforementioned situations. Research Fellows: Elena Suárez Cisneros (IDIBAPS) Collaborators: Gemma Casals (Hospital Clínic) Roser Casamitjana (Hospital Clínic) Salvadora Cívico (Hospital Clínic) Marta Guimerà (Hospital Clínic) José Luís Ballescá (Hospital Clínic) Mª Angels Martínez-Zamora (Hospital Clínic) Joana Peñarrubia Alonso (Funació Clínic) Radical cervix resection piece obtained via laparoscopic surgery from a young patient with invasive cervical cancer, but with a wish to preserve fertility. 144 AREA 3 Liver, digestive system and metabolism Gynecological endocrinology and human reproduction the pathogenesis of ovarian hyperstimulation syndrome, with the exploration of new ovarian stimulation or endometrial preparation protocols allowing improved results in assisted reproduction techniques. 3. Optimization of the surgical management of diseases of the reproductive apparatus. Designed to analyze the role of the surgical variables allowing improvement of the results and reduction of the morbidity in the surgical treatment of benign and malignant disorders of the female reproductive apparatus. This also implies defining the prognostic value of HPV (human papillomavirus) detection and viral typing as prognostic markers of the neoplastic evolution of precancerous lesions of the cervix. PUBLICATIONS ORIGINALS I.F.: 89,86 1 Martinez-Zamora MA, Tassies D, Carmona F, Espinosa G, Cerverac R, Reverter JC, Balasch J. Clot lysis time and thrombin activatable fibrinolysis inhibitor in severe preeclampsia with or without associated antiphospholipid antibodies. J REPROD IMMUNOL, 2010. 86:133140. I.F.:2,52. 2 Bennasar M, Martinez JM, Gomez O, Bartrons J, Olivella A, Puerto B, Gratacos E. Accuracy of four-dimensional spatiotemporal image correlation echocardiography in the prenatal diagnosis of congenital heart defects. ULTRASOUND OBST GYN, 2010. 36:458-464. I.F.:3,15. rience. INT J GYNECOL CANCER, 2010. 20:173-178. I.F.:2,18. 7 Bergeron C, Ordi J, Schmidt D, Trunk MJ, Keller T, Ridder R. Conjunctive p16(INK4a) Testing Significantly Increases Accuracy in Diagnosing HighGrade Cervical Intraepithelial Neoplasia. AM J CLIN PATHOL, 2010. 133:395406. I.F.:2,47. 8 Reina MF, Ciaravino H, Llovera N, Castelo-Branco C. Contraception knowledge and sexual behaviour in secondary school students. GYNECOL ENDOCRINOL, 2010. 26:479-483. I.F.:1,36. 9 Cruz-Martinez R, Moreno-Alvarez Pahisa J, Martinez-Roman S, Caparros X, Vilalta A, Rull R, Pons F. Added Value of Intraoperative Real-Time Imaging in Searches for Difficult-to-Locate Sentinel Nodes. J NUCL MED, 2010. 51:12191225. I.F.:6,42. O, Hernandez-Andrade E, Castanon M, Done E, Martinez JM, Puerto B, Deprest J, Gratacos E. Contribution of intrapulmonary artery Doppler to improve prediction of survival in fetuses with congenital diaphragmatic hernia treated with fetal endoscopic tracheal occlusion. ULTRASOUND OBST GYN, 2010. 35:572-577. I.F.:3,15. 4 Castelo-Branco C, Steinvarcel F, 10 Penarrubia J, Peralta S, Fabregues Osorio A, Ros C, Balasch J. Atherogenic metabolic profile in PCOS patients: role of obesity and hyperandrogenism. GYNECOL ENDOCRINOL, 2010. 26:736742. I.F.:1,36. F, Carmona F, Casamitjana R, Balasch J. Day-5 inhibin B serum concentrations and antral follicle count as predictors of ovarian response and live birth in assisted reproduction cycles stimulated with gonadotropin after pituitary suppression. FERTIL STERIL, 2010. 94:2590-2595. I.F.:3,97. 3 Vidal-Sicart S, Paredes P, Zanon G, 5 DelPino M, Torne A, Alonso I, Mula R, Masoller N, Fuste V, Ordi J. Colposcopy Prediction of Progression in Human Papillomavirus Infections With Minor Cervical Lesions. OBSTET GYNECOL, 2010. 116:1324-1331. I.F.:4,36. 6 Pahisa J, Martinez-Roman S, Torne A, Fuste P, Alonso I, Lejarcegui JA, Balasch J. Comparative Study of Laparoscopically Assisted Radical Vaginal Hysterectomy and Open WertheimMeigs in Patients With Early-Stage Cervical Cancer Eleven Years of Expe- 11 Castelo-Branco C, Palacios S, Ferrer-Barriendos J, Alberich X. Do Patients Lie? An Open Interview vs. a Blind Questionnaire on Sexuality. J SEX MED, 2010. 7:873-880. I.F.:4,88. 12 Valduvieco I, Rovirosa A, Colomo L, DeSanJuan A, Pahisa J, Biete A. Endometrial stromal sarcoma. Is there a place for radiotherapy?. CLIN TRANSL ONCOL, 2010. 12:226-230. I.F.:1,15. 145 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM Gynecological endocrinology and human reproduction 13 Molina R, Auge JM, Escudero JM, Filella X, Zanon G, Pahisa J, Farrus B, Munoz M, Velasco M. Evaluation of tumor markers (HER-2/neu oncoprotein, CEA, and CA 15.3) in patients with locoregional breast cancer: prognostic value. TUMOR BIOL, 2010. 31:171-180. I.F.:1,94. 14 Borras A, Gomez O, Sanz M, Martinez JM, Puerto B. Feticide Followed by Mifepristone-Misoprostol Regimen for Midtrimester Termination of Pregnancy in Two Cases of Complete Placenta Previa. FETAL DIAGN THER, 2010. 28:114-116. I.F.:0,91. 15 DeSanjose S, Quint WGV, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, Tous S, Felix A, Bravo LE, Shin HR, Vallejos CS, DeRuiz PA, Lima MA, Guimera N, Clavero O, Alejo M, Llombart-Bosch A, Cheng-Yang C, Tatti SA, Kasamatsu E, Iljazovic E, Odida M, Prado R, Seoud M, Grce M, Usubutun A, Jain A, Suarez GAH, Lombardi LE, Banjo A, Menendez C, Domingo EJ, Velasco J, Nessa A, Chichareon SCB, Qiao YL, Lerma E, Garland SM, Sasagawa T, Ferrera A, Hammouda D, Mariani L, Pelayo A, Steiner I, Oliva E, Meijer CJLM, AlJassar WF, Cruz E, Wright TC, Puras A, Llave CL, Tzardi M, Agorastos T, Garcia-Barriola V, Clavel C, Ordi J, Andujar M, Castellsague X, Sanchez GI, Nowakowski AM, Bornstein J, Munoz N, Bosch FX. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. LANCET ONCOL, 2010. 11:1048-1056. I.F.:14,47. 16 Cruz-Martinez R, Figueras F, Hernandez-Andrade E, Puerto B, Gratacos E. Longitudinal brain perfusion changes in near-term small-forgestational-age fetuses as measured by spectral Doppler indices or by 146 fractional moving blood volume. AM J OBSTET GYNECOL, 2010. 203:-. I.F.:3,28. 17 Casals G, Ordi J, Creus M, Fabregues F, Carmona F, Casamitjana R, Balasch J. Osteopontin and alpha V beta 3 integrin as markers of endometrial receptivity: the effect of different hormone therapies. REPROD BIOMED ONLINE, 2010. 21:349-359. I.F.:2,38. 18 Sanjuan A, Escaramis G, VidalSicart S, Illa M, Zanon G, Pahisa J, Rubi S, Velasco M, Santamaria G, Farrus B, Munoz M, Garcia Y, Fernandez PL, Pons F. Predicting Non-Sentinel Lymph Node Status in Breast Cancer Patients with Sentinel Lymph Node Involvement: Evaluation of Two Scoring Systems. BREAST J, 2010. 16:134140. I.F.:1,61. 19 Sanz-Cortes M, Martinez JM, Bennasar M, Puerto B, Graracos E. Prenatal diagnosis of tuberous sclerosis and analysis using magnetic resonance spectroscopy. ULTRASOUND OBST GYN, 2010. 36:522-524. I.F.:3,15. 20 Fuste V, DelPino M, Perez A, Garcia A, Torne A, Pahisa J, Ordi J. Primary squamous cell carcinoma of the vagina: human papillomavirus detection, p16INK4A overexpression and clinicopathological correlations. HISTOPATHOLOGY, 2010. 57:907916. I.F.:3,86. 21 Molina R, Auge JM, Farrus B, Zanon G, Pahisa J, Munoz M, Torne A, Filella X, Escudero JM, Fernandez P, Velasco M. Prospective Evaluation of Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 15.3 (CA 15.3) in Patients with Primary Locoregional Breast Cancer. CLIN CHEM, 2010. 56:1148-1157. I.F.:6,26. 22 Martinez JM, Gomez O, Bennasar M, Olivella A, Crispi F, Puerto B, Gratacos E. The ‘question mark’ sign as a new ultrasound marker of tetralogy of Fallot in the fetus. ULTRASOUND OBST GYN, 2010. 36:556560. I.F.:3,15. 23 Castelo-Branco C, Coloma JL. The role of intranasal estradiol spray in the management of moderate to severe vasomotor symptoms in menopausal women. GYNECOL ENDOCRINOL, 2010. 26:23-29. I.F.:1,36. 24 Martinez-Zamora MA, Creus M, Tassies D, Bove A, Reverter JC, Carmona F, Balasch J. Thrombin activatable fibrinolysis inhibitor and clot lysis time in women with recurrent miscarriage associated with the antiphospholipid syndrome. FERTIL STERIL, 2010. 94:24372440. I.F.:3,97. 25 Castelo-Branco C, Cortes X, Ferrer M. Treatment persistence and compliance with a combination of calcium and vitamin D. CLIMACTERIC, 2010. 13:578-584. I.F.:2,57. 26 Arjona JE, Serrano JJ, Povedano B, Carrasco S, Castelo-Branco C. Unintended pregnancy after longterm Essure microinserts placement. FERTIL STERIL, 2010. 94:2793-2795. I.F.:3,97. Reviews I.F.: 12,55 1 Cervera R, Balasch J. Autoimmunity and Recurrent Pregnancy Losses. CLIN REV ALLERG IMMU, 2010. 39:148-152. I.F.:2,60. 2 Balasch J. Ageing and infertility: an overview. GYNECOL ENDOCRINOL, 2010. 26:855-860. I.F.:1,36. AREA 3 Liver, digestive system and metabolism Gynecological endocrinology and human reproduction 3 Castelo-Branco C, Cancelo MJ. Comprehensive clinical management of hirsutism. GYNECOL ENDOCRINOL, 2010. 26:484-493. I.F.:1,36. 4 Gameiro CM, Romao F, CasteloBranco C. Menopause and aging Changes in the immune system-A review. MATURITAS, 2010. 67:316-320. I.F.:2,09. 5 Martinez-Maestre MA, GonzalezCejudo C, Machuca G, Torrejon R, Castelo-Branco C. Periodontitis and osteoporosis: a systematic review. CLIMACTERIC, 2010. 13:523-529. I.F.:2,57. 6 Al-Azzawi F, Bitzer J, Brandenburg U, Castelo-Branco C, Graziottin A, Kenemans P, Lachowsky M, Mimoun S, Nappi RE, Palacios S, Schwenkhagen A, Studd J, Wylie K, Zahradnik HP. Therapeutic options for postmenopausal female sexual dysfunction. CLIMACTERIC, 2010. 13:103-120. I.F.:2,57. Editorials I.F.: 0,77 1 Munoz M, Pahisa J, Caparros FX, Vidal-Sicart S. Sentinel lymph node and neoadjuvant therapy in breast cancer. REV ESP MED NUCL, 2010. 29:319-320. I.F.:0,77. Grants for research in progress Balasch J. Caracterización del proteoma del epitelio y del estroma endometriales y expresión proteica diferencial en la ventana de implantación. Sponsored by: Fundación Salud 2000, PI040634. Amount: 0,00 euros. Duration: 01/01/2009-31/12/2011. Balasch J. Grup de Fisiopatologia de la Reproducció Humana. Sponsored by: Generalitat de Catalunya, 2009 SGR 1099. Amount: 0,00 euros. Duration: 01/01/2009-31/12/2013. Ordi J. Patrones de expresión de miRNA en la progresión y la transformación maligna de las lesiones precursoras del cáncer de cérvix uterino. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1084. Amount: 61.710,00 euros. Duration: 01/01/2010-31/12/2012. TORNE, AURELI. Valor clínico de la infección múltiple por virus del papiloma humano (VPH) en pacientes con lesiones premalignas y cáncer de cuello uterino. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1524. Amount: 50.215,00 euros. Duration: 01/01/2010-31/12/2012. Thesis Martinez JM, Puerto B. Aplicación de la ecografía 4D-STIC (Spatio temporal image correlation) en el diagnóstico prenatal de las cardiopatías. PhD student: Maria del mar Bennasar Sans. Balasch J. Efectos de los fármacos empleados para la estimulación ovárica sobre las células foliculares. Implicaciones en el síndrome de hiperestimulación ovárica. Sponsored by: Ministerio Sanidad y Consumo, PI070355. Amount: 47.190,00 euros. Duration: 01/01/200830/12/2010. 147 AREA 3 Team envolved in: LIVER, DIGESTIVE SYSTEM AND METABOLISM CIBER en enfermedades raras (CIBERer) Fetal and perinatal medicine Strategic Objectives Group Members TEAM LEADER Eduard Gratacós (Hospital Clínic) Tel.: 93 227 99 46 Fax: 93 227 56 05 E-mail: gratacos@clinic.ub.es The principal strategic objective is to search for solutions to prenatal diseases, identifying the mechanisms involved in fetal brain and cardiac reprogramming, developing new technologies allowing an early diagnosis, and identifying potential therapeutic targets. Other objectives of the team are the development and consolidation of the existing lines of work in different fields, such as perinatal infections, HIV and neonatal infection, fetal therapy and surgery, screening strategies and prediction of fetal and maternal pathology in large populations, preeclampsia and prematureness. Idibaps members: Antoni Borrell (Hospital Clínic) Francesc Botet (Hospital Clínic) Vicenç Cararach (Hospital Clínic) Xavier Carbonell (Hospital Clínic) Elena Casals (Hospital Clínic) Francesc Figueras (Hospital Clínic) Josep Figueras (Hospital Clínic) Josep Maria Martinez-Crespo (Hospital Clínic) Montserrat Palacio (Hospital Clínic) Postdoctoral fellows: Emilia Ruthy Acosta-Rojas (Fundació Clínic-CIBER-ER) Fátima Crispi (IDIBAPS) Nelly Fabiola Padilla (Fundació Clínic) Magdalena Sanz (IDIBAPS) Research Fellows: Ivan Amat-Roldan (Fundació Clínic) Montse Comas (Hospital Clínic) Anna González (pre-doc IDIBAPS) Alvaro Pérez (IDIBAPS) Dafnis Batallé (CIBER-ER) Jesús Mª Domínguez (CIBER-ER) Violeta Tenorio (Fundació Clínic) Mónica Cruz-Lemini (Fundació Clínic) Patricia Garcia (Fundació Clínic) Stefan Savchev (Fundació Clínic) Technicians: Imma Mercade (Fundació Clínic) Marina Coll (Fundació Clínic) Ariadna Arbat (Fundació Clínic) Nursing Staff: Angela Arranz (Fundació Clínic) Administrative Staff: Maite Aguilera (Fundació Clínic) Estefanía Callado (Fundació Clínic) Pere Lorente (Fundació Clínic) Collaborators: Jordi Bellart (Hospital Clínic) Olga Gómez (Hospital Clínic) Anna Gonce (Hospital Clínic) Xavier Miracle (Hospital Clínic) Mª Dolors Salvía (Hospital Clínic) Iratxe Torre (Fundació Clínic-Sara Borrell) Rogelio Cruz (Fundació Clínic) Elisenda Eixarch (IDIBAPS-Rio Hortega) Joan Junyent (Fundació Clínic) Teresa Cobo (IDIBAPS - Río Hortega) Mar Benassar (Hospital Clínic) Leticia Vinyoles (Fundació Clínic) Alba Camacho (Fundació Clínic) Marta García (Fundació Clínic) Visiting Scientists: R. Bartrons D. Valsky Iosefine Stergitou 148 Main Lines of Research 1. Neurological damage of fetal and perinatal origin. Characterization of the physiopathology and development of methods for the diagnosis and treatment of prenatal brain damage, with preferential use of fetal growth retardation as a model. The group possesses an important interdisciplinary structure for the characterization and prediction of perinatal brain damage, with special attention to the fetal reprogramming mechanisms secondary to chronic hypoxia. The line is structured into major interrelated areas: fetal and neonatal brain imaging (ultrasound, moving blood fraction and MRI- DTI-RMS), neurological damage biomarkers, and follow-up of neurological development over the long term. 2. Cardiac function and cardiovascular programming in the fetus. The aim of this research line is to characterize cardiac function and develop methods for the prediction and treatment of fetal programming in the context of cardiac dysfunction in fetuses and infants. This includes new echocardiographic markers AREA 3 Liver, digestive system and metabolism FETAL AND PERINATAL MEDICINE of fetal myocardial function, biochemical and genomic markers of ischemia and immune/endothelial hyperactivation. 3. Fetal therapy and surgery. As members of the European Eurofoetus group, we study the fetal surgical treatment of complications of monochorial gestation and congenital diaphragmatic herniation, and the tissue engineering repair of fetal membranes. Screening of aneuploidy and maternal disease markers. 4. Perinatal pathology. This is a mixed line that groups projects relating to prematureness (chorioamnionitis, aggressive nutrition), clinical pathology (diabetes, autoimmune diseases), preeclampsia and placental disorders (developing methods for early prediction), HIV and pregnancy, neonatal respiratory disease (study of pulmonary inflammation and prevention of bronchopulmonary dysplasia), and investigation of neonatal infection (perinatal and nosocomial infections, respiratory syncytial virus infection, etc.). PUBLICATIONS Originals I.F.: 120,82 1 Sola R, Bruckert E, Valls RM, Narejos S, Luque X, Castro-Cabezas M, Domenech G, Torres F, Heras M, Farres X, Vaquer JV, Martinez JM, Almaraz MC, Anguera A. Soluble fibre (Plantago ovata husk) reduces plasma low-density lipoprotein (LDL) cholesterol, triglycerides, insulin, oxidised LDL and systolic blood pressure in hypercholesterolaemic patients: A randomised trial. ATHEROSCLEROSIS, 2010. 211:630-637. I.F.:4,52. 2 Bennasar M, Martinez JM, Gomez O, Bartrons J, Olivella A, Puerto B, Gratacos E. Accuracy of four-dimensional spatiotemporal image correlation echocardiography in the prenatal diagnosis of congenital heart defects. ULTRASOUND OBST GYN, 2010. 36:458-464. I.F.:3,15. 3 Cruz-Martinez R, Moreno-Alvarez O, Hernandez-Andrade E, Castanon M, Done E, Martinez JM, Puerto B, Deprest J, Gratacos E. Contribution of intrapulmonary artery Doppler to improve prediction of survival in fetuses with congenital diaphragmatic hernia treated with fetal endoscopic tracheal occlusion. ULTRASOUND OBST GYN, 2010. 35:572-577. I.F.:3,15. 4 Borras A, Gomez O, Sanz M, Martinez JM, Puerto B. Feticide Followed by Mifepristone-Misoprostol Regimen for Midtrimester Termination of Pregnancy in Two Cases of Complete Placenta Previa. FETAL DIAGN THER, 2010. 28:114116. I.F.:0,91. 5 Cruz-Martinez R, Figueras F, Hernandez-Andrade E, Puerto B, Gratacos E. Longitudinal brain perfusion changes in near-term small-for-gestational-age fetuses as measured by spectral Doppler indices or by fractional moving blood volume. AM J OBSTET GYNECOL, 2010. 203:-. I.F.:3,28. 6 Sanz-Cortes M, Martinez JM, Bennasar M, Puerto B, Graracos E. Prenatal diagnosis of tuberous sclerosis and analysis using magnetic resonance spectroscopy. ULTRASOUND OBST GYN, 2010. 36:522-524. I.F.:3,15. 7 Martinez JM, Gomez O, Bennasar M, Olivella A, Crispi F, Puerto B, Gratacos E. The ‘question mark’ sign as a new ultrasound marker of tetralogy of Fallot in the fetus. ULTRASOUND OBST GYN, 2010. 36:556-560. I.F.:3,15. 8 Sanz-Cortes M, Figueras F, Bargallo N, Padilla N, Amat-Roldan I, Gratacos E. Abnormal brain microstructure and metabolism in small-for-gestational-age term fetuses with normal umbilical artery Doppler. ULTRASOUND OBST GYN, 2010. 36:159-165. I.F.:3,15. 9 Martinez JM, Comas M, Borrell A, Bennasar M, Gomez O, Puerto B, Gratacos E. Abnormal first-trimester ductus venosus blood flow: a marker of cardiac defects in fetuses with normal karyotype and nuchal translucency. ULTRASOUND OBST GYN, 2010. 35:267-272. I.F.:3,15. 10 Illa M, Bennasar M, Eixarch E, Berge R, Font C, Palacio M. Acute Coronary Artery Vasospasm Associated with Misoprostol for Termination of Pregnancy. FETAL DIAGN THER, 2010. 27:174-177. I.F.:0,91. 11 Badenas C, Rodriguez-Revenga L, Morales C, Mediano C, Plaja A, PerezIribarne MM, Soler A, Clusellas N, Borrell A, Sanchez MA, Miro E, Sanchez A, Mila M, Jimenez W. Assessment of QF-PCR as the First Approach in Prenatal Diagnosis. J MOL DIAGN, 2010. 12:828-834. I.F.:3,41. 12 Moreno R, Martinez-Gonzalez I, Rosal M, Farwati A, Gratacos E, Aran JM. Characterization of Mesenchymal Stem 149 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM FETAL AND PERINATAL MEDICINE Team Members Cells Isolated from the Rabbit Fetal Liver. STEM CELLS DEV, 2010. 19:15791588. I.F.:4,15. 13 Munoz M, Arigita M, Bennasar M, Soler A, Sanchez A, Borrell A. Chromosomal anomaly spectrum in early pregnancy loss in relation to presence or absence of an embryonic pole. FERTIL STERIL, 2010. 94:2564-2568. I.F.:3,97. 14 Botet F, Figueras J, CarbonellEstrany X, Arca G. Effect of maternal clinical chorioamnionitis on neonatal morbidity in very-low birthweight infants: a case-control study. J PERINAT MED, 2010. 38:269-273. I.F.:1,74. 15 Skupski DW, Chervenak FA, Mccullough LB, Bancalari E, Haumont D, Simeoni U, Saugstad O, Donn S, Arabin B, Greenough A, Donzelli G, Levene M, Sen C, Carbonell X, Dudenhausen JW, Vladareanu R, Antsaklis A, Papp Z, Aksit M, Carrapato M. Ethical dimensions of periviability. J PERINAT MED, 2010. 38:579-583. I.F.:1,74. 16 Crispi F, Bijnens B, Figueras F, Bartrons J, Eixarch E, LeNoble F, Ahmed A, Gratacos E. Fetal Growth Restriction Results in Remodeled and Less Efficient Hearts in Children. CIRCULATION, 2010. 121:2427-U123. I.F.:14,82. 17 Esteban FJ, Padilla N, SanzCortes M, DeMiras JR, Bargallo N, Villoslada P, Gratacos E. Fractaldimension analysis detects cerebral changes in preterm infants with and without intrauterine growth restriction. NEUROIMAGE, 2010. 53:1225-1232. I.F.:5,74. 18 Xuncla M, Badenas C, Dominguez M, Rodriguez-Revenga L, Madrigal I, Jimenez L, Soler A, Borrell A, Sanchez A, Mila M. Fragile X syndrome 150 prenatal diagnosis: parental attitudes and reproductive responses. REPROD BIOMED ONLINE, 2010. 21:560-565. I.F.:2,38. 19 Bennasar M, Martinez JM, Gomez O, Figueras F, Olivella A, Puerto B, Gratacos E. Intra- and interobserver repeatability of fetal cardiac examination using four-dimensional spatiotemporal image correlation in each trimester of pregnancy. ULTRASOUND OBST GYN, 2010. 35:318-323. I.F.:3,15. 20 Figueras-Aloy J, Rodriguez-Miguelez JM, Iriondo-Sanz M, Salvia-Roiges MD, Botet-Mussons F, CarbonellEstrany X. Intravenous Immunoglobulin and Necrotizing Enterocolitis in Newborns With Hemolytic Disease. PEDIATRICS, 2010. 125:139-144. I.F.:4,69. 21 Cruz-Martinez R, Figueras F, Moreno-Alvarez O, Martinez JM, Gomez O, Hernandez-Andrade E, Gratacos E. Learning curve for lung area to head circumference ratio measurement in fetuses with congenital diaphragmatic hernia. ULTRASOUND OBST GYN, 2010. 36:32-36. I.F.:3,15. 22 Moreno-Alvarez O, Cruz-Martinez R, Hernandez-Andrade E, Done E, Gomez O, Deprest J, Gratacos E. Lung tissue perfusion in congenital diaphragmatic hernia and association with the lung-to-head ratio and intrapulmonary artery pulsed Doppler. ULTRASOUND OBST GYN, 2010. 35:578-582. I.F.:3,15. 23 Oros D, Figueras F, Cruz-Martinez R, Padilla N, Meler E, HernandezAndrade E, Gratacos E. Middle versus anterior cerebral artery Doppler for the prediction of perinatal outcome and neonatal neurobehavior in term small-for-gestational-age fetuses with normal umbilical artery Doppler. ULTRASOUND OBST GYN, 2010. 35:456461. I.F.:3,15. 24 Gomez O, Borras A, Rabanal A, Palacio M, Carceller A, Coll O, Gratacos E. Mifepristone-misoprostol midtrimester abortion: impact of gestational age on the induction-to-abortion interval. CONTRACEPTION, 2010. 81:97-101. I.F.:2,37. 25 Boer K, England K, Godfried MH, Thorne C, Newell ML, Mahdavi S, Giaquinto C, Rampon O, Mazza A, DeRossi A, Worner IG, Mok J, DeJose MI, Martinez BL, Pena JM, Garcia JG, Lopez JRA, Rodriguez MCG, Asensi-Botet F, Otero MC, Perez-Tamarit D, Scherpbier HJ, Kreyenbroek M, Nellen FJB, Naver L, Bohlin AB, Lindgren S, Kaldma A, Belfrage E, Levy J, Barlow P, Manigart Y, Hainaut M, Goetghebuer T, Brichard B, DeBruycker JJ, Thiry N, Waterloos H, Viscoli C, DeMaria A, Bentivoglio G, Ferrero S, Gotta C, Mur A, Paya A, Lopez-Vilchez MA, Carreras R, Valerius NH, Rosenfeldt V, Coll O, Suy A, Perez JM, Fortuny C, Boguna J, Savasi V, Fiore S, Crivelli M, Vigano A, Giacomet V, Cerini C, Raimondi C, Zuccotti G, Alberico S, Tropea M, Businelli C, Taylor GP, Lyall EGH, Penn Z, Buffolano W, Tiseo R, Martinelli P, Sansone M, Maruotti G, Agangi A, Tibaldi C, Marini S, Masuelli G, Benedetto C, Niemiec T, Marczynska M, Dobosz S, Popielska J, Oldakowska A, Malyuta R, Semenenko I, Pilipenko T. Mode of delivery in HIV-infected pregnant women and prevention of mother-to-child transmission: changing practices in Western Europe. HIV MED, 2010. 11:368-378. I.F.:2,88. 26 Carbonell-Estrany X, Simoes EAF, Dagan R, Hall CB, Harris B, Hultquist M, Connor EM, Losonsky GA. Motavizumab for Prophylaxis of Respiratory Syncytial Virus in High-Risk Children: A Noninferiority Trial. PEDIATRICS, 2010. 125:E35-E51. I.F.:4,69. 27 Stensballe LG, Fullarton JR, Carbonell-Estrany X, Simoes EAF. Population based external validation of a European predictive model for respiratory syncytal virus hospitalization of premature infants AREA 3 Liver, digestive system and metabolism FETAL AND PERINATAL MEDICINE born 33 to 35 weeks of gestational age. PEDIATR INFECT DIS J, 2010. 29:374376. I.F.:2,85. 28 Gonce A, Borrell A, Meler E, Arigita M, Martinez JM, Botet F, Sanchez A, Gratacos E. Prevalence and perinatal outcome of dichorionic and monochorionic twins with nuchal translucency above the 99(th) percentile and normal karyotype. ULTRASOUND OBST GYN, 2010. 35:1418. I.F.:3,15. 29 Meler E, Figueras F, Mula R, Crispi F, Benassar M, Gomez O, Gratacos E. Prognostic Role of Uterine Artery Doppler in Patients with Preeclampsia. FETAL DIAGN THER. 27:8-13. I.F.:0,91. 30 Bodri D, Guillen JJ, Lopez M, Vernaeve V, Coll O. Racial disparity in oocyte donation outcome: a multiethnic, matched cohort study. HUM REPROD, 2010. 25:436-442. I.F.:3,86. 31 Benavides-Serralde JA, Hernandez-Andrade E, Figueroa-Diesel H, Oros D, Feria LA, Scheier M, Figueras F, Gratacos E. Reference Values for Doppler Parameters of the Fetal Anterior Cerebral Artery throughout Gestation. GYNECOL OBSTET INVES, 2010. 69:3339. I.F.:1,05. 32 Valsky DV, Eixarch E, Martinez JM, Crispi F, Gratacos E. Selective intrauterine growth restriction in monochorionic twins: pathophysiology, diagnostic approach and management dilemmas. SEMIN FETAL NEONAT M, 2010. 15:342-348. I.F.:2,74. 33 Srisupundit K, Brady PD, Devriendt K, Fryns JP, Cruz-Martinez R, Gratacos E, Deprest JA, Vermeesch JR. Targeted array comparative genomic hybridisation (array CGH) identifies genomic imbalances associated with isolated congenital diaphragmatic hernia (CDH). PRENATAL DIAG, 2010. 30:1198-1206. I.F.:1,71. 34 Meler E, Figueras F, Bennasar M, Gomez O, Crispi F, Gratacos E. The prognostic role of uterine artery Doppler investigation in patients with severe early-onset preeclampsia. AM J OBSTET GYNECOL, 2010. 202:-. I.F.:3,28. 35 Padilla N, Perapoch J, Carrascosa A, Acosta-Rojas R, Botet F, Gratacos E. Twelve-month neurodevelopmental outcome in preterm infants with and without intrauterine growth restriction. ACTA PAEDIATR, 2010. 99:1498-1503. I.F.:1,77. 36 Munim S, Figueras F, Shah SM, Khan F, Gardosi J. Ultrasound estimation of fetal weight: A formula for a Pakistani population. J OBSTET GYNAECOL RE, 2010. 36:479-483. I.F.:0,78. 37 Comas M, Crispi F, Cruz-Martinez R, Martinez JM, Figueras F, Gratacos E. Usefulness of myocardial tissue Doppler vs conventional echocardiography in the evaluation of cardiac dysfunction in earlyonset intrauterine growth restriction. AM J OBSTET GYNECOL, 2010. 203:-. I.F.:3,28. 38 Carbonell-Estrany X, Simoes EAF, Fullarton JR, Ferdynus C, Gouyon JB. Validation of a model to predict hospitalization due to RSV of infants born at 3335 weeks’ gestation. J PERINAT MED, 2010. 38:411-417. I.F.:1,74. Reviews I.F.: 5,69 1 Lopez M, Coll O. Chronic Viral Infections and Invasive Procedures: Risk of Vertical Transmission and Current Recommendations. FETAL DIAGN THER, 2010. 28:1-8. I.F.:0,91. 2 Valsky DV, Eixarch E, Martinez JM, Gratacos E. Selective intrauterine growth restriction in monochorionic diamniotic twin pregnancies. PRENATAL DIAG, 2010. 30:719-726. I.F.:1,71. 3 Deprest JA, Flake AW, Gratacos E, Ville Y, Hecher K, Nicolaides K, Johnson MP, Luks FI, Adzick NS, Harrison MR. The making of fetal surgery. PRENATAL DIAG, 2010. 30:653-667. I.F.:1,71. 4 Arca G, Botet F, Palacio M, Carbonell-Estrany X. Timing of umbilical cord clamping: New thoughts on an old discussion. J MATERN-FETAL NEO M, 2010. 23:1274-1285. I.F.:1,36. Editorials I.F.: 1,19 1 Deprest J, Breysem L, Gratacos E, Nicolaides K, Claus F, Debeer A, Smet MH, Proesmans M, Fayoux P, Storme L. Tracheal side effects following fetal endoscopic tracheal occlusion for severe congenital diaphragmatic hernia. PEDIATR RADIOL, 2010. 40:670-673. I.F.:1,19. Multicentrics I.F.: 13,66 1 Zhang WH, Deneux-Tharaux C, Brocklehurst P, Juszczak E, Joslin M, Alexander S. Effect of a collector bag for measurement of postpartum blood loss after vaginal delivery: cluster randomised trial in 13 European countries. BRIT MED J, 2010. 340:-. I.F.:13,66. Grants for research in progress Coll JO. Paediatric European Network Treatment AIDS and European Collaborative Study on HIV-infected pregnant women and their children. Sponsored by: European Commission, LSHPCT-2006-018865. Amount: 0,00 euros. Duration: 01/03/2006-28/02/2010. Gratacos E. IP- Soft tissue engineering for congenital birth defects in 151 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM FETAL AND PERINATAL MEDICINE children: new treatment modalities for spina bifida, urogenital and abdominal wall defects (EuroSTEC). Sponsored by: European Commision, LSHBCT-2006-037409. Amount: 91.500,00 euros. Duration: 01/01/2007-31/12/2011. Palacio M. Progesterona vaginal como tratamiento de mantenimiento de gestantes con amenaza de parto pretérmino. (Promesa). Sponsored by: Ministerio Sanidad y Consumo, EC07/90023. Amount: 296.450,00 euros. Duration: 29/10/2007-30/12/2010. Gratacos E. Novel ultrasound-based tridimensional tools for structural and fucntional evaluation of interest in human organs. (Uvolumes). Sponsored by: European Commision , PIAPGA-2008-219911. Amount: 695.550,00 euros. Duration: 01/08/2008-31/07/2012. Gratacos E. A multidisciplinary research programme for the evaluation of diagnostic techniques and intervention. Measures for preantal brain damage using growth restriction as a model. Sponsored by: Cerebra Foundation, CEREBRA_07_001. Amount: 850.930,00 euros. Duration: 01/10/2007-30/09/2013. Gratacos E. Clinical use of assesing reginal brain circulation perfusion to identify long term neurodevelopmental anomalies in small for gestational age fetuses (SGA). Sponsored by: Thrasher Research Fund, THRASHER08_001. Amount: 289.792,00 euros. Duration: 01/04/2009-31/03/2012. Gratacos E. eVV-endovascular vision. Sponsored by: Generalitat de Catalunya (ACC1Ó), VALTEC09-1-0048. Amount: 76.744,42 euros. Duration: 30/06/200930/06/2011. Figueras F. Acciones estratégicas en salud. Cambios hemodinámicas adaptativos a la insuficiencia placentaria crónica y relación con la lesión neurológica 152 perinatal en modelo animal de coneja gestante. Sponsored by: FIS, PI08/0230. Amount: 43.802,00 euros. Duration: 01/01/2009-31/12/2011. vascular assisted vision. Sponsored by: EUROPEAN COMISSION, 251356. Amount: 379.879,00 euros. Duration: 01/09/201030/08/2014. Gratacos E. Desarrollo de marcadores predictivos y búsqueda de mecanismos moleculares responsables de la reprogramación cardíaca en la restricción de crecimiento fetal. Sponsored by: MINISTERIO DE EDUCACIÓN, SAF2009_08815. Amount: 96.800,00 euros. Duration: 01/01/2010-31/12/2012. Palacio M. PROgesterona vaginal como tratamiento de Mantenimiento en gEStantes con Amenaza de parto pretérmino. Ensayo clínico aleatorizado, enmascarado a doble ciego y controlado con placebo. Sponsored by: MINISTERIO DE SANIDAD, POLÍTICA SOCIAL E IGUALDAD, TRA-096. Amount: 52.932,85 euros. Duration: 01/01/201031/12/2011. Borrell A. Aplicación clínica del genotipado RHD fetal en sangre materna en una población general de estantes RHD negativas. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/90539. Amount: 41.745,00 euros. Duration: 01/01/2010-31/12/2011. Figueras F. Evaluación de fracción sanguínea en movimiento como estrategia de cribado de hipoxia crónica cerebral fetal para la perdicción de alteraciones del neurodesarrollo. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/90391. Amount: 56.870,00 euros. Duration: 01/01/2010-31/12/2011. Gratacos E. Evaluación de la eficacia de un algoritmo combinando variables biológicas maternas, ecografía y marcadores bioquímicos para la predicción de preeclampsia y retraso de crecimiento intrauterino en primer trimestre de gestación. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/90404. Amount: 38.720,00 euros. Duration: 01/01/201030/06/2011. Gratacos E. Diagnóstico precoz en niños con daño cerebral y trastornos del aprendizaje. Sponsored by: FUNDACION CAJA NAVARRA, 14802. Amount: 14.422,69 euros. Duration: 01/01/2010-31/12/2010. Gratacos E. eVV- endoVascularVision: new endoscopic tools for real time Gratacos E. Biomarcadors quantitatius d’imatge: Nous mètodes per a la predicció del neurodesenvolupament anormal en nens amb retard de creixement fetal basats en connectòmica. Sponsored by: CAIXA D’ESTALVIS I PENSIONS, 10/503. Amount: 1.228.315,00 euros. Duration: 03/12/201031/12/2013. Thesis Figueras-Aloy J. Seguimiento del desarrollo psicomotor de prematuros extremos mediante la Escala del Desarrollo Infantil de Kent (EDIK) cumplimnetada por los padres y situación neuroevolutiva a los 2 y 5 años. PhD student: Elena Alcover Bloch. Martinez JM, Puerto B. Aplicación de la ecografia 4D-STIC (Spatio temporal image correlation) en el diagnóstico prenatal de las cardiopatías. PhD student: Maria del mar Bennasar Sans. Gratacos E. Cerebral and cardiac doppler parameters in the identification of fetuses with late-onset intrauterine growth restriction at risk of adverse perinatal and neurobehavioral outcome. PhD student: Rogelio Cruz Martinez. Figueras F. Perinatal and neurodevelopmental outcome of late-onset growth restricted fetuses. PhD student: Daniel Orós López. AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM Metabolic regulation and molecular pathology Strategic Objectives Group Members TEAM LEADER Josep Carreras (Facultat Medicina UB) Tel.: 93 402 45 41 Fax: 93 403 58 82 E-mail: jcarreras@ub.edu Idibaps members: Ferran Climent (Facultat de Medicina UB) Roser Cussó (Facultat de Medicina UB) 1. Study of rabbit and rat muscle metabolism and proteome in fast and slow fibers, and the modifications associated with electrostimulation and training work. 2. Use of biochemical markers to determine muscle damage. 3. Study of the metabolic alterations of the transplanted heart and its preservation. 4. Study of apoptosis extrinsic pathway in the transplanted heart and its blockage. Main Lines of Research 1. Study of the fast and slow muscle Research Fellows: Feliu Roset (Facultat de Medicina) Maria Carmen Eraso (Facultat de Medicina) Technicians: Mario Guerrero (Facultat de Medicina) Anna Belén Sánchez (Facultat de Medicina) PUBLICATIONS proteome in trained and sedentary rats. 2. Metabolic analyses of human muscle biopsies in relation to training. 3. Study of the serum fast and slow myosins as muscle damage markers. Effect of exercise in athletes and diabetics. 4. Reversal of metabolic block in the transplanted heart based on TATFLIPS proteins. 5. Use of TAT-FLIPS protein to block apoptosis in the transplanted heart. Collaborators: Joan Aureli Cadefau Surroca (Facultat de Medicina) Anna Novials (IDIBAPS) Laura Brugnara (IDIBAPS) Andreu Farran Codina (Facultat de Farmàcia) Mª Antonia Lizárraga (Facultat Medicina, Bellvitge) Originals I.F.: 4,35 1 Gorostiaga EM, NavarroAmezqueta I, Cusso R, Hellsten Y, Calbet JAL, Guerrero M, Granados C, Gonzalez-Izal M, Ibanez J, Izquierdo M. Anaerobic Energy Expenditure and Mechanical Efficiency during Exhaustive Leg Press Exercise. PLOS ONE, 2010. 5:-. I.F.:4,35. Grants for research in progress Cusso R. Marcadores moleculares de la lesión muscular. Sponsored by: TRACE Ministerio de Ciencia e Innovación, PET2008-0224. Amount: 72.000,00 euros. Duration: 01/01/2009-31/12/2010. Cusso R. Astronaut exercise prescriptions promoting Health and fitness on hearth. Sponsored by: Agencia Europea de l‘Espai, ESAA0-2010. Amount: 300.000,00 euros. Duration: 01/01/201031/12/2013. Cusso R. Marcadors de lesió muscular i de tendó. Fundació MuscleTech. Sponsored by: Fundación FC Barcelona, Generalitat de Catalunya, La Caixa, ESA-A0-2010. Amount: 100.000,00 euros. Duration: 01/01/2010-31/12/2013. Penetration of PTD-galactosidase in erythrocytes (left) and myocytes (right). Cusso R. Valoración de las isoformas de miosina como marcadores de lesión muscular en jugadores de fútbol y baloncesto durante una temporada deportiva. Sponsored by: Consejo Superior de Deportes, 042/UPB10/11. Amount: 12.000,00 euros. Duration: 01/01/201031/12/2011. 153 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM Team involved in: Viral hepatitis in the immune competent host and in liver transplant patients Strategic Objectives Group Members TEAM LEADER Xavier Forns (Hospital Clínic) Tel.: 93 227 54 99 E-mail: xforns@clinic.ub.es Idibaps members: Jose M Sánchez-Tapias (Hospital Clínic) Josep Maria Barrera (Hospital Clínic) Miquel Bruguera (Hospital Clínic) Josep Costa (Hospital Clínic) Miquel Navasa (Hospital Clínic) Research Fellows: Jakub Dragun (Marie Curie) Stella Martínez (Fundació Clínic) Mairene Coto (MAEC-AECI) Gonzalo Crespo (Hospital Clínic) Laura Mensa (CIBERehd) Investigation of epidemiological, pathogenic, diagnostic and therapeutic aspects of hepatitis virus infections in immune competent patients and liver transplant recipients. Main Lines of Research 1. Study of host factors in relation to the natural history and treatment response among patients with chronic hepatitis C. In this setting, mention should be made of the studies which the group is carrying out on the influence of polymorphisms of the IL28B gene (which encodes for interferon lambda-3) upon the natural history and antiviral treatment response of chronic hepatitis C (in immune competent individuals and liver transplant recipients). In transplant patients with hepatitis C, our group has shown that the presence of a favorable IL28B polymorphism in the recipient, if associated with the favorable polymorphism in the donor liver, significantly increases the antiviral treatment response (Fig. 1). In the coming months, evaluation will be made of the role of this polymorphism in relation to the natural history of chronic hepatitis C virus infection. 2. Development of models for the in vitro study of the hepatitis C virus (HCV). At present there is only a single model for studying the complete life cycle of HCV. This is a limited model, since it is based on the culture of a single cell line, in which only one viral strain grows. Over the last year we have started the development of new cell culture systems based on different cell lines with incorporated markers, allowing the detection of viral replication and the screening of biological samples with considerable rapidity. The ultimate aim of these studies is to establish one or more HCV culture systems allowing the growth and adaptation of viruses from biological samples, and which are therefore more representative of real life situations. 3. Detection of HCV antigens in liver tissue. This is a project which in a sense represents continuity of the work started in 2008 with the purpose of characterizing the expression of HCV penetration receptors (claudin-1, occludin SR-B1 and CD81). Following completion of this project, we wish to detect viral antigens in liver tissue. While this may seem an easy project, to date it has not been possible to detect these antigens in a reproducible manner. Since we have samples from transplant patients with Technicians: Patricia González (CIBERehd) Nursing Staff: Concepció Bartrés (Fundació Clínic) Collaborators: Sofia Pérez del Pulgar (CIBERehd) Georgios Koutsoudakis (CIBERehd) Influence of polymorphisms of the interleukin-28B (IL28B) gene upon antiviral treatment response in liver transplant patients with hepatitis C. Those patients with a favorable polymorphism (CC) and who receive a liver from an IL28 CC donor have a high probability of healing the infection with interferon and ribavirin. 154 AREA 3 Liver, digestive system and metabolism VIRAL HEPATITIS IN THE IMMUNE COMPETENT HOST AND IN LIVER TRANSPLANT PATIENTS very high viral loads, and taking advantage of the experience gained over the past years with confocal microscopy and immunohistochemistry techniques, we aim to evaluate the presence of different viral antigens in liver biopsies. Success with the project could have clinical applications in aspects as relevant as the differential diagnosis of rejection and the recurrence of hepatitis C after transplantation. 4. Noninvasive diagnosis of chronic hepatitis C. This is a consolidated line of research within the group. Over the past years, different studies by our group have demonstrated the diagnostic validity of transient elastometry (TE, Fibroscan) in diagnosing advanced liver fibrosis or portal hypertension in patients with HCV infection and subjected to liver transplantation. During 2009 and 2010, other non-invasive markers of liver fibrosis have been evaluated (such as the combination of different serum markers of fibrogenesis). Within a more ambitious project (LiverBiomark) forming part of the Ciberehd, the group has proposed the utilization of metabolomics in an attempt to secure the early identification of those patients with hepatitis C presenting a risk of developing serious forms of the disease (in both immune competent individuals and in liver transplant recipients). 5. Treatment of chronic hepatitis C. Logically, our group continues to focus great effort on improving the efficacy and safety of antiviral therapy in patients with chronic HCV infection. Different aspects are included within this line of research: 1) Participation in clinical trials of new antiviral molecules (in both early stages and in pre-marketing phases); and 2) Study of the predictive factors of treatment response and designing of models allowing a reliable prediction of treatment results – particularly as regards the prediction of infection relapse in patients that have been able to achieve negative conversion of HCV during treatment. In the last year we have found that direct antiviral drug treatment (therefore not requiring interferon) is able to definitively eliminate HCV, and thus heal the chronic infection. This is an important step in the field of hepatitis, which will lead to radical changes in treatment in the next 10 years. PUBLICATIONS Originals I.F.:90,08 1 Linares L, Cervera C, Hoyo I, Sanclemente G, Marco F, Cofan F, Ricart MJ, Navasa M, Moreno A. Klebsiella pneumoniae Infection in Solid Organ Transplant Recipients: Epidemiology and Antibiotic Resistance. TRANSPL P, 2010. 42:2941-2943. I.F.:0,99. 2 Baccaro ME, Pepin MN, Guevara M, Colmenero J, Torregrosa JV, MartinLlahi M, Sola E, Esforzado N, Fuster J, Campistol JM, Arroyo V, Navasa M, Garcia-Valdecasas J, Gines P. Combined liver-kidney transplantation in patients with cirrhosis and chronic kidney disease. NEPHROL DIAL TRANSPL, 2010. 25:2356-2363. I.F.:3,31. 3 Morales JM, Campistol JM, Dominguez-Gil B, Andres A, Esforzado N, Oppenheimer F, Castellano G, Fuertes A, Bruguera M, Praga M. Long-Term Experience With Kidney Transplantation From Hepatitis C-Positive Donors Into Hepatitis C-Positive Recipients. AM J TRANSPLANT, 2010. 10:2453-2462. I.F.:6,43. 4 Benitez CE, Puig-Pey I, Lopez M, Martinez-Llordella M, Lozano JJ, Bohne F, Londono MC, Garcia-Valdecasas JC, Bruguera M, Navasa M, Rimola A, Sanchez-Fueyo A. ATG-Fresenius Treatment and Low-Dose Tacrolimus: Results of a Randomized Controlled Trial in Liver Transplantation. AM J TRANSPLANT, 2010. 10:2296-2304. I.F.:6,43. 5 Bellot P, Garcia-Pagan JC, Frances R, Abraldes JG, Navasa M, PerezMateo M, Such J, Bosch J. Bacterial DNA Translocation Is Associated With Systemic Circulatory Abnormalities and Intrahepatic Endothelial Dysfunction in Patients With Cirrhosis. HEPATOLOGY, 2010. 52:2044-2052. I.F.:10,84. 6 Vilaplana C, Montane E, Pinto S, Barriocanal AM, Domenech G, Torres F, Cardona PJ, Costa J. Double-blind, randomized, placebo-controlled Phase I Clinical Trial of the therapeutical antituberculous vaccine RUTI (R). VACCINE, 2010. 28:1106-1116. I.F.:3,62. 7 Moreno M, Chaves JF, Sancho-Bru P, Ramalho F, Ramalho LN, Mansego ML, Ivorra C, Dominguez M, Conde L, Millan C, Mari M, Colmenero J, Lozano JJ, Jares P, Vidal J, Forns X, Arroyo V, Caballeria J, Gines P, Bataller R. Ghrelin Attenuates Hepatocellular Injury and Liver Fibrogenesis in Rodents and Influences Fibrosis Progression in Humans. HEPATOLOGY, 2010. 51:974-985. I.F.:10,84. 8 Ramirez S, Perez-Del-Pulgar S, Carrion JA, Coto-Llerena M, Mensa L, Dragun J, Garcia-Valdecasas JC, Navasa M, Forns X. Hepatitis C virus superinfection of liver grafts: a detailed analysis of early exclusion of non-dominant virus strains. J GEN VIROL, 2010. 91:11831188. I.F.:3,26. 9 Carrion JA, Torres F, Crespo G, Miquel R, Garcia-Valdecasas JC, Navasa M, Forns X. Liver Stiffness Identifies Two Different Patterns of Fibrosis Progression in Patients with Hepatitis C Virus Recurrence After Liver Transplantation. HEPATOLOGY, 2010. 51:23-34. I.F.:10,84. 10 Fernandez-Rodriguez CM, Alonso S, Martinez SM, Forns X, Sanchez-Tapias JM, Rincon D, Rodriguez-Caravaca G, Barcena R, Serra MA, Romero-Gomez M, Fernandez I, Garcia-Samaniego J, Fuente J, Sola R, Moreno-Otero R, Planas R. Peginterferon Plus Ribavirin and Sustained Virological Response in HCV-Related Cirrhosis: Outcomes and Factors Predicting Response. AM J GASTROENTEROL, 2010. 105:21642172. I.F.:6,01. 155 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM VIRAL HEPATITIS IN THE IMMUNE COMPETENT HOST AND IN LIVER TRANSPLANT PATIENTS 11 Plans P, Costa J, Dominguez A, Torner N, Borras E, Plasencia A. Prevalence of Protective Measles Virus Antibody Levels in Umbilical Cord Blood Samples in Catalonia, Spain. CLIN VACCINE IMMUNOL, 2010. 17:691-694. I.F.:2,37. 12 Carrion JA, Navasa M, Forns X. Retransplantation in patients with hepatitis C recurrence after liver transplantation. J HEPATOL, 2010. 53:962970. I.F.:7,82. 13 Carrion JA, Fernandez-Varo G, Bruguera M, Garcia-Pagan JC, GarciaValdecasas JC, Perez-Del-Pulgar S, Forns X, Jimenez W, Navasa M. Serum Fibrosis Markers Identify Patients With Mild and Progressive Hepatitis C Recurrence After Liver Transplantation. GASTROENTEROLOGY, 2010. 138:147-158. I.F.:12,90. 14 Lens S, Crespo G, Carrion JA, Miquel R, Navasa M. Severe acute hepatitis in the dress syndrome: Report of two cases. ANN HEPATOL, 2010. 9:198-201. I.F.:1,67. 15 Ruiz-Antoran B, Escasany AA, Ferraz AV, Carreras ID, Riba N, Escudero SM, Costa J, Santiago MBS, Laredo L, Quintana JAD, Castillo JR, Abad-Santos F, Herrera CP, DeRada BSD, Ontanon EG. Use of non-specific intravenous human immunoglobulins in Spanish hospitals; need for a hospital protocol. EUR J CLIN PHARMACOL, 2010. 66:633-641. I.F.:2,74. Editorials I.F.:18,66 1 Navasa M, Bruix J. Multifaceted Perspective of the Waiting List for Liver Transplantation: The Value of Pharmacokinetic Models. HEPATOLOGY, 2010. 51:12-15. I.F.:10,84. 156 2 Forns X, Bruix J. Treating hepatitis C in patients with cirrhosis: The effort is worth it. J HEPATOL, 2010. 52:624-626. I.F.:7,82. Clinical Guidelines I.F.:7,82 1 Forns X, Et AL. EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J HEPATOL. 50:227-242. I.F.:7,82. Multicentrics I.F.:43,66 1 Kwo PY, Lawitz EJ, Mccone J, Schiff ER, Vierling JM, Pound D, Davis MN, Galati JS, Gordon SC, Ravendhran N, Rossaro L, Anderson FH, Jacobson IM, Rubin R, Koury K, Pedicone LD, Brass CA, Chaudhri E, Albrecht JK. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. LANCET, 2010. 376:705-716. I.F.:30,76. 2 Zeuzem S, Sulkowski MS, Lawitz EJ, Rustgi VK, Rodriguez-Torres M, Bacon BR, Grigorescu M, Tice AD, Lurie Y, Cianciara J, Muir AJ, Cronin PW, Pulkstenis E, Subramanian GM, Mchutchison JG. Albinterferon Alfa-2b Was Not Inferior to Pegylated Interferonalpha in a Randomized Trial of Patients With Chronic Hepatitis C Virus Genotype 1. GASTROENTEROLOGY, 2010. 139:1257-1266. I.F.:12,90. Grants for research in progress Forns X. Entry Inhibitors for the treatment of HCV Infection. Sponsored by: European Commission, MRTN-CT-2006-035599. Amount: 245.901,26 euros. Duration: 01/10/2006-30/09/2010. Forns X. Caracterización de la expresión hepática de los receptores de entrada del virus de la hepatitis C y su relación con la cinética de infección del injerto y la evolución clínica después del trasplante hepático. Sponsored by: Ministerio de Ciencia e Innovación, PI080239. Amount: 92.081,00 euros. Duration: 01/01/2009-31/12/2011. Thesis Forns X. Tratamiento de la hepatitis crónica C antes y después del trasplante Hepático (TH) y diagnóstico no invasivo de su recurrencia tras el TH. PhD student: Jose Antonio Carrion Rodríguez. Forns X. Estudio de la evolución genética y la compartimentalización del virus de la hepatitis C. PhD student: Santseharay Ramirez Almeida. AREA 3 Team involved in: LIVER, DIGESTIVE SYSTEM AND METABOLISM Physiopathology and treatment of ascites and altered renal function in liver cirrosis Strategic Objectives Group Members TEAM LEADER Vicente Arroyo (Hospital Clínic) Tel.: 93 227 17 24 Fax: 93 312 94 03 E-mail: varroyo@clinic.ub.es This is an interdisciplinary group that investigates the mechanisms and treatment of liver fibrotic inflammation leading to cirrhosis, as well as the pathogenesis and treatment of the multiorgan complications derived from the existence of established liver cirrhosis. Main Lines of Research Idibaps members: Ramón Bataller (Hospital Clínic) Joan Clària (Hospital Clínic) Pere Ginès (Hospital Clínic) Mónica Guevara (IDIBAPS) Wladimiro Jiménez (Hospital Clínic) Manuel Morales-Ruiz (Hospital Clínic) Javier Fernández-Gómez (Hospital Clínic) Postdoctoral fellows: Josefa Ros (FIS-IDIBAPS) Ana González-Périz (CIBERehd) Esther Titos (CIBERehd) Guillermo Fernandez Varó (CIBERehd) Marta López-Parra (MCyT) Pau Sancho (Fundació Clínic) Gregori Casals (Fundació Clínic) Research Fellows: Raquell Horrillo (Generalitat de Catalunya) Marta Martín (Hospital Clínic) Montserrat Moreno (CIBERehd) Montserrat Pauta (FPI-MEC) Jordi Ribera (CIBERehd) Marcos Martínez-Clemente (MEC) Eva Morán (FPU-MEC) Juan Acevedo (Hospital Clínic) Marcella Marinelli (Fundació Clínic) Cristina López Vicario (IDIBAPS) Vedrana Reichemback (Fundació Clínic) Silvia Affò (IDIBAPS) Oriol Morales (IDIBAPS) José Altamirano (IDIBAPS) Gustavo Henrique Santos Pereira (Fundació Clinic) Claudia Fagundes Gonçalves (Fundació Clinic) Elsa Solà (Hospital Clinic) Bibiana Rius Boadas (Fundació Clínic) Verónica García Alonso (FPI MEC) Daniel Rodrigo Torres (FPU-MEC) Javier Michelena (CIBERehd) Ignacio Barrau (Fundació Clínic) Denisse Oro Bozzini (Fundació Clínic) Technicians: Montse Bernat (Hospital Clínic) Cristina Díez (Hospital Clínic) Carmen Escofet (Hospital Clínic) Cristina Millán (IDIBAPS) Anabel Martinez (IDIBAPS) Carmen Cano (Hospital Clínic) Nursing Staff: Miriam Castro (CIBERehd) Raquel Cela (Hospital Clínic) Collaborators: Jordi Colmenero (Hospital Clínic) Marco Pavesi (CIBERehd) 1. Molecular determinants of liver inflammation. Role of the Kupffer cells. 2. Acute bacterial infections in cirrhosis. 3. Physiopathology and treatment of hepatorenal syndrome and renal failure associated with bacterial infections. 4. Evaluation of cirrhotic myocardiopathy. 5. Relationship between hepatic encephalopathy and alterations in renal function in cirrhosis. 6. Pathogenesis, clinical implications and treatment of hyponatremia. 7. Evaluation of different brain MRI techniques in cirrhotic patients. Relationship to hepatic encephalopathy. 8. Role of endogenous cannabinoids in the physiopathology of arterial vasodilatation. 9. Application of genomics and gene therapy to liver dysfunction. 10. Angiogenesis, endothelial dysfunction, edema and vascular remodeling in liver cirrhosis. 11. Pathogenesis of liver fibrosis: cellular bases and identification of new therapeutic strategies. 12. Physiopathology and treatment of arterial vasodilatation. 13. Physiopathology and treatment of ascites. 14. Artificial liver support systems. 15. Identification of new therapeutic targets in alcoholic hepatitis. 157 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM PHYSIOPATHOLOGY AND TREATMENT OF ASCITES AND ALTERED RENAL FUNCTION IN LIVER CIRRHOSIS PUBLICATIONS Originals I.F.:240,99 1 Tolosana JM, Mont L, Sitges M, Berruezo A, Delgado V, Vidal B, Tamborero D, Morales M, Batlle M, Roig E, Castel MA, Perez-Villa F, Godoy M, Brugada J. Plasma tissue inhibitor of matrix metalloproteinase-1 (TIMP-1): an independent predictor of poor response to cardiac resynchronization therapy. EUR J HEART FAIL, 2010. 12:492-498. I.F.:3,71. 2 Baccaro ME, Pepin MN, Guevara M, Colmenero J, Torregrosa JV, MartinLlahi M, Sola E, Esforzado N, Fuster J, Campistol JM, Arroyo V, Navasa M, Garcia-Valdecasas J, Gines P. Combined liver-kidney transplantation in patients with cirrhosis and chronic kidney disease. NEPHROL DIAL TRANSPL, 2010. 25:2356-2363. I.F.:3,31. 6 Carrion JA, Fernandez-Varo G, Bruguera M, Garcia-Pagan JC, Garcia-Valdecasas JC, Perez-Del-Pulgar S, Forns X, Jimenez W, Navasa M. Serum Fibrosis Markers Identify Patients With Mild and Progressive Hepatitis C Recurrence After Liver Transplantation. GASTROENTEROLOGY, 2010. 138:147-158. I.F.:12,90. 7 Horrillo R, Gonzalez-Periz A, MartinezClemente M, Lopez-Parra M, Ferre N, Titos E, Moran-Salvador E, Deulofeu R, Arroyo V, Claria J. 5-Lipoxygenase Activating Protein Signals Adipose Tissue Inflammation and Lipid Dysfunction in Experimental Obesity. J IMMUNOL, 2010. 184:3978-3987. I.F.:5,65. 8 Martinez-Clemente M, Ferre N, Moreno M, Dominguez M, Colmenero J, Peinado VI, Barbera JA, Arroyo V, Gines P, Caballeria J, Bataller R. Cigarette Smoking Exacerbates Nonalcoholic Fatty Liver Disease in Obese Rats. HEPATOLOGY, 2010. 51:15671576. I.F.:10,84. Gonzalez-Periz A, Lopez-Parra M, Horrillo R, Titos E, Moran-Salvador E, Miquel R, Arroyo V, Funk CD, Claria J. 5-Lipoxygenase Deficiency Reduces Hepatic Inflammation and Tumor Necrosis Factor alpha-Induced Hepatocyte Damage in Hyperlipidemia-Prone ApoE-Null Mice. HEPATOLOGY, 2010. 51:817-827. I.F.:10,84. 4 Badenas C, Rodriguez-Revenga L, 9 Moles A, Tarrats N, Morales A, Morales C, Mediano C, Plaja A, PerezIribarne MM, Soler A, Clusellas N, Borrell A, Sanchez MA, Miro E, Sanchez A, Mila M, Jimenez W. Assessment of QF-PCR as the First Approach in Prenatal Diagnosis. J MOL DIAGN, 2010. 12:828-834. I.F.:3,41. Dominguez M, Bataller R, Caballeria J, Garcia-Ruiz C, Fernandez-Checa JC, Mari M. Acidic Sphingomyelinase Controls Hepatic Stellate Cell Activation and in Vivo Liver Fibrogenesis. AM J PATHOL, 2010. 177:1214-1224. I.F.:5,67. 3 Azzalini L, Ferrer E, Ramalho LN, 5 Moreno M, Chaves JF, Sancho-Bru P, Ramalho F, Ramalho LN, Mansego ML, Ivorra C, Dominguez M, Conde L, Millan C, Mari M, Colmenero J, Lozano JJ, Jares P, Vidal J, Forns X, Arroyo V, Caballeria J, Gines P, Bataller R. Ghrelin Attenuates Hepatocellular Injury and Liver Fibrogenesis in Rodents 158 and Influences Fibrosis Progression in Humans. HEPATOLOGY, 2010. 51:974985. I.F.:10,84. 10 Altamirano J, Zapata L, Poblano M, Rodriguez A, Camargo L, Martinez B, Bataller R. Acute Pylephlebitis Following Gastrointestinal Infection: An Unrecognized Cause of Septic Shock. SOUTH MED J, 2010. 103:956-959. I.F.:0,92. 11 Melgar-Lesmes P, Casals G, Pauta M, Ros J, Reichenbach V, Bataller R, Morales-Ruiz M, Jimenez W. Apelin Mediates the Induction of Profibrogenic Genes in Human Hepatic Stellate Cells. ENDOCRINOLOGY, 2010. 151:53065314. I.F.:4,75. 12 Altamirano J, Bataller R. Cigarette smoking and chronic liver diseases. GUT, 2010. 59:1159-1162. I.F.:9,36. 13 Gines P, Wong F, Watson H, Terg R, Bruha R, Zarski JP, Dudley F. Clinical trial: short-term effects of combination of satavaptan, a selective vasopressin V-2 receptor antagonist, and diuretics on ascites in patients with cirrhosis without hyponatraemia - a randomized, double-blind, placebocontrolled study. ALIMENT PHARM THER, 2010. 31:834-845. I.F.:4,36. 14 Martinez-Clemente M, Ferre N, Titos E, Horrillo R, Gonzalez-Periz A, Moran-Salvador E, Lopez-Vicario C, Miquel R, Arroyo V, Funk CD, Claria J. Disruption of the 12/15-Lipoxygenase Gene (Alox15) Protects Hyperlipidemic Mice from Nonalcoholic Fatty Liver Disease. HEPATOLOGY, 2010. 52:1980-1991. I.F.:10,84. 15 Wong F, Gines P, Watson H, Horsmans Y, Angeli P, Gow P, Minini P, Bernardi M. Effects of a selective vasopressin V-2 receptor antagonist, satavaptan, on ascites recurrence after paracentesis in patients with cirrhosis. J HEPATOL, 2010. 53:283-290. I.F.:7,82. 16 VanDeVeire S, Stalmans I, Heindryckx F, Oura H, Tijeras-Raballand A, Schmidt T, Loges S, Albrecht I, Jonckx B, Vinckier S, VanSteenkiste C, Tugues S, Rolny C, DeMol M, Dettori D, Hainaud P, Coenegrachts L, Contreres JO, VanBergen T, Cuervo H, Xiao WH, LeHenaff C, Buysschaert I, Masouleh BK, Geerts A, Schomber T, Bonnin P, Lambert V, Haustraete J, Zacchigna S, Rakic JM, Jimenez W, Noel A, Giacca M, Colle I, Foidart JM, Tobelem G, Morales-Ruiz M, Vilar J, Maxwell P, Vinores SA, Carmeliet AREA 3 Liver, digestive system and metabolism PHYSIOPATHOLOGY AND TREATMENT OF ASCITES AND ALTERED RENAL FUNCTION IN LIVER CIRRHOSIS G, Dewerchin M, Claesson-Welsh L, Dupuy E, VanVlierberghe H, Christofori G, Mazzone M, Detmar M, Collen D, Carmeliet P. Further Pharmacological and Genetic Evidence for the Efficacy of PlGF Inhibition in Cancer and Eye Disease. CELL, 2010. 141:178-190. I.F.:31,15. 17 Sancho-Bru P, Juez E, Moreno M, Khurdayan V, Morales-Ruiz M, Colmenero J, Arroyo V, Brenner DA, Gines P, Bataller R. Hepatocarcinoma cells stimulate the growth, migration and expression of pro-angiogenic genes in human hepatic stellate cells. LIVER INT, 2010. 30:31-41. I.F.:2,99. 18 Sola E, Lens S, Guevara M, MartinLlahi M, Fagundes C, Pereira G, Pavesi M, Fernandez J, Gonzalez-Abraldes J, Escorsell A, Mas A, Bosch J, Arroyo V, Gines P. Hyponatremia in Patients Treated With Terlipressin for Severe Gastrointestinal Bleeding Due to Portal Hypertension. HEPATOLOGY, 2010. 52:1783-1790. I.F.:10,84. 19 Fernandez-Varo G, Melgar-Lesmes P, Casals G, Pauta M, Arroyo V, MoralesRuiz M, Ros J, Jimenez W. Inactivation of extrahepatic vascular Akt improves systemic hemodynamics and sodium excretion in cirrhotic rats. J HEPATOL, 2010. 53:1041-1048. I.F.:7,82. 20 Ki SH, Park O, Zheng MQ, MoralesIbanez O, Kolls JK, Bataller R, Gao B. Interleukin-22 Treatment Ameliorates Alcoholic Liver Injury in a Murine Model of Chronic-Binge Ethanol Feeding: Role off Signal Transducer and Activator of Transcription 3. HEPATOLOGY, 2010. 52:1291-1300. I.F.:10,84. 21 Padrissa-Altes S, Zaouali MA, Franco-Gou R, Bartrons R, Boillot O, Rimola A, Arroyo V, Rodes J, Peralta C, RoselloCatafau J. Matrix Metalloproteinase 2 in Reduced-Size Liver Transplantation: Beyond the Matrix. AM J TRANSPLANT, 2010. 10:1167-1177. I.F.:6,43. 22 Kluwe J, Pradere JP, Gwak GY, Mencin A, DeMinicis S, Osterreicher CH, Colmenero J, Bataller R, Schwabe RF. Modulation of Hepatic Fibrosis by c-Jun-N-Terminal Kinase Inhibition. GASTROENTEROLOGY, 2010. 138:347-359. I.F.:12,90. 23 Nazar A, Pereira GH, Guevara M, Martin-Llahi M, Pepin MN, Marinelli M, Sola E, Baccaro ME, Terra C, Arroyo V, Gines P. Predictors of Response to Therapy with Terlipressin and Albumin in Patients with Cirrhosis and Type 1 Hepatorenal Syndrome. HEPATOLOGY, 2010. 51:219-226. I.F.:10,84. 24 Titos E, Ferre N, Lozano JJ, Horrillo R, Lopez-Parra M, Arroyo V, Claria J. Protection from hepatic lipid accumulation and inflammation by genetic ablation of 5-lipoxygenase. PROSTAG OTH LIPID M, 2010. 92:54-61. I.F.:2,56. 25 Moreno M, Gonzalo T, Kok RJ, Sancho-Bru P, VanBeuge M, Swart J, Prakash J, Temming K, Fondevila C, Beljaars L, Lacombe M, VanDerHoeven P, Arroyo V, Poelstra K, Brenner DA, Gines P, Bataller R. Reduction of Advanced Liver Fibrosis by Short-Term Targeted Delivery of an Angiotensin Receptor Blocker to Hepatic Stellate Cells in Rats. HEPATOLOGY, 2010. 51:942-952. I.F.:10,84. 26 Guevara M, Baccaro ME, Rios J, Martin-Llah M, Uriz J, DelArbol LR, Planas R, Monescillo A, Guarner C, Crespo J, Banares R, Arroyo V, Gines P. Risk factors for hepatic encephalopathy in patients with cirrhosis and refractory ascites: relevance of serum sodium concentration. LIVER INT, 2010. 30:1137-1142. I.F.:2,99. 27 Albillos A, Nieto M, Ubeda M, Munoz L, Fraile B, Reyes E, Lledo L, Blanco I, Pastor O, Salas C, Lario M, Monserrat J, Bataller R, Alvarez-Mon M. The biological response modifier AM3 attenuates the inflammatory cell response and hepatic fibrosis in rats with biliary cirrhosis. GUT, 2010. 59:943-952. I.F.:9,36. 28 Romero-Gomez M, Jover M, DelCampo JA, Royo JL, Hoyas E, Galan JJ, Montoliu C, Baccaro E, Guevara M, Cordoba J, Soriano G, Navarro JM, Martinez-Sierra C, Grande L, Galindo A, Mira E, Manes S, Ruiz A. Variations in the Promoter Region of the Glutaminase Gene and the Development of Hepatic Encephalopathy in Patients With Cirrhosis A Cohort Study. ANN INTERN MED, 2010. 153:281-294. I.F.:16,23. Reviews I.F.:12,46 1 Salerno F, Guevara M, Bernardi M, Moreau R, Wong F, Angeli P, GarciaTsao G, Lee SS. Refractoryascites: pathogenesis, definition and therapy of a severe complication in patients with cirrhosis. LIVER INT, 2010. 30:937-947. I.F.:2,99. 2 Sola E, Gines P. Renal and circulatory dysfunction in cirrhosis: Current management and future perspectives. J HEPATOL, 2010. 53:1135-1145. I.F.:7,82. 3 Gonzalez-Periz A, Claria J. Resolution of Adipose Tissue Inflammation. THESCIENTIFICWORLDJO, 2010. 10:832-856. I.F.:1,66. Editorials I.F.:1,65 1 Claria J. Resolution of Acute Inflammation and the Role of Lipid Mediators. THESCIENTIFICWORLDJO, 2010. 10:1553-1555. I.F.:1,66. 159 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM PHYSIOPATHOLOGY AND TREATMENT OF ASCITES AND ALTERED RENAL FUNCTION IN LIVER CIRRHOSIS Clinical Guidelines I.F.:7,82 1 Gines P, Angeli P, Lenz K, Møller S, Moore K, Moreau R, Merkel C, Ring-Larsen H, Bernardi M, Garcia-Tsao G, Hayers P. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis European Association for the Study of the Liver. J HEPATOL, 2010. 53:397-417. I.F.:7,82. 160 Jimenez W. Remodelado tisular y disfunción circulatoria en modelos experimentales de enfermedad hepática. Identificación y caracterización de nuevas dianas terapéuticas. Sponsored by: Ministerio de Ciencia e Innovación, SAF2009-08839. Amount: 254.100,00 euros. Duration: 01/10/200930/09/2012. Grants for research in progress Bataller R. Projecte TRACE 2009. Desarrollo de un test genético para predecir la progresión de la fibrosis en pacientes con hepatitis crónica C” (POLIGEN). Sponsored by: Ministerio de Ciencia e Innovación, PET2008_0304. Amount: 121.000,00 euros. Duration: 01/03/2009-28/02/2011. Gines P. Efecto de la administración prolongada de albúminay midodrina en la prevención de complicaciones en pacientes en lista de espera de transplante hepático. Sponsored by: Ministerio Sanidad y Consumo, EC07/90077. Amount: 666.710,00 euros. Duration: 29/10/2007-30/12/2010. Bataller R. Investigación traslacional en pacientes con hepatopatías crónicas: desarrollo de métodos pronósticos e identificación de nuevas dianas terapéuticas. Sponsored by: Instituto de Salud Carlos III (FIS), PI08/0237. Amount: 135.762,00 euros. Duration: 01/01/2009-31/12/2012. Guevara M. Estudio Aleatorizado y controlado sobre la eficacia de la albúmina en la prevención de las complicaciones de pacientes de cirrosis en la lista de espera de trasplante hepático. Sponsored by: Ministerio Sanidad y Consumo, PI070443. Amount: 105.875,00 euros. Duration: 26/11/2007-30/12/2010. Arroyo V. Investigació hepàtica: Recerca bàsica i experimental. Sponsored by: AGAUR, 2009SGR3009. Amount: 43.680,00 euros. Duration: 01/01/2009-31/12/2013. Gines P. Grup de recerca en hepatologia clínica. Sponsored by: AGAUR, 2009SGR1401. Amount: 45.760,00 euros. Duration: 01/01/2009-31/12/2013. Claria J. Participación de los mediadores lipídicos derivados del ácido araquidónico en el desarrollo y progresión de la inflamación y esteatosis hepática. Efecto de los ácidos grasos poliinsaturados Omega-3. Sponsored by: Ministerio Educación y Ciencia, SAF2006-03191. Amount: 244.420,00 euros. Duration: 01/10/2006-30/09/2010. Gines P. Disfunción Renal en la cirrosis hepática: Investigación de nuevos métodos diagnósticos y terapéuticos. Sponsored by: Ministerio de Ciencia e Innovación Instituto de Salud Carlos III, PI 080126. Amount: 427.952,80 euros. Duration: 01/01/200831/12/2012. Morales M. Función fisiopatológica de la activación de las células endoteliales hepáticas en la cirrosis. Posibles implicaciones terapéuticas. Sponsored by: Ministerio Educación y Ciencia, SAF2007-63069. Amount: 229.900,00 euros. Duration: 01/10/2007-04/10/2010. Claria J. Papel de los mediadores lipídicos en la inflamación del tejido adiposo y su influencia sobre la respuesta esteatogénica del higado en la obesidad. Sponsored by: Ministerio de Educación, SAF2009_08767. Amount: 330.330,01 euros. Duration: 01/01/2010-31/12/2012. Jimenez W. Remodelado tisular y disfunción circulatoria en modelos experimentales de enfermedad hepática. Identificación y caracterización de nuevas dianas terapeuticas. Sponsored by: MINISTERIO DE EDUCACIÓN, SAF2009_08839. Amount: 254.100,01 euros. Duration: 01/01/2010-31/12/2012. Bataller R. Hepatic Microfluidic Bioreactor. Sponsored by: Katholieke Universiteit Leuven, FP7-2010-TESTING_1. Amount: 276.801,80 euros. Duration: 03/02/201002/02/2015. Jimenez W. Grupo de Investigación traslacional en nuevas estrategias de diagnóstico y tratamiento de la enfermedad hepática. Sponsored by: GENERALITAT DE CATALUNYA, 2009_SGR_1496. Amount: 42.640,00 euros. Duration: 20/08/2009-31/12/2013. Thesis Claria J. Paper de la ciclooxigenasa-2 i la 5-lipooxigenasa en la inflamació hepàtica i del teixit adipós. PhD student: Raquel Horrillo Saura. Jimenez W. Fisiopatologia del edema y de la formacion de ascitis en la cirrosis hepática experimental. PhD student: Pedro Melgar Lesmes. Bataller R. Investigación de nuevas estrategias terapeúticas para la inflamación y la fibrosis hepática. PhD student: Montserrat Moreno Sanchez. AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM Team involved in: HEPATIC ONCOLOGY Strategic Objectives Group Members TEAM LEADER Jordi Bruix (Hospital Clínic) Tel.: 93 227 98 03 Fax: 93 227 57 92 E-mail: jbruix@clinic.ub.es This multidiscipline group, internationally known as the Barcelona Clinic Liver Cancer (BCLC) group, carries out clinical research into hepatocellular carcinoma and translation research. The objective is to investigate both the efficacy of clinical and therapeutic interventions and the mechanisms that regulate the progression of this disease. Main Lines of Research Idibaps members: M. Carmen Ayuso (Hospital Clínic) Concepció Bru (Hospital Clínic) Josep Fuster (Hospital Clínic) Josep M. Llovet (ICREA) Ramon Vilana (Hospital Clínic) Research Fellows: Clara Alsinet (Fundació Clínic) María Reig (IDIBAPS) Carlos Rodriguez de Lope (Hospital Clínic) Helena Cornella (IDIBAPS) Silvia Tremosini (Fundació Clínic) Technicians: Juan M. López (Fundació Clínic) Ingrid Rengel (CIBERehd) Nursing Staff: Adela Godoy (Fundació Clínic) Neus Llarch (Fundació Clínic) Administrative Staff: Núria Pérez (Fundació Clínic) Diana Segarra (CIBERehd) Ariadna Farré (IDIBAPS) Collaborators: Loreto Boix (CIBERehd) Judit Peix (CIBERehd) Manel Solé (Hospital Clínic) Victoria Tovar (IDIBAPS) Alejandro Forner (CIBERehd) Jordi Rimola (CDIC) Marta Burrel (CDIC) Maria Isabel Real (CDIC) Lluís Bianchi (CDIC) Augusto Villanueva (Ciberehd) M. Angeles García-Criado (Hospital Clínic) At clinical level, work is done in the definition of new diagnostic tools and, with a view to evaluating treatment efficacy, the optimum criteria for indicating radical treatment are perfected (surgical resection, transplantation, percutaneous approach with ablation) – with the aim of ensuring maximum efficacy in terms of both survival and associated morbidity. In the treatment setting, evaluations are made of the options for improving the efficacy of non-curative therapies which have been shown to improve survival (arterial chemical embolization, sorafenib). In this sense, phase 1, 2 and 3 studies are carried out and led at international level, with a view to determining the efficacy of new molecular agents. At the same time, evaluations are being made of the efficacy of antiangiogenic treatment to prevent relapse after surgical treatment or ablation. Likewise, prevention studies are being conducted in patients with liver cirrhosis. In relation to translation research, studies are being made of the pathogenesis of hepatocellular carcinoma, together with the analysis of new signaling pathways and genomic aberrations implicated in the development of the tumor, as well as the identification of novel therapeutic targets. An international genomic research consortium has been created in hepatocellular carcinoma, in collaboration with the Mount Sinai Medical School, Harvard University and the Instituto di Tumori in Milan, which has consolidated a tissue bank of capital importance. Diagnosis of early stage HCC based on staining with GPC3 (A), HSP70 (B) and GS (C). RESEARCH GROUP Translational research in liver oncology Group Leader: Josep M. Llovet (ICMDM) The group was created in the year 2006 with the purpose of conducting genomic studies in hepatocellular carcinoma and of identifying therapeutic targets and new molecular treatments. We have established two lines of research in the context of an international consortium (HCC Genomic Project), organized by Dr. Llovet, and involving the participation of the BCLC-Clínic-IDIBAPS, the Mount Sinai School of Medicine (NY), the Dana-Farber Cancer Institute and the Broad Institute (Boston), and the National Tumor Institute (Milan):1. Genomics. Identification of the genomic alterations in hepatocellular carcinoma (HCC), and clarification of their implications in relation to diagnosis and treatment. Integral analysis of the transcriptome (oligonucleotide microarrays) and of the genomic aberrations (SNP arrays). Identification of markers for the early diagnosis of HCC.2. Signaling pathways and molecular therapies. Identification of the role of the signal transduction pathways in the pathogenesis of HCC, and identification of new therapeutic targets and new molecular treatments. We are currently studying the signaling pathways corresponding to Akt/mTOR, EGFR-Ras-MAPK, IGF and Wnt, in human samples, cell lines and experimental animals. Recently, the group has been coordinating a European Project, FP-7-HEALTH (HEPTROMIC) with 6 academic centers and two companies, with the purpose of exploring the prognostic oncogenes and potential treatment targets in liver cancer. 161 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM HEPATIC ONCOLOGY Team Members PUBLICATIONS Originals I.F.: 62,23 1 Baccaro ME, Pepin MN, Guevara M, Colmenero J, Torregrosa JV, Martin-Llahi M, Sola E, Esforzado N, Fuster J, Campistol JM, Arroyo V, Navasa M, Garcia-Valdecasas J, Gines P. Combined liver-kidney transplantation in patients with cirrhosis and chronic kidney disease. NEPHROL DIAL TRANSPL, 2010. 25:2356-2363. I.F.:3,31. 2 Marti J, Fuster J, Hotter G, Sola AM, Deulofeu R, Modolo MM, Loera MA, Ferrer J, Fondevila C, Garcia-Valdecasas JC. Serum neutrophil gelatinase-associated lipocalin in patients with colorectal liver metastases: preliminary results of an exploratory prospective study. INT J BIOL MARKER, 2010. 25:21-26. I.F.:1,42. 3 Cabibbo G, Enea M, Attanasio M, Bruix J, Craxi A, Camma C. A MetaAnalysis of Survival Rates of Untreated Patients in Randomized Clinical Trials of Hepatocellular Carcinoma. HEPATOLOGY, 2010. 51:1274-1283. I.F.:10,84. 4 Greten TF, Forner A, Korangy F, N’kontchou G, Barget N, Ayuso C, Ormandy LA, Manns MP, Beaugrand M, Bruix J. A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma. BMC CANCER, 2010. 10:-. I.F.:2,74. 5 Plessier A, Darwish-Murad S, Hernandez-Guerra M, Consigny Y, Fabris F, Trebicka J, Heller J, Morard I, Lasser L, Langlet P, Denninger MH, Vidaud D, Condat B, Hadengue A, Primignani M, Garcia-Pagan JC, Janssen HLA, Valla D. Acute Portal Vein Thrombosis Unrelated to Cirrhosis: A Prospective Multicenter Follow-up Study. HEPATOLOGY, 2010. 51:210218. I.F.:10,84. 162 6 Tovar V, Alsinet C, Villanueva A, Hos- Reviews hida Y, Chiang DY, Sole M, Thung S, Moyano S, Toffanin S, Minguez B, Cabellos L, Peix J, Schwartz M, Mazzaferro V, Bruix J, Llovet JM. IGF activation in a molecular subclass of hepatocellular carcinoma and pre-clinical efficacy of IGF-1R blockage. J HEPATOL, 2010. 52:550-559. I.F.:7,82. Zender L, Villanueva A, Tovar V, Sia D, Chiang DY, Llovet JM. Cancer gene discovery in hepatocellular carcinoma. J HEPATOL, 2010. 52:921-929. I.F.:7,82. 7 Vilana R, Forner A, Bianchi L, Garcia- 2 Forner A, Reig ME, DeLope CR, Criado A, Rimola J, DeLope CR, Reig M, Ayuso C, Bru C, Bruix J. Intrahepatic Peripheral Cholangiocarcinoma in Cirrhosis Patients May Display a Vascular Pattern Similar to Hepatocellular Carcinoma on Contrast-Enhanced Ultrasound. HEPATOLOGY, 2010. 51:2020-2029. I.F.:10,84. Bruix J. Current Strategy for Staging and Treatment: The BCLC Update and Future Prospects. SEMIN LIVER DIS, 2010. 30:61-74. I.F.:5,17. 8 Hessheimer AJ, Forner A, Varela M, Bruix J. Metabolic risk factors are a major comorbidity in patients with cirrhosis independent of the presence of hepatocellular carcinoma. EUR J GASTROEN HEPAT, 2010. 22:1239-1244. I.F.:1,66. 9 Fondevila C, Hessheimer AJ, Taura P, Sanchez O, Calatayud D, DeRiva N, Munoz J, Fuster J, Rimola A, Garcia-Valdecasas JC. Portal Hyperperfusion: Mechanism of Injury and Stimulus for Regeneration in Porcine Small-for-Size Transplantation. LIVER TRANSPLANT, 2010. 16:364-374. I.F.:3,72. 10 Taura P, Fuster J, Mercadal J, Martinez-Palli G, Fondevila C, Blasi A, Balust J, Garcia-Valdecasas JC. The use of beta-adrenergic drugs improves hepatic oxygen metabolism in cirrhotic patients undergoing liver resection. J HEPATOL, 2010. 52:340-347. I.F.:7,82. 11 Varela M, Reig M, DeLaMata M, Matilla A, Bustamante J, Pascual S, Turnes J, Aracil C, DelVal A, Pascasio JM, Rodriguez M, Bruix J. Treatment approach of hepatocellular carcinoma in Spain. Analysis of 705 patients from 62 centers. MED CLIN-BARCELONA, 2010. 134:569-576. I.F.:1,23. I.F.: 40,02 1 3 Villanueva A, Minguez B, Forner A, Reig M, Llovet JM. Hepatocellular Carcinoma: Novel Molecular Approaches for Diagnosis, Prognosis, and Therapy. ANNU REV MED, 2010. 61:317-328. I.F.:9,94. 4 Lencioni R, Llovet JM. Modified RECIST (mRECIST) Assessment for Hepatocellular Carcinoma. SEMIN LIVER DIS, 2010. 30:52-60. I.F.:5,17. 5 Hoshida Y, Toffanin S, Lachenmayer A, Villanueva A, Minguez B, Llovet JM. Molecular Classification and Novel Targets in Hepatocellular Carcinoma: Recent Advancements. SEMIN LIVER DIS, 2010. 30:35-51. I.F.:5,17. 6 Villanueva A, Hoshida Y, Toffanin S, Lachenmayer A, Alsinet C, Savic R, Cornella H, Llovet JM. New Strategies in Hepatocellular Carcinoma: Genomic Prognostic Markers. CLIN CANCER RES, 2010. 16:4688-4694. I.F.:6,75. Editorials I.F.: 108,53 1 Navasa M, Bruix J. Multifaceted Perspective of the Waiting List for Liver Transplantation: The Value of Pharmacokinetic Models. HEPATOLOGY, 2010. 51:12-15. I.F.:10,84. AREA 3 Liver, digestive system and metabolism HEPATIC ONCOLOGY 2 Forns X, Bruix J. Treating hepatitis C in patients with cirrhosis: The effort is worth it. J HEPATOL, 2010. 52:624-626. I.F.:7,82. 3 Forner A, Bruix J. Ablation for hepatocellular carcinoma: Is there need to have a winning technique?. J HEPATOL, 2010. 52:310-312. I.F.:7,82. 4 DeLope CR, Bruix J. Failure of interferon to prevent disease progression and liver cancer in hepatitis C virus infection: proof of absence or absence of proof?. GASTROENTEROLOGY, 2010. 138:777779. I.F.:12,90. 5 Lachenmayer A, Hoshida Y, Llovet JM. Hippo tumor supressor pathway: novel implications for the treatment of hepatocellular carcinoma. GASTROENTEROLOGY, 2010. 139:692-694. I.F.:12,90. 6 Boix L, Bruix J. MicroRNA analysis for outcome prediction in hepatitis B virusrelated liver cancer. GASTROENTEROLOGY, 2010. 138:1624-1626. I.F.:12,90. 7 Toffanin S, Villanueva A, Llovet JM. miRNA delivery: emerging therapy for hepatocellular carcinoma. GASTROENTEROLOGY, 2010. 138 (3):1202-1204. I.F.:12,90. 8 Toffanin S, Friedman SL, Llovet JM. Obesity, Inflammatory Signaling, and Hepatocellular Carcinoma-An Enlarging Link. CANCER CELL, 2010. 17:115-117. I.F.:25,29. 9 Bruix J, Llovet JM. Two Decades of Advances in Hepatocellular Carcinoma Research FOREWORD. SEMIN LIVER DIS, 2010. 30:1-2. I.F.:5,17. Clinical Guidelines I.F.: 2,21 1 Ferenci P, Fried M, Labrecque D, Bruix J, Sherman M, Omata M, Heathcote J, Piratsivuth T, Kew M, Otegbayo JA, Zheng SS, Sarin S, Hamid SS, Modawi SB, Fleig W, Fedail S, Thomson A, Khan A, Malfertheiner P, Lau G, Carillo FJ, Krabshuis J, LeMair A. Hepatocellular Carcinoma (HCC) A Global Perspective. J CLIN GASTROENTEROL, 2010. 44:239-245. I.F.:2,21. Multicentrics I.F.: 28,90 1 Paoletti X, Oba K, Burzykowski T, Michiels S, Ohashi Y, Pignon JP, Rougier P, Sakamoto J, Sargent D, Sasako M, VanCutsem E, Buyse M. Benefit of Adjuvant Chemotherapy for Resectable Gastric Cancer A Meta-analysis. JAMA-J AM MED ASSOC, 2010. 303:1729-1737. I.F.:28,90. Grants for research in progress Bru C. Integración de las diferentes técnicas de imagen médica en una única imagen multimodal. Desarrollo de distintos modelos de aplicación. Angiología cerebral y cardiológica (TC, RM, SPECT). Sponsored by: Ministerio de Industria Turismo y Comercio, CDTEAM. Amount: 428.000,00 euros. Duration: 17/01/200618/01/2010. Llovet JM. Papel de la vía de señalización del IGF en el carcinoma hepatocelular (CHC). Terapia molecular in vitro e in vivo. Sponsored by: Ministerio Educación y Ciencia, SAF2007-61898. Amount: 209.330,00 euros. Duration: 01/10/200704/10/2010. Llovet JM. Integrative genomic analysis in hepatocellular carcinoma. Sponsored by: National Institutes of Health, 1R01DK076986-01. Amount: 142.780,00 euros. Duration: 08/10/2007-31/07/2012. tumorales en líneas celulares derivadas de carcinoma hepatocelular humano. Sponsored by: Fondo de Investigación Sanitaria, PI080146. Amount: 105.754,00 euros. Duration: 01/01/2009-30/12/2011. Bruix J. Grup de Recerca Consolidat -Oncologia Hepàtica- Barcelona Clinic Liver Cancer (BCLC). Sponsored by: AGAUR. (Generalitat de Catalunya), SGR 1100. Amount: 47.840,00 euros. Duration: 01/01/2009-31/12/2014. Llovet JM. Grup de Recerca SingularRecerca Translacional en Oncologia Hepàtica. Sponsored by: AGAUR (Generalitat de Catalunya), SGR 1186. Amount: 41.600,00 euros. Duration: 01/01/200931/12/2014. Llovet JM. AACR-Landon INNOVATION Award for International Collaborations AACR Annual Meeting, Denver, USA. Sponsored by: American Association for Cancer Research, 0000. Amount: 74.900,00 euros. Duration: 01/06/200901/06/2011. Llovet JM. Genomic predictors and oncogenic drivers in hepatocellular carcinoma. Sponsored by: EUROPEAN COMISSION, 259744. Amount: 796.901,00 euros. Duration: 01/11/2010-30/10/2013. Llovet JM. Oncogenic addiction and gatekeepper genes in hepatocellular carcinoma. Sponsored by: AMERICAN ASSOCIATION FOR CANCER RESEARCH, 09-60-27-LLOV. Amount: 100.000,00 euros. Duration: 01/07/2009-30/06/2011. Thesis Bruix J. Actitud a seguir ante la detección de una lesión focal inferior o igual a 2 cm de tamaño en un paciente con cirrosis hepática. PhD student: Alejandro Forner Gonzalez. Bruix J. Identificación y caracterización de la población de células madre adultas 163 AREA 3 Team involved in: LIVER, DIGESTIVE SYSTEM AND METABOLISM LIVER HEMODYNAMICS AND PORTAL HYPERTENSION. DIGESTIVE BLEEDING SECONDARY TO RUPTURED ESOPHAGEAL VARICOSE VEINS Strategic Objectives Group Members TEAM LEADER Jaume Bosch (Hospital Clínic) Tel.: 93 227 57 90 Fax: 93 227 93 48 E-mail: jbosch@clinic.ub.es Idibaps members: Ramon Deulofeu (Hospital Clínic) Àngels Escorsell (Hospital Clínic) Mercè Fernández Lobato (IDIBAPS) Joan C. García-Pagán (Hospital Clínic) Mª Rosa Gilabert (Hospital Clínic) Carles Nicolau (Hospital Clínic) Juan Manuel Salmerón (Hospital Clínic Juan González-Abraldes (Hospital Clínic) Postdoctoral fellows: Aina Rodríguez (CIBERehd) Jordi Gracia-Sancho (CIBERehd) Research Fellows: Marta Divi (FIS) Marcos Pasarín (FIS) Sebastián Raffa (Fundació Clínic) Eva Erice (CIBERehd) Susana Seijó (Beca Río Hortega) Mario d’Amico (IDIBAPS) Vincenzo La Mura (Fundació Clínic) Lucía Russo (CIBERehd) Andrea Ribeiro (Fundació Clínic) Giusi Marrone (ISCIII) Javier Gallego (CIBERehd) Marc Mejías (SAF) 164 Eugeni Rosado (CIBERehd) Eyal Ashkenazi (CIBERehd) Mª Gabriela Delgado Navas (Fundació Clínic) Marco di Pascoli (EASL) Enric Reverter (Fundació Clínic) Federica Cerini (MRLD) Cintia de Meireles (MRLD) Maeva Guillaume (Aide Jeunes Chercheurs) Dinesh Mani Tripathi (ACI-COLABORA 2009-0938) Technicians: Esther García (CIBERehd) Héctor García (CIBERehd) Montse Monclús (Idibaps) Nursing Staff: Rosa Sáez (CIBERehd) Collaborators: Annalisa Berzigotti (Hospital Clínic) The gaining of in-depth knowledge of the mechanisms underlying portal hypertension – the main complication of liver diseases – and development of new treatments for this syndrome, and new noninvasive assessment techniques. Main Lines of Research 1. Factors regulating liver microcirculation under normal conditions and in cirrhosis, based on isolated liver perfusion studies and studies in liver sinusoid endothelial cells. 2. Intrahepatic endothelial dysfunction in liver cirrhosis. 3. Post-transcriptional regulation of endothelial nitric oxide synthase (eNOS) activity. Relevance in the treatment of portal hypertension. 4. Regulation of the transcription of liver sinusoid endothelial cell protecting genes: relevance in the physiopathology of portal hypertension and in ex vivo liver preservation. 5. Regulation of the development of collateral circulation, hyperdynamic circulation and liver fibrogenesis by angiogenic factors. 6. New noninvasive methods for evaluating cirrhosis. 7. Randomized clinical studies of novel treatments for portal hypertension. 8. Hepatic vascular diseases. AREA 3 Liver, digestive system and metabolism LIVER HEMODYNAMICS AND PORTAL HYPERTENSION. DIGESTIVE BLEEDING SECONDARY TO RUPTURED ESOPHAGEAL VARICOSE VEINS PUBLICATIONS Originals I.F.: 211,12 1 Martinez E, Larrousse M, Podzamczer Tracing of liver venous pressure gradient. RESEARCH GROUP Regulation of liver microcirculation in cirrhosis and hepatic vascular diseases Group Leader: Juan Carlos García-Pagán (Hospital Clínic) One of the mechanisms responsible for the development of portal hypertension and its serious consequences is the increase in portal resistance observed within the cirrhotic liver. Part of this increase is dynamic and amenable to modification by means of drugs. Therefore, improved knowledge based on experimental models in animals of the cellular, biochemical and molecular mechanisms regulating this dynamic component will allow us to design new strategies for the treatment of these disorders.Liver vascular disorders, particularly Budd-Chiari syndrome and non-cirrhotic portal thrombosis, are infrequent causes of portal hypertension. This complicates progress in our knowledge of these illnesses, their prognosis and treatments. This circumstance is of particular relevance, since these diseases mainly affect young patients with a potentially long life expectancy. For a number of years, our group has served as a reference center for these illnesses – thus allowing us to propose new treatment options and to advance in furthering our knowledge. RESEARCH GROUP Angiogenesis in liver diseases Group Leader: Mercè Fernandez Lobato (IDIBAPS) We focus our research on the implication and regulation of angiogenesis in the physiopathology of portal hypertension. Recent studies in experimental models of portal hypertension have shown that angiogenesis or the formation of new blood vessels is crucial to two of the most important components of the physiopathology of portal hypertension: the formation of portosystemic collateral vessels and the development of hyperdynamic splanchnic circulation. The results of these studies may contribute valuable information with a view to improving our knowledge of the molecular mechanisms implicated in the physiopathology of portal hypertension and chronic liver diseases – these being a leading cause of mortality and an important indication for liver transplantation both in this country and worldwide. Our aim is that the studies of this project can lead to the development of new therapeutic approaches designed to reduce the morbidity and mortality of patients diagnosed with these disorders. D, Perez I, Gutierrez F, Lonca M, Barragan P, Deulofeu R, Casamitjana R, Mallolas J, Pich J, Gatell JM. Abacavir-based therapy does not affect biological mechanisms associated with cardiovascular dysfunction. AIDS, 2010. 24:F1-F9. I.F.:4,91. 2 Puig-Pey I, Bohne F, Benitez C, Lopez M, Martinez-Llordella M, Oppenheimer F, Lozano JJ, Gonzalez-Abraldes J, Tisone G, Rimola A, Sanchez-Fueyo A. Characterization of gamma delta T cell subsets in organ transplantation. TRANSPL INT, 2010. 23:1045-1055. I.F.:3,25. 3 Collado S, Coll E, Deulofeu R, Guerrero L, Pons M, Cruzado JM, De LaTorre B, Vera M, Azqueta M, Nicolau C, Cases A. Prevalence of cardiovascular disease in uraemia and relevance of cardiovascular risk factors. NEFROLOGIA, 2010. 30:342-348. I.F.:0,53. 4 Marti J, Fuster J, Hotter G, Sola AM, Deulofeu R, Modolo MM, Loera MA, Ferrer J, Fondevila C, Garcia-Valdecasas JC. Serum neutrophil gelatinase-associated lipocalin in patients with colorectal liver metastases: preliminary results of an exploratory prospective study. INT J BIOL MARKER, 2010. 25:21-26. I.F.:1,42. 5 Sala-Vila A, Cofan M, Perez-Heras A, Nunez I, Gilabert R, Junyent M, MateoGallego R, Cenarro A, Civeira F, Ros E. Fatty acids in serum phospholipids and carotid intima-media thickness in Spanish subjects with primary dyslipidemia. AM J CLIN NUTR, 2010. 92:186-193. I.F.:6,31. 6 Junyent M, Gilabert R, Jarauta E, Nunez I, Cofan M, Civeira F, Pocovi M, Mallen M, Zambon D, Almagro F, Vega J, Tejedor D, Ros E. Impact of low-density lipoprotein receptor mutational class on 165 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM LIVER HEMODYNAMICS AND PORTAL HYPERTENSION. DIGESTIVE BLEEDING SECONDARY TO RUPTURED ESOPHAGEAL VARICOSE VEINS Team Members carotid atherosclerosis in patients with familial hypercholesterolemia. ATHEROSCLEROSIS, 2010. 208:437-441. I.F.:4,52. 7 Melgosa MT, Ricci GL, GarciaPagan JC, Blanco I, Escribano P, Abraldes JG, Roca J, Bosch J, Barbera JA. Acute and Long-Term Effects of Inhaled Iloprost in Portopulmonary Hypertension. LIVER TRANSPLANT, 2010. 16:348-356. I.F.:3,72. 8 Sebastia C, Peri L, Salvador R, Bunesch L, Revuelta I, Alcaraz A, Nicolau C. Multidetector CT of Living Renal Donors: Lessons Learned from Surgeons. RADIOGRAPHICS, 2010. 30:1875-1890. I.F.:2,75. 9 Bellot P, Garcia-Pagan JC, Frances R, Abraldes JG, Navasa M, Perez-Mateo M, Such J, Bosch J. Bacterial DNA Translocation Is Associated With Systemic Circulatory Abnormalities and Intrahepatic Endothelial Dysfunction in Patients With Cirrhosis. HEPATOLOGY, 2010. 52:2044-2052. I.F.:10,84. 10 Carrion JA, Fernandez-Varo G, Bruguera M, Garcia-Pagan JC, GarciaValdecasas JC, Perez-Del-Pulgar S, Forns X, Jimenez W, Navasa M. Serum Fibrosis Markers Identify Patients With Mild and Progressive Hepatitis C Recurrence After Liver Transplantation. GASTROENTEROLOGY, 2010. 138:147-158. I.F.:12,90. 11 Horrillo R, Gonzalez-Periz A, Martinez-Clemente M, Lopez-Parra M, Ferre N, Titos E, Moran-Salvador E, Deulofeu R, Arroyo V, Claria J. 5-Lipoxygenase Activating Protein Signals Adipose Tissue Inflammation and Lipid Dysfunction in Experimental Obesity. J IMMUNOL, 2010. 184:3978-3987. I.F.:5,65. 166 12 Sola E, Lens S, Guevara M, Martin-Llahi M, Fagundes C, Pereira G, Pavesi M, Fernandez J, GonzalezAbraldes J, Escorsell A, Mas A, Bosch J, Arroyo V, Gines P. Hyponatremia in Patients Treated With Terlipressin for Severe Gastrointestinal Bleeding Due to Portal Hypertension. HEPATOLOGY, 2010. 52:1783-1790. I.F.:10,84. 13 Plessier A, Darwish-Murad S, Hernandez-Guerra M, Consigny Y, Fabris F, Trebicka J, Heller J, Morard I, Lasser L, Langlet P, Denninger MH, Vidaud D, Condat B, Hadengue A, Primignani M, Garcia-Pagan JC, Janssen HLA, Valla D. Acute Portal Vein Thrombosis Unrelated to Cirrhosis: A Prospective Multicenter Follow-up Study. HEPATOLOGY, 2010. 51:210218. I.F.:10,84. 14 Tandon P, Saez R, Berzigotti A, Abraldes JG, Garcia-Pagan JC, Bosch J. A Specialized, Nurse-Run Titration Clinic: A Feasible Option for Optimizing beta-Blockade in Non-Clinical Trial Patients. AM J GASTROENTEROL, 2010. 105:1917-1921. I.F.:6,01. 15 Coll M, Martell M, Raurell I, Ezkurdia N, Cuenca S, HernandezLosa J, Esteban R, Guardia J, Bosch J, Genesca J. Atrophy of mesenteric sympathetic innervation may contribute to splanchnic vasodilation in rat portal hypertension. LIVER INT, 2010. 30:593-602. I.F.:2,99. 16 Mehta G, Abraldes JG, Bosch J. Developments and controversies in the management of oesophageal and gastric varices. GUT, 2010. 59:701705. I.F.:9,36. 17 Nicolau C, Bunesch L, Sebastia C, Salvador R. Diagnosis of bladder cancer: contrast-enhanced ultrasound. ABDOM IMAGING, 2010. 35:494-503. I.F.:1,79. 18 Thabut D, D’amico G, Tan P, DeFranchis R, Fabricius S, Lebrec D, Bosch J, Bendtsen F. Diagnostic performance of Baveno IV criteria in cirrhotic patients with upper gastrointestinal bleeding: Analysis of the F7 liver-1288 study population. J HEPATOL, 2010. 53:1029-1034. I.F.:7,82. 19 Garcia-Pagan JC, Caca K, Bureau C, Laleman W, Appenrodt B, Luca A, Abraldes JG, Nevens F, Vinel JP, Mossner J, Bosch J. Early Use of TIPS in Patients with Cirrhosis and Variceal Bleeding.. NEW ENGL J MED, 2010. 362:2370-2379. I.F.:47,05. 20 Pietrobattista A, Luciani M, Abraldes JG, Candusso M, Pancotti S, Soldati M, Monti L, Torre G, Nobili V. Extrahepatic portal vein thrombosis in children and adolescents: Influence of genetic thrombophilic disorders. WORLD J GASTROENTERO, 2010. 16:6123-6127. I.F.:2,09. 21 Mas A, Escorsell A, Fernandez J. Liver Transplantation for Acute Liver Failure: A Spanish Perspective. TRANSPL P, 2010. 42:619-621. I.F.:0,99. 22 Miraglia R, Luca A, Maruzzelli L, Spada M, Riva S, Caruso S, Maggiore G, Gridelli B, Bosch J. Measurement of hepatic vein pressure gradient in children with chronic liver diseases. J HEPATOL, 2010. 53:624-629. I.F.:7,82. 23 Berzigotti A, Bellot P, DeGottardi A, Garcia-Pagan JC, Gagnon C, Spenard J, Bosch J. NCX-1000, a Nitric Oxide-Releasing Derivative of UDCA, Does Not Decrease Portal Pressure in Patients With Cirrhosis: Results of a Randomized, DoubleBlind, Dose-Escalating Study. AM J GASTROENTEROL, 2010. 105:10941101. I.F.:6,01. AREA 3 Liver, digestive system and metabolism LIVER HEMODYNAMICS AND PORTAL HYPERTENSION. DIGESTIVE BLEEDING SECONDARY TO RUPTURED ESOPHAGEAL VARICOSE VEINS 24 To-Figueras J, Lopez RM, Deu- 30 Bargallo X, Carrera A, Sala- lofeu R, Herrero C. Preliminary report Hyperhomocysteinemia in patients with acute intermittent porphyria. METABOLISM, 2010. 59:1809-1810. I.F.:2,59. Blanch X, Santamaria G, Morro R, Llusa M, Gilabert R. Ultrasound-anatomic correlation of the peripheral nerves of the upper limb. SURG RADIOL ANAT, 2010. 32:305-314. I.F.:0,93. 25 Mejias M, Garcia-Pras E, Gallego J, Mendez R, Bosch J, Fernandez M. Relevance of the mTOR signaling pathway in the pathophysiology of splenomegaly in rats with chronic portal hypertension. J HEPATOL, 2010. 52:529-539. I.F.:7,82. 26 Tandon P, Abraldes JG, Berzigotti A, Garcia-Pagan JC, Bosch J. Reninangiotensin-aldosterone inhibitors in the reduction of portal pressure: A systematic review and meta-analysis. J HEPATOL, 2010. 53:273-282. I.F.:7,82. 27 La Mura V, Abraldes JG, Berzigotti A, Erice E, Flores-Arroyo A, Garcia-Pagan JC, Bosch J. Right Atrial Pressure Is Not Adequate to Calculate Portal Pressure Gradient in Cirrhosis: A Clinical-Hemodynamic Correlation Study. HEPATOLOGY, 2010. 51:21082116. I.F.:10,84. 28 Iqbal F, Item CB, Vilaseca MA, Jalan A, Muhl A, Couce ML, Duat A, Delgado MP, Bosch J, Puche A, Campistol J, Pineda M, Bodamer OA. The identification of novel mutations in the biotinidase gene using denaturing high pressure liquid chromatography (dHPLC). MOL GENET METAB, 2010. 100:42-45. I.F.:2,90. 29 Berzigotti A, Abraldes JG, Tandon P, Erice E, Gilabert R, GarciaPagan JC, Bosch J. Ultrasonographic evaluation of liver surface and transient elastography in clinically doubtful cirrhosis. J HEPATOL, 2010. 52:846853. I.F.:7,82. Reviews I.F.: 54,87 1 Garcia-Tsao G, Bosch J. Current Concepts: Management of Varices and Variceal Hemorrhage in Cirrhosis. NEW ENGL J MED, 2010. 362:823832. I.F.:47,05. 2 Bosch J, Abraldes JG, Fernandez M, Garcia-Pagan JC. Hepatic endothelial dysfunction and abnormal angiogenesis: New targets in the treatment of portal hypertension. J HEPATOL, 2010. 53:558-567. I.F.:7,82. Editorials I.F.: 13,83 1 De Gottardi A, Abraldes JG. An uncommon cause of massive scrotal enlargement. LIVER INT, 2010. 30:995-995. I.F.:2,99. 2 Bosch J. Carvedilol for Portal Hypertension in Patients with Cirrhosis. HEPATOLOGY, 2010. 51:2214-2218. I.F.:10,84. Grants for research in progress Garcia-Pagan JC. Mecanismos moleculares de la disfunción endotelial intrahepática en la cirrosis. Nuevas dianas terapéuticas de la hipertensión portal. Sponsored by: Ministerio Educación y Ciencia, SAF2007-61298. Amount: 222.156,00 euros. Duration: 01/10/2007-04/10/2010. Gonzalez-Abraldes J. Insulino resistencia y disfunción endotelial sinusoidal en las hepatopatías crónicas. Mecanismos moleculares y significación clínica. Sponsored by: FIS, PI08/0193. Amount: 42.592,00 euros. Duration: 01/01/2009-30/12/2011. Mercè Fernández Lobato. Regulación de la angiogénesis en la hipertensión portal y la cirrosis hepática. Evaluación de nuevos enfoques terapéuticos. Sponsored by: Ministerio de Ciencia e Innovación, SAF2008-02461. Amount: 121.000,00 euros. Duration: 01/01/2009-01/01/2012. Mercè Fernández Lobato. Regulació de l’angiogènesi en la hipertensió portal. Avaluació de noves estratègies terapèutiques. Sponsored by: Fundació Marató TV3, MARATO-081210. Amount: 118.497,50 euros. Duration: 01/01/2009-01/01/2012. Escorsell A. Eficacia y seguridad de la prótesis esofágica autoexpandible versus sonda-balón de sengstaken como tratamiento hemostático de emergencia en pacientes con hemorragia aguda por varices esofágicas y fracaso del tratamiento farmacólogico y endoscópico. Sponsored by: Fondo de Investigaciones Sanitarias de la Seguridad Social, FIS PI 08/0504. Amount: 0,00 euros. Duration: 01/01/2009-31/12/2011. Bosch J. Reconocimiento GRUP DE RECERCA CONSOLIDAT-AGAUR: “HEMODINAMICA HEPATICA I HIPERTENSIO PORTAL”. Sponsored by: Generalitat de Catalunya, 2009_ SGR_1108. Amount: 47.840,00 euros. Duration: 01/01/2009-31/12/2013. Bosch J. Mecanismos celulares y moleculares en la hipertensión portal no cirrótica. Sponsored by: Ministerio Ciencia e Innovación 167 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM LIVER HEMODYNAMICS AND PORTAL HYPERTENSION. DIGESTIVE BLEEDING SECONDARY TO RUPTURED ESOPHAGEAL VARICOSE VEINS (FCCI-ACI-Colabora), ACI2009-0938. Amount: 95.000,00 euros. Duration: 01/12/2009-30/11/2012. Bosch J. Estudio multicéntrico, aleatorizado, doble-ciego, controlado con placebo, sobre la eficacia del tratamiento de beta-bloqueantes para prevenir la descompensación de la cirrosis con hipertensión portal. Sponsored by: Fondo de Investigación Sanitaria (FIS), EC 08/00091 . Amount: 134.310,00 euros. Duration: 01/01/2009-30/12/2011. Bosch J. Hepatic hemodynamics and portal hypertension in cirrhosis. Advances in the pathophysiology, non-invasive evaluation and therapy. (Clinical & experimental studies). Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1261. Amount: 655.215,00 euros. Duration: 01/01/201031/12/2013. Bosch J. Asociación de estatinas al tratamiento estándar en la prevención de la recidiva hemorrágica en pacientes con cirrosis y hemorragia por varices.. Sponsored by: MINISTERIO DE SANIDAD, POLITICA SOCIAL E IGUALDAD, TRA-074. Amount: 204.000,00 euros. Duration: 01/01/2010-31/12/2011. Bosch J. Estudio multicéntrico, aleatorizado, doble-ciego, controlado con placebo, sobre la eficacia del tratamiento con beta-bloqueantes para la prevención de la descompensación de la cirrosis con hipertensión portal. Sponsored by: INSTITUTO DE SALUD CARLOS III, EC08/00091. Amount: 134.310,00 euros. Duration: 01/01/2009-30/12/2011. 168 Thesis Bosch J. Valor pronóstico de nuevos parámetros hemodinámicos en el tratamiento de la hipertensión portal. PhD student: Vincenzo La Mura. Bosch J, Fernandez M. Implicació de l’ angiogènesi en al patofisiologia de la hipertensió portal. PhD student: Marc Mejias Hernández. Bosch J, Garcia-Pagan JC. Implicaciones pronósticas de la reducción farmacologica de la presión portal en pacientes con cirrosis hepatica. Mecanismos fisiopatologicos de no respuesta a los betabloqueantes y nuevas estrategias terapéuticas. PhD student: Juan Turnes Vázquez. AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM Team involved in: Inflammatory bowel disease (IBD) Group Members TEAM LEADER Julián Panés (Hospital Clínic) Tel.: 93 227 54 18 Fax: 93 227 93 87 E-mail: jpanes@clinic.ub.es Idibaps members: Josep Mª Bordas (Hospital Clínic) Faust Feu (Hospital Clínic) Glòria Lacima (Hospital Clínic) Josep Llach (Hospital Clínic) Josep M. Piqué (Hospital Clínic) Azucena Salas (IDIBAPS) Elena Ricart (Hospital Clínic) Salvadora Delgado (Hospital Clínic) Miquel Sans (IDIBAPS) Strategic Objectives Main Lines of Research The strategic objectives of the research group in inflammatory bowel disease comprise aspects relating to the physiopathology, diagnosis and treatment of these disorders, as specified by the following points: •The development of new treatment strategies for Crohn’s disease and ulcerative colitis, focused on cell therapy and the identification of new therapeutic targets susceptible to pharmacological modulation. •Further in-depth knowledge of the genetic and environmental factors responsible for susceptibility and the course of the disease, with a view to designing personalized therapies. •Optimization of the radiological and biochemical diagnostic techniques with the aim of adapting treatment to the needs of each individual patient, avoiding invasive explorations. 1. Hematopoietic stem cell autotransplantation in refractory Crohn’s disease in conventional treatment and biological therapies. 2. Evaluation of the efficacy and safety of treatment with autologous dendritic cells derived from peripheral blood monocytes in refractory Crohn’s disease. 3. Optimization of magnetic resonance imaging and ultrasound techniques with contrast injection, for evaluation of the extent and severity of the inflammatory lesions in Crohn’s disease and ulcerative colitis. 4. Evaluation of the prognostic value of the magnetic resonance imaging findings in predicting the course of the disease and treatment response. 5. Characterization of the genetic factors determining susceptibility and phenotype in Crohn’s disease and ulcerative colitis. Construction of diagnostic genetic chips. 6. Study of the environmental factors influencing susceptibility and the course of inflammatory bowel disease. Research Fellows: Marisol Veny (Fundació Clínic) Maria del Carme Masamunt (Fundació Clínic) Raquel Cabezón (Fundació Clínic) Rut Mora (IDIBAPS) Technicians: Carolina España (Ciberhed) Miriam Esteller (CIBERehd) Nursing Staff: Susana Pinó (Fundació Clínic) Marta Gallego (Hospital Clínic) Anna Ramírez (CIBERehd) Collaborators: Montserrat Aceituno (Hospital Clínic) Orlando García (Hospital Clínic) Ingrid Ordás (Hospital Clínic) Daniel Benítez (CIBERehd) Culture of intestinal fibroblasts. Vimentin positivity. 169 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM Inflammatory bowel disease (IBD) Team Members PUBLICATIONS Originals I.F.: 115,79 1 Gonzalo V, Lozano JJ, Munoz J, Balaguer F, Pellise M, DeMiguel CR, Andreu M, Jover R, Llor X, Giraldez MD, Ocana T, Serradesanferm A, Alonso-Espinaco V, Jimeno M, Cuatrecasas M, Sendino O, Castellvi-Bel S, Castells A. Aberrant Gene Promoter Methylation Associated with Sporadic Multiple Colorectal Cancer. PLOS ONE, 2010. 5:-. I.F.:4,35. 2 Hanauer SB, Panes J, Colombel JF, Bloomfield R, Schreiber S, Sandborn WJ. Clinical trial: impact of prior infliximab therapy on the clinical response to certolizumab pegol maintenance therapy for Crohn’s disease. ALIMENT PHARM THER, 2010. 32:384-393. I.F.:4,36. 3 Rimola J, Ordas I, Rodriguez S, Panes J. Colonic Crohn’s disease: value of magnetic resonance colonography for detection and quantification of disease activity. ABDOM IMAGING, 2010. 35:422-427. I.F.:1,79. 4 Bujanda L, Sarasqueta C, Hijona E, Hijona L, Cosme A, Gil I, Elorza JL, Asensio JI, Larburu S, Enriquez-Navascues JM, Jover R, Balaguer F, Llor X, Bessa X, Andreu M, Paya A, Castells A. Colorectal cancer prognosis twenty years later. WORLD J GASTROENTERO, 2010. 16:862-867. I.F.:2,09. 5 DelRio AS, Baudet JS, Rodriguez AN, DeLosRios RCF, Franco IS, Tormo JRA, Munoz DS, Llach J, Molina AH, Parra-Blanco A, Acosta JAD. Development and validation of quality standards for colonoscopy. MED CLIN-BARCELONA, 2010. 134:49-56. I.F.:1,23. 6 Sendino O, Fernandez-Esparrach G, Sole M, Colomo L, Pellise M, Llach J, Navarro S, Bordas JM, Gines A. Endoscopic ultrasonography-guided brushing increases cellular diagnosis of pancreatic cysts: A prospective study. DIGEST LIVER DIS, 2010. 42:877-881. I.F.:2,97. 170 7 Fernandez-Esparrach G, Sendino O, Sole M, Pellise M, Colomo L, Pardo A, Martinez-Palli G, Arguello L, Bordas JM, Llach J, Gines A. Endoscopic ultrasoundguided fine-needle aspiration and trucut biopsy in the diagnosis of gastric stromal tumors: a randomized crossover study. ENDOSCOPY, 2010. 42:292-299. I.F.:5,55. 8 Franke A, Mcgovern DPB, Barrett JC, Wang K, Radford-Smith GL, Ahmad T, Lees CW, Balschun T, Lee J, Roberts R, Anderson CA, Bis JC, Bumpstead S, Ellinghaus D, Festen EM, Georges M, Green T, Haritunians T, Jostins L, Latiano A, Mathew CG, Montgomery GW, Prescott NJ, Raychaudhuri S, Rotter JI, Schumm P, Sharma Y, Simms LA, Taylor KD, Whiteman D, Wijmenga C, Baldassano RN, Barclay M, Bayless TM, Brand S, Buning C, Cohen A, Colombel JF, Cottone M, Stronati L, Denson T, DeVos M, D’inca R, Dubinsky M, Edwards C, Florin T, Franchimont D, Gearry R, Glas J, VanGossum A, Guthery SL, Halfvarson J, Verspaget HW, Hugot JP, Karban A, Laukens D, Lawrance I, Lemann M, Levine A, Libioulle C, Louis E, Mowat C, Newman W, Panes J, Phillips A, Proctor DD, Regueiro M, Russell R, Rutgeerts P, Sanderson J, Sans M, Seibold F, Steinhart AH, Stokkers PCF, Torkvist L, Kullak-Ublick G, Wilson D, Walters T, Targan SR, Brant SR, Rioux JD, D’amato M, Weersma RK, Kugathasan S, Griffiths AM, Mansfield JC, Vermeire S, Duerr RH, Silverberg MS, Satsangi J, Schreiber S, Cho JH, Annese V, Hakonarson H, Daly MJ, Parkes M. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. NAT GENET, 2010. 42:1118-U121. I.F.:34,28. 9 Schreiber S, Colombel JF, Bloomfield R, Nikolaus S, Scholmerich J, Panes J, Sandborn WJ. Increased Response and Remission Rates in Short-Duration Crohn’s Disease With Subcutaneous Certolizumab Pegol: An Analysis of PRECiSE 2 Randomized Maintenance Trial Data. AM J GASTROENTEROL, 2010. 105:1574-1582. I.F.:6,01. 10 Veny M, Esteller M, Ricart E, Pique JM, Panes J, Salas A. Late Crohn’s disease patients present an increase in peripheral Th17 cells and cytokine production compared with early patients. ALIMENT PHARM THER, 2010. 31:561-572. I.F.:4,36. 11 Loras C, Gisbert JP, Minguez M, Merino O, Bujanda L, Saro C, Domenech E, Barrio J, Andreu M, Ordas I, Vida L, Bastida G, Gonzalez-Huix F, Piqueras M, Ginard D, Calvet X, Gutierrez A, Abad A, Torres M, Panes J, Chaparro M, Pascual I, Rodriguez-Carballeira M, Fernandez-Banares F, Viver JM, Esteve M. Liver dysfunction related to hepatitis B and C in patients with inflammatory bowel disease treated with immunosuppressive therapy. GUT, 2010. 59:1340-1346. I.F.:9,36. 12 Lacima G, Pera M, Amador A, Escaramis G, Pique JM. Long-term results of biofeedback treatment for faecal incontinence: a comparative study with untreated controls. COLORECTAL DIS, 2010. 12:742-749. I.F.:2,41. 13 Sylla P, Rattner DW, Delgado S, Lacy AM. NOTES transanal rectal cancer resection using transanal endoscopic microsurgery and laparoscopic assistance. SURG ENDOSC, 2010. 24:1205-1210. I.F.:3,31. 14 Lacy A, Ibarzabal A, Pando E, Adelsdorfer C, Delitala A, Corcelles R, Delgado S, Vidal J. Revisional Surgery After Sleeve Gastrectomy. SURG LAPARO ENDO PER, 2010. 20:351-356. I.F.:0,83. 15 Fernandez-Esparrach G, Bordas JM, Giraldez MD, Gines A, Pellise M, Sendino O, Martinez-Palli G, Castells A, Llach J. Severe Complications Limit Long-Term Clinical Success of Self-Expanding Metal Stents in Patients With Obstructive Colorectal Cancer. AM J GASTROENTEROL, 2010. 105:10871093. I.F.:6,01. AREA 3 Liver, digestive system and metabolism Inflammatory bowel disease (IBD) 16 Abuli A, Bessa X, Gonzalez JR, RuizPonte C, Caceres A, Munoz J, Gonzalo V, Balaguer F, Fernandez-Rozadilla C, Gonzalez D, DeCastro L, Clofent J, Bujanda L, Cubiella J, Rene JM, Morillas JD, Lanas A, Rigau J, Garcia AM, Latorre M, Salo J, Banares FF, Arguello L, Pena E, Vilella A, Riestra S, Carreno R, Paya A, Alenda C, Xicola RM, Doyle BJ, Jover R, Llor X, Carracedo A, Castells A, Castellvi-Bel S, Andreu M. Susceptibility Genetic Variants Associated With Colorectal Cancer Risk Correlate With Cancer Phenotype. GASTROENTEROLOGY, 2010. 139:788-U129. I.F.:12,90. 17 Fernandez-Esparrach G, Estepar RS, Guarner-Argente C, Martinez-Palli G, Navarro R, DeMiguel CR, Cordova H, Thompson CC, Lacy AM, Donoso L, Ayuso-Colella JR, Gines A, Pellise M, Llach J, Vosburgh KG. The role of a computed tomography-based image registered navigation system for natural orifice transluminal endoscopic surgery: a comparative study in a porcine model. ENDOSCOPY, 2010. 42:1096-1103. I.F.:5,55. 18 Nunes T, Barreiro-DeAcosta M, Nos P, Marin-Jimenez I, Bermejo F, Ceballos D, Iglesias E, Gomez-Senent S, Torres Y, Ponferrada A, Arevalo JA, Hernandez V, Calvet X, Ginard D, Monfort D, Chaparro M, Mancenido N, Dominguez-Antonaya M, Villalon C, Perez-Calle JL, Munoz C, Nunez H, Carpio D, Aramendiz R, Bujanda L, Estrada-Oncins S, Hermida C, Barrio J, Casis MB, DuenasSadornil MC, Fernandez L, Calvo-Cenizo MM, Botella B, DeFrancisco R, Ayala E, Sans M. Usefulness of oral beclometasone dipropionate in the treatment of active ulcerative colitis in clinical practice: The RECLICU Study. J CROHNS COLITIS, 2010. 4:629-636. I.F.:1,73. 19 Guarner-Argente C, Cordova H, MartinezPalli G, Navarro R, Cuatrecasas M, DeMiguel CR, Beltran M, Lacy AM, Gines A, Pellise M, Llach J, Fernandez-Esparrach G. Yes, we can: reliable colonic closure with the Padlock-G clip in a survival porcine study (with video). GASTROINTEST ENDOSC, 2010. 72:841-844. I.F.:6,71. Reviews I.F.: 4,36 1 Garcia-Bosch O, Ricart E, Panes J. Re- management of Crohn’s disease: Definitions and diagnosis. J CROHNS COLITIS, 2010. 4:7-27. I.F.:1,73. 2 view article: stem cell therapies for inflammatory bowel disease - efficacy and safety. ALIMENT PHARM THER, 2010. 32:939952. I.F.:4,36. Sanjuan X, Salas A, Lloreta J, Walsh PM. Colorectal Cancer OncoGuia: surgical pathology report guidelines. CLIN TRANSL ONCOL. 12:211-213. I.F.:1,15. Editorials Grants for research in progress I.F.: 38,16 1 Lanas A, Calvet X, Feu F, Ponce J, Gisbert JP, Barkun A. First spanish consensus on peptic ulcer bleeding management. MED CLIN-BARCELONA, 2010. 135:608616. I.F.:1,23. 2 Veny M, Salas A, Panes J. Is Lack of “Education” a Mechanism Driving Loss of Tolerance in Crohn’s Disease?. GASTROENTEROLOGY, 2010. 139:1056-1058. I.F.:12,90. 3 Panes J, Ricart E, Rimola J. New MRI modalities for assessment of inflammatory bowel disease. GUT, 2010. 59:1308-1309. I.F.:9,36. 4 Salas A, Panes J. The 2-phase model of Crohn’s disease: from immune defect to hyperresponse. GASTROENTEROLOGY, 2010. 138:1204-1206. I.F.:12,90. 5 Sans M. Trying to Reconcile Genetic Findings with Resistance to Lymphocyte Apoptosis in Crohn’s Disease Pathogenesis. DIGESTION, 2010. 81:244-245. I.F.:1,77. Panes J. Terapia con células dendríticas tolerogénicas en la enfermedad de Crohn refractaria. Sponsored by: MINISTERIO DE EDUCACIÓN, SAF2009_07272. Amount: 254.100,00 euros. Duration: 01/01/2010-31/12/2012. Sans M. ECCO Fellowship 2010 Agreement. Prize awarded to Dr. Sans for ECCO’s interest in supporting future research in the field of “Molecular determinations of homing of stem cells in IBD.”. Sponsored by: European Crohn’s & Colitis Organisation ECCO, 10/311. Amount: 30.000,00 euros. Duration: 09/09/2010-09/09/2011. Panes J. Tratamiento de la enfermedad de Crohn refractaria con células dendríticas reguladoras: estudio piloto.. Sponsored by: MINISTERIO DE SANIDAD, POLITICA SOCIAL E IGUALDAD, TRA-097. Amount: 155.856,00 euros. Duration: 01/01/2010-31/12/2011. Clinical Guidelines Sans M. Estudio de la fibrogénesis intestinal en la enfermedad de Crohn. Evaluación de nuevas estratégias para el tratamiento de la fibrosis intestinal. Sponsored by: MINISTERIO DE EDUCACIÓN, SAF2008-03676. Amount: 84.700,00 euros. Duration: 01/01/2009-31/12/2010. 1 Thesis I.F.: 2,88 VanAssche G, Dignass A, Panes J, Beaugerie L, Karagiannis J, Allez M, Ochsenkuhn T, Orchard T, Rogler G, Louis E, Kupcinskas L, Mantzaris G, Travis S, Stange E. The second European evidencebased Consensus on the diagnosis and Castells A, Pique JM. Prevención del cáncer colorrectal: Nuevas estrategias de cribado, vigilancia y quimioprofilaxis. PhD student: Francisco Rodriguez Moranta. 171 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM Team involved in: Cholestasis and bone pathology Group Members TEAM LEADER Albert Parés (Hospital Clínic) Tel.: 93 227 57 53 Fax: 93 451 55 22 E-mail: apares@clinic.ub.es TEAM LEADER Núria Guanyabens (Hospital Clínic) Tel.: 93 227 54 00 (Ext.: 2235) E-mail: nguana@clinic.ub.es Strategic Objectives Main Lines of Research 1. Study of the epidemiology, pathogen- The research lines of this team are divided into two research groups. esis, diagnosis and treatment of adult chronic cholestatic disorders and autoimmune hepatitis. 2. Knowledge of the pathogenic mechanisms underlying pruritus and osteoporosis in primary biliary cirrhosis. 3. Definition of the therapeutic potential of different artificial liver support procedures in liver failure. 4. Investigation of the pathogenic and therapeutic aspects of metabolic bone diseases. RESEARCH Group Cholestasis Group Leader: Albert Pares (Hospital Clínic) 1. Epidemiology, natural history and therapeutic response of chronic cholestatic disorders in adults. Determination of the prevalence and incidence of cholestatic disorders in adults in Spain, and definition of the factors associated with the forms of presentation of primary biliary cirrhosis – particularly of its asymptomatic forms. Evaluation of the factors conditioning treatment response, and proposition of new treatment regimens in patients showing suboptimum response to ursodeoxycholic acid. Relevance of the anionic exchanger AE2. 2. Diagnosis of autoimmune hepatitis. Development of a new diagnostic procedure for autoimmune hepatitis, based on peptide mapping – a project conducted in collaboration with 6 centers in Europe and one in Israel. Idibaps members: Antoni Mas (Hospital Clínic) M. Lluisa Álvarez (Hospital Clínic) Pilar Peris (Hospital Clínic) Ana Monegal Brancós (Hospital Clínic) Research Fellows: Pau Bosch (Fundació Clínic) Technicians: Marta Dubreuil (CIBERehd) Nursing Staff: Lucia Lorente (CIBERehd) Rosana Ahuir (CIBERehd) Collaborators: Mª Jesús Martinez de Osaba (Hospital Clinic) Àngels Martinez-Ferrer (Hospital Clínic) Silvia Ruiz-Gaspá (CIBERehd) 172 3. Pruritus in chronic cholestasis and treatment response to albumin dialysis: proteomic analysis. Evaluation of treatment response based on albumin dialysis in patients with chronic cholestasis and refractory pruritus, and identification of the eliminated peptides and proteins using MARS. Study of the skin of these patients, in order to identify potential molecules associated with pruritus. Evaluation of the bile acid fractions and their eliminated conjugates based on the MARS system, and their relationship to diminished pruritus. 4. Pathogenesis of osteoporosis and fracture development in primary biliary cirrhosis and other chronic cholestatic disorders. In collaboration with the Bone Metabolic Diseases group, evaluation of the factors underlying fractures in primary biliary cirrhosis, and the proposal of new therapeutic modalities for increasing bone mass. Likewise, investigation is conducted into the repercussion of retained bile acids and bilirubin in cholestasis upon the development of bone disease. 5. Artificial liver support. Evaluation of the safety and efficacy of different bioartificial liver and hepatic support systems in treating acute liver failure and exacerbated chronic liver failure. An open-label, prospective randomized study versus conventional treatment involving cryopreserved human hepatocytes from organs not apt for transplantation. AREA 3 Liver, digestive system and metabolism CHOLESTASIS AND BONE PATHOLOGY PUBLICATIONS ORIGINALS I.F.: 59,69 1 Effect of dialysis with albumin (MARS) on pruritus in patients with chronic cholestasis. VAS: visual analogue scale. RESEARCH GROUP Bone metabolic disease Group Leader: Nuria Guanyabens (Hospital Clínic) 1. Osteoporosis in premenopausal women and in males. Study of the clinical characteristics and mechanisms involved in the development of the disorder. 2. Osteoporosis in primary biliary cirrhosis. Clinical and “in vitro” analysis. Evaluation of the key factors in the low development of bone mass and the appearance of fractures, and proposal of new therapeutic protocols. In addition, evaluation of the effect of bilirubin and bile acids upon primary osteoblasts in culture. 3. Osteoporosis in liver transplantation. Evaluation of the hormonal changes regulating bone remodeling in this pathology. 4. Analysis of the efficacy of vertebroplasty. Evaluation of the clinical usefulness and the complications of this procedure in the treatment of pain secondary to recent vertebral fracture due to osteoporosis. 5. Evaluation of bone remodeling regulators. Evaluation of the role of sclerostin and, through this protein, investigation of the influence of osteocytes upon bone loss associated with glucocorticoid treatment and immobilization. Ruiz-Gaspa S, Guanabens N, Enjuanes A, Peris P, Martinez-Ferrer A, DeOsaba MJM, Gonzalez B, Alvarez L, Monegal A, Combalia A, Pares A. Lithocholic acid downregulates vitamin D effects in human osteoblasts. EUR J CLIN INVEST, 2010. 40:25-34. I.F.:2,64. 2 Enjuanes A, Ruiz-Gaspa S, Peris P, Ozalla D, Alvarez L, Combalia A, DeOsaba MJM, Monegal A, Pares A, Guanabens N. The effect of the alendronate on OPG/RANKL system in differentiated primary human osteoblasts. ENDOCRINE, 2010. 37:180-186. I.F.:1,28. 3 Gay M, Carrascal M, Gorga M, Pares A, Abian J. Characterization of peptides and proteins in commercial HSA solutions. PROTEOMICS, 2010. 10:172-181. I.F.:4,43. 4 Sola E, Lens S, Guevara M, MartinLlahi M, Fagundes C, Pereira G, Pavesi M, Fernandez J, Gonzalez-Abraldes J, Escorsell A, Mas A, Bosch J, Arroyo V, Gines P. Hyponatremia in Patients Treated With Terlipressin for Severe Gastrointestinal Bleeding Due to Portal Hypertension. HEPATOLOGY, 2010. 52:1783-1790. I.F.:10,84. 5 Mas A, Escorsell A, Fernandez J. Liver Transplantation for Acute Liver Failure: A Spanish Perspective. TRANSPL P, 2010. 42:619-621. I.F.:0,99. 6 Hernandez MV, Peris P, Monegal A, Reyes R, Muxi A, Gifre L, Guanabens N. Effects of Intravenous Pamidronate on Renal Function, Bone Mineral Metabolism and Bone Mass in Patients With Severe Osteoporosis. AM J MED SCI, 2010. 339:225-229. I.F.:1,20. 7 Casas F, Borras JM, Ferrer F, Guanyabens N, Gutierrez R, Leon C, Lopez J, Mellado B, Morote J, Puig J, Ribal J, Serra A, Valls V, Zapatero A. Evidencebased consensus recommendations to improve the quality of life in prostate cancer treatment. CLIN TRANSL ONCOL, 2010. 12(5):346-355. I.F.:1,15. 8 Guanabens N, Cerda D, Monegal A, Pons F, Caballeria L, Peris P, Pares A. Low Bone Mass and Severity of Cholestasis Affect Fracture Risk in Patients With Primary Biliary Cirrhosis. GASTROENTEROLOGY, 2010. 138:23482356. I.F.:12,90. 9 Palenzuela L, Mas A, Montaner J, Cordoba J. Matrix Metalloproteinase-9 in Fulminant Hepatic Failure. HEPATOLOGY, 2010. 51:1475-1476. I.F.:10,84. 10 Arboleya L, Diaz-Curiel M, DelRio L, Blanch J, Diez-Perez A, Guanabens N, Quesada JM, Sosa M, Gomez C, Munoz-Torres M, Ramirez E, Combalia J. Prevalence of vertebral fracture in postmenopausal women with lumbar osteopenia using MorphoXpress (R) (OSTEOXPRESS Study). AGING CLIN EXP RES, 2010. 22:419-426. I.F.:1,26. 11 Gabaroi DC, Peris P, Monegal A, Albaladejo C, Martinez MA, Muxi A, DeOsaba MJM, Suris X, Guanabens N. Search for hidden secondary causes in postmenopausal women with osteoporosis. MENOPAUSE, 2010. 17:135-139. I.F.:3,08. 12 Enjuanes A, Ruiz-Gaspa S, Peris P, Ozalla D, Alvarez L, Combalia A, DeOsaba MJM, Monegal A, Pares A, Guanabens N. The effect of the alendronate on OPG/RANKL system in differentiated primary human osteoblasts. ENDOCRINE, 2010. 37:322-328. I.F.:1,28. 173 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM CHOLESTASIS AND BONE PATHOLOGY 13 Pares A, Herrera M, Aviles J, Sanz M, Mas A. Treatment of resistant pruritus from cholestasis with albumin dialysis: Combined analysis of patients from three centers. J HEPATOL, 2010. 53:307-312. I.F.:7,82. Reviews I.F.: 3,05 1 Guanabens N, Pares A. Liver and bone. ARCH BIOCHEM BIOPHYS, 2010. 503:84-94. I.F.:3,05. Grants for research in progress Pares A. Enfermedades hepáticas autoinmunes. Nuevos procedimientos diagnósticos mediante mapeo peptídico. Sponsored by: Instituto de Salud Carlos III, PI07/1318E (E-RARE). Amount: 220.220,00 euros. Duration: 01/01/2008-31/12/2010. Peris P. Efecte de la vertebroplàstia percutània en la qualitat de vida dels pacients amb dolor relacionat amb fractures vertebrals osteoporòtiques. Comparació amb el tractament conservador. Sponsored by: Fundació Marató TV3, 0000. Amount: 149.844,00 euros. Duration: 01/01/2007-01/01/2010. Pares A. Prurito de la colestasis: fisiopatología y análisis proteómico. Sponsored by: Ministerio de Ciencia y Tecnología, SAF200804012. Amount: 96.800,00 euros. Duration: 01/01/2009-31/12/2011. Guanyabens N. Influencia de la bilirrubina y los ácidos biliares sobre la formación ósea. Estudio “in vitro” en osteoblastos humanos. Sponsored by: Ministeri Sanitat i Consum , PI080105. Amount: 91.113,00 euros. Duration: 01/01/2009-30/12/2011. 174 Peris P. Efecte de la vertebroplastia percutània en la qualitat de vida dels pacients amb dolor relacionat amb fractures vertrebals osteroporòtiques. Comparació amb el tractament conservador. Sponsored by: FUNDACIÓ LA MARATÓ DE TV3, 071710. Amount: 149.844,00 euros. Duration: 13/02/2008-30/08/2011. AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM Team involved in: Mitochondrial regulation of cell death and steatohepatitis Group Members TEAM LEADER José Carlos Fernández-Checa (IIBB-CSIC) Tel.: 93 227 57 09 Fax: 93 363 83 01 Idibaps members: Joan Caballeria (Hospital Clínic) Anna Colell (IIBB-CSIC) Carmen García Ruíz (IIBB-CSIC) Montserrat Marí (IDIBAPS) Albert Morales (IIBB-CSIC) Strategic Objectives Main Lines of Research 1. Determination of intracellular signaling and the role of mitochondria in cell susceptibility in inflammation, hypoxia and chemotherapy, and their relevance in relation to liver carcinogenesis. 2. Determination of the mechanisms of cholesterol and sphingolipid participation in hepatocellular death in different disorders such as non-alcoholic steatohepatitis (NASH) or ischemia/ reperfusion damage. 3. Analysis of the role of free cholesterol in patients with non-alcoholic steatohepatitis. 4. Contribution of the physicochemical properties of the mitochondrial membrane in cell death. 1. Ischemia-reperfusion liver cell damage mechanisms and their regulation based on antioxidant and antiinflammatory strategies. 2. Sphingolipid and mitochondrial oxidative stress regulation of cell death. 3. Regulation of cholesterol homeostasis in patients and experimental models of non-alcoholic steatohepatitis. 4. Mechanisms responsible for cholesterol mitochondrial transit. 5. Role of cholesterol in hepatocellular carcinoma response to chemotherapy. 6. Role of cholesterol and mitochondrial GSH in Alzheimer’s disease. 7. Contribution of acid sphingomyelinase to liver fibrosis. Postdoctoral fellows: Laura Conde de la Rosa (CSIC) Claudia Von Montfort (CSIC) Research Fellows: Anna Fernández (McyT) Anna Moles (FIS) Raquel Fucho (CIBERehd) Nuria Matias (MCyT) Nuria Tarrats (FIS) Elisabeth Barbero (CSIC) Cristina Bárcena (IDIBAPS) Laura Martínez (MCyT) Milica Stefanovic (CSIC) Technicians: Susana Núñez Pozuelo (Ciberehd) In vivo analysis of the liver production of reactive oxygen species (ROS) of mitochondrial origin based on two-photon confocal microscopy. The induction of nutritional liver steatosis was carried out by administering a high-cholesterol (HC) diet or a choline-deficient diet (Lombarda) during 48 hours. The administration of DCF and TMRE was carried out via the portal vein, examining the fluorescence emission of both probes in intact liver in vivo with two-photon confocal microscopy. 175 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM MITOCHONDRIAL REGULATION OF CELL DEATH AND STEATOHEPATITIS PUBLICATIONS Originals Three lines in which we have obtained important results are: 1. Alterations of the mitochondrial antioxidants glutathione and S-adenosylmethionine in the development of non-alcoholic steatohepatitis (NASH). A diet deficient in methionine and choline is the typically applied animal model of nonalcoholic steatohepatitis (NASH), since it reflects the steatosis, mitochondrial dysfunction, liver cell damage, oxidative stress, inflammation and fibrosis characteristic of the human disease. Our study in the Journal of Biological Chemistry shows that methionine deficiency is specifically the cause of the decrease in mitochondrial antioxidant defense (glutathione and S-adenosylmethionine) and of the increase in mitochondrial membrane rigidity. These mitochondrial alterations favor liver cell sensitivity to “second impacts” such as the inflammatory cytokines. For this reason, therapies with permeable pro-glutathion compounds can be effective for avoiding the progression of non-alcoholic steatohepatitis. 2. Acid sphingomyelinase participates in the activation of stellate cells and in liver fibrosis. Hepatic stellate cells (HSCs) participate in the development of liver fibrosis through their transdifferentiation/activation to yield myofibroblast-type cells. Acid sphingomyelinase (ASMase) is a known sphingolipid enzyme that regulates liver cell death induced by oxidative stress and through the mediation of death receptors. Our article 176 in the American Journal of Pathology shows that ASMase is activated during HSC activation in parallel to an increase in catepsin B and D processing. The pharmacological inhibition of ASMase or its genic silencing reduces catepsin activation and the trans-differentiation and proliferation of HSCs. In samples from patients with fibrosis induced by non-alcoholic steatohepatitis (NASH), the ASMase/catepsin axis is clearly increased compared with the situation found in healthy subjects. These results point to the importance of the ASMase/ catepsin pathway in HSC activation, and suggest that their antagonism may prove relevant in the treatment of liver fibrosis. 3. Growth arrest-specific 6 (GAS6) protein induces liver protection against murine ischemia/ reperfusion (I/R) damage. While GAS6 is known to promote cell growth and survival during cell repair and the development of different organs, its participation in the protection and posterior repair of liver cell damage caused by ischemia/reperfusion had not been previously explored. Our paper published in Hepatology evidences that GAS6 activates post-ischemic protection mechanisms (AKT) in the liver, and that animals deficient in this protein are highly sensitive to I/R. Moreover, recombinant GAS6 is able to protect the ischemic liver, administered to both wild-strain animals and animals deficient in this protein. Thus, GAS6 appears as a liver protective molecule and as a potential therapeutic target for increasing protection against I/R and possibly also against other hepatotoxic stimuli. I.F.: 70,69 1 Azzalini L, Ferrer E, Ramalho LN, Moreno M, Dominguez M, Colmenero J, Peinado VI, Barbera JA, Arroyo V, Gines P, Caballeria J, Bataller R. Cigarette Smoking Exacerbates Nonalcoholic Fatty Liver Disease in Obese Rats. HEPATOLOGY, 2010. 51:1567-1576. I.F.:10,84. 2 Moreno M, Chaves JF, Sancho-Bru P, Ramalho F, Ramalho LN, Mansego ML, Ivorra C, Dominguez M, Conde L, Millan C, Mari M, Colmenero J, Lozano JJ, Jares P, Vidal J, Forns X, Arroyo V, Caballeria J, Gines P, Bataller R. Ghrelin Attenuates Hepatocellular Injury and Liver Fibrogenesis in Rodents and Influences Fibrosis Progression in Humans. HEPATOLOGY, 2010. 51:974-985. I.F.:10,84. 3 Moles A, Tarrats N, Morales A, Dominguez M, Bataller R, Caballeria J, Garcia-Ruiz C, Fernandez-Checa JC, Mari M. Acidic Sphingomyelinase Controls Hepatic Stellate Cell Activation and in Vivo Liver Fibrogenesis. AM J PATHOL, 2010. 177:1214-1224. I.F.:5,67. 4 Montero J, Mari M, Colell A, Morales A, Basanez G, Garcia-Ruiz C, Fernandez-Checa JC. Cholesterol and peroxidized cardiolipin in mitochondrial membrane properties, permeabilization and cell death. BBA-BIOENERGETICS, 2010. 1797:1217-1224. I.F.:3,69. 5 Llacuna L, Barcena C, BellidoMartin L, Fernandez L, Stefanovic M, Mari M, Garcia-Ruiz C, FernandezCheca JC, DeFrutos PG, Morales A. Growth Arrest-Specific Protein 6 Is Hepatoprotective Against Murine Ischemia/Reperfusion Injury. HEPATOLOGY, 2010. 52:1371-1379. I.F.:10,84. AREA 3 Liver, digestive system and metabolism MITOCHONDRIAL REGULATION OF CELL DEATH AND STEATOHEPATITIS 6 Vazquez-Chantada M, FernandezRamos D, Embade N, MartinezLopez N, Varela-Rey M, Woodhoo A, Luka Z, Wagner C, Anglim PP, Finnell RH, Caballeria J, Laird-Offringa IA, Gorospe M, Lu SC, Mato JM, Martinez-Chantar ML. HuR/MethylHuR and AUF1 Regulate the MAT Expressed During Liver Proliferation, Differentiation, and Carcinogenesis. GASTROENTEROLOGY. 138:1943U97. I.F.:12,90. 7 Barr J, Vazquez-Chantada M, Alonso C, Perez-Cormenzana M, Mayo R, Galan A, Caballeria J, Martin-Duce A, Tran A, Wagner C, Luka Z, Lu SC, Castro A, LeMarchand-Brustel Y, Martinez-Chantar ML, Veyrie N, Clement K, Tordjman J, Gual P, Mato JM. Liquid Chromatography-Mass SpectrometryBased Parallel Metabolic Profiling of Human and Mouse Model Serum Reveals Putative Biomarkers Associated with the Progression of Nonalcoholic Fatty Liver Disease. J PROTEOME RES, 2010. 9:45014512. I.F.:5,13. 8 Rodriguez-Suarez E, Duce AM, Caballeria J, Arrieta FM, Fernandez E, Gomara C, Alkorta N, Ariz U, Martinez-Chantar ML, Lu SC, Elortza F, Mato JM. Non-alcoholic fatty liver disease proteomics. PROTEOM CLIN APPL, 2010. 4:362-371. I.F.:1,88. 9 Fernandez-Checa JC, Fernandez A, Morales A, Mari M, Garcia-Ruiz C, Colell A. Oxidative Stress and Altered Mitochondrial Function in Neurodegenerative Diseases: Lessons From Mouse Models. CNS NEUROL DISORD-DR, 2010. 9:439454. I.F.:3,57. 10 Caballero F, Fernandez A, Matias N, Martinez L, Fucho R, Elena M, Caballeria J, Morales A, Fernandez-Checa JC, Garcia-Ruiz C. Specific Contribution of Methionine and Choline in Nutritional Nonalcoholic Steatohepatitis Impact on mitochondrial S-Adenosyl-L-Methionine and glutathione. J BIOL CHEM, 2010. 285:18528-18536. I.F.:5,33. Reviews I.F.: 10,97 1 Seth D, El-Guindy NBD, Apte M, Mari M, Dooley S, Neuman M, Haber PS, Kundu GC, Darwanto A, DeVilliers WJ, Vonlaufen A, Xu Z, Phillips P, Yang S, Goldstein D, Pirola RM, Wilson JS, Moles A, Fernandez A, Colell A, Garcia-Ruiz C, Fernandez-Checa JC, Meyer C, MeindlBeinker NM. Alcohol, Signaling, and ECM Turnover. ALCOHOL CLIN EXP RES, 2010. 34:4-18. I.F.:3,39. 2 Mari M, Colell A, Morales A, VonMontfort C, Garcia-Ruiz C, Fernandez-Checa JC. Redox Control of Liver Function in Health and Disease. ANTIOXID REDOX SIGN, 2010. 12:1295-1331. I.F.:7,58. Grants for research in progress Mari M. Catepsinas en la Fibrosis Hepática: Regulación por TNF. Sponsored by: Ministerio Sanidad y Consumo, PI070193. Amount: 217.800,00 euros. Duration: 26/11/2007-30/12/2010. Carmen Garcia Ruiz. Papel de los esfingolipidos en la esteatohepatitis no alcohólica y resistencia a la insulina hepática. Sponsored by: Ministerio Educación y Ciencia, SAF200802199. Amount: 100.000,00 euros. Duration: 01/01/2009-31/12/2011. Colell A. Papel del colesterol y la autofagia en la muerte celular inducida por péptidos beta-amiloides. Sponsored by: Ministerio Educación y Ciencia, SAF2008- 04974. Amount: 80.000,00 euros. Duration: 01/01/2009-31/12/2010. García C. Papel de la ceramida y los esfingolípidos en la estetohepatitis. Sponsored by: Fundación de Investigación Médica Mútua Madrileña, 0000. Amount: 21.500,00 euros. Duration: 31/12/2008-30/12/2011. Fernández-Checa JC. Mitochondrial cholesterol and sphingolipids in ALD: trafficking and cross-talk with the ER. Sponsored by: National Institute of Alcohol Abuse and Alcoholism (NIAAA -NIH), P50-AA11999 . Amount: 614.293,00 euros. Duration: 01/01/2009-31/12/2013. Caballeria J. Desarrollo de métodos diagnósticos no invasivos para el diagnóstico y pronóstico de las enfermedades hepáticas inducidas por el alcohol. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1164. Amount: 122.210,00 euros. Duration: 01/01/2010-31/12/2012. Fernández-Checa JC. Mitocondria y cáncer: papel del colesterol, GSH y cardiolipina en la regulación de la permeabilización de la membrana mitocondrial y muerte celular. Sponsored by: Ministerio Educación y Ciencia, SAF200911417. Amount: 359.950,00 euros. Duration: 01/01/2010-31/12/2012. Morales A. Interacción parénquimaestroma en patologías hepáticas asociadas al eje inflamación-cáncer e isquemia/reperfusión: implicaciones terapéuticas. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/00056. Amount: 120.000,00 euros. Duration: 01/01/2010-31/12/2012. 177 AREA 3 Team involved in: LIVER, DIGESTIVE SYSTEM AND METABOLISM LIVER TRANSPLANTATION AND GRAFT VIABILITY Strategic Objectives Group Members Investigation of clinical, mechanistic and therapeutic aspects of liver transplantation. TEAM LEADER Antoni Rimola (Hospital Clínic) Tel.: 93 227 57 53 Fax: 93 451 55 22 E-mail: arimola@clinic.ub.es Main Lines of Research 1. Ischemia-reperfusion liver damage in different models: warm ischemia; experimental liver transplantation in the rat with normal reduced or steatosic grafts; experimental liver transplantation in the pig with whole or partial grafts, or grafts obtained from donors in asystolia; and liver transplantation in humans. 2. Immune suppression, with special interest in three fields: immune tolerance of the allograft, biomarkers of the effects of immune suppressors, and identification of populations with different risks of rejection. Idibaps members: Constantino Fondevila (Hospital Clínic) Juan C. García-Valdecasas (Hospital Clínic) Martí Manyalich (Hospital Clínic) Albert Sánchez Fueyo (Hospital Clínic) Joan Rosselló-Catafau (IIBB-CSIC) Carmen Peralta (IDIBAPS) Brunet, Mercedes (Hospital Clínic) Postdoctoral fellows: Felix Bohne (Deutsche Forschungsgemeinschaft) Isabel Puig-Pey (CIRIT) Araní Casillas (Soc. Catalana de Trasplantament) Susana Padrissa (MCyT) Research Fellows: Lourdes Rafael-Valdivia (Fundació Clínic) Belinda Martínez (Fundació Clínic) Amine Zauali (IDIBAPS) Xavier Muñoz (CIBERehd) Isabel Alfany (IDIBAPS) 178 Mª Carlota Londoño (Hospital Clínic, Premi Final Residència) Ana Teresa Menjívar (Fundació Clínic) Technicians: Anna Rodríguez (CIBEREHD) Mariangeles Bintanel (IDIBAPS) Nursing Staff: Pilar Sesé (IDIBAPS) Collaborators: David Calatayud (Hospital Clínic) Jose Fuster (Hospital Clínic) Marta Massip (CIBERehd) Marta López (IDIBAPS) Olga Millán (CIBEREHD) Chloë Ballesté (UB) Visiting Scientists: Eleonora Boncompagni (EASL) Ex vivo normothermal perfusion machine with oxygenation for the liver. The essential elements are an organ receptacle, a perfusion pump, an oxygenator and a heater. The graft shows the drainage of bile from the perfused liver. AREA 3 Liver, digestive system and metabolism LIVER TRANSPLANTATION AND GRAFT VIABILITY Team Members PUBLICATIONS Originals I.F.: 110,83 1 Puig-Pey I, Bohne F, Benitez C, Lopez M, Martinez-Llordella M, Oppenheimer F, Lozano JJ, GonzalezAbraldes J, Tisone G, Rimola A, Sanchez-Fueyo A. Characterization of gamma delta T cell subsets in organ transplantation. TRANSPL INT, 2010. 23:1045-1055. I.F.:3,25. 2 Baccaro ME, Pepin MN, Guevara M, Colmenero J, Torregrosa JV, Martin-Llahi M, Sola E, Esforzado N, Fuster J, Campistol JM, Arroyo V, Navasa M, Garcia-Valdecasas J, Gines P. Combined liver-kidney transplantation in patients with cirrhosis and chronic kidney disease. NEPHROL DIAL TRANSPL, 2010. 25:2356-2363. I.F.:3,31. 3 Brouard S, Puig-Pey I, Lozano JJ, Pallier A, Braud C, Giral M, Guillet M, Londono MC, Oppenheimer F, Campistol JM, Soulillou JP, Sanchez-Fueyo A. Comparative Transcriptional and Phenotypic Peripheral Blood Analysis of Kidney Recipients Under Cyclosporin A or Sirolimus Monotherapy. AM J TRANSPLANT, 2010. 10:2604-2614. I.F.:6,43. 4 Marti J, Fuster J, Hotter G, Sola AM, Deulofeu R, Modolo MM, Loera MA, Ferrer J, Fondevila C, GarciaValdecasas JC. Serum neutrophil gelatinase-associated lipocalin in patients with colorectal liver metastases: preliminary results of an exploratory prospective study. INT J BIOL MARKER, 2010. 25:21-26. I.F.:1,42. 5 Guillen D, Cofan F, Ros E, Millan O, Cofan M, Brunet M. Biomarker Assessment of the Immunomodulator Effect of Atorvastatin in Stable Renal Transplant Recipients and Hypercholesterolemic Patients. MOL DIAGN THER, 2010. 14:357-366. I.F.:2,17. 6 Benitez CE, Puig-Pey I, Lopez M, Martinez-Llordella M, Lozano JJ, Bohne F, Londono MC, Garcia-Valdecasas JC, Bruguera M, Navasa M, Rimola A, Sanchez-Fueyo A. ATG-Fresenius Treatment and Low-Dose Tacrolimus: Results of a Randomized Controlled Trial in Liver Transplantation. AM J TRANSPLANT, 2010. 10:2296-2304. I.F.:6,43. 7 Ramirez S, Perez-Del-Pulgar S, Carrion JA, Coto-Llerena M, Mensa L, Dragun J, Garcia-Valdecasas JC, Navasa M, Forns X. Hepatitis C virus superinfection of liver grafts: a detailed analysis of early exclusion of nondominant virus strains. J GEN VIROL, 2010. 91:1183-1188. I.F.:3,26. 8 Carrion JA, Torres F, Crespo G, Miquel R, Garcia-Valdecasas JC, Navasa M, Forns X. Liver Stiffness Identifies Two Different Patterns of Fibrosis Progression in Patients with Hepatitis C Virus Recurrence After Liver Transplantation. HEPATOLOGY, 2010. 51:23-34. I.F.:10,84. 9 Carrion JA, Fernandez-Varo G, Bruguera M, Garcia-Pagan JC, Garcia-Valdecasas JC, Perez-Del-Pulgar S, Forns X, Jimenez W, Navasa M. Serum Fibrosis Markers Identify Patients With Mild and Progressive Hepatitis C Recurrence After Liver Transplantation. GASTROENTEROLOGY, 2010. 138:147-158. I.F.:12,90. 10 Padrissa-Altes S, Zaouali MA, Franco-Gou R, Bartrons R, Boillot O, Rimola A, Arroyo V, Rodes J, Peralta C, Rosello-Catafau J. Matrix Metalloproteinase 2 in Reduced-Size Liver Transplantation: Beyond the Matrix. AM J TRANSPLANT, 2010. 10:11671177. I.F.:6,43. 11 Moreno M, Gonzalo T, Kok RJ, Sancho-Bru P, VanBeuge M, Swart J, Prakash J, Temming K, Fondevila C, Beljaars L, Lacombe M, VanDerHoeven P, Arroyo V, Poelstra K, Brenner DA, Gines P, Bataller R. Reduction of Advanced Liver Fibrosis by ShortTerm Targeted Delivery of an Angiotensin Receptor Blocker to Hepatic Stellate Cells in Rats. HEPATOLOGY, 2010. 51:942-952. I.F.:10,84. 12 Fondevila C, Hessheimer AJ, Taura P, Sanchez O, Calatayud D, DeRiva N, Munoz J, Fuster J, Rimola A, Garcia-Valdecasas JC. Portal Hyperperfusion: Mechanism of Injury and Stimulus for Regeneration in Porcine Small-for-Size Transplantation. LIVER TRANSPLANT, 2010. 16:364-374. I.F.:3,72. 13 Taura P, Fuster J, Mercadal J, Martinez-Palli G, Fondevila C, Blasi A, Balust J, Garcia-Valdecasas JC. The use of beta-adrenergic drugs improves hepatic oxygen metabolism in cirrhotic patients undergoing liver resection. J HEPATOL, 2010. 52:340-347. I.F.:7,82. 14 BenMosbah I, Rosello-Catafau J, Alfany-Fernandez I, Rimola A, Parellada PP, Mitjavila MT, Lojek A, BenAbdennebi H, Boillot O, Rodes J, Peralta C. Addition of Carvedilol to University Wisconsin Solution Improves Rat Steatotic and Nonsteatotic Liver Preservation. LIVER TRANSPLANT, 2010. 16:163-171. I.F.:3,72. 15 Vidal O, Valentini M, Ginesta C, Espert JJ, Marti J, Martinez A, Ruiz C, Soliva R, Martrat A, Benarroch G, Garcia-Valdecasas JC. Appendectomy using single-incision laparoscopic surgery: experience in an emergency department. EMERGENCIAS, 2010. 22:361-364. I.F.:3,08. 179 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM LIVER TRANSPLANTATION AND GRAFT VIABILITY Team Members 16 Millan O, Benitez C, Guillen D, Lopez A, Rimola A, Sanchez-Fueyo A, Brunet M. Biomarkers of immunoregulatory status in stable liver transplant recipients undergoing weaning of immunosuppressive therapy. CLIN IMMUNOL, 2010. 137:337-346. I.F.:3,86. 17 Zaouali MA, BenMosbah I, Boncompagni E, BenAbdennebi H, Mitjavila MT, Bartrons R, Freitas I, Rimola A, Rosello-Catafau J. Hypoxia inducible factor-1 alpha accumulation in steatotic liver preservation: Role of nitric oxide. WORLD J GASTROENTERO, 2010. 16:3499-3509. I.F.:2,09. 18 Sanchez-Fueyo A. Identification of tolerant recipients following liver transplantation. INT IMMUNOPHARMACOL, 2010. 10:1501-1504. I.F.:2,21. 19 Zaouali MA, Padrissa-Altes S, BenMosbah I, Alfany-Fernandez I, Massip-Salcedo M, Casillas-Ramirez A, Bintanel-Morcillo M, Boillot O, Serafin A, Rimola A, Rodes J, RoselloCatafau J, Peralta C. Improved Rat Steatotic and Nonsteatotic Liver Preservation by the Addition of Epidermal Growth Factor and Insulin-Like Growth Factor-I to University of Wisconsin Solution. LIVER TRANSPLANT, 2010. 16:1098-1111. I.F.:3,72. 20 Zaouali MA, Padrissa-Altes S, BenMosbah I, BenAbdennebi H, Boillot O, Rimola A, Saidane-Mosbahi D, Rosello-Catafau J. Insulin like growth factor-1 increases fatty liver preservation in IGL-1 solution. WORLD J GASTROENTERO, 2010. 16:5693-5700. I.F.:2,09. 180 21 Pascual J, DelCastillo D, Cabello M, Pallardo L, Grinyo JM, Fernandez AM, Brunet M. Interaction Between Everolimus and Tacrolimus in Renal Transplant Recipients: A Pharmacokinetic Controlled Trial. TRANSPLANTATION, 2010. 89:994-1000. I.F.:3,50. 22 Vidal O, Valentini M, Ginesta C, Marti J, Espert JJ, Benarroch G, Garcia-Valdecasas JC. Laparoendoscopic single-site surgery appendectomy. SURG ENDOSC, 2010. 24:686-691. I.F.:3,31. 23 Zaouali MA, BenMosbah I, BenAbdennebi H, Calvo M, Boncompagni E, Boillot O, Peralta C, Rosello-Catafau J. New Insights Into Fatty Liver Preservation Using Institute Georges Lopez Preservation Solution. TRANSPL P, 2010. 42:159-161. I.F.:0,99. 24 Zaouali MA, BenMosbah I, Padrissa-Altes S, Calvo M, BenAbdennebi H, Saidane-Mosbahi D, Bjaoui M, Garcia-Gil FA, Panisello A, RoselloCatafau J. Relevance of Epidermal Growth Factor to Improve Steatotic Liver Preservation in IGL-1 Solution. TRANSPL P, 2010. 42:3070-3075. I.F.:0,99. 25 Marmol F, Sanchez J, Lopez D, Martinez N, Xaus C, Peralta C, Rosello-Catafau J, Mitjavila MT, PuigParellada P. Role of Oxidative Stress and Adenosine Nucleotides in the Liver of Aging Rats. PHYSIOL RES, 2010. 59:553-560. I.F.:1,43. 26 Manyalich M, Paredes D, Balleste C, Menjivar A. The PIERDUB Project: International Project on Education and Research in Donation at University of Barcelona: Training University Students About Donation and Transplantation. TRANSPL P, 2010. 42:117-120. I.F.:0,99. Reviews I.F.: 5,45 1 Miro JM, Ricart MJ, Trullas JC, Cofan F, Cervera C, Brunet M, Tuset M, Manzardo C, Oppenheimer F, Moreno A. Simultaneous Pancreas-Kidney Transplantation in HIV-infected Patients: A Case Report and Literature Review. TRANSPL P, 2010. 42:3887-3891. I.F.:0,99. 2 Garcia-Valdecasas JC, Fondevila C. In-vivo normothermic recirculation: an update. CURR OPIN ORGAN TRAN, 2010. 15:173-176. I.F.:1,22. 3 Londono MC, Lopez MC, SanchezFueyo A. Minimization of immunosuppression in adult liver transplantation: new strategies and tools. CURR OPIN ORGAN TRAN, 2010. 15:685-690. I.F.:1,22. 4 Zaouali MA, BenAbdennebi H, Padrissa-Altes S, Mahfoudh-Boussaid A, Rosello-Catafau J. Pharmacological strategies against cold ischemia reperfusion injury. EXPERT OPIN PHARMACO, 2010. 11:537-555. I.F.:2,02. Editorials I.F.: 6,43 1 Fondevila C. Is Extracorporeal Support Becoming the New Standard for the Preservation of DCD Grafts?. AM J TRANSPLANT, 2010. 10:1341-1342. I.F.:6,43. Multicentrics I.F.: 33,74 1 Paoletti X, Oba K, Burzykowski T, Michiels S, Ohashi Y, Pignon JP, Rougier P, Sakamoto J, Sargent D, Sasako M, VanCutsem E, Buyse M. Benefit of Adjuvant Chemotherapy for Resectable Gastric Cancer A Meta-analysis. JAMA-J AM MED ASSOC, 2010. 303:1729-1737. I.F.:28,90. AREA 3 Liver, digestive system and metabolism LIVER TRANSPLANTATION AND GRAFT VIABILITY 2 Kuypers DRJ, LeMeur Y, Cantarovich M, Tredger MJ, Tett SE, Cattaneo D, Tonshoff B, Holt DW, Chapman J, VanGelder T. Consensus Report on Therapeutic Drug Monitoring of Mycophenolic Acid in Solid Organ Transplantation. CLIN J AM SOC NEPHRO, 2010. 5:341-358. I.F.:4,84. Grants for research in progress Sanchez A. IP: Reprogramming the Immune System for the Establishment of Tolerance. Sponsored by: European Commision, 512090. Amount: 154.200,00 euros. Duration: 01/09/200728/02/2010. Martorell J, Rimola A, Millan O, Ruiz A. Valor predictivo de parámetros inmológicos pre-trasplante del receptor y de donante en el desarrollo de rechazo e infección en el trasplante hepático. Sponsored by: FIS, PS09/00418. Amount: 92.565,00 euros. Duration: 01/01/201031/12/2012. Sanchez A. Métodos para inducir y diagnosticar la tolerancia inmunológica en el trasplante hepático. Sponsored by: Ministerio de Educación y Ciencia España, Programa I+D, SAF2008-04092. Amount: 130.000,00 euros. Duration: 01/12/2008-31/12/2011. Sanchez A. Effect of rapamycin on tolerance biomarkers in liver transplantation. Sponsored by: Immune Tolerance Network (Consorcio financiado por el National Institute of Health, USA), Sirolimus Liver Tolerance. Amount: 172.932,00 euros. Duration: 01/11/2009-30/11/2011. Sanchez A. Impact of hepatitis C virus infection on tolerance acquisition after liver transplantation. Sponsored by: Roche Organ Transplantation Research Foundation, ROTRF. Amount: 200.000,00 euros. Duration: 01/09/2007-30/09/2010. Fondevila C. Efecto de la modificación farmacológica del flujo portal sobre la aparición del síndrome “small-forsize” en el trasplante hepático en cerdos. Sponsored by: FIS, PI080273. Amount: 74.052,00 euros. Duration: 01/01/2009-30/12/2011. Brunet M. Estudio multicéntrico para la validación de los biomarcadores de elección que reflejen la respuesta individual de los pacientes trasplantados de órganos sólidos al tratamiento inmunosupresor. Sponsored by: Fondo de Investigación Sanitaria, PI080300. Amount: 61.952,00 euros. Duration: 01/01/2008-31/12/2011. Peralta C. Una conservación acuosa para la conservación de órganos. Sponsored by: CIDEM, Generalitat de Catalunya, VALTEC08-2-0033. Amount: 88.203,00 euros. Duration: 01/03/2009-31/03/2011. Peralta C. Regulación del RBP4 en trasplante de higados esteatósicos. Sponsored by: MINISTERIO DE EDUCACIÓN, BFU2009_07410. Amount: 133.100,00 euros. Duration: 01/01/2010-31/12/2012. Peralta C. Mecanismos de protección del precondicionamiento isquémico en el injerto esteatósico. Sponsored by: FIS, PI060021. Amount: 89.540,00 euros. Duration: 01/01/2007-31/03/2010. Thesis Fondevila C, Garcia-Valdecasas JC. La perfusión normotérmica “ex-situ” como continuación de la “Recirculación Normotérmica” en la obtención de injertos hepáticos procedentes de donantes a corazón parado. PhD student: David Calatayud Mizrahi. Peralta C, Rosello-Catafau J. Noves dianes terapèutiques en el trasplantament de fetge amb empelt de mida reduïda. PhD student: Susagna Padrissa Altes. Sanchez-Fueyo A. Phenotypic and transcriptional biomarkets in organ transplantation. PhD student: Isabel Puig-pey Comas. Manyalich M. European living donor psychosocial follow-up (ELIPSY). Sponsored by: Executive Agency for Health and Consumers (EAHC), by the Commission of the European Communities, 20081104. Amount: 498.835,00 euros. Duration: 30/12/200930/05/2012. Rimola A. Valor predictivo de parametros inmunológicos pretrasplante del receptor y del donante en el desarrollo de rechazo e infección en el trasplante hepático. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/0418. Amount: 92.565,00 euros. Duration: 01/01/2010-31/12/2012. 181 AREA 3 Team involved in: LIVER, DIGESTIVE SYSTEM AND METABOLISM GASTROINTESTINAL AND PANCREATIC ONCOLOGY Strategic Objectives Group Members TEAM LEADER Antoni Castells (Hospital Clínic) Tel.: 93 227 57 39 Fax: 93 227 55 89 E-mail: castells@clinic.ub.es The gaining of in-depth knowledge of the mechanisms underlying the development and progression of gastrointestinal and pancreatic premalignant and malignant lesions, with a view to defining new diagnostic, therapeutic and/or preventive strategies. Main Lines of Research Idibaps members: Juan Ramon Ayuso (Hospital Clínic) Sergi Castellví (IDIBAPS) José Ignacio Elizalde (Hospital Clínic) Laureano Fernández-Cruz (Hospital Clínic) Àngels Ginès(Hospital Clínic) Antonio Lacy (Hospital Clínic) Salvador Navarro (Hospital Clínic) Maria Pellisé (Hospital Clínic) Glòria Fernández (Hospital Clínic) Francesc Balaguer Prunes (Hospital Clínic) Postdoctoral fellows: Mariana Rickmann Ashwell (CIBERehd, Hospital Clinic) Research Fellows: Victòria Gonzalo Pascual (Hospital Clínic) Oriol Sendino Garcia (Hospital Clínic) Mª Dolores Giráldez Jiménez (Hospital Clínic) María López-Cerón Pinilla (Fundació Clínic) Xavier Borrat (Hospital Clínic) Leticia Moreira Ruiz (Hospital Clínic) 182 Technicians: Jennifer Muñoz Sancho (CIBERehd, Hospital Clínic) Georgina Ramirez Ramal (Fundació Clínic) Esther Samper Lirola (CIBERehd, Hospital Clínic) Nursing Staff: Teresa Ocaña Bombardo (Hospital Clínic) Cristina Rodríguez de Miguel (Fundació Clínic) Anna Serradesanferm Fabregas (Hospital Clínic) Collaborators: Pere Gambús Cerillo (Hospital Clínic) Eva Vaquero Raya (Hospital Clínic) Virginia Alonso Espinaco (CIBERehd, Hospital Clínic) Meritxell Gironella Cos (CIBERehd. Hospital Clínic) Imma Garrell Lluis (CAPSE) The activity of the research group in gastrointestinal and pancreatic oncology is divided into four areas, and these in turn correspond to different lines of investigation: 1. Physiopathology of colorectal cancer: • Hereditary forms of colorectal cancer, screening and vigilance. • Genetic susceptibility in colorectal cancer. • Epigenetics of colorectal cancer. 2. Physiopathology of pancreatic cancer: • Implication of microRNAs in pancreatic cancer. •Epithelial-mesenchymal transition in the local and metastatic spread of pancreatic cancer. 3. Research and innovation in endoscopy: • Endoscopic ultrasound. • Advanced diagnostic techniques. • Endoscopic therapies. 4. Research and innovation in surgery: • Surgery for colorectal cancer. • Surgery for pancreatic cancer. AREA 3 Liver, digestive system and metabolism GASTROINTESTINAL AND PANCREATIC ONCOLOGY Team Members PUBLICATIONS Originals I.F.: 132,71 1 Balaguer F, Link A, Lozano JJ, Cuatrecasas M, Nagasaka T, Boland CR, Goel A. Epigenetic Silencing of miR-137 Is an Early Event in Colorectal Carcinogenesis. CANCER RES, 2010. 70:6609-6618. I.F.:7,54. 2 Sanchez-Tillo E, Lazaro A, Torrent R, Cuatrecasas M, Vaquero EC, Castells A, Engel P, Postigo A. ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1. ONCOGENE, 2010. 29:3490-3500. I.F.:7,14. 3 Arostegui JI, Saldana MDL, Pascal M, Clemente D, Aymerich M, Balaguer F, Goel A, DelCastillo CF, Rius J, Plaza S, Robledillo JCL, Juan M, Ibanez M, Yague J. A Somatic NLRP3 Mutation as a Cause of a Sporadic Case of Chronic Infantile Neurologic, Cutaneous, Articular Syndrome/Neonatal-Onset Multisystem Inflammatory Disease Novel Evidence of the Role of LowLevel Mosaicism as the Pathophysiologic Mechanism Under. ARTHRITIS RHEUM-US, 2010. 62:1158-1166. I.F.:7,33. 4 Plessier A, Darwish-Murad S, Hernandez-Guerra M, Consigny Y, Fabris F, Trebicka J, Heller J, Morard I, Lasser L, Langlet P, Denninger MH, Vidaud D, Condat B, Hadengue A, Primignani M, Garcia-Pagan JC, Janssen HLA, Valla D. Acute Portal Vein Thrombosis Unrelated to Cirrhosis: A Prospective Multicenter Follow-up Study. HEPATOLOGY, 2010. 51:210-218. I.F.:10,84. 5 Gonzalo V, Lozano JJ, Munoz J, Balaguer F, Pellise M, DeMiguel CR, Andreu M, Jover R, Llor X, Giraldez MD, Ocana T, Serradesanferm A, Alonso-Espinaco V, Jimeno M, Cuatrecasas M, Sendino O, Castellvi-Bel S, Castells A. Aberrant Gene Promoter Methylation Associated with Sporadic Multiple Colorectal Cancer. PLOS ONE, 2010. 5:-. I.F.:4,35. 6 Bujanda L, Sarasqueta C, Hijona E, Hijona L, Cosme A, Gil I, Elorza JL, Asensio JI, Larburu S, Enriquez-Navascues JM, Jover R, Balaguer F, Llor X, Bessa X, Andreu M, Paya A, Castells A. Colorectal cancer prognosis twenty years later. WORLD J GASTROENTERO, 2010. 16:862-867. I.F.:2,09. 7 Sendino O, Fernandez-Esparrach G, Sole M, Colomo L, Pellise M, Llach J, Navarro S, Bordas JM, Gines A. Endoscopic ultrasonography-guided brushing increases cellular diagnosis of pancreatic cysts: A prospective study. DIGEST LIVER DIS, 2010. 42:877-881. I.F.:2,97. 8 Fernandez-Esparrach G, Sendino O, Sole M, Pellise M, Colomo L, Pardo A, MartinezPalli G, Arguello L, Bordas JM, Llach J, Gines A. Endoscopic ultrasound-guided fine-needle aspiration and trucut biopsy in the diagnosis of gastric stromal tumors: a randomized crossover study. ENDOSCOPY, 2010. 42:292299. I.F.:5,55. 9 Sylla P, Rattner DW, Delgado S, Lacy AM. NOTES transanal rectal cancer resection using transanal endoscopic microsurgery and laparoscopic assistance. SURG ENDOSC, 2010. 24:1205-1210. I.F.:3,31. 10 Lacy A, Ibarzabal A, Pando E, Adelsdorfer C, Delitala A, Corcelles R, Delgado S, Vidal J. Revisional Surgery After Sleeve Gastrectomy. SURG LAPARO ENDO PER, 2010. 20:351-356. I.F.:0,83. 11 Fernandez-Esparrach G, Bordas JM, Giraldez MD, Gines A, Pellise M, Sendino O, Martinez-Palli G, Castells A, Llach J. Severe Complications Limit Long-Term Clinical Success of Self-Expanding Metal Stents in Patients With Obstructive Colorectal Cancer. AM J GASTROENTEROL, 2010. 105:10871093. I.F.:6,01. 12 Abuli A, Bessa X, Gonzalez JR, RuizPonte C, Caceres A, Munoz J, Gonzalo V, Balaguer F, Fernandez-Rozadilla C, Gonzalez D, DeCastro L, Clofent J, Bujanda L, Cubiella J, Rene JM, Morillas JD, Lanas A, Rigau J, Garcia AM, Latorre M, Salo J, Banares FF, Arguello L, Pena E, Vilella A, Riestra S, Carreno R, Paya A, Alenda C, Xicola RM, Doyle BJ, Jover R, Llor X, Carracedo A, Castells A, Castellvi-Bel S, Andreu M. Susceptibility Genetic Variants Associated With Colorectal Cancer Risk Correlate With Cancer Phenotype. GASTROENTEROLOGY, 2010. 139:788U129. I.F.:12,90. 183 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM GASTROINTESTINAL AND PANCREATIC ONCOLOGY Team Members 13 Fernandez-Esparrach G, Estepar RS, Guarner-Argente C, Martinez-Palli G, Navarro R, DeMiguel CR, Cordova H, Thompson CC, Lacy AM, Donoso L, Ayuso-Colella JR, Gines A, Pellise M, Llach J, Vosburgh KG. The role of a computed tomography-based image registered navigation system for natural orifice transluminal endoscopic surgery: a comparative study in a porcine model. ENDOSCOPY, 2010. 42:1096-1103. I.F.:5,55. 18 tinez-Palli G, Navarro R, Cuatrecasas M, DeMiguel CR, Beltran M, Lacy AM, Gines A, Pellise M, Llach J, Fernandez-Esparrach G. Yes, we can: reliable colonic closure with the Padlock-G clip in a survival porcine study (with video). GASTROINTEST ENDOSC, 2010. 72:841-844. I.F.:6,71. Fernandez-Rozadilla C, Tarrio R, Clofent J, DeCastro L, Brea-Fernandez A, Bessa X, Abuli A, Andreu M, Jover R, Xicola R, Llor X, Castells A, Castellvi-Bel S, Carracedo A, Ruiz-Ponte C. Colorectal Cancer Susceptibility Quantitative Trait Loci in Mice as a Novel Approach to Detect LowPenetrance Variants in Humans: A Two-Stage Case-Control Study. CANCER EPIDEM BIOMAR, 2010. 19:619-623. I.F.:4,31. 15 Fernández-Esparrach G, Matthes 19 Obstein KL, Martins FP, Fernandez- EL, Maurice D, Enderle M, Thompson CC, Carr-Locke DL. A novel device for endoscopic submucosal dissection that combines water-jet submucosal hydrodissection and elevation with electrocautery: initial experience in a porcine model. GASTROINTEST ENDOSC, 2010. 71:615-618. I.F.:6,71. Esparrach G, Thompson CC. Endoscopic ultrasound-guided celiac plexus neurolysis using a reverse phase polymer. WORLD J GASTROENTERO, 2010. 16:728-731. I.F.:2,09. 14 Guarner-Argente C, Cordova H, Mar- 16 Alfaro I, Ocana T, Castells A, Cordero C, Ponce M, Cajal TRY, Andreu M, Bujanda L, Herraiz M, Molina AJH, FernandezBanares F, Riestra-Menendez S, Gargallo C, Ruiz A, Bustamante M, Blanco I, DeJuan FM. Characteristics of patients with familial adenomatous polyposis in Spain. First results of the Spanish Registry of Familial Adenomatous Polyposis. MED CLIN-BARCELONA, 2010. 135:103-108. I.F.:1,23. 17 Tomlinson IPM, Dunlop M, Campbell H, Zanke B, Gallinger S, Hudson T, Koessler T, Pharoah PD, Niittymaki I, Tuupanen S, Aaltonen LA, Hemminki K, Lindblom A, Forsti A, Sieber O, Lipton L, VanWezel T, Morreau H, Wijnen JT, Devilee P, Matsuda K, Nakamura Y, CastellviBel S, Ruiz-Ponte C, Castells A, Carracedo A, Ho JWC, Sham P, Hofstra RMW, Vodicka P, Brenner H, Hampe J, Schafmayer C, Tepel J, Schreiber S, Volzke H, Lerch MM, 184 Schmidt CA, Buch S, Moreno V, Villanueva CM, Peterlongo P, Radice P, Echeverry MM, Velez A, Carvajal-Carmona L, Scott R, Penegar S, Broderick P, Tenesa A, Houlston RS. COGENT (COlorectal cancer GENeTics): an international consortium to study the role of polymorphic variation on the risk of colorectal cancer. BRIT J CANCER, 2010. 102:447-454. I.F.:4,35. 20 Link A, Balaguer F, Shen Y, Nagasaka T, Lozano JJ, Boland CR, Goel A. Fecal MicroRNAs as Novel Biomarkers for Colon Cancer Screening. CANCER EPIDEM BIOMAR, 2010. 19:1766-1774. I.F.:4,31. 21 Maurel J, Martins AS, Poveda A, Lopez-Guerrero JA, Cubedo R, Casado A, Martinez-Trufero J, Ayuso JR, LopezPousa A, Garcia-Albeniz X, DelMuro XG, De Alava E. Imatinib Plus Low-Dose Doxorubicin in Patients With Advanced Gastrointestinal Stromal Tumors Refractory to High-Dose Imatinib A Phase I-II Study by the Spanish Group for Research on Sarcomas. CANCER-AM CANCER SOC, 2010. 116:3692-3701. I.F.:5,42. 22 Perez-Carbonell L, Alenda C, Paya A, Castillejo A, Barbera VM, Guillen C, Rojas E, Acame N, Gutierrez-Avino FJ, Castells A, Llor X, Andreu M, Soto JL, Jover R. Methylation Analysis of MLH1 Improves the Selection of Patients for Genetic Testing in Lynch Syndrome. J MOL DIAGN, 2010. 12:498-504. I.F.:3,41. 23 Borras E, Pineda M, Blanco I, Jewett EM, Wang F, Teule A, Caldes T, Urioste M, Martinez-Bouzas C, Brunet J, Balmana J, Torres A, Cajal TRY, Sanz J, Perez-Cabornero L, Castellvi-Bel S, Alonso A, Lanas A, Gonzalez S, Moreno V, Gruber SB, Rosenberg NA, Mukherjee B, Lazaro C, Capella G. MLH1 Founder Mutations with Moderate Penetrance in Spanish Lynch Syndrome Families. CANCER RES, 2010. 70:7379-7391. I.F.:7,54. 24 Mora M, Ricart MJ, Casamitjana R, Astudillo E, Lopez I, Jimenez A, Fernandez-Cruz L, Esmatjes E. Pancreas and kidney transplantation: long-term endocrine function. CLIN TRANSPLANT, 2010. 24:E236-E240. I.F.:2,00. 25 Moize V, Moize L, Lacy A, Vidal J. Pica secondary to iron deficiency 1 year after gastric bypass. SURG OBES RELAT DIS, 2010. 6:316-318. I.F.:3,86. 26 Fernandez-Rozadilla C, DeCastro L, Clofent J, Brea-Fernandez A, Bessa X, Abuli A, Andreu M, Jover R, Xicola R, Llor X, Castells A, Castellvi-Bel S, Carracedo A, Ruiz-Ponte C. Single Nucleotide Polymorphisms in the Wnt and BMP Pathways and Colorectal Cancer Risk in a Spanish Cohort. PLOS ONE, 2010. 5:-. I.F.:4,35. Reviews I.F.: 4,25 1 Link A, Balaguer F, Goel A. Cancer chemoprevention by dietary polyphenols: Promising role for epigenetics. BIOCHEM PHARMACOL, 2010. 80:1771-1792. I.F.:4,25. Editorials I.F.: 12,89 1 Castellvi-Bel S, Castells A. Differential risk depending on parental origin: a new layer of complexity for genetic susceptibility variants. GASTROENTEROLOGY, 2010. 139:689-690. I.F.:12,90. AREA 3 Liver, digestive system and metabolism GASTROINTESTINAL AND PANCREATIC ONCOLOGY Clinical Guidelines I.F.: 10,41 1 Navarro S, Vaquero E, Maurel J, Bombi JA, DeJuan C, Feliu J, Cruz LF, Gines A, Girela E, Rodriguez R, Sabater L. Recommendations for diagnosis, staging and treatment of pancreatic cancer (Part I). Grupo Español de Consenso en Cáncer de Páncreas. MED CLIN-BARCELONA, 2010. 134:643-655. I.F.:1,23. 2 Navarro S, Vaquero E, Maurel J, Bombi JA, DeJuan C, Feliu J, Cruz LF, Gines A, Girela E, Rodriguez R, Sabater L. Recommendations for diagnosis, staging and treatment of pancreatic cancer (Part II). MED CLIN-BARCELONA, 2010. 134:692-702. I.F.:1,23. 3 Balmana J, Castells A, Cervantes A. Familial colorectal cancer risk: ESMO Clinical Practice Guidelines. ANN ONCOL, 2010. 21:v78-v81. I.F.:5,65. 4 Sanjuan X, Salas A, Lloreta J, Walsh PM. Colorectal Cancer OncoGuia: surgical pathology report guidelines. CLIN TRANSL ONCOL, 2010. 12:211-213. I.F.:1,15. 5 ManchonWalsh P, Borras JM, Ferro T, Espinas JA. Colorectal Cancer OncoGuia. CLIN TRANSL ONCOL. 12:188-210. I.F.:1,15. Grants for research in progress Castells A. Cribado del cáncer colorrectal en población de riesgo intermedio: estudio multicéntrico, aleatorizado y controlado en el que se compara la prueba de detección de sangre oculta en heces mediante método inmunológico y la colonoscopia. Sponsored by: Fundación de la Asociación Española Contra el Cáncer (AECC), AECC_07/185. Amount: 300.000,00 euros. Duration: 01/03/2007-30/06/2011. Castells A. Hipermetilación de la región promotora de los genes MLH1, MGMT, CDKN2A, RASSF1A, CDX1 y SFRP1 en mucosa colorrectal no tumoral como factor favorecedor del desarrollo del cáncer colorrectal. Sponsored by: Comisión Interministerial de Ciencia y Tecnologia (CICYT), SAF-200764873. Amount: 145.200,00 euros. Duration: 02/07/2007-31/12/2010. Castellvi S, Castells A, Balaguer F, Giraldez M, Ocaña T. Caracterización clínica, histológica y molecular del cáncer colorrectal diagnosticado antes de los 50 años. Sponsored by: Fundación Investigación Médica Mutua Madrileña, PI040296. Amount: 30.000,00 euros. Duration: 15/07/2008-15/07/2010. Castellvi S, Castells A, Balaguer F, Gonzalo V. Genetic study of common hereditary bowel cancers in Hispania and the Americas (CHIBCHA). Sponsored by: European Commission, 7th Framework Programme, PI040378. Amount: 63.338,00 euros. Duration: 01/06/2009-30/11/2012. Fernandez M, Almela M, Bombi JA, Delgado S, Filella X, Gines A, Lacy A, Llach J, Martinez G, Rodriguez C, Pellise M. Estudio comparativo de los cambios fisiológicos e inmunológicos de la NOTES utilizando diferentes vías de acceso versus la laparoscopia. Sponsored by: Instituto de Salud Carlos III, PI08/90026. Amount: 97.526,00 euros. Duration: 01/01/2009-01/06/2010. Gironella M, Castells A, Navarro S, Miquel R, Gines A, Alonso V, Gonzalo V. Implicación de los microRNAs en la fisiopatología y quimioresistencia del cáncer de páncreas. Sponsored by: Fundación Mutua Madrileña, FMM-MG2008-11. Amount: 50.000,00 euros. Duration: 31/07/2008-31/07/2011. Castells A. Grup de Recerca en Oncología Gastrointestinal i Pancreàtica . Sponsored by: Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR), 2009-SGR849. Amount: 50.960,00 euros. Duration: 01/07/2009-30/06/2014. Vaquero EC, Rickmann M, Navarro S, Miquel R. Transición Epitelio-Mesénquima y reclutamiento de fibrocitos en el desarrollo y extensión del cáncer de Páncreas. Sponsored by: Instituto de Salud Carlos III, PI080280. Amount: 70.543,00 euros. Duration: 01/01/2008-31/12/2010. Castellvi S, Pique JM, Giraldez M, Ocaña T. Componentes genéticos comunes y de baja penetrancia implicados en cáncer colorrectal: correlación genotipo-fenotipo e identificación de variantes genómicas de riesgo. Sponsored by: Fondo de Investigación Sanitaria, FIS08/0024. Amount: 95.469,00 euros. Duration: 01/01/2009-31/12/2011. Castells A. Convenio de colaboración entre la Fundació Clínic y la AECC para el proyecto “Cribado del cáncer colorrectal en población de riesgo intermedio: estudio multicéntrico, aleatorizado y controlado en el que se compara la prueba de detección de sangre oculta e. Sponsored by: Asociación Española Contra el Cáncer, CP040377. Amount: 60.000,00 euros. Duration: 09/10/2008-30/06/2011. Castells A. Subproductos de la desinfección y otros determinantes ambientales, genéticos y moleculares del cáncer colorrectal. Sponsored by: Instituto de Salud Carlos III, PI080533. Amount: 244.420,00 euros. Duration: 01/01/2009-31/12/2012. Pellise M. Implicación de los focos de criptas aberrantes en la carcinogénesis colorrectal: estudio morfológico con técnicas de endoscopia avanzada y caracterización molecular. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/0669. Amount: 68.365,00 euros. Duration: 01/01/2010-31/12/2012. Thesis Castells A, Navarro S. Neoplasias quísticas del páncreas: Análisis descriptivo y factores predictivos de malignidad. PhD student: Ana Celia Adet Caldelari. Vaquero E. Estudio de los tocotrienoles como inductores de muerte programada en las células estrelladas del páncreas. PhD student: Mariana Rickmann Ashwell. Castells A, Pique JM. Prevención del cáncer colorrectal: Nuevas estrategias de cribado, vigilancia y quimioprofilaxis. PhD student: Francisco Rodriguez Moranta. 185 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM Team envolved in: CIBER en enfermedades raras (CIBERer) Hereditary metabolic diseases Strategic Objectives Group Members TEAM LEADER Antonia Ribes (Hospital Clínic) Tel.: 93 227 56 72 (Ext.: 9340) Fax: 93 227 56 68 E-mail: aribes@clinic.ub.es The strategic objective of our group is to investigate the genetic and biochemical bases, as well as the physiopathological mechanisms, of hereditary metabolic diseases. The ultimate aim is to develop new diagnostic and therapeutic strategies. On the other hand, we conducttranslational research, stimulating the transfer of knowledge from basic research to the clinical practice setting, and vice versa. Main Lines of Research Idibaps members: Paz Briones (CSIC) Laura Gort (Hospital Clínic) Teresa Pàmpols (Hospital Clínic) Mª Josep Coll (Hospital Clínic) Postdoctoral fellows: Frederic Tort (CIBERer) Aleix Navarro-Sastre (CIBERer) Angela Arias (CIBERer) Research Fellows: Judith Macías (Fundació Niemann Pick) Nuria Bujan (FIS) Aida Font (FIS) Leslie Matalonga (Fundació Clínic) Within the general line of hereditary metabolic diseases, our concrete research lines are based on the following: 1. In vitro therapeutic approaches. This study involves the testing of chemical and peptide libraries. Selection has been made of disease stop mutations and mis-sense mutations previously identified by our group. We make use of fibroblasts IPI cells and neuron cultures as cell models. 2. CoQ10 deficiency. We are carrying out the biochemical selection of patients with CoQ10 deficiency, based on the study of the mitochondrial respiratory chain and the analysis of the metabolic pathways, using stable isotopes in fibroblasts from the previously selected patients. Posteriorly, in patients that prove negative for mutations of the genes known to date, an exome analysis will be made to identify the gene causing the disease. 3. Cerebral creatine deficiency. Our group has been a pioneer in the identification of patients with cerebral creatine deficiency. At present we are centered on the evaluation of different creatine derivatives with the purpose of establishing a treatment for creatine transport deficiency. these creatine uptake studies are carried out in neurons derived from IPI cells and HUVEC and HBMEC cells silenced with interference RNA. 4. mtDNA depletion. A nucleotide metabolic defect may give rise to mitochondrial DNA depletion. Since we have identified patients with these characteristics, without mutations of the genes known to date, our objective is to explore new genes capable of explaining the disease. 5. Type C Niemann-Pick disease. The study of patients with this disorder has been carried out in a knock-in murine model, with a view to gaining further knowledge of the underlying physiopathology. On the other hand, this model will be used to test different drugs that act upon proteosomal degradation. Collaborators: Marisa Girós (Hospital Clínic) Judit Garcia-Villoria (Hospital Clínic) José Luis Marin (Hospital Clínic) Rosa Maria López (Hospital Clínic) Calculation of the number of mitochondrial DNA copies, based on real-time PCR. 186 AREA 3 Liver, digestive system and metabolism HEREDITARY METABOLIC DISEASES Team Members PUBLICATIONS Originals I.F.: 59,95 1 Navarro-Sastre A, Garcia-Silva MT, Martin-Hernandez E, Lluch M, Briones P, Ribes A. Functional splicing assay supporting that c.70 + 5G > A mutation in the MPV17 gene is disease causing. J INHERIT METAB DIS, 2010. :-. I.F.:3,60. 2 Puisac B, Arnedo M, Casale CH, Ribate MP, Castiella T, Ramos FJ, Ribes A, Perez-Cerda C, Casals N, Hegardt FG, Pie J. Differential HMG-CoA lyase expression in human tissues provides clues about 3-hydroxy-3-methylglutaric aciduria. J INHERIT METAB DIS, 2010. 33:405-410. I.F.:3,60. 3 Fons C, Arias A, Sempere A, Poo P, Pineda M, Mas A, Lopez-Sala A, Garcia-Villoria J, Vilaseca MA, Ozaez L, Lluch M, Artuch R, Campistol J, Ribes A. Response to creatine analogs in fibroblasts and patients with creatine transporter deficiency. MOL GENET METAB, 2010. 99:296-299. I.F.:2,90. 4 Pineda M, Montero R, Aracil A, O’callaghan MM, Mas A, Espinos C, Martinez-Rubio D, Palau F, Navas P, Briones P, Artuch R. Coenzyme Q(10)Responsive Ataxia: 2-Year-Treatment Follow-up. MOVEMENT DISORD, 2010. 25:1262-1268. I.F.:4,01. 5 Quintana E, Pineda M, Font A, Vilaseca MA, Tort F, Ribes A, Briones P. Dihydrolipoamide dehydrogenase (DLD) deficiency in a Spanish patient with myopathic presentation due to a new mutation in the interface domain. J INHERIT METAB DIS, 2010. :-. I.F.:3,60. 6 VanKuilenburg ABP, Dobritzsch D, Meijer J, Meinsma R, Benoist JF, Assmann B, Schubert S, Hoffmann GF, Duran M, DeVries MC, Kurlemann G, Eyskens FJM, Greed L, Sass JO, Schwab KO, Sewell AC, Walter J, Hahn A, Zoetekouw L, Ribes A, Lind S, Hennekam RCM. Dihydropyrimidinase deficiency: Phenotype, genotype and structural consequences in 17 patients. BBA-MOL BASIS DIS, 2010. 1802:639-648. I.F.:4,14. 7 Serra-Perez A, Planas AM, NunezO’mara A, Berra E, Garcia-Villoria J, Ribes A, Santalucia T. Extended ischemia prevents HIF1alpha degradation at reoxygenation by impairing prolyl-hydroxylation: role of Krebs cycle metabolites. J BIOL CHEM, 2010. 285:18217-18224. I.F.:5,33. 8 Marti R, Nascimento A, Colomer J, Lara MC, Lopez-Gallardo E, RuizPesini E, Montoya J, Andreu AL, Briones P, Pineda M. Hearing Loss in a Patient With the Myopathic Form of Mitochondrial DNA Depletion Syndrome and a Novel Mutation in the TK2 Gene. PEDIATR RES, 2010. 68:151154. I.F.:2,61. 9 Pampols T. Inherited Metabolic Rare Disease. ADV EXP MED BIOL, 2010. 686:397-431. I.F.:2,02. 10 Serrano M, Garcia-Silva MT, Martin-Hernandez E, O’callaghan MD, Quijada P, Martinez-Aragon A, Ormazabal A, Blazquez A, Martin MA, Briones P, Lopez-Gallardo E, RuizPesini E, Montoya J, Artuch R, Pineda M. Kearns-Sayre syndrome: Cerebral folate deficiency, MRI findings and new cerebrospinal fluid biochemical features. MITOCHONDRION, 2010. 10:429-432. I.F.:4,15. 11 Urreizti R, Moya-Garcia AA, Pino-Angeles A, Cozar M, Langkilde A, Fanhoe U, Esteves C, Arribas J, Vilaseca MA, Perez-Duenas B, Pineda M, Gonzalez V, Artuch R, Baldellou A, Vilarinho L, Fowler B, Ribes A, Sanchez-Jimenez F, Grinberg D, Balcells S. Molecular characterization of five patients with homocystinuria due to severe methylenetetrahydrofolate reductase deficiency. CLIN GENET, 2010. 78:441-448. I.F.:3,30. 12 Quintana E, Gort L, Busquets C, Navarro-Sastre A, Lissens W, Moliner S, Lluch M, Vilaseca MA, DeMeirleir L, Ribes A, Briones P. Mutational study in the PDHA1 gene of 40 patients suspected of pyruvate dehydrogenase complex deficiency. CLIN GENET, 2010. 77:474-482. I.F.:3,30. 13 Serrano M, Martins C, PerezDuenas B, Gomez-Lopez L, Murgui E, Fons C, Garcia-Cazorla A, Artuch R, Jara F, Arranz JA, Haberle J, Briones P, Campistol J, Pineda M, Vilaseca MA. Neuropsychiatric Manifestations in Late-Onset Urea Cycle Disorder Patients. J CHILD NEUROL, 2010. 25:352-358. I.F.:1,59. 14 Amorosi CA, Treslova H, DodelsonDeKremer R, Coll MJ, Dvorakova L, OllerRamirez AM. Novel human pathological mutations. Gene symbol: ABCD1. Disease: X-linked adrenoleukodystrophy. HUM GENET, 2010. 127:486-487. I.F.:4,52. 15 Sempere A, Arias A, Farre G, Garcia-Villoria J, Rodriguez-Pombo P, Desviat LR, Merinero B, Garcia-Cazorla A, Vilaseca MA, Ribes A, Artuch R, Campistol J. Study of inborn errors of metabolism in urine from patients with unexplained mental retardation. J INHERIT METAB DIS, 2010. 33:1-7. I.F.:3,60. 16 Flanagan JM, Mcmahon G, Chia SHB, Fitzpatrick P, Tighe O, O’neill C, Briones P, Gort L, Kozak L, Magee A, Naughten E, Radomyska B, Schwartz M, Shin JS, Strobl WM, Tyfield LA, Waterham HR, Russell H, Bertorelle G, Reichardt JKV, Mayne PD, Croke 187 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM HEREDITARY METABOLIC DISEASES DT. The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations. HEREDITY, 2010. 104:148-154. I.F.:4,12. 17 Garcia-Villoria J, Gort L, Madrigal I, Fons C, Fernandez C, NavarroSastre A, Mila M, Briones P, GarciaCazorla A, Campistol J, Ribes A. X-inactivation of HSD17B10 revealed by cDNA analysis in two female patients with 17 beta-hydroxysteroid dehydrogenase 10 deficiency. EUR J HUM GENET, 2010 . 18:1353-1355. I.F.:3,56. Grants for research in progress Pampols T. Defining targets for therapeutics in Spinal Muscular Atrophy (GENAME). Grupo 5. Sponsored by: Genoma España, GenEsp2006-07/107. Amount: 101.280,00 euros. Duration: 01/03/2007-28/02/2010. Briones P. Estudios bioquímicos y mutacionales en pacientes con deficiencias primarias de CoQ. Selección bioquímica de pacientes y análisis de la vía metabólica mediante sustratos marcados con isótopos estables. Sponsored by: Fondo de Investigación Sanitaria, FIS 08/00082. Amount: 157.905,00 euros. Duration: 01/01/2009-31/12/2011. Ribes A. Automatización de métodos de diagnóstico molecular de enfermedades mitocondriales. Parte 4, Hospital Clínic: Depleción de mtDNA; Cálculo del número de copias de mtDNA y obtención de valores de referencia según edad y tejido. Sponsored by: Fondo de Investigación Sanitaria, ETES PI08/90348. Amount: 70.785,00 euros. Duration: 01/01/200931/12/2010. 188 Ribes A. Desarrollo de compuestos capaces de inducir la lectura de codones de terminación temprana (PTCs). Sponsored by: Fondo de Investigación Sanitaria. BCN-Peptides, 0000. Amount: 300.000,00 euros. Duration: 01/01/2009-31/12/2012. Ribes A. Estudios de captación de creatina, con distintos preparados de la misma, en neuronas derivadas de células IPS y en células HUVEC silenciadas con RNA de interferencia. Sponsored by: Fondo de Investigación Sanitaria, PS09/02128. Amount: 61.710,00 euros. Duration: 01/01/2010-31/12/2012. Ribes A. Diagnóstico, fisiopatología y tratamiento en la deficiencia cerebral de creatina. Subproyecto 4. Estudios de captación de creatina, con distintos preparados de la misma, en neuronas derivadas de células IPS y en células HUVEC silenciadas con RNA de INTERF. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/2128. Amount: 61.710,00 euros. Duration: 01/01/2010-31/12/2012. AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM Team involved in: GENOMIC PROGRAMMING OF BETA CELLS AND DIABETES Strategic Objectives Group Members TEAM LEADER Jorge Ferrer (Hospital Clínic) Tel.: 93 227 54 00 (Ext.: 4542) Fax: 93 312 94 09 E-mail: jferrer@clinic.ub.es Idibaps members: Ildem Akerman (IDIBAPS) 1. Use of genomic tools for establishing the genetic and epigenetic mechanisms that modify the risk of developing diabetes. 2. Identification of pathogenic mechanisms and new therapeutic options for monogenic forms of diabetes. 3. Discovery of new pancreatic regeneration pathways. Main Lines of Research 1. Pancreatic regeneration and programming. 2. Epigenomic regulation of beta cells and diabetes. 3. Monogenic diabetes. For further information: www.betacellregulation.net Research Fellows: Joris van Arensbergen (Fundació Clínic) Myriam Solar (Fundació Clínic) Ignasi Moran (Fundació Clínic) Miguel Angel Correa (Marie Curie, IDIBAPS) Nikolina Nakic (Marie Curie, IDIBAPS) Technicians: Vanessa Grau (CIBERDEM) Xavier Garcia (CIBERDEM) Collaborators: Takao Nammo (IDIBAPS) Lorenzo Pasquali (IDIBAPS) Miguel Angel Maestro (CIBERDEM) Santiago Rodriguez (IDIBAPS) Immunofluorescence of E13.5 mouse embryonic pancreas. Nuclear staining of ductal cells, hnf1b (blue). Nuclear staining of endocrine cells, nkx2.2 (red). Cytoplasmic staining of acinar cells, CPA1 (green). 189 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM GENOMIC PROGRAMMING OF BETA CELLS AND DIABETES PUBLICATIONS Originals I.F.: 64,59 1 Gaulton KJ, Nammo T, Pasquali L, Simon JM, Giresi PG, Fogarty MP, Panhuis TM, Mieczkowski P, Secchi A, Bosco D, Berney T, Montanya E, Mohlke KL, Lieb JD, Ferrer J. A map of open chromatin in human pancreatic islets. NAT GENET, 2010. 42:255-U41. I.F.:34,28. 2 Van Arensbergen J, GarciaHurtado J, Moran I, Maestro MA, Xu XB, VanDeCasteele M, Skoudy AL, Palassini M, Heimberg H, Ferrer J. Derepression of Polycomb targets during pancreatic organogenesis allows insulin-producing beta-cells to adopt a neural gene activity program. GENOME RES, 2010. 20:722-732. I.F.:11,34. 3 Boj SF, Petrov D, Ferrer J. Epistasis of Transcriptomes Reveals Synergism between Transcriptional Activators Hnf1 alpha and Hnf4 alpha. PLOS GENET, 2010. 6:-. I.F.:9,53. 4 Garin I, Edghill EL, Akerman I, Rubio-Cabezas O, Rica I, Locke JM, Maestro MA, Alshaikh A, Bundak R, DelCastillo G, Deeb A, Deiss D, Fernandez JM, Godbole K, Hussain K, O’connell M, Klupa T, Kolouskova S, Mohsin F, Perlman K, Sumnik Z, Rial JM, Ugarte E, Vasanthi T, Johnstone K, Flanagan SE, Martinez R, Castano C, Patch AM, Fernandez-Rebollo E, Raile K, Morgan N, Harries LW, Castano L, Ellard S, Ferrer J, DeNanclares G, Hattersley AT. Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis. P NATL ACAD SCI USA, 2010. 107:3105-3110. I.F.:9,43. 190 Grants for research in progress Ferrer J. Analysis of the plasticity of pancreatic duct cells. Sponsored by: JUVENILE DIABETES RES.FOUNDATION, 26-2008-633. Amount: 498.901,00 euros. Duration: 01/08/2008-31/07/2010. Ferrer J. Regulación epigenética y plasticidad de las células beta pancreáticas. Sponsored by: Ministerio de Ciencia e Innovación, 0000. Amount: 358.160,00 euros. Duration: 01/01/2009-31/12/2011. Ferrer J. Collaborative European Effort to Develop Diabetes Diagnosis. Sponsored by: VII Programa Marc, UE, 223211. Amount: 196.363,00 euros. Duration: 01/12/2008-30/11/2012. Ferrer J. Biology of Liver and Pancreatic Development and Disease. Sponsored by: VII Programa Marc, UE, 238821. Amount: 377.055,77 euros. Duration: 01/09/2009-31/08/2013. Ferrer J. Empleo de epigenomas celulares para optimizar la terapia celular a partir de células madre. Sponsored by: MINISTERIO DE EDUCACIÓN, PLE2009-0162. Amount: 265.000,00 euros. Duration: 01/11/200901/11/2011. AREA 3 Team involved in: LIVER, DIGESTIVE SYSTEM AND METABOLISM DIABETES: METABOLIC AND MOLECULAR NETWORKS Strategic Objectives Group Members TEAM LEADER Ramon Gomis (Hospital Clínic) Tel.: 93 227 98 84 Fax: 93 451 66 38 E-mail: rgomis@clinic.ub.es 1. Molecular mechanisms regulating plasticity of the islets in diabetes and obesity. 2. Molecular determinants regulating pancreatic beta-cell function: etiopathogenic role in diabetes. 3. Diabetes andobesity as cardiovascular disease. Main Lines of Research Idibaps members: Roser Casamitjana (Hospital Clínic) Ignacio Conget (Hospital Clínic) Enric Esmatjes (Hospital Clínic) Rosa Gasa (IDIBAPS) Marcelina Parrizas (IDIBAPS) Joan Marc Servitja (IDIBAPS) Josep Vidal (Hospital Clínic) Anna Novials (IDIBAPS) Marc Claret (IDIBAPS) Pablo Miguel García-Roves Carles Lerin (IDIBAPS) Antonio Ceriello (IDIBAPS) Postdoctoral fellows: Rebeca Fernández (CIBERDEM) Sandra Rebuffat (CIBERDEM) Maud Soty (CIBERDEM) Paola Casini (IDIBAPS) Nathalie Nicod (IDIBAPS) Sara Cervantes (IDIBAPS) Rita Malpique (IDIBAPS) Elena Gonzalez (CIBERDEM) Research Fellows: Esther Llagostera (Universitat de Barcelona) Joana Duarte (Fundació Clínic) Miriam Ejarque (IDIBAPS) Fabian Pardo (Fundació Clínic) Gemma Pujadas (Fundació Clínic) Montse Visa (Fundació Clínic) Alba Moreno (IDIBAPS) Katerina Papageorgiou (IDIBAPS) Silvia Canivell (IDIBAPS) Lisa Cadavez (IDIBAPS) Marc Schneeberger (Universitat de Barcelona) Marta Pradas (Fundació Clínic) Mariona Balfego (Fundació Clínic) Technicians: Carlos Castaño (CIBERDEM) Yaiza Esteban (CIBERDEM) Ainhoa García (CIBERDEM) Marta Julià (CIBERDEM) Sandra Piquer (CIBERDEM) Lidia Sanchez (IDIBAPS) Nursing Staff: Judith Viaplana (IDIBAPS) Mercè Lara (CIBERDEM) Dietists: Serafín Murillo (CIBERDEM) 1. Analysis of the transcriptional circuits regulating the beta-cell population and its function. 2. Description of the modulating effects of the transcription factors neuroD1 and neurogenin 3 in the embryonic development of the pancreas. 3. Description of the molecular pathways involved in the antiobesity and antidiabetic effects of sodium tungstate in experimental animals. 4. Impact of normal blood glucose upon endothelial dysfunction: use of treatments with insulin pumps. 5. Determination of the role of the hypothalamus in the control of energy homeostasis in obesity. 6. Analysis of the epigenetic regulation of adipogenesis. 7. Determination of the molecular effects of SNP rs7903146 of TCF7L2 and its role in the risk of developing diabetes. For further information: www.diabetisiobesitat.org www.ciberdem.org Collaborators: María José Coves (CIBERDEM) Marga Gimenez (Hospital Clínic) Belén Nadal (Universitat de Barcelona) Alexandra Felicia Hanzu (IDIBAPS) Laura Brugnara (CIBERDEM) Lilliam Flores (Hospital Clínic) Emilio Ortega (Hospital Clínic) Pere Leyes (Hospital Clínic) 191 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM DIABETES: METABOLIC AND MOLECULAR NETWORKS PUBLICATIONS Originals I.F.: 84,13 1 Martinez E, Larrousse M, Podzamczer D, Perez I, Gutierrez F, Lonca M, Barragan P, Deulofeu R, Casamitjana R, Mallolas J, Pich J, Gatell JM. Abacavir-based therapy does not affect biological mechanisms associated with cardiovascular dysfunction. AIDS, 2010. 24:F1-F9. I.F.:4,91. 2 Expression of b-site amyloidogenic cleavage of precursor protein-cleaving enzyme (BACE) in the human pancreas. BACE (red), insulin (blue) and glucagon (green) (BACE co-localization with insulin: magenta). Penarrubia J, Peralta S, Fabregues F, Carmona F, Casamitjana R, Balasch J. Day-5 inhibin B serum concentrations and antral follicle count as predictors of ovarian response and live birth in assisted reproduction cycles stimulated with gonadotropin after pituitary suppression. FERTIL STERIL, 2010. 94:2590-2595. I.F.:3,97. 3 Casals G, Ordi J, Creus M, FaRESEARCH GROUP Pancreatic islets: biomarkers and function Group Leader: Ramon Gomis (IDIBAPS) The group headed by Dr. Ramon Gomis investigates the physiology of pancreatic islets and adipose tissue, and the causes leading to dysfunction of these tissues. A central aspect of these studies is the determination of the molecular mechanisms implicated in cell mass balance at both embryonic development level and as refers to adult age – with special emphasis on cell regeneration and apoptotic processes. RESEARCH GROUP Molecular and metabolic alterations in diabetes Group Leader: Anna Novials (IDIBAPS) The main line of research of the group headed by Dr. Novials involves the study of the molecular, genetic and environmental factors critical to pancreatic beta-cell dysfunction and destruction in type 2 diabetes. 192 bregues F, Carmona F, Casamitjana R, Balasch J. Osteopontin and alpha V beta 3 integrin as markers of endometrial receptivity: the effect of different hormone therapies. REPROD BIOMED ONLINE, 2010. 21:349-359. I.F.:2,38. 4 Moreno M, Chaves JF, SanchoBru P, Ramalho F, Ramalho LN, Mansego ML, Ivorra C, Dominguez M, Conde L, Millan C, Mari M, Colmenero J, Lozano JJ, Jares P, Vidal J, Forns X, Arroyo V, Caballeria J, Gines P, Bataller R. Ghrelin Attenuates Hepatocellular Injury and Liver Fibrogenesis in Rodents and Influences Fibrosis Progression in Humans. HEPATOLOGY, 2010. 51:974-985. I.F.:10,84. 5 Lacy A, Ibarzabal A, Pando E, Adelsdorfer C, Delitala A, Corcelles R, Delgado S, Vidal J. Revisional AREA 3 Liver, digestive system and metabolism DIABETES: METABOLIC AND MOLECULAR NETWORKS Team Members Surgery After Sleeve Gastrectomy. SURG LAPARO ENDO PER, 2010. 20:351-356. I.F.:0,83. 6 Casas S, Casini P, Piquer S, Altirriba J, Soty M, Cadavez L, Gomis R, Novials A. BACE2 plays a role in the insulin receptor trafficking in pancreatic beta-cells. AM J PHYSIOL-ENDOC M, 2010. 299:E1087-E1095. I.F.:4,40. 7 Flores L, Osaba MJM, Andreu A, Moize V, Rodriguez L, Vidal J. Calcium and Vitamin D Supplementation after Gastric Bypass Should Be Individualized to Improve or Avoid Hyperparathyroidism. OBES SURG, 2010. 20:738-743. I.F.:2,93. 8 Ceriello A, Esposito K, Ihnat M, Thorpe J, Giugliano D. Effect of acute hyperglycaemia, longterm glycaemic control and insulin on endothelial dysfunction and inflammation in Type 1 diabetic patients with different characteristics. DIABETIC MED, 2010. 27:911-917. I.F.:2,87. 9 Komajda M, Mcmurray JJV, Beck-Nielsen H, Gomis R, Hanefeld M, Pocock SJ, Curtis PS, Jones NP, Home PD. Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial. EUR HEART J, 2010. 31:824-831. I.F.:9,80. 10 Musri MM, Carmona MC, Hanzu FA, Kaliman P, Gomis R, Parrizas M. Histone Demethylase LSD1 Regulates Adipogenesis. J BIOL CHEM, 2010. 285:3003430041. I.F.:5,33. 11 Moize VL, Pi-Sunyer X, Mochari H, Vidal J. Nutritional Pyramid for Post-gastric Bypass Patients. OBES SURG. , 2010 20:1133-1141. I.F.:2,93. 12 Murillo S, Brugnara L, Novials A. One year follow-up in a group of half-marathon runners with type-1 diabetes treated with insulin analogues. J SPORT MED PHYS FIT, 2010. 50:506-510. I.F.:0,76. 13 Hanzu F, Gomis R, Coves MJ, Viaplana J, Palomo M, Andreu A, Szpunar J, Vidal J. Proof-of-concept trial on the efficacy of sodium tungstate in human obesity. DIABETES OBES METAB, 2010. 12:1013-1018. I.F.:4,13. 14 Andreu A, Moize V, Rodriguez L, Flores L, Vidal J. Protein Intake, Body Composition, and Protein Status Following Bariatric Surgery. OBES SURG, 2010. 20:1509-1515. I.F.:2,93. 15 Esmatjes E, Montana X, Real MI, Blanco J, Conget I, Casamitjana R, Rovira M, Gomis R, Marin P. Regeneration of insulin production by autologous bone marrow blood autotransplantation in patients with type 1 diabetes. DIABETOLOGIA, 2010. 53:786-789. I.F.:6,55. 16 Fernandez-Real JM, Valdes S, Manco M, Chico B, Botas P, Campo A, Casamitjana R, Delgado E, Salvador J, Fruhbeck G, Mingrone G, Ricart W. Surfactant Protein D, a Marker of Lung Innate Immunity, Is Positively Associated With Insulin Sensitivity. DIABETES CARE, 2010. 33:847-853. I.F.:6,72. 17 Gimenez M, Lara M, Conget I. Sustained Efficacy of Continuous Subcutaneous Insulin Infusion in Type 1 Diabetes Subjects with Recurrent Non-Severe and Severe Hypoglycemia and Hypoglycemia Unawareness: A Pilot Study. DIABETES TECHNOL THE, 2010. 12:517-521. I.F.:2,62. 18 Luque-Ramirez M, Portoles GR, Varela C, Albero R, Halperin I, Moreiro J, Soto A, Casamitjana R. The Efficacy of Octreotide LAR as Firstline Therapy for Patients with Newly Diagnosed Acromegaly is Independent of Tumor Extension: Predictive Factors of Tumor and Biochemical Response. HORM METAB RES, 2010. 42:38-44. I.F.:2,69. 19 ltirriba J, Gasa R, Casas S, Ramirez-Bajo MJ, Ros S, GutierrezDalmau A, DeVilla MCR, Barbera A, Gomis R. The role of transmembrane protein 27 (TMEM27) in islet physiology and its potential use as a beta cell mass biomarker. DIABETOLOGIA, 2010. 53:1406-1414. I.F.:6,55. Reviews I.F.: 5,12 1 Ceriello A, Ihnat MA. ‘Glycaemic variability’: a new therapeutic challenge in diabetes and the critical care setting. DIABETIC MED, 2010. 27:862-867. I.F.:2,87. 2 Ceriello A. The glucose triad and its role in comprehensive glycaemic control: current status, future management. INT J CLIN PRACT, 2010. 64:1705-1711. I.F.:2,25. Editorials I.F.: 6,72 1 Ceriello A. Point: Postprandial Glucose Levels Are a Clinically Important Treatment Target. DIABETES CARE, 2010. 33:1905-1907. I.F.:6,72. 193 AREA 3 LIVER, DIGESTIVE SYSTEM AND METABOLISM DIABETES: METABOLIC AND MOLECULAR NETWORKS Grants for research in progress Servitja JM. Estudio de la respuesta del islote pancreático a la hipoxia: papel de HIF-1. Sponsored by: Ministerio Educación y Ciencia, BFU2006-09072. Amount: 75.020,00 euros. Duration: 01/10/2006-30/11/2011. Esmatjes E. Efectos del by-pass gástrico sobre la presión arterial y la disfunción endotelial en personas con obesidad grave. Sponsored by: Ministerio Sanidad y Consumo, PI070124. Amount: 44.770,00 euros. Duration: 01/01/2006-31/12/2010. Gomis R. Dianes moleculares inducidas por tungstato en la obesidad. Sponsored by: Ministerio Educación y Ciencia, SAF200607382. Amount: 560.000,00 euros. Duration: 01/10/200630/09/2011. Gomis R. FOOD FOR LIFE-Supporting Healthy Lifestyles in the Mediterranean Area. Sponsored by: Marie Curie Actions - International Research Staff Exchange Scheme , FP7- PEOPLE - IRSES - 2008. Amount: 54.000,00 euros. Duration: 01/01/2009-31/12/2011. Gomis R. The role of adipose tissue in obesity: beta cell crosstalk (ADIBET). Sponsored by: FP7 PEOPLE-2007-3-1-IAPP , 218131. Amount: 465.597,00 euros. Duration: 01/01/2008-31/12/2011. Gomis R. Diabetis experimental, investigació cel·lular i molecular en models de diabetis experimental. Sponsored by: Direcció General de Recerca. Generalitat 194 de Catalunya: Ajuts de suport als grups de recerca de Catalunya (SGR), 2009 SGR 1426. Amount: 53.040,00 euros. Duration: 01/01/2009-31/12/2013. Gomis R. Papel de la fracción noadipocitaria del tejido adiposo visceral en el inicio y la propagación de la enfermedad aterotrombótica. Sponsored by: I Beca Boston Scientific de Investigación Cardiovascular en Diabetes (Sociedad Española de Diabetes), 0000. Amount: 4.500,00 euros. Duration: 01/01/2009-31/12/2011. Gasa R. Cascada transcripcional inducida por neurogenina3 en el páncreas: estudio de los factores de transcripción math6 y ebf1. Sponsored by: Ministerio de Ciencia e Innovación, BFU2008-02299/ BMC. Amount: 100.000,00 euros. Duration: 01/01/2009-31/12/2011. Novials A. Papel del enzima bace (beta-site amyloid precursor protein cleaving enzyme) en la funcionalidad del islote pancreático. Sponsored by: Ministerio de Sanidad, PI080088. Amount: 75.504,00 euros. Duration: 01/01/2009-31/12/2011. Marcelina Parrizas. Papel de la demetilasa de histonas LSD1 en la adipogénesis. Sponsored by: MINISTERIO DE EDUCACIÓN, BFU2009-09988. Amount: 98.010,01 euros. Duration: 01/01/2010-31/12/2012. Servitja JM. Epigenetic control of gene expression in pancreatic islets. Sponsored by: EUROPEAN FOUNDATION FOR THE STUDY OF DIABETES, EFSD/LILLY_10_001. Amount: 50.000,00 euros. Duration: 08/05/2010-07/11/2012. Claret M. Role of hypothalamic mitochondrial fusion in appetite and body weight control: potential therapeutic target for the treatment of obesity.. Sponsored by: ASSOC CAT UNIVERSITATS PUBLIQUES - ACUP, 2010ACUP_00275. Amount: 71.859,53 euros. Duration: 01/12/2010-30/11/2012. Vidal J. GLP-1 y resolución tras el bypass gástrico de la diabetes tipo 2 asociada a obesidad. Sponsored by: FUNDACION DE INVESTIGACION MEDICA MUTUA, AP62572009. Amount: 65.000,00 euros. Duration: 03/08/200931/07/2011. Vidal J. Estudi aleatoritzat prospectiu sobre els efectes del tractament mèdic intensiu amb o sense bypass gàstric en Y de Roux, sobre el gruix de la íntima mitja carotídea en malalts amb obesitat grau I. Sponsored by: AGENCIA D’AVALUACIÓ DE TECNOLOGIA MÈDICA, 401/17/2008. Amount: 70.541,00 euros. Duration: 01/12/200930/11/2012. Claret M. Role of miRNAs in hypothalamic populations of neurons upon energy and glucose homeostasis: potential targets for obesity and diabetes treatment. Sponsored by: INSTITUTO DE SALUD CARLOS III, CP09/00233. Amount: 196.875,00 euros. Duration: 20/01/2010-19/01/2016. AREA 3 Liver, digestive system and metabolism DIABETES: METABOLIC AND MOLECULAR NETWORKS Thesis Gomis R. Bases Moleculares del efecto del tungstato de sodio sobre la plasticidad pancreática y Tmem27. PhD student: Jordi Altirriba Gutierrez. Carmona MC, Gomis R. Efecte Hipotalàmic del tungstat de sodi i la seva relació amb la via de la leptina: una possible teràpia antiobesitat. PhD student: Marta Amigo Correig. Gomis R. Plasticitat de la cèlula Beta en l’ obesitat. PhD student: Nuria Palau Balaña. 195 4 4 Clinical and experimental neuroscience Neuropharmacology and experimental neuropathology 198 Brain ischemia: Clinical and experimental studies 203 Neurodegenerative diseases: Clinical and experimental research 206 Neurophysiology and functional studies of the nervous system 211 Secondary lesions due to chronic alcohol ingestion, muscle pathology 212 Cellular biology of pathological processes 218 Biological bases of psychiatric disorders and nuclear psychiatry 221 Neuropsychology 233 Systems neuroscience 236 Clinical and experimental neuroimmunology 240 Neurobiology Unit 244 AREA 4 Team envolved in: Clinical and experimental neuroscience CIBER en enfermedades neurodegenerativas (CIBERned) & CIBER en salud mental (CIBERsam) RETIC en envejecimiento y fragilidad (RETICEF) Neuropharmacology and experimental neuropathology Strategic Objectives GROUP Members Furthering of knowledge of the physiopathological mechanisms of neurological and psychiatric diseases and neurotoxic and aging processes of the central nervous system, with a view to identifying new cellular and functional targets and proposing new treatments. TEAM LEADER Guadalupe Mengod (IIBB-CSIC) Tel.: 93 363 83 23 Fax: 93 636 83 01 E-mail: gmlnqr@iibb.csic.es RESEARCH GROUP Systems neuropharmacology group Idibaps members: Albert Adell (IIBB-CSIC) Francesc Artigas (IIBB-CSIC) Analia Bortolozzi (IDIBAPS) Anna Castañé (IIBB-CSIC) Pau Celada (IDIBAPS) Roser Cortés (IIBB-CSIC) Rosa Cristòfol (IIBB-CSIC) Sebastià Pons (IIBB-CSIC) Eduard Rodriguez Farré (IIBB-CSIC) Coral Sanfeliu (IIBB-CSIC) Josep Saura (Facultat de Medicina UB) Joan Serratosa (IIBB-CSIC) Carme Solà (IIBB-CSIC) Cristina Suñol (IIBB-CSIC) Josep Maria Tusell (IIBB-CSIC) Mª Teresa Vilaró (IIBB-CSIC) Research Fellows: Julián de Almeida (FPI-MCyT) Mercedes Barzi (FPI-IDIBAPS) Jordi Berenger (CSIC) Victor Briz (FPI-IDIBAPS) 198 Yoelvis García (Marató TV3-IDIBAPS) Núria Gresa (I3P-CSIC) Emily Johansson (FPI-CSIC) Pilar Mancera (Marató TV3) Mercè Masana (I3P-CSIC) Cristina Sanabra (FPIIDIBAPS) Marco Straccia (I3P-CSIC) Anna García (FPI-IDIBAPS) Giuseppe Mocci (JAE-CSIC) Rocío Rodríguez-Minguela (CIBERNED) Susana Revilla (FPU-MICINN) Eva Troyano (FPI-CSIC) Aina Palou (FPI-IDIBAPS) Antonio Herrera-Camacho (FPI-IDIBAPS) Guido Dentesano (Marató TV3) Cristina Viéitez (La Caixa) Núria Paúl (IIBB-CSIC) Laura Jiménez (IDIBAPS) Maurizio Riga (IDIBAPS) Technicians: Mireia Galofré (Fundació Clínic) Group Leader: Francesc Artigas (IIBB-CSIC) Leticia Campa (IIBB-CSIC) Rocío Martín-Álvarez (IIBB – CSIC) Anghara Menéndez (IDIBAPS) Albert Parull (IIBB-CSIC) Sara Sánchez-Redondo (CIBERESP) Verónica Paz (CIBERSAM) Silvia Serrano (CIBERNED) Noemí Jurado (CSIC) Jofre Serret (RETICS) Irene Porcar (IIBB-CSIC) Rosario Ruiz (UB) The group studies the neuronal circuits implicated in the physiopathology and treatment of depression and schizophrenia. Special emphasis is placed on the prefrontal cortex and anatomically and functionally related areas. It also explored chemical neurotransmission processes and physiology in animal models of mental disease, with a view to identifying new therapeutic targets. Administrative Staff: María Jaramillo (CIBERSAM) RESEARCH GROUP Neuronal proliferation control group Collaborators: Elisenda Rodríguez Vargas (IIBB-CSIC) Xavier López Gil (IIBB-CSIC) Laia Lladó (IIBB-CSIC) Noemí Santana (CIBERSAM) Tamara Romón (IDIBAPS) Tony Valente (IDIBAPS) Beatriz Caballero (CIBERESP) Group Leader: Sebastián Pons (IIBB-CSIC) This group centers its efforts on the description of mechanisms implicated in the regulation of neuronal proliferation. Specifically, it studies the molecules opposing proliferation induced by the Sonic Hedgehog oncogene in cerebellar granular cells. AREA 4 Clinical and experimental neuroscience Neuropharmacology and experimental neuropathology PUBLICATIONS Originals I.F.: 105,96 1 Human astrocytes suffer inflammatory morphological changes and apoptosis (arrow) under amyloid beta and pro-oxidant treatment. Cultures are stained with anti-GFAP and bisbenzimide. Scale bar = 20 µm. RESEARCH GROUP Neurotoxicity and neurodegeneration mechanisms group RESEARCH GROUP Molecular neuropharmacology group Group Leader: Guadalupe Mengod (IIBB-CSIC) Group Leader: Cristina Suñol (IIBB-CSIC) The group carries out studies on cytotoxicity, oxidative stress, synaptic functions and proteomics, for the determination of altered targets in toxicity and aging processes of the central nervous system. It also focuses on neuroprotective strategies and the development of in vitro methods for predicting neurotoxicity. The group studies neurotransmission and its anatomical, cellular and molecular aspects implicated in neurodegenerative disorders with an inflammatory component. The objective is to identify and characterize new targets for therapeutic action. RESEARCH GROUP Cellular neurobiology group Group Leader: Josep Saura (IIBB-CSIC) It has been suggested that glial activation plays an important role in the development of many neurodegenerative disorders. Glial activation is an inflammation-type process that takes place in the presence of neuron damage, and implies morphological changes as well as changes in the expression of different molecules in both astrocytes and microglial cells. It is still not clear whether glial activation is a consequence of neuron degradation or a phenomenon that precedes such degradation. The principal objective is to obtain information allowing the development of new strategies capable of contributing to the prevention of neurodegenerative processes characterized by chronic glial activation, based on adequate animal and cellular models. We are exploring the implication of certain transcription factors(C/EBPs and NF-B) and other proteins (CD200, CD200R, TREM) in the glial activation process and in the associated neurotoxicity. Our hypothesis is that modulation of the function of these proteins may constitute a therapeutic target in relation to the neuroinflammation and neuron damage observed in neurodegenerative diseases. We conduct in vitro and in vivo studies using experimental animals, primary cell cultures (mixed glial cultures, cultures enriched with microglia, astrocytes or neurons, mixed neuron-glia cultures) and cell lines. We are specialized in histological, cytological and molecular and cellular biology techniques. Vendrell I, Carrascal M, Campos F, Abian J, Suñol C. Methylmercury disrupts the balance between phosphorylated and nonphosphorylated cofilin in primary cultures of mice cerebellar granule cells A proteomic study. TOXICOL APPL PHARM, 2010. 242:109-118. I.F.:3,36. 2 Suñol C, Babot Z, Cristofol R, Sonnewald U, Waagepetersen HS, Schousboe A. A Possible Role of the Non-GAT1 GABA Transporters in Transfer of GABA From GABAergic to Glutamatergic Neurons in Mouse Cerebellar Neuronal Cultures. NEUROCHEM RES, 2010. 35:1384-1390. I.F.:2,72. 3 Ejarque-Ortiz A, Gresa-Arribas N, Straccia M, Mancera P, Sola C, Tusell JM, Serratosa J, Saura J. CCAAT/Enhancer Binding Protein Delta in Microglial Activationº. J NEUROSCI RES, 2010. 88:11131123. I.F.:2,99. 4 Scorza MC, Castane A, Bortolozzi A, Artigas F. Clozapine does not require 5-HT1A receptors to block the locomotor hyperactivity induced by MK-801 Clz and MK801 in KO1A mice. NEUROPHARMACOLOGY, 2010. 59:112-120. I.F.:3,91. 5 DeAlmeida J, Mengod G. D2 and D4 dopamine receptor mRNA distribution in pyramidal neurons and GABAergic subpopulations in monkey prefrontal cortex: implications for schizophrenia treatment. NEUROSCIENCE, 2010. 170:11331139. I.F.:3,29. 199 AREA 4 Clinical and experimental neuroscience Neuropharmacology and experimental neuropathology Team Members 6 DeGortari P, Mengod G. Dopamine D1, D2 and mu-opioid receptors are co-expressed with adenylyl cyclase 5 and phosphodiesterase 7B mRNAs in striatal rat cells. BRAIN RES, 2010. 1310:37-45. I.F.:2,46. 12 Mataix L, Cortes R, Scorza MC, Gingrich JA, Toth M, Artigas F. Dopamine release induced by atypical antipsychotics in prefrontal cortex requires 5-HT1A receptors but not 5-HT2A receptors. INT J NEUROPSYCHOPH, 2010. 13:12991314. I.F.:4,87. Martin-Ibanez R, Crespo E, Urban N, Sergent-Tanguy S, Herranz C, Jaumot M, Valiente M, Long JE, Pineda JR, Andreu C, Rubenstein JLR, Marin O, Georgopoulos K, Mengod G, Farinas I, Bachs O, Alberch J, Canals JM. Ikaros-1 Couples Cell Cycle Arrest of Late Striatal Precursors With Neurogenesis of Enkephalinergic Neurons. J COMP NEUROL, 2010. 518:329351. I.F.:3,72. 8 Martin-Carrasco M, Otermin P, 13 7 Bortolozzi A, Masana M, Diaz- Perez-Camo V, Pujol J, Aguera L, Martin MJ, Gobartt AL, Pons S, Balana M. EDUCA study: Psychometric properties of the Spanish version of the Zarit Caregiver Burden Scale. AGING MENT HEALTH, 2010. 14:705-711. I.F.:1,13. 9 Garcia I, Mayol G, Rodriguez E, Sunol M, Gershon TR, Rios J, Cheung NKV, Kieran MW, George RE, PerezAtayde AR, Casala C, Galvan P, DeTorres C, Mora J, Lavarino C. Expression of the neuron-specific protein CHD5 is an independent marker of outcome in neuroblastoma. MOL CANCER, 2010. 9:-. I.F.:4,16. 10 Galofre M, Babot Z, Garcia DA, Iraola S, Rodriguez-Farre E, Forsby A, Suñol C. GABA(A) receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity. NEUROTOXICOL TERATOL, 2010. 32:52-61. I.F.:3,27. 11 Aschner M, Levin ED, Suñol C, Olopade JO, Helmcke KJ, Avila DS, Sledge D, Ali RH, Upchurch L, Donerly S, Linney E, Forsby A, Ponnuru P, Connor JR. Gene-environment 200 interactions: Neurodegeneration in non-mammals and mammals. NEUROTOXICOLOGY, 2010. 31:582-588. I.F.:2,92. Moreno M, Cardona D, Gomez MJ, Sanchez-Santed F, Tobena A, Fernandez-Teruel A, Campa L, Suñol C, Escarabajal MD, Torres C, Flores P. Impulsivity Characterization in the Roman High- and Low-Avoidance Rat Strains: Behavioral and Neurochemical Differences. NEUROPSYCHOPHARMACOL, 2010. 35:1198-1208. I.F.:6,99. 17 Slevin M, Matou-Nasri S, Turu M, Luque A, Rovira N, Badimon L, Boluda S, Potempa L, Sanfeliu C, DeVera N, Krupinski J. Modified C-Reactive Protein Is Expressed by Stroke Neovessels and Is a Potent Activator of Angiogenesis In Vitro. BRAIN PATHOL, 2010. 20:151165. I.F.:5,90. 18 Ventura M, Mateo F, Serratosa J, Salaet I, Carujo S, Bachs O, Pujol MJ. Nuclear translocation of glyceraldehyde3-phosphate dehydrogenase is regulated by acetylation. INT J BIOCHEM CELL B, 2010. 42:1672-1680. I.F.:4,89. 19 Llado-Pelfort L, Assie MB, Newman-Tancredi A, Artigas F, Celada P. Preferential in vivo action of F15599, a novel 5-HT1A receptor agonist, at postsynaptic 5-HT1A receptors. BRIT J PHARMACOL, 2010. 160:1929-1940. I.F.:5,20. 20 Vidal R, Valdizan EM, Vilaro MT, 14 Pazos A, Castro E. Reduced signal transduction by 5-HT4 receptors after long-term venlafaxine treatment in rats. BRIT J PHARMACOL, 2010. 161:695706. I.F.:5,20. 15 Briz V, Galofre M, Suñol C. Reduction of Glutamatergic Neurotransmission by Prolonged Exposure to Dieldrin Involves NMDA Receptor Internalization and Metabotropic Glutamate Receptor 5 Downregulation. TOXICOL SCI, 2010. 113:138-149. I.F.:4,81. Garcia-Matas S, DeVera N, Aznar AO, Marimon JM, Adell A, Planas AM, Cristofol R, Sanfeliu C. In Vitro and In Vivo Activation of Astrocytes by Amyloid-beta is Potentiated by ProOxidant Agents. J ALZHEIMERS DIS, 2010. 20:229-245. I.F.:3,83. Gresa-Arribas N, Serratosa J, Saura J, Sola C. Inhibition of CCAAT/ enhancer binding protein delta expression by chrysin in microglial cells results in anti-inflammatory and neuroprotective effects. J NEUROCHEM, 2010. 115:526-536. I.F.:4,00. 16 Sans-Fons MG, Sole S, Sanfeliu C, Planas AM. Matrix Metalloproteinase-9 and Cell Division in Neuroblastoma Cells and Bone Marrow Macrophages. AM J PATHOL, 2010. 177:2870-2885. I.F.:5,67. 21 22 Castane A, Theobald DEH, Robbins TW. Selective lesions of the dorsomedial striatum impair serial spatial reversal learning in rats. BEHAV BRAIN RES, 2010. 210:74-83. I.F.:3,22. 23 Martinez-Boubeta C, Balcells L, Cristofol R, Sanfeliu C, Rodriguez E, Weissleder R, Lope-Piedrafita S, Simeonidis K, Angelakeris M, Sandiumenge F, Calleja A, Casas L, Monty C, Martinez B. Self-assembled multifunctional Fe/ AREA 4 Clinical and experimental neuroscience Neuropharmacology and experimental neuropathology MgO nanospheres for magnetic resonance imaging and hyperthermia. NANOMED-NANOTECHNOL, 2010. 6:362-370. I.F.:5,44. 24 Mnie-Filali O, Amraei MG, Berimbarek S, Archer-Lahlou E, Penas-Cazorla R, Vilaro MT, Boye SM, Pineyro G. Serotonin 4 receptor (5-HT4R) internalization is isoform-specific: Effects of 5-HT and RS67333 on isoforms A and B. CELL SIGNAL, 2010. 22:501-509. I.F.:4,09. 25 Barzi M, Berenguer J, Menendez A, Alvarez-Rodriguez R, Pons S. Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base. J CELL SCI, 2010. 123:62-69. I.F.:6,14. 26 Mori F, Perez-Torres S, DeCaro R, Porzionato A, Macchi V, Beleta J, Gavalda A, Palacios JM, Mengod G. The human area postrema and other nuclei related to the emetic reflex express cAMP phosphodiesterases 4B and 4D. J CHEM NEUROANAT, 2010. 40:36-42. I.F.:1,75. Reviews I.F.: 10,08 1 Adell A. Lu-AA21004, a multimodal serotonergic agent, for the potential treatment of depression and anxiety. IDRUGS, 2010. 13:900-910. I.F.:1,93. 2 Artigas F. The prefrontal cortex: a target for antipsychotic drugs. ACTA PSYCHIAT SCAND, 2010. 121:11-21. I.F.:3,73. 3 Lopez-Gil X, Artigas F, Adell A. Unraveling Monoamine Receptors Involved in the Action of Typical and Atypical Antipsychotics on Glutamatergic and Serotonergic Transmission in Prefrontal Cortex. CURR PHARM DESIGN, 2010. 16:502-515. I.F.:4,41. Editorials I.F.: 9,23 1 Adell A. New Strategies in the Search of Antipsychotic Drugs. CURR PHARM DESIGN, 2010. 16:486-487. I.F.:4,41. 2 Suñol C. Use of Gene Expression of Neural Markers in Cultured Neural Cells to Identify Developmental Neurotoxicants. TOXICOL SCI, 2010. 113:1-3. I.F.:4,81. Grants for research in progresss Sanfeliu C. Counteracting Alzheimer’s disease progession: effects of early-environmental treatments on the triple-transgenic 3xTgAD mic. Sponsored by: Fundació Marató TV3, 62931. Amount: 120.000,00 euros. Duration: 14/03/2007-13/03/2010. Serratosa J. Excitotoxic mechanisms, neuroinflammatory response and seric factors in experimental and human amyotrophyc lateral esclerosis. Sponsored by: Fundació Marató TV3, 63031. Amount: 84.372,00 euros. Duration: 02/03/2007-01/03/2010. Amount: 223.877,51 euros. Duration: 22/05/2007-31/12/2010. Artigas F. Modulación serotoninérgica de la corteza prefrontal: relevancia en el tratamiento de la depresión y la esquizofrenia. Sponsored by: Ministerio Educación y Ciencia, SAF2007-62378. Amount: 430.760,00 euros. Duration: 01/10/2007-04/10/2011. Suñol C. Optimization and pre-validation of an in vitro test strategy for predicting human acute toxicity (ACute-Tox). Sponsored by: European Commission, LSHB-CT-2004-512051. Amount: 259.797,00 euros. Duration: 01/01/2005-30/06/2010. Sanfeliu C. Red temática de investigación cooperativa en envejecimiento y fragilidad (RETICEF). Sponsored by: Ministerio Sanidad y Consumo, RD06/0013/1004. Amount: 74.954,00 euros. Duration: 01/01/200807/10/2010. Saura J. ¿Es C/EBPbeta una diana para atenuar la respuesta neuroinflamatoria asociada a enfermedades neurodegenerativas?. Sponsored by: Ministerio Sanidad y Consumo, PI070455. Amount: 88.330,00 euros. Duration: 01/01/2008-31/12/2010. Adell A. Alteraciones de las conexiones de la corteza prefrontal en el modelo de esquizofrenia de antagonismo NMDA. Sitio de acción y mecanismo de los fármacos antipsicóticos. Sponsored by: Ministerio Sanidad y Consumo, PI070111. Amount: 152.460,00 euros. Duration: 26/11/2007-30/06/2011. Celada MP. Actividad cortical y alucinaciones. Nuevo modelo experimental para la identificación de dianas terapeuticas en esquizofrenia. Sponsored by: Instituto de Salud Carlos III, PS09/01245. Amount: 74.415,00 euros. Duration: 01/01/201031/12/2012. Artigas F. Monoaminergic neurotransmission in prefrontal cortex: Target for augmentation strategies in schizophrenia. Sponsored by: SENYFundació - Schizophrenia Research Foundation, SenyFund_07_002. Artigas F. Estudio del mecanismo de acción de la estimulación cerebral profunda sobre la neurotransmisión serotoninérgica y dopaminérgica. Sponsored by: Ministerio de Ciencia e Innovación, 201020E046. 201 AREA 4 Clinical and experimental neuroscience Neuropharmacology and experimental neuropathology Team Members Amount: 45.000,00 euros. Duration: 01/01/2010-03/06/2011. Bortolozzi A. In vivo silencing of 5-HT2A receptor and serotonin transporter by RNA interference mechanism. Relevance to the cognitive-affective disorder in schizophrenia and depression. Sponsored by: Instituto de Salud Carlos III, P91C. Amount: 48.000,00 euros. Duration: 02/06/2009-02/06/2011. Artigas F. Grup de Recerca Consolidat, Neuroquímica i Neurofarmacologia. Sponsored by: Generalitat de Catalunya, 2009SGR220. Amount: 49.920,00 euros. Duration: 01/01/2009-31/12/2013. Artigas F. Novel Methods leading to New Medications in Depression and Schizophrenia (NEWMEDS). Sponsored by: IMI JU, (Comisión Europea - CE y la Federación Europea de Industrias y Asociaciones Farmacéuticas EFPIA), Grant Agreement N° 115008. Amount: 416.232,00 euros. Duration: 01/09/2009-31/08/2014. Cortés R. Estudio de la aplicación de nanopartículas metálicas para usos de diagnóstico y terapéutica de enfermedades del sistema nervioso central. Sponsored by: Ministerio de Ciencia en Innovación, PET2008-0066. Amount: 19.965,00 euros. Duration: 01/03/2009-28/02/2011. Pons S. de la proliferación de los precursores de neuronas granulares del cerebelo. Sponsored by: Instituto de Investigaciones Biomedicas de Barcelona CSIC, MCI BFU2008-024024BFI. Amount: 185.000,00 euros. Duration: 01/01/2009-31/12/2011. Joan Serratosa Serda. Mecanismes excitotòxics, resposta inflamatòria i factors sèrics en l’escelorosi lateral amiotròfica humana i ex- 202 perimental. Sponsored by: Fundació Marató TV3, V-2006-TV063031-O. Amount: 84.372,00 euros. Duration: 01/03/2008-31/10/2010. Solá C. Inhibición de la activación glial como diana terapéutica en enfermedades neurodegenerativas. Sponsored by: FIS, PI081396. Amount: 191.906,00 euros. Duration: 01/01/2009-31/12/2011. Cortés R. Títol del projecte: Expresión de marcadores neuronales en demencias: enfermedad de los granos argirófilos y Alzheimer. Sponsored by: MICINN - Instituto de Salud Carlos III, PS09/01087. Amount: 124.025,00 euros. Duration: 01/01/2010-31/12/2012. Sanfeliu C. Implicación de la sirtuina 1 en procesos neurodegenerativos. Sponsored by: MICINN, SAF200913093-C02-02. Amount: 181.500,00 euros. Duration: 01/01/2010-31/12/2012. Mengod G. Neuroinflamación: Regulación molecular de la señalización por AMPc en el modelo EAE murino de esclerosis múltiple. Sponsored by: Comisión Interministerial de Ciencia y Tecnología, SAF2009-11052. Amount: 30.000,00 euros. Duration: 01/01/2010-31/12/2010. Mengod G. Fármacos innovadores para la esclerosis múltiple. Sponsored by: Fundación Española para la Ciencia y Tecnología (FECYT), INC-0367. Amount: 150.000,00 euros. Duration: 01/01/2010-31/12/2011. Artigas F, Bortolozzi A. DENDRIA Modulación de los genes asociados al sistema serotonérgico con moléculas RNA antisentido (siRNA) y su efecto en modelo. Sponsored by: nLife Therapeutics, 10/166. Amount: 97.500,00 euros. Duration: 01/07/201031/12/2013. Celada MP. DENDRIA -Estudios de la actividad oscilatoria cortical. Sponsored by: BRAINco Biopharma, S.L., 10/156. Amount: 24.200,00 euros. Duration: 01/07/2010-31/12/2013. Artigas F. Deep Brain Stimulation in patients with Resistant Major Depressive Disorder. Mechanism of action, clinical and preclinical studies. Sponsored by: Instituto de Salud Carlos III, P82. Amount: 20.000,00 euros. Duration: 21/11/2008-21/11/2011. Sanfeliu C. Disfunción cerebral durante el envejecimiento: relevancia para la enfermedad de Alzheimer (BrainAge). Sponsored by: MICINN, CSD2010-00045. Amount: 0,00 euros. Duration: 27/12/2010-26/12/2015. Vilaró MT. Efecto de la activación de receptores 5-HT4 de serotonina sobre la deposición del péptido amiloide Aß‚ en un ratón triple transgénico de la enfermedad de Alzheimer. Sponsored by: MICINN - Instituto de Salud Carlos III, PS09/00468. Amount: 59.500,00 euros. Duration: 01/01/201031/12/2012. Thesis Sanfeliu C. El ejercicio físico voluntario como terapia para la enfermedad de Alzheimer. Estudio en ratones tripletransgénicos 3xTg-AD. PhD student: Yoelvis Garcia Mesa. Artigas F, Celada MP. Paper del receptor 5HT 1A en el mecanisme d’ acció de psicofàrmacs. PhD student: Laia Lladó Pelfort. AREA 4 Clinical and experimental neuroscience Brain ischemia: Clinical and experimental studies Strategic Objectives GROUP Members TEAM LEADER Anna M. Planas (IIBB-CSIC) Tel.: 93 363 83 27 Fax: 93 363 83 01 E-mail: ampfat@iibb.csic.es Study of cerebrovascular pathology from the clinical and basic perspective, with special emphasis on inflammation and immune response, as well as on the use of neuroimaging techniques. The ultimate aim is to develop therapeutic strategies in application to stroke. Idibaps members: Ángel Chamorro (Hospital Clínic) Tomàs Santalucia (IDIBAPS) Luisa Camon (IIBB-CSIC) Nuria de Vera (IIBB-CSIC) Emili Martínez (IIBB-CSIC) Esther Pozas (IDIBAPS) Justicia, Carles (IIBB-CSIC) Cervera, Álvaro (Hospital Clínic) Valérie Petegnief (IIBB-CSIC) Research Fellows: Sergi Amaro (FIS) Miriam Font Nieves de la Vega (MEC) Manuel Gómez-Choco (Fundació Clínic) Anna Serra (IDIBAPS) Xabier Urra (FIS) Isabel Pérez de Puig (IDIBAPS) Xavier de la Rosa Siles (CSIC) Fernando Yepes Calderón (CSIC) Unai Perpiñá Martín (IDIBAPS) Collaborators: Víctor Obach (Hospital Clínic) Marta Vargas (Fundació Clínic) Fernando Pérez Asensio (Juan de la Cierva, CSIC) Guadalupe Soria (contracte I3P, CSIC) Leonardo J. Márquez (IIBB-CSIC) Luca Maggioni (IDIBAPS) Glòria Sans Fons (IDIBAPS) Study of the rat brain using magnetic resonance imaging. A) Fractional anisotropy map offering information on the magnitude of white matter fibre anisotropy, showing the anatomy of the rat brain. Control of the coronal section at three different levels of the brain. B) The same brain sections, with a colour-code map providing information on the threedimensional orientation of the white matter fibres using the diffusion tensor imaging (DTI) technique. C) Coronal sections of fractional anisotropy map images of the brain of an animal 7 days after occlusion of the middle cerebral artery during 90 minutes. D) Colour-code map of the same ischemic brain sections. Technicians: Noelia Montoya (IDIBAPS) Francisca Ruiz (IDIBAPS) 203 AREA 4 Clinical and experimental neuroscience Brain ischemia: Clinical and experimental studies PUBLICATIONS Main Lines of Research Originals I.F.: 90,59 1. Immunological mechanisms implicated in the progression of ischemic stroke and in the appearance of infectious complications. Study of inflammatory and innate immune responses in stroke. Genetic aspects of immune response. 2. Identification of new antioxidant treatments in stroke. Preclinical studies of the protective effects of these treatments and of the mechanisms involved. Design and conduction of a phase IIb study involving the administration of uric acid in stroke treated with rtPA. 3. Use of intraarterial rescue treatments with rtPA in patients previously treated with intravenous rtPA and selected by multimodal imaging techniques. 4. Neuroimaging in brain ischemia: application of magnetic resonance (MR) techniques for the in vivo noninvasive monitorization of patients and experimental animals in relation to anatomical and functional parameters of brain damage – including immune response. 5. Signals implicated in neuron death and survival in ischemia: role of endoplasmic reticulum stress and molecular regulation of hypoxiainducible factor (HIF-1a). 6. Neurological repair and neurogenesis in brain ischemia: effect of inflammation upon neurogenesis. Cervera A, Planas AM, Justicia C, Urra X, Jensenius JC, Torres F, Lozano F, Chamorro A. Genetically-Defined Deficiency of Mannose-Binding Lectin Is Associated with Protection after Experimental Stroke in Mice and Outcome in Human Stroke. PLoS ONE, 2010. 5:-. I.F.:4,35. 1 2 7 Rodriguez G, Soria G, Coll E, Rubio L, Barbosa-Barros L, Lopez-Iglesias C, Planas AM, Estelrich J, DeLaMaza A, Lopez O. Bicosomes: Bicelles in Dilute Systems. BIOPHYS J, 2010. 99:480488. I.F.:4,39. 8 Serra-Perez A, Planas AM, NunezO’mara A, Berra E, Garcia-Villoria J, Ribes A, Santalucia T. Extended ischemia prevents HIF1alpha degradation at reoxygenation by impairing prolyl-hydroxylation: role of Krebs cycle metabolites. J BIOL CHEM, 2010. 285:18217-18224. I.F.:5,33. Ederle J, Dobson J, Featherstone RL, Bonati LH, VanDerWorp HB, et al. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. LANCET, 2010. 375:985-997. I.F.:30,76. 3 9 Canas N, Gorina R, Planas AM, Garcia-Matas S, DeVera N, Aznar AO, Marimon JM, Adell A, Planas AM, Cristofol R, Sanfeliu C. In Vitro and In Vivo Activation of Astrocytes by Amyloid-beta is Potentiated by Pro-Oxidant Agents. J ALZHEIMERS DIS, 2010. 20:229-245. I.F.:3,83. 4 Sans-Fons MG, Sole S, Sanfeliu C, Planas AM. Matrix Metalloproteinase-9 and Cell Division in Neuroblastoma Cells and Bone Marrow Macrophages. AM J PATHOL, 2010. 177:2870-2885. I.F.:5,67. 5 Slevin M, Matou-Nasri S, Turu M, Luque A, Rovira N, Badimon L, Boluda S, Potempa L, Sanfeliu C, DeVera N, Krupinski J. Modified CReactive Protein Is Expressed by Stroke Neovessels and Is a Potent Activator of Angiogenesis In Vitro. BRAIN PATHOL, 2010. 20:151-165. I.F.:5,90. 6 Perez-Asensio FJ, DeLaRosa X, Jimenez-Altayo F, Gorina R, Martinez E, Messeguer A, Vila E, Chamorro A, Planas AM. Antioxidant CR-6 protects 204 against reperfusion injury after a transient episode of focal brain ischemia in rats. J CEREBR BLOOD F MET, 2010. 30:638-652. I.F.:5,46. Verges J, Montell E, Garcia AG, Lopez MG. Chondroitin sulfate inhobits Lipopolysaccharide-inducedinflammation in rat astrocytes by preventing nuclear factor kappa activation. NEUROSCIENCE, 2010. 167:872-879. I.F.:3,29. 10 Chamorro A. Dual antiplatelet therapy is not optimal for stroke prevention in patients with atrial fibrillation. INT J STROKE, 2010. 5:28-29. I.F.:2,87. 11Paco S, Pozas E, Aguado F. Secretogranin III Is an Astrocyte Granin That Is Overexpressed in Reactive Glia. CEREB CORTEX, 2010. 20:1386-1397. I.F.:6,98. 12 Ramos-Cabrer P, Justicia C, Wiedermann D, Hoehn M. Stem Cell Mediation of Functional Recovery after Stroke in the Rat. PLOS ONE, 2010. 5:-. I.F.:4,35. 13 Amaro S, Canovas D, Castellanos M, Gallego J, Marti-Fabregas J, Segura T, Chamorro A. The URICO-ICTUS study, AREA 4 Clinical and experimental neuroscience Brain ischemia: Clinical and experimental studies a phase 3 study of combined treatment with uric acid and rtPA administered intravenously in acute ischaemic stroke patients within the first 4 center dot 5 h of onset of symptoms. INT J STROKE, 2010. 5:325-328. I.F.:2,87. 14 Casteels C, Martinez E, Bormans G, Camon L, DeVera N, Baekelandt V, Planas AM, VanLaere K. Type 1 cannabinoid receptor mapping with [F-18]MK9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism. EUR J NUCL MED MOL I. 37:2354-2363. I.F.:4,53. Grants for research in progress Planas A. Diagnostic for Molecular Imaging. European Network of Excellence. Sponsored by: European Community. Sixth Framework Programme (Life Sciences, genomics and biotechnology for health), LSHB-CT-2005-512146. Amount: 400.000,00 euros. Duration: 01/04/200530/03/2010. Planas A. Affording recovery in Stroke (ARISE). Sponsored by: European Community. Seventh Framework Programme (Life Sciences,), 0000. Amount: 558.079,00 euros. Duration: 01/04/200801/03/2013. Esther Pozas. Neurogenesis endógena e inflamación en la isquemia cerebral en modelos experimentales murinos y en pacientes con ictus. Sponsored by: Ministerio de Sanidad y Consumo (FIS), PI070917. Amount: 214.170,00 euros. Duration: 01/01/2008-31/12/2010. Tomás Santalucía. Efecto de la glucosa sobre la función de HIF-1alfa en neuronas y glía sometidas a isquemia y estímulos proinflamatorios. Sponsored by: Programa Nacional de Biomedicina (MICINN), SAF2008-04515-C02-02. Amount: 84.700,00 euros. Duration: 01/01/2009-31/12/2011. Valerie Petegnief. Mecanismos de muerte y neuroprotección en la isquemia cerebral. Efecto de la inflamación y papel de la UPR. Sponsored by: Ministerio de Ciencia e Innovación (FIS), PI081932. Amount: 80.586,00 euros. Duration: 01/01/2009-01/12/2011. Carles Justicia. Estudio de la función cerebral por resonancia magnética de alto campo en modelos experimentales de isquemia: Degeneración y regeneración de la sustancia blanca. Sponsored by: Ministerio de Ciencia e innovación (FIS), PI081880. Amount: 171.215,00 euros. Duration: 01/01/2009-31/12/2011. Planas A. Inflamación y respuesta inmune innata como dianas terapéuticas en la isquemia cerebral. Sponsored by: Programa Nacional de Biomedicina (MICINN), 0000. Amount: 255.000,00 euros. Duration: 01/01/2009-31/12/2011. Chamorro A. Estudio de marcadores inmunológicos circulantes y tisulares (tejido linfoide y cerebro) y de su relación pronóstica en el paciente con ictus isquémico. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1313. Amount: 259.545,00 euros. Duration: 01/01/201031/12/2012. Thesis Santalucia T, Planas A. Efecte de la glucosa en un model d’isquèmia in vitro: modulació del factor induït per hipòxia i de la mort cel·lular programada. PhD student: Anna Serra-Pérez. Chamorro A, Planas A. Implicaciones Clínicas y pronósticas del síndrome de inmunodepresión mediado por el ictus agudo. PhD student: Xabier Urra Ruin. 205 AREA 4 Clinical and experimental neuroscience Team envolved in: CIBER en enfermedades neurodegenerativas (CIBERned) Neurodegenerative diseases: Clinical and experimental research Strategic Objectives GROUP Members TEAM LEADER Eduardo Tolosa (Hospital Clínic) Tel.: 93 227 57 85 E-mail: etolosa@clinic.ub.es Idibaps members: Mario Ezquerra (Fundació Clínic) Conxita Marín (IDIBAPS) Maria Josep Martí (Hospital Clínic) José Luís Molinuevo (Hospital Clínic) Esteban Muñoz (Hospital Clínic) Francesc Valldeoriola (Hospital Clínic) Albert Lladó (Hospital Clínic) Raquel Sánchez del Valle (Hospital Clínic) Lorena Rami (Fundació Clínic) Postdoctoral fellows: Beatriz Bosch (IDIBAPS Pharmacog) Anna Antonell (IDIBAPS Consolider) Cristina Solé Padulles (Fundació Clinic) Research Fellows: Yaroslau Compta (Hospital Clínic) Carles Gaig (ISC3, Hospital Clínic) Claustre Pont (CIBERNED) Teresa Botta Judith Navarro (Hospital Clínic) Magda Castellví (Hospital Clínic) Juan Fortea (Hospital Clínic) Mircea Balasa (Hospital Clínic) Jaume Olives (Fundació Clínic) Rebeca Adánez (Fundació Clínic) 206 1. Development of research projects, with results that may find short term application, with a view to improving the diagnosis and treatment of degenerative neurological diseases. Many of the research lines are linked to clinical research protocols of the Clinic Hospital Department of Neurology. 2. Investigation of the molecular mechanisms implicated in dopaminergic neuron degeneration and in the physiopathology of the motor complications induced by drug treatment, in experimental models of Parkinson’s disease and other movement disorders. Technicians: Esther Aguilar (Fundació Clínic) Mercè Bonastre (CIBERNED) Eva Caballero (Grup Suport Generalitat) Manel Fernández (Fundació Clínic) Maria Teresa Buongiorno (Fundació Clínic) Ana Camara (Fundació Clínic) Nursing Staff: Rosa Maria Álvarez (Fundació Clínic) Collaborators: Rubén Fernández-Santiago (IDIBAPS) Results of a brain transcriptomic study using Heat map analysis showed partial segregation of the expression profiles of controls, idiopathic PD (IPD) and LRRK2-associated mutation PD (MPD). IPD and controls have expression patterns that are clearly different, while MPD tissues show heterogeneous patterns - two resembling controls and one resembling IPD. This suggests the presence of different transcription processes in the putamen of MPD versus IPD. AREA 4 Clinical and experimental neuroscience Neurodegenerative diseases: Clinical and experimental research Main Lines of Research 1. Genetic analyses, biological markers and experimental therapies in Parkinson’s disease and other movement disorders. Genetic and expression studies in parkinsonisms. 2. Studies in in vivo and in vitro experimental modelsof the physiopathological mechanisms involved in Parkinson’s disease and other movement disorders. 3. Genetic and diagnostic and predictive marker studies in Alzheimer’s disease and other dementias. Experimental functional neuroimaging studies in healthy and in pathological aging. 4. Study of the biological and molecular bases of Alzheimer’s disease and Parkinson’s disease in preclinical stages: mild cognitive impairment and pre-motor Parkinson’s disease. 5. Study of neurogenesis in the subventricular zone, olfactory bulb and striate nucleus in experimental models of Parkinson’s disease and tardive dyskinesia. RESEARCH GROUP Parkinson’s disease and movement disorders Group Leader: Eduardo Tolosa (Hospital Clínic) We have consolidated the line of genetics in degenerative disorders, particularly Parkinson’s disease. This year we have explored or published different studies on genetic brain expression of genes potentially implicated in progressive supranuclear paralysis (isoforms of tau, CRHR1, IMP5, cdk5, GSK3 and saitohin). In addition, we have determined the frequency of the most common mutations of the LRRK2 gene in patients with Parkinson’s disease seen in our Department, and in cases of parkinsonism in the Neurological Tissue Bank. Team Members PUBLICATIONS Originals I.F.: 188,85 1 Iranzo A, Lomena F, Stockner H, Valldeoriola F, Vilaseca I, Salamero M, Molinuevo JL, Serradell M, Duch J, Pavia J, Gallego J, Seppi K, Hogl B, Tolosa E, Poewe W, Santamaria J. Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. LANCET NEUROL, 2010. 9:1070-1077. I.F.:18,13. 2 Iranzo A, Isetta V, Molinuevo JL, Serradell M, Navajas D, Farre R, Santamaria J. Electroencephalographic slowing heralds mild cognitive impairment in idiopathic REM sleep behavior disorder. SLEEP MED, 2010. 11:534539. I.F.:3,70. 3 Llado A, Fortea J, Ojea T, Bosch B, Sanz P, Valls-Sole J, Clarimon J, Molinuevo JL, Sanchez-Valle R. A novel PSEN1 mutation (K239N) associated with Alzheimer’s disease with wide range age of onset and slow progression. EUR J NEUROL, 2010. 17:994996. I.F.:2,51. 4 Guardia-Laguarta C, Pera M, Clarimon J, Molinuevo JL, Sanchez-Valle R, Llado A, Coma M, Gomez-Isla T, Blesa R, Ferrer I, Lleo A. Clinical, Neuropathologic, and Biochemical Profile of the Amyloid Precursor Protein 1716F Mutation. J NEUROPATH EXP NEUR, 2010. 69:53-59. I.F.:4,56. 5 Bosch B, Batres-Faz D, Rami L, Arenaza-Urquijo EM, FernandezEspejo D, Junque C, Sole-Padulles C, Sanchez-Valle R, Bargallo N, Falcon C, Molinuevo JL. Cognitive reserve modulates task-induced activations and deactivations in healthy elders, amnestic mild cognitive impairment and mild Alzheimer’s disease. CORTEX, 2010. 46:451-461. I.F.:4,06. 6 VanDeerlin VM, Sleiman PMA, Martinez-Lage M, Chen-Plotkin A, Wang LS, Graff-Radford NR, Dickson DW, Rademakers R, Boeve BF, Grossman M, Arnold SE, Mann DMA, Pickering-Brown SM, Seelaar H, Heutink P, VanSwieten JC, Murrell JR, Ghetti B, Spina S, Grafman J, Hodges J, Spillantini MG, Gilman S, Lieberman AP, Kaye JA, Woltjer RL, Bigio EH, Mesulam M, Al-Sarraj S, Troakes C, Rosenberg RN, White CL, Ferrer I, Llado A, Neumann M, Kretzschmar HA, Hulette CM, Welsh-Bohmer KA, Miller BL, Alzualde A, DeMunain AL, Mckee AC, Gearing M, Levey AI, Lah JJ, Hardy J, Rohrer JD, Lashley T, Mackenzie IRA, Feldman HH, Hamilton RL, Dekosky ST, VanDerZee J, Kumar-Singh S, VanBroeckhoven C, Mayeux R, Vonsattel JPG, Troncoso JC, Kril JJ, Kwok JBJ, Halliday GM, Bird TD, Ince PG, Shaw PJ, Cairns NJ, Morris JC, Mclean CA, Decarli C, Ellis WG, Freeman SH, Frosch MP, Growdon JH, Perl DP, Sano M, Bennett DA, Schneider JA, Beach TG, Reiman EM, Woodruff BK, Cummings J, Vinters HV, Miller CA, Chui HC, Alafuzoff I, Hartikainen P, Seilhean D, Galasko D, Masliah E, Cotman CW, Tunon MT, Martinez MCC, Munoz DG, Carroll SL, Marson D, Riederer PF, Bogdanovic N, Schellenberg GD, Hakonarson H, Trojanowski JQ, Lee VMY. Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP43 inclusions. NAT GENET, 2010. 42:234-U34. I.F.:34,28. 7 Ibarretxe-Bilbao N, Ramirez-Ruiz B, Junque C, Marti MJ, Valldeoriola F, Bargallo N, Juanes S, Tolosa E. Differential progression of brain atrophy in Parkinson’s disease with and without visual hallucinations. J NEUROL 207 AREA 4 Clinical and experimental neuroscience Neurodegenerative diseases: Clinical and experimental research Team Members NEUROSUR PS, 2010. 81:650-657. I.F.:4,87. 8 Timmermann L, Pauls KAM, Wieland K, Jech R, Kurlemann G, Sharma N, Gill SS, Haenggeli CA, Hayflick SJ, Hogarth P, Leenders KL, Limousin P, Malanga CJ, Moro E, Ostrem JL, Revilla FJ, Santens P, Schnitzler A, Tisch S, Valldeoriola F, Vesper J, Volkmann J, Woitalla D, Peker S. Dystonia in neurodegeneration with brain iron accumulation: outcome of bilateral pallidal stimulation. BRAIN, 2010. 133:701-712. I.F.:9,49. Fortea J, Sala-Llonch R, BartresFaz D, Bosch B, Llado A, Bargallo N, Molinuevo JL, Sanchez-Valle R. Increased Cortical Thickness and Caudate Volume Precede Atrophy in PSEN1 Mutation Carriers. J ALZHEIMERS DIS, 2010. 22:909-922. I.F.:3,83. 9 13 Stocchi F, Rascol O, Kieburtz Valldeoriola F, Regidor I, MinguezCastellanos A, Lezcano E, GarciaRuiz P, Rojo A, Salvador A, Castro A, Grandas F, Kulisevsky J, Marti MJ, Martinez-Martin P, Relova L, Rumia J, Camara A, Burguera JA, Linazasoro G, DeVal JL, Obeso J, Rodriguez-Oroz MC, Tolosa E. Efficacy and safety of pallidal stimulation in primary dystonia: results of the Spanish multicentric study. J NEUROL NEUROSUR PS, 2010. 81:65-69. I.F.:4,87. 10 Guerreiro RJ, Baquero M, Blesa R, Boada M, Bras JM, Bullido MJ, Calado A, Crook R, Ferreira C, Frank A, Gomez-Isla T, Hernandez I, Lleo A, Machado A, Martinez-Lage P, Masdeu J, Molina-Porcel L, Molinuevo JL, Pastor P, Perez-Tur J, Relvas R, Oliveira CR, Ribeiro MH, Rogaeva E, Sa A, Samaranch L, Sanchez-Valle R, Santana I, Tarraga L, Valdivieso F, Singleton A, Hardy J, Clarimon J. Genetic screening of Alzheimer’s disease genes in Iberian and African samples yields novel mutations in presenilins and APP. NEUROBIOL AGING, 2010. 31:725-731. I.F.:5,94. 11 Sala-Llonch R, Bosch B, Arenaza-Urquijo EM, Rami L, Bargallo N, Junque C, Molinuevo JL, Bartres-Faz D. Greater Default-Mode Network 208 Abnormalities Compared to High Order Visual Processing Systems in Amnestic Mild Cognitive Impairment: An Integrated Multi-Modal MRI Study. J ALZHEIMERS DIS, 2010. 22:523539. I.F.:3,83. 12 K, Poewe W, Jankovic J, Tolosa E, Barone P, Lang AE, Olanow CW. Initiating Levodopa/Carbidopa Therapy With and Without Entacapone in Early Parkinson Disease The STRIDE-PD Study. ANN NEUROL, 2010. 68:18-27. I.F.:9,32. 14 Coelho M, Marti MJ, Tolosa E, Ferreira JJ, Valldeoriola F, Rosa M, Sampaio C. Late-stage Parkinson’s disease: the Barcelona and Lisbon cohort. J NEUROL, 2010. 257:15241532. I.F.:2,90. 15 Sanchez-Benavides G, GomezAnson B, Molinuevo JL, Blesa R, Monte GC, Buschke H, Pena-Casanova J. Medial Temporal Lobe Correlates of Memory Screening Measures in Normal Aging, MCI, and AD. J GERIATR PSYCH NEUR, 2010. 23:100-108. I.F.:1,92. 16 Emre M, Tsolaki M, Bonuccelli U, Destee A, Tolosa E, Kutzelnigg A, Ceballos-Baumann A, Zdravkovic S, Bladstrom A, Jones R. Memantine for patients with Parkinson’s disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebocontrolled trial. LANCET NEUROL, 2010. 9:969-977. I.F.:18,13. 17 Laugel V, Dalloz C, Durand M, Sauvanaud F, Kristensen U, Vincent MC, Pasquier L, Odent S, CormierDaire V, Gener B, Tobias ES, Tolmie JL, Martin-Coignard D, Drouin-Garraud V, Heron D, Journel H, Raffo E, Vigneron J, Lyonnet S, Murday V, Gubser-Mercati D, Funalot B, Brueton L, DelPozo JS, Munoz E, Gennery AR, Salih M, Noruzinia M, Prescott K, Ramos L, Stark Z, Fieggen K, Chabrol B, Sarda P, Edery P, Bloch-Zupan A, Fawcett H, Pham D, Egly JM, Lehmann AR, Sarasin A, Dollfus H. Mutation Update for the CSB/ERCC6 and CSA/ ERCC8 Genes Involved in Cockayne Syndrome. HUM MUTAT, 2010. 31:113-126. I.F.:6,89. 18 Llado A, Sanchez-Valle R, Rey MJ, Mercadal P, Almenar C, LopezVillegas D, Fortea J, Molinuevo JL. New mutation in the PSEN1 (E120G) gene associated with early onset Alzheimer’s disease. NEUROLOGIA, 2010. 25:13-16. I.F.:0,60. 19 Costa J, Gonzalez HA, Valldeoriola F, Gaig C, Tolosa E, Valls-Sole J. Nonlinear Dynamic Analysis of Oscillatory Repetitive Movements in Parkinson’s Disease and Essential Tremor. MOVEMENT DISORD. 25:2577-2586. I.F.:4,01. 20 Ibarretxe-Bilbao N, Junque C, Marti MJ, Valldeoriola F, Vendrell P, Bargallo N, Zarei M, Tolosa E. Olfactory Impairment in Parkinson’s Disease and White Matter Abnormalities in Central Olfactory Areas: A Voxel-Based Diffusion Tensor Imaging Study. MOVEMENT DISORD, 2010. 25:1888-1894. I.F.:4,01. 21 Barone P, Poewe W, Albrecht S, Debieuvre C, Massey D, Rascol O, Tolosa E, Weintraub D. Pramipexole for the treatment of depressive symptoms in patients with Parkinson’s AREA 4 Clinical and experimental neuroscience Neurodegenerative diseases: Clinical and experimental research disease: a randomised, double-blind, placebo-controlled trial. LANCET NEUROL, 2010. 9:573-580. I.F.:18,13. Disease: A Randomized, Placebo-Controlled Study. MOVEMENT DISORD, 2010. 25:896-905. I.F.:4,01. 22 Kollensperger M, Geser F, Ndayi- 26 Beyer K, Domingo-Sabat M, saba JP, Boesch S, Seppi K, Ostergaard K, Dupont E, Cardozo A, Tolosa E, Abele M, Klockgether T, Yekhlef F, Tison F, Daniels C, Deuschl G, Coelho M, Sampaio C, Bozi M, Quinn N, Schrag A, Mathias CJ, Fowler C, Nilsson CF, Widner H, Schimke N, Oertel W, DelSorbo F, Albanese A, Pellecchia MT, Barone P, Djaldetti R, Colosimo C, Meco G, Gonzalez-Mandly A, Berciano J, Gurevich T, Giladi N, Galitzky M, Rascol O, Kamm C, Gasser T, Siebert U, Poewe W, Wenning GK. Presentation, Diagnosis, and Management of Multiple System Atrophy in Europe: Final Analysis of the European Multiple System Atrophy Registry. MOVEMENT DISORD, 2010. 25:2604-2612. I.F.:4,01. Santos C, Tolosa E, Ferrer I, Ariza A. The decrease of beta-synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies. BRAIN, 2010. 133:3724-3733. I.F.:9,49. 23 Sanchez-Benavides G, GomezAnson B, Quintana M, Vives Y, Manero RM, Sainz A, Blesa R, Molinuevo JL, Pena-Casanova J. Problem-solving abilities and frontal lobe cortical thickness in healthy aging and mild cognitive impairment. J INT NEUROPSYCH SOC, 2010. 16:836-845. I.F.:2,77. 24 Montagut N, Sanchez-Valle R, Castellvi M, Rami L, Molinuevo JL. Relearning vocabulary. A comparative analysis between a case of dementia and Alzheimer’s disease with predominant compromise of language. REV NEUROLOGIA, 2010. 50:152-156. I.F.:1,23. 25 Eggert K, Squillacote D, Barone P, Dodel R, Katzenschlager R, Emre M, Lees AJ, Rascol O, Poewe W, Tolosa E, Trenkwalder C, Onofrj M, Stocchi F, Nappi G, Kostic V, Potic J, Ruzicka E, Oertel W. Safety and Efficacy of Perampanel in Advanced Parkinson’s 27 Rami L, Bosch B, Sanchez-Valle R, Molinuevo JL. The memory alteration test (M@T) discriminates between subjective memory complaints, mild cognitive impairment and Alzheimer’s disease. ARCH GERONTOL GERIAT, 2010. 50:171-174. I.F.:1,36. Reviews I.F.: 41,00 1 Marin C, Obeso JA. Catechol-Omethyltransferase inhibitors in preclinical models as adjuncts of L-dopa treatment. INT REV NEUROBIOL, 2010. 95:191-205. I.F.:4,02. 2 Valls-Pedret C, Molinuevo JL, Rami L. Early diagnosis of Alzheimer’s disease: the prodromal and preclinical phase. REV NEUROLOGIA, 2010. 51:471-480. I.F.:1,23. 3 Pont-Sunyer C, Marti MJ, Tolosa E. Focal limb dystonia. EUR J NEUROL, 2010. 17:22-27. I.F.:2,51. 4 Valldeoriola F, Camara A. Intraduodenal infusion of levodopa. REV NEUROLOGIA, 2010. 51:41-48. I.F.:1,23. 5 Obeso JA, Rodriguez-Oroz MC, Goetz CG, Marin C, Kordower JH, Rodriguez M, Hirsch EC, Farrer M, Schapira AHV, Halliday G. Missing pieces in the Parkinson’s disease puzzle. NAT MED, 2010. 16:653-661. I.F.:27,14. 6 Kagi G, Bhatia KP, Tolosa E. The role of DAT-SPECT in movement disorders. J NEUROL NEUROSUR PS, 2010. 81:5-12. I.F.:4,87. Editorials I.F.: 2,51 1 Tolosa E, Molinuevo JL. Cognition in essential tremor: should we worry about progressive cognitive decline?. EUR J NEUROL, 2010. 17:1227-1228. I.F.:2,51. Multicentrics I.F.: 16,34 1 Cubo E, Martin PM, Martin-Gonzalez JA, Rodriguez-Blazquez C, Kulisevsky J. Motor Laterality Asymmetry and Nonmotor Symptoms in Parkinson’s Disease. MOVEMENT DISORD, 2010. 25:70-75. I.F.:4,01. 2 Cubo E, Martin PM, Gonzalez M, Bergareche A, Campos V, Fernandez JM, Alvarez M, Bayes A, RODRIGUEZ-BALZQUEZ. What contributes to driving ability in Parkinson’s disease. DISABIL REHABIL, 2010. 32:374-378. I.F.:1,56. 3 Forjaz MJ, Ayala A, RodriguezBlazquez C, Frades-Payo B, MartinezMartin P. Assessing autonomic symptoms of Parkinson’s disease with the SCOPA-AUT: a new perspective from Rasch analysis. EUR J NEUROL, 2010. 17:273-279. I.F.:2,51. 4 Feldman HH, Doody RS, Kivipelto M, Sparks DL, Waters DD, Jones RW, Schwam E, Schindler R, Hey-Hadavi J, Demicco DA, Breazna A. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease LEADe. NEUROLOGY, 2010. 74:956964. I.F.:8,17. 209 AREA 4 Clinical and experimental neuroscience Neurodegenerative diseases: Clinical and experimental research Team Members Grants for research in progress Marti M. Combined use of neuropsychological, biochemical, and neuroimaging biomarkers for assessment of risk of dementia in Parkinson disease. Sponsored by: Fundació Marató TV3, 60510. Amount: 105.970,00 euros. Duration: 06/02/2007-05/02/2010. Tolosa E. Genetic and environment factors influencing disease expression in Parkinson’s disease caused by LRRK2 mutations. Clinical and imaging studies in LRRK2 mutation carriers without parkinsonism. Sponsored by: Fundació Marató TV3, 061130/31. Amount: 122.845,00 euros. Duration: 02/03/2007-01/03/2010. Valldeoriola F. Estudio de la enervación simpática cardíaca a través de gammagrafía con 123I-MIBG en la enfermedad de parkinson, parkinsonismo vascular y en pacientes con mutaciones del gen LRRK2. Sponsored by: Ministerio Sanidad y Consumo, PI070426. Amount: 67.125,96 euros. Duration: 26/11/2007-30/12/2010. Tolosa E. Síntomas no-motores e integridad de la vía nigroestriatal en portadores “asintomáticos” de mutaciones en el gen LRRK2. Sponsored by: Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS), PI080155. Amount: 77.319,00 euros. Duration: 01/10/2008-31/10/2011. Marti M, Tolosa E, Valldeoriola F, Compta Y. Valor predictivo y diagnóstico de demencia en la enfermedad de parkinson de los marcadores de patología tau y beta-amiloide en líquido cefalorraquídeo y tomografía de emisión de positrones. Sponsored by: Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS), PI080236. Amount: 189.728,00 euros. Duration: 01/01/2009-31/12/2011. 210 Tolosa E. Grup de recerca de malalties neurològiques. Sponsored by: AGAUR (Agència de Gestió d’Ajuts Universitaris i de Recerca -Generalitat de Catalunya), 2009 SGR1019. Amount: 72.800,00 euros. Duration: 01/01/2009-31/12/2013. Ezquerra M. Factores genéticos y ambientales modificadores de la expresividad de las mutaciones del gen LRRK2 en la enfermedad de Parkinson. Sponsored by: Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS), CP06/00126. Amount: 18.050,00 euros. Duration: 01/01/2007-31/12/2013. Marin C. Disfunción olfativa en la enfermedad de Parkinson y su relación con la neurogénesis en la zona subventricular: estudio funcional, molecular e in vitro en el parkinsonismo experimental. Sponsored by: Ministerio de Ciencia e Innovación: Fondo de Investigaciones Sanitarias (FIS), PI080060. Amount: 122.331,00 euros. Duration: 01/01/2009-31/12/2011. Ezquerra M. Identificación de biomarcadores de mirnas en el líquido cefalorraquídeo con interés diagnóstico para la enfermedad de Parkinson y otros parkinsonismos relacionados. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1038. Amount: 86.515,00 euros. Duration: 01/01/2010-31/12/2012. Tolosa E. European Project on Mendelian Forms of Parkinson’s Disease. Sponsored by: Eberhard-Karls Universitaet Tuebingen, 241791. Amount: 34.204,50 euros. Duration: 01/04/2010-31/03/2013. Molinuevo JL. Disfunción cerebral durante el envejecimiento: relevancia para la enfermedad de Alzheimer. Sponsored by: MINISTERIO DE CIENCIA E INNOVACION, CSD2010-00045. Amount: 428.000,00 euros. Duration: 27/12/2010-26/12/2015. Marti M. Combined use of neuropsychological, biochemical, and neuroimaging biomarkers for assessment of risk of dementia in Parkinson disease.. Sponsored by: FUNDACIÓ LA MARATÓ DE TV3, 060510. Amount: 105.970,00 euros. Duration: 06/02/2007-05/11/2010. Sanchez R. Estudio portadores de mutaciones determinantes de demencias monogénicas en fase preclínica: valoración cognitiva, estudio por RMN de volúmenes y conectividad cerebral y de marcadores en LCR. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI080036. Amount: 44.770,00 euros. Duration: 01/01/2009-30/12/2011. Tolosa E. Grup de recerca de malalties neurològiques. Sponsored by: GENERALITAT DE CATALUNYA, 2009_ SGR_1019. Amount: 72.800,00 euros. Duration: 15/09/2009-31/12/2013. Rami L. Caracterización de sujetos con pérdida objetiva o subjetiva de memoria mediante biomarcadores de enfermedad de alzheimer. Análisis de líquido cefalorraquídeo y resonancia magnética como predictores de la evolución cognitiva.. Sponsored by: INSTITUTO DE SALUD CARLOS III, CP08/00147. Amount: 223.287,50 euros. Duration: 07/01/2009-06/01/2015. Thesis Bartres D, Molinuevo JL. Influencia de la reserva cognitiva en la estructura y funcionalidad cerebral en el envejecimiento sano y patologico. PhD student: Beatriz Bosch Capdevila. AREA 4 Team envolved in: Clinical and experimental neuroscience RETIC en Oftalmología (OFTARED) Neurophysiology and functional studies of the nervous system Strategic Objectives GROUP Members TEAM LEADER Josep Valls Solé (Hospital Clínic) Tel.: 93 227 54 13 Fax: 93 227 57 83 E-mail: javalls@clinic.ub.es Idibaps members: Mar Carreño (Hospital Clínic) Xavier Gasull (Facultat de Medicina UB) Arcadi Gual (Facultat de Medicina UB) Alejandro Iranzo (Hospital Clínic) Joan Santamaria (Hospital Clínic) Expansion of scientific knowledge on functional aspects of the nervous system, with maximum integration of the basic and clinical aspects, fundamentally using neurophysiological techniques. From the clinical perspective, the principal objectives are the characterization of the neurophysiological aspects of motor control and perception, and the physiopathological aspects of neuromuscular diseases, sleep disturbances, epilepsy, and conditions characterized by neuropathic pain. In basic research, the principal objectives are the characterization of the cellular physiological mechanisms in both ocular physiology and in the context of neuronal hyper-excitability in neuropathic pain, and the in-depth study of the synaptic transmission modulatory mechanisms. Main Lines of Research 1. The participation of subcortical motor systems in the execution of movements, postural maintenance and reflex control. Study of the alarm circuits based on auditory or somatosensory stimuli. Prepulse phenomena. 2. Physiology and physiopathology of neuropathic pain. Study of nociceptive evoked potentials. Reflex reactions of the autonomous nervous system in response to nociceptive stimulation. Conscious sensory perception. Research Fellows: Elena Abad (Facultat de Medicina) Germán Cuesto Gil (IDIBAPS) Enrique Emilio Syriani (Facultat de Medicina) Gisela Lorente (Facultat de Medicina) Monica Serradell (Fundació Clínic) Astrid Tulleuda (Facultat de Medicina) Jordi Casanova (IDIBAPS) Javier Aparicio (Hospital Clínic) Carlos David Castillo (Hospital clínic) Olga Sierra Bernat (IDIBAPS) Merche Morales (IDIBAPS) Gerard Callejo Martin (Facultat de Medicina) Collaborators: Antonio Donaire (Hospital Clínic) Jordi Palés (Facultat de Medicina) Xavier Sala Blanch (Hospital Clínic) Carles Gaig (Hospital Clínic) Miguel Morales (IDIBAPS) Schematic representation of the experiment carried out to examine subjective perception of a somatosensory stimulus. The patient is subjected to electroencephalographic and electromyographic monitorization and is placed in front of a computer showing a clock with 60 conventional divisions but with a single needle travelling at a speed of 2560 ms per full cycle. The patient is instructed to state the number between 1 and 60 marked by the needle at the moment of stimulus perception. The perception time is determined by subtracting the number stated by the patient from the number corresponding to actual application of the stimulus. The perception time can be checked with the potentials evoked by the stimulus and the reaction time, and reveals the time required for processing of the somatosensory impulse to become conscious. 211 AREA 4 Clinical and experimental neuroscience Neurophysiology and functional studies of the nervous system PUBLICATIONS 3. Study of sleep and its disturbances in different disorders. Numbness. Sleep multiple latency testing. Restless legs syndrome. Periodic leg movements during sleep. 4. Epileptic phenomena and their treatment. Status epilepticus. Monitoring of epileptic seizures. Video-EEG and epidural recording. Epileptic crisis recordings with functional magnetic resonance imaging. 5. The role of actin in the regulation of synaptic transmission. Characterization of the leak channels implicated in neuronal hyper-excitability and cell memory, in neurons of the dorsal root ganglia. 6. Physiology of aqueous humor drainage and physiopathology of glaucoma. Ocular pathology in aging. Physiology of the cells of the ocular trabecular meshwork. RESEARCH GROUP Neurophysiology Group Leader: Xavier Gasull (UB) Within the field of neurophysiology, the group is interested in establishing the functions of different ion channels in the regulation of different cell processes. In particular, at neuron level, we are investigating different ion channels implicated in cellular excitability in sensory neurons of the dorsal root ganglia and trigeminal ganglion, and their relationship with neuropathic pain. On the other hand, in trabecular cells that regulate aqueous humor flow in the eye, we are exploring the role of the cytoskeleton and of different ion channels in the functioning of these cells and their relationship with the physiopathology of glaucoma. 212 Originals I.F.: 107,69 and Essential Tremor. MOVEMENT DISORD, 2010. 25:2577-2586. I.F.:4,01. 1 Hor H, Kutalik Z, Dauvilliers Y, Valsesia 6 Kumru H, Vidal J, Kofler M, Portell A, Lammers GJ, Donjacour CEHM, Iranzo A, Santamaria J, Adrados RP, Vicario JL, Overeem S, Arnulf I, Theodorou I, Jennum P, Knudsen S, Bassetti C, Mathis J, Lecendreux M, Mayer G, Geisler P, Beneto A, Petit B, Pfister C, Burki JV, Didelot G, Billiard M, Ercilla G, Verduijn W, Claas FHJ, Vollenwider P, Waeber G, Waterworth DM, Mooser V, Heinzer R, Beckmann JS, Bergmann S, Tafti M. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. NAT GENET, 2010. 42:786-U80. I.F.:34,28. 2 Iranzo A, Lomena F, Stockner H, Valldeoriola F, Vilaseca I, Salamero M, Molinuevo JL, Serradell M, Duch J, Pavia J, Gallego J, Seppi K, Hogl B, Tolosa E, Poewe W, Santamaria J. Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. LANCET NEUROL, 2010. 9:10701077. I.F.:18,13. 3 Iranzo A, Isetta V, Molinuevo JL, Serradell M, Navajas D, Farre R, Santamaria J. Electroencephalographic slowing heralds mild cognitive impairment in idiopathic REM sleep behavior disorder. SLEEP MED, 2010. 11:534-539. I.F.:3,70. 4 E, Valls-Sole J. Alterations in Excitatory and Inhibitory Brainstem Interneuronal Circuits after Severe Spinal Cord Injury. J NEUROTRAUM, 2010. 27:721-728. I.F.:4,25. 7 Pintor L, Bailles E, Matrai S, Carreno M, Donaire A, Boget T, Setoain X, Rumia J, Bargallo N. Efficiency of Venlafaxine in Patients With Psychogenic Nonepileptic Seizures and Anxiety and/or Depressive Disorders. J NEUROPSYCH CLIN N, 2010. 22:401-408. I.F.:2,34. 8 Lauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, Nolano M, Merkies ISJ, Polydefkis M, Smith AG, Sommer C, Valls-Sole J. European Federation of Neurological Societies/ Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the EFNS and PNS. EUR J NEUROL, 2010. 17:903-E49. I.F.:2,51. 9 Lauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, Noland M, Merkies ISJ, Polydefkis M, Smith AG, Sommer C, Valls-Sole J. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the EFNS and PNS.. J PERIPHER NERV SYST, 2010. 15:79-92. I.F.:3,62. Llado A, Fortea J, Ojea T, Bosch B, Sanz P, Valls-Sole J, Clarimon J, Molinuevo JL, Sanchez-Valle R. A novel PSEN1 mutation (K239N) associated with Alzheimer’s disease with wide range age of onset and slow progression. EUR J NEUROL, 2010. 17:994-996. I.F.:2,51. Nijhuis LBO, Allum JHJ, Valls-Sole J, Overeem S, Bloem BR. First Trial Postural Reactions to Unexpected Balance Disturbances: A Comparison With the Acoustic Startle Reaction. J NEUROPHYSIOL, 2010. 104:2704-2712. I.F.:3,48. 5 Costa J, Gonzalez HA, Valldeoriola F, 11 Penalva JB, Opisso E, Medina J, Gaig C, Tolosa E, Valls-Sole J. Nonlinear Dynamic Analysis of Oscillatory Repetitive Movements in Parkinson’s Disease Corrons M, Kumru H, Vidal J, Valls-Sole J. H reflex modulation by transcranial magnetic stimulation in spinal cord injury 10 AREA 4 Clinical and experimental neuroscience Neurophysiology and functional studies of the nervous system subjects after gait training with electromechanical systems. SPINAL CORD, 2010. 48:400-406. I.F.:1,78. 12 Weiss D, Wachter T, Breit S, Jacob SN, Pomper JK, Asmus F, Valls-Sole J, Plewnia C, Gasser T, Gharabaghi A, Kruger R. Involuntary eyelid closure after STNDBS: evidence for different pathophysiological entities. J NEUROL NEUROSUR PS, 2010. 81:1002-1007. I.F.:4,87. 13 Carreno M, Garcia-Alvarez D, Maestro I, Fernandez S, Donaire A, Boget T, Rumia J, Pintor L, Setoain X. Malignant autosomal dominant frontal lobe epilepsy with repeated episodes of status epilepticus: successful treatment with vagal nerve stimulation. EPILEPTIC DISORD, 2010. 12:155-158. I.F.:1,20. 14 Sansa G, Iranzo A, Santamaria J. Obstructive sleep apnea in narcolepsy. SLEEP MED, 2010. 11:93-95. I.F.:3,70. 15 Soto O, Valls-Sole J, Kumru H. Paired-Pulse Transcranial Magnetic Stimulation During Preparation for Simple and Choice Reaction Time Tasks. J NEUROPHYSIOL, 2010. 104:1392-1400. I.F.:3,48. 16 Sanchez-Gistau V, Pintor L, Sugranyes G, Bailles E, Carreno M, Donaire A, Boget T, Setoain X, Bargallo N, Rumia J. Prevalence of interictal psychiatric disorders in patients with refractory temporal and extratemporal lobe epilepsy in Spain. A comparative study. EPILEPSIA, 2010. 51:1309-1313. I.F.:4,05. 17 Kumru H, Murillo N, Samso JV, Valls-Sole J, Edwards D, Pelayo R, ValeroCabre A, Tormos JM, Pascual-Leone A. Reduction of Spasticity With Repetitive Transcranial Magnetic Stimulation in Patients With Spinal Cord Injury. NEUROREHAB NEURAL RE, 2010. 24:435441. I.F.:5,40. 18 Aiguabella M, Falip M, Veciana M, Bruna J, Palasi A, Corral L, Herrero JI, Boluda S, Mora J, Iranzo A, Serrano C. Refractory nonconvulsive status epilepticus in Creutzfeldt-Jakob disease. EPILEPTIC DISORD, 2010. 12:239-242. I.F.:1,20. 19 Queralt A, Valls-Sole J, Castellote JM. Speeding up gait initiation and gaitpattern with a startling stimulus. GAIT POSTURE, 2010. 31:185-190. I.F.:2,58. 20 Perez-Diaz H, Iranzo A, Santamaria J. Zolpidem-induced sleep-related behavioural disorders. NEUROLOGIA, 2010. 25:491-497. I.F.:0,60. Reviews I.F.: 12,91 1 Deval E, Gasull X, Noel J, Salinas M, Baron A, Diochot S, Lingueglia E. Acid-Sensing Ion Channels (ASICs): Pharmacology and implication in pain. PHARMACOL THERAPEUT, 2010. 128:549-558. I.F.:8,90. 2 Hogl B, Arnulf I, Comella C, Ferreira J, Iranzo A, Tilley B, Trenkwalder C, Poewe W, Rascol O, Sampaio C, Stebbins GT, Schrag A, Goetz CG. Scales to Assess Sleep Impairment in Parkinson’s Disease: Critique and Recommendations. MOVEMENT DISORD, 2010. 25:2704-2716. I.F.:4,01. Grants for research in progress Valls J. Intervencions sobre els components sensorial i emocional de les respostes a estímuls de dolor en pacients amb dolor neuropàtic crònic (Interventions on emotional responses to pain stimuli in patients with chronic neuropathic pain). Sponsored by: Fundació Marató TV3, 71930. Amount: 121.502,00 euros. Duration: 25/02/2008-24/02/2011. Morales M. Synaptic recovery. A new therapy in Alzheimer Disease. Sponsored by: Fundación CIEN. Proyecto Alzheimer Reina Sofia, 0000. Amount: 50.000,00 euros. Duration: 01/01/2008-31/12/2011. Valls J. Mecanismos fisiopatológicos en la cronificación del dolor neuropático y en el origen del síndrome regional complejo. Sponsored by: Instituto de Salud Carlos III, PI080266. Amount: 55.418,00 euros. Duration: 31/12/200830/12/2011. Gual A. Patologia ocular del envejecimiento, calidad visual y calidad de vida. Redes temáticas de centros (RETIC). Sponsored by: Ministerio de Sanidad y Consumo, RD07/0062/0006. Amount: 22.500,00 euros. Duration: 01/01/2007-31/12/2012. Gasull X. El canal de leak TRESK en la excitabilidad neuronal nociceptiva: implicaciones en el dolor neuropático. Sponsored by: FIS, Ministerio de Sanidad y Consumo, PI080014. Amount: 76.351,00 euros. Duration: 01/01/200931/12/2011. Gual A. Lab. Neurofisiologia. Grup consolidat Generalitat de Catalunya. Sponsored by: Generalitat de Catalunya, SGR869. Amount: 42.640,00 euros. Duration: 01/01/2009-31/12/2013. Donaire A. Utilidad de la resonancia magnética funcional ictal en la localización del área epileptógena en pacientes pediátricos con epilepsia focal fármacorresistente. Sponsored by: FISETES, 0000. Amount: 30.000,00 euros. Duration: 01/01/2009-31/12/2010. Valls J. Intervencions sobre els components sensorial i emocional de les respostes a estímuls de dolor en pacients amb dolor neuropàtic crònic (Interventions on emotional responses to pain stimuli in patients with chronic neuropathic pain). Sponsored by: FUNDACIÓ LA MARATÓ DE TV3, 071930. Amount: 121.502,00 euros. Duration: 25/02/2008-31/05/2011. 213 AREA 4 Clinical and experimental neuroscience Team envolved in: CIBER en enfermedades raras (CIBERer) & CIBER en fisiopatología de la obesidad y nutrición (CIBERobn) Secondary lesions due to chronic alcohol ingestion, muscle pathology Strategic Objectives GROUP Members TEAM LEADER Álvaro Urbano Márquez (Hospital Clínic) Tel.: 93 227 55 39 Fax: 93 227 55 39 E-mail: urbano@clinic.ub.es Idibaps members: Francesc Cardellach (Hospital Clínic) Ramón Estruch (Hospital Clínic) Joaquin Fernández (Hospital Clínic) Josep M. Grau (Hospital Clínic) Ferran Masanes (Hospital Clínic) José Maria Nicolás (Hospital Clínic) Emilio Sacanella (Hospital Clínic) Postdoctoral fellows: Glòria Garrabou (CIBERER) Mireia Urpí (Sara Borrell FCRB) Sara Arranz (Sara Borrell) Research Fellows: Rosas Casas (PREDIMED) Ana García Martínez (SAF08) Constanza Morén (CIBERER-FIPSE) Georgina Espígol (PostMIR ISCIII) Marc Corbera (Marató TV3) Sergio Prieto (SAF08) Ester Planas (SAF08) Anna Sandra Hernàndez (Hospital Clínic) Jordi Casanova (PostMIR ISCIII) Gemma Chiva (Beca Manuel de Oya) Palmira Valderas (becària UB) 214 Marco Alba (Hospital Clinic) Itziar Tavera (Hospital Clinic) Sarai Córdoba (Estudiant de Màster) Marc Catalán (Estudiant de Màster) Francesc Borrisser (Estudiant de Màster) Maria Boto (FPU-MICINN) Technicians: Esther Tobias (PAS UB) Mireia Nicolàs (CIBERER) Mercedes Morales (Marató TV3) Nursing Staff: Laia de Lama (PREDIMED) Administrative Staff: Maria Ángeles Galán Dietists: Concha Viñas (PREDIMED) Olalla Rey (PREDIMED) Collaborators: Emilia Antunez (Facultat de Medicina) Xavier Bosch (Hospital Clínic) Edwin Saúl Romero (CNIC) 1. Study of the pathological mechanisms of alcohol upon the organ cells and its pathological effects at neurological and cardiocirculatory level. 2. Importance of alcohol in intracytosolic calcium transport. 3. Effect of food upon the prevention of chronic diseases and cancer. 4. Prognosis of alcoholic myocardiopathy and its best management options. 5. Study of muscle and myocardial apoptosis in subjects presenting chronic alcohol abuse. 6. Study of the physiopathology of muscle diseases, particularly as regards the muscle immunohistochemical, immunogenetic and angiogenic changes (prognostic factors) in inflammatory myopathies. 7. Study of metabolic myopathic disorders, particularly relating to glycogenosis and myoadenylate deaminase deficiency. 8. Study of myocardial regeneration in alcoholic myocardiopathy. 9. Clinical and functional repercussions of chronic fatigue syndrome. 10. Study of the moderate consumption of wine and the Mediterranean diet in the prevention of cardiovascular diseases. 11. Study of primary mitochondrial myopathic disorders in the adult and of secondary mitochondrial involvement in different pathological and toxic situations. 12. Study of the physiopathological mechanisms involved in the development of systemic vasculitis. Our future challenges are: 1. Furthering of knowledge of the action of alcohol upon signals translation and the appearance of apoptosis at muscle and myocardial level, and of the AREA 4 Clinical and experimental neuroscience Secondary lesions due to chronic alcohol ingestion, muscle pathology 2. 3. 4. 5. 6. 7. 8. 9. impact that alterations in mitochondrial DNA and in the mitochondrial respiratory chain may have upon degenerative diseases such as Alzheimer’s disease, inflammatory myopathy and inclusion body diseases. Furthering of knowledge of the prognostic factors in dermatomyositis, with a view to allowing early identification of those cases requiring stronger treatment measures (anti-TNF agents, gammaglobulins). Characterization of the clinical and morphological aspects of metabolic muscle diseases (glycogenosis and MDA deficiency). Study of sarcopenia in the geriatric population. In-depth investigation of the mitochondrial toxicity of antiretroviral drugs and carbon monoxide (CO). Proteomic studies to clarify the mechanisms of skeletal and cardiac muscle damage secondary to alcohol exposure. Study of myocardial cell regeneration from stem cells in the myocardium of chronic alcoholic patients. Study of serum and urine biomarkers in relation to food consumption and changes in cardiovascular disease risk factors. In-depth study of the mechanisms involved in the development of systemic vasculitis. 3. Study of mitochondrial diseases, with special emphasis on biochemical and genetic investigations in different cell substrates. 4. Analysis of mitochondrial respiration and DNA in muscle, adipose tissue and lymphocytes of HIV-infected patients subjected to antiretroviral therapy. 5. Effect of smoking, carbon monoxide, neuroleptic drugs and antibiotics upon the mitochondrial function. 6. Mitochondrial dysfunction in sepsis. II Vascular inflammation: 1. Expressions of cytokines and growth factors in vascular inflammatory lesions and their relationship with phenotypic expression, complications and the prognosis of systemic vasculitis. 2. Study of the interactions among lymphocytes, endothelium and extracellular matrix in the development and perpetuation of vascular inflammation and in the mechanisms that participate in vascular occlusion and regeneration. 3. Development of a questionnaire for evaluating quality of life in patients with giant cell arteritis (international study). 4. Expression of angiogenic and antiangiogenic factors as prognostic data in dermatomyositis. IIIPrevention and treatment of cardiovascular diseases: 1. Research is being carried out into the relationship between alcohol and arterial hypertension; the evolution of alcoholic myocardiopathy, the role of phenolic derivatives in wine and alcohol as influencing factors in the development of atherosclerosis; the effect of nicotine and aging upon mitochondrial respiration; and the presence of growth factors and adhesion molecules in angiogenesis, apoptosis, myocardiopathy and alcoholic myopathy. 2. Study of the effects of moderate wine consumption, the Mediterranean diet and other polyphenol-rich products in the primary prevention of cardiovascular disease and other degenerative disorders. 3. Proteomic studies of skeletal and cardiac muscle in relation to the pathogenesis of tissue damage secondary to alcohol exposure. Main Lines of Research I Research Group in Muscle and Mitochondrial Function: 1. Histological, histochemical and immunohistochemical study of muscle diseases. 2. Study of mitochondrial function in patients susceptible to mitochondrial disorders of genetic (primary) or toxic (secondary) origin. Gomori trichromic staining of a muscle fibre in a patient with HIV infection showing mitochondrial toxicity due to antiretroviral treatment with zidovudine (AZT). The white arrows indicate the presence of so-called raggedred fibres, suggestive of toxic myopathy. 215 AREA 4 Clinical and experimental neuroscience Secondary lesions due to chronic alcohol ingestion, muscle pathology Team Members PUBLICATIONS Originals I.F.: 65,52 1 Smithson A, Perello R, Aibar J, Espinosa G, Tassies D, Freire C, Castro P, Suarez B, Lozano F, Nicolas JM. Genotypes Coding for Low Serum Levels of Mannose-Binding Lectin Are Underrepresented among Individuals Suffering from Noninfectious Systemic Inflammatory Response Syndrome. CLIN VACCINE IMMUNOL, 2010. 17:447-453. I.F.:2,37. 2 Lozano E, Segarra M, Corbera-Bellalta M, Garcia-Martinez A, Espigol-Frigole G, Pla-Campo A, Hernandez-Rodriguez J, Cid MC. Increased expression of the endothelin system in arterial lesions from patients with giant-cell arteritis: association between elevated plasma endothelin levels and the development of ischaemic events. ANN RHEUM DIS, 2010. 69:434-442. I.F.:8,11. 3 7 Prieto RM, Fiol M, Perello J, Estruch R, Ros E, Sanchis P, Grases F. Effects of Mediterranean diets with low and high proportions of phytate-rich foods on the urinary phytate excretion. EUR J NUTR, 2010. 49:321-326. I.F.:2,87. 8 Corella D, Carrasco P, Fito M, MartinezGonzalez MA, Salas-Salvado J, Aros F, Lapetra J, Guillen M, Ortega-Azorin C, Warnberg J, Fiol M, Ruiz-Gutierrez V, Serra-Majem L, Martinez JA, Ros E, Estruch R. Gene-environment interactions of CETP gene variation in a high cardiovascular risk Mediterranean population. J LIPID RES, 2010. 51:27982807. I.F.:4,92. 9 Noguera A, Moren C, Rovira N, Sanchez E, Garrabou G, Nicolas M, Munoz-Almagro C, Cardellach F, Miro O, Fortuny C. Evolution of Mitochondrial DNA Content After Planned Interruption of HAART in HIV-Infected Pediatric Patients. AIDS RES HUM RETROV, 2010. 26:1015-1018. I.F.:2,18. Zazpe I, Estruch R, Toledo E, SanchezTainta A, Corella D, Bullo M, Fiol M, Iglesias P, Gomez-Gracia E, Aros F, Ros E, Schroder H, Serra-Majem L, Pinto X, Lamuela-Raventos R, Ruiz-Gutierrez V, Martinez-Gonzalez MA. Predictors of adherence to a Mediterranean-type diet in the PREDIMED trial. EUR J NUTR, 2010. 49:91-99. I.F.:2,87. 4 10 Perona JS, Covas MI, Fito M, Cabello- Xarau SN, Romay MA, Martinez JMM, Clanchet JD, Prat ER, Sola JF. Multiple chemical sensitivity: Epidemiological, clinical and prognostic differences between occupational and non-occupational cases. MED CLIN-BARCELONA, 2010. 135:52-58. I.F.:1,23. 5 Lohse B, Psota T, Estruch R, Zazpe I, Sorli JV, Salas-Salvado J, Serra M, Krall JS, Marquez F, Ros E. Eating Competence of Elderly Spanish Adults Is Associated with a Healthy Diet and a Favorable Cardiovascular Disease Risk Profile. J NUTR, 2010. 140:1322-1327. I.F.:4,09. 216 6 Llorente-Cortes V, Estruch R, Mena MP, Ros E, Gonzalez MAM, Fito M, LamuelaRaventos RM, Badimon L. Effect of Mediterranean diet on the expression of proatherogenic genes in a population at high cardiovascular risk. ATHEROSCLEROSIS, 2010. 208:442-450. I.F.:4,52. Moruno R, Aros F, Corella D, Ros E, Garcia M, Estruch R, Martinez-Gonzalez MA, Ruiz-Gutierrez V. Reduction in systemic and VLDL triacylglycerol concentration after a 3-month Mediterranean-style diet in highcardiovascular-risk subjects. J NUTR BIOCHEM, 2010. 21:892-898. I.F.:4,29. 11 Razquin C, Martinez JA, Martinez-Gonzalez MA, Salas-Salvado J, Estruch R, Marti A. A 3-year Mediterranean-style dietary intervention may modulate the association between adiponectin gene variants and body weight change. EUR J NUTR, 2010. 49:311-319. I.F.:2,87. 12 Estruch R. Anti-inflammatory effects of the Mediterranean diet: the experience of the PREDIMED study. P NUTR SOC, 2010. 69:333-340. I.F.:4,32. 13 Selva-O’callaghan A, Grau JM, Gamez-Cenzano C, Vidaller-Palacin A, Martinez-Gomez X, Trallero-Araguas E, Andia-Navarro E, Vilardell-Tarres M. Conventional Cancer Screening versus PET/ CT in Dermatomyositis/Polymyositis. AM J MED, 2010. 123:558-562. I.F.:4,47. 14 Urpi-Sarda M, Llorach R, Khan N, Monagas M, Rotches-Ribalta M, LamuelaRaventos R, Estruch R, Tinahones FJ, Andres-Lacueva C. Effect of Milk on the Urinary Excretion of Microbial Phenolic Acids after Cocoa Powder Consumption in Humans. J AGR FOOD CHEM, 2010. 58:4706-4711. I.F.:2,47. 15 Cuatrecasas G, Gonzalez MJ, Alegre C, Sesmilo G, Fernandez-Sola J, Casanueva FF, Garcia-Fructuoso F, Poca-Dias V, Izquierdo JP, Puig-Domingo M. High Prevalence of Growth Hormone Deficiency in Severe Fibromyalgia Syndromes. J CLIN ENDOCR METAB, 2010. 95:4331-4337. I.F.:6,20. 16 Roson B, Monte R, Gamallo R, Puerta R, Zapatero A, Fernandez-Sola J, Pastor I, Giron JA, Laso J. Prevalence and routine assessment of unhealthy alcohol use in hospitalized patients. EUR J INTERN MED, 2010. 21:458-464. I.F.:1,39. 17 Prieto S, Grau JM. The geoepidemiology of autoimmune muscle disease. AUTOIMMUN REV, 2010. 9:A330-A334. I.F.:6,37. Reviews I.F.: 8,12 1 Lopez-Miranda J, Perez-Jimenez F, Ros E, DeCaterina R, Badimon L, Covas MI, Escrich E, Ordovas JM, Soriguer F, Abia R, DeLaLastra CA, Battino M, Core- AREA 4 Clinical and experimental neuroscience Secondary lesions due to chronic alcohol ingestion, muscle pathology lla D, Chamorro-Quiros J, Delgado-Lista J, Giugliano D, Esposito K, Estruch R, Fernandez-Real JM, Gaforio JJ, LaVecchia C, Lairon D, Lopez-Segura F, Mata P, Menendez JA, Muriana FJ, Osada J, Panagiotakos DB, Paniagua JA, PerezMartinez P, Perona J, Peinado MA, Pineda-Priego M, Poulsen HE, Quiles JL, Ramirez-Tortosa MC, Ruano J, SerraMajem L, Sola R, Solanas M, Solfrizzi V, DeLaTorre-Fornell R, Trichopoulou A, Uceda M, Villalba-Montoro JM, Villar-Ortiz JR, Visioli F, Yiannakouris N. Olive oil and health: Summary of the II international conference on olive oil and health consensus report, Jaen and Cordoba (Spain) 2008. NUTR METAB CARDIOVAS, 2010. 20:284-294. I.F.:3,52. 2 Selva-O’callaghan A, Trallero-Araguas E, Grau-Junyent JM, Labrador-Horrillo M. Malignancy and myositis: novel autoantibodies and new insights. CURR OPIN RHEUMATOL, 2010. 22:627-632. I.F.:4,60. Editorials I.F.: 35,59 1 Estruch R, Lamuela-Raventos RM. Alcohol, wine and cardiovascular disease, two sides of the same coin. INTERN EMERG MED, 2010. 5:277-279. I.F.:2,37. 2 Grau JM, Prieto-Gonzalez S. Biologic agents in myositis: unsolved questions. MED CLIN-BARCELONA, 2010. 135:263264. I.F.:1,23. 3 Grau JM, Cardellach F. Rare diseases and the internal medicine specialist. MED CLIN-BARCELONA, 2010. 134:540-541. I.F.:1,23. 4 Jubany LI, Selva-O’callaghan A, PerezVega C, Grau-Junyent JM, HernandezLosa J, Vilardell-Tarres M. The patient has the diagnosis. LANCET, 2010. 376:14361436. I.F.:30,76. Grants for research in progress Estruch R. Balance beneficio / riesgo del contenido en polifenoles y alcohol del vino: bases científicas de los efectos del consumo moderado de vino sobre el sistema cardiovascular. Sponsored by: Ministerio Educación y Ciencia, AGL200614228-C03-01. Amount: 38.720,00 euros. Duration: 01/10/2006-31/12/2010. Estruch R. Efectos de tomate procesado casero sobre los biomarcadores inflamatorios relacionados con la arteriosclerosis. Sponsored by: Ministerio Educación y Ciencia, AGL2007-66638-C02-02. Amount: 100.430,00 euros. Duration: 01/12/200730/11/2010. Estruch R. Bases biológicas de los Efectos Protectores de la Dieta Mediterránea en la Enfermedad Cardiovascular: Efectos sobre la adiposidad, hormonas relacionadas y marcadores de inflamación. Sponsored by: Ministerio Sanidad y Consumo, PI070473. Amount: 333.960,00 euros. Duration: 26/11/2007-30/12/2010. Estruch R. Alimentación saludable en la prevención primaria de enfermedades crónicas: la Red PREDIMED. Sponsored by: Instituto de Salud Carlos III, RD06/0045/1003. Amount: 27.840,00 euros. Duration: 29/02/2008-31/12/2011. Estruch R. Effects of a mediterranean diet intervention on atherosclerotic burden measured by imaging techniques and systemic biomarkers. PREDIMED. (Effects of a 2-year Mediterranean diet intervention on 3T MRI-monitored carotid plaque progression and vulnerability). Sponsored by: Centro Nacional de Investigaciones Cardiovasculares (CNIC), 06-2007-S01. Amount: 53.062,79 euros. Duration: 01/01/2008-31/12/2011. Cardellach F, Coll JO, Hernandez AS, Garrabou G, Morén C. Toxicidad mitocon- drial inducida por el consumo de tabaco en gestantes y sus recién nacidos. Sponsored by: FIS ISCIII, PI080229. Amount: 40.250,00 euros. Duration: 01/01/2009-31/12/2011. Estruch R, Sacanella E, Masanes F, Chiva G, Casas R. Desarrollo de biomarcadores de consumo y de efecto de un patrón de alimentación Mediterranea en la prevención de la enfermedad cardiovascular. Una aproximación metabolómica. Sponsored by: Ministerio de Ciencia e Innovación, AGL2009-13906-C02-01. Amount: 90.000,00 euros. Duration: 01/01/201031/12/2013. Estruch R. Desarrollo de biomarcadores de consumo y efecto de un patrón de alimentación mediterráneo en la prevención de la enfermedad cardiovascular: biomarcadores de inflamación y estabilidad de la placa de AT. Sponsored by: MINISTERIO DE EDUCACIÓN, AGL2009_13906_C02_02. Amount: 108.900,00 euros. Duration: 01/01/201031/12/2012. Grau J. Grup de recerca muscular. Sponsored by: GENERALITAT DE CATALUNYA, 2009_SGR_1158. Amount: 0,01 euros. Duration: 23/09/2009-31/12/2013. Grau J. Anticossos antitransglutaminasa en biòpsies musculars de pacients amb miopatia inflamatòria. Sponsored by: FIS-ISCIII, PI08/0450. Amount: 33.880,00 euros. Duration: 01/01/2008-31/12/2010. Grau J. Grup de Recerca Consolidat SGR 1158. Sponsored by: AGAUR-Generalitat de Catalunya, 48/227.06/09. Amount: 0,00 euros. Duration: 01/01/2009-31/12/2012. Thesis Andres-Lacueva C, Estruch R, Monagas M. Interaction between cocoa polyphenols and inflammatory biomarkers of atherosclerosis in high-risk subjects for cardiovascular disease. PhD student: Nasiruddin Khan. 217 AREA 4 Clinical and experimental neuroscience Team envolved in: CIBER en enfermedades neurodegenerativas (CIBERned) & Red de Terapia Celular Cellular biology of pathological processes Strategic Objectives GROUP Members TEAM LEADER Jordi Alberch (Facultat de Medicina UB) Tel.: 93 403 52 85 Fax: 93 402 19 07 Idibaps members: Josep M. Canals (Facultat de Medicina UB) Gustavo Egea (Facultat de Medicina UB) Esther Perez (Facultat de Medicina UB) Silvia Gines (Facultat de Medicina UB) Postdoctoral fellows: Albert Giralt (Facultat de Medicina) Miriam Esgleas (RETICS, IDIBAPS) Ana Saavedra (CIBERNED, UB) Verónica Brito (CHDI Foundation) Juan Manuel Durán (UB) Research Fellows: Olga Carretón (UB) Laura Rué (UB) Laia Salcedo (FPI, UB) Javier Selva (UB) 218 Enrique Gutiérrez (CIRIT) Mar Puigdellívol (CHDI Foundation) Adrià Sicart (UB) Marta Anglada (FPI, UB) Andreas Mezger (PLE2009, UB) Mónica Pardo (PLE2009, UB) Carla Serra (FPI, UB) Technicians: Cristina Herranz (RETICS, IDIBAPS) Ana López (CIBERNED) Maite Muñoz (Facultat de Medicina) Josep Barrachina (Facultat de Medicina) Collaborators: Raquel Martín-Ibáñez (CIBERNEDUB) Bet Sarri (Facultat de Medicina) Xavier Xifro (UG) 1. Study of the cellular and molecular bases involved in neuronal dysfunction and death associated with basal ganglia neurodegenerative disorders, fundamentally Huntington’s disease. Our aim is to identify intracellular pathways – both neuroprotective and apoptotic – that are selectively altered in the affected neuron populations, with the ultimate purpose of identifying new therapeutic targets in the management of these neurodegenerative diseases. 2. Identification of the mechanisms participating in the cognitive defects seen in Huntington’s disease. Knowledge of these mechanisms will make it possible to develop new treatments for avoiding the cognitive disorders induced by the mutated huntingtin gene. 3. Characterization of the mechanisms of neuron differentiation of stem cells from different organs. Our aim is to identify different extrinsic and intrinsic factors contributing to neuron differentiation, with the aim of employing stem cells in cell substitution therapies. 4. Exploration of the molecular mechanisms involved in the interaction of the cytoskeleton with the cell endomembrane system as structural and functional support in secretory and endocytic membrane traffic. Studies are also made of the way in which this interaction is altered in certain diseases such as alcoholism and other conditions with a strong cardiovascular base such as Marfan syndrome and Loeys-Dietz syndrome. Main Lines of Research 1. Molecular bases of the interaction of actin dynamics with the Golgi apparatus and secretory traffic. 2. Role of diacylglycerol and phosphatidic acid in the formation of transport vesicles and in the structural organization of the Golgi apparatus. 3. Study of the signaling pathways that regulate the cytoskeleton and actin dynamics, altered by ethanol and other toxic agents. 4. Intracellular traffic and cytokine receptor signaling (TGF-beta). 5. Study of the implication of neurotrophic factors in the physiopathology and treatment AREA 4 Clinical and experimental neuroscience Cellular biology of pathological processes of neurodegenerative diseases of the basal ganglia. 6. Study of the intracellular signaling cascades implicated in the degeneration of striatal and hippocampal neurons in Huntington’s disease. 7. Study of the mechanisms underlying the differentiation of stem cells into neurons, for application to cellular therapy in neurodegenerative diseases such as Huntington’s chorea. PUBLICATIONS Originals I.F.: 65,35 1 Martin-Ibanez R, Crespo E, Urban N, Sergent-Tanguy S, Herranz C, Jaumot M, Valiente M, Long JE, Pineda JR, Andreu C, Rubenstein JLR, Marin O, Georgopoulos K, Mengod G, Farinas I, Bachs O, Alberch J, Canals JM. Ikaros-1 Couples Cell Cycle Arrest of Late Striatal Precursors With Neurogenesis of Enkephalinergic Neurons. J COMP NEUROL. 518:329-351. I.F.:3,72. 2 Distribution of optineurin (red) and Golgi (green) in neuron precursors. The nucleus is stained with Topro-3 (blue). RESEARCH GROUP Membrane traffic Group Leader: Gustavo Egea (UB) The objective of this group is to understand the principles that control and regulate transport of the membrane components (lipids and proteins) within the cell. In particular, we are investigating the interaction of the transport intermediaries (vesicles and tubules) with the actin cytoskeleton and its associated proteins and regulators (myosins and Rho GTPases). We are also exploring the way in which lipid homeostasis (particularly referred to diacylglycerol) participates in the organization and traffic of membranes and in the formation of transport intermediaries. Lastly, we wish to establish the physiopathological bases whereby ethanol alters nerve cell function and the mechanism underlying internalization of the receptors of cytokines such as TGF-beta in the smooth muscle cells of the coronary vessels in cardiovascular patients. Twohig JP, Roberts MI, Gavalda N, Rees-Taylor EL, Giralt A, Adams D, Brooks SP, Bull MJ, Calder CJ, Cuff S, Yong AA, Alberch J, Davies A, Dunnett SB, Tolkovsky AM, Wang ECY. Age-Dependent Maintenance of Motor Control and Corticostriatal Innervation by Death Receptor 3. J NEUROSCI. 30:3782-3792. I.F.:7,18. 3 DelToro D, Xifro X, Pol A, Humbert S, Saudou F, Canals JM, Alberch J. Altered cholesterol homeostasis contributes to enhanced excitotoxicity in Huntington’s disease. J NEUROCHEM. 115:153-167. I.F.:4,00. 4 Giralt A, Friedman HC, CanedaFerron B, Urban N, Moreno E, Rubio N, Blanco J, Peterson A, Canals JM, Alberch J. BDNF regulation under GFAP promoter provides engineered astrocytes as a new approach for long-term protection in Huntington’s disease. GENE THER. 17:1294-1308. I.F.:4,75. 5 Estevez M, Fernandez-Ulibarri I, Martinez E, Egea G, Samitier J. Changes in the internal organization of the cell by microstructured substrates. SOFT MATTER. 6:582-590. I.F.:4,87. 6 Gines S, Paoletti P, Alberch J. Impaired TrkB-mediated ERK1/2 Acti- vation in Huntington Disease Knock-in Striatal Cells Involves Reduced p52/ p46 Shc Expression. J BIOL CHEM. 285:21537-21548. I.F.:5,33. 7 Urban N, Martin-Ibanez R, Herranz C, Esgleas M, Crespo E, Pardo M, Crespo-Enriquez I, Mendez-Gomez HR, Waclaw R, Chatzi C, Alvarez S, Alvarez R, Duester G, Campbell K, DeLera AR, Vicario-Abejon C, Martinez S, Alberch J, Canals JM. Nolz1 promotes striatal neurogenesis through the regulation of retinoic acid signaling. NEURAL DEV. 5:21-. I.F.:3,39. 8 Saavedra A, Garcia-Martinez JM, Xifro X, Giralt A, Torres-Peraza JF, Canals JM, Diaz-Hernandez M, Lucas JJ, Alberch J, Perez-Navarro E. PH domain leucine-rich repeat protein phosphatase 1 contributes to maintain the activation of the PI3K/Akt prosurvival pathway in Huntington’s disease striatum. CELL DEATH DIFFER. 17:324-335. I.F.:8,24. 9 Rocher-Ros V, Marco S, Mao JH, Gines S, Metzger D, Chambon P, Balmain A, Saura CA. Presenilin modulates EGFR signaling and cell transformation by regulating the ubiquitin ligase Fbw7. ONCOGENE. 29:29502961. I.F.:7,14. 10 Selva J, Martinez SE, Buceta D, Rodriguez-Vazquez MJ, Blanco MC, Lopez-Quintela MA, Egea G. Silver Sub-nanoclusters Electrocatalyze Ethanol Oxidation and Provide Protection against Ethanol Toxicity in Cultured Mammalian Cells. J AM CHEM SOC. 132:6947-6954. I.F.:8,58. 11 Graus F, Boronat A, Xifro X, Boix M, Svigelj V, Garcia A, Palomino A, Sabater L, Alberch J, Saiz A. The expanding clinical profile of anti-ampa receptor encephalitis. NEUROLOGY. 74:857-859. I.F.:8,17. 219 AREA 4 Clinical and experimental neuroscience Secondary lesions due to chronic alcohol ingestion, muscle pathology Team Members Grants for research in progress Alberch J. Development of neuroprotectve strategies with BDNF in Huntington’s Disease. Sponsored by: Fundació Marató TV3, 62010. Amount: 187.500,00 euros. Duration: 15/02/2007-14/02/2010. Canals JM. Red de Terapia Celular. Sponsored by: Ministerio Sanidad y Consumo, RD06/0010/0006. Amount: 409.198,00 euros. Duration: 01/01/2007-31/12/2011. Perez E. Estudio de mecanismos moleculares implicados en la vulnerabilidad. Sponsored by: Instituto de Salud, PI071183. Amount: 125.840,00 euros. Duration: 15/10/2007-14/09/2010. Egea G. Nanotecnologías en Biomedicina. Sponsored by: Ministerio de Ciencia e Innovación (MICINN), CONSOLIDER-INGENIO 2010-0012. Amount: 0,00 euros. Duration: 01/01/2006-31/12/2010. Alberch J. Generación de nuevos modelos de enfermedad de Huntington para valorar el papel del BDNF en los mecanismos patogénicos y en nuevas perspectivas terapéuticas. Sponsored by: Ministerio de Ciencia e Innovación (MICINN), SAF2008-04360. Amount: 266.000,00 euros. Duration: 01/01/2009-31/12/2011. Alberch J. Habilitación de salas GMP para el programa de terapia celular de la Facultat de Medicina. Sponsored by: Ministerio de Ciencia e Innovación (MICINN), PLE2009-0128. Amount: 950.000,00 euros. Duration: 01/11/2009-31/10/2012. Canals JM. Mejora de la supervivencia y diferenciación de células madre neu- 220 rales humanas para terapia celular de la enfermedad de Huntington. Sponsored by: Ministerio de Ciencia e Innovación (MICINN), PLE2009-0089. Amount: 950.000,00 euros. Duration: 01/11/200931/10/2012. Gines, S. Role of p75 Neurotrophin Receptor in Huntington’s Disease. Sponsored by: HIGH Q FOUNDATION - INC -OFICIAL, A-3468. Amount: 159.145,00 euros. Duration: 01/05/2010-30/04/2012. Gines, S. Role of Cdk5 in Striatal and Hippocamapl Pathology in Huntingtons Disease. Sponsored by: HIGH Q FOUNDATION - INC -OFICIAL, A-3880. Amount: 152.557,00 euros. Duration: 01/11/2010-31/10/2012. Egea G. Red Nacional sobre Integración funcional del tráfico de membranas, la señalización intracelular y la dinámica del citoesqueleto. Sponsored by: Ministerio de Ciencia e Innovación (MICINN), BFU2008-03958-E/BMC. Amount: 30.000,00 euros. Duration: 01/11/200930/12/2012. Egea G. La dinámica de la actina y la homeostasis del diacilglicerol en la organización del aparato de Golgi. Sponsored by: Ministerio de Ciencia e Innovación (MICINN), BFU2009-07186(BMC). Amount: 260.000,00 euros. Duration: 01/01/2009-31/12/2012. Egea G. Nanotecnologías en Biomedicina. Sponsored by: Ministerio de Ciencia e Innovación (MICINN), 20100012. Amount: 0,00 euros. Duration: 01/01/2006-14/09/2011. Gines, S. Estudio de las cascadas de señalización asociadas a la activación dopaminérgica y glutamatérgica como estrategia terapéutica en modelos murinos de la enfermedad de Huntington: Papel de la vía de Cdk5. Sponsored by: Ministerio de Ciencia e Innovación, SAF2009-07077. Amount: 108.900,00 euros. Duration: 01/01/200931/12/2012. Canals JM. Caracterización de nuevos factores de transcripción para la diferencaicaión neuronal de células madre para la enfermedad neurodegenerativa de Huntington. Sponsored by: Ministerio de Ciencia e Innovación (MICINN), SAF2009-07774. Amount: 217.800,00 euros. Duration: 01/01/2010-31/12/2012. Alberch J. Fisiopatología de las enfermedades neurodegenerativas. Sponsored by: Generalitat de Catalunya, SGR200900326. Amount: 45.760,00 euros. Duration: 01/01/2009-31/12/2013. Canals JM. Terapia Celular: Implicación de células madre adultas. Sponsored by: CMRB-Generalitat de Catalunya, PROMT-0901. Amount: 0,00 euros. Duration: 01/01/2010-31/12/2011. Thesis Canals JM. Caracterizacion de los factores de transcripcion de la familia Ikaros durante el desarrollo estriatal. PhD student: Desamparats Crespo March. Alberch J. Estudio de los procesos activadores de la patologia en la enfermedad de Huntington: Alteraciones en la plasticidad sinaptica y perspectivas terapeuticas. PhD student: Albert Giralt Torroella. Gines S. Estudio de las vías de supervivencia y muerte neuronal en modelos de la nefermedad de Huntington. PhD student: Paola Paoletti Rubia. AREA 4 Team envolved in: Clinical and experimental neuroscience CIBER en Salud Mental (CIBERsam) Biological bases of psychiatric disorders and nuclear psychiatry Strategic Objectives GROUP Members TEAM LEADER Miguel Bernardo (Hospital Clínic) Tel.: 93 227 54 00 (Ext.: 3142) Fax: 93 227 55 48 E-mail: bernardo@clinic.ub.es Idibaps members: Josefina Castro (Hospital Clínic) Rosa Catalán (Hospital Clínic) Cristobal Gastó (Hospital Clínic) Antoni Gual (Hospital Clínic) Fernando Gutierrez (Hospital Clínic) Amalia Lafuente (TU) Luisa Lázaro (Hospital Clínic) Francisco J. Lomeña (Hospital Clínic) Anabel Martínez-Arán (Hospital Clínic) Guillem Masana (Hospital Clínic) Eduard Parellada (Hospital Clínic) Luis Pintor (Hospital Clínic) Mercè Torra (Hospital Clínic) Manuel Valdés (Hospital Clínic) Eduard Vieta (Hospital Clínic) Antonio Benabarre (Hospital Clínic) Rocío Martín-Santos (Hospital Clínic) Francesc Colom (Fundació Clínic) Lluïsa Garcia (Hospital Clínic) Inmaculada Baeza (Hospital Clínic) Astrid Morer Liñán (Hospital Clínic) Susana Andrés (Hospital Clínic) Rafel Penadés (Hospital Clínic) Technicians: M Alicia Durán (Fundació Clínic) Rosa Maria Palaus (Fundació Clínic) Nursing Staff: Ana Meseguer (CIBERSAM) Administrative Staff: Anna Folch (CIBERSAM) Collaborators: Jordi Blanch (Hospital Clínic) Mercè Comes (Hospital Clínic) Jose Manuel Goikolea (Hospital Clínic) Ester Gómez (Hospital Clínic) Joana Guarch (Hospital Clínic) Teodoro Marcos (Hospital Clínic) Sergi Mas Herrero (Associat) Victor Navarro (Hospital Clínic) Joan de Pablo (Hospital Clínic) Maria Reinares (CIBERSAM) Jose Toro (Hospital Clínic) Carla Torrent (CIBERSAM) Elena de la Serna (CIBERSAM) Patricia Gasso (Fundació Clínic) Eva Baillés (Fundació Clínic) Montse Batllé (IDIBAPS) Piero Castro Loli (Fund. Clinic) Anna Crescenti (FI, Generalitat) Caterina del Mar Bonnin (IDIBAPS) José Sánchez-Moreno (CIBERSAM) Carolina Franco (Hospital Clinic) Isabella Pachiarotti (CIBERSAM) Adriane R. Rosa (IDIBAPS) Marc Valentí (IDIBAPS) Clemente Garcia-Rizo (Hospital Clínic) Andrea Murru (Fundació Clinic) Brisa Solé (IDIBAPS) Rosa Calvo (Hospital Clinic) Miquel Bioque (CIBERSAM) Alicia Valiente (Hospita Clínic) Cristina V. Oliveira (Fundació Clínic) Claudia Cullell (CIBERSAM) Esther Jimenez (IDIBAPS) Alessandra Nivoli (Fundació Clínic) Pere Castellví (CIBERSAM) Núria Cruz (CIBERSAM) Javier Goti (Hospital Clínic) Rosa Díaz (Hospital Clínic) Maria Teresa Plana (Hospital Clínic) Vanessa Sánchez (Hospital Clínic) Soledad Romero (Hospital Clínic) Bibiana Cabrera (Fundació Clínic) Enric Buisan (ForumClinic) Nuria Pujol (IDIBAPS) Olga Puig (Hospital Clínic) Our group studies serious psychiatric disorders from the neurobiological and therapeutic perspectives, based on the following 6 research lines: bipolar disorders, schizophrenia and depression-anxiety, pediatric psychiatry and psychology, psychiatric intervention in medical pathology and alcoholism. Main Lines of Research The bipolar disorders program mainly investigates the neurobiological and anatomofunctional mechanisms implicated in the development of the disease (genetics, neuromodulators, hormone factors and neuroimaging) and its relapses, the clinical course and neuropsychological consequences, the efficacy of drug treatments and novel therapies, and psychological interventions for the early detection and prevention of recurrences – increasing treatment compliance and improving the efficacy of the therapeutic strategies applied to bipolar disorder. The strategic objectives are to investigate the causes and mechanisms involved in the etiopathogenesis of bipolar disorder, and to investigate new treatments with a view to improving the prognosis of the disease. The schizophrenia program focuses research on the first schizophrenic episodes and on resistant and comorbid schizophrenia, through functional neuroimaging (brain perfusion and receptors SPECT, PET and functional magnetic resonance imaging). Sensory and cognitive neuroactivation studies have been made with frontal activation neuropsychological tests and dopaminergic receptor occupation studies, as well as studies of the presynaptic dopaminergic function. Likewise, plasma metabolites of dopamine have been investigated as biological indicators of relapse in a prospective longitudinal follow-up and treatment response study. We have 221 AREA 4 Clinical and experimental neuroscience Biological bases of psychiatric disorders and nuclear psychiatry examined the role of schizophrenia in the development of cardiovascular and metabolic diseases, and secondarily also the role of antipsychotic drugs. The pharmacogenetics of antipsychotic drugs has been studied to assess the efficacy and safety of these drugs on the basis of the individual patient genetic characteristics. Specifically, we have analyzed the pharmacogenetics of the extrapyramidal effects caused by antipsychotic drug therapy, the polymorphisms associated with the risk of schizophrenia, and new pharmacogenetic techniques for implantation at healthcare and hospital level. A psychoeducational program has been introduced, adopting new knowledge transmission and exchange formulas, with the application of new technologies and offering rigorous and communicatively adequate contents. The new FòrumClínic web is an interactive program designed to increase patient autonomy in relation to personal health. A program is being developed for characterizing and preventing second psychotic episodes, in order to design preventive strategies allowing us to influence the course of the disease. The Alcohol Unit is the reference in Catalonia for the treatment of alcohol dependency. We are one of the main research groups in Spain and at present are attempting to consolidate a European leadership position in the setting of short interventions designed to reduce consumption among alcohol consumers at risk. A number of research lines are being conducted in the context of the Alcohol Unit. The main lines are the following: Prospective longitudinal study of alcoholic disease; Follow-up of a cohort of 850 patients starting treatment in 1987 in the Catalan Drug Dependencies Network (Xarxa Catalana de Drogodependències); 222 Screening instruments and techniques for early detection and short counselling in alcohol-consumers at risk in the hospital setting and in primary care; Evaluation and prognosis of alcoholic patients candidates for liver transplantation; treatment of smoking in alcoholic patients; and Evaluation of the European alcohol policies and their public health impact. The line relating to depression aims to implement new psychopathological and biological endophenotypic methods in application to major depression, with the development of mechanisms for the analysis of the mechanism of action of antidepressant drugs based on the platelet model of depression (developed together with the hemostasis group led by Prof. Ginés-Escolar); the investigation of neurotrophic factors (BDNF) in depressive patients; and the exploration of factors conditioning the residual symptoms of major depression. The main research lines of the pediatric psychiatry and psychology research group of the Clinic hospital are the following: • Schizophrenia and bipolar disorder: Study and follow-up of the first psychotic episodes, cognitive rehabilitation of adolescent patients with schizophrenia, study of children and adolescents with a high genetic risk of developing schizophrenia and bipolar disorder (offspring of patients with such disorders), study of the prodromic manifestations of psychotic disorders in children and adolescents, and study of the tolerance and safety of antidepressants in children and adolescents. • Anorexia and bulimia nervosa, and obsessive-compulsive disorder: Study of the common and differential alterations (genetic, neuropsychological and neuroimaging) of anorexia nervosa and obsessivecompulsive disorder, study of MRI image of a healthy control of the study; genotype-phenotype and environment interaction. Application of a predictive model in first psychotic episodes. new management approaches (psychological and pharmacological) in bulimia and anorexia nervosa, and study of autoimmune alterations in obsessive behavior and in anorexia. • Others: mention should be made of the investigation of addictive behaviors, analyzing the percentages of patients seen in the Department of Pediatric Psychiatry with different disorders and who moreover consume, abuse of or show dependency of toxic substances – exploring the efficacy of new multimodal management modalities for addictive behavior in adolescents. In addition, the study line of the efficacy and safety of psychoactive drugs in children and adolescents focuses on the evaluation and follow-up of the side effects of these drugs in children and adolescents, as well as on the identification of pharmacogenetic predictors of drug response in such patients. The study line in autistic spectrum disorders explores the efficacy of new psychological and pharmacological treatments in these disorders, with examination of the neuropsychological profile of children with high-function autistic spectrum disorders and the correlation to clinical variables. Mention also should be made of the line for the development AREA 4 Clinical and experimental neuroscience Biological bases of psychiatric disorders and nuclear psychiatry and validation of scales in application to different pathologies or symptoms. In turn, the line referred to attention deficit hyperactivity disorder (ADHA) involves the neuropsychological, clinical and neuroimaging assessment of predominantly inattentive children versus children with combinedtype attention deficit. Lastly, the research line in autoimmune/Tourette syndrome explores the inflammatory and autoimmune processes, and their relation to serious psychiatric pathology, in children and adolescents. The line of psychiatric intervention in clinical pathology has focused research on knowledge of the psychiatric alterations seen in the main neurological diseases: dementia, multiple sclerosis, epilepsy, Parkinson’s disease and Huntington’s disease. The study of psychiatric disease and psychological aspects associated with medical-surgical hospital processes in turn addresses: transplantation, delirium, psychiatric problems in clinical patients admitted to a general hospital, the evaluation of predictive variables and factors associated with suicide in a general hospital. Studies are also made of the biological markers and therapeutic aspects of major depression. Investigations likewise have been conducted into personality disorders: the structure of the diagnostic systems, their relationship to adjustment to the environment and the validation of new models and instruments. For further information: FòrumClínic www.forumclinic.org Centro de Investigación Biomédica En Red de Salud Mental (CIBERSAM) www.cibersam.es RESEARCH GROUP Schizophrenia Group Leader: Miquel Bernardo (Hospital Clínic) The Clinical Schizophrenia Group (GEC) has been recognized as a consolidated research group (2005SGR00223; 2009SGR1295) by the Agency for the Management of University and Research Aids (Agència de Gestió d’Ajuts Universitaris i de Recerca, AGAUR) since the year 2005. This is an interdisciplinary group composed of psychiatrists, psychologists, neuropsychologists, nurses, physicians specialized in nuclear medicine, physicists, pharmacologists, toxicologists and biochemists linked to the Clinic Hospital and the University of Barcelona. Ours is a group of investigators forming part of the Clinical Schizophrenia Program (PEC) and working in disorders related to schizophrenia. This is a clinical care, research and teaching program at both hospital and outpatient level that includes different management and research protocols designed to address problems raised by schizophrenia and which integrates the different resources of the Barcelona Clinic Hospital. In the year 2007, the group became a constituting member of the Network of Mental Diseases and Affective and Psychotic Disorders (REMTAP), and in 2008 we likewise became a constituting member of the Center of Biomedical Research in Mental Health Network (CIBERSAM) (www.cibersam.es).The Clinical Schizophrenia Group centers its research on the study of the first schizophrenic episodes, schizophrenia starting in childhood/adolescence, and resistant and comorbid schizophrenia. The main research lines are physical health, neuroimaging, neuropsychology and psychometric assessment, genetics psychological education, neurobiology and neuropsychopharmacology in schizophrenia, with a supervisor for each of them, under the coordination of Dr. Miguel Bernardo. Another research line focuses on childhood- and adolescent-onset schizophrenia – these representing a high risk population for schizophrenia. This line is conducted in close collaboration with the Department of Childhood and Adolescent Psychiatry of the Clinic Hospital, directed by Dr. Castro, together with Drs. Baeza, Lázaro and Sánchez-Gistau (Study of high genetic risk for schizophrenia and early onset schizophrenia). RESEARCH GROUP Bipolar disorders Group Leader: Eduard Vieta (Hospital Clínic) The bipolar disorder program has been recognized as a consolidated research group (2009 SGR 1022) by the Agency for the Management of University and Research Aids (Agència de Gestió d’Ajuts Universitaris i de Recerca, AGAUR). The bipolar disorders program fundamentally investigates the neurobiological and anatomofunctional mechanisms involved in the development of the disease and its clinical course, comorbidity with other diseases, the implicated neurocognitive mechanisms, and the search for new pharmacological, biophysical and psychosocial treatments designed to improve the prognosis and quality of life of the patients. The program is characterized by a multidiscipline approach and includes psychiatrists, psychologists, pharmacologists, biologists, nurses, social workers and personnel in training. Our group has pioneered effort in the characterization of associated neurocognitive dysfunction, in the development of new drug treatments, and in the implementation of psychoeducational techniques targeted at both patients and their relatives. As a result of such research and innovation, the main international diagnostic and treatment guides document these contributions and recommend their application in clinical practice. Our program is carried out in active collaboration with other groups of the IDIBAPS, with other groups of the CIBERSAM, and with European and other international research centers, with a view to conducting multicenter studies with a special dedication to translational and innovative investigation. 223 AREA 4 Clinical and experimental neuroscience Biological bases of psychiatric disorders and nuclear psychiatry PUBLICATIONS Emergent Group Clinical depression group Originals I.F.: 271,16 Group Leader: Cristóbal Gasto (Hospital Clínic) Our group is specialized in the investigation of the neurobiological bases and clinical indicators of depression associated with treatment response and the course of this disease. It has been estimated that depression affects 10% of all people at some point in their lives. Depression is currently one of the most important health problems, particularly considering its slow and sometimes incomplete resolution. This disorder significantly interferes with the normal functions of the patients and their relatives, and implies a suicide risk in more than 10% of cases. The project of the World Health Organization (WHO) for the year 2020 considers that depression will be the second cause of disability after cardiovascular disease. In Europe it has been estimated that about 30 million people suffer some form of depression, generating an annual cost of approximately 100 billion euros. Our group is actively involved in the early detection and treatment of this disease, and its comorbidities (medical and psychiatric). The genetic and neuroendocrine markers we are investigating have contributed better understanding of the physiopathological mechanisms of depression. Likewise, a number of investigators in our group are actively working on the design of new individual- and group-based pharmacological and psychotherapeutic management strategies. RESEARCH GROUP Research group in pediatric psychiatry and psychology Group Leader: Josefina Castro (Hospital Clínic) The research group in childhood psychology and psychiatry of the Clinic Hospital forms part of the Department of Childhood and Adolescent Psychiatry, which has developed three fields: healthcare, teaching and research. These fields are all clearly interrelated with a view to affording better healthcare, with standardized protocols and evaluation and teaching at preand post-graduate level. Our aim is to facilitate both clinical research and collaboration with groups specialized in genetics, neuroimaging and neurobiology. The group is predominantly composed of members of the Department of Childhood Psychology and Psychiatry, and is integrated within the Biological Bases of Psychiatric Disorders group (coordinated by Dr. M. Bernardo). It also forms part of the CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental) of the Carlos III Healthcare Institute. In addition, it has established important collaboration agreements with the Department of Adult Psychiatry of the Clinic Hospital (especially as refers to schizophrenia, bipolar disorder and addictive behavior), as well as with other centers at international 224 level, such as the Childhood Psychiatry Group of the ECNP (European College of Neuopsychopharmacology), with which relevant aspects of childhood psychopharmacology are investigated in the context of different projects, the University of Pittsburgh Medical Center, Neuroimaging Laboratory, Western Psychiatric Institute and Clinic, Pittsburgh (United States), with which studies are made in relation to bipolar disorder, and the Child and Adolescent Psychiatry Yale Child Study Center, New Haven (United States), with which aspects relating to autoimmunity are studied. Our research objectives are the study of the manifestations, causes and treatment of the most serious and/or prevalent disorders found in these age groups: schizophrenia and bipolar disorder, anorexia and bulimia nervosa, obsessive-compulsive behavior, autistic disorders, attention deficit disorders, and addictive behaviors. In parallel, other lines have been developed related to the efficacy and safety of psychoactive drugs in children and adolescents, the development and validation of assessment scales, and the investigation of autoimmunity and psychiatric disease such as Tourette syndrome. 1 Fernandez-Egea E, Parellada E, Lomena F, Falcon C, Pavia J, Mane A, Horga G, Bernardo M. (18)FDG PET study of amygdalar activity during facial emotion recognition in schizophrenia. EUR ARCH PSY CLIN N, 2010. 260:69-76. I.F.:2,75. 2 Gomez-Caro A, Garcia S, Reguart N, Arguis P, Sanchez M, Gimferrer JM, Marrades R, Lomena F. Incidence of occult mediastinal node involvement in cNO non-small-cell lung cancer patients after negative uptake of positron emission tomography/ computer tomography scan. EUR J CARDIO-THORAC, 2010. 37:11681174. I.F.:2,40. 3 Pintor L, Bailles E, Matrai S, Carreno M, Donaire A, Boget T, Setoain X, Rumia J, Bargallo N. Efficiency of Venlafaxine in Patients With Psychogenic Nonepileptic Seizures and Anxiety and/or Depressive Disorders. J NEUROPSYCH CLIN N, 2010. 22:401-408. I.F.:2,34. 4 Carreno M, Garcia-Alvarez D, Maestro I, Fernandez S, Donaire A, Boget T, Rumia J, Pintor L, Setoain X. Malignant autosomal dominant frontal lobe epilepsy with repeated episodes of status epilepticus: successful treatment with vagal nerve stimulation. EPILEPTIC DISORD, 2010. 12:155-158. I.F.:1,20. 5 Sanchez-Gistau V, Pintor L, Sugranyes G, Bailles E, Carreno M, Donaire A, Boget T, Setoain X, Bargallo N, Rumia J. Prevalence of interictal psychiatric disorders in patients with refractory temporal and extratemporal lobe epilepsy in Spain. A comparative study. EPILEPSIA, 2010. 51:13091313. I.F.:4,05. AREA 4 Clinical and experimental neuroscience Biological bases of psychiatric disorders and nuclear psychiatry 6 Martin-Santos R, Torrens M, Poudevida S, Langohr K, Cuyas E, Pacifici R, Farre M, Pichini S, DeLaTorre R. 5-HTTLPR polymorphism, mood disorders and MDMA use in a 3-year follow-up study. ADDICT BIOL, 2010. 15:15-22. I.F.:4,73. 7 ElMallakh RS, Vieta E, Rollin L, Marcus R, Carson WH, Mcquade R. A comparison of two fixed doses of aripiprazole with placebo in acutely relapsed, hospitalized patients with bipolar disorder I (manic or mixed) in subpopulations (CN138-007). EUR NEUROPSYCHOPHARM, 2010. 20:776-783. I.F.:3,68. SCHIZOPHR RES, 2010. 121:66-74. I.F.:4,46. 12 Vieta E, Owen R, Baudelet C, Mcquade RD, Sanchez R, Marcus RN. Assessment of safety, tolerability and effectiveness of adjunctive aripiprazole to lithium/valproate in bipolar mania: a 46-week, open-label extension following a 6-week double-blind study. CURR MED RES OPIN, 2010. 26:1485-1496. I.F.:2,50. 13 Donner J, Haapakoski R, Ezer S, Castro-Fornieles J, Caldu X, AndresPerpina S, Lazaro L, Bargallo N, Falcon C, Plana MT, Junque C. A cross-sectional and follow-up functional MRI study with a working memory task in adolescent anorexia nervosa. NEUROPSYCHOLOGIA, 2010. 48:4111-4116. I.F.:4,35. Melen E, Pirkola S, Gratacos M, Zucchelli M, Anedda F, Johansson LE, Soderhall C, Orsmark-Pietras C, Suvisaari J, Martin-Santos R, Torrens M, Silander K, Terwilliger JD, Wickman M, Pershagen G, Lonnqvist J, Peltonen L, Estivill X, D’amato M, Kere J, Alenius H, Hovatta I. Assessment of the Neuropeptide S System in Anxiety Disorders. BIOL PSYCHIAT, 2010. 68:474-483. I.F.:8,93. 9 14 Costas J, Gratacos M, Escaramis 8 Mas S, Bernardo M, Gasso P, Alvarez S, Garcia-Rizo C, Bioque M, Kirkpatrick B, Lafuente A. A Functional Variant Provided Further Evidence for the Association of ARVCF With Schizophrenia. AM J MED GENET B, 2010. 153B:1052-1059. I.F.:3,48. 10 Vieta E, Nuamah IF, Lim P, Yuen EC, Palumbo JM, Hough DW, Berwaerts J. A randomized, placebo- and activecontrolled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorder. BIPOLAR DISORD, 2010. 12:230-243. I.F.:5,50. 11 Rametti G, Junque C, Bartres-Faz D, Zubiaurre-Elorza L, Catalan R, Penades R, Bargallo N, Bernardo M. Anterior cingulate and paracingulate sulci morphology in patients with schizophrenia. G, Martin-Santos R, DeDiego Y, BacaGarcia E, Canellas F, Estivill X, Guillamat R, Guitart M, Gutierrez-Zotes A, GarciaEsteve L, Mayoral F, Molto MD, Phillips C, Roca M, Carracedo A, Vilella E, Sanjuan J. Association study of 44 candidate genes with depressive and anxiety symptoms in post-partum women. J PSYCHIATR RES, 2010. 44:717-724. I.F.:3,72. 15 Tohen M, Vieta E, Gonzalez-Pinto A, Reed C, Lin D. Baseline Characteristics and Outcomes in Patients With First Episode or Multiple Episodes of Acute Mania. J CLIN PSYCHIAT, 2010. 71:255261. I.F.:5,22. 16 Goti J, Diaz R, Serrano L, Gonzalez L, Calvo R, Gual A, Castro J. Brief intervention in substance-use among adoles- cent psychiatric patients: a randomized controlled trial. EUR CHILD ADOLES PSY, 2010. 19:503-511. I.F.:1,65. 17 Plaza A, Garcia-Esteve L, Ascaso C, Navarro P, Gelabert E, Halperin I, Valdes M, Martin-Santos R. Childhood sexual abuse and hypothalamus-pituitary-thyroid axis in postpartum major depression. J AFFECT DISORDERS, 2010. 122:159-163. I.F.:3,76. 18 Kirkpatrick B, Garcia-Rizo C, Tang K, Fernandez-Egea E, Bernardo M. Cholesterol and triglycerides in antipsychotic-naive patients with nonaffective psychosis. PSYCHIAT RES, 2010. 178:559-561. I.F.:2,37. 19 Bonnin CM, Martinez-Aran A, Torrent C, Pacchiarotti I, Rosa AR, Franco C, Murru A, Sanchez-Moreno J, Vieta E. Clinical and neurocognitive predictors of functional outcome in bipolar euthymic patients: A long-term, follow-up study. J AFFECT DISORDERS, 2010. 121:156160. I.F.:3,76. 20 Baeza I, Flamarique I, Garrido JM, Horga G, Pons A, Bernardo M, Morer A, Lazaro ML, Castro-Fornieles J. Clinical Experience Using Electroconvulsive Therapy in Adolescents with Schizophrenia Spectrum Disorders. J CHILD ADOL PSYCHOP, 2010. 20:205-209. I.F.:2,59. 21 DeLaSerna E, Mayoral M, Baeza I, Arango C, Andres P, Bombin I, Gonzalez C, Rapado M, Robles O, RodriguezSanchez JM, Zabala A, Castro-Fornieles J. Cognitive Functioning in Children and Adolescents in Their First Episode of Psychosis Differences Between Previous Cannabis Users and Nonusers. J NERV MENT DIS, 2010. 198:159-162. I.F.:1,77. 225 AREA 4 Clinical and experimental neuroscience Biological bases of psychiatric disorders and nuclear psychiatry Team Members 22 Sala R, Axelson DA, Castro- 27 Fusar-Poli P, Bhattacharyya S, 33 Rosa AR, Reinares M, Michalak Fornieles J, Goldstein TR, Ha W, Liao FZ, Gill MK, Iyengar S, Strober MA, Goldstein BI, Yen S, Hower H, Hunt J, Ryan ND, Dickstein D, Keller MB, Birmaher B. Comorbid Anxiety in Children and Adolescents With Bipolar Spectrum Disorders: Prevalence and Clinical Correlates. J CLIN PSYCHIAT, 2010. 71:1344-1350. I.F.:5,22. Allen P, Crippa JA, Borgwardt S, MartinSantos R, Seal M, O’carroll C, Atakan Z, Zuardi AW, Mcguire P. Effect of image analysis software on neurofunctional activation during processing of emotional human faces. J CLIN NEUROSCI, 2010. 17:311-314. I.F.:1,17. EE, Bonnin CM, Sole B, Franco C, Comes M, Torrent C, Kapczinski F, Vieta E. Functional Impairment and Disability across Mood States in Bipolar Disorder. VALUE HEALTH, 2010. 13:984-988. I.F.:3,03. 23 Saus E, Brunet A, Armengol L, Alonso P, Crespo JM, FernandezAranda F, Guitart M, Martin-Santos R, Menchon JM, Navines R, Soria V, Torrens M, Urretavizcaya M, Valles V, Gratacos M, Estivill X. Comprehensive copy number variant (CNV) analysis of neuronal pathways genes in psychiatric disorders identifies rare variants within patients. J PSYCHIATR RES, 2010. 44:971-978. I.F.:3,72. 24 Torres A, Navarro P, Garcia-Esteve L, Tarragona MJ, Ascaso C, Herreras Z, Gelabert E, Imaz M, Roca A, Subira S, Martin-Santos R. Detecting Domestic Violence: Spanish External Validation of the Index of Spouse Abuse. J FAM VIOLENCE, 2010. 25:275286. I.F.:0,94. 25 Vieta E, DeArce R, JimenezArriero MA, Rodriguez A, Balanza V, Cobaleda S. Detection of Subclinical Depression in Bipolar Disorder: A Cross-Sectional, 4-Month Prospective Follow-Up Study at Community Mental Health Services (SIN-DEPRES). J CLIN PSYCHIAT, 2010. 71:1465-1474. I.F.:5,22. 26 Gonzalez-Pinto A, Alberich S, Barbeito S, Alonso M, Vieta E, Martinez-Aran A, Saenz M, Lopez P. Different profile of substance abuse in relation to predominant polarity in bipolar disorder The Vitoria long-term follow-up study. J AFFECT DISORDERS, 2010. 124:250-255. I.F.:3,76. 226 28 Lopez-Jaramillo C, Lopera-Vasquez J, Gallo A, Ospina-Duque J, Bell V, Torrent C, Martinez-Aran A, Vieta E. Effects of recurrence on the cognitive performance of patients with bipolar I disorder: implications for relapse prevention and treatment adherence. BIPOLAR DISORD, 2010. 12:557-567. I.F.:5,50. 29 VanDerLoos MLM, Mulder P, Hartong EGTM, Blom MBJ, Vergouwen AC, VanNoorden MS, Timmermans MA, Vieta E, Nolen WA. Efficacy and safety of two treatment algorithms in bipolar depression consisting of a combination of lithium, lamotrigine or placebo and paroxetine. ACTA PSYCHIAT SCAND, 2010. 122:246-254. I.F.:3,73. 30 Cruz N, Sanchez-Moreno J, Torres F, Goikolea JM, Valenti M, Vieta E. Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis. INT J NEUROPSYCHOPH, 2010. 13:5-14. I.F.:4,87. 34 Rosa AR, Bonnin CM, Vazquez GH, Reinares M, Sole B, TabaresSeisdedos R, Balanza-Martinez V, Gonzalez-Pinto A, Sanchez-Moreno J, Vieta E. Functional impairment in bipolar II disorder: Is it as disabling as bipolar I?. J AFFECT DISORDERS, 2010. 127:7176. I.F.:3,76. 35 Montoya A, Tohen M, Vieta E, Casillas M, Chacon F, Polavieja P, Gilaberte I. Functioning and symptomatic outcomes in patients with bipolar I disorder in syndromal remission: A 1-year, prospective, observational cohort study. J AFFECT DISORDERS, 2010. 127:50-57. I.F.:3,76. 36 Colom F, Reinares M, Pacchiarotti I, Popovic D, Mazzarini L, Martinez-Aran A, Torrent C, Rosa A, Palomino-Otiniano R, Franco C, Bonnin CM, Vieta E. Has number of previous episodes any effect on response to group psychoeducation in bipolar patients? A 5-year follow-up post hoc analysis. ACTA NEUROPSYCHIATR, 2010. 22:50-53. I.F.:0,94. 37 32 Penades R, Catalan R, Puig O, Gomez-Gil E, Navines R, DeOsaba MJM, Diaz-Ricart M, Escolar G, Salamero M, Martin-Santos R, Galan A, Gasto C. Hormonal responses to the 5-HT1A agonist buspirone in remitted endogenous depressive patients after long-term imipramine treatment. PSYCHONEUROENDOCRINO, 2010. 35:481-489. I.F.:4,19. Masana G, Pujol N, Navarro V, Guarch J, Gasto C. Executive function needs to be targeted to improve social functioning with Cognitive Remediation Therapy (CRT) in schizophrenia. PSYCHIAT RES, 2010. 177:41-45. I.F.:2,37. Angst J, Meyer TD, Adolfsson R, Skeppar P, Carta M, Benazzi F, Lu RB, Wu YH, Yang HC, Yuan CM, Morselli P, Brieger P, Katzmann J, Leao IAT, DelPorto JA, Moreno DH, Moreno RA, Soares 31 Morer A, Chae W, Henegariu O, Bothwell ALM, Leckman JF, Kawikova I. Elevated expression of MCP-1, IL-2 and PTPR-N in basal ganglia of Tourette syndrome cases. BRAIN BEHAV IMMUN, 2010. 24:1069-1073. I.F.:5,06. 38 AREA 4 Clinical and experimental neuroscience Biological bases of psychiatric disorders and nuclear psychiatry OT, Vieta E, Gamma A. Hypomania: a transcultural perspective. WORLD PSYCHIATRY, 2010. 9:41-49. I.F.:4,38. 39 Garcia-Portilla MP, Saiz PA, Benabarre A, Florez G, Bascaran MT, Diaz EM, Bousono M, Bobes J. Impact of substance use on the physical health of patients with bipolar disorder. ACTA PSYCHIAT SCAND, 2010. 121:437-445. I.F.:3,73. Aran A, Vieta E. Lithium Treatment Effects on the Neuropsychological Functioning of Patients With Bipolar I Disorder. J CLIN PSYCHIAT, 2010. 71:1055-1060. I.F.:5,22. 45 Nivoli AMA, Murru A, Vieta E. Lithium: Still a Cornerstone in the LongTerm Treatment in Bipolar Disorder?. NEUROPSYCHOBIOLOGY, 2010. 62:2735. I.F.:2,15. 40 Valdes M, Collado A, Bargallo N, 46 Aspiazu S, Mosquera F, Ibanez Vazquez M, Rami L, Gomez E, Salamero M. Increased Glutamate/Glutamine Compounds in the Brains of Patients With Fibromyalgia A Magnetic Resonance Spectroscopy Study. ARTHRITIS RHEUM-US, 2010. 62:1829-1836. I.F.:7,33. B, Vega P, Barbeito S, Lopez P, DeAzua SR, Ugarte A, Vieta E, Gonzalez-Pinto A. Manic and depressive symptoms and insight in first episode psychosis. PSYCHIAT RES, 2010. 178:480-486. I.F.:2,37. 41 Gonzalez-Pinto AM, Dardennes R, DeZelicourt M, Lopez P, Oliveros RG, Vieta E, Barbeito S, Echevarria E, Fagnani F. In-patient care costs of patients with bipolar I disorder: A comparison between two European centers. J AFFECT DISORDERS, 2010. 121:152155. I.F.:3,76. 47 Moreno C, Merchan-Naranjo J, Alvarez M, Baeza I, Alda JA, MartinezCantarero C, Parellada M, Sanchez B, DeLaSerna E, Giraldez M, Arango C. Metabolic effects of second-generation antipsychotics in bipolar youth: comparison with other psychotic and nonpsychotic diagnoses. BIPOLAR DISORD, 2010. 12:172-184. I.F.:5,50. 42 Gasso P, Mas S, Crescenti A, Alva- 48 Rojo E, Pino O, Guilera G, Gomezrez S, Parramon G, Garcia-Rizo C, Parellada E, Bernardo M, Lafuente A. Lack of association between antipsychoticinduced extrapyramidal symptoms and polymorphisms in dopamine metabolism and transport genes. PSYCHIAT RES, 2010. 175:173-175. I.F.:2,37. 43 Alvarez S, Mas S, Gasso P, Bernardo M, Parellada E, Lafuente A. Lack of association between schizophrenia and polymorphisms in dopamine metabolism and transport genes. FUND CLIN PHARMACOL, 2010. 24:741-747. I.F.:2,37. Benito J, Purdon SE, Crespo-Facorro B, Cuesta MJ, Franco M, Martinez-Aran A, Segarra N, Tabares-Seisdedos R, Vieta E, Bernardo M, Mesa F, Rejas J. Neurocognitive diagnosis and cut-off scores of the Screen for Cognitive Impairment in Psychiatry (SCIP-S). SCHIZOPHR RES, 2010. 116:243-251. I.F.:4,46. 49 Baldessarini RJ, Bolzani L, Cruz N, Jones PB, Lai M, Lepri B, Perez J, Salvatore P, Tohen M, Tondo L, Vieta E. Onset-age of bipolar disorders at six international sites. J AFFECT DISORDERS, 2010. 121:143-146. I.F.:3,76. 44 Lopez-Jaramillo C, Lopera-Vasquez 50 Bhattacharyya S, Morrison PD, J, Ospina-Duque J, Garcia J, Gallo A, Cortez V, Palacio C, Torrent C, Martinez- Fusar-Poli P, Martin-Santos R, Borgwardt S, Winton-Brown T, Nosarti C, O’carroll CM, Seal M, Allen P, Mehta MA, Stone JM, Tunstall N, Giampietro V, Kapur S, Murray RM, Zuardi AW, Crippa JA, Atakan Z, Mcguire PK. Opposite Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Human Brain Function and Psychopathology. NEUROPSYCHOPHARMACOL, 2010. 35:764-774. I.F.:6,99. 51 Colom F, Cruz N, Pacchiarotti I, Mazzarini L, Goikolea JM, Popova E, Torrent C, Vietac E. Postpartum bipolar episodes are not distinct from spontaneous episodes: Implications for DSM-V. J AFFECT DISORDERS, 2010. 126:61-64. I.F.:3,76. 52 Rapado-Castro M, Soutullo C, Fraguas D, Arango C, Paya B, CastroFornieles J, Gonzalez-Pinto A, Parellada M, Graell M, Baeza I, Bombin I. Predominance of Symptoms Over Time in Early-Onset Psychosis: A Principal Component Factor Analysis of the Positive and Negative Syndrome Scale. J CLIN PSYCHIAT, 2010. 71:327-337. I.F.:5,22. 53 Castro-Fornieles J, Diaz R, Goti J, Calvo R, Gonzalez L, Serrano L, Gual A. Prevalence and Factors Related to Substance Use among Adolescents with Eating Disorders. EUR ADDICT RES, 2010. 16:61-68. I.F.:1,23. 54 Vieta E, Morralla C. Prevalence of mixed mania using 3 definitions. J AFFECT DISORDERS, 2010. 125:6173. I.F.:3,76. 55 Mazzarini L, Colom F, Pacchiarotti I, Nivoli AMA, Murru A, Bonnin CM, Cruz N, Sanchez-Moreno J, Kotzalidis GD, Girardi P, Tatarelli R, Vieta E. Psychotic versus non-psychotic bipolar II disorder. J AFFECT DISORDERS, 2010. 126:55-60. I.F.:3,76. 227 AREA 4 Clinical and experimental neuroscience Biological bases of psychiatric disorders and nuclear psychiatry Team Members 56 De La Serna E, Baeza I, Toro J, Andres S, Puig O, Sanchez-Guistau V, Romero S, Bernardo M, Castro-Fornieles J. Relationship between clinical and neuropsychological characteristics in child and adolescent first degree relatives of subjects with schizophrenia. SCHIZOPHR RES, 2010. 116:159-167. I.F.:4,46. 57 Garin O, Ayuso-Mateos JL, Almansa J, Nieto M, Chatterji S, Vilagut G, Alonso J, Cieza A, Svetskova O, Burger H, Racca V, Francescutti C, Vieta E, Kostanjsek N, Raggi A, Leonardi M, Ferrer M. Research Validation of the “World Health Organization Disability Assessment Schedule, WHODAS-2” in patients with chronic diseases. HEALTH QUAL LIFE OUT, 2010. 8:-. I.F.:2,46. 58 Fonseca F, Gratacos M, Escaramis G, DeCid R, Martin-Santos R, FernandezEspejo E, Estivill X, Torrens M. Response to Methadone Maintenance Treatment is Associated with the MYOCD and GRM6 Genes. MOL DIAGN THER, 2010. 14:171-178. I.F.:2,17. 59 Parellada E, Kouniakis F, Siurkute A, Schreiner A, Don L. Safety and efficacy of long-acting injectable risperidone in daily practice: an open-label, noninterventional, prospective study in schizophrenia and related disorders. INT CLIN PSYCHOPHARM, 2010. 25:149-154. I.F.:3,35. 60 Filho AS, Hetem LAB, Ferrari MCF, Trzesniak C, Martin-Santos R, Borduqui T, Osorio FD, Loureiro SR, Busatto G, Zuardi AW, Crippa JAS. Social anxiety disorder: what are we losing with the current diagnostic criteria?. ACTA PSYCHIAT SCAND, 2010. 121:216-226. I.F.:3,73. 61 Meneses-Gaya C, Crippa JAS, Zuardi AW, Loureiro SR, Hallak JEC, 228 Trzesniak C, DeSousa JPM, Chagas MHN, Souza RM, Martin-Santos R. The Fast Alcohol Screening Test (FAST) is as Good as the AUDIT to Screen Alcohol Use Disorders. SUBST USE MISUSE, 2010. 45:1542-1557. I.F.:0,73. 67 DeDios C, Ezquiaga E, Garcia A, Soler B, Vieta E. Time spent with symptoms in a cohort of bipolar disorder outpatients in Spain: A prospective, 18-month follow-up study. J AFFECT DISORDERS, 2010. 125:74-81. I.F.:3,76. 62 Reinares M, Colom F, Rosa AR, 68 Plana T, Gracia R, Mendez I, Pintor Bonnin CM, Franco C, Sole B, Kapczinski F, Vieta E. The impact of staging bipolar disorder on treatment outcome of family psychoeducation. J AFFECT DISORDERS, 2010. 123:81-86. I.F.:3,76. L, Lazaro L, Castro-Fornieles J. Total serum cholesterol levels and suicide attempts in child and adolescent psychiatric inpatients. EUR CHILD ADOLES PSY, 2010. 19:615-619. I.F.:1,65. 63 Fagundo AB, Cuyas E, Verdejo- 69 Vieta E, Locklear J, Gunther O, Ek- Garcia A, Khymenets O, Langohr K, Martin-Santos R, Farre M, DeLaTorre R. The influence of 5-HTT and COMT genotypes on verbal fluency in ecstasy users. J PSYCHOPHARMACOL, 2010. 24:1381-1393. I.F.:3,65. man M, Miltenburger C, Chatterton ML, Astrom M, Paulsson B. Treatment Options for Bipolar Depression A Systematic Review of Randomized, Controlled Trials. J CLIN PSYCHOPHARM, 2010. 30:579-590. I.F.:5,09. 64 Selva-Vera G, Balanza-Martinez 70 Gonzalez-Ortega I, Rosa A, Albe- V, Salazar-Fraile J, Sanchez-Moreno J, Martinez-Aran A, Correa P, Vieta E, Tabares-Seisdedos R. The switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of cognitive deficits. A pilot study in individuals with schizophrenia. BMC PSYCHIATRY, 2010. 10:-. I.F.:1,83. rich S, Barbeito S, Vega P, Echeburua E, Vieta E, Gonzalez-Pinto A. Validation and Use of the Functioning Assessment Short Test in First Psychotic Episodes. J NERV MENT DIS, 2010. 198:836-840. I.F.:1,77. 65 Torres X, Bailles E, Collado A, Taberner J, Gutierrez F, Peri JM, Arias A, Fullana MA, Valdes M. The Symptom Checklist-Revised (SCL-90-R) is Able to Discriminate Between Simulation and Fibromyalgia. J CLIN PSYCHOL, 2010. 66:774-790. I.F.:1,53. 66 Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW, Moller HJ, Kasper S. The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Update 2010 on the treatment of acute bipolar depression. WORLD J BIOL PSYCHIA, 2010. 11:81109. I.F.:5,56. 71 Rosa AR, Cruz N, Franco C, Haro JM, Bertsch J, Reed C, Aarre TF, Sanchez-Moreno J, Vieta E. Why Do Clinicians Maintain Antidepressants in Some Patients With Acute Mania? Hints From the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM), a Large Naturalistic Study. J CLIN PSYCHIAT, 2010. 71:1000-1006. I.F.:5,22. 72 Reed C, Goetz I, Vieta E, Bassi M, Haro JM. Work impairment in bipolar disorder patients - results from a two-year observational study (EMBLEM). EUR PSYCHIAT, 2010. 25:338-344. I.F.:3,08. 73 Gasso P, Mas S, Alvarez S, Trias G, Bioque M, Oliveira C, Bernardo M, Lafuente A. Xenobiotic metabolizing and transporter genes: gene-gene inte- AREA 4 Clinical and experimental neuroscience Biological bases of psychiatric disorders and nuclear psychiatry ractions in schizophrenia and related disorders. PHARMACOGENOMICS, 2010. 11:1725-1731. I.F.:3,89. 74 Vieta E, Ramey T, Keller D, English PA, Loebel AD, Miceli J. Ziprasidone in the treatment of acute mania: a 12-week, placebo-controlled, haloperidol-referenced study. J PSYCHOPHARMACOL, 2010. 24:547-558. I.F.:3,65. 75 Bowden CL, Vieta E, Ice KS, Schwartz JH, Wang PP, Versavel M. Ziprasidone Plus a Mood Stabilizer in Subjects With Bipolar I Disorder: A 6-Month, Randomized, Placebo-Controlled, Double-Blind Trial. J CLIN PSYCHIAT, 2010. 71:130-137. I.F.:5,22. reviews I.F.: 35,65 1 Baldessarini RJ, Vieta E, Calabrese 5 Tamayo JM, Zarate CA, Vieta E, Vazquez G, Tohen M. Level of response and safety of pharmacological monotherapy in the treatment of acute bipolar I disorder phases: a systematic review and meta-analysis. INT J NEUROPSYCHOPH, 2010. 13:813-832. I.F.:4,87. 6 Balanza-Martinez V, Selva G, Martinez-Aran A, Prickaerts J, Salazar J, Gonzalez-Pinto A, Vieta E, TabaresSeisdedos R. Neurocognition in bipolar disorders-A closer look at comorbidities and medications. EUR J PHARMACOL, 2010. 626:87-96. I.F.:2,59. 7 Martin-Santos R, Fagundo AB, Crippa JA, Atakan Z, Bhattacharyya S, Allen P, Fusar-Poli P, Borgwardt S, Seal M, Busatto GF, Mcguire P. Neuroimaging in cannabis use: a systematic review of the literature. PSYCHOL MED, 2010. 40:383-398. I.F.:5,01. 8 2 Bonnin CM, Martinez-Aran A, San- Castro-Fornieles J, Garcia AI, Lazaro L, Andres-Perpina S, Falcon C, Plana MT, Bargallo N. Prefrontal brain metabolites in short-term weight-recovered adolescent anorexia nervosa patients. PROG NEURO-PSYCHOPH, 2010. 34:10491053. I.F.:2,82. chez-Moreno J, Torrent C, Franco C, Pacchiarotti I, Vieta E. Bipolar disorder, cognitive functioning and hypothalamic-pituitary-thyroid axis. ACTAS ESP PSIQUIATRI, 2010. 38:223-228. I.F.:0,52. Valenti M, Morer A, Lazaro ML, Bernardo M, Castro-Fornieles J. Repeated transcranial magnetic stimulation in children and adolescents. REV NEUROLOGIA, 2010. 50:230-234. I.F.:1,23. JR, Tohen M, Bowden CL. Bipolar Depression: Overview and Commentary. HARVARD REV PSYCHIAT, 2010. 18:143-157. I.F.:1,34. 3 Berk L, Hallam KT, Colom F, Vieta E, Hasty M, Macneil C, Berk M. Enhancing medication adherence in patients with bipolar disorder. HUM PSYCHOPHARM CLIN, 2010. 25:1-16. I.F.:2,50. 4 Avila CC, Cabello M, Cieza A, Vieta E, Ayuso-Mateos JL. Functioning and disability in bipolar disorders: a systematic review of literature using the ICF as a reference. BIPOLAR DISORD, 2010. 12:473-482. I.F.:5,50. 9 10 Yatham LN, Torres IJ, Malhi GS, Frangou S, Glahn DC, Bearden CE, Burdick KE, Martinez-Aran A, Dittmann S, Goldberg JF, Ozerdem A, Aydemir O, Chengappa KNR. The International Society for Bipolar Disorders-Battery for Assessment of Neurocognition (ISBD-BANC). BIPOLAR DISORD, 2010. 12:351-363. I.F.:5,50. 11 Smith LA, Cornelius VR, Azorin JM, Perugi G, Vieta E, Young AH, Bow- den CL. Valproate for the treatment of acute bipolar depression: Systematic review and meta-analysis. J AFFECT DISORDERS, 2010. 122:1-9. I.F.:3,76. Editorials I.F.: 27,03 1 Gual A. A case of double exclusion. EUR J PUBLIC HEALTH, 2010. 20:618-618. I.F.:2,31. 2 Colom F. Achieving remission and recovery in bipolar disorder. J CLIN PSYCHIAT, 2010. 71:e32-e32. I.F.:5,22. 3 Gual A. Conflicts of interest. A golden standard to generalize in addiction research. ADDICTION, 2010. 105:199200. I.F.:3,84. 4 Vieta E. Individualizing treatment for patients with schizoaffective disorder. J CLIN PSYCHIAT, 2010. 71:e26e26. I.F.:5,22. 5 Vieta E. Long-term treatment of bipolar depression and other issues. J CLIN PSYCHIAT, 2010. 71:e07-e07. I.F.:5,22. 6 Vieta E. Role of antidepressants in bipolar depression. J CLIN PSYCHIAT, 2010. 71:e21-e21. I.F.:5,22. Grants for research in progress Bernardo M. Diabetes in Neuropsychiatric Disorders. (subaward nº 07-20846A1. Sponsored by: National Institutes of Health - EU, 1R01DK069265-01A1 S02078- . Amount: 352.201,00 euros. Duration: 01/04/2005-31/03/2010. 229 AREA 4 Clinical and experimental neuroscience Biological bases of psychiatric disorders and nuclear psychiatry Team Members Masana G. Ensayo doble ciego controlado con placebo de la eficacia de reboxetina y citalopram como tratamiento coadyuvante de los antipsicóticos de segunda generación en el tratamiento de los símtomas negativos de la esquizofrenia. Sponsored by: Ministerio Sanidad y Consumo, EC07/90553. Amount: 15.730,00 euros. Duration: 29/10/2007-30/12/2010. Gasto C. Estrategias terapeuticas en trastorno depresivo mayor resistente a tratamiento con inhibidores selectivos de la recaptación de serotonina. Ensayo clínico pragmático, paralelo. Aleatorizado con evaluación enmascarada. Sponsored by: Ministerio Sanidad y Consumo, EC07/90825. Amount: 14.036,00 euros. Duration: 29/10/2007-30/12/2010. Gutierrez F. Una taxonimía con base empírica para los transtornos de la personalidad: reorganización factorial del Eje II (DSM-IV). Sponsored by: INSTITUTO DE SALUD CARLOS III, PI070033. Amount: 9.317,00 euros. Duration: 26/11/2007-30/12/2010. Castro J. Características psicopatológicas, neuropsicológicas y de neuroimagen comunes y diferenciales en niños y adolescentes hijos de pacientes con esquizofrenia o con transtorno bipolar. Sponsored by: Ministerio Sanidad y Consumo, PI070066. Amount: 58.080,00 euros. Duration: 26/11/2007-30/12/2010. Penades R. Análisis de los efectos del tratamiento de rehabilitación cognitiva en la esquizofrenia mediante técnicas de neuroimagen funcional. Sponsored by: Ministerio Sanidad y Consumo, PI070258. Amount: 61.226,00 euros. Duration: 26/11/2007-30/12/2010. Lazaro L. Estudio de la relación clínica y genética entre un subgrupo de pa- 230 cientes con anorexia nerviosa y pacientes con trastorno obsesivo compulsivo en niños y adolescentes. Sponsored by: Ministerio Sanidad y Consumo, PI070350. Amount: 47.916,00 euros. Duration: 26/11/2007-30/12/2010. Gual T. Standardizing Measurement of Alcohol Related Troubles. Sponsored by: INSTYTUT PSYCHIATRII I NEUROLOGII (IPIN), 2007308. Amount: 27.275,37 euros. Duration: 01/09/2008-31/08/2010. Martinez A. Eficacia de la rehabilitación cognitiva en pacientes con trastorno bipolar: estudio aleatorizado controlado para evaluar la mejoría de las disfunciones cognitivas y el impacto sobre el funcionamiento psicosocial. Sponsored by: Instituto de Salud Carlos III, CP07/00144. Amount: 92.591,00 euros. Duration: 01/02/2008-31/01/2011. Lazaro L. Anàlisi dels polimorfismes en gens candidats en el trastorn obsessiucompulsiu d’inici primerenc. Relació amb alteracions cerebrals i dimensions simptomàtiques. Sponsored by: Fundació Marató TV3, PI040588. Amount: 164.000,00 euros. Duration: 01/01/201031/12/2012. Castro J. Marcadores de pronóstico y neurodegeneración en primeros episodios psicóticos en niños y adolescentes: seguimiento longitudinal a 5 años. Sponsored by: Fundación Alicia Koplowitz, CP040501. Amount: 11.805,00 euros. Duration: 17/07/2009-17/07/2011. Castro J. Seguiment a dos anys de nens i adolescents fills de pacients amb esquizofrènia o trastorn bipolar. Sponsored by: Fundació Marató TV3, PI040582. Amount: 182.356,00 euros. Duration: 01/01/2010-30/12/2012. Gutierrez F. Eficacia comparada de cuatro modelos diagnósticos de Trastorno de la Personalidad. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI040232. Amount: 72.963,00 euros. Duration: 01/01/2009-31/01/2011. Bernardo M. Interacción genotipofenotipo y ambiente. Aplicación a un modelo predictivo en primeros episodios psicóticos. Sponsored by: FIS (ISCIII). , PI080208. Amount: 399.663,00 euros. Duration: 01/01/2009-31/12/2011. Parellada E. Apoptosis y cambios estructurales progresivos en pacientes con un primer episodio de esquizofrenia: estudio longitudinal y multimodal de neuroimagen y biología molecular. Sponsored by: FIS (ISCIII) , PI080055. Amount: 68.728,00 euros. Duration: 01/01/2009-31/12/2011. Catalan R. Identificación de predictores clínicos, neurohormonales, farmacogenéticos en la respuesta terapéutica a clozapina en pacientes diagnosticados de Esquizofrenia Refractaria . Sponsored by: FIS (ISCIII) , EC81/00331 . Amount: 33.517,00 euros. Duration: 01/01/200931/12/2011. Bernardo M. Reconocimiento como Grupo Consolidado de Investigación. Sponsored by: Agència de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya , 2009SGR1295 . Amount: 47.840,00 euros. Duration: 01/01/200931/12/2014. Vieta E. Grup de Recerca Consolidat de la Generalitat de Catalunya . Sponsored by: Generalitat de Catalunya , 2009_ SGR_1022. Amount: 44.720,00 euros. Duration: 01/01/2009-31/12/2013. Vieta E. Eficacia comparativa de dos estrategias de intervención psicosocial (neurocognitiva versus psicoeducativa) como tratamiento coadyuvante al farmacológico versus tratamiento habitual en el trastorno bipolar . Sponsored by: Instituto de Salud Carlos III, PI08/90094. AREA 4 Clinical and experimental neuroscience Biological bases of psychiatric disorders and nuclear psychiatry Amount: 29.040,00 euros. Duration: 01/01/2009-31/12/2010. Vieta E. European Network of Bipolar Research Expert Centres (ENBREC) . Sponsored by: European Union, 223102. Amount: 85.550,00 euros. Duration: 01/01/2009-31/12/2010. Martinez A. Discapacidad en el trastorno bipolar e impacto funcional de una estrategia de intervención neurocognitiva. Sponsored by: FIS, PI080180. Amount: 130.680,00 euros. Duration: 01/01/200931/12/2011. Martin Santos R, Navines R, Valdes M. Estudio farmacogenético y de predicción de la depresión inducida por el tratamiento con interferón alfa pegilado y ribavirina en pacientes con hepatitis C crónica (ESTUDIO PSIGEN-VHC). Sponsored by: Fondo Investigación Sanitaria, EC08/00201. Amount: 0,00 euros. Duration: 01/01/2009-31/12/2010. Martin Santos R, Garcia L, Gutierrez F, Navines R, Imaz ML. Grup de Recerca en “Vulnerabilitat, psicopatologia i gènere” Modalitat Grup de recerca emergent. Sponsored by: Generalitat de Catalunya, SGR 2009/1435. Amount: 0,00 euros. Duration: 01/01/200931/12/2013. Garcia L, Imaz ML, Botet F, Ascaso C, Salamero M. Estudio farmacogenético y de seguridad clínica en niños de madres tratadas con inhibidores selectivos de la recaptación de serotonina durante el embarazo: evaluación del funcionamiento cognitivo conductual a los 5 años de edad. Sponsored by: European Comission, EC08/00170. Amount: 0,00 euros. Duration: 01/01/2009-31/12/2011. Pintor L. Análisis de los indicadores clínicos que diferencian entre crisis epilépticas y crisis no epilépticas psicógenas (CNEP): Hacia un mejor diagnóstico dife- rencial a través de un cuestionario de sospecha diagnóstica. Sponsored by: Fondo de Investigaciones Sanitarias (FIS), PI080111. Amount: 17.908,00 euros. Duration: 01/01/200931/12/2011. Gual A. Alcohol Public Health Research Alliance (AMPHORA). Sponsored by: Comissió Europea, 0000. Amount: 502.741,00 euros. Duration: 01/01/2009-31/12/2013. Vieta E. Discapacidad y funcionamiento en el trastorno bipolar: seguimiento a los 3 años. (FPU). Sponsored by: Ministerio de Educación y Ciencia, AP2008-01923. Amount: 40.060,84 euros. Duration: 20/07/200919/12/2011. Colom F. A study of response predictors to psychoeducation in bipolar disorder. Sponsored by: Instituto de Salud Carlos III, CP08/00140. Amount: 220.149,00 euros. Duration: 01/01/2009-31/12/2011. Benabarre A. Identificación de variables clínicas, sociológicas y genéticas predictoras de la respuesta al tratamiento eutimizante en el Trastorno Bipolar. Sponsored by: Instituto de Salud Carlos III, PI080247. Amount: 20.207,00 euros. Duration: 01/01/2009-31/12/2011. Colom F. Factores neurobiológicos, cognitivos y clínicos asociados al pronóstico clínico y funcional a un año de seguimiento de la psicoeducación en el trastorno bipolar. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1044. Amount: 170.005,00 euros. Duration: 01/01/2010-31/12/2012. Morer A. Inflamación, autoinmunidad y psicopatología: estudio en niños y adolescentes con patología psiquiátrica aguda y en hijos de ma- dres afectadas de lupus eritematoso sistémico. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1347. Amount: 84.095,00 euros. Duration: 01/01/2010-31/12/2012. Vieta E. The neural correlates of euthymic cognitive impairment in bipolar disorder. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1893. Amount: 15.730,00 euros. Duration: 01/01/2010-31/12/2012. Castro J. Paediatric European Risperidone Studies. Sponsored by: RADBOUD UNIVERSITEIT NIJMEGEN, 241959. Amount: 181.500,00 euros. Duration: 01/05/2010-30/04/2015. Castro J. Two year follow-up study of children and adolescent offspring of subjects with schizophrenia or bipolar disorders. Sponsored by: FUNDACIÓ LA MARATÓ DE TV3, 091630. Amount: 182.356,25 euros. Duration: 29/01/2010-28/01/2013. Lazaro L. Analysis of polimorphisms in candidate genes in early onset obsessive-compulsive disorder. Relationship with cerebral abnormalit and symptom dimensions. Sponsored by: FUNDACIÓ LA MARATÓ DE TV3, 091710. Amount: 164.000,00 euros. Duration: 29/01/2010-28/01/2013. Andres S. Trastornos de la Conducta Alimentaria, veinte años después. Estudio de estado psicopatológico y físico y su relación con el funcionamiento general. Sponsored by: INSTITUTO DE LA MUJER, 234/09. Amount: 43.484,00 euros. Duration: 03/02/2010-02/02/2012. Gomez E. Adaptación psicosocial, calidad de vida, y demanda de asistencia sanitaria durante 10 años en personas diagnosticadas de trastorno de la identidad de género. Sponsored by: 231 AREA 4 Clinical and experimental neuroscience Biological bases of psychiatric disorders and nuclear psychiatry Team Members INSTITUTO DE LA MUJER, 238/09. Amount: 15.107,00 euros. Duration: 03/02/2010-02/02/2012. Castro J. Suicidality: Treatment Occurring in Paediatrics. Sponsored by: University College London UCL, 261411. Amount: 157.500,00 euros. Duration: 01/11/2010-30/04/2014. Garcia L. Violencia sexual, estrés agudo y calidad de vida: estudio de los factores de riesgo en las mujeres atendidas en urgencias tras una agresión sexual. Sponsored by: INSTITUTO DE LA MUJER, 235/09. Amount: 33.471,00 euros. Duration: 03/02/2010-02/02/2013. Bernardo M. Antipsicóticos típicos vs. atípicos; impacto de la farmacogenética en la farmacocinética, la ocupación de receptores estriatales y la aparición se sintomatología extrapiramidal.. Sponsored by: MINISTERIO DE SANIDAD, POLITICA SOCIAL E IGUALDAD, TRA-065. Amount: 134.211,60 euros. Duration: 01/01/2010-31/12/2011. Martin Santos R. Estudio farmacogenético y de predicción de la depresión inducida por el tratamiento de la hepatitis C crónica con interferón alfa pegilado y rivabirina. Estudio psigen-vhc. subproyecto coordinado I. Sponsored by: INSTITUTO DE SALUD CARLOS III, EC08/00201. Amount: 46.827,00 euros. Duration: 01/01/2009-31/05/2011. Garcia L. Estudio farmacogenético y de seguridad clínica en hijos de madres tratadas con antidepresivos ISRS durante el embarazo: Evaluación del funcionamiento cognitivoconductual a los 5 años. Sponsored by: INSTITUTO DE SALUD CARLOS III, EC08/00170. Amount: 177.870,00 euros. Duration: 01/01/200930/12/2011. 232 Catalan R. Identificación de predictores clínicos, neurohormonales, farmacogenéticos en la respuesta terapéutica a clozapina en pacientes diagnosticados de esquizofrenia refractaria.. Sponsored by: INSTITUTO DE SALUD CARLOS III, EC08/00184. Amount: 33.517,00 euros. Duration: 01/01/2009-30/12/2011. Lazaro L. Identificación de predictores farmacogenéticos en la respuesta terapéutica a fluoxetina en pacientes diagnosticados de trastorno obsesivocompulsivo en la infancia y la adolescencia. Sponsored by: Fundación Alicia Koplowitz, PS09/00468. Amount: 73.700,00 euros. Duration: 01/01/201031/12/2011. Thesis Colom F, Vieta E. Diagnostic specifiers of the onset, course and outcome of bipolar disorder. PhD student: Nuria Cruz Culebra. Parellada E, Bernardo M. Diferencias en la respuesta a pruebas de reconocimiento facial de las emociones entre pacientes esquizofrénicos deficitarios versus esquizofrénicos no deficitarios. PhD student: Emilio Fernandez Egea. Martin-Santos R. Depresión posparto y rasgos de la personalidad. PhD student: Gelabert Arbiol E. AREA 4 Clinical and experimental neuroscience Neuropsychology Group Members Strategic Objectives TEAM LEADER Carme Junqué (Facultat Medicina UB) Tel.: 93 403 44 46 Fax: 93 403 92 98 E-mail: cjunque@ub.edu Idibaps members: Núria Bargalló (Hospital Clínic) David Bartrés-Faz (Facultat de Medicina UB) Teresa Boget (Hospital Clínic) Teodor Marcos (Hospital Clínic) José M. Mercader (Hospital Clínic) Manuel Salamero (Hospital Clínic) Josep M. Serra (Universitat de Barcelona) Pere Vendrell (Facultat de Medicina UB) Postdoctoral fellows: Naroa Ibarretxe (MEC) Bárbara Segura (UB) Research Fellows: Davinia Fernández (MEC) Joana B. Pereira (MICINN) Leire Zubiaurre (MICINN) Eider Martinez de Arenaza (DGR) Eva Palacios (IDIBAPS) Roser Sala (Becari projecte) Didac Vidal (DGR) Nuria Pujol (Rio Hortega) Technicians: Silvia Juanes (UB) Study of the consequences of cerebral lesions and dysfunctions in relation to behavior and cognition. The technique preferentially used in our studies is magnetic resonance imaging in its structural and functional applications. We are equipped with a neuroimaging laboratory with different high-performance workstations. Main Lines of Research 1. Neuropsychology and neuroimaging in normal aging and in degenerative diseases. Neuroanatomical and neurofunctional bases of cognitive impairment in normal aging, Pakinson’s disease and Alzheimer’s disease. This line makes use of combined structural and functional magnetic resonance imaging to detect early alterations in brain connectivity prior to clear cerebral atrophy caused by neuron death. Identification of the symptoms prior to actual clinical manifestations in degenerative diseases is a challenge for treatment intervention aiming to slow the neurodegenerative processes. As a subline, mention should be made of the study of the contribution of the cognitive reserve variables in the degree of cognitive deterioration associated with age and dementia, as well as of the neuroanatomical and neurophysiological bases of this phenomenon. 2. Cerebral plasticity. Long-term consequences of brain damage. In the field of cerebral plasticity we investigate the changes in brain structure and function detectable by magnetic resonance imaging that are induced by transcranial electric stimulation. This technique can be used to simulate reversible lesions or to investigate the changes in brain connectivity in normal subjects and also in degenerative processes. Another line of interest in which work is being done is the study of cerebral language response in patients who as a result of head injuries are in a chronic vegetative state or minimally responsive state. Brain response in the absence of motor response can have clear consequences in the differential diagnosis of these two conditions. Likewise in head injury patients, we study the relationship between the long-term cognitive sequelae and the white matter alterations identified by diffusion tensor imaging (DTI), and also analyze the changes in the cortical layer related to alterations attributable to diffuse axonal damage. 3. Development of imaging techniques to study the areas of the brain implicated in the higher function alterations in epileptic patients, based on functional magnetic resonance imaging. The aim of this line of research is to develop cognitive paradigms such as those relating to speech, perception or memory, based on functional magnetic resonance imaging techniques - validating and applying them to clinical practice with a view to predicting neuropsychological sequelae and investigating cerebral plasticity mechanisms. Regional reductions in thalamus morphology in trauma patients in the vegetative state (VS) and minimum consciousness state (MCS).The color bar indicates the value of F. The dorsomedial nucleusis correlated to the degree of patient disability. 233 AREA 4 Clinical and experimental neuroscience Neuropsychology PUBLICATIONS originals I.F.: 100,84 1 Serra-Grabulosa JM, Adan A, Falcon C, Bargallo N. Glucose and caffeine effects on sustained attention: an exploratory fMRI study. HUM PSYCHOPHARM CLIN, 2010. 25:543-552. I.F.:2,50. 2 Iranzo A, Lomena F, Stockner H, Valldeoriola F, Vilaseca I, Salamero M, Molinuevo JL, Serradell M, Duch J, Pavia J, Gallego J, Seppi K, Hogl B, Tolosa E, Poewe W, Santamaria J. Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapideye-movement sleep behaviour disorder: a prospective study. LANCET NEUROL, 2010. 9:1070-1077. I.F.:18,13. 3 Sanz-Cortes M, Figueras F, Bargallo N, Padilla N, Amat-Roldan I, Gratacos E. Abnormal brain microstructure and metabolism in small-for-gestational-age term fetuses with normal umbilical artery Doppler. ULTRASOUND OBST GYN, 2010. 36:159165. I.F.:3,15. 4 Esteban FJ, Padilla N, Sanz-Cortes M, DeMiras JR, Bargallo N, Villoslada P, Gratacos E. Fractal-dimension analysis detects cerebral changes in preterm infants with and without intrauterine growth restriction. NEUROIMAGE, 2010. 53:1225-1232. I.F.:5,74. 5 Bosch B, Batres-Faz D, Rami L, ArenazaUrquijo EM, Fernandez-Espejo D, Junque C, Sole-Padulles C, Sanchez-Valle R, Bargallo N, Falcon C, Molinuevo JL. Cognitive reserve modulates task-induced activations and deactivations in healthy elders, amnestic mild cognitive impairment and mild Alzheimer’s disease. CORTEX, 2010. 46:451-461. I.F.:4,06. 6 Ibarretxe-Bilbao N, Ramirez-Ruiz B, Junque C, Marti MJ, Valldeoriola F, Bargallo N, Juanes S, Tolosa E. Differential progression 234 of brain atrophy in Parkinson’s disease with and without visual hallucinations. J NEUROL NEUROSUR PS, 2010. 81:650-657. I.F.:4,87. 7 Sala-Llonch R, Bosch B, Arenaza-Urquijo EM, Rami L, Bargallo N, Junque C, Molinuevo JL, Bartres-Faz D. Greater Default-Mode Network Abnormalities Compared to High Order Visual Processing Systems in Amnestic Mild Cognitive Impairment: An Integrated MultiModal MRI Study. J ALZHEIMERS DIS, 2010. 22:523-539. I.F.:3,83. 8 Fortea J, Sala-Llonch R, Bartres-Faz D, Bosch B, Llado A, Bargallo N, Molinuevo JL, Sanchez-Valle R. Increased Cortical Thickness and Caudate Volume Precede Atrophy in PSEN1 Mutation Carriers. J ALZHEIMERS DIS, 2010. 22:909-922. I.F.:3,83. 9 Ibarretxe-Bilbao N, Junque C, Marti MJ, Valldeoriola F, Vendrell P, Bargallo N, Zarei M, Tolosa E. Olfactory Impairment in Parkinson’s Disease and White Matter Abnormalities in Central Olfactory Areas: A Voxel-Based Diffusion Tensor Imaging Study. MOVEMENT DISORD, 2010. 25:1888-1894. I.F.:4,01. 10 Pintor L, Bailles E, Matrai S, Carreno M, Donaire A, Boget T, Setoain X, Rumia J, Bargallo N. Efficiency of Venlafaxine in Patients With Psychogenic Nonepileptic Seizures and Anxiety and/or Depressive Disorders. J NEUROPSYCH CLIN N, 2010. 22:401-408. I.F.:2,34. 11 Carreno M, Garcia-Alvarez D, Maestro I, Fernandez S, Donaire A, Boget T, Rumia J, Pintor L, Setoain X. Malignant autosomal dominant frontal lobe epilepsy with repeated episodes of status epilepticus: successful treatment with vagal nerve stimulation. EPILEPTIC DISORD, 2010. 12:155-158. I.F.:1,20. 13 Castro-Fornieles J, Caldu X, AndresPerpina S, Lazaro L, Bargallo N, Falcon C, Plana MT, Junque C. A cross-sectional and follow-up functional MRI study with a working memory task in adolescent anorexia nervosa. NEUROPSYCHOLOGIA, 2010. 48:4111-4116. I.F.:4,35. 14 Rametti G, Junque C, Bartres-Faz D, Zubiaurre-Elorza L, Catalan R, Penades R, Bargallo N, Bernardo M. Anterior cingulate and paracingulate sulci morphology in patients with schizophrenia. SCHIZOPHR RES, 2010. 121:66-74. I.F.:4,46. 15 Gomez-Gil E, Navines R, DeOsaba MJM, Diaz-Ricart M, Escolar G, Salamero M, MartinSantos R, Galan A, Gasto C. Hormonal responses to the 5-HT1A agonist buspirone in remitted endogenous depressive patients after long-term imipramine treatment. PSYCHONEUROENDOCRINO, 2010. 35:481-489. I.F.:4,19. 16 Valdes M, Collado A, Bargallo N, Vazquez M, Rami L, Gomez E, Salamero M. Increased Glutamate/Glutamine Compounds in the Brains of Patients With Fibromyalgia A Magnetic Resonance Spectroscopy Study. ARTHRITIS RHEUM-US, 2010. 62:1829-1836. I.F.:7,33. 17 Solana E, Poca MA, Sahuquillo J, Benejam B, Junque C, Dronavalli M. Cognitive and motor improvement after retesting in normal-pressure hydrocephalus: a real change or merely a learning effect? Clinical article. J NEUROSURG, 2010. 112:399-409. I.F.:2,59. 18 Fernandez-Espejo D, Junque C, Cruse D, Bernabeu M, Roig-Rovira T, Fabregas N, Rivas E, Mercader JM. Combination of diffusion tensor and functional magnetic resonance imaging during recovery from the vegetative state. BMC NEUROL, 2010. 10:-. I.F.:2,11. 12 Sanchez-Gistau V, Pintor L, Sugranyes 19 Carrillo B, Gomez-Gil E, Rametti G, G, Bailles E, Carreno M, Donaire A, Boget T, Setoain X, Bargallo N, Rumia J. Prevalence of interictal psychiatric disorders in patients with refractory temporal and extratemporal lobe epilepsy in Spain. A comparative study. EPILEPSIA, 2010. 51:1309-1313. I.F.:4,05. Junque C, Gomez A, Karadi K, Segovia S, Guillamon A. Cortical activation during mental rotation in male-to-female and female-to-male transsexuals under hormonal treatment. PSYCHONEUROENDOCRINO, 2010. 35:12131222. I.F.:4,19. AREA 4 Clinical and experimental neuroscience Neuropsychology 20 Sanchez-Castaneda C, Rene R, Ramirez-Ruiz B, Campdelacreu J, Gascon J, Falcon C, Calopa M, Jauma S, Juncadella M, Junque C. Frontal and Associative Visual Areas Related to Visual Hallucinations in Dementia with Lewy Bodies and Parkinson’s Disease with Dementia. MOVEMENT DISORD, 2010. 25:615622. I.F.:4,01. 21 Grau-Olivares M, Arboix A, Junque C, Arenaza-Urquijo EM, Rovira M, Bartres-Faz D. Progressive Gray Matter Atrophy in Lacunar Patients with Vascular Mild Cognitive Impairment. CEREBROVASC DIS, 2010. 30:157-166. I.F.:3,54. 22 Fernandez-Espejo D, Junque C, Bernabeu M, Roig-Rovira T, Vendrell P, Mercader JM. Reductions of Thalamic Volume and Regional Shape Changes in the Vegetative and the Minimally Conscious States. J NEUROTRAUM, 2010. 27:1187-1193. I.F.:4,25. 23 Segura B, Jurado MA, Freixenet N, Bargallo N, Junque C, Arboix A. White matter fractional anisotropy is related to processing speed in metabolic syndrome patients: a case-control study. BMC NEUROL, 2010. 10:-. I.F.:2,11. Reviews I.F.: 2,82 1 Castro-Fornieles J, Garcia AI, Lazaro L, Andres-Perpina S, Falcon C, Plana MT, Bargallo N. Prefrontal brain metabolites in short-term weight-recovered adolescent anorexia nervosa patients. PROG NEURO-PSYCHOPH. 34:1049-1053. I.F.:2,82. Grants for research in progress Bargallo N. Usefulness of ictal functional MRI in localization of epileptogenic area in patients with refractory focal epilepsy. Sponsored by: Fundació Marató TV3, 60910. Amount: 115.135,00 euros. Duration: 15/02/2007-14/02/2010. Salamero M. Desarrollo y validación en una nueva escala de somnolencia de aplicación clínica. Sponsored by: Ministerio Sanidad y Consumo, PI070318. Amount: 179.624,50 euros. Duration: 26/11/200730/12/2010. Junqué C. Distinció de la Generalitat de Catalunya per a la Promoció de la Recerca Universitària. Sponsored by: Generalitat de Catalunya, UNI/2001/2004. Amount: 180.522,00 euros. Duration: 31/12/2004-31/12/2010. Bargallo N. Red española de investigación en patología infecciosa (REIPI). Sponsored by: Instituto de Salud Carlos III, RD06/0008/1013. Amount: 20.500,00 euros. Duration: 29/02/2008-31/12/2010. Junqué C. Aplicación de la resonancia magnética estructural y funcional al estudio del estado vegetativo y el estado de mínima conciencia en los traumatismos craneo encefálicos. Sponsored by: Ministerio Educación y Ciencia, SAF 2007-66077. Amount: 28.000,00 euros. Duration: 01/01/2008-31/12/2010. y genéticas y la función y estructura cerebrales en el envejecimiento sano y patológico. Sponsored by: Ministerio de Ciencia e Innovación, 052296. Amount: 50.000,00 euros. Duration: 01/01/201031/12/2013. Bartres D. Prediction of cognitive properties of new drug candidates for neurodegenerative diseases in early clinical development. Sponsored by: Cordis Europa, 052297. Amount: 660.950,00 euros. Duration: 01/01/2010-31/12/2015. Thesis Bartres D, Molinuevo JL. Influencia de la reserva cognitiva en la estructura y funcionalidad cerebral en el envejecimiento sano y patológico. PhD student: Beatriz Bosch Capdevila. Junque C. The vegetative and the minimally conscious state: brain function, connectivity and structural abnormalities. PhD student: Davinia Fernández Espejo. Junqué C. Ajuts de Suport als grups de Recerca. Sponsored by: DURSI - Departament d’Universitats, Recerca i Societat de la Informació, 2009SGR941. Amount: 58.240,00 euros. Duration: 01/01/200931/12/2013. Marcos T. Estudio de la eficacia de la rehabilitación cognitiva en el trastorno depresivo mayor refractario al tratamiento farmacológico. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/90126. Amount: 26.620,00 euros. Duration: 01/01/2010-31/12/2011. Bartres D. Relación entre variables de reserva cerebral de tipo ambientales 235 AREA 4 Clinical and experimental neuroscience Systems neuroscience Strategic Objectives Group Members TEAM LEADER Maria Victoria Sánchez Vives (ICREA-IDIBAPS) Tel.: 93 227 5400 (Ext.: 4301) Fax: 93 227 1890 E-mail: msanche3@clinic.ub.es Recently, the growing knowledge of synaptic physiology and brain circuits, together with the development of new instruments with which to register, analyze and model the activity of a large number of neurons has made it possible to address one of the great pending challenges in neuroscience: to understand the relationship between the activity of the neuron population and behavioral performance. The objective of the systems neuroscience group is to address this challenge combining experimental studies in basal ganglia, hippocampal and cortical networks with a theoretical approach. Main Lines of Research Idibaps members: Albert Compte (IDIBAPS) David Robbe (IDIBAPS) Perla Kaliman (IDIBAPS) Jaime de la Rocha (IDIBAPS) Enrique Pérez-Garci (IDIBAPS) Postdoctoral fellows: Daniel Perez Marcos (IDIBAPS) Ramón Reig (IDIBAPS) David Borland (IDIBAPS) Ilias Bergstrom (IDIBAPS) Pavel Rueda-Orozco (IDIBAPS) Alexander Roxin (IDIBAPS) Rita Almeida (IDIBAPS) Klaus Wimmer (IDIBAPS) Lucila Kargieman (IDIBAPS) Francesca Barbieri Research Fellows: Maria Cano Colino Daniel Jercog Diego López Pigozzi Maria Pérez Zabalza Marcel Ruiz Mejias María Jesús Álvarez López (FI-AGAUR) 236 María Umpierrez Thomas Gener Juan Abolafia Salvador de la Torre Marco Castro (IDIBAPS) Juan Pablo Ramírez Mahaluf Technicians: Carolina Sales Carbonell Collaborators: Vanessa Fernandez Descalzo (IDIBAPS) Xavier Palomer Lorena Pérez Méndez Laura Ciria Luis Zapata (IDIBAPS) Marcelina Párrizas (IDIBAPS) Mercè Pallàs (CIBERNED - UB) Julita de la Vega (La Caixa, IDIBAPS) Visiting Scientists: Maurizio Mattia (Istituto Superiore di Sanità, Roma) Duane Q. Nykamp (Univ. Minnesota, USA) Electrical activity generation and control mechanisms in neuronal networks – specifically, in the brain cortex.Hippocampal and subicular mechanisms of spatial processing.Neuronal activity synchronization mechanisms in cortical networks.Distributed cortical network mechanisms implicated in selective attention, working memory and executive control.Simple motor coding (head movement, lever activation) based on striatal clustering.Mechanism of information transfer between networks.Effect of cannabinoids on high-voltage axes.Use of virtual reality in neuroscience, in the context of theEVENT Lab (Virtual Environments in Neuroscience and Technology), in collaboration with Mel Slater (University of Barcelona).Effect of behavioral interventions on the epigenetic regulation of processes implicated in chronic diseases and related to aging. 1. Cortical networks and EVENT Lab (Virtual Environments in Neuroscience and Technology). Headed by Dr. Maria Victòria Sánchez (IDIBAPS). Neuronal connectivity and cellular and synaptic properties determine and give shape to the emergent population activity (spontaneous or invoked) generated by the neuronal networks. At the same time, such activity has effects upon the network, with the regulation of relevant mechanisms such as synaptic plasticity. We are interested in different aspects of the activity generated: the mechanisms that regulate it, the information AREA 4 Clinical and experimental neuroscience Systems neuroscience it encodes, and the consequences of this activity upon the network. The impact which the different cellular processes (e.g., ion channel activation) have upon the resultant network activity tends to be non-intuitive and unpredictable – thus making it necessary to adopt a theoretical and experimental approach. As regards the information encoded by the network activity, we have worked with different sensory modalities (visual, tactile, auditory), and are presently especially interested in the spatial processing that occurs in the hippocampal complex. Lastly, integration of the cortical information giving rise to bodily representation and the combination of braincomputer interfaces and virtual reality for understanding these processes, is another research line of our group, as part of the EVENT Lab. For further information: www.sanchez-vives.org www.event-lab.org 2. Theoretical neurobiology of the cortical networks. Headed by Dr. Albert Compte (IDIBAPS). Our research is aimed at clarifying the mechanisms that operate in the cortical microcircuit, with a view to conducting computations of relevance to behavior. The tools we use are computerimplemented cortical network models seeking biological plausibility at all times, and technically sophisticated dataanalyzing tools. We work in parallel at two levels: on one hand, we model the activity of the cortical microcircuit in order to understand and quantify the mechanisms underlying the generation of population activity in the circuit, and on the other we study the physiological bases of cognitive capacities such as working memory and selective attention, and their dysfunction in psychiatric disorders. For further information: http://complab.fcrb.es 3. Physiology and basal ganglia networks and regulation with cannabinoids. Headed by Dr. David Robbe (IDIBAPS). The principal objective of the laboratory is to understand the processing of cognitive and motor-sensory (cortical) information in the basal ganglia - a group of subcortical nuclei that are essential for motor coordination and the formation of habits, and which are implicated in Parkinson’s disease and in addictions. Surprisingly, the excellent description of the anatomical characteristics of the basal ganglia (BG) has given rise to two opposed reference models of processing carried out in the BG. In the first model, the BG have been modelled as independent information processing channels, while the other model postulates that the ganglia act as cortical input integrators. In order to address this controversy, we use largescale electrophysiological recording techniques (silica catheters, tetrodes) in the course of specific motor activities, in combination with advanced analytical tools and pharmacological perturbation (cannabinoids). For further information: http://neuro.fcrb.es/BasalGangLab/ RobbeLab/Welcome.html and mindfulness-based stress reduction trainings in humans) on the epigenetic regulation of processes such as oxidative stress and inflammation, which are at the root of most chronic and aging-related diseases. 5. Cortical Circuit Dynamics Group. Headed by Dr. Jaime de la Rocha (IDIBAPS). The main focus of our research is the study of the circuit mechanisms underlying perception and decision making. In particular we are interested in the neural basis of auditory representation and its dependence on brain state and other contextual variables. We investigate the generation of ongoing cortical activity, its impact on perception and guiding decisions. We are particularly interested in the variability and co-variability observed in the sensory-evoked responses of cortical neurons, the mechanisms which generate them and their role in a neural code. We combine population cortical recordings in rats, quantitative analysis and computational modeling to address these questions. For further information: http://neuro.fcrb.es/delaRochaLab 4. Neuroepigenetics lab. Headed by Perla Kaliman (IDIBAPS). It is now accepted that brain networks and genetic information in adults are both sensitive and responsive to experience. An increasing number of studies in animal models are starting to show that behavioral interventions can induce changes in epigenetic codes in the nervous system that may be critical for synaptic plasticity and complex processes such as memory, learning and stress resistance. In this context, our research is aimed at identifying behavioral-induced molecular biomarkers associated with adaptive psychological and physiological changes. Accordingly, we investigate the effect of behavioral interventions (e.g. voluntary exercise and enriched environment in rodents 237 AREA 4 Clinical and experimental neuroscience Systems neuroscience PUBLICATIONS 6. Laboratory of Dendritic Computation. Headed by Enrique PerezGarci (IDIBAPS). It is becoming clear now that dendrites can be considered as active excitable entities which can be subject to modulation by different neurotransmitters (Dendritic Neuromodulation). With the emergence of imaging and electrophysiological approaches to study dendritic physiology, I believe the field is poised to explore the fundamentals of dendritic computation. With this in mind, I aim to take advantage of these developments and combined them with pharmacological and molecular biological tools, to get a more detailed picture of the impact of interacting sub-cellular dendritic regions and their modulation for determining the firing output of the neuron. The apical tuft of layer 5 pyramidal neurons is innervated by a large number of inhibitory inputs with unknown functions. Inhibitory postsynaptic potentials (IPSPs) evoked by distal GABAergic terminals have little or no direct impact on the somato-axonic compartment of the neuron. A possible role for these inhibitory inputs is to modulate the so called Na+-Ca2+ spikes that occur in the apical tuft. My research work focuses on the molecular mechanisms by which GABA mediates the inhibition of such regenerative processes. In particular, activation of metabotropic GABAb receptors exerts an inhibitory control of dendritic spikes by means of a very refined molecular machinery. Research Techniques: •Simultaneous whole-cell recordings along the somato-dendritic axis of layer 5 pyramidal neurons using the in vitro slice preparation. •Ca2+ fluorescence recordings. •Pharmacology. 238 Originals I.F.: 51,07 1 Musri MM, Carmona MC, Hanzu FA, Kaliman P, Gomis R, Parrizas M. Histone Demethylase LSD1 Regulates Adipogenesis. J BIOL CHEM, 2010. 285:3003430041. I.F.:5,33. 2 Lundqvist M, Compte A, Lansner A. Bistable, Irregular Firing and Population Oscillations in a Modular Attractor Memory Network. PLOS COMPUT BIOL, 2010. 6:-. I.F.:5,76. 3 Slater M, Spanlang B, Sanchez-Vives MV, Blanke O. First Person Experience of Body Transfer in Virtual Reality. PLoS ONE, 2010. 5:-. I.F.:4,35. 4 Fernandez V, Salamero O, Espinet B, Sole F, Royo C, Navarro A, Camacho F, Bea S, Hartmann E, Amador V, Hernandez L, Agostinelli C, Sargent RL, Rozman M, Aymerich M, Colomer D, Villamor N, Swerdlow SH, Pileri SA, Bosch F, Piris MA, Montserrat E, Ott G, Rosenwald A, Lopez-Guillermo A, Jares P, Serrano S, Campo E. Genomic and Gene Expression Profiling Defines Indolent Forms of Mantle Cell Lymphoma. CANCER RES, 2010. 70:1408-1418. I.F.:7,54. 5 Bermejo-Martin JF, Martin-Loeches I, Rello J, Anton A, Almansa R, Xu LL, Lopez-Campos G, Pumarola T, Ran LS, Ramirez P, Banner D, Ng DC, Socias L, Loza A, Andaluz D, Maravi E, GomezSanchez MJ, Gordon M, Gallegos MC, Fernandez V, Aldunate S, Leon C, Merino P, Blanco J, Martin-Sanchez F, Rico L, Varillas D, Iglesias V, Marcos MA, Gandia F, Bobillo F, Nogueira B, Rojo S, Resino S, Castro C, DeLejarazu RO, Kelvin D. Host adaptive immunity deficiency in severe pandemic influenza. CRIT CARE, 2010. 14:-. I.F.:4,93. 6 DeLaPena N, Weil P, Llobera J, Giannopoulos E, Pomes A, Spanlang B, Friedman D, Sanchez-Vives MV, Slater M. Immersive Journalism: Immersive Virtual Reality for the First-Person Experience of News. PRESENCE-TELEOP VIRT, 2010. 19:291-301. I.F.:1,24. 7 Sanchez-Vives MV, Mattia M, Compte A, Perez-Zabalza M, Winograd M, Descalzo VF, Reig R. Inhibitory Modulation of Cortical Up States. J NEUROPHYSIOL, 2010. 104:1314-1324. I.F.:3,48. 8 Ardid S, Wang XJ, Gomez-Cabrero D, Compte A. Reconciling Coherent Oscillation with Modulation of Irregular Spiking Activity in Selective Attention: Gamma-Range Synchronization between Sensory and Executive Cortical Areas. J NEUROSCI, 2010. 30:28562870. I.F.:7,18. 9 Brotons-Mas JR, Montejo N, O’mara SM, Sanchez-Vives MV. Stability of subicular place fields across multiple light and dark transitions. EUR J NEUROSCI, 2010. 32:648-658. I.F.:3,42. 10 Reig R, Mattia M, Compte A, Belmonte C, Sanchez-Vives MV. Temperature Modulation of Slow and Fast Cortical Rhythms. J NEUROPHYSIOL, 2010. 103:1253-1261. I.F.:3,48. 11 Sanchez-Vives MV, Spanlang B, Frisoli A, Bergamasco M, Slater M. Virtual Hand Illusion Induced by Visuomotor Correlations. PLoS ONE, 2010. 5:-. I.F.:4,35. Reviews I.F.: 3,48 1 Nowak LG, Sanchez-Vives MV, Mccormick DA. Spatial and Temporal Features of Synaptic to Discharge Receptive Field Transformation in Cat Area 17. J NEUROPHYSIOL, 2010. 103:677697. I.F.:3,48. AREA 4 Clinical and experimental neuroscience Systems neuroscience Grants for research in progress Kaliman P. Identificación de vias de señalización molecular reguladas por DMPK (Myotonic Dystrophy Protein Kinase) y su papel en el desarrollo de las alteraciones metabólicas asociadas a la Distrofia Miotónica. Sponsored by: Ministerio Educación y Ciencia, SAF2007-63353. Amount: 145.200,00 euros. Duration: 01/10/200704/10/2010. Robbe D. Dynamic of neuronal network interactions in the basal ganglia. Sponsored by: EUROPEAN COMISSION, 230976. Amount: 100.000,00 euros. Duration: 01/09/2008-31/08/2012. Sanchez-Vives MV. Synthetic Forager. Amount: European Commission, 217148. Amount: 320.309,10 euros. Duration: 15/01/2008-14/01/2011. Sanchez-Vives MV, Compte A. Estudi de tècniques avançades de modelització i estimulació neuronalModalitat Projectes en Recerca Industrial i Desenvolupament Experimental - Projectes Comuns. Sponsored by: GENERALITAT DE CATALUNYA - CIDEM, RD08-20013. Amount: 190.054,18 euros. Duration: 15/07/2008-15/07/2010. Sanchez-Vives MV. Grups Consolidats de Recerca “Neurociencias de Sistemas”. Sponsored by: AGAUR, 2009 SGR1363. Amount: 45.760,00 euros. Duration: 01/01/200931/12/2013. Compte A. Mecanismos de redes distribuidas en memoria de trabajo y atención selectiva. Sponsored by: MINISTERIO DE EDUCACIÓN, BFU2009_09537. Amount: 234.740,00 euros. Duration: 01/01/201031/12/2012. Sanchez-Vives MV. Beaming through augmented media for natural networked gatherings. Sponsored by: Starlab Barcelona SL, 248620. Amount: 540.313,00 euros. Duration: 01/01/2010-31/12/2013. Sanchez-Vives MV. Virtual Embodiment and Robotic Re-Embodiment. Sponsored by: UNIVERSITAT DE BARCELONA FACULTAT DE MEDICINA, 257695. Amount: 552.700,00 euros. Duration: 01/06/201031/05/2015. Sanchez-Vives MV. Optimización de la respuesta terapéutica a la modulación de estímulos auditivos. Sponsored by: iSOFT SANIDAD, S.A, IPT-300000-2010-0010. Amount: 450.207,00 euros. Duration: 22/06/2010-31/12/2013. Thesis Kaliman P. Impact of aging and physical exercise on transcriptional and epigenetic profiles (brain and cardiac studies). PhD student: María Umpiérrez. Kaliman P. Estudio epigenético y transcripcional de un modelo murino de envejecimiento acelerado (estudio en linfocitos). PhD student: María Jesús Álvarez López. Sanchez-Vives MV. Real time analysis of hippocampal activity for the control of external devices.. PhD student: Julita de la Vega Arias. Robbe D. Basal Ganglia and the control of locomotion. Sponsored by: EUROPEAN COMISSION, 253873. Amount: 161.293,00 euros. Duration: 01/10/201030/09/2012. Sanchez-Vives MV. Dinámica cortical en los diferentes estados de activación de la red. Sponsored by: Ministerio de Ciencia y Tecnologia (MICINN), BFU2008-01371/BFI. Amount: 285.000,00 euros. Duration: 01/01/2009-31/12/2011. Sanchez-Vives MV. Synaptic drugs for cognitive disorders: identifying new targets for pharmacological intervention. Sponsored by: CRG - CENTRE REGULACIO GENOMICA, FLEJEUNE_2010_001. Amount: 7.374,91 euros. Duration: 27/05/2010-26/05/2012. Robbe D. Entendiendo los efectos de los canabinoides en los episodios epilépticos en la red talamocortical Tipo de proyecto: A. Sponsored by: Ministerio de Educación y Ciencia, BFU200803946/BFI. Amount: 90.000,00 euros. Duration: 01/01/2009-31/12/2011. De La Rocha J. Network dynamics of auditory cortex and the impact of correlations on the encoding of sensory information. Sponsored by: EUROPEAN COMISSION, FP7-PEOPLE-IRG-10_01. Amount: 100.000,00 euros. Duration: 01/09/2010-31/08/2014. 239 AREA 4 clinical and experimental neuroscience Team envolved in: Clinical and experimental neuroimmunology GROUP Members Strategic Objectives TEAM LEADER Francesc Graus (Hospital Clínic) Tel.: 93 227 57 85 Fax: 93 227 57 83 E-mail: fgraus@clinic.ub.es 1. The principal objective of the neuroimmunology group is the study of inflammation of the central nervous system, and of the mechanisms that are involved in this inflammatory response, and their implication in neurological disorders - fundamentally multiple sclerosis, autoimmune encephalitis and paraneoplastic neurological disorders. 2. Identification and characterization of factors implicated in the pathogenesis of gliomas, based on the study of proteins that control the maintenance, differentiation and migration of normal neural stem cells. Main Lines of Research Idibaps members: Pablo Villoslada (IDIBAPS) Moreno, Beatriz (IDIBAPS) Núria de la Iglesia (IDIBAPS) Lidia Sabater (Fundació Clínic) Albert Saiz (Hospital Clínic) Yolanda Blanco (Hospital Clínic) Postdoctoral fellows: Begonya Otal (IDIBAPS) Valeria Colafrancesco (IDIBAPS) Research Fellows: Inna Pertsovskaya (IDIBAPS) Oihana Errea (IDIBAPS) Ion Agirrezabal (FIS) Anna Boronat (FIS) Sara Llufriu (Río Hortega) Francesco Mannara (Fundació Clínic) Marta Moreno (FPI) Iñigo Gabilondo (IDIBAPS) 240 Technicians: Begoña Fernández (IDIBAPS) Alice Taubes (IDIBAPS) Nagore Escala (IDIBAPS) Mercè Albà (Fundació Clínic) Eva Caballero (Fundació Clínic) 1. Study of autoimmune mechanisms in paraneoplastic neurological disorders. 2. Synaptic autoimmunity study in encephalitis and other autoimmune diseases of the central nervous system. 3. Development of biomarkers and new therapies in application to multiple sclerosis and other neurological diseases. Nursing Staff: Montserrat Artola (REEM, Red Española Esclerosis Múltiple) Administrative Staff: Juan Alejandro Virgili (REEM) Berta Alcahud (REEM) Gemma Castillo (Fundació Clínic) Collaborators: Ana Catafau (IDIBAPS) Bernardo Sanchez-Dalmau (Hospital Clínic) Automatic segmentation of the corpus callosum through diffusion tensor imaging and 3D-T1 imaging using FSL software. In this way it is possible to determine the volumetric characteristics of this structure, which is frequently altered in multiple sclerosis. Accepted for the 17th Annual Meeting of the Organization for Human Brain Mapping (Quebec, June 2011). AREA 4 Clinical and experimental neuroscience clinical and experimental neuroimmunology 4. Functional imaging in neuroimmunology. 5. Study of the molecular bases of glioma pathogenesis: Identification and functional characterization of new factors implicated in the maintenance, differentiation and/or migration of neural stem cells, and study of the role of these factors in the initiation and invasion of gliomas. RESEARCH GROUP Pathogenesis and new treatments in multiple sclerosis Group Leader: Pablo Villoslada (IDIBAPS) The great challenge for our research team is to apply our discoveries to the clinical management of patients with multiple sclerosis. By late 2010 we plan to enter the clinical phase of the study of methylthioadenosine as treatment in cases of multiple sclerosis. As the coordinating team of the RETICS REEM (Spanish Multiple Sclerosis Network - www.reem. es), another of our strategic objectives is the transverse diffusion of knowledge and optimum use of synergies, with a view to transferring the advances in research to the clinical practice setting and to patients. Lastly, the group has a constant commitment to innovation, both in terms of the generation of patents and as regards the creation of spinoff companies to cover the gap in financing existing between basic research and the clinical phase development of new drugs on the part of the biopharmaceutical industry. Web of the group: www.reem.es/idibaps/team.html RESEARCH GROUP Immunopathogenesis of paraneoplastic neurological disorders Group Leader: Francesc Graus (Hospital Clínic) Paraneoplastic neurological disorders manifest in cancer patients generally in very early stages, and their correct diagnosis is essential for detecting the tumor and for preventing progression of the neurological disease. Our group has made a fundamental contribution to confirmation of the immunological cause of these disorders, and is an international reference center for the evaluation of antineuronal antibodies associated to paraneoplastic neurological disorders. The group is interested in the characterization of antineuronal antibodies and corresponding antigens of potential diagnostic or pathogenic relevance in relation to these diseases. Some of the antibodies identified by our group, such as anti-Hu, anti-Tr or anti-SOX1, are currently used on a routine basis as predictors of paraneoplastic neurological disorders. PUBLICATIONS Originals I.F.: 98,76 1 Esteban FJ, Padilla N, SanzCortes M, DeMiras JR, Bargallo N, Villoslada P, Gratacos E. Fractaldimension analysis detects cerebral changes in preterm infants with and without intrauterine growth restriction. NEUROIMAGE, 2010. 53:1225-1232. I.F.:5,74. 2 Graus F, Boronat A, Xifro X, Boix M, Svigelj V, Garcia A, Palomino A, Sabater L, Alberch J, Saiz A. The expanding clinical profile of anti-ampa receptor encephalitis. NEUROLOGY, 2010. 74:857-859. I.F.:8,17. 3 Lancaster E, Lai MZ, Peng XY, Hughes E, Constantinescu R, Raizer J, Friedman D, Skeen MB, Grisold W, Kimura A, Ohta K, Iizuka T, Guzman M, Graus F, Moss SJ, Balice-Gordon R, Dalmau J. Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: Case series and characterisation of the antigen. LANCET NEUROL, 2010. 9:67-76. I.F.:18,13. 4 Villoslada P. Biomarkers for multiple sclerosis. DRUG NEWS PERSPECT, 2010. 23:585-595. I.F.:2,10. 5 Liimatainen S, Peltola M, Sabater L, Fallah M, Kharazmi E, Haapala AM, Dastidar P, Knip M, Saiz A, Peltola J. Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy. EPILEPSIA, 2010. 51:760-767. I.F.:4,05. 6 Blanco Y, Hankiewicz K, Llufriu S, Sabater L, Graus F, Saiz A. Clinical spectrum associated with aquaporin-4 antibodies (NMO-IgG). NEUROLOGIA, 2010. 25:5-12. I.F.:0,60. 241 AREA 4 Clinical and experimental neuroscience Clinical and experimental neuroimmunology Team Members 7 Ducray F, Graus F, Vigliani MC, Antoine JC, Rogemond V, Saiz A, Honnorat J. Delayed onset of a second paraneoplastic neurological syndrome in eight patients. J NEUROL NEUROSUR PS, 2010. 81:937-939. I.F.:4,87. 8 Robinson-Agramonte MA, Goncal- 18 Llufriu S, Pujol T, Blanco Y, Hankiewi- I, Brieva L, Bufill E, Cano A, Carmona O, Escartin A, Marco M, Moral E, Munteis E, Nos C, Pericot I, Perkal H, Ramio-Torrenta L, Ramo-Tello C, Saiz A, Sastre-Garriga J, Tintore M, Vaque J, Montalban X. Multiple sclerosis epidemiological situation update: pertinence and set-up of a population based registry of new cases in Catalonia. REV NEUROLOGIA, 2010. 50:623-633. I.F.:1,23. cz K, Squarcia M, Berenguer J, Villoslada P, Graus F, Saiz A. T2 hypointense rims and ring-enhancing lesions in MS. MULT SCLER, 2010. 16:1317-1325. I.F.:3,28. ves CAS, Portela VL, Saiz-Hinarejos A, Oses PJ, Motta SL, Muller AP, Gonzalez MEM, DeSouza ODG. Differential Regulation of IgG-NMO Autoantibodies on S100Beta Protein and Disability in Relapsing Neuromyelitis Optica. NEUROIMMUNOMODULAT, 2010. 17:177-179. I.F.:2,03. 13 Saiz A, Graus F. Neurologic Com- 9 14 Giometto B, Grisold W, Vitaliani Soffietti R, Baumert BG, Bello L, VonDeimling A, Duffau H, Frenay M, Grisold W, Grant R, Graus F, HoangXuan K, Klein M, Melin B, Rees J, Siegal T, Smits A, Stupp R, Wick W. Guidelines on management of lowgrade gliomas: report of an EFNSEANO* Task Force. EUR J NEUROL, 2010. 17:1124-1133. I.F.:2,51. 10 Lai MZ, Huijbers MGM, Lancaster E, Graus F, Bataller L, BaliceGordon R, Cowell JK, Dalmau J. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. LANCET NEUROL, 2010. 9:776-785. I.F.:18,13. 11 Marignier R, Chenevier F, Rogemond V, Smitt PS, Renoux C, Cavillon G, Androdias G, Vukusic S, Graus F, Honnorat J, Confavreux C. Metabotropic Glutamate Receptor Type 1 Autoantibody-Associated Cerebellitis A Primary Autoimmune Disease?. ARCH NEUROL-CHICAGO, 2010. 67:627-630. I.F.:6,31. 242 12 Otero S, Batlle J, Bonaventura plications of Hematopoietic Cell Transplantation. SEMIN NEUROL, 2010. 30:287-295. I.F.:2,53. R, Graus F, Honnorat J, Bertolini G. Paraneoplastic Neurologic Syndrome in the PNS Euronetwork Database A European Study From 20 Centers. ARCH NEUROL-CHICAGO, 2010. 67:330-335. I.F.:6,31. 15 Moreno B, Fernandez-Diez B, DiPenta A, Villoslada P. Preclinical studies of methylthioadenosine for the treatment of multiple sclerosis. MULT SCLER, 2010. 16:1102-1108. I.F.:3,28. 16 Martinez-Forero I, Pelaez-Lopez A, Villoslada P. Steady State Detection of Chemical Reaction Networks Using a Simplified Analytical Method. PLOS ONE, 2010. 5:-. I.F.:4,35. 17 Goni J, Martincorena I, Corominas-Murtra B, Arrondo G, Ardanza-Trevijano S, Villoslada P. Switcher-Random-Walks: a cognitiveinspired mechanism for network exploration. INT J BIFURCAT CHAOS, 2010. 20:913-922. I.F.:0,92. 19 Alcina A, Vandenbroeck K, Otaegui D, Saiz A, Gonzalez JR, Fernandez O, Cavanillas ML, Cenit MC, Arroyo R, Alloza I, Garcia-Barcina M, Antiguedad A, Leyva L, Izquierdo G, Lucas M, Fedetz M, Pinto-Medel MJ, Olascoaga J, Blanco Y, Comabella M, Montalban X, Urcelay E, Matesanz F. The autoimmune disease-associated KIF5A, CD226 and SH2B3 gene variants confer susceptibility for multiple sclerosis. GENES IMMUN, 2010. 11:439-445. I.F.:4,22. Reviews I.F.: 6,18 1 Graus F, Saiz A, Dalmau J. Antibodies and neuronal autoimmune disorders of the CNS. J NEUROL, 2010. 257:509-517. I.F.:2,90. 2 Freedman MS, Bar-Or A, Atkins HL, Karussis D, Frassoni F, Lazarus H, Scolding N, Slavin S, LeBlanc K, Uccelli A. The therapeutic potential of mesenchymal stem cell transplantation as a treatment for multiple sclerosis: consensus report of the International MSCT Study Group. MULT SCLER, 2010. 16:503-510. I.F.:3,28. Multicentrics I.F.: 3,28 1 De Stefano N, Curtin F, Stubinski B, Blevins G, Drulovic J, Issard D, Shotekov P, Gasperini C. Rapid benefits of a new formulation of subcutaneous interferon beta-1a in relapsing-remitting multiple sclerosis. MULT SCLER, 2010. 16:888-892. I.F.:3,28. AREA 4 Clinical and experimental neuroscience clinical and experimental neuroimmunology Grants for research in progress Villoslada P. United europeans for the development of pharmacogenomics in multiple sclerosis. Sponsored by: European Comisión. Marie Curie Training Network, PITN-GA- 212877. Amount: 198.422,00 euros. Duration: 15/09/2008-15/09/2011. Villoslada P. Análisis de la respuesta al tratamiento con interferon beta en la esclerosis múltiple mediante biología de sistemas. Sponsored by: Fundación Mutua Madrileña, FMM-2008-061. Amount: 45.000,00 euros. Duration: 01/07/2008-31/12/2010. Villoslada P. Estudio del daño axonal en esclerosis múltiple mediante estudios de neuroimagen de la vía óptica. Sponsored by: Instituto de Salud Carlos III, PS09/00259. Amount: 245.000,00 euros. Duration: 01/01/2010-31/12/2012. Villoslada P. Estudio de la dinámica remitente-recurrente en depresión mayor mediante el análisis de redes de conectividad funcional por resonancia magnética funcional: implicaciones para la terapia. Sponsored by: Fundació Marató TV3, 0000. Amount: 345.000,00 euros. Duration: 01/01/2010-31/12/2012. Graus F. Anticuerpos contra de antígenos de membrana neuronal en síndormes neurológicos paraneoplásicos del sistema nervioso central. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/0193. Amount: 413.215,00 euros. Duration: 01/01/2010-31/12/2012. Villoslada P. Studying the relapsing dynamics of major depression through network analysis of fMRI connectivity maps: inplications for therapy.. Sponsored by: FUNDACIÓ LA MARATÓ DE TV3, 091430. Amount: 237.325,00 euros. Duration: 29/01/2010-28/01/2013. De La Iglesia N. Factores de mantenimiento y diferenciación de células madre neurales como actores principales en la patogénesis de los gliomas. Sponsored by: MINISTERIO DE EDUCACIÓN, BFU2009_14616. Amount: 145.200,00 euros. Duration: 01/01/2010-31/12/2012. Villoslada P. Terapia neuroprotectora para EM mediante agonistas del Factor de Crecimiento Nervioso (NGF). Sponsored by: MINISTERIO DE EDUCACIÓN, INC-0059. Amount: 14.500,00 euros. Duration: 01/01/201031/12/2011. by: ADVANCELL-Advanced in vitro cell techno., IPT-010000-2010-0035. Amount: 487.254,00 euros. Duration: 25/06/2010-31/12/2012. Saiz A. Trasplante autólogo de células madre mesenquimales en esclerosis múltiple: ensayo clínico fase II aleatorizado, doble-ciego y cruzado con placebo. Sponsored by: MINISTERIO DE SANIDAD, POLÍTICA SOCIAL E IGUALDAD, TRA-066. Amount: 181.986,36 euros. Duration: 01/01/201031/12/2011. Villoslada P. Congreso Internacional de Neuroinmunología. Sponsored by: MINISTERIO DE CIENCIA E INNOVACION, SAF2010-09238-E. Amount: 20.000,00 euros. Duration: 01/06/201031/05/2011. Villoslada P. Congress of the International Society of Neuroimmunology (ISNI). Sponsored by: GENERALITAT DE CATALUNYA, 2010 ARCS1 00329. Amount: 3.000,00 euros. Duration: 26/10/201030/10/2010. Graus F, Dalmau J. Clinical spectrum and cellular and synaptic mechanisms of autoimmune synaptic encephalitides. Sponsored by: FUNDACIÓ LA MARATÓ DE TV3, 101530. Amount: 283.200,00 euros. Duration: 10/12/2010-09/12/2013. Saiz A. Analysis of new antigens in seronegative (NMO-IgG/AQP4) neuromyelitis optica (Devic disease). Sponsored by: FUNDACIÓ LA MARATÓ DE TV3, 101610. Amount: 162.500,00 euros. Duration: 10/12/2010-09/12/2013. Mahy N, Villoslada P. Nuevas aproximaciones terapéuticas para la Esclerosis Múltiple y la Esclerosis Lateral Amiotrófica: efectos modificadores de la enfermedad y neuroprotección. Sponsored 243 AREA 4 Clinical and experimental neuroscience Team envolved in: CIBER en enfermedades neurodegenerativas (CIBERned) Neurobiology Unit Strategic Objectives GROUP Members TEAM LEADER Ramon Trullàs (IIBB-CSIC) Tel.: 93 363 83 03 Fax: 93 363 83 24 Idibaps members: Nicole Mahy (Facultat de Medicina UB) Manuel Rodríguez (Facultat de Medicina UB) Research Fellows: Montse Batlle (Facultat de Medicina) Lluís Benítez (IIBB-CSIC) Javier Ortega (Facultat de Medicina) Joana Figueiro-Silva (IIBB-CSIC) Margot Martínez (IDIBAPS) Technicians: Carmen Andrade (Facultat de Medicina) Nuria Serra (IIBB-CSIC) Natalia Castro (IIBB-CSIC) Collaborators: Kevin Clayton (CIBERNED) Marco Pugliese (Facultat de Medicina) Petar Podlesniy (IDIBAPS) José Manuel Vidal-Taboada (Facultat de Medicina) 244 The Neurobiology Unit investigates molecular mechanisms of excitotoxic and apoptotic neuron death with the objective of identifying new therapeutic targets for the management of neurodegenerative diseases. Another objective is to gain knowledge of the mechanisms regulating neurogenesis in the adult brain. Main Lines of Research 1. Investigation of the biochemical mechanisms causing excitotoxic neuron death. This project postulates that the inhibition of phospholipid synthesis is a key mechanism in neuron death produced by over-activation of glutamatergic receptors. 2. Investigation of the function of neuronal pentraxin 1 (NP1) during programmed neuron death, with the hypothesis that inhibition of the expression of this protein may constitute a new treatment for chronic neurodegenerative disorders. 3. Study of the mechanism by which the KATP channel modulates microglial activation, thereby allowing the in vivo and in vitro characterization of the neuroprotective and neurotoxic effect of microglia in situations of brain damage, through the activation and blockade of this channel. 4. Investigation of the role of the glia in the neurogenesis mechanisms associated with chronic neurodegeneration in the hippocampus of the adult brain. 5. Investigation of the efficacy and safety of anti-A beta immunotherapy as treatment for Alzheimer’s disease. We have shown that shortly after activation of the apoptotic death program, NP1 synthesis begins and is directed towards the mitochondria, where the protein facilitates Bax activation. Blocking the synthesis of NP1 prevents Bax activation and arrests the apoptotic death process. We have also shown that excitotoxic hippocampal damage induces a chronic neurodegenerative process with the migration of neuroblasts from the subventricular zone towards the damaged hippocampus – this inducing neurogenesis independent of that intrinsic to the actual hippocampus. Likewise, in the early stages of excitotoxic damage, the microglia undergoes a change in phenotype, evolving from neuroprotective activity towards a more proinflammatory profile. Under these conditions, we have shown that activation of the microglial KATP channels reduces this proinflammatory activity and reduces neuronal damage. Excitatory synapses in cortical neurons. Blue: VGLUT1 glutamate vesicular transporter. Red: SYNAPSIN presynaptic protein. Green: GLUR2 glutamate receptor subunit. Magenta: SYNAPSINVGLUT1 distribution in excitatory pre-synaptic endings. White: distribution of the three proteins, showing the pre-synaptic compartment of the excitatory synapses. AREA 4 Clinical and experimental neuroscience Neurobiology Unit PUBLICATIONS Originals I.F.: 16,78 1 Pugliese M, Rodriguez MJ, Gimeno-Bayon J, Pujadas L, Billett EE, Wells C, Mahy N. Alzheimer’s Disease Modifies Progenitor Cell Expression of Monoamine Oxidase B in the Subventricular Zone. J NEUROSCI RES, 2010. 88:25882597. I.F.:2,99. 2 Alberdi E, Sanchez-Gomez MV, Cavaliere F, Perez-Samartin A, Zugaza JL, Trullas R, Domercq M, Matute C. Amyloid beta oligomers induce Ca2+ dysregulation and neuronal death through activation of ionotropic glutamate receptors. CELL CALCIUM, 2010. 47:264-272. I.F.:4,29. 3 Ortiz O, Delgado-Garcia JM, Espadas I, Bahi A, Trullas R, Dreyer JL, Gruart A, Moratalla R. Associative Learning and CA3-CA1 Synaptic Plasticity Are Impaired in D1R Null, Drd1a(-/-) Mice and in Hippocampal siRNA Silenced Drd1a Mice. J NEUROSCI, 2010. 30:12288-12300. I.F.:7,18. 4 Pugliese M, Carrasco JL, Gomez-Anson B, Andrade C, Zamora A, Rodriguez MJ, Mascort J, Mahy N. Magnetic resonance imaging of cerebral involutional changes in dogs as markers of aging An innovative tool adapted from a human visual rating scale. VET J, 2010. 186:166-171. I.F.:2,32. Grants for research in progress Mahy N. Validación del efecto neuroprotector de la glibenclamida en la isquemia cerebral. Sponsored by: MINISTERIO DE EDUCACIÓN Y CIENCIA, PET2007-0450. Amount: 61.045,00 euros. Duration: 12/09/2008-11/09/2010. Trullas R. Regulación de proteinas sinapticas por la pentraxina neuronal y disfuncion sinaptica en modelos de alzheimer. Sponsored by: Ministerio de Ciencia e Innovación, SAF200803514. Amount: 229.900,00 euros. Duration: 01/01/2009-31/12/2011. Mahy N. Grup de Neuroquímica FM. Sponsored by: AGAUR (Generalitat de Catalunya), 2009SGR1380. Amount: 45.760,00 euros. Duration: 01/01/2009-31/12/2012. Mahy N, Villoslada P. Nuevas aproximaciones terapéuticas para la Esclerosis Múltiple y la Esclerosis Lateral Amiotrófica: efectos modificadores de la enfermedad y neuroprotección. Sponsored by: ADVANCELL-Advanced in vitro cell techno., IPT-010000-20100035. Amount: 487.254,00 euros. Duration: 25/06/2010-31/12/2012. 245 5 5 oncology and HAEMATOLOGY Biological markers in oncology 248 Human and experimental functional oncomorphology 250 Diagnosis and therapy in oncology 256 Molecular genetics 260 Genetics 262 Melanoma: imaging, genetics and immunology 265 Hematopoietic progenitor cell transplantation 268 Hematological oncology 272 Physiopathology and molecular bases in hematology 279 Hemotherapy – hemostasis 282 Molecular and translational oncology 286 Cell proliferation and signaling 290 AREA 5 Oncology and haematology Biological markers in oncology Strategic Objectives Group Members TEAM LEADER Rafael Molina (Hospital Clínic Facultat de Medicina) Tel.: 93 227 54 00 E-mail: rmolina@clinic.ub.es Idibaps members: Xavier Filella (Hospital Clínic) Antonio Maria Ballesta (Hospital Clínic - UB) Research Fellows: Jose M. Escudero (Hospital Clínic) Technicians: M. Sánchez (Fundació Bosch i Gimpera) Collaborators: C. Aparicio (Hospital Clínic) F. Coca (Hospital Clínic) Amàlia Lafuente (Facultat de Medicina) M. Portas (Hospital Clínic) S. Román (Hospital Clínic) M. Sasot (Hospital Clínic) José María Auge Fradera (Fundació Clínic) The activity of the group is fundamentally circumscribed to the setting of applied clinical research, and takes place in collaboration with different clinical groups both within and outside the Hospital Clínic of Barcelona. Main Lines of Research 1. Circulating tumor markers. Development of new techniques for the study of biological markers, which are the peripheral expression of the presence of malignant tumors. Study of the usefulness of proPSA in the diagnosis of prostate cancer. Evaluation of new tumor markers such as: ProGRP (progastrin releasing peptide), of use in undifferentiated small cell lung carcinoma, epididymal protein HE4, of great interest in ovarian cancer; andthymidine kinase for lung tumors. Comparison of the clinical application of the isoforms of squamous cell carcinoma-associated antigen, and evaluation of the S-100 isoforms and their implication in the study of malignant melanoma. 2. Consolidation of diagnostic guides to the clinical use of tumor markers. Collaboration with European and North American groups for establishing consensus and publishing clinical guides. Diffusion of these guides at national level through the Cancer Biological Markers Commission, created by members of the group, within the scientific committee of the Spanish Society of Biochemistry and Molecular Pathology. 3. Incorporation of a quantitative technique for the detection of circulating cells of epithelial tumors (CECs), and improvement of the methods to obtain, separate and quantify them based on the detection of mRNA encoding for cytokeratin-19. Evaluation of the clinical interest of this methodology in application to breast and prostate 248 AREA 5 Oncology and haematology Biological markers in oncology neoplasms. Study of mutations of oncogenes and suppressor genes based on PCR-SSCP techniques (ras and p53), and p16 and p14 methylation studies. 4. Collaboration in the colon and rectal cancer population screening program through the detection of occult blood in stools. During the last year over 15,000 asymptomatic individuals have been analyzed. 5. Development of a software application for establishing risk in patients with symptoms suggestive of lung cancer, assessing risk based on the determination of 6 tumors markers, with orientation regarding the histological type (small cell or non-small cell carcinoma). In process of license obtainment for diffusion. 6. Investigation of cytokine involvement in cancer development and progression. We are consolidating research into the clinical usefulness of cytokines in cancer patients. This line is preferentially developed in hematological and urological neoplasms. 7. Markers used in pharmacogenetics. Study of the genetic polymorphisms implicated in metabolism and pharmacological targets. This line is particularly focused on predicting the safety and efficacy of antineoplastic drugs. During the last year we have developed high performance genotyping techniques, such as minisequencing-SBE. PUBLICATIONS Originals I.F.: 20,19 1 Alcover J, Filella X, Luque P, Molina R, Izquierdo L, Auge JM, Alcaraz A. Prognostic Value of IL-6 in Localized Prostatic Cancer. ANTICANCER RES, 2010. 30:4369-4372. I.F.:1,43. 2 Molina R, Auge JM, Escudero JM, Filella X, Zanon G, Pahisa J, Farrus B, Munoz M, Velasco M. Evaluation of tumor markers (HER-2/neu oncoprotein, CEA, and CA 15.3) in patients with locoregional breast cancer: prognostic value. TUMOR BIOL, 2010. 31:171-180. I.F.:1,94. 3 Molina R, Auge JM, Farrus B, Zanon G, Pahisa J, Munoz M, Torne A, Filella X, Escudero JM, Fernandez P, Velasco M. Prospective Evaluation of Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 15.3 (CA 15.3) in Patients with Primary Locoregional Breast Cancer. CLIN CHEM, 2010. 56:1148-1157. I.F.:6,26. 4 Moreno C, Hodgson K, Ferrer G, Elena M, Filella X, Pereira A, Baumann T, Montserrat E. Autoimmune cytopenia in chronic lymphocytic leukemia: prevalence, clinical associations, and prognostic significance. BLOOD, 2010. 116:4771-4776. I.F.:10,56. 249 AREA 5 Team envolved in: Oncology and haematology Red temática de investigación cooperativa de cáncer Human and experimental functional oncomorphology Strategic Objectives Group Members TEAM LEADER Elías Campo Güerri (Hospital Clínic) Tel.: 93 227 54 50 Fax: 93 227 57 17 E-mail: ecampo@clinic.ub.es 1. Identification of genetic and molecular mechanisms implicated in the development and progression of human neoplasms. 2. Development of strategies for transferring to clinical practice the knowledge generated by basic research on human tumors. Identification of parameters allowing the improved diagnosis and prognosis of neoplastic disease, and the identification of possible therapeutic targets. Main Lines of Research Idibaps members: Llúcia Alós (Hospital Clínic) Virginia Amador (IDIBAPS) Silvia M. Beà (Fundació Clínic) Josep Antoni Bombí (Hospital Clínic) Pedro Luis Fernández (Hospital Clínic) Lluis Hernández Pous (IDIBAPS) Pedro Jares (Hospital Clínic) Carme Mallofré (Hospital Clínic) Alfons Nadal (Hospital Clinic) Antonio Palacín (Hospital Clínic) Antonio Postigo (ICREA - IDIBAPS) José Francisco Ramírez (Hospital Clínic) Teresa María Ribalta (Hospital Clínic) Manel Solé (Hospital Clínic) Antonio Martínez Pozo (Hospital Clínic) Lluis Colomo (Hospital Clínic) Postdoctoral fellows: Ana Enjuanes Guardiola (IDIBAPS) Research Fellows: Julia Calvo Castillo (Fundació Clínic) Alba Navarro López (MCyT) Cristina Royo Moreno (MCyT) Raquel Bermudo Gascón (IDIBAPS) Maria Carmela Vegliante (Fundació Clínic) Adriana García Herrera (Hospital Clínic) Lourdes Sánchez Cid (IDIBAPS) Jara Palomero Gorrindo (MCyT) Marta Kulis (Fundació Clínic) 250 Technicians: Laura Pla Rodríguez (IDIBAPS) Miriam Prieto Beato (IDIBAPS) Montse Sánchez Reina (IDIBAPS) Sara Guijarro Gallardo (Fundació Clínic) Concepción Muñoz Lozano (IDIBAPS) Eva Fernández López (Fundació Clínic - CDB) Laura Gelabert Blesa (IDIBAPS) Cristina Capdevilla (Fundació Clinic) Mónica Marín (CDB - XBTC) Noelia García Martínez (Fundació Clínic) Silvia Martín (Fundació Clínic) Nursing Staff: Judith Safont (Fundació Clínic) Administrative Staff: Carmen Muro (Fundació Clínic) Nathalie Villahoz (Fundació Clínic) Staticians: Guillem Clot Razquin (Fundació Clínic) Collaborators: Rosa Miquel Morera (Hospital Clínic) Laura Conde del Campo (Fundació Clínic) Ester Sánchez Tilló (IDIBAPS) Magdalena Pinyol Martínez (IDIBAPS) Roberto Alonso Gil (Fundació Clínic) 1. Lymphoid neoplasms a) Study of the alterations of the molecular mechanisms related to the cell cycle, genomic instability and the transcriptional expression profiles involved in the development and progression of these tumors as biomarkers of clinicopathological relevance. b) Functional study of molecular factors that may contribute to tumor pathogenesis, and which therefore may be candidates for the development of novel guided treatment strategies. 2. Solid neoplasms a) Study of the molecular mechanisms of invasion and metastasis, transcriptional expression profiles implicated in the development and progression of different human tumors in relation to development, biological aggressivity (adhesion molecules) and therapeutic options. We focus mainly on breast and prostate tumors as neoplasms under hormone influence, and urological tumors and airway neoplasms – including head and neck tumors. b) Study of the possible criteria of treatment response and prognosis in neurological tumors. AREA 5 Oncology and haematology Human and experimental functional oncomorphology Microarray platforms allow the massive-scale analysis of genic expression profiles. In our group we use this technique in translation research of human lymphomas, as can be seen in the image, where cluster analysis allows us to detect new types of lymphomas at molecular level that also exhibit different clinical behaviors. RESEARCH GROUP Molecular pathology of solid tumors Group Leader: Pedro Luis Fernández (Hospital Clínic) The group studying the progression of solid neoplasms has continued with the analysis of different tumor types, including urological, breast, neurological and head and neck neoplasms. In reference to prostate cancer, mention may be made of the investigation of practical applications of its genetic signature, based on the analysis of surplus biopsy material. Different potential partners in the industry have been contacted to this effect. In addition, in collaboration with the group of Dr. Thomson, or the IBM-CSIC in Barcelona, studies have been of cellular models of prostate cancer with different aggressivity profiles and phenotypes, and which are being extended to “in vivo” studies in mice. In breast cancer, analyses have been made of the transcriptional profiles of primary infiltrating ductal carcinomas and their lymph node metastases, which have allowed us to define genetic signatures of disease progression and potential metabolic pathways affected by them in the early metastatic process. Furthermore, inverse genetic studies based on transcriptomic results have given rise to the discovery of genic alterations in chromosomes 5 and 12 that may help to differentiate tumors with lymph node metastatic potential. In reference to neural neoplasms, confirmation and validation studies are ongoing, referred to the candidate genes EPHB1, BNIP3 and STAT1, obtained from the genic expression analyses of glioblastomas in patients with an unusually prolonged survival. These identified genes are implicated in signaling pathways and intercellular interactions, in the development and function of the nervous system, and in cell movement and cancer. On the other hand, analyses are being continued of 1p and 19q by FISH in oligodendrogial tumors and their morphological correlation, and of the clinical course and prognostic or predictive value of the methylation status of MGMT in malignant gliomas amenable to treatment with alkylating agents. In 2010, we have introduced the study of a new diagnostic and prognostic marker of malignant gliomas, known as IDH1, the full potential role of which remains to be defined. The research line in head and neck disorders explores the genetic alterations characterizing premalignant lesions of the oral cavity, with special emphasis on those that may be predictive of the development of oral carcinoma. In addition, analyses are made of the molecular alterations implicated in laryngeal cancer, and particularly of acquisition of the metastatic phenotype. Emergent Group Transcriptional regulation of genic expression Group Leader: Antonio Postigo (IDIBAPS) The laboratory investigates mechanisms involved in the regulation of genic expression during cell differentiation and in cancer, using as models the ZEB transcription factors. The ZEB1 and ZEB2 proteins regulate key events during embryonic development, the truncal maintenance of normal stem cells and cancer cells, the differentiation of many tissues, tumor invasion, and metastasis. The main lines of research being developed are the following: - Study of the mechanisms by which ZEB1 and ZEB2 regulate E-cadherin and epithelialmesenchymal transition (EMT) during tumor invasion and carcinoma metastasis.- Role of the ZEB1 and ZEB2 proteins in genic regulation during normal hematopoietic differentiation and its malignant transformation.Figure legend: ZEB1 and BRG1 regulate the initial phases of tumor invasion in carcinomas. 251 AREA 5 Oncology and haematology Human and experimental functional oncomorphology Team Members PUBLICATIONS Originals I.F.: 317,65 1 Lujan B, Hakim S, Moyano S, Nadal A, Caballero M, Diaz A, Valera A, Carrera M, Cardesa A, Alos L. Activation of the EGFR/ERK pathway in high-grade mucoepidermoid carcinomas of the salivary glands. BRIT J CANCER, 2010. 103:510-516. I.F.:4,35. 2 Diaz A, Alos L, Leon A, Mozos A, Caballero M, Martinez A, Plana M, Gallart T, Gil C, Leal M, Gatell JM, Garcia F. Factors associated with collagen deposition in lymphoid tissue in long-term treated HIV-infected patients. AIDS, 2010. 24:2029-2039. I.F.:4,91. 3 Alvarez-Martinez MJ, Miro JM, Valls ME, Mas J, DeLaBellacasa JP, Sued O, Sole M, Rivas PV, DeLazzari E, Benito N, Garcia F, Agusti C, Wilson PE, Gatell JM, DeAnta MTJ, Meshnick SR, Moreno A. Prevalence of dihydropteroate synthase genotypes before and after the introduction of combined antiretroviral therapy and their influence on the outcome of Pneumocystis pneumonia in HIV-1-infected patients. DIAGN MICR INFEC DIS, 2010. 68:60-65. I.F.:2,45. 4 Sanchez-Tillo E, Lazaro A, Torrent R, Cuatrecasas M, Vaquero EC, Castells A, Engel P, Postigo A. ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1. ONCOGENE, 2010. 29:3490-3500. I.F.:7,14. 5 Martinez-Olondris P, Sibila O, Agusti C, Rigol M, Soy D, Esquinas C, Piner R, Luque N, Guerrero L, Quera MA, Marco F, DeLaBellacasa JP, Ramirez J, Torres A. An experimental model of pneumonia induced by methicillin- 252 resistant Staphylococcus aureus in ventilated piglets. EUR RESPIR J, 2010. 36:901-906. I.F.:5,53. 6 Rigol M, Solanes N, Farre J, Roura S, Roque M, Berruezo A, Bellera N, Novensa L, Beng DT, Prat-Vidal C, Huzman MA, Batlle M, Hoefsloot M, Sitges M, Ramirez J, Dantas AP, Merino A, Sanz G, Brugada J, Bayes-Genis A, Heras M. Effects of Adipose Tissue-Derived Stem Cell Therapy After Myocardial Infarction: Impact of the Route of Administration. J CARD FAIL, 2010. 16:357366. I.F.:3,25. 7 Criado E, Sanchez M, Ramirez J, Arguis P, DeCaralt TM, Perea RJ, Xaubet A. Pulmonary Sarcoidosis: Typical and Atypical Manifestations at High-Resolution CT with Pathologic Correlation. RADIOGRAPHICS, 2010. 30:1567-U155. I.F.:2,75. 8 Izquierdo L, Truan D, Mengual L, Mallofre C, Alcaraz A. HER-2/AKT Expression in Upper Urinary Tract Urothelial Carcinoma: Prognostic Implications. ANTICANCER RES, 2010. 30:24392445. I.F.:1,43. 9 Sanjuan A, Escaramis G, Vidal-Sicart S, Illa M, Zanon G, Pahisa J, Rubi S, Velasco M, Santamaria G, Farrus B, Munoz M, Garcia Y, Fernandez PL, Pons F. Predicting Non-Sentinel Lymph Node Status in Breast Cancer Patients with Sentinel Lymph Node Involvement: Evaluation of Two Scoring Systems. BREAST J, 2010. 16:134-140. I.F.:1,61. 10 Molina R, Auge JM, Farrus B, Zanon G, Pahisa J, Munoz M, Torne A, Filella X, Escudero JM, Fernandez P, Velasco M. Prospective Evaluation of Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 15.3 (CA 15.3) in Patients with Primary Locoregional Breast Cancer. CLIN CHEM, 2010. 56:1148-1157. I.F.:6,26. 11 Moreno M, Chaves JF, Sancho-Bru P, Ramalho F, Ramalho LN, Mansego ML, Ivorra C, Dominguez M, Conde L, Millan C, Mari M, Colmenero J, Lozano JJ, Jares P, Vidal J, Forns X, Arroyo V, Caballeria J, Gines P, Bataller R. Ghrelin Attenuates Hepatocellular Injury and Liver Fibrogenesis in Rodents and Influences Fibrosis Progression in Humans. HEPATOLOGY, 2010. 51:974-985. I.F.:10,84. 12 Lacima G, Pera M, Amador A, Escaramis G, Pique JM. Long-term results of biofeedback treatment for faecal incontinence: a comparative study with untreated controls. COLORECTAL DIS, 2010. 12:742-749. I.F.:2,41. 13 Fernandez V, Salamero O, Espinet B, Sole F, Royo C, Navarro A, Camacho F, Bea S, Hartmann E, Amador V, Hernandez L, Agostinelli C, Sargent RL, Rozman M, Aymerich M, Colomer D, Villamor N, Swerdlow SH, Pileri SA, Bosch F, Piris MA, Montserrat E, Ott G, Rosenwald A, Lopez-Guillermo A, Jares P, Serrano S, Campo E. Genomic and Gene Expression Profiling Defines Indolent Forms of Mantle Cell Lymphoma. CANCER RES, 2010. 70:14081418. I.F.:7,54. 14 Martin M, Segui MA, Anton A, Ruiz A, Ramos M, Adrover E, Aranda I, Rodriguez-Lescure A, Grosse R, Calvo L, Barnadas A, Isla D, DelPrado PM, Borrego M, Zaluski J, Arcusa A, Munoz M, Vega JM, Mel JR, Munarriz B, Llorca C, Jara C, Alba E, Florian J, Li JF, Garcia-Asenjo JA, Saez A, Rios M, Almenar S, Peiro G, Lluch A. Adjuvant Docetaxel for High-Risk, Node-Negative Breast Cancer.. NEW ENGL J MED, 2010. 363:2200-2210. I.F.:47,05. 15 Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, Yang YD, Xu WH, Shaffer AL, Wright G, Xiao WM, Powell J, Jiang JK, Thomas CJ, Ro- AREA 5 Oncology and haematology Human and experimental functional oncomorphology senwald A, Ott G, Muller-Hermelink HK, Gascoyne RD, Connors JM, Johnson NA, Rimsza LM, Campo E, Jaffe ES, Wilson WH, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Pierce SK, Staudt LM. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. NATURE, 2010. 463:88-U97. I.F.:34,48. 19 16 Gutierrez-Garcia G, Colomo L, Villa- Perez-Magan E, DeLope AR, Ribalta T, Ruano Y, Campos-Martin Y, Perez-Bautista G, Garcia JF, GarciaClaver A, Fiano C, Hernandez-Moneo JL, Mollejo M, Melendez B. Differential expression profiling analyses identifies downregulation of 1p, 6q, and 14q genes and overexpression of 6p histone cluster 1 genes as markers of recurrence in meningiomas. NEURO-ONCOLOGY, 2010. 12:1278-1290. I.F.:4,98. mor N, Arenillas L, Martinez A, Cardesa T, Garcia-Herrera A, Setoain X, Rodriguez S, Ghita G, Abrisqueta P, Gine E, Bosch F, Campo E, Montserrat E, Lopez-Guillermo A. Clinico-biological characterization and outcome of primary nodal and extranodal diffuse large B-cell lymphoma in the rituximab era. LEUKEMIA LYMPHOMA, 2010. 51:1225-1232. I.F.:2,40. Bermudo R, Abia D, Benitez D, Carrio A, Vilella R, Ortiz AR, Thomson TM, Fernandez PL. Discovery of genomic alterations through coregulation analysis of closely linked genes: a frequent gain in 17q25.3 in prostate cancer. ANN NY ACAD SCI, 2010. 1210:17-24. I.F.:2,67. 17 21 Costa D, Valera S, Carrio A, Arias Crowther-Swanepoel D, Broderick P, DiBernardo MC, Dobbins SE, Torres M, Mansouri M, Ruiz-Ponte C, Enjuanes A, Rosenquist R, Carracedo A, Jurlander J, Campo E, Juliusson G, Montserrat E, Smedby KE, Dyer MJS, Matutes E, Dearden C, Sunter NJ, Hall AG, MainouFowler T, Jackson GH, Summerfield G, Harris RJ, Pettitt AR, Allsup DJ, Bailey JR, Pratt G, Pepper C, Fegan C, Parker A, Oscier D, Allan JM, Catovsky D, Houlston RS. Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk. NAT GENET, 2010. 42:132-U59. I.F.:34,28. 18 Rui LX, Emre NCT, Kruhlak MJ, Chung HJ, Steidl C, Slack G, Wright GW, Lenz G, Ngo VN, Shaffer AL, Xu WH, Zhao H, Yang YD, Lamy L, Davis RE, Xiao WM, Powell J, Maloney D, Thomas CJ, Moller P, Rosenwald A, Ott G, MullerHermelink HK, Savage K, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Weisenburger DD, Chan WC, Gascoyne RD, Levens D, Staudt LM. Cooperative Epigenetic Modulation by Cancer Amplicon Genes. CANCER CELL, 2010. 18:590-605. I.F.:25,29. 20 A, Munoz C, Rozman M, Belkaid M, Coutinho R, Nomdedeu B, Campo E. Do we need to do fluorescence in situ hybridization analysis in myelodysplastic syndromes as often as we do?. LEUKEMIA RES, 2010. 34:1437-1441. I.F.:2,36. 22 Gine E, Martinez A, Villamor N, Lopez-Guillermo A, Camos M, Martinez D, Esteve J, Calvo X, Muntanola A, Abrisqueta P, Rozman M, Rozman C, Bosch F, Campo E, Montserrat E. Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia (“accelerated” chronic lymphocytic leukemia) with aggressive clinical behavior. HAEMATOL-HEMATOL J, 2010. 95:1526-1533. I.F.:6,42. 23 Mani H, Climent F, Colomo L, Pittaluga S, Raffeld M, Jaffe ES. Gall Bladder and Extrahepatic Bile Duct Lymphomas: Clinicopathological Observations and Biological Implications. AM J SURG PATHOL, 2010. 34:1277-1286. I.F.:4,06. 24 Valera A, Balague O, Colomo L, Martinez A, Delabie J, Taddesse-Heath L, Jaffe ES, Campo E. IG/MYC Rearrangements are the Main Cytogenetic Alteration in Plasmablastic Lymphomas. AM J SURG PATHOL, 2010. 34:1686-1694. I.F.:4,06. 25 Espinet B, Salaverria I, Bea S, Ruiz-Xiville N, Balague O, Salido M, Costa D, Carreras J, Rodriguez-Vicente AE, Garcia JL, Hernandez-Rivas JM, Calasanz MJ, Siebert R, Ferrer A, Salar A, Carrio A, Polo N, Garcia-Marco JA, Domingo A, Gonzalez-Barca E, Romagosa V, Marugan I, LopezGuillermo A, Milla F, Mate JL, Luno E, Sanzo C, Collado R, Oliver I, Monzo S, Palacin A, Gonzalez T, Sant F, Salinas R, Ardanaz MT, Font L, Escoda L, Florensa L, Serrano S, Campo E, Sole F. Incidence and Prognostic Impact of Secondary Cytogenetic Aberrations in a Series of 145 Patients with Mantle Cell Lymphoma. GENE CHROMOSOME CANC, 2010. 49:439-451. I.F.:3,86. 26 Bonin S, Hlubek F, Benhattar J, Denkert C, Dietel M, Fernandez PL, Hofler G, Kothmaier H, Kruslin B, Mazzanti CM, Perren A, Popper H, Scarpa A, Soares P, Stanta G, Groenen PJTA. Multicentre validation study of nucleic acids extraction from FFPE tissues. VIRCHOWS ARCH, 2010. 457:309317. I.F.:2,31. 27 Hartmann EM, Campo E, Wright G, Lenz G, Salaverria I, Jares P, Xiao WM, Braziel RM, Rimsza LM, Chan WC, Weisenburger DD, Delabie J, Jaffe ES, Gascoyne RD, Dave SS, Mueller-Hermelink HK, Staudt LM, Ott G, Bea S, Rosenwald A. Pathway discovery in mantle cell lymphoma by integrated analysis of high-resolution gene expression and copy number profiling. BLOOD, 2010. 116:953-961. I.F.:10,56. 253 AREA 5 Oncology and haematology Human and experimental functional oncomorphology Team Members 28 Massi D, Franchi A, Alos L, Cook M, DiPalma S, Enguita AB, Ferrara G, Kazakov DV, Mentzel T, Michal M, Panelos J, Rodriguez-Peralto JL, Santucci M, Tragni G, Zioga A, Tos APD. Primary cutaneous leiomyosarcoma: clinicopathological analysis of 36 cases. HISTOPATHOLOGY, 2010. 56:251-262. I.F.:3,86. 29 Yakirevich E, Sabo E, Klorin G, Alos L, Cardesa A, Ellis GL, Shumway BS, Gnepp DR. Primary mucin-producing tumours of the salivary glands: a clinicopathological and morphometric study. HISTOPATHOLOGY, 2010. 57:395-409. I.F.:3,86. 30 Santamaria G, Velasco M, Bargallo X, Caparros X, Farrus B, Fernandez PL. Radiologic and Pathologic Findings in Breast Tumors with High Signal Intensity on T2-weighted MR Images. RADIOGRAPHICS, 2010. 30:533-548. I.F.:2,75. 31 Willers IM, Isidoro A, Ortega AD, Fernandez PL, Cuezva JM. Selective inhibition of beta-F1-ATPase mRNA translation in human tumours. BIOCHEM J, 2010. 426:319-326. I.F.:5,16. 32 Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, Delaney A, Jones SJ, Iqbal J, Weisenburger DD, Bast MA, Rosenwald A, Muller-Hermelink HK, Rimsza LM, Campo E, Delabie J, Braziel RM, Cook JR, Tubbs RR, Jaffe ES, Lenz G, Connors JM, Staudt LM, Chan WC, Gascoyne RD. TumorAssociated Macrophages and Survival in Classic Hodgkin’s Lymphoma. NEW ENGL J MED, 2010. 362:875-885. I.F.:47,05. 33 Crowther-Swanepoel D, Mansouri M, Enjuanes A, Vega A, Smedby KE, Ruiz-Ponte C, Jurlander J, Juliusson G, Montserrat E, Catovsky D, 254 Campo E, Carracedo A, Rosenquist R, Houlston RS. Verification that common variation at 2q37.1, 6p25.3, 11q24.1, 15q23, and 19q13.32 influences chronic lymphocytic leukaemia risk. BRIT J HAEMATOL, 2010. 150:473-479. I.F.:4,60. 34 Papadopoulou V, Postigo A, Sanchez-Tillo E, Porter ACG, Wagner SD. ZEB1 and CtBP form a repressive complex at a distal promoter element of the BCL6 locus. BIOCHEM J, 2010. 427:541-550. I.F.:5,16. Reviews I.F.: 2,75 1 Castaner E, Alguersuari A, Gallardo X, Andreu M, Pallardo Y, Mata JM, Ramirez J. When to Suspect Pulmonary Vasculitis: Radiologic and Clinical Clues. RADIOGRAPHICS, 2010. 30:33-U59. I.F.:2,75. Editorials I.F.: 8,35 1 Bea S. Amplifications and target genes in diffuse large B-cell lymphoma: real targets or consequences of structural features of the genome?. LEUKEMIA LYMPHOMA, 2010. 51:743-744. I.F.:2,40. 2 Horcajada JP, Perea RJ, Ribalta T, Gonzalez-Martin J. An 80-year-old male with pleural effusion and mediastinal lymph nodes. MED CLINBARCELONA, 2010. 135:700-706. I.F.:1,23. 3 Leal L, Vicente MA, Mascaro JM, Bombi JA, Gonzalez-Ensenat MA. Picture of the Month - Denounement and Discussion - Kindler Syndrome. ARCH PEDIAT ADOL MED, 2010. 164:875876. I.F.:4,73. Clinical Guidelines I.F.: 2,46 1 Navarro S, Vaquero E, Maurel J, Bombi JA, DeJuan C, Feliu J, Cruz LF, Gines A, Girela E, Rodriguez R, Sabater L. Recommendations for diagnosis, staging and treatment of pancreatic cancer (Part I). Grupo Español de Consenso en Cáncer de Páncreas. MED CLIN-BARCELONA, 2010. 134:643-655. I.F.:1,23. 2 Navarro S, Vaquero E, Maurel J, Bombi JA, DeJuan C, Feliu J, Cruz LF, Gines A, Girela E, Rodriguez R, Sabater L. Recommendations for diagnosis, staging and treatment of pancreatic cancer (Part II). MED CLIN-BARCELONA, 2010. 134:692-702. I.F.:1,23. Multicentrics I.F.: 34,48 1 Hudson TJ, Anderson W, Aretz A, Barker AD, Bell C, et al. International network of cancer genome projects. NATURE, 2010. 464:993-998. I.F.:34,48. Grants for research in progress Jares P. Identification of Tumor Supressor Genes, Epigenetic Portrait, and Genotyping of Mantle Cell Lymphomas. Sponsored by: Lymphoma Research Foundation, 07/168. Amount: 186.883,00 euros. Duration: 01/05/2007-30/04/2010. Postigo A. Regulación de la Cadherina e y de la capacidad invasiva/metastásica de tumores epiteliales por la familia ZEB de represores transcripcionales. Sponsored by: Ministerio Educación y Ciencia, BFU2007-60302/BMC. Amount: 121.000,00 euros. Duration: 01/10/2007-04/10/2010. AREA 5 Oncology and haematology Human and experimental functional oncomorphology Campo E. Red temática de investigación cooperativa de cáncer. Sponsored by: Ministerio Sanidad y Consumo, RD06/0020/0039. Amount: 455.296,66 euros. Duration: 01/01/2007-31/12/2011. Martinez A. Estudio de la activación de las vías de supervivencia y apoptosis en respuesta al estrés secretor dependiente del retículo endoplasmítico en linfomas de células grandes como una nueva diana terapéutica. Sponsored by: Ministerio Sanidad y Consumo, PI080095. Amount: 90.145,00 euros. Duration: 01/01/200801/12/2012. Bea S. Estudio de las Alteraciones Genómicas y los Perfiles de Expresión de Neoplasias Linfoides. Identificación de genes diana implicados en el desarrollo y progresión de estas neoplasias y definición de su impacto clínico. Sponsored by: Instituto de Salud Carlos III, PI080077. Amount: 74.052,00 euros. Duration: 31/12/2008-30/12/2011. Amador V. Estudio de los mecanismos responsables de la estabilización de skp2 en los linfomas humanos. Sponsored by: Ministerio de Educación y Ciencia, V-2006-RC-2110-0. Amount: 15.000,00 euros. Duration: 30/05/2007-19/08/2012. Campo E. Molecular Signatures to Improve Diagnosis and Outcome Prediction in Lymphomas. Sponsored by: National Institutes of Health, USA, 5 U01 CA114778-03. Amount: 510.948,00 euros. Duration: 31/07/2007-31/05/2010. Campo E. Caracterización Genética y Molecular de Alta Resolución de Neoplasias Linfoides. Implicaciones patogenéticas y clínicas. Sponsored by: Ministerio de Ciencia e Innovación, SAF200803630. Amount: 600.000,00 euros. Duration: 01/01/2009-31/12/2013. Campo E. Estudio de la Genómica de la Leucemia Linfocítica Crónica. Sponsored by: Instituto de Salud Carlos III, 0000. Amount: 10.000.000,00 euros. Duration: 27/03/2009-31/12/2012. Campo E. Ajuts per donar suport a les activitats dels grups de recerca. Sponsored by: Generalitat de Catalunya, 2009, SGR_992. Amount: 58.240,00 euros. Duration: 30/06/200931/12/2013. Ribalta T. Ayuda a grupo emergente “Grupo de estudio de Tumores del Sistema Nervioso Central. Sponsored by: Fundación para la Investigación Sanitaria en Castilla-La Mancha (FISCAM), 0000. Amount: 30.559,20 euros. Duration: 01/01/2010-31/12/2012. Jares P. Identificación de potenciales genes supresores de tumores en neoplasias linfoides y análisis de su implicación en el desarrollo y progresión de estas neoplasias. Sponsored by: Asociación Española contra el cáncer, PI09 09/004. Amount: 18.000,00 euros. Duration: 13/10/2008-22/01/2011. Fernandez PL. Análisis de los fenotipos CSC y EMT y su potencial modulación por miRNA en la progresión de los tumores mamarios y próstáticos. Sponsored by: Ministerio de Ciencia e Innovación FIS, PI080274. Amount: 97.000,00 euros. Duration: 01/01/200931/12/2011. 60.000,00 euros. Duration: 01/01/201031/12/2011. Campo E. Procurement of 40 paired pre- and post-chemotherapy samples of DNA derived from peripheral blood for TCGA analysis. Sponsored by: European Commission, HHSN261201000076I. Amount: 15.000,00 euros. Duration: 08/09/201007/09/2012. Thesis Campo E. Factors pronòstics en neoplàsies limfoides B de cèl·lula petita. PhD student: Joaquim Carreras Esteban. Nadal A. Mecanismos moleculares implicados en el desarrollo del carcinoma escamoso de laringe. PhD student: Laura Conde del Campo. Ribalta T. Fatal Human Tick-Borne Encephalitis: Immunohistochemical characterisation of viral distribution and inflammatory reaction. PhD student: Ellen Gelpi Mantius. Fernandez PL. Perfiles transcripcionales del cáncer de próstata. PhD student: Raquel Bermudo Gascón. Amador V. Papel de los factores de transcripción High-Mobility Group (HMG) en los Linformas Malignos Agresivos. Sponsored by: MINISTERIO DE EDUCACIÓN, BFU2009_09235. Amount: 170.609,99 euros. Duration: 01/01/2010-31/12/2012. Postigo A. Regulación transcripcional de la cadherina E y de la capacidad invasiva y metastática de tumores de colon. Sponsored by: Fundació Privada Olga Torres (FOT), FOT_09_002. Amount: 255 AREA 5 Team envolved in: Oncology and haematology Factores de riesgo, evolución y tratamiento de las enfermedades cardiovasculares y sus mecanismos (RECAVA) & Red temática de investigación cooperativa de cáncer Diagnosis and therapy in oncology Strategic Objectives Group Members TEAM LEADER Francesca Pons (Hospital Clínic) Tel.: 93 227 54 82 Fax: 93 451 81 37 E-mail: fpons@clinic.ub.es Idibaps members: Albert Biete (Hospital Clínic) Carles Conill (Hospital Clínic) David Fuster (Hospital Clínic) Xavier Setoain (Hospital Clínic) Martín Velasco (Hospital Clínic) Sergi Vidal-Sicart (Hospital Clínic) Marià Monzó (Universitat de Barcelona) Laura Oleaga (Hospital Clínic) Maria Africa Muxí Collaborators: Sebastián Capurro (Hospital Clínic) Francesc Casas (Hospital Clínic) Lluís Donoso Bach (Hospital Clínic) Blanca Farrús (Hospital Clínic) Mario Pagés (Hospital Clínic) Teresa Pujol (Hospital Clínic) Sonia Rodríguez (Hospital Clínic) Angels Rovirosa (Hospital Clínic) Marcelo Sánchez (Hospital Clínic) Gorane Santamaría (Hospital Clínic) Eugènia Verger (Hospital Clínic) Pilar Paredes (Hospital Clínic) Francisco Lomeña (Hospital Clínic) Javier Pavía (Hospital Clínic) Francisco Campos (Hospital Clínic) 256 1. Development of techniques for improving the diagnosis, prognostic evaluation and treatment response assessment in oncological patients. 2. Development and application of new therapies in oncology. Main Lines of Research 1. Molecular studies in embryonic and tumor cells: applications to pharmacogenomics. Two types of studies are carried out: one type analyzes and compares microRNA patterns in embryonic and tumor tissues, and the other uses allelic discrimination to analyze polymorphic profiles (SNPs) in oncological patients, with a view to selecting more specific treatments. 2. Effects of synchrotron radiation upon the neoplastic cell. In this study, which is carried out jointly with Barcelona Autonomous University (UAB), comparison is made of the biological action of synchrotron radiation (currently the Grenoble system until the UAB Alba unit comes into operation) with conventional X-rays used in radiotherapy. The cell-sensitizing effectiveness of gold nanoparticles and cisplatin is also studied. 3. Irradiation of melanoma lymph node metastases. A study is made of the role of the postoperative irradiation of melanoma lymph node metastases in the locoregional control of the disease. 4. Breast cancer imaging diagnosis. Two types of studies are carried out. One type of study uses 10G needle biopsies to improve the presurgical diagnosis of breast tumors, particularly in application to those with microcalcifications. The aim is to minimize the number of surgical biopsies required for establishing the diagnosis. The other type of study assesses the response to neoadjuvant chemotherapy in breast cancer based on breast MRI evaluation. 5. Gammagraphic (scintigraphic) detection of the sentinel node. Lymphogammagraphy and posterior use of an external detection probe during surgery serves to identify and remove the sentinel node. This technique makes it possible to avoid 75% of all unnecessary lymphadenectomies. The use of a portable gammacamera during surgery offers additional advantages. 6. Application of positron emission tomography (PET-CT) in oncology. PET studies are made for the staging and control of treatment response in different types of tumors, including lymphomas, breast cancer and digestive tract lesions. We plan to use an intraoperative PET probe to improve the detection of tumor lesions. Patient with endometrial carcinoma and drainage in the paraaortic region (A). A portable gammacamera was used to locate the sentinel node (B). The real time images (C) were decisive in removal of the sentinel node (yellow arrow), through coincidence of the 125-I signal (green circle) with the activity of the node (D). AREA 5 Oncology and haematology Diagnosis and therapy in oncology PUBLICATIONS Originals I.F.: 67,05 1 Ramos-Casals M, Brito-Zeron P, Perez-De-Lis M, Diaz-Lagares C, Bove A, Soto MJ, Jimenez I, Belenguer R, Siso A, Muxi A, Pons F. Clinical and Prognostic Significance of Parotid Scintigraphy in 405 Patients with Primary Sjogren’s Syndrome. J RHEUMATOL, 2010. 37:585-590. I.F.:3,85. 2 Vidal-Sicart S, Paredes P, Zanon G, Pahisa J, Martinez-Roman S, Caparros X, Vilalta A, Rull R, Pons F. Added Value of Intraoperative Real-Time Imaging in Searches for Difficultto-Locate Sentinel Nodes. J NUCL MED, 2010. 51:1219-1225. I.F.:6,42. 3 Valduvieco I, Rovirosa A, Colomo L, DeSanJuan A, Pahisa J, Biete A. Endometrial stromal sarcoma. Is there a place for radiotherapy?. CLIN TRANSL ONCOL, 2010. 12:226-230. I.F.:1,15. 4 Molina R, Auge JM, Escudero JM, Filella X, Zanon G, Pahisa J, Farrus B, Munoz M, Velasco M. Evaluation of tumor markers (HER-2/neu oncoprotein, CEA, and CA 15.3) in patients with locoregional breast cancer: prognostic value. TUMOR BIOL, 2010. 31:171-180. I.F.:1,94. 5 Sanjuan A, Escaramis G, Vidal-Sicart S, Illa M, Zanon G, Pahisa J, Rubi S, Velasco M, Santamaria G, Farrus B, Munoz M, Garcia Y, Fernandez PL, Pons F. Predicting Non-Sentinel Lymph Node Status in Breast Cancer Patients with Sentinel Lymph Node Involvement: Evaluation of Two Scoring Systems. BREAST J, 2010. 16:134-140. I.F.:1,61. 6 Molina R, Auge JM, Farrus B, Zanon G, Pahisa J, Munoz M, Torne A, Filella X, Escudero JM, Fernandez P, Velasco M. Prospective Evaluation of Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 15.3 (CA 15.3) in Patients with Primary Locoregional Breast Cancer. CLIN CHEM, 2010. 56:1148-1157. I.F.:6,26. 7 Hernandez MV, Peris P, Monegal A, Reyes R, Muxi A, Gifre L, Guanabens N. Effects of Intravenous Pamidronate on Renal Function, Bone Mineral Metabolism and Bone Mass in Patients With Severe Osteoporosis. AM J MED SCI, 2010. 339:225-229. I.F.:1,20. 8 Guanabens N, Cerda D, Monegal A, Pons F, Caballeria L, Peris P, Pares A. Low Bone Mass and Severity of Cholestasis Affect Fracture Risk in Patients With Primary Biliary Cirrhosis. GASTROENTEROLOGY, 2010. 138:23482356. I.F.:12,90. 9 Gabaroi DC, Peris P, Monegal A, Albaladejo C, Martinez MA, Muxi A, DeOsaba MJM, Suris X, Guanabens N. Search for hidden secondary causes in postmenopausal women with osteoporosis. MENOPAUSE, 2010. 17:135-139. I.F.:3,08. 10 Pintor L, Bailles E, Matrai S, Carreno M, Donaire A, Boget T, Setoain X, Rumia J, Bargallo N. Efficiency of Venlafaxine in Patients With Psychogenic Nonepileptic Seizures and Anxiety and/or Depressive Disorders. J NEUROPSYCH CLIN N, 2010. 22:401-408. I.F.:2,34. 11Carreno M, Garcia-Alvarez D, Maestro I, Fernandez S, Donaire A, Boget T, Rumia J, Pintor L, Setoain X. Malignant autosomal dominant frontal lobe epilepsy with repeated episodes of status epilepticus: successful treatment with vagal nerve stimulation. EPILEPTIC DISORD, 2010. 12:155-158. I.F.:1,20. 12 Sanchez-Gistau V, Pintor L, Sugranyes G, Bailles E, Carreno M, Donaire A, Boget T, Setoain X, Bargallo N, Rumia J. Prevalence of interictal psychiatric disorders in patients with refractory temporal and extratemporal lobe epilepsy in Spain. A comparative study. EPILEPSIA, 2010. 51:13091313. I.F.:4,05. 13 Gutierrez-Garcia G, Colomo L, Villamor N, Arenillas L, Martinez A, Cardesa T, Garcia-Herrera A, Setoain X, Rodriguez S, Ghita G, Abrisqueta P, Gine E, Bosch F, Campo E, Montserrat E, Lopez-Guillermo A. Clinico-biological characterization and outcome of primary nodal and extranodal diffuse large B-cell lymphoma in the rituximab era. LEUKEMIA LYMPHOMA, 2010. 51:1225-1232. I.F.:2,40. 14 Santamaria G, Velasco M, Bargallo X, Caparros X, Farrus B, Fernandez PL. Radiologic and Pathologic Findings in Breast Tumors with High Signal Intensity on T2-weighted MR Images. RADIOGRAPHICS, 2010. 30:533-548. I.F.:2,75. 15 Vidal-Sicart S, Aukema TS, Vogel WV, Hoefnagel CA, Valdes-Olmos RA. Added value of prone position technique for PET-TAC in breast cancer patients. REV ESP MED NUCL, 2010. 29:230-235. I.F.:0,77. 16 Vila A, Sanchez-Reyes A, Conill C, Gispert JD, Trampal C, Lainez C, Vayreda J, Pedro A. Comparison of positron emission tomography (PET) and computed tomography (CT) for better target volume definition in radiation therapy planning. CLIN TRANSL ONCOL, 2010. 12:367-373. I.F.:1,15. 257 AREA 5 Oncology and haematology Diagnosis and therapy in oncology Team Members 17 Torregrosa JV, Fuster D, Gentil MA, Marcen R, Guirado L, Zarraga S, Bravo J, Burgos D, Monegal A, Muxi A, Garcia S. Open-Label Trial: Effect of Weekly Risedronate Immediately After Transplantation in Kidney Recipients. TRANSPLANTATION, 2010. 89:1476-1481. I.F.:3,50. 18 Chawla S, Oleaga L, Wang SM, 1 Navarro A, Monzo M. MicroRNAs in Human Embryonic and Cancer Stem Cells. YONSEI MED J, 2010. 51:622-632. I.F.:0,77. 2 Torregrosa JV, Felez I, Fuster D. Usefulness of imaging techniques in secondary hyperparathyroidism. NEFROLOGIA, 2010. 30:158-167. I.F.:0,53. Krejza J, Wolf RL, Woo JH, O’rourke DM, Judy KD, Grady MS, Melhem ER, Poptani H. Role of Proton Magnetic Resonance Spectroscopy in Differentiating Oligodendrogliomas from Astrocytomas. J NEUROIMAGING, 2010. 20:3-8. I.F.:1,72. Editorials I.F.: 6,06 19 1 Munoz M, Pahisa J, Caparros FX, Pinero A, Gimenez J, VidalSicart S, Intra M. Selective sentinel lymph node biopsy and primary systemic therapy in breast cancer. TUMORI, 2010. 96:17-23. I.F.:0,86. 20 Gonzalez JA, Chust M, Delgado R, Gomez A, Rodriguez N, Ruiz MJ, Casas F. Spanish radiobiological pattern of care in lung cancer: a GOECP/ SEOR study. CLIN TRANSL ONCOL, 2010. 12:292-298. I.F.:1,15. 21 Oleaga L, Dalal SS, Weigele JB, Hurst RW, Lee J, Voorhees A, Melhem ER. The role of time-resolved 3D contrast-enhanced MR angiography in the assessment and grading of cerebral arteriovenous malformations. EUR J RADIOL, 2010. 74:E118E122. I.F.:2,65. 22 Artells R, Moreno I, Diaz T, Martinez F, Gel B, Navarro A, Ibeas R, Moreno J, Monzo M. Tumour CD133 mRNA expression and clinical outcome in surgically resected colorectal cancer patients. EUR J CANCER, 2010. 46:642-649. I.F.:4,12. 258 Reviews I.F.: 1,30 Vidal-Sicart S. Sentinel lymph node and neoadjuvant therapy in breast cancer. REV ESP MED NUCL, 2010. 29:319-320. I.F.:0,77. 2 Domenech B, Fuster D, Haddad S, Setoain X, Lafuente S, Pons F. Arterial thrombosis of the renal graft diagnosed with Tc-99m-MAG 3 renogram in a female patient with polycystosis. REV ESP MED NUCL, 2010. 29:40-41. I.F.:0,77. 3 Olmos RAV, Vidal-Sicart S, Nieweg OE. Technological innovation in the sentinel node procedure: towards 3-D intraoperative imaging. EUR J NUCL MED MOL I, 2010. 37:1449-1451. I.F.:4,53. Grants for research in progress Setoain FJ. Development and validation of an automatic dose injection system for ictal spect in epilepsy. Sponsored by: Fundació Marató TV3, 60610. Amount: 89.357,00 euros. Duration: 06/02/2007-05/02/2010. Fuster D. Utilidad de la tomografía por Emisión de Positrones con Tomografía Computerizada Integrada (PET/TC) en la estadificación inicial y en la monitorización de la respuesta a la quimioradioterapia neoadyuvante del adenocarcinoma gástrico. Sponsored by: Ministerio Sanidad y Consumo, PI070270. Amount: 41.573,18 euros. Duration: 26/11/2007-30/12/2010. Pons F. Valoración de la PET-TC (Tomografía de Emisión de PositronesTomografía Computarizada) de baja dosis sin utilización de contraste radiológico como única exploración de imagen para la estadificación y re-estadificación de los linfomas. Sponsored by: Ministerio Sanidad y Consumo, PI070277. Amount: 86.573,08 euros. Duration: 26/11/2007-30/12/2010. Muxi A. RECAVA - Factores de Riesgo, Evolución y Tratamiento de las Enfermedades Cardiovasculares y sus Mecanismos. Sponsored by: INSTITUTO DE SALUD CARLOS III, RD06/0014/0024. Amount: 20.940,00 euros. Duration: 01/01/200731/12/2010. Pons F. Red temática de investigación cooperativa de cáncer. Sponsored by: Ministerio Sanidad y Consumo, RD06/0020/0038. Amount: 7.140,00 euros. Duration: 01/01/200731/12/2010. AREA 5 Oncology and haematology Diagnosis and therapy in oncology Monzó M. Utilidad clínica de biomarcadores tumorales mediante análisis de microarrays de microRNAs en sangre periférica de pacientes con cáncer colorrectal. Sponsored by: Ministerio de Sanidad y Consumo, PS09/00547. Amount: 86.515,00 euros. Duration: 01/01/200931/12/2012. Thesis Biete A. Radioterapia hipofraccionada acelerada como tratamiento curativo del cáncer de próstata localizado: Análisis prospectivo de la toxicidad aguda y de la toxicidad tardía. PhD student: Victor Angel Macias Hernandez. Santamaria G. Resonancia magnética dinámica del carcinoma in situ de mama: utilida en la planificación del tratamiento quirúrgico y relación de la captación neoplásica con la microvascularización tumoral y la expresión del factor de permeabilidad vascular. Sponsored by: Sociedad Española de Radiología Médica, 04-GSO-INVESTIGACIONSERAM-2007. Amount: 3.000,00 euros. Duration: 01/04/200831/10/2010. Monzó M. Utilidad clínica de biomarcadores tumorales mediante analisis de microarrays de microRNAs en sangre periférica de pacientes con cáncer colorrectal. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/0547. Amount: 86.515,00 euros. Duration: 01/01/2010-31/12/2012. Vidal S. Utilidad clínica del SPECT-CT y una gammacamara portátil para la detección del ganglio centinela en el cáncer de cérvix y endometrio. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1108. Amount: 56.870,00 euros. Duration: 01/01/2010-31/12/2012. Pons F. Imatge Molecular en Medicina Nuclear. Sponsored by: GENERALITAT DE CATALUNYA, 2009_SGR_1049. Amount: 69.680,00 euros. Duration: 15/09/2009-31/12/2013. 259 AREA 5 Oncology and haematology Molecular genetics Group Members TEAM LEADER Cristóbal Mezquita (Facultat Medicina UB) Tel.: 93 402 45 18 Fax: 93 403 52 79 Idibaps members: Jovita Mezquita (Facultat de Medicina UB) Rafael Oliva (Hospital Clínic i Facultat de Medicina UB) Josep Oriola (Hospital Clínic i Facultat de Medicina UB) Strategic Objectives Main Lines of Research The research group comprises the laboratories ofGene Expression and Cancer and Human Genetics. Our research work is set within the paradigm of current physiology: the study of genic expression mechanisms as a new approach to the study of the functions of the body. On one hand, our work is presently directed towards the proteomic and molecular characterization of spermatozoa in infertile patients and controls, while on the other, studies are made of the mechanisms involved in angiogenesis and in tumor cell invasion. The group has traditionally worked in relation to mechanisms of genic expression and differentiation of the spermatogenic germinal line, and more recently on the mechanisms involved in angiogenesis and in tumor cell invasion. One of the relevant subjects has been the identification of numerous new proteins of the spermatozoon, with consideration of the potential for transmission to the oocyte and epigenetic function (Oliva et al., 2010). We have also contributed to the identification of alterations Research Fellows: Sara de Mateo (Fundació Clínic) Meritxell Jodar (Fundació Clinic) Rubén Azpiazu (Fundació Clinic) Judit Castillo (Fundació Clinic) Technicians: Montserrat Pau (Facultat de Medicina) Collaborators: Betlem Mezquita (Facultat de Medicina) José Manuel Vidal (Facultat de Medicina) Juan Martínez (Fundació Clínic) Josep Lluís Ballescà (Hospital Clínic) Principal changes in chromatin structure during spermatogenesis and in the early stages of development. The spermatozoon is able to transmit epigenetic information through the methylation pattern of different genes, through the differential distribution of genes in the regions associated to nucleohistone and nucleoprotamine, and through the proteome transmitted to the oocyte (Oliva et al., Proteomics 2009; 9:1004-17). 260 AREA 5 Oncology and haematology Molecular genetics in relation to protamines in the sperm nucleus, predictive of the results of assisted reproduction techniques (de Mateo et al., 2010). In another line of research we have completed a mutational study of the genes encoding for protamines 1 and 2 in infertile patients – identifying different new mutations, polymorphisms and haplotypes (Jodar et al., 2010). One of the important challenges is to elucidate the basic mechanisms that operate in the nucleus-histone, nucleus-protamine transition during spermatogenesis, and to clarify the way in which its alterations may lead to alterations in the epigenetic information of the spermatozoon. An additional challenge will be the translation of important basic investigational findings to the clinical setting. In relation to the tumor invasion mechanisms, the main challenge will be to determine the mechanisms implicated in regulating the genic expression of the new family of intracellular truncated forms of the VEGFR-1 molecule which we have characterized in our laboratory. PUBLICATIONS Originals I.F.: 2,94 1 Mezquita B, Mezquita J, Pau M, Mezquita C. A Novel Intracellular Isoform of VEGFR-1 Activates Src and Promotes Cell Invasion in MDAMB-231 Breast Cancer Cells. J CELL BIOCHEM, 2010. 110:732-742. I.F.:2,94. Grants for research in progress Thesis Oliva R. Proteomic and molecular characterization of human spermatozoa in infertile patients and controls. PhD student: Sara de Mateo López, Universitat de Barcelona. Oliva R. Proteomic and molecular characterization of human spermatozoa in infertile patients and control. PhD student: Sara de Mateo Lopez. Oliva R. Caracterización proteómica y genómica del núcleo del espermatozoide humano normal y de sus alteraciones en pacientes infértiles. Sponsored by: Ministerio de Ciencia e Innovación, BFU200907118. Amount: 187.550,00 euros. Duration: 31/12/2009-30/12/2012. For further information: www.fisiologia.net www.ub.edu/humangen 261 AREA 5 Team envolved in: Oncology and haematology CIBER en enfermedades raras (CIBERer) Genetics Strategic Objectives Group Members TEAM LEADER Montserrat Milà (Hospital Clínic) Tel.: 93 227 54 00 (Ext.: 2784) Fax: 93 227 56 97 E-mail: mmila@clinic.ub.es Idibaps members: Anna Carrió (Hospital Clínic) Carmen Herrero (Hospital Clínic) Mario Lecha (Hospital Clínic) Ester Margarit (Hospital Clínic) Aurora Sánchez (Hospital Clínic) Anna Soler (Hospital Clínic) Jordi To-Figueras (Hospital Clínic) Characterization of rare hereditary diseases in the clinical, cytogenetic and molecular contexts. There are four main lines of research. Each line has the strategic objectives defined by the supporting research projects. In this context, the study of mental retardation (MR) and identification of the causal genetic factors are fundamented upon the application of high performance array CGH and Next Sequencing Generation (NSG) technologies. On the other hand, the study of fragile X–associated tremor/ataxia syndrome (FXTAS) aims to identify a biological marker allowing us to establish a presymptomatic diagnosis of FXTAS in carriers of the premutation in the FMR1 gene, based on study of the miRNA profile. Regarding the porphyrias, the strategic objective is to advance in our knowledge of the correlation genotype – phenotype: biochemical and clinical expression. Main Lines of Research Collaborators: Cèlia Badenas (Hospital Clínic) Irene Mademont Irene Madrigal (CIBERER) Carmen Morales (Hospital Clínic) Laia Rodriguez Revenga (CIBERER) Mar Xunclà (Fundació Clínic) 262 1. Identification of the genetic bases of mental retardation (MR) of genetic origin, both syndromic and non-syndromic, using the new NSG technologies. Application of massive sequencing to different groups of clinically well characterized MR will allow us to identify new genes and establish new molecular bases in MR. Application is also planned to the study of familial mental retardation and to sporadic cases of non-syndromic MR. 2. Fragile X syndrome: Study of the pathologies associated with premutation of the FMR1 gene: POIFX (Premature ovarian insufficienciy), FXTAS (Fragile X Tremor Ataxia Syndrome), and fibromyalgia associated with the FMR1 gene. Study of the microRNA and ASFMR1 gene expression profiles as possible susceptibility factors for FXTAS. MRI images showing characteristic findings in FXTAS. 1a. Axial FLAIR- MCP sign (middle cerebellar peduncle hyperintensities); 1b. Axial T1- Cerebellar and pontine atrophy; 1c. Coronal T1- Cerebral atrophy; 1d. Axial FLAIRHyperintensities in the cerebral white matter. 3. Detection of cryptic chromosomal imbalances and the identification of new phenotypes, based on cytogenetic - molecular techniques. One is conducted in the prenatal and postnatal diagnostic setting. The aim is to characterize chromosomal imbalances in fetuses with congenital anomalies and a normal karyotype, based on the use of CGH arrays. 4. Study of the genotype-phenotype correlation and expression mechanisms of porphyria. The research lines aim to establish the following: •Advance in the study of the alterations in iron regulation and metabolism in skin and erythropoietic porphyria. •Investigate the role of modifier genes that modulate the clinical expression of erythropoietic porphyria. •Study of new serum and urine biomarkers of acute porphyria severity of use in clinical practice. The group will remain a member of the “European Porphyria Initiative” network as a reference center for the diagnosis, investigation and treatment of porphyria. AREA 5 Oncology and haematology Genetics PUBLICATIONS Originals I.F.: 78,70 1 Vera-Recabarren MA, Garcia-Carrasco M, Ramos-Casals M, Herrero C. Comparative analysis of subacute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus: clinical and immunological study of 270 patients. BRIT J DERMATOL, 2010. 162:91-101. I.F.:4,26. presence or absence of an embryonic pole. FERTIL STERIL, 2010. 94:25642568. I.F.:3,97. 7 Xuncla M, Badenas C, Dominguez M, Rodriguez-Revenga L, Madrigal I, Jimenez L, Soler A, Borrell A, Sanchez A, Mila M. Fragile X syndrome prenatal diagnosis: parental attitudes and reproductive responses. REPROD BIOMED ONLINE, 2010. 21:560-565. I.F.:2,38. 2 Vera-Recabarren MA, Garcia-Ca- 8 Gonce A, Borrell A, Meler E, Arigita rrasco M, Ramos-Casals M, Herrero C. Cutaneous lupus erythematosus: clinical and immunological study of 308 patients stratified by gender. CLIN EXP DERMATOL, 2010. 35:729735. I.F.:1,55. M, Martinez JM, Botet F, Sanchez A, Gratacos E. Prevalence and perinatal outcome of dichorionic and monochorionic twins with nuchal translucency above the 99(th) percentile and normal karyotype. ULTRASOUND OBST GYN, 2010. 35:14-18. I.F.:3,15. 3 Herrero-Gonzalez JE, Iranzo P, Benitez D, Lozano F, Herrero C, Mascaro JM. Correlation of Immunological Profile with Phenotype and Disease Outcome in Pemphigus. ACTA DERM-VENEREOL, 2010. 90:401405. I.F.:3,01. 4 Portillo K, Santos S, Madrigal I, Blanco I, Pare C, Borderias L, Peinado VI, Roca J, Mila M, Barbera JA. Study of the BMPR2 Gene in Patients with Pulmonary Arterial Hypertension. ARCH BRONCONEUMOL, 2010. 46:129-134. I.F.:2,17. 5 Badenas C, Rodriguez-Revenga L, Morales C, Mediano C, Plaja A, Perez-Iribarne MM, Soler A, Clusellas N, Borrell A, Sanchez MA, Miro E, Sanchez A, Mila M, Jimenez W. Assessment of QF-PCR as the First Approach in Prenatal Diagnosis. J MOL DIAGN, 2010. 12:828-834. I.F.:3,41. 6 Munoz M, Arigita M, Bennasar M, Soler A, Sanchez A, Borrell A. Chromosomal anomaly spectrum in early pregnancy loss in relation to 9 To-Figueras J, Lopez RM, Deulofeu R, Herrero C. Preliminary report Hyperhomocysteinemia in patients with acute intermittent porphyria. METABOLISM, 2010. 59:1809-1810. I.F.:2,59. 10 Garcia-Villoria J, Gort L, Madrigal I, Fons C, Fernandez C, Navarro-Sastre A, Mila M, Briones P, Garcia-Cazorla A, Campistol J, Ribes A. X-inactivation of HSD17B10 revealed by cDNA analysis in two female patients with 17 betahydroxysteroid dehydrogenase 10 deficiency. EUR J HUM GENET, 2010. 18:1353-1355. I.F.:3,56. 11 Bermudo R, Abia D, Benitez D, Carrio A, Vilella R, Ortiz AR, Thomson TM, Fernandez PL. Discovery of genomic alterations through coregulation analysis of closely linked genes: a frequent gain in 17q25.3 in prostate cancer. ANN NY ACAD SCI, 2010. 1210:17-24. I.F.:2,67. 12 Madrigal I, Rodriguez-Revenga L, Costa L, Xuncla M, Sanchez A, Mila M. A study of subtelomeric rearrange- ments in 300 patients with mental retardation and multiple congenital anomalies: their clinical and molecular characterisation. REV NEUROLOGIA, 2010. 51:465-470. I.F.:1,23. 13 Demenais F, Mohamdi H, Chaudru V, Goldstein AM, Bishop JAN, Bishop DT, Kanetsky PA, Hayward NK, Gillanders E, Elder DE, Avril MF, Azizi E, VanBelle P, Bergman W, BianchiScarra G, Bressac-DePaillerets B, Calista D, Carrera C, Hansson J, Harland M, Hogg D, Hoiom V, Holland EA, Ingvar C, Landi MT, Lang JM, Mackie RM, Mann GJ, Ming ME, Njauw CJ, Olsson H, Palmer J, Pastorino L, Puig S, Randerson-Moor J, Stark M, Tsao H, Tucker MA, VanDerVelden P, Yang XR, Gruis N. Association of MC1R Variants and Host Phenotypes With Melanoma Risk in CDKN2A Mutation Carriers: A GenoMEL Study. J NATL CANCER I, 2010. 102:1568-1583. I.F.:14,07. 14 Romanelli V, Belinchon A, Benito-Sanz S, Martinez-Glez V, Gracia-Bouthelier R, Heath KE, Campos-Barros A, Garcia-Minaur S, Fernandez L, Meneses H, LopezSiguero JP, Guillen-Navarro E, GomezPuertas P, Wesselink JJ, Mercado G, Esteban-Marfil V, Palomo R, Mena R, Sanchez A, DelCampo M, Lapunzina P. CDKN1C (p57(Kip2)) Analysis in Beckwith-Wiedemann Syndrome (BWS) Patients: Genotype-Phenotype Correlations, Novel Mutations, and Polymorphisms. AM J MED GENET A, 2010. 152A:1390-1397. I.F.:2,40. 15 Mademont-Soler I, Morales C, Armengol L, Soler A, Sanchez A. Description of the Smallest Critical Region for Dandy-Walker Malformation in Chromosome 13 in a Girl With a Cryptic Deletion Related to t(6;13) (q23;q32). AM J MED GENET A, 2010. 152A:2308-2312. I.F.:2,40. 263 AREA 5 Oncology and haematology Genetics Team Members 16 Munoz-Santos C, Guilabert A, Moreno N, To-Figueras J, Badenas C, Darwich E, Herrero C. Familial and Sporadic Porphyria Cutanea Tarda Clinical and Biochemical Features and Risk Factors in 152 Patients. MEDICINE, 2010. 89:69-74. I.F.:5,05. 17 Darwich E, To-Figueras J, Badenas C, Herrero C. Hepatoerythropoietic Porphyria and Familial Porphyria Cutanea Tarda in Spanish Patients: G281E Mutation in the Uroporphyrinogen Decarboxylase Gene. ARCH DERMATOL, 2010. 146:1313-1314. I.F.:4,76. 18 Rodriguez-Revenga L, Pagonabarraga J, Gomez-Anson B, Lopez-Mourelo O, Madrigal I, Xuncla M, Kulisevsky J, Mila M. Motor and mental dysfunction in mother-daughter transmitted FXTAS. NEUROLOGY, 2010. 75:1370-1376. I.F.:8,17. 19 Morales C, Cuatrecasas E, Mademont-Soler I, Clusellas N, Peruga E, Catala V, Garrido C, Mila M, Soler A, Sanchez A. Non-mosaic trisomy 20 of paternal origin in chorionic villus and amniotic fluid also detected in fetal blood and other tissues. EUR J MED GENET, 2010. 53:197-200. I.F.:1,57. 20 Xuncla M, Rodriguez-Revenga L, Madrigal I, Jimenez D, Mila M, Badenas C. Protocol proposal for Friedreich ataxia molecular diagnosis using fluorescent and triplet repeat primed polymerase chain reaction. TRANSL RES, 2010. 156:309-314. I.F.:2,06. 264 21 Mademont-Soler I, Morales C, Bruguera J, Madrigal I, Clusellas N, Margarit E, Sanchez A, Soler A. Subtelomeric MLPA: is it really useful in prenatal diagnosis?. PRENATAL DIAG, 2010. 30:1165-1169. I.F.:1,71. 22 Madrigal I, Fernandez-Burriel M, Rodriguez-Revenga L, Cabrera JC, Marti M, Mur A, Mila M. Xq26.2q26.3 microduplication in two brothers with intellectual disabilities: clinical and molecular characterization. J HUM GENET, 2010. 55:822826. I.F.:2,55. Reviews I.F.: 1,89 1 Fernandez EL, Pares L, Ajuria I, Bandres F, Castanyer B, Campos F, Farre C, Pou L, Queralto JM, To-Figueras J. State of the art in therapeutic drug monitoring. CLIN CHEM LAB MED, 2010. 48:437-446. I.F.:1,89. Grants for research in progress To-Figueras J. European Porphyria Network: providing better healthcare for patients and their families. Sponsored by: European Commision, PHEA 2006107. Amount: 5.332,13 euros. Duration: 01/04/2007-31/03/2010. Mila M. Clinical and molecular study of fxtas syndrome (fragile X tremor Ataxia Syndrome). Sponsored by: Fundació Marató TV3, 60810. Amount: 170.000,00 euros. Duration: 30/01/2007-29/01/2010. Mila M. Caracterización y estudio de la implicación de las variaciones en número de copia en pacientes con retraso mental ligado a cromosoma X. Sponsored by: Fundación Ramón Areces, Areces_06_001. Amount: 50.000,00 euros. Duration: 25/06/2007-24/06/2010. Sánchez A. Caracterización de desequilibrios cromosómicos, análisis de los puntos de rotura en reordenamientos aparentes equilibrados e identificación de cromosomas marcadores mediante microdisección cromosómica y posterior análisis con técnicas de array-CGH y/o. Sponsored by: Ministerio Sanidad y Consumo, PI070385. Amount: 56.870,00 euros. Duration: 26/11/2007-30/12/2010. Mila M. Estudio de los perfiles de expresión de microRNAS y del gen ASFMR1 como factores de susceptibilidad para el desarrollo del síndrome FXTAS. Sponsored by: INSTITUTO DE SALUD CARLOS III, PIO9/0413. Amount: 74.415,00 euros. Duration: 01/01/2010-31/12/2012. Soler N. Utilidad del tratamiento antibiótico en las agudizaciones de la enfermedad pulmonar obstructiva crónica (EPOC) sin purulencia en el esputo: ensayo clinico aleatorizado, controlado y doble ciego de eficacia y seguridad. Sponsored by: INSTITUTO DE SALUD CARLOS III, EC08/00061. Amount: 109.505,00 euros. Duration: 01/01/2009-30/12/2011. AREA 5 Oncology and haematology Melanoma: imaging, genetics and immunology Strategic Objectives Group Members TEAM LEADER Susana Puig (Hospital Clínic) Tel.: 93 227 54 00 (Ext.: 2891) Fax: 93 227 54 38 E-mail: spuig@clinic.ub.es Idibaps members: Ramón Vilella (Hospital Clínic) Josep Malvehy (Hospital Clínic) 1. Development of noninvasive imaging techniques for the diagnosis of melanoma. 2. Study of the genetic bases implicated in susceptibility to melanoma and melanoma photocarcinogenesis. 3. Development of treatment study strategies in melanoma and skin cancer: target-specific molecular, immunological and photoprotection therapies. 4. Application of artificial intelligence systems for evaluating complex data in melanoma, combining imaging, epidemiological, clinical and molecular information. 5. Development of models of humanized mouse skin for the study of photoprotection and photocarcinogenesis. Main Lines of Research Research Fellows: Zighe Ogbah (Fundació Clínic) Joan Anton Puig (CIBERER) Gabriel Salerni (Fundació Clínic) Technicians: Remedios Cervera (CIBERER) Dani Gabriel (Fundació Clínic) Pablo Iglesias (Fundació Clínic) Jordi Milà (Hospital Clínic) Luchi Millan (Hospital Clínic) Collaborators: Paula Aguilera (Hospital Clínic) Pedro Arguís (Hospital Clínic) Celia Badenas (Hospital Clínic) Cristina Carrera (Hospital Clínic) Antonio Campo (Hospital Clínic) Carlos Conill (Hospital Clínic) Melinda González (IDIBAPS) Ramon Rull (Hospital Clínic) Sergi Vidal (Hospital Clínic) Ramón Vilana (Hospital Clínic) Pedro Zaballos (UB) Teresa Castel (Hospital Clínic) Antoni Vilalta (Hospital Clínic) José Palou (Hospital Clínic) Our main lines of research, and some of the most relevant results obtained to date, are the following: 1. Dermatoscopy and digital dermatoscopy. In dermatoscopy studies are being made of the diagnostic criteria of different disorders that have still not been well characterized, the correlations with other imaging techniques, the impact upon the management of patients at risk, and the relationship between dermatoscopy and the genetic profile of the patients. In digital dermatoscopy we are examining the use of full body maps and digital dermatoscopy in the follow-up of patients at risk. 1.1 Definition of new dermatoscopic criteria in different dermatological processes (dermatofibromas, angiokeratomas, botryomycosis, blue nevus, xanthogranuloma, leishmaniasis, lichenoid keratosis, collision tumors). 1.2 Development of dermatoscopy for introduction in primary care, in pathology and dermatology (development of combined clinical dermatoscopic algorithms for the identification of melanomas that are difficult to diagnose). 1.3 Combined dermatoscopic and ultrasound protocol of the primary tumor for preoperative Breslow score estimation. 2. Confocal microscopy in vivo. Description of new algorithms, study of the evolution of lesions, new classifications and the use of telemedicine. 2.1 Definition of criteria in nodular melanoma. 2.2 Creation of a differential diagnostic algorithm for melanocytic and non-melanocytic lesions. 2.3 Characterization of pigmented basal cell carcinomas. 2.4 Study of the use of confocal microscopy for the correct treatment of achromatic or poorly delimited lesions (delimitation of surgical margins or control of relapses). 2.5 Use of ex vivo confocal microscopy for application to Mohs surgery. 3. Genetic epidemiology. Study of melanoma susceptibility genes in familial melanoma and in sporadic melanoma. Study of nevogenicity and risk genes in melanoma. Study of pigmentation and risk genes in melanoma. Identification of new genes and new mechanisms of melanoma susceptibility using Genome Wide Scan. 3.1 Penetrance and phenotypic expression studies in patients and families carrying known CDKN2A and p14arf mutations. 3.2 Study of the effect of polymorphisms of the MC1R gene as modifier gene and low penetrance gene in relation to melanoma risk, and in reference to the clinical and dermatoscopic aspects of melanomas. 3.3 Identification of new melanoma and nevogenicity susceptibility genes based on the study of homozygous genome regions. 265 AREA 5 Oncology and haematology Melanoma: imaging, genetics and immunology PUBLICATIONS Originals I.F.: 62,31 1 Bermudo R, Abia D, Benitez D, Carrio A, Vilella R, Ortiz AR, Thomson TM, Fernandez PL. Discovery of genomic alterations through coregulation analysis of closely linked genes: a frequent gain in 17q25.3 in prostate cancer. ANN NY ACAD SCI, 2010. 1210:17-24. I.F.:2,67. 2 Demenais F, Mohamdi H, Chau4. Study of the mechanisms involved in melanoma carcinogenesis and photocarcinogenesis. 4.1 Analysis of oral photoprotection. Study of genetic (CDKN2A, MC1R)/environmental interaction (UVR) in melanoma risk. Study of the influence of ultraviolet radiation (UVR) (UVA; UVB; UVA/UVB) in the dermatoscopic, histological and immunohistochemical characteristics of melanocytic nevi. 4.2 Dermatoscopic and genetic characterization of the different Clark nevi in dysplastic nevus syndrome, in relation to c9orf14 polymorphisms. 4.3 Investigation of somatic mutations of NRAS, BRAF, cKIT, genomic amplifications of different oncogenes, and genomic losses of 9p21 (MLPA) in melanoma. 4.4 Expression studies (MAGE and others) in melanoma. 4.5 Development of experimental models of gene/gene, gene/ environment interactions between CDKN2A and MC1R. Expression studies in keratinocytes, melanocytes and fibroblasts according to their genetic profile. 5. Development of new treatment strategies for melanoma. 5.1 Hyperthermal perfusion of extremities. 5.2 Vaccines and new therapeutic targets in melanoma. 5.3 Electrochemotherapy in melanoma. 6. Evaluation of immune response in melanoma. 6.1 Genetic expression arrays and studies of SNPs associated with prognosis and treatment response. dru V, Goldstein AM, Bishop JAN, Bishop DT, Kanetsky PA, Hayward NK, Gillanders E, Elder DE, Avril MF, Azizi E, VanBelle P, Bergman W, Bianchi-Scarra G, Bressac-DePaillerets B, Calista D, Carrera C, Hansson J, Harland M, Hogg D, Hoiom V, Holland EA, Ingvar C, Landi MT, Lang JM, Mackie RM, Mann GJ, Ming ME, Njauw CJ, Olsson H, Palmer J, Pastorino L, Puig S, Randerson-Moor J, Stark M, Tsao H, Tucker MA, VanDerVelden P, Yang XR, Gruis N. Association of MC1R Variants and Host Phenotypes With Melanoma Risk in CDKN2A Mutation Carriers: A GenoMEL Study. J NATL CANCER I, 2010. 102:1568-1583. I.F.:14,07. 3 Lovato L, Salerni G, Puig S, Carrera C, Palou J, Malvehy J. Adult Xanthogranuloma Mimicking Basal Cell Carcinoma: Dermoscopy, Reflectance Confocal Microscopy and Pathological Correlation. DERMATOLOGY, 2010. 220:66-70. I.F.:2,74. 4 Gil I, Segura S, Martinez-Escala E, Lloreta J, Puig S, Velez M, Pujol RM, Herrero-Gonzalez JE. Dermoscopic and Reflectance Confocal Microscopic Features of Exogenous Ochronosis. ARCH DERMATOL, 2010. 146:1021-1025. I.F.:4,76. 266 AREA 5 Oncology and haematology Melanoma: imaging, genetics and immunology 5 Haliasos HC, Zalaudek I, Malvehy J, Lanschuetzer C, Hinter H, HofmannWellenhof R, Braun R, Marghoob AA. Dermoscopy of Benign and Malignant Neoplasms in the Pediatric Population. SEMIN CUTAN MED SURG, 2010. 29:218-231. I.F.:1,81. 6 Zaballos P, Carulla M, Ozdemir F, Zalaudek I, Banuls J, Llambrich A, Puig S, Argenziano G, Malvehy J. Dermoscopy of pyogenic granuloma: a morphological study. BRIT J DERMATOL, 2010. 163:1229-1237. I.F.:4,26. 7 Aspizua SG, Garcia M, Murillas R, Retamosa L, Illera N, Duarte B, Holguin A, Puig S, Hernandez MI, Meana A, Jorcano JL, Larcher F, Carretero M, DelRio M. Development of a Bioengineered Skin-Humanized Mouse Model for Psoriasis Dissecting Epidermal-Lymphocyte Interacting Pathways. AM J PATHOL, 2010. 177:3112-3124. I.F.:5,67. 8 Kalkhoran S, Milne O, Zalaudek I, Puig S, Malvehy J, Kelly JW, Marghoob AA. Historical, Clinical, and Dermoscopic Characteristics of Thin Nodular Melanoma. ARCH DERMATOL, 2010. 146:311-318. I.F.:4,76. 9 Garcia M, Llames S, Garcia E, Meana A, Cuadrado N, Recasens M, Puig S, Nagore E, Illera N, Jorcano JL, DelRio M, Larcher F. In Vivo Assessment of Acute UVB Responses in Normal and Xeroderma Pigmentosum (XP-C) Skin-Humanized Mouse Models. AM J PATHOL, 2010. 177:865-872. I.F.:5,67. 10 Branstrom R, Chang YM, Kasparian N, Affleck P, Tibben A, Aspinwall LG, Azizi E, Baron-Epel O, Battistuzzi L, Bruno W, Chan M, Cuellar F, Debniak T, Pjanova D, Ertmanski S, Figl A, Gonzalez M, Hayward NK, Hocevar M, Kanet- sky PA, Leaf SL, VanNieuwpoort FA, Heisele O, Palmer J, Peric B, Puig S, Ruffin AD, Schadendorf D, Gruis NA, Brandberg Y, Newton-Bishop J. Melanoma risk factors, perceived threat and intentional tanning: an international online survey. EUR J CANCER PREV, 2010. 19:216-226. I.F.:2,21. 11 Branstrom R, Kasparian NA, Chang YM, Affleck P, Tibben A, Aspinwall LG, Azizi E, Baron-Epel O, Battistuzzi L, Bergman W, Bruno W, Chan M, Cuellar F, Debniak T, Pjanova D, Ertmanski S, Figl A, Gonzalez M, Hayward NK, Hocevar M, Kanetsky PA, Leachman SA, Heisele O, Palmer J, Peric B, Puig S, Schadendorf D, Gruis NA, Newton-Bishop J, Brandberg Y. Predictors of Sun Protection Behaviors and Severe Sunburn in an International Online Study. CANCER EPIDEM BIOMAR, 2010. 19:21992210. I.F.:4,31. 12 DiStefani A, Campbell TM, Malvehy J, Massone C, Soyer HP, Hofmann-Wellenhof R. Shiny white streaks: An additional dermoscopic finding in melanomas viewed using contact polarised dermoscopy. AUSTRALAS J DERMATOL, 2010. 51:295-298. I.F.:0,97. 13 Argenziano G, Kittler H, Ferrara G, Rubegni P, Malvehy J, Puig S, Cowell L, Stanganelli I, DeGiorgi V, Thomas L, Bahadoran P, Menzies SW, Piccolo D, Marghoob AA, Zalaudek I. Slow-growing melanoma: a dermoscopy follow-up study. BRIT J DERMATOL, 2010. 162:267-273. I.F.:4,26. 14 Keratosis in Lichenoid Keratosis with Sequential Dermoscopy Imaging. DERMATOLOGY, 2010. 220:103-109. I.F.:2,74. 15 Zalaudek I, Kittler H, Blum A, Hofmann-Wellenhof R, Marghoob AA, Malvehy J, Menzies SW, Puig S, Soyer P, Stolz W, Argenziano G. Who benefits from prophylactic surgical removal of “dysplastic” nevi?. J DTSCH DERMATOL GES, 2010. 8:279-280. I.F.:1,40. Clinical Guidelines I.F.: 4,12 1 Garbe C, Peris K, Hauschild A, Saiag P, Middleton M, Spatz A, Grob JJ, Malvehy J, Newton-Bishop J, Stratigos A, Pehamberger H, Eggermont A. Diagnosis and treatment of melanoma: European consensus-based interdisciplinary guideline. EUR J CANCER, 2010. 46:270-283. I.F.:4,12. Grants for research in progress Puig S. NoE - Genetic and environmental risk factors for melanoma: translation into behavioural change. Sponsored by: European Commission, LSHMCT-2006-018702. Amount: 322.173,00 euros. Duration: 01/12/2005-30/11/2010. Puig S. Identificación de genes implicados en desarrollo y progresión de melanoma mediante la caracterización de regiones homozigotas. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1393. Amount: 217.800,00 euros. Duration: 01/01/2010-31/12/2012. Zaballos P, Salsench E, Serrano P, Cuellar F, Puig S, Malvehy J. Studying Regression of Seborrheic 267 AREA 5 Team envolved in: Oncology and haematology Red temática de investigación cooperativa de cáncer Hematopoietic progenitor cell transplantation Strategic Objectives Group Members TEAM LEADER Álvaro Urbano-Ispizúa (Hospital Clínic) Tel.: 93 227 54 75 Fax: 93 227 98 11 E-mail: aurbano@clinic.ub.es Idibaps members: Enric Carreras (Hospital Clínic) Francesc Fernández-Avilés (Hospital Clínic) Pedro Marín (Hospital Clínic) Carmen Martínez Muñoz (Hospital Clínic) Montserrat Rovira (Hospital Clínic) In the last few years our group has developed basic and translational research lines, thanks to collaboration with other research groups of the Clinic Hospital (Department of Immunology, Department of Hemostasis) and of the Medical School (Department of Human Anatomy). Very recently, we have established research space of our own in the CEK, and have expanded our collaboration with other research groups – particularly in reference to cell therapy. Likewise, we have started the expansion of hematopoietic precursors from umbilical cord blood based on co-cultures of mesenchymal cells and research lines in antitumor cell therapy, anti-infectious treatment and cell immune modulation. Functional studies of genic polymorphisms have also been started. Lastly, we plan to develop an important line of research in the field of the pharmacokinetics, pharmacodynamics and pharmacogenomics of immune modulators, as well as in the development of in vitro predictive models of graft-versus-host disease. Main Lines of Research Clinical research lines Postdoctoral fellows: Beatriz Martin Antonio (IDIBAPS) Technicians: Anna Mantecon (Fundació Clínic) Nuria Montfort (Hospital Clínic) Nursing Staff: Ariadna Domènech (Fundació Clínic) 268 Collaborators: Josep Mensa (Hospital Clínic) Alfons Navarro (Facultat de Medicina UB) Marià Monzó (Facultat de Medicina UB) Maribel Díaz Ricart (Hospital Clínic) 1. Assessment of new hematopoietic precursor transplantation (HPT) indications. Treatment of diseases such as amyloidosis, POEMS syndrome, scleromyxedema, autoimmune disorders (multiple sclerosis, Crohn’s disease, lupus erythematosus), primary myelofibrosis or paroxysmal nocturnal hemoglobinuria – these being diseases in which our group has the most extensive experience in the country. AREA 5 Oncology and haematology Hematopoietic progenitor cell transplantation 2. Evaluation of new progenitor sources (high-complexity hematopoietic precursor transplantation). The lack of compatible siblings for all patients amenable to hematopoietic precursor transplantation is leading to the development of transplants from non-consanguineous donors or umbilical cord blood. We are the most active group in the country in relation to these high complexity procedures, which represent 30% of our activity. 3. Evaluation of new transplant modalities: •Domiciliary autogenic HPT (the only such program in Europe, awarded on several occasions by the scientific and healthcare societies) – a modality which we aim to extend to domiciliary allogenic HPT. •Umbilical cord blood cell transplantation administered via the intraosseous route – an innovating modality which we and another European center are analyzing. 4. Studies addressing the prevention and treatment of the main complications of HPT. Prevention and treatment of graftversus-host disease with new agents (anti-IL-2 receptor antibodies, new anti-thymocyte globulins, alemtuzumab and cell therapy using mesenchymal cells). Participation in different multicenter studies. Basic and translational research lines 1. Study of the post-HPT complications originating from endothelial dysfunction. Different early complications appearing after HPT, such as veno-occlusive syndrome, capillary rupture syndrome, thrombotic microangiopathy, graft syndrome, and idiopathic pneumonia syndrome, appear to originate from endothelial dysfunction. Our project aims to characterize such dysfunction and then to seek effective preventive and treatment options. This research line is supported by two FIS grants and an aid from the German José Carreras Foundation. 2. Study of immune reconstitution following HPT. Following characterization of immune reconstitution in HPT from bone marrow, peripheral blood and in reduced intensity regimens, we plan to assess immune reconstitution in the transplantation of umbilical cord blood – this not ever having been achieved to date. A. Sphere obtained after one week of bone marrow isolated nestin-positive mesenchymal cell culture. 3. Study of the impact of genic polymorphisms upon the complications and outcomes of HPT. Following demonstration of the impact of the mannose-binding lectin variants upon the incidence of fungal infections, of the NOD2/ CARD15 gene variants upon survival and the incidence of bronchiolitis obliterans and, more recently, of the impact of the NLRP2 and NLRP3 gene variants upon HPT survival, we plan to continue this line of research, assessing new polymorphisms that may affect the evolution of HPT. 4. Study of new techniques for the early diagnosis of infections in HPT. Following the advances made in the early diagnosis of fungal diseases (galactomannan antigen, highresolution CAT) and viral infections (CMV antigenemia and PCR applied to all herpes viruses and other pathogens), which have facilitated our healthcare activities, we plan to continue evaluating new diagnostic techniques (quantitative PCR for EBV, the application of PCR to tissue samples, biological markers in bronchoalveolar lavage, and PET scan assessment of infections). B. Sphere expansion after four weeks of culture. 269 AREA 5 Oncology and haematology Hematopoietic progenitor cell transplantation Team Members PUBLICATIONS Originals I.F.: 43,66 1 Escurriol V, Cofan M, MorenoIribas C, Larranaga N, Martinez C, Navarro C, Rodriguez L, Gonzalez CA, Corella D, Ros E. Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort. J LIPID RES, 2010. 51:618624. I.F.:4,92. 2 Esmatjes E, Montana X, Real MI, Blanco J, Conget I, Casamitjana R, Rovira M, Gomis R, Marin P. Regeneration of insulin production by autologous bone marrow blood autotransplantation in patients with type 1 diabetes. DIABETOLOGIA, 2010. 53:786-789. I.F.:6,55. 3 DeLaCamara R, Jarque I, Sanz MA, Grau S, Casado MA, Sabater FJ, Carreras E. Economic evaluation of posaconazole vs fluconazole in the prevention of invasive fungal infections in patients with GVHD following haematopoietic SCT. BONE MARROW TRANSPL, 2010. 45:925-932. I.F.:3,00. 4 Palomo M, Diaz-Ricart M, Carbo C, Rovira M, Fernandez-Aviles F, Martine C, Ghita G, Escolar G, Carreras E. Endothelial Dysfunction after Hematopoietic Stem Cell Transplantation: Role of the Conditioning Regimen and the Type of Transplantation. BIOL BLOOD MARROW TR, 2010. 16:985-993. I.F.:3,15. 5 Carreras E, Fernandez-Aviles F, Silva L, Guerrero M, DeLarrea CF, Martinez C, Rosinol L, Lozano M, Marin P, Rovira M. Engraftment syndrome after auto-SCT: analysis of diagnostic criteria and risk factors in a large series from a single center. BONE MARROW TRANSPL, 2010. 45:14171422. I.F.:3,00. 270 6 DeLarrea CF, Rosinol L, Cibeira MT, Rozman M, Rovira M, Blade J. Extensive soft-tissue involvement by plasmablastic myeloma arising from displaced humeral fractures. EUR J HAEMATOL, 2010. 85:448-451. I.F.:2,35. 7 Carreras E, Cahn JY, Puozzo C, Kroger N, Sanz G, Buzyn A, Bacigalupo A, Vernant JP. Influence on Busilvex (R) Pharmacokinetics of Clonazepam Compared to Previous Phenytoin Historical Data. ANTICANCER RES, 2010. 30:2977-2984. I.F.:1,43. 8 Pinana JL, Valcarcel D, FernandezAviles F, Martino R, Rovira M, Barba P, Martinez C, Brunet S, Sureda A, Carreras E, Sierra J. MTX or mycophenolate mofetil with CsA as GVHD prophylaxis after reduced-intensity conditioning PBSCT from HLA-identical siblings. BONE MARROW TRANSPL, 2010. 45:1449-1456. I.F.:3,00. 9 DeLarrea CF, Martinez C, Gaya A, Lopez-Guillermo A, Rovira M, Fernandez-Aviles F, Lozano M, Bosch F, Esteve J, Nomdedeu B, Montserrat E, Carreras E. Salvage chemotherapy with alternating MINE-ESHAP regimen in relapsed or refractory Hodgkin’s lymphoma followed by autologous stem-cell transplantation. ANN ONCOL, 2010. 21:1211-1216. I.F.:5,65. 10 Martinez C, Virgili N, Cuerda C, Chicharro L, Gomez P, Moreno JM, Alvarez J, Marti E, Matia P, Penacho MA, Garde C, DeLuis D, Gonzalo M, Lobo G. Transversal study on the prevalence of metabolic bone disease (MBD) and home parenteral nutrition (HPN) in Spain: Data from Nadya Grop. NUTR HOSP, 2010. 25:920-924. I.F.:1,07. 11 Ferra C, Sanz J, DeLaCamara R, Sanz G, Bermudez A, Valcarcel D, Rovira M, Serrano D, Caballero D, Espigado I, Morgades M, Heras I, Solano C, Duarte R, Barrenetxea C, GarciaNoblejas A, Diez-Martin JL, Iriondo A, Carreras E, Sierra J, Sanz MA, Ribera JM. Unrelated Transplantation for Poor-Prognosis Adult Acute Lymphoblastic Leukemia: Long-Term Outcome Analysis and Study of the Impact of Hematopoietic Graft Source. BIOL BLOOD MARROW TR, 2010. 16:957966. I.F.:3,15. 12 Cordonnier C, Rovira M, Maertens J, Olavarria E, Faucher C, Bilger K, Pigneux A, Cornely OA, Ullmann AJ, Bofarull RM, DeLaCamara R, Weisser M, Liakopoulou E, Abecasis M, Heussel CP, Pineau M, Ljungman P, Einsele H. Voriconazole for secondary prophylaxis of invasive fungal infections in allogeneic stem cell transplant recipients: results of the VOSIFI study. HAEMATOL-HEMATOL J, 2010. 95:1762-1768. I.F.:6,42. Reviews I.F.: 15,66 1 DeLaCamara R, Mensa J, Carreras E, Estrella MC, Rodriguez JAG, Gobernado M, Picazo J, Aguado JM, Sanz MA. Antifungal prophylaxis in oncohematologic patients: Literature review and recommendations. MED CLIN-BARCELONA, 2010. 134:222233. I.F.:1,23. 2 Blade J, Rosinol L, Cibeira MT, Rovira M, Carreras E. Hematopoietic stem cell transplantation for multiple myeloma beyond 2010. BLOOD, 2010. 115:3655-3663. I.F.:10,56. AREA 5 Oncology and haematology Hematopoietic progenitor cell transplantation 3 Coppell JA, Richardson PG, Soiffer R, Martin PL, Kernan NA, Chen A, Guinan E, Vogelsang G, Krishnan A, Giralt S, Revta C, Carreau NA, Iacobelli M, Carreras E, Ruutu T, Barbui T, Antin JH, Niederwieser D. Hepatic Veno-Occlusive Disease following Stem Cell Transplantation: Incidence, Clinical Course, and Outcome. BIOL BLOOD MARROW TR, 2010. 16:157-168. I.F.:3,15. 4 Vallejo C, Rovira M. Prophylaxis and treatment of invasive fungal infection in neutropenic patients. REV ESP QUIM, 2010. 23:177-183. I.F.:0,73. Multicentrics I.F.: 10,56 1 Gorin NC, Labopin M, Reiffers J, Milpied N, Blaise D, Witz F, DeWitte T, Meloni G, Attal M, Bernal T, Rocha V. Higher incidence of relapse in patients with acute myelocytic leukemia infused with higher doses of CD34(+) cells from leukapheresis products autografted during the first remission. BLOOD, 2010. 116:3157-3162. I.F.:10,56. Carreras E. Disfunción endotelial post-trasplante hematopoyético. Impacto de los agentes empleados en el régimen de acondicionamiento y análisis de posibles agentes protectores. Sponsored by: Ministerio de Sanidad y Consumo, PI080156. Amount: 61.952,00 euros. Duration: 01/01/2009-31/12/2011. Martinez Munoz C. Estudio de la farmacogenómica y la farmacodinámica de los inmunosupresores en el trasplante alogénico de progenitores hemopoyéticos y su implicación en las reacciones injerto contra huésped e injerto-contra-tumor. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1043. Amount: 67.760,00 euros. Duration: 01/01/2010-31/12/2012. Urbano A. Papel de los factores inducidos por hipoxia (HIFs), Notch, Oct4 y de microRNAs en la patogenia y transformación de los síndromes mielodisplásicos a leucemia aguda. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI08/1137. Amount: 29.499,20 euros. Duration: 29/07/2010-30/12/2011. Grants for research in progress Urbano A. Red temática de investigación cooperativa de cáncer. Sponsored by: INSTITUTO DE SALUD CARLOS III, RD06/0020/0012. Amount: 107.539,01 euros. Duration: 01/01/2007-31/12/2010. Carreras E. Characterization of endothelial dysfunction that develops in haematopoietic stem cell transplantation: role in the main complications appearing early after transplantation. Sponsored by: Deutsche Jose Carreras LeukämieStiftung eV, R07/41v. Amount: 185.000,00 euros. Duration: 30/01/200830/09/2010. 271 AREA 5 Team envolved in: Oncology and haematology Red temática de investigación cooperativa de cáncer Hematological oncology Strategic Objectives Group Members TEAM LEADER Francisco Cervantes (Hospital Clínic) Tel.: 93 227 54 75 E-mail: fcervan@clinic.ub.es Idibaps members: Prof. Emili Montserrat (Hospital Clínic) Joan Bladé (Hospital Clínic) Jordi Esteve (Hospital Clínic) Armando López-Guillermo (Hospital Clínic) Research Fellows: Anna Gaya (Hospital Clínic) Marta Pratcorona (IDIBAPS) Gonzalo Gutierrez (Hospital Clínic) Margheritta Maffioli (Fundació Clínic) Marina Díaz Beyá (Fundació Clínic) Alejandra Martínez Trillos (Fundació Clínic) Carlos Fernández de Larrea (Fundació Clínic) Raquel Jiménez (Fundació Clínic) Kate Hodgson (Fundació Clínic) Gerardo Ferrer (Fundació Clínic) Nursing Staff: Sonia Chaves (Hospital Clínic) Eva Carrera (Hospital Clínic) Administrative Staff: Maria José Sánchez Melero (Hospital Clínic) Cristina Cerrato (Hospital Clínic) 272 The main strategic objectives of our team are clinical, applied and basic research in hematological oncology. The team is structured into three study groups of three major disease categories. Main Lines of Research 1. Study of lymphoid neoplasms. 2. Multiple myeloma and other monoclonal gammapathies. 3. Study of myeloid neoplasms. Staticians: Antonio de la Riva (Fundació Clínic) Mª Carmen Pastor (Fundació Clínic) Montserrat Pérez (Fundació Clínic) Collaborators: Benet Nomdedeu (Hospital Clínic) Laura Rosiñol (Hospital Clínic) Arturo Pereira (Hospital Clínic) Eduardo Arellano (Hospital Clínic) Maria Teresa Cibeira (Hospital Clínic) Alfons Navarro (Universitat de Barcelona) Dolors Costa ( Hospital Clínic) Ana Carrió (Hospital Clínic) Eva Giné (Hospital Clínic) AREA 5 Oncology and haematology Hematological oncology RESEARCH GROUP Lymphoid neoplasms study group Group Leader: Armando López (Hospital Clínic) Lymphomas •Investigation of the progression mechanisms of the disease. •Study of minimum residual disease and its clinical significance. •Genomic profiles of the different types of lymphoma and their clinical significance (in collaboration with the National Cancer Institute (USA) and the Leukemia Lymphoma Molecular Profiling Project (LLMPP)). •New prognostic models in T cell lymphomas (collaboration in international studies, particularly the International T-cell Lymphomas Project. University of Nebraska) and follicular lymphoma. •Utility of PET in evaluating the response of lymphomas and chronic lymphocytic leukemia (CLL). •Genic profile of Hodgkin lymphoma. •Phase I-II clinical trials with new drugs (bevacizumab, bortezomib, anti-CD40, aplidin, GA101, etc.), and international phase III trials to establish new indications in lymphomas (PRIMA and ZAR studies) Chronic lymphocytic leukemia •Mechanisms of progression of the disease. •Biology of ZAP-70 in relation to BCR. •Analysis of transforming CLL. •Influence of the cellular microenvironment upon the disease. •Study of the immunological alterations and immune reconstitution in chronic lymphocytic leukemia (CLL Global Research Foundation project). •Evaluation of cellular proliferation in CLL. •Study of autoimmune phenomena. •Multiparametric analysis of prognostic factors in CLL. - Phase I/II and III clinical trials. RESEARCH GROUP Myeloma and other monoclonal gammapathies study group Group Leader: Joan Blade (Hospital Clínic) •Studies on the role of angiogenesis inhibitors in the treatment of multiple myeloma. •Clinico-biological studies on the progression mechanisms of monoclonal gammapathy of uncertain significance and quiescent myeloma. •Phase I, II and III clinical trials with new drugs (thalidomide, bortezomib, lenalidomide, deacetylase histone inhibitors, aplidin, anti-IL-6 antibodies and anti-CD40 antibodies, heat shock protein-90 inhibitors). •Clinical trials in the treatment of primary amyloidosis (transplantation, therapy with lenalidomide). RESEARCH GROUP Myeloid neoplasms study group Group Leader: Francisco Cervantes (Hospital Clínic) Myeloproliferative neoplasms •Analysis and final evaluation of the Spanish protocol for the treatment of chronic myeloid leukemia with scaled doses of imatinib versus imatinib in combination with interferon(CML/PETHEMA). •Treatment of CML with new tyrosine kinase inhibitors. •Role of the polymorphisms of the genes encoding for the imatinib transporter proteins in resistance to therapy with imatinib in CML. •Thrombotic mechanisms in chronic myeloproliferative syndromes. •Primary myelofibrosis prognostic studies. •Analysis of the relationship between the mutational status and allelic load of JAK2 and MPL, haplotype 46/1 of the JAK2 gene, and the initial characteristics, evolutive pattern and prognosis of myelofibrosis. Acute leukemias •Biological prognostic factors in intermediate cytogenetic risk AML: genetic mutations, genic expression profile, microRNA expression pattern. •Analysis of the microRNA expression pattern in AML with translocation (8;16)/rearrangement MYST3-CREBBP. •Biological and clinical characterization of acute leukemia with multiline dysplasia. •Analysis of the prognostic value of molecular markers in AML in relation to the outcome of hematopoietic progenitor cell transplantation. •Phase II and III clinical trials of drugs for the treatment of AML (midostaurin, Mylotarg, amonafide, AC220, azacytidine). •Sequential allogenic hematopoietic precursor transplantation strategy for the treatment of refractory or relapsing AML. Myeloproliferative syndromes •Natural history and prognosis of myelodysplastic syndromes. - transfusional sensitization. - prognostic importance of transfusion requirements. •Cytogenetic and molecular alterations in myelodysplastic syndromes. - Prognostic implications of cytogenetic alterations. - translocations and myelodysplastic syndromes. - microRNA in myelodysplastic syndromes. •Treatment of myelodysplastic syndromes. 273 AREA 5 Oncology and haematology Hematological oncology Team Members PUBLICATIONS Originals I.F.: 243,89 1 Segarra M, Lozano E, CorberaBellalta M, Vilardell C, Cibeira MT, Esparza J, Izco N, Blade J, Cid MC. Thalidomide decreases gelatinase production by malignant B lymphoid cell lines through disruption of multiple integrin-mediated signaling pathways. HAEMATOL-HEMATOL J, 2010. 95:456-463. I.F.:6,42. 2 Fernandez V, Salamero O, Espinet B, Sole F, Royo C, Navarro A, Camacho F, Bea S, Hartmann E, Amador V, Hernandez L, Agostinelli C, Sargent RL, Rozman M, Aymerich M, Colomer D, Villamor N, Swerdlow SH, Pileri SA, Bosch F, Piris MA, Montserrat E, Ott G, Rosenwald A, Lopez-Guillermo A, Jares P, Serrano S, Campo E. Genomic and Gene Expression Profiling Defines Indolent Forms of Mantle Cell Lymphoma. CANCER RES, 2010. 70:1408-1418. I.F.:7,54. 3 Moreno C, Hodgson K, Ferrer G, Elena M, Filella X, Pereira A, Baumann T, Montserrat E. Autoimmune cytopenia in chronic lymphocytic leukemia: prevalence, clinical associations, and prognostic significance. BLOOD, 2010. 116:4771-4776. I.F.:10,56. 4 Gutierrez-Garcia G, Colomo L, Villamor N, Arenillas L, Martinez A, Cardesa T, Garcia-Herrera A, Setoain X, Rodriguez S, Ghita G, Abrisqueta P, Gine E, Bosch F, Campo E, Montserrat E, Lopez-Guillermo A. Clinico-biological characterization and outcome of primary nodal and extranodal diffuse large B-cell lymphoma in the rituximab era. LEUKEMIA LYMPHOMA, 2010. 51:1225-1232. I.F.:2,40. 274 5 Crowther-Swanepoel D, Brode- 8 DeLarrea CF, Rosinol L, Cibeira rick P, DiBernardo MC, Dobbins SE, Torres M, Mansouri M, Ruiz-Ponte C, Enjuanes A, Rosenquist R, Carracedo A, Jurlander J, Campo E, Juliusson G, Montserrat E, Smedby KE, Dyer MJS, Matutes E, Dearden C, Sunter NJ, Hall AG, Mainou-Fowler T, Jackson GH, Summerfield G, Harris RJ, Pettitt AR, Allsup DJ, Bailey JR, Pratt G, Pepper C, Fegan C, Parker A, Oscier D, Allan JM, Catovsky D, Houlston RS. Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk. NAT GENET, 2010. 42:132-U59. I.F.:34,28. MT, Rozman M, Rovira M, Blade J. Extensive soft-tissue involvement by plasmablastic myeloma arising from displaced humeral fractures. EUR J HAEMATOL, 2010. 85:448-451. I.F.:2,35. 6 Gine E, Martinez A, Villamor N, Lopez-Guillermo A, Camos M, Martinez D, Esteve J, Calvo X, Muntanola A, Abrisqueta P, Rozman M, Rozman C, Bosch F, Campo E, Montserrat E. Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia (“accelerated” chronic lymphocytic leukemia) with aggressive clinical behavior. HAEMATOL-HEMATOL J, 2010. 95:1526-1533. I.F.:6,42. 7 Espinet B, Salaverria I, Bea S, Ruiz-Xiville N, Balague O, Salido M, Costa D, Carreras J, Rodriguez-Vicente AE, Garcia JL, Hernandez-Rivas JM, Calasanz MJ, Siebert R, Ferrer A, Salar A, Carrio A, Polo N, Garcia-Marco JA, Domingo A, Gonzalez-Barca E, Romagosa V, Marugan I, LopezGuillermo A, Milla F, Mate JL, Luno E, Sanzo C, Collado R, Oliver I, Monzo S, Palacin A, Gonzalez T, Sant F, Salinas R, Ardanaz MT, Font L, Escoda L, Florensa L, Serrano S, Campo E, Sole F. Incidence and Prognostic Impact of Secondary Cytogenetic Aberrations in a Series of 145 Patients with Mantle Cell Lymphoma. GENE CHROMOSOME CANC, 2010. 49:439-451. I.F.:3,86. 9 Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, Guglielmelli P, Pungolino E, Caramella M, Maffioli M, Pascutto C, Lazzarino M, Cazzola M, Tefferi A. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). BLOOD, 2010. 115:1703-1708. I.F.:10,56. 10 Sanchez-Espiridion B, Montalban C, Lopez A, Menarguez J, Sabin P, Ruiz-Marcellan C, Ramos R, Rodriguez J, Canovas A, Camarero C, Canales M, Alves J, Arranz R, Acevedo A, Salar A, Serrano S, Bas A, Moraleda JM, Sanchez-Godoy P, Burgos F, Rayon C, Fresno MF, Larana JG, Garcia-Cosio M, Santonja C, Lopez JL, Llanos M, Mollejo M, GonzalezCarrero J, Marin A, Forteza J, GarciaSanz R, Tomas JF, Morente MM, Piris MA, Garcia JF. A molecular risk score based on 4 functional pathways for advanced classical Hodgkin lymphoma. BLOOD, 2010. 116:E12-E17. I.F.:10,56. 11 Mateos MV, Oriol A, MartinezLopez J, Gutierrez N, Teruel AI, DePaz R, Garcia-Larana J, Bengoechea E, Martin A, Mediavilla JD, Palomera L, DeArriba F, Gonzalez Y, Hernandez JM, Sureda A, Bello JL, Bargay J, Penalver FJ, Ribera JM, Martin-Mateos ML, Garcia-Sanz R, Cibeira MT, Ramos MLM, Vidriales MB, Paiva B, Montalban MA, Lahuerta JJ, Blade J, SanMiguel JF. Bortezomib, melpha- AREA 5 Oncology and haematology Hematological oncology lan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myelom. LANCET ONCOL, 2010. 11:934-941. I.F.:14,47. 12 Lahuerta JJ, Mateos MV, Martinez-Lopez J, Grande C, DeLaRubia J, Rosinol L, Sureda A, Garcia-Larana J, Diaz-Mediavilla J, Hernandez-Garcia MT, Carrera D, Besalduch J, DeArriba F, Oriol A, Escoda L, Garcia-Frade J, Rivas-Gonzalez C, Alegre A, Blade J, SanMiguel JF. Busulfan 12 mg/ kg plus melphalan 140 mg/m(2) versus melphalan 200 mg/m(2) as conditioning regimens for autologous transplantation in newly diagnosed multiple myeloma patients included in the PETHEMA/GEM2000 study. HAEMATOL-HEMATOL J, 2010. 95:1913-1920. I.F.:6,42. 13 Ribera JM, Oriol A, Gonzalez M, Vidriales B, Brunet S, Esteve J, DelPotro E, Rivas C, Moreno MJ, Tormo M, Martin-Reina V, Sarra J, Parody R, DeOteyza JP, Bureo E, Bernal MT. Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final resullts of the CSTIBES02 trial. HAEMATOLHEMATOL J, 2010. 95:87-95. I.F.:6,42. 14 Cervantes F, Lopez-Garrido P, Montero MI, Jonte F, Martinez J, Hernandez-Boluda JC, Calbacho M, Sureda A, Perez-Rus G, Nieto JB, Perez-Lopez C, Roman-Gomez J, Gonzalez M, Pereira A, Colomer D. Early intervention during imatinib therapy in patients with newly diagnosed chronic-phase chronic myeloid leukemia: a study of the Spanish PETHEMA group. HAEMATOL-HEMATOL J, 2010. 95:1317-1324. I.F.:6,42. 15 Martinez-Trillos A, Gaya A, Maffioli M, Arellano-Rodrigo E, Calvo X, Diaz-Beya M, Cervantes F. Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients. ANN HEMATOL, 2010. 89:1233-1237. I.F.:2,92. 16 Ernst T, Chase AJ, Score J, Hidalgo-Curtis CE, Bryant C, Jones AV, Waghorn K, Zoi K, Ross FM, Reiter A, Hochhaus A, Drexler HG, Duncombe A, Cervantes F, Oscier D, Boultwood J, Grand FH, Cross NCP. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. NAT GENET, 2010. 42:722U109. I.F.:34,28. 17 Alvarez-Larran A, Cervantes F, Pereira A, Arellano-Rodrigo E, PerezAndreu V, Hernandez-Boluda JC, Ayats R, Salvador C, Muntanola A, Bellosillo B, Vicente V, HernandezNieto L, Burgaleta C, Xicoy B, Besses C. Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. BLOOD, 2010. 116:1205-1210. I.F.:10,56. 18 Ballen KK, Shrestha S, Sobocinski KA, Zhang MJ, Bashey A, Bolwell BJ, Cervantes F, Devine SM, Gale RP, Gupta V, Hahn TE, Hogan WJ, Kroger N, Litzow MR, Marks DI, Maziarz RT, Mccarthy PL, Schiller G, Schouten HC, Roy V, Wiernik PH, Horowitz MM, Giralt SA, Arora M. Outcome of Transplantation for Myelofibrosis. BIOL BLOOD MARROW TR, 2010. 16:358-367. I.F.:3,15. 19 Mateos MV, Cibeira MT, Richardson PG, Prosper F, Oriol A, DeLaRubia J, Lahuerta JJ, Garcia-Sanz R, Extremera S, Szyldergemajn S, Corrado C, Singer H, Mitsiades CS, Anderson KC, Blade J, SanMiguel J. Phase II Clinical and Pharmacokinetic Study of Plitidepsin 3-Hour Infusion Every Two Weeks Alone or with Dexamethasone in Relapsed and Refractory Multiple Myeloma. CLIN CANCER RES, 2010. 16:3260-3269. I.F.:6,75. 20 Buda G, Ricci D, Huang CC, Favis R, Cohen N, Zhuang SH, Harousseau JL, Sonneveld P, Blade J, Orlowski RZ. Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in patients with advanced multiple myeloma treated with bortezomib and pegylated liposomal doxorubicin. ANN HEMATOL, 2010. 89:1133-1140. I.F.:2,92. 21 Mohty M, Labopin M, Volin L, Gratwohl A, Socie G, Esteve J, Tabrizi R, Nagler A, Rocha V. Reduced-intensity versus conventional myeloablative conditioning allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation. BLOOD, 2010. 116:44394443. I.F.:10,56. 22 Ludwig H, Bolejack V, Crowley J, Blade J, SanMiguel J, Kyle RA, Rajkumar SV, Shimizu K, Turesson I, Westin J, Sonneveld P, Cavo M, Boccadoro M, Palumbo A, Tosi P, Harousseau JL, Attal M, Barlogie B, Stewart AK, Durie B. Survival and Years of Life Lost in Different Age Cohorts of Patients With Multiple Myeloma. J CLIN ONCOL, 2010. 28:1599-1605. I.F.:17,79. 23 Diaz-Beya M, Rozman M, Pratcorona M, Torrebadell M, Camos M, Aguilar JLI, Esteve J. The prognostic value of multilineage dysplasia in de novo acute myeloid leukemia patients with intermediate-risk cytogenetics is dependent on NPM1 mutational status. BLOOD, 2010. 116:6147-6148. I.F.:10,56. 275 AREA 5 Oncology and haematology Hematological oncology Team Members 24 Barbui T, Carobbio A, Cervantes F, Vannucchi AM, Guglielmelli P, Antonioli E, Alvarez-Larran A, Rambaldi A, Finazzi G, Barosi G. Thrombosis in primary myelofibrosis: incidence and risk factors. BLOOD, 2010. 115:778782. I.F.:10,56. 25 Tefferi A, Siragusa S, Hussein K, Schwager SM, Hanson CA, Pardanani A, Cervantes F, Passamonti F. Transfusion-dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis-prognostic relevance is independent of IPSS or karyotype. AM J HEMATOL, 2010. 85:14-17. I.F.:2,61. 26 Guillem VM, Cervantes F, Martinez J, Alvarez-Larran A, Collado M, Camos M, Sureda A, Maffioli M, Marugan I, Hernandez-Boluda JC. XPC genetic polymorphisms correlate with the response to imatinib treatment in patients with chronic phase chronic myeloid leukemia. AM J HEMATOL, 2010. 85:482-486. I.F.:2,61. Reviews I.F.: 76,54 1 Blade J, Rosinol L, Cibeira MT, Rovira M, Carreras E. Hematopoietic stem cell transplantation for multiple myeloma beyond 2010. BLOOD, 2010 . 115:3655-3663. I.F.:10,56. 2 Gine E, Gutierrez-Garcia G, Lopez-Guillermo A. Current immunochemotherapy strategies in follicular lymphoma. ADV THER, 2010. 27:704713. I.F.:0,94. 276 3 Ludwig H, Beksac M, Blade J, 6 Blade J, Dimopoulos M, Rosinol Boccadoro M, Cavenagh J, Cavo M, Dimopoulos M, Drach J, Einsele H, Facon T, Goldschmidt H, Harousseau JL, Hess U, Ketterer N, Kropff M, Mendeleeva L, Morgan G, Palumbo A, Plesner T, SanMiguel J, Shpilberg O, Sondergeld P, Sonneveld P, Zweegman S. Current Multiple Myeloma Treatment Strategies with Novel Agents: A European Perspective. ONCOLOGIST, 2010. 15:6-25. I.F.:6,70. L, Rajkumar SV, Kyle RA. Smoldering (Asymptomatic) Multiple Myeloma: Current Diagnostic Criteria, New Predictors of Outcome, and Follow-Up Recommendations. J CLIN ONCOL, 2010. 28:690-697. I.F.:17,79. 4 Kyle RA, Durie BGM, Rajkumar SV, Landgren O, Blade J, Merlini G, Kroger N, Einsele H, Vesole DH, Dimopoulos M, SanMiguel J, AvetLoiseau H, Hajek R, Chen WM, Anderson KC, Ludwig H, Sonneveld P, Pavlovsky S, Palumbo A, Richardson PG, Barlogie B, Greipp P, Vescio R, Turesson I, Westin J, Boccadoro M. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. LEUKEMIA, 2010. 24:11211127. I.F.:8,30. 5 Dimopoulos MA, Terpos E, Chanan-Khan A, Leung N, Ludwig H, Jagannath S, Niesvizky R, Giralt S, Fermand JP, Blade J, Comenzo RL, Sezer O, Palumbo A, Harousseau JL, Richardson PG, Barlogie B, Anderson KC, Sonneveld P, Tosi P, Cavo M, Rajkumar SV, Durie BGM, SanMiguel J. Renal Impairment in Patients With Multiple Myeloma: A Consensus Statement on Behalf of the International Myeloma Working Group. J CLIN ONCOL, 2010. 28:4976-4984. I.F.:17,79. 7 Delforge M, Blade J, Dimopoulos MA, Facon T, Kropff M, Ludwig H, Palumbo A, VanDamme P, San-Miguel JF, Sonneveld P. Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues. LANCET ONCOL, 2010. 11:1086-1095. I.F.:14,47. Editorials I.F.: 27,75 1 Montserrat E. Advances in Biology and Therapy of Chronic Lymphocytic Leukemia Preface. BEST PRACT RES CL HA, 2010. 23:1-2. I.F.:3,13. 2 Moreno C, Montserrat E. Genetic lesions in chronic lymphocytic leukemia: what’s ready for prime time use?. HAEMATOL-HEMATOL J, 2010. 95:12-15. I.F.:6,42. 3 lade J, Rosinol L, Cibeira MT, DeLarrea CF. How to Treat Multiple Myeloma: Thoughts on a Multicentre Survey in Germany. ONKOLOGIE, 2010. 33:577-578. I.F.:1,23. 4 Blade J, Cibeira MT, Rosinol L. Novel drugs for the treatment of multiple myeloma. HAEMATOL-HEMATOL J, 2010. 95:702-704. I.F.:6,42. 5 Blade J, Rosinol L. Refining “total therapy” for myeloma. BLOOD, 2010. 115:4152-4153. I.F.:10,56. AREA 5 Oncology and haematology Hematological oncology Clinical Guidelines I.F.: 4,15 Multicentrics I.F.: 51,46 1 Garcia-Sanz R, Alegre A, Capote 1 FJ, Hernandez JM, Rosinol L, DeLaRubia J, Sureda A, DeArriba F, Bargay J, Mediavilla JD, Garcia-Larana J, Lahuerta JJ, Mateos MV, Prosper F, Miguel JS, Blade J. Guidelines for the use of bisphosphonates in multiple myeloma: Recommendations of the expert committee of the Spanish Myeloma Group from the PETHEMA group. MED CLIN-BARCELONA, 2010. 134:268-278. I.F.:1,23. 2 Palumbo A, Davies F, Kropff M, Blade J, Delforge M, DaCosta FL, Sanz RG, Schey S, Facon T, Morgan G, Moreau P. Consensus guidelines for the optimal management of adverse events in newly diagnosed, transplantineligible patients receiving melphalan and prednisone in combination with thalidomide (MPT) for the treatment of multiple myeloma. ANN HEMATOL, 2010. 89:803-811. I.F.:2,92. Hudson TJ, Anderson W, Aretz A, Barker AD, Bell C, et al. International network of cancer genome projects. NATURE, 2010. 464:993-998. I.F.:34,48. 2 Oriol A, Vives S, Hernandez-Rivas JM, Tormo M, Heras I, Rivas C, Bethencourt C, Moscardo F, Bueno J, Grande C, DelPotro E, Guardia R, Brunet S, Bergua J, Bernal T, Moreno MJ, Calvo C, Bastida P, Feliu E, Ribera JM. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group. HAEMATOL-HEMATOL J, 2010. 95:589-596. I.F.:6,42. 3 Sanz MA, Montesinos P, Rayon C, Holowiecka A, DeLaSerna J, Milone G, DeLisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, Gonzalez J, Diaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, Gonzalez JD, Lowenberg B. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. BLOOD, 2010. 115:5137-5146. I.F.:10,56. Grants for research in progress Cervantes F. European Treatment and Outcome Study for CML. Sponsored by: European Comission (European LeukemiaNet), 07/350. Amount: 90.000,00 euros. Duration: 01/07/2007-30/06/2010. Cervantes F. Red temática de investigación cooperativa de cáncer. Sponsored by: Ministerio Sanidad y Consumo, RD06/0020/0004. Amount: 34.800,00 euros. Duration: 01/01/2007-31/12/2010. Blade J. Red temática de investigación cooperativa de cáncer. Sponsored by: INSTITUTO DE SALUD CARLOS III, RD06/0020/0005. Amount: 181.999,51 euros. Duration: 01/01/2007-31/12/2010. Montserrat E. Red temática de investigación cooperativa de cáncer. Sponsored by: Ministerio Sanidad y Consumo, RD06/0020/0051. Amount: 313.946,32 euros. Duration: 01/01/2007-31/12/2010. Montserrat E. Diseño de un sistema clínico-biológico para el pronóstico de los pacientes con leucemia linfática crónica (LLC). Sponsored by: Instituto Carlos III- Ministerio de Ciencia e Innovación, PI080304. Amount: 225.786,00 euros. Duration: 01/01/2009-31/12/2011. 277 AREA 5 Oncology and haematology Hematological oncology Team Members Montserrat E. Grup de Recerca Consolidat: Unitat Clínico-Biològica per a l’estudi de limfomes i síndromes limproliferatives. Sponsored by: Generalitat de Catalunya. Ajuts a grups de recerca, SGR 1008. Amount: 43.680,00 euros. Duration: 01/01/2009-31/12/2013. Montserrat E. Unitat Clínico-biològica per l’Estudi de Limfomes i Síndromes Limfoproliferatives. Sponsored by: GENERALITAT DE CATALUNYA, 2009_SGR_1008. Amount: 43.680,00 euros. Duration: 23/09/200931/12/2013. Blade J. Impacto de la variabilidad genética individual mediante el análisis de single neucleotide polymorphisms (SNPS) en la respuesta al tratamiento en el mieloma múltiple. Sponsored by: Instituto Carlos III- Ministerio de Ciencia e Innovación, PI080147. Amount: 11.400,00 euros. Duration: 01/01/2009-31/12/2011. Thesis Esteve J. Generación de un índice pronóstico molecular en los enfermos con LMA de riego citogenético intermedio: análisis de mutaciones, nivel de expresión génico y patrón de expresión microRNA. Sponsored by: Instituto Carlos III- Ministerio de Ciencia e Innovación, PI080158. Amount: 138.908,00 euros. Duration: 01/01/2009-31/12/2011. Bosch F. Biología y valor pronóstico del compartimento celular proliferante en la leucemia linfática crónica. Sponsored by: Instituto Carlos IIIMinisterio de Ciencia e Innovación, PI080211. Amount: 228.811,00 euros. Duration: 01/01/2009-31/12/2011. Lopez A. Estudio de la expresión de las citoquinas y receptores de citoquinas en los diferentes tipos de linfomas T periféricos. Correlación con los perfiles genotípicos y significado clinicopatológico. Sponsored by: Instituto Carlos III. Ministerio de Ciencia e Innovación, PI070409. Amount: 193.963,00 euros. Duration: 01/01/2008-31/12/2010. 278 Bosch F. Estudi del fenomen de la transformació histològica en síndromes limfoproliferatives indolents. PhD student: Eva Giné Soca. Cervantes F. Vacunas con células dendríticas y pépticos en el tratamiento de las enfermedades neoplásicas. PhD student: Marta Gomez Nuñez. AREA 5 Team envolved in: Oncology and haematology Red temática de investigación cooperativa de cáncer Physiopathology and molecular bases in hematology Strategic Objectives Group Members TEAM LEADER Dolors Colomer (Hospital Clínic) Tel.: 93 227 54 00 (Ext.: 2269) Fax: 93 227 55 72 E-mail: dcolomer@clinic.ub.es Idibaps members: Josep Lluís Aguilar (Hospital Clínic) Marta Aymerich (Hospital Clínic) Teresa Estrach (Hospital Clínic) Gael Roue (Fundació Clínic) Maria Rozman (Hospital Clínic) Neus Villamor (Hospital Clínic) Joan Lluís Vives Corrons (Hospital Clínic) Patricia Pérez Galán (IDIBAPS) Epidemiological, genetic, molecular and physiopathological study of malignant hematological diseases and erythrocyte pathology. Main Lines of Research 1. Molecular bases of apoptosis regulation induced by drugs in lymphoid neoplasms. Evaluation of new strategies for the treatment of these disorders. 2. Cytological, immunophenotypic and molecular study of malignant hematological diseases. Development of new technologies for the diagnosis and follow-up of minimum residual disease. 3. Promotion of cooperative strategies in the molecular diagnostic setting of leukemias and lymphomas. 4. Design and implementation of internal and external quality control programs. 5. Cutaneous T and B cell lymphomas. Clinical, histopathological and immunophenotypic study. Prognostic factors and epidemiology. 6. Molecular study of the congenital alterations of erythrocytes and of the physiopathological mechanisms intervening in the production and destruction of erythrocytes as a cause of anemia or erythrocytosis. 7. Genetic and epidemiological study of hemoglobin diseases and thalassemias. Postdoctoral fellows: Mónica Lopez (Hospital Clínic, RTICC) Ifigènia Saborit (IDIBAPS) Maria del Mar Mañu (ENERCA) Research Fellows: Laia Rosich (IDIBAPS) Silvia Xargay (Ministerio Ciencia e Innovacion) Roser Mas (Fundació Clínic) Arnau Montraveta (FPI, MICINN) Laura Olaya (ENERCA) Technicians: Sandra Cabezas (Fundació Clínic) Laura Jimenez (IDIBAPS, RTICC) Jocabed Roldan (IDIBAPS, RTICC) Synergism between GX15-070, a BCL-2 protein inhibitor, and bortezomib, a proteosome inhibitor in mantle cell lymphoma (MCL). A) Primary cells of MCL affected patients were incubated with 5 or 10 nM of bortezomib and different doses of GX15-070 (0.1-1 mM) during 18 hours. Cytotoxicity was evaluated by flow cytometry, using annexin V-APC labelling. The associated arrows indicate similar cytotoxicities (cases 4 and 7). The arrows in cases 2 and 9 indicate that incubation with GX15-070 sensitizes the cells to bortezomib. B) Analysis of the expression of Mcl-1, Bak and Noxa via western blot after incubation for 18 h with GX15-070 1 mM and/or bortezomib 5 nM. C) Immunoprecipitation with Mcl-1 and posterior development with Bak and Noxa in cells treated with GX15-070 1 mM and/or bortezomib 5 nM during 5 hours. 279 AREA 5 Oncology and haematology Physiopathology and molecular bases in hematology Team Members PUBLICATIONS Originals I.F.: 78,59 1 Arostegui JI, Saldana MDL, Pascal M, Clemente D, Aymerich M, Balaguer F, Goel A, DelCastillo CF, Rius J, Plaza S, Robledillo JCL, Juan M, Ibanez M, Yague J. A Somatic NLRP3 Mutation as a Cause of a Sporadic Case of Chronic Infantile Neurologic, Cutaneous, Articular Syndrome/ Neonatal-Onset Multisystem Inflammatory Disease Novel Evidence of the Role of Low-Level Mosaicism as the Pathophysiologic Mechanism Under. ARTHRITIS RHEUM-US, 2010. 62:1158-1166. I.F.:7,33. 2 Fernandez V, Salamero O, Espinet B, Sole F, Royo C, Navarro A, Camacho F, Bea S, Hartmann E, Amador V, Hernandez L, Agostinelli C, Sargent RL, Rozman M, Aymerich M, Colomer D, Villamor N, Swerdlow SH, Pileri SA, Bosch F, Piris MA, Montserrat E, Ott G, Rosenwald A, Lopez-Guillermo A, Jares P, Serrano S, Campo E. Genomic and Gene Expression Profiling Defines Indolent Forms of Mantle Cell Lymphoma. CANCER RES, 2010. 70:1408-1418. I.F.:7,54. 3 Gutierrez-Garcia G, Colomo L, Villamor N, Arenillas L, Martinez A, Cardesa T, Garcia-Herrera A, Setoain X, Rodriguez S, Ghita G, Abrisqueta P, Gine E, Bosch F, Campo E, Montserrat E, Lopez-Guillermo A. Clinico-biological characterization and outcome of primary nodal and extranodal diffuse large B-cell lymphoma in the rituximab era. LEUKEMIA LYMPHOMA, 2010. 51:1225-1232. I.F.:2,40. 280 4 Costa D, Valera S, Carrio A, Arias 8 Diaz-Beya M, Rozman M, Pratco- A, Munoz C, Rozman M, Belkaid M, Coutinho R, Nomdedeu B, Campo E. Do we need to do fluorescence in situ hybridization analysis in myelodysplastic syndromes as often as we do?. LEUKEMIA RES, 2010. 34:14371441. I.F.:2,36. rona M, Torrebadell M, Camos M, Aguilar JLI, Esteve J. The prognostic value of multilineage dysplasia in de novo acute myeloid leukemia patients with intermediate-risk cytogenetics is dependent on NPM1 mutational status. BLOOD, 2010. 116:6147-6148. I.F.:10,56. 5 Gine E, Martinez A, Villamor N, Lopez-Guillermo A, Camos M, Martinez D, Esteve J, Calvo X, Muntanola A, Abrisqueta P, Rozman M, Rozman C, Bosch F, Campo E, Montserrat E. Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia (“accelerated” chronic lymphocytic leukemia) with aggressive clinical behavior. HAEMATOL-HEMATOL J, 2010. 95:1526-1533. I.F.:6,42. 6 DeLarrea CF, Rosinol L, Cibeira MT, Rozman M, Rovira M, Blade J. Extensive soft-tissue involvement by plasmablastic myeloma arising from displaced humeral fractures. EUR J HAEMATOL, 2010. 85:448-451. I.F.:2,35. 7 Cervantes F, Lopez-Garrido P, Montero MI, Jonte F, Martinez J, Hernandez-Boluda JC, Calbacho M, Sureda A, Perez-Rus G, Nieto JB, Perez-Lopez C, Roman-Gomez J, Gonzalez M, Pereira A, Colomer D. Early intervention during imatinib therapy in patients with newly diagnosed chronic-phase chronic myeloid leukemia: a study of the Spanish PETHEMA group. HAEMATOL-HEMATOL J, 2010. 95:1317-1324. I.F.:6,42. 9 Lopez-Royuela N, Perez-Galan P, Galan-Malo P, Yuste VJ, Anel A, Susin SA, Naval J, Marzo I. Different contribution of BH3-only proteins and caspases to doxorubicin-induced apoptosis in p53-deficient leukemia cells. BIOCHEM PHARMACOL, 2010. 79:1746-1758. I.F.:4,25. 10 Gulbis B, Eleftheriou A, Angastiniotis M, Ball S, Surralles J, Castella M, Heimpel H, Hill A, Corrons JLV. Epidemiology of Rare Anaemias in Europe. ADV EXP MED BIOL, 2010. 686:375-396. I.F.:2,02. 11 White HE, Matejtschuk P, Rigsby P, Gabert J, Lin F, Wang YL, Branford S, Muller MC, Beaufils N, Beillard E, Colomer D, Dvorakova D, Ehrencrona H, Goh HG, ElHousni H, Jones D, Kairisto V, Kamel-Reid S, Kim DW, Langabeer S, Ma ESK, Press RD, Romeo G, Wang LH, Zoi K, Hughes T, Saglio G, Hochhaus A, Goldman JM, Metcalfe P, Cross NCP. Establishment of the first World Health Organization International Genetic Reference Panel for quantitation of BCR-ABL mRNA. BLOOD, 2010. 116:E111-E117. I.F.:10,56. 12 Muniesa C, Estrach T, Pujol RM, Gallardo F, Garcia-Muret P, Climent J, Servitje O. Folliculotropic mycosis fungoides: Clinicopathological features and outcome in a series of 20 cases. J AM ACAD DERMATOL, 2010. 62:418-426. I.F.:4,11. AREA 5 Oncology and haematology Physiopathology and molecular bases in hematology 13 Mollinedo F, DeLaIglesia-Vicente J, Gajate C, DeMendoza AEH, Villa-Pulgarin JA, DeFrias M, Roue G, Gil J, Colomer D, Campanero MA, Blanco-Prieto MJ. In vitro and In vivo Selective Antitumor Activity of Edelfosine against Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia Involving Lipid Rafts. CLIN CANCER RES, 2010. 16:2046-2054. I.F.:6,75. 14 Salgado R, Servitje O, Gallardo F, Vermeer MH, Ortiz-Romero PL, Karpova MB, Zipser MC, Muniesa C, Garcia-Muret MP, Estrach T, Salido M, Sanchez-Schmidt J, Herrera M, Romagosa V, Suela J, Ferreira BI, Cigudosa JC, Barranco C, Serrano S, Dummer R, Tensen CP, Sole F, Pujol RM, Espinet B. Oligonucleotide Array-CGH Identifies Genomic Subgroups and Prognostic Markers for Tumor Stage Mycosis Fungoides. J INVEST DERMATOL, 2010. 130:1126-1135. I.F.:5,54. Reviews I.F.: 7,64 1 Saborit-Villarroya I, Roue G, Lopez-Guerra M, Alonso R, XargayTorrent S, Rosich L, Colomer D. Cell Death Targeting Therapies in B Lymphoid Malignancies. CURR DRUG TARGETS, 2010. 11:769-780. I.F.:3,93. 2 Lopez-Guerra M, Colomer D. NF-kappa B as a therapeutic target in chronic lymphocytic leukemia. EXPERT OPIN THER TAR, 2010. 14:275288. I.F.:3,71. Grants for research in progress Aymerich M. Desarrollo de un biobanco para muestras biológicas prospectivas de pacientes oncológicos como soporte a la investigación biomédica. Sponsored by: Ministerio Sanidad y Consumo, PI070301. Amount: 153.428,00 euros. Duration: 26/11/2007-30/12/2010. Colomer D. Red temática de investigación cooperativa de cáncer. Sponsored by: Ministerio Sanidad y Consumo, RD06/0020/0014. Amount: 127.900,46 euros. Duration: 01/01/2007-31/12/2010. Colomer D. Utilización de terapias selectivas contra rutas de señalización desreguladas en neoplasias linfoides. Mecanismos de acción y estrategias de sensibilización. Sponsored by: MINISTERIO DE EDUCACIÓN, SAF2009_09503. Amount: 254.100,00 euros. Duration: 01/01/201031/12/2012. Vives JL. Creation of a catalan network for the diagnosis and clinical management of rare anemias due to major haemoglobinopathies. Sponsored by: FUNDACIÓ LA MARATÓ DE TV3, 101730. Amount: 168.795,00 euros. Duration: 14/12/2010-13/12/2013. Vives JL. European Reference Network of Expert Centres in Rare Anaemias . Sponsored by: European Commission- Executive Agency for Health and Consumers, 2008 12 10. Amount: 1.193.799,97 euros. Duration: 01/06/2009-31/05/2012. Colomer D. Dianes terapèutiques i noves tècniques diagnòstiques en neoplasies limfoides. Sponsored by: Generalitat de Catalunya, 2009_ SGR_967. Amount: 43.680,00 euros. Duration: 15/09/2009-31/12/2013. Roue G. Identificación de nuevas dianas terapéuticas para mejorar la actividad de VELCADE TM en el linfoma de células del manto. Sponsored by: ISCIII, CP07/00072. Amount: 42.000,00 euros. Duration: 01/01/2007-31/12/2010. Roue G. Identificación de nuevas dianas terapéuticas para mejorar la actividad del velcade en el linfoma de células del manto. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/0060. Amount: 99.825,00 euros. Duration: 01/01/2010-31/12/2012. 281 AREA 5 Team envolved in: Oncology and haematology Determinantes genéticos y ambientales de la disfunción vascular (HERACLES) Hemotherapy – hemostasis Group Members TEAM LEADER Ginés Escolar (Hospital Clínic) Tel.: 93 227 54 00 (Ext.: 2306) E-mail: gescolar@clinic.ub.es Idibaps members: Antonio Ordinas (Hospital Clínic) Maribel Díaz-Ricart (Hospital Clínic) Ana M. Galán (Fundació Clínic) Pablo García de Frutos (CSIC) Miquel Lozano (Hospital Clínic) Anna M. Merino (Hospital Clínic) Joan Monteagudo (Hospital Clínic) Arturo Pereira (Hospital Clínic) Juan Carles Reverter (Hospital Clínic) Cristina Ch. Sanz (Hospital Clínic) M. Dolors Tàssies (Hospital Clínic) Postdoctoral fellows: Irene López-Vilchez (IDIBAPS) Research Fellows: Marta Palomo de Udaeta (Fundació Clínic) Carolina Caballo Gordillo (Fundació Clínic) Strategic Objectives Main Lines of Research 1. Study of the basic mechanisms regulating blood cell function and of the interactions between such cells, with the vascular wall, and with other cells. 2. Evaluation of congenital and acquired defects in hemostasis and their pharmacological and/or transfusional correction. 3. Laboratory characterization of bleeding and thrombotic phenotypes and genotypes. 4. Analysis of the efficacy and safety of new strategies for sparing blood component transfusions. 5. Development and evaluation of the efficacy of synthetic platelet substitutes. 6. Characterization of animal models of hemostasis, preferentially in mice. 1. Study of the mechanisms involved in the development of bleeding and thrombotic disorders. Proteomic study for determining the changes in the vascular system and in the different blood cells in thrombotic and bleeding disorders. 2. Evaluation of the physiological and pathological implications of circulating and/or intraplatelet tissue factor in atherothrombosis. 3. Characterization of endothelial dysfunction as a common factor in the development of complications associated with multiple diseases. A physiological, biochemical and proteomic approach. 4. New therapeutic measures in autoimmune diseases of a fundamentally humoral character. Incompatible ABO kidney transplantation as a model. 5. Evaluation of the participation of serotoninergic and purinergic mechanisms in platelet function. Study of the antithrombotic potential of pharmacological inhibitors. 6. Role of the phenotype/genotype of fibrinolysis and its repercussions upon global or specific functional tests in hemorrhagic and thrombotic pathology. 7. Study of the GAS6 vitamin K-dependent protein in hemostasis and the vascular wall, using knockout mice for this gene. Technicians: Marc Pino (Hospital Clínic) Patricia Molina Moreno (Fundació Clínic) Collaborators: Rosa Brugués (Hospital Clínic) Gabriela Gutiérrez (Hospital Clínic) M.Rosa Hernández (Fundació Clínic) Josep M. Jou (Hospital Clínic) Begoña Hurtado Villarejo (JAEDOC-CSIC) Cristina Aresté (JAEDOC-CSIC) Joan Cid Vidal (Hospital Clínic) Eduardo Arellano Rodrigo (Hospital Clínic) 282 Ultrastructural studies of washed platelets exposed to microvesicles rich in FT (MV-FT). A) Resting platelets. B) After the first minute of activation with MV-FT, the latter are found in different sizes within the open platelet canalicular system (arrow), and platelet activation is observed with loss of shape and signs of partial degranulation. C) After 5 minutes, the platelets return to their resting state, but retain the internalized MV-FT. AREA 5 Oncology and haematology Hemotherapy – hemostasis PUBLICATIONS Originals I.F.: 93,91 1 Martinez-Zamora MA, Tassies D, Carmona F, Espinosa G, Cerverac R, Reverter JC, Balasch J. Clot lysis time and thrombin activatable fibrinolysis inhibitor in severe preeclampsia with or without associated antiphospholipid antibodies. J REPROD IMMUNOL, 2010. 86:133-140. I.F.:2,52. 2 Smithson A, Perello R, Aibar J, Espinosa G, Tassies D, Freire C, Castro P, Suarez B, Lozano F, Nicolas JM. Genotypes Coding for Low Serum Levels of MannoseBinding Lectin Are Underrepresented among Individuals Suffering from Noninfectious Systemic Inflammatory Response Syndrome. CLIN VACCINE IMMUNOL, 2010. 17:447-453. I.F.:2,37. 3 Basora M, Pereira A, Soriano A, Martinez-Pastor JC, Sanchez-Etayo G, Tio M, Salazar F. Allogeneic blood transfusion does not increase the risk of wound infection in total knee arthroplasty. VOX SANG, 2010. 98:124-129. I.F.:2,59. 4 Rigol M, Solanes N, Farre J, Roura S, Roque M, Berruezo A, Bellera N, Novensa L, Beng DT, Prat-Vidal C, Huzman MA, Batlle M, Hoefsloot M, Sitges M, Ramirez J, Dantas AP, Merino A, Sanz G, Brugada J, Bayes-Genis A, Heras M. Effects of Adipose Tissue-Derived Stem Cell Therapy After Myocardial Infarction: Impact of the Route of Administration. J CARD FAIL, 2010. 16:357-366. I.F.:3,25. 5 Diaz-Ricart M, Brunso L, Pino M, Navalon F, Jou JM, Heras M, White JG, Escolar G. Preanalytical treatment of EDTA-anticoagulated blood to ensure stabilization of the mean platelet volume and component measured with the ADVIA counters. THROMB RES, 2010. 126:E30-E35. I.F.:2,41. 6 Oppenheimer F, Revuelta I, Serra N, Lozano M, Gutierrez-Dalmau A, Esforzado N, Cofan F, Ricart MJ, Torregrosa JV, Crespo M, Paredes D, Martorell J, Alcaraz A, Campistol JM. ABO incompatible living donor kidney transplantation: a dream come true. Experience of Hospital Clinic of Barcelona. NEFROLOGIA, 2010. 30:54-63. I.F.:0,53. 7 Martinez-Zamora MA, Creus M, Tassies D, Bove A, Reverter JC, Carmona F, Balasch J. Thrombin activatable fibrinolysis inhibitor and clot lysis time in women with recurrent miscarriage associated with the antiphospholipid syndrome. FERTIL STERIL, 2010. 94:2437-2440. I.F.:3,97. 8 Llacuna L, Barcena C, BellidoMartin L, Fernandez L, Stefanovic M, Mari M, Garcia-Ruiz C, FernandezCheca JC, DeFrutos PG, Morales A. Growth Arrest-Specific Protein 6 Is Hepatoprotective Against Murine Ischemia/Reperfusion Injury. HEPATOLOGY, 2010. 52:1371-1379. I.F.:10,84. 9 Gomez-Gil E, Navines R, DeOsaba MJM, Diaz-Ricart M, Escolar G, Salamero M, Martin-Santos R, Galan A, Gasto C. Hormonal responses to the 5-HT1A agonist buspirone in remitted endogenous depressive patients after long-term imipramine treatment. PSYCHONEUROENDOCRINO, 2010. 35:481-489. I.F.:4,19. 10 Moreno C, Hodgson K, Ferrer G, Elena M, Filella X, Pereira A, Baumann T, Montserrat E. Autoimmune cytopenia in chronic lymphocytic leukemia: prevalence, clinical associations, and prognostic significance. BLOOD, 2010. 116:47714776. I.F.:10,56. 11 Palomo M, Diaz-Ricart M, Carbo C, Rovira M, Fernandez-Aviles F, Martine C, Ghita G, Escolar G, Carreras E. Endothelial Dysfunction after Hematopoietic Stem Cell Transplantation: Role of the Conditioning Regimen and the Type of Transplantation. BIOL BLOOD MARROW TR, 2010. 16:985-993. I.F.:3,15. 12 Carreras E, Fernandez-Aviles F, Silva L, Guerrero M, DeLarrea CF, Martinez C, Rosinol L, Lozano M, Marin P, Rovira M. Engraftment syndrome after auto-SCT: analysis of diagnostic criteria and risk factors in a large series from a single center. BONE MARROW TRANSPL, 2010. 45:1417-1422. I.F.:3,00. 13 DeLarrea CF, Martinez C, Gaya A, Lopez-Guillermo A, Rovira M, Fernandez-Aviles F, Lozano M, Bosch F, Esteve J, Nomdedeu B, Montserrat E, Carreras E. Salvage chemotherapy with alternating MINE-ESHAP regimen in relapsed or refractory Hodgkin’s lymphoma followed by autologous stem-cell transplantation. ANN ONCOL, 2010. 21:1211-1216. I.F.:5,65. 14 Cervantes F, Lopez-Garrido P, Montero MI, Jonte F, Martinez J, Hernandez-Boluda JC, Calbacho M, Sureda A, Perez-Rus G, Nieto JB, Perez-Lopez C, Roman-Gomez J, Gonzalez M, Pereira A, Colomer D. Early intervention during imatinib therapy in patients with newly 283 AREA 5 Oncology and haematology Hemotherapy – hemostasis Team Members diagnosed chronic-phase chronic myeloid leukemia: a study of the Spanish PETHEMA group. HAEMATOL-HEMATOL J, 2010. 95:13171324. I.F.:6,42. 15 Alvarez-Larran A, Cervantes F, Pereira A, Arellano-Rodrigo E, Perez-Andreu V, Hernandez-Boluda JC, Ayats R, Salvador C, Muntanola A, Bellosillo B, Vicente V, Hernandez-Nieto L, Burgaleta C, Xicoy B, Besses C. Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in lowrisk essential thrombocythemia. BLOOD, 2010. 116:1205-1210. I.F.:10,56. 16 Hurtado B, Abasolo N, Munoz X, Garcia N, Benavente Y, Rubio F, DeFrutos PG, Krupinski J, Sala N. Association study between polymorphims in GAS6-TAM genes and carotid atherosclerosis. THROMB HAEMOSTASIS, 2010. 104:592-598. I.F.:4,45. 17 Reesink HW, Panzer S, Mcquilten ZK, Wood EM, Marks C, Wendel S, Trigo F, Biagini S, Olyntho S, Devine DV, Mumford I, Cazenave JP, Rasongles P, Garraud O, Richard P, Schooneman F, Vezon G, AlRadwan R, Brand A, Hervig T, Castro E, Lozano M, Navarro L, Puig L, Almazan C, Maclennan S, Cardigan R, Franklin IM, Prowse C. Pathogen inactivation of platelet concentrates. VOX SANG, 2010. 99:85-95. I.F.:2,59. 284 18 Pellitero S, Reverter JL, Tassies D, Pizarro E, Monteagudo J, Salinas I, Aguilera E, Sanmarti A, Reverter JC. Polymorphisms in platelet glycoproteins Ia and IIIa are associated with arterial thrombosis and carotid atherosclerosis in type 2 diabetes. THROMB HAEMOSTASIS, 2010. 103:630-637. I.F.:4,45. 19 Lozano M, Heddle N, Williamson LM, Wang G, Aubuchon JP, Dumont LJ. Practices associated with ABO-incompatible platelet transfusions: a BEST Collaborative international survey. TRANSFUSION, 2010. 5:1743-1748. I.F.:2,98. 20 Tadokoro K, Reesink HW, Panzer S, Chabanel A, Santailler G, Guerin T, Socquet D, David B, Labrune JL, Lin CK, Tsoi WC, Letowska M, Antoniewicz-Papis J, Naniewicz J, Dudziak K, Lachert E, Lozano M, Schneider K, Snyder EL, Champion MH. Problems with irradiators. VOX SANG, 2010. 98:7884. I.F.:2,59. 21 Sanz C, Ghita G, Franquet C, Martinez I, Pereira A. Red-bloodcell alloimmunization and female sex predict the presence of HLA antibodies in patients undergoing liver transplant. VOX SANG, 2010. 99:261-266. I.F.:2,59. 22 Brunso L, Segura D, Monreal L, Escolar G, White JG, Diaz-Ricart M. The secretory mechanisms in equine platelets are independent of cytoskeletal polymerization and occur through membrane fusion. PLATELETS, 2010. 21:658-666. I.F.:2,27. Editorials I.F.: 7,91 1 Beya MD, Pereira A, Merino A. Erythrophagocytosis in cold agglutinin disease. TRANSFUSION, 2010. 50:2310-2310. I.F.:2,98. 2 Hurtado B, DeFrutos PG. GAS6 in systemic inflammatory diseases: with and without infection. CRIT CARE, 2010. 14:-. I.F.:4,93. Multicentrics I.F.: 2,98 1 Cazenave JP, Follea G, Bardiaux L, Boiron JM, Lafeuillade B, Debost M, Lioure B, Harousseau JL, Tabrizi R, Cahn JY, Michallet M, Ambruso D, Schots R, Tissot JD, Sensebe L, Kondo T, Mccullough J, Rebulla P, Escolar G, Mintz P, Heddle NM, Goodrich RP, Bruhwyler J, Le C, Cook RJ, Stouch B. A randomized controlled clinical trial evaluating the performance and safety of platelets treated with MIRASOL pathogen reduction technology. TRANSFUSION. 50:2362-2375. I.F.:2,98. AREA 5 Oncology and haematology Hemotherapy – hemostasis Grants for research in progress Reverter JC. Cancer y Tromboembolismo: Importancia de la generación de trombina relacionada con las micropartículas procoagulantes circulantes y los polimorfirmos de las mismas en el desarrollo de trombosis en los pacientes de cancer. Sponsored by: Ministerio Sanidad y Consumo, PI070387. Amount: 106.480,00 euros. Duration: 26/11/2007-30/12/2010. Galan A. Desarrollo de preparaciones con actividad hemostática como alternativa a la transfusión plaquetaria y al tratamiento procoagulante. Sponsored by: Ministerio de Educación y Ciencia, PET2007-0169. Amount: 147.015,00 euros. Duration: 12/09/2008-11/09/2010. Escolar G. Red HERACLES: Determinantes genéticos y ambientales de la disfunción vascular. Sponsored by: Instituto de Salud Carlos III, RD06/0009/1003. Amount: 40.133,94 euros. Duration: 29/02/2008-31/12/2010. Escolar G. Desarrollo de modelos de coagulopatía dilucional y evaluación comparativa de eficacia correctora con distintos concentrados de factores de la coagulación. Sponsored by: Ministerio de Ciencia e Innovación, PET2008-0231. Amount: 77.440,00 euros. Duration: 01/03/200928/02/2011. García P. Mecanismos de activación plaquetar en la interacción plaquetaendotelio. Sponsored by: Ministerio de Educación y Ciencia. Programa Nacional de Biología Fundamental, BFU2007-61699/BFI. Amount: 142.780,00 euros. Duration: 01/01/2008-31/12/2010. Marin PJ. Adaptación de la zona blanca del Hospital Clínic de Barcelona a las Normas de Correcta Fabricación de Medicamentos de Uso Humano. Sponsored by: Ministerio de Ciencia e Innovación, PLE09-135 . Amount: 360.000,00 euros. Duration: 01/01/2010-31/12/2010. Galan A. El sistema serotoninérgico: una concexión entre los mecanismos de la depresión mayor, la inflamación y el riesgo cardiovascular. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/0664. Amount: 79.860,00 euros. Duration: 01/01/201031/12/2012. Escolar G. Papel de Los receptores ligados a proteína G y los mecanismos de señalización mediados por kinasas en la internalización y expresión del factor tisular por plaquetas: Implicaciones en la trombogénesis. Sponsored by: MINISTERIO DE EDUCACIÓN, SAF2009_10365. Amount: 145.200,01 euros. Duration: 01/01/2010-31/12/2012. García P. Thrombus stabilization as therapeutic target: from in vitro studies to animal models. Sponsored by: Fundació Marató de TV3, 0000. Amount: 291.125,00 euros. Duration: 01/01/2009-31/12/2011. 285 AREA 5 Team envolved in: Oncology and haematology Red temática de investigación cooperativa de cáncer Molecular and translational oncology Strategic Objectives Group Members TEAM LEADER Dr. Pere Gascón Vilaplana (Hospital Clínic) Tel.: 93 227 54 02 Fax: 93 454 65 20 E-mail: gascon@clinic.ub.es Idibaps members: Juan José Grau (Hospital Clínic) Joan Maurel (Hospital Clínic) Begoña Mellado (Hospital Clínic) Núria Viñolas (Hospital Clínic) Cristina Nadal (Hospital Clínic) Reguart, Noemí (Hospital Clínic) Muñoz, Montserrat (Hospital Clínic) Vanessa Almendro (IDIBAPS) Postdoctoral fellows: Anna Vidal (Fundació Clínic) Technicians: Raquel Longarón (Fundació Clínic) Eva Maria Pastor (Fundació Clínic) Mireia Parés Guerrero (Fundació Clínic) Laia Viñals Galí (Fundació Clínic) Nursing Staff: Àngels Olivera (Hospital Clínic) Administrative Staff: Marta Digón (Hospital Clínic) 286 Collaborators: Elisabet Ametller (Fundació Clínic) Jordi Codony (Fundació Clínic) Susana Garcia Recio (Fundació Clínic) Cristina Mayordomo (Fundació Bosch i Gimpera) Mercedes Marin (Fundació Clínic) Laura Vidal (Hospital Clínic) Laura Visa (Hospital Clínic, Emili Letang) Xabier García-Albéniz (Hospital Clínic, Josep Font) Estela Pineda (Hospital Clínic, Emili Letang) Jordi Alcaraz (Unitat Biofísica i Bioenginyeria, UB) Ana Arance (Hospital Clínic) The strategic objectives of the laboratory are centered in three fields: 1. A purely scientific area corresponding to the consolidation of the investigational lines and groups that work in each of them. 2. A second area corresponding to the obtainment of aids and funding for research, in order to ensure the good functioning of the laboratory. 3. A third area established in recent years aims to expand the laboratory - this process being completed this year with the transfer to the new CEK Building. This will make it possible to contract new investigators needed for the laboratory research objectives. The first of the mentioned areas (scientific) comprises a qualitative and quantitative increase in scientific production. In particular, the colorectal and breast cancer stem cell lines are in their early stages. Both the subject and the quality of research can attract investigators interested in a stay, in preparing a doctoral thesis, or in becoming part of the laboratory personnel. In this sense we have incorporated three new biologists into the group. As regards the second area (funding of research), we must continue with the same criterion established years ago in order to ensure the continuity of all the research lines and facilitate the recruitment/contracting of new personnel members. At present, the laboratory has four FISS grants (2007, 2008, 2009, 2009), Networks funding from the Carlos III Institute, three aids from the Spanish Association Against Cancer (2007, 2008, 2009), and different research grants from the CELLEX Foundation. Main Lines of Research 1. Tumor chemoresistance mechanisms. 1.1. Resistance mechanisms in colorectal cancer linked to the AREA 5 Oncology and haematology Molecular and translational oncology extrinsic apoptotic pathway, in vitro and in vivo (Joan Maurel). 1.2. Change in Fas receptor signaling during the acquisition of chemoresistance in colon cancer (Vanessa Almendro; Susana Garcia; Elisabet Ametller). 1.3. Epithelial-mesenchymal transition and resistance to chemotherapy (Elisabet Ametller; Vanessa Almendro; Cristina Mayordomo). 1.4. Resistance to antitumor drugs in head and neck cancer (Principal investigator: Juan J. Grau. Collaborators: Carmen Muñoz; Miguel Caballero; Andrea Tagliapietra; Mariano Monzó). 1.5. Electrochemotherapy in solid tumors. Study of electroporation. (Principal investigator: Juan J. Grau. Collaborators: Carmen Muñoz; Miguel Caballero. 1.6. Implication of IGF-1R and MMP-7 in the mechanisms of resistance to chemotherapy and antibodies against tyrosine kinase receptors. Therapeutic strategies for the reversal of chemoresistance (IDIBAPS: Joan Maurel; Jordi Codony; Mercedes Marín. Germans Trias i Pujol Hospital: Albert Abad; Eva Martínez; Anna Martínez). 1.7. Characterization of the role of MMP-7 in resistance to bevacizumab in colon cancer (Joan Maurel; Estela Pineda; Jordi Codony; Mercedes Marín; Cristobal Mezquita; Jovita Mezquita; Betlem Mezquita). 1.8. Platform in orthotopic murine platforms characterized by the study of new drugs in pancreatic cancer (IDIBAPS: Joan Maurel; Pere Gascón; Salvador Navarro; David Fuster; Rosa Miquel; Jordi Codony. University of Barcelona: Adela Mazo; Sandra Pérez-Torras; Anna Vidal-Pla; Nerea Urtasun. CETIR: Yolanda González;Ignasi Carrió). 2. Stem cells, microenvironment and mechanisms of metastasis. 2.1. Implications of substance P in the regulation of avb3 and a5b1 3. 4. 5. 6. 7. 8. 9. in breast cancer cell lines (Pere Gascón; Vanessa Almendro; Susana Garcia). 2.2. Interaction between GPCRs and RTKs (Vanessa Almendro; Elisabet Ametller; Susana Garcia). 2.3. Role of the PPT-I gene in the metastatic process (Pere Gascón; Vanessa Almendro; Cristina Mayordomo; Elisabet Ametller). 2.4. Pre-angiogenic micrometastases of circulating cells (Cristina Nadal). 2.5. Mechanisms of liver metastasis in colorectal cancer (Cristina Nadal). Pharmacodynamic studies and prediction of therapeutic response. 3.1. Predictive and pharmacodynamic study of the response to neoadjuvant chemotherapy in prostate cancer. (Begoña Mellado). 3.2. Mechanisms and markers of chemoresistance in prostate cancer. Therapeutic strategies for the reversal of chemoresistance. (Begoña Mellado; Jordi Codony; Mercedes Marín). Study on the determination and characterization of circulating tumor cells. 4.1. In prostate cancer (Begoña Mellado). 4.2. In breast cancer (Montse Muñoz; Xavier González). Micro-RNAs in the development and prognosis of non-small cell lung cancer. Nuria Viñolas. Study of the tumor and stroma interactions in non-small cell lung cancer (NSCLC): role of fibroblasts associated with cancer in NSCLC. N. Reguart; J. Alcaraz; Marta Puig. Effect of anomalous hardening of tumor tissue in NSCLC. J. Alcaraz; N. Reguart; Marta Puig. Study of sensitivity to trastuzumab in relation to the expression of topoisomerase I. Xavi González; Montse Muñoz; Ana Arance. Characterization of the metastatic profile of malignant melanoma in circulating cells and primary tumors. Ana Arance; Laura Visa. PUBLICATIONS Originals I.F.: 131,60 1 Gomez-Caro A, Garcia S, Reguart N, Arguis P, Sanchez M, Gimferrer JM, Marrades R, Lomena F. Incidence of occult mediastinal node involvement in cNO non-small-cell lung cancer patients after negative uptake of positron emission tomography/computer tomography scan. EUR J CARDIO-THORAC, 2010. 37:1168-1174. I.F.:2,40. 2 Molina R, Auge JM, Escudero JM, Filella X, Zanon G, Pahisa J, Farrus B, Munoz M, Velasco M. Evaluation of tumor markers (HER-2/neu oncoprotein, CEA, and CA 15.3) in patients with locoregional breast cancer: prognostic value. TUMOR BIOL, 2010. 31:171-180. I.F.:1,94. 3 Sanjuan A, Escaramis G, Vidal-Sicart S, Illa M, Zanon G, Pahisa J, Rubi S, Velasco M, Santamaria G, Farrus B, Munoz M, Garcia Y, Fernandez PL, Pons F. Predicting Non-Sentinel Lymph Node Status in Breast Cancer Patients with Sentinel Lymph Node Involvement: Evaluation of Two Scoring Systems. BREAST J, 2010. 16:134-140. I.F.:1,61. 4 Casas F, Borras JM, Ferrer F, Guanyabens N, Gutierrez R, Leon C, Lopez J, Mellado B, Morote J, Puig J, Ribal J, Serra A, Valls V, Zapatero A. Evidencebased consensus recommendations to improve the quality of life in prostate cancer treatment. CLIN TRANSL ONCOL, 2010. 12(5):346-355. I.F.:1,15. 5 Maurel J, Martins AS, Poveda A, Lopez-Guerrero JA, Cubedo R, Casado A, Martinez-Trufero J, Ayuso JR, LopezPousa A, Garcia-Albeniz X, DelMuro XG, DeAlava E. Imatinib Plus Low-Dose Doxorubicin in Patients With Advanced Gastrointestinal Stromal Tumors Refractory to High-Dose Imatinib A Phase 287 AREA 5 Oncology and haematology Molecular and translational oncology Team Members I-II Study by the Spanish Group for Research on Sarcomas. CANCER-AM CANCER SOC, 2010. 116:3692-3701. I.F.:5,42. 6 Martin M, Segui MA, Anton A, Ruiz A, Ramos M, Adrover E, Aranda I, Rodriguez-Lescure A, Grosse R, Calvo L, Barnadas A, Isla D, DelPrado PM, Borrego M, Zaluski J, Arcusa A, Munoz M, Vega JM, Mel JR, Munarriz B, Llorca C, Jara C, Alba E, Florian J, Li JF, Garcia-Asenjo JA, Saez A, Rios M, Almenar S, Peiro G, Lluch A. Adjuvant Docetaxel for High-Risk, Node-Negative Breast Cancer.. NEW ENGL J MED, 2010. 363:2200-2210. I.F.:47,05. 7 Gascon P, Fuhr U, Sorgel F, KinzigSchippers M, Makhson A, Balser S, Einmahl S, Muenzberg M. Development of a new G-CSF product based on biosimilarity assessment. ANN ONCOL, 2010. 21:1419-1429. I.F.:5,65. 8 Gascon P, Pirker R, DelMastro L, Durrwell L. Effects of CERA (continuous erythropoietin receptor activator) in patients with advanced non-small-cell lung cancer (NSCLC) receiving chemotherapy: results of a phase II study. ANN ONCOL, 2010. 21:2029-2039. I.F.:5,65. 9 Arnal-Estape A, Tarragona M, Morales M, Guiu M, Nadal C, Massague J, Gomis RR. HER2 Silences Tumor Suppression in Breast Cancer Cells by Switching Expression of C/EBP beta Isoforms. CANCER RES, 2010. 70:9927-9936. I.F.:7,54. 10 Maio M, Mackiewicz A, Testori A, Trefzer U, Ferraresi V, Jassem J, Garbe C, Lesimple T, Guillot B, Gascon P, Gilde K, Camerini R, Cognetti F. Large Randomized Study of Thymosin alpha 1, Interferon Alfa, or Both in Combination With Dacar- 288 bazine in Patients With Metastatic Melanoma. J CLIN ONCOL, 2010. 28:1780-1787. I.F.:17,79. 11 Rojo F, Gracias E, Villena N, Cruz T, Corominas JM, Corradino I, Cedeno M, Campas C, Osorio M, Iznaga N, Bellosillo B, Rovira A, Marsoni S, Gascon P, Serrano S, Sessa C, Crombet T, Albanell J. Pharmacodynamic Trial of Nimotuzumab in Unresectable Squamous Cell Carcinoma of the Head and Neck: A SENDO Foundation Study. CLIN CANCER RES, 2010. 16:2474-2482. I.F.:6,75. 12 Fernandez-Martos C, Pericay C, Aparicio J, Salud A, Safont M, Massuti B, Vera R, Escudero P, Maurel J, Marcuello E, Mengual JL, Saigi E, Estevan R, Mira M, Polo S, Hernandez A, Gallen M, Arias F, Serra J, Alonso V. Phase II, Randomized Study of Concomitant Chemoradiotherapy Followed by Surgery and Adjuvant Capecitabine Plus Oxaliplatin (CAPOX) Compared With Induction CAPOX Followed by Concomitant Chemoradiotherapy and Surgery in Magnetic Resonance Imaging-Defined, L. J CLIN ONCOL, 2010. 28:859-865. I.F.:17,79. 13 Trabal J, Leyes P, Forga M, Maurel J. Potential usefulness of an EPA-enriched nutritional supplement on chemotherapy tolerability in cancer patients without overt malnutrition. NUTR HOSP, 2010. 25:736-740. I.F.:1,07. 14 Martin-Broto J, Gutierrez A, Garcia-Del-Muro X, Lopez-Guerrero JA, Martinez-Trufero J, DeSande LM, Lainez N, Maurel J, DeJuan A, Losa F, Andres R, Casado A, Tejido PG, Blanco R, Carles J, Bellmunt J, Gomez-Espana A, Ramos R, MartinezSerra J, Llombart-Bosch A, Poveda A. Prognostic time dependence of deletions affecting codons 557 and/or 558 of KIT gene for relapse-free survival (RFS) in localized GIST: a Spanish Group for Sarcoma Research (GEIS) Study. ANN ONCOL, 2010. 21:15521557. I.F.:5,65. 15 Ametller E, Garcia-Recio S, Costamagna D, Mayordomo C, Fernandez-Nogueira P, Carbo N, PastorArroyo EM, Gascon P, Almendro V. Tumor promoting effects of CD95 signaling in chemoresistant cells. MOL CANCER, 2010. 9:-. I.F.:4,16. Reviews I.F.: 10,37 1 Tusquets I, Garcia-Estevez L, Adrover E, Calvo L, Alvarez I, Mata JG, Fernandez Y, Margueli M, Segui MA, Rodriguez C, Lescure AR, Colomer R, Gascon P, Martin M, Alba E, Barnadas A, Llombart A, Albanell J, Lluch A. Current controversies in the management of breast cancer. CLIN TRANSL ONCOL, 2010. 12:278-286. I.F.:1,15. 2 Estevez LG, Alvarez I, Segui MA, Munoz M, Margeli M, Miro C, Rubio C, Lluch A, Tusquets I. Current perspectives of treatment of ductal carcinoma in situ. CANCER TREAT REV, 2010. 36:507-517. I.F.:5,30. 3 Almendro V, Garcia-Recio S, Gascon P. Tyrosine Kinase Receptor Transactivation Associated to G Protein-Coupled Receptors. CURR DRUG TARGETS, 2010. 11:11691180. I.F.:3,93. Editorials I.F.: 0,76 1 Munoz M, Pahisa J, Caparros FX, Vidal-Sicart S. Sentinel lymph node and neoadjuvant therapy in breast cancer. REV ESP MED NUCL, 2010. 29:319-320. I.F.:0,77. AREA 5 Oncology and haematology Molecular and translational oncology Clinical Guidelines I.F.: 2,46 1 Navarro S, Vaquero E, Maurel J, Bombi JA, DeJuan C, Feliu J, Cruz LF, Gines A, Girela E, Rodriguez R, Sabater L. Recommendations for diagnosis, staging and treatment of pancreatic cancer (Part I). Grupo Español de Consenso en Cáncer de Páncreas.. MED CLIN-BARCELONA, 2010. 134:643-655. I.F.:1,23. 2 Navarro S, Vaquero E, Maurel J, Bombi JA, DeJuan C, Feliu J, Cruz LF, Gines A, Girela E, Rodriguez R, Sabater L. Recommendations for diagnosis, staging and treatment of pancreatic cancer (Part II). MED CLIN-BARCELONA, 2010. 134:692702. I.F.:1,23. Multicentrics I.F.: 49,30 1 Paoletti X, Oba K, Burzykowski T, Michiels S, Ohashi Y, Pignon JP, Rougier P, Sakamoto J, Sargent D, Sasako M, VanCutsem E, Buyse M. Benefit of Adjuvant Chemotherapy for Resectable Gastric Cancer A Meta-analysis. JAMA-J AM MED ASSOC, 2010. 303:1729-1737. I.F.:28,90. 2 Beyer J. Prognostic Factors in Patients With Metastatic Germ Cell Tumors Who Experienced Treatment Failure With Cisplatin-Based FirstLine Chemotherapy. J CLIN ONCOL, 2010. 28:4906-4911. I.F.:17,79. 3 Steinberg MH, Mccarthy WF, Castro O, Ballas SK, Armstrong FD, Smith W, Ataga K, Swerdlow P, Kutlar A, Decastro L, Waclawiw MA. The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up. AM J HEMATOL, 2010. 85:403-408. I.F.:2,61. Grants for research in progress Gascon P. Mecanismos de transactivación de los miembros de la familia ERB-B en cáncer de mama: importancia de las neuroquininas y la neurogénesis. Sponsored by: Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS) , PI080022. Amount: 71.632,00 euros. Duration: 01/01/2009-31/12/2011. Gascon P. Red temática de investigación cooperativa de Cáncer. Sponsored by: Instituto de Salud Carlos III, RED07/0020/2014. Amount: 34.716,57 euros. Duration: 01/01/2009-31/12/2010. Grau JJ. Efectividad y seguridad de la electroquimioterapia en el tratamiento de tumores sólidos. Sponsored by: Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS) , PI09/90664. Amount: 58.144,00 euros. Duration: 01/01/2010-31/12/2011. Reguart N. Papel de los fibroblastos asociados a tumores (cafs) en el carcinoma broncogénico de pulmón: mecanismos de interacción en modelos de cultivo celular 3d. Sponsored by: Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS) , PS09/01377. Amount: 86.515,00 euros. Duration: 01/01/2010-31/12/2013. Gascon P. La célula stem tumoral: estudios moleculares sobre mecanismos de metástasis. Sponsored by: Fundació CELLEX, 0000. Amount: 360.000,00 euros. Duration: 01/01/2009-31/12/2013. Reguart N. Contribució dels fibroblastes asociats a tumors (cafs) en el carcinoma pulmonar estudiat en models de cultivo tridimensionals. Sponsored by: AECC 2009, 0000. Amount: 18.000,00 euros. Duration: 01/01/2010-31/12/2012. Reguart N. Papel de los fibroblastos asociados a tumores (CAFS) en el carcinoma broncogénico de pulmón: mecanismos de interacción de modelos de cultivo celular 3D. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/1377. Amount: 86.515,00 euros. Duration: 01/01/2010-31/12/2012. Grau JJ. Efectividad y seguridad de la electroquimioterapia en el tratamiento de tumores sólidos. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/90664. Amount: 56.144,00 euros. Duration: 01/01/201031/12/2011. Reguart N. Contribución de los fibroblastos asociados a tumores (CAFs) al cáncer de pulmón estudiada con modelos de cultivo celular tridimensionales. Sponsored by: ASOCIACION ESPAÑOLA CONTRA EL CANCER, 10/103. Amount: 18.000,00 euros. Duration: 22/02/2010-21/02/2012. Maurel J. Papel de MMP-7 en la transactivación IGF-1R-EGFR y la resistencia intrínseca a los inhibidores de Epidermal Growth Factor Receptor (EGFR) en cáncer colorectal. Sponsored by: FUNDACION DE INVESTIGACION MEDICA MUTUA MADRILEÑA, AP75002010. Amount: 10.000,00 euros. Duration: 17/09/2010-16/09/2011. Gascon P. El papel de las taquininas en el proceso metástasico. Sponsored by: Fundació CELLEX, 0000. Amount: 500.000,00 euros. Duration: 01/01/2009-31/12/2013. 289 AREA 5 Team envolved in: Oncology and haematology Red temática de investigación cooperativa de cáncer Cell proliferation and signaling Strategic Objectives Group Members The general goal of the group is the analysis of the mechanisms involved in cell cycle progression and signaling in health and disease. TEAM LEADER Oriol Bachs (Facultat de Medicina UB) Tel.: 93 403 52 86 Fax: 93 402 19 07 Idibaps members: Neus Agell (Facultat de Medicina UB) Rosa Aligué (Facultat de Medicina UB) Carles Enrich (Facultat de Medicina UB) Albert Pol (ICREA) Francesc Tebar (Facultat de Medicina UB) Montserrat Jaumot (Facultat Medicina UB) Maria Jesús Pujol (Facultat Medicina UB) Research Fellows: María Pérez (Facultat de Medicina) Raffaella Pippa (Facultat Medicina) Sandra Vilà de Muga (Facultat de Medicina) Marta Sanchez (Facultat de Medicina) Serena Orlando (IDIBAPS) Albert Herms (IDIBAPS) Meritxell Reverter (Facultat Medicina) Adam Kassan (IDIBAPS) Alba Llopis (Facultat Medicina) Carles Barceló (Facultat Medicina) Natalia de Olano (Facultat de Medicina) Anna Alvarez-Guaita (Facultat de Medicina) Atilla Biçer (Facultat de Medicina) 290 Main Lines of Research Eugenia Cisneros (Facultat de Medicina) Amaia Ercilla (Facultat de Medicina) Amaia Ercilla (Facultat de Medicina) Mariona Gelabert (Facultat de Medicina) Alba Gómez (Facultat de Medicina) Noelia Paco (Facultat de Medicina) Anna Perearnau (Facultat de Medicina) David Soriano (Facultat de Medicina) Maite Vidal-Quadras (Facultat de Medicina) Gemma Ventura (IDIBAPS) Technicians: Sonia Brun (Facultat de Medicina) Alba Fajardo (Facultat de Medicina) María Molinos (Facultat de Medicina) Eulalia Rius (Facultat de Medicina) David Gimenez (Facultad Medicina) Collaborators: Marta Bosch (IDIBAPS) Teresa Royo (IDIBAPS) Edurne Gallastegui (Facultat de Medicina) Carles Rentero (IDIBAPS) 1. Cell proliferation and Cancer: The objective of this line of research is the analysis of the mechanisms involved in cell cycle regulation and its alterations during tumorigenesis: - Role of the CKI p27(Kip1) on the regulation of transcription, splicing and translation of genes involved in tumorigenesis: •Cell cycle regulation by protein acetylation. •Role of calmodulin in nuclear functions. 2. Cell cycle: signal transduction and checkpoints: The main topics in this research line are the analysis of: the regulation of the functionality of K-Ras by Calmodulin-binding and by phosphorylation; the regulation of p21CIP1 localization and the relevance of its binding to calmodulin and its phosphorylation; and, the DNA replication checkpoint in not transformed versus transformed cell lines. 3. Signaling and regulation of the cell cycle: In eukaryotic organisms, the response to stress insults is through the activation of the MAP kinases pathway, Progression through the cell cycle is dependent on external stimuli and failure to correctly integrate the induced signals can lead to accumulation of genetic damage contributing to cancer development. Understanding how signaling networks and the cellular responses are regulated is one of the most crucial objectives in biomedical research. The aim of this research focuses AREA 5 Oncology and haematology Cell proliferation and signaling Co-localitzation of p27 (green) and PCAF (red) during apoptosis. on identifying the molecular mechanisms by which cell cycle is regulated by stress-activated protein kinases. 4. Endocytosis, membrane trafficking and signaling: This line of research include the following activities: •Study of endocytosis and membrane trafficking in polarized cells, such as hepatocytes and in non-polarized cells. •Study the role of calmodulin in the regulation of trafficking and signalling of EGFR. •Study the role of Annexin A6 in the transport of caveolin, the formation of caveolae, homeostasis of cholesterol and signaling of Ras/MAPK. 5. Lipid trafficking and storage: The aim of our project is to characterize in health and disease, the cellular processes regulated or deregulated by the accumulation of lipids within cells. With an special attention to the cellular cost of accumulation of cholesterol in the organelles and the role of the caveolin protein in the regulation of these mechanisms. 291 AREA 5 Oncology and haematology Cell proliferation and signaling Team Members PUBLICATIONS Originals I.F.: 41,72 1 Martin-Ibanez R, Crespo E, Urban N, Sergent-Tanguy S, Herranz C, Jaumot M, Valiente M, Long JE, Pineda JR, Andreu C, Rubenstein JLR, Marin O, Georgopoulos K, Mengod G, Farinas I, Bachs O, Alberch J, Canals JM. Ikaros-1 Couples Cell Cycle Arrest of Late Striatal Precursors With Neurogenesis of Enkephalinergic Neurons. J COMP NEUROL, 2010. 518:329351. I.F.:3,72. 2 Ventura M, Mateo F, Serratosa J, Salaet I, Carujo S, Bachs O, Pujol MJ. Nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase is regulated by acetylation. INT J BIOCHEM CELL B, 2010. 42:1672-1680. I.F.:4,89. 7 Abella N, Brun S, Calvo M, Tapia O, Weber JD, Berciano MT, Lafarga M, Bachs O, Agell N. Nucleolar Disruption Ensures Nuclear Accumulation of p21 upon DNA Damage. TRAFFIC, 2010. 11:743-755. I.F.:6,26. Grants for research in progress 3 Enrich C. Red temática investigación cooperativa de cáncer. Sponsored by: Ministerio Sanidad y Consumo, RD06/0020/0008. Amount: 114.109,24 euros. Duration: 01/01/2007-31/12/2010. 4 Bachs O. Red temática de investigación cooperativa de cáncer. Sponsored by: Ministerio Sanidad y Consumo, RD06/0020/0010. Amount: 840.000,00 euros. Duration: 01/01/2006-31/12/2011. DelToro D, Xifro X, Pol A, Humbert S, Saudou F, Canals JM, Alberch J. Altered cholesterol homeostasis contributes to enhanced excitotoxicity in Huntington’s disease. J NEUROCHEM, 2010. 115:153-167. I.F.:4,00. Grewal T, Koese M, Rentero C, Enrich C. Annexin A6-regulator of the EGFR/Ras signalling pathway and cholesterol homeostasis. INT J BIOCHEM CELL B, 2010. 42:580-584. I.F.:4,89. 5 Woudenberg J, Rembacz KP, VanDenHeuvel FAJ, WoudenbergVrenken TE, Buist-Homan M, Geuken M, Hoekstra M, Deelman LE, Enrich C, Henning RH, Moshage H, Faber KN. Caveolin-1 Is Enriched in the Peroxisomal Membrane of Rat Hepatocytes. HEPATOLOGY, 2010. 51:1744-1753. I.F.:10,84. 292 6 Alvarez-Moya B, Lopez-Alcala C, Drosten M, Bachs O, Agell N. K-Ras4B phosphorylation at Ser181 is inhibited by calmodulin and modulates K-Ras activity and function. ONCOGENE, 2010. 29:5911-5922. I.F.:7,14. Enrich C. Ras/Mapk signalling regulates colesterol efflux. Sponsored by: Fundació Marató TV3, 0000. Amount: 198.125,00 euros. Duration: 01/01/2008-31/12/2010. Bachs O. Proteored. Sponsored by: Genoma España, 0000. Amount: 217.329,30 euros. Duration: 01/06/2005-01/06/2010. Agell N. Regulación de la función de K-Ras y su localización en microdominios de membrana plasmática por unión a calmodulina y fosforilación en Ser181. Sponsored by: Ministerio de Educación y Ciencia, SAF2007-60491. Amount: 263.780,00 euros. Duration: 01/10/200730/09/2010. Aligué R. La MAP quinasa p38 y la MAPKAP en la señalización de respuesta a estrés y el control del ciclo celular. Sponsored by: MINISTERIO DE EDUCACIÓN, BFU-2009-10778/BMC. Amount: 150.000,00 euros. Duration: 01/01/2009-31/12/2011. Bachs O. Papel del regulador del ciclo celular p27Kip1 en la oncogénesis. Sponsored by: MINISTERIO DE EDUCACIÓN, SAF2009- 07769 (GEN). Amount: 459.800,00 euros. Duration: 01/01/2009-31/12/2012. Bachs O. Proteored. Sponsored by: Genoma España, SAF2009- 07769 (GEN). Amount: 264.000,00 euros. Duration: 01/01/2005-31/12/2011. Bachs O. Proliferació Cel·lular. Sponsored by: Grups de Recerca de la Generalitat de Catalunya, 2009 SGR 1382. Amount: 43.680,00 euros. Duration: 01/01/2009-31/12/2013. Enrich C. Ras/MAPK signaling regulates cholesterol efflux. Sponsored by: MARATÒ DE TV3, PI040236. Amount: 198.125,00 euros. Duration: 01/01/2009-31/12/2011. Enrich C. Endocitosi, tràfic i senyalització. Sponsored by: Grups de Recerca de la Generalitat de Catalunya, 2009 SGR 1526. Amount: 47.840,00 euros. Duration: 01/01/2009-31/12/2013. AREA 5 Oncology and haematology Cell proliferation and signaling Enrich C. Estudio de l tráfico intracelular de la caveolina, formación de caveolas y la señalización: papel de la annexin A6. Sponsored by: MCINN, BFU2009-10335. Amount: 359.370,00 euros. Duration: 01/01/201031/12/2012. Pol A. Hepatic and brain mitochondrial cholesterol/glycosphingolipids and altered metabolism contribute to the pathology of Niemann Pick type C disease and caveolinopathies. Sponsored by: Fundació Marató de TV3, PI041315. Amount: 147.686,00 euros. Duration: 01/01/201031/12/2014. Thesis Agell N. Regulación de la funcionalidad de K-Ras4B por unión A Cam y fosforilación de la Ser 181. PhD student: Blanca Alvarez Moya. Bachs O. Paper de P27kip1 en la respiració cel·lular. PhD student: Ignasi Salaet Madorran. Pol A. Mechanism of Lipid Droplet formation. Sponsored by: MICINN, CONSOLIDER-INGENIO 2010, CSD2009.00016. Amount: 420.000,00 euros. Duration: 01/01/200931/12/2014. Pol A. Intracellular accumulation of lipids: Role of CAV1, molecular mechanisms and implications on cell proliferation. Sponsored by: MICINN, BFU2008-00345. Amount: 210.000,00 euros. Duration: 01/01/200831/12/2011. Tebar F. Función de PKCdelta y calmodulina en la regulación de la dinámica del citoesqueleto de actina y del tráfico intracelular del factor de crecimiento epidérmico. Sponsored by: MICINN, BFU2009-13526/BMC. Amount: 157.300,00 euros. Duration: 01/01/2010-31/12/2012. Tebar F. Integración funcional del tráfico de membranas, la señalización intracelular y la dinámica del citoesqueleto. Sponsored by: MICINN, BFU2006-26075-E/BMC. Amount: 30.000,00 euros. Duration: 01/01/2009-31/12/2011. 293 TransversAL Research Groups Barcelona Centre for International Health Research (CRESIB) 296 Clinical pharmacology 298 Transversal group for research in primary care 302 Research in nursing 305 transversal research groups Barcelona Centre for International Health Research (CRESIB) CRESIB SENIOR RESEARCHERS Research Professors: Pedro L. Alonso Hernando del Portillo Joaquim Gascón Edward B. Hayes Clara Menéndez Ivo Mueller Jaume Ordi Robert Pool Tomàs Pumarola Antoni Trilla Jordi Vila Associate Research Professors: John J. Aponte Carlota Dobaño Marjolein Gysels Alfredo Mayor 296 IDIBAPS’ area 6 of International Health became in 2006 a new CERCA research centre monographic in international health, the Barcelona Centre for International Health Research (CRESIB, Hospital Clínic – Universitat de Barcelona) from which IDIBAPS is a Trustee together with the Generalitat de Catalunya, the Hospital Clínic and the Univesitat de Barcelona. CRESIB has more than 85 researchers from different backgrounds including molecular biology, genetics, immunology, microbiology, epidemiology, clinics, statistics, medical anthropology and health economy. CRESIB’s mission is to improve global health through research and training. The Centre is scientifically organized in a matrix to maximize interaction between researchers and promote multidisciplinary, translational and crosscutting research in order to achieve its mission (See Figure). CRESIB collaborates with more than 100 research centres in 40 countries, but we have stable strategic partnerships: •In Mozambique the Manhiça Health Research Centre (CISM), studying the most prevalent diseases in sub- transversAL research groups Barcelona Centre for International Health Research (CRESIB) Saharan Africa such as malaria, HIV/ AIDS, tuberculosis, pneumonia and other bacterial invasive diseases and diarrheal disease. •In Morocco we develop a broad portfolio of activities in maternal and child health in partnership with the Ministry of Health, the University Hospital of Rabat and two main women’s and children’s hospitals. •In Bolivia we work together with the Universidad Mayor de San Simón, the Viedma Hospital, CEADES and the Ministry of Health to improve the understanding of the epidemiology, clinical presentation and immunology of Chagas disease and develop new diagnostic and treatment tools. The centre’s scientific output has grown continuously over the last years in terms of both volume and the impact factor of its publications, with 84 original articles and an impact factor of 324 in 2010. Highlights of our results in 2010 • CRESIB lead the Malaria Eradication Research Agenda (malERA) initiative which brought together more than 250 scientists from 36 countries in a series of consultations with the aim of identifying the research and development priorities to potentially eradicate malaria. The results will be published at the beginning of 2011 in a special issue of PLoS Medicine. • Several studies have assessed the immune response to malaria infection in pregnancy and the effect of HIV infection, suggesting a higher efficacy of the Intermittent Preventive Treatment for malaria in pregnancy (IPTp) among HIV-positive mothers. • A novel immune spleen evasion mechanism for Plasmodium vivax has been described • CRESIB promoted the creation of the Ibero-American network NHEPACHA, which aims to accelerate the development of new diagnostic and treatment tools for Chagas disease. • 3.3% of the HIV seronegative adult patients presenting with fever at the Manhiça District Hospital (Mozambique) were found to have Acute HIV Infection. These individuals may be hypertransmitters and could be targets for the positive prevention of sexually-transmitted HIV. • The Microbicide Development Program completed its MDP301 Phase III trial of a candidate microbicide, which included a social science component led by CRESIB who developed an innovative mixed-methods model for studying adherence and sexual behavior. • A new efflux pump contributing to resistance to different classes of antibiotics has been characterized. • Procalcitonin and reactive-C-protein have been shown to be potential markers to differentiate viral and bacterial pneumonia in a malariaendemic area. • CRESIB researchers participated in the international Brighton Collaboration process to develop a casedefinition for viscerotropic disease as an adverse event after yellow fever vaccination. For further information: www.cresib.cat www.manhica.org 297 transversal research groups Clinical pharmacology Strategic Objectives Group Members TEAM LEADER Xavier Carné (Hospital Clínic) Tel.: 93 227 91 68 Fax: 93 227 98 77 E-mail: xcarne@clinic.ub.es Idibaps members: Joan Albert Arnaiz (Hospital Clínic) Gonzalo Calvo (Hospital Clínic) José Ríos (IDIBAPS) Ferran Torres (IDIBAPS) Collaborators: Begoña Gómez (Hospital Clínic) Amalia Lafuente (UB) Neus Riba (Hospital Clínic) Josep Ribas (Hospital Clínic) Ana Cruceta (Fundació Clínic) Judit Pich (Fundació Clínic) Sara Varea (Fundació Clínic) Núria Sanz (Fundació Clínic) Carles Codina (Hospital Clínic) 298 The team carries out clinical research support activities with different Departments: 1. The Clinical Trials Agency, together with the Department of Pharmacy, provides support of all technical and administrative aspects related to clinical trials carried out in the Clinic Hospital - IDIBAPS. The Agency serves as a single window for sponsors and investigators, and as secretary to the CREC of the Clinic Hospital (Clinical Research Ethics Committee). 2. The CTU (Clinical Trials Unit), provides support for the conduction of clinical trials on the part of the investigators of the institution that act as sponsors, in aspects related to study design, implementation and monitorization. 3. The Statistical and Methodological Support Unit (USEM) offers counselling in trial data analysis and planning. 4. The Pharmacoepidemiology and Therapeutic Evaluation Unit, offers support of activities in pharmacovigilance, epidemiology and the evaluation of drugs in our setting. transversAL research groups Clinical pharmacology 5. The team collaborates with Dr. Amàlia Lafuente (UB) of the Pharmacology Unit of the University of Barcelona, who conducts studies relating genetics to drug substance activity and response. 6. Lastly, the team participates in the trial follow-up committees known as DSMB (Data and Safety Monitoring Boards), in charge of external supervision of the course of the clinical trials, and of deciding the pertinence of their continuity over time. Main Lines of Research • Ethics in clinical research. • Clinical trials, design and methodology. • Statistical support of clinical research. • Pharmacovigilance and pharmacoepidemiology. • Pharmacogenetics and pharmacogenomics. PUBLICATIONS originals I.F.: 78,15 1 Izquierdo I, Borja J, Rovira S, Pelagio P, Torres F, Cebrecos J, GarciaRafanell J. Comparative bioavailability study of triflusal oral solution vs. triflusal capsules in healthy subjects A single, randomized, two-way cross-over, open-label phase I study. ARZNEIMITTEL-FORSCH, 2010. 60:36-41. I.F.:0,69. 2 Carretero M, Fontanals J, Agusti M, Arguis M, Martinez-Ocon J, Ruiz A, Rios J. Monitoring in resuscitation: Comparison of cardiac output measurement between pulmonary artery catheter and NICO. RESUSCITATION, 2010. 81:404-409. I.F.:2,71. 3 Roca O, Riera J, Torres F, Masclans JR. High-Flow Oxygen Therapy in Acute Respiratory Failure. RESP CARE, 2010. 55:408-413. I.F.:1,52. 4 Salvador L, Valero R, Carazo J, Caral L, Rios J, Carrero E, Tercero J, DeRiva N, Hurtado P, Ferrer E, Fabregas N. Pressure Inside the Neuroendoscope: Correlation With Epidural Intracranial Pressure During Neuroendoscopic Procedures. J NEUROSURG ANESTH, 2010. 22:240-246. I.F.:2,41. 5 Poggio D, DeRetana PF, Borda D, Hortua P, Asuncion J, Rios J. Analysis of the Clinical Score Progressions During the First Year After First MTPJ Fusion. FOOT ANKLE INT, 2010. 31:578-583. I.F.:1,10. 6 Llupia A, Garcia-Basteiro AL, Olive V, Costas L, Rios J, Quesada S, Varela P, Bayas JM, Trilla A. New interventions to increase influenza vaccination rates in health care workers. AM J INFECT CONTROL, 2010. 38:476-481. I.F.:3,01. 7 Kuchinke W, Ohmann C, Yang Q, Salas N, Lauritsen J, Gueyffier F, Leizorovicz A, Schade-Brittinger C, Wittenberg M, Voko Z, Gaynor S, Cooney M, Doran P, Maggioni A, Lorimer A, Torres F, Mcpherson G, Charwill J, Hellstrom M, Lejeune S. Heterogeneity prevails: the state of clinical trial data management in Europe - results of a survey of ECRIN centres. TRIALS, 2010. 11:-. I.F.:2,02. 8 Lloberes P, Lozano L, Sampol G, Romero O, Jurado MJ, Rios J, Untoria MD, Tovar JL. Obstructive sleep apnoea and 24-h blood pressure in patients with resistant hypertension. J SLEEP RES, 2010. 19:597-602. I.F.:3,50. 9 Cesarini C, Monreal L, Armengou L, Delgado MA, Rios J, Jose-Cunilleras E. Association of Admission Plasma D-Dimer Concentration with Diagnosis and Outcome in Horses with Colic. J VET INTERN MED, 2010. 24:1490-1497. I.F.:2,17. 10 Marti S, Pallero M, Ferrer J, Rios J, Rodriguez E, Morell F, Munoz X. Predictors of mortality in chest wall disease treated with noninvasive home mechanical ventilation. RESP MED, 2010. 104:1843-1849. I.F.:2,33. 11 Lozano LK, Tovar JL, Sampol G, Romero O, Jurado MJ, Segarra A, Espinel E, Rios J, Untoria MD, Lloberes P. Continuous positive airway pressure treatment in sleep apnea patients with resistant hypertension: a randomized, controlled trial. J HYPERTENS, 2010. 8:2161-2168. I.F.:4,99. 12 Armengou L, Monreal L, Delgado MA, Rios J, Cesarini C, Jose-Cunilleras E. Low-Molecular-Weight Heparin Dosage in Newborn Foals. J VET INTERN MED, 2010. 24:11901195. I.F.:2,17. 299 transversal research groups Clinical pharmacology 13 Esteva-Font C, Wang XY, Ars E, Guillen-Gomez E, Sans L, Saavedra IG, Torres F, Torra R, Masilamani S, Ballarin JA, Fernandez-Llama P. Are Sodium Transporters in Urinary Exosomes Reliable Markers of Tubular Sodium Reabsorption in Hypertensive Patients? NEPHRON PHYSIOL, 2010. 114:P25-P34. I.F.:2,53. 14 Miro JM, Manzardo C, Pich J, Domingo P, Ferrer E, Arribas JR, Ribera E, Arrizabalaga J, Lonca M, Cruceta A, DeLazzari E, Fuster M, Podzamczer D, Plana M, Gatell JM. Immune Reconstitution in Severely Immunosuppressed Antiretroviral-Naive HIV Type 1-Infected Patients Using a Nonnucleoside Reverse Transcriptase Inhibitor-Based or a Boosted Protease Inhibitor-Based Antiretroviral Regimen: Three-Year Results. AIDS RES HUM RETROV, 2010. 26:747-757. I.F.:2,18. 15 Martinez E, Larrousse M, Llibre JM, Gutierrez F, Saumoy M, Antela A, Knobel H, Murillas J, Berenguer J, Pich J, Perez I, Gatell JM. Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study. AIDS, 2010. 24:1697-1707. I.F.:4,91. 16 Cervera A, Planas AM, Justicia C, Urra X, Jensenius JC, Torres F, Lozano F, Chamorro A. Genetically-Defined Deficiency of Mannose-Binding Lectin Is Associated with Protection after Experimental Stroke in Mice and Outcome in Human Stroke. PLoS ONE, 2010. 5:-. I.F.:4,35. 17 Sola R, Bruckert E, Valls RM, Narejos S, Luque X, Castro-Cabezas M, Domenech G, Torres F, Heras M, Farres X, Vaquer JV, Martinez JM, Almaraz MC, Anguera A. Soluble fibre (Plantago ovata husk) reduces plasma low-density lipoprotein (LDL) 300 cholesterol, triglycerides, insulin, oxidised LDL and systolic blood pressure in hypercholesterolaemic patients: A randomised trial. ATHEROSCLEROSIS, 2010. 211:630-637. I.F.:4,52. 18 Tamborero D, Mont L, Berruezo A, Guasch E, Rios J, Nadal M, Matiello M, Andreu D, Sitges M, Brugada J. Circumferential pulmonary vein ablation: Does use of a circular mapping catheter improve results? A prospective randomized study. HEART RHYTHM, 2010. 7:612-618. I.F.:4,56. 19 Vilaplana C, Montane E, Pinto S, Barriocanal AM, Domenech G, Torres F, Cardona PJ, Costa J. Doubleblind, randomized, placebo-controlled Phase I Clinical Trial of the therapeutical antituberculous vaccine RUTI (R). VACCINE, 2010. 28:1106-1116. I.F.:3,62. 20 Carrion JA, Torres F, Crespo G, Miquel R, Garcia-Valdecasas JC, Navasa M, Forns X. Liver Stiffness Identifies Two Different Patterns of Fibrosis Progression in Patients with Hepatitis C Virus Recurrence After Liver Transplantation. HEPATOLOGY, 2010. 51:23-34. I.F.:10,84. 21 Guevara M, Baccaro ME, Rios J, Martin-Llah M, Uriz J, DelArbol LR, Planas R, Monescillo A, Guarner C, Crespo J, Banares R, Arroyo V, Gines P. Risk factors for hepatic encephalopathy in patients with cirrhosis and refractory ascites: relevance of serum sodium concentration. LIVER INT, 2010. 30:1137-1142. I.F.:2,99. 22 Garcia I, Mayol G, Rodriguez E, Sunol M, Gershon TR, Rios J, Cheung NKV, Kieran MW, George RE, Perez-Atayde AR, Casala C, Galvan P, DeTorres C, Mora J, Lavarino C. Expression of the neuron-specific pro- tein CHD5 is an independent marker of outcome in neuroblastoma. MOL CANCER, 2010. 9:-. I.F.:4,16. 23 Cruz N, Sanchez-Moreno J, Torres F, Goikolea JM, Valenti M, Vieta E. Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis. INT J NEUROPSYCHOPH, 2010. 13:5-14. I.F.:4,87. Multicentrics I.F.: 22,52 1 Friis-Moller N, Thiebaut R, Reiss P, Weber R, Monforte AD, DeWit S, El-Sadr W, Fontas E, Worm S, Kirk O, Phillips A, Sabin CA, Lundgren JD, Law MG. Predicting the risk of cardiovascular disease in HIV-infected patients: the Data collection on Adverse Effects of Anti-HIV Drugs Study. EUR J CARDIOV PREV R, 2010. 17:491-501. I.F.:2,51. 2 Smith C, Sabin CA, Lundgren JD, Thiebaut R, Weber R, Law M, Monforte AD, Kirk O, Friis-Moller N, Phillips A, Reiss P, El-Sadr W, Pradier C, Worm SW. Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D study The Data Collection on Adverse Events of Anti-HIV drugs (D:A:D) Study Group. AIDS, 2010. 24:1537-1548. I.F.:4,91. 3 Worm SW, Sabin C, Weber R, Reiss P, El-Sadr W, Dabis F, DeWit S, Law M, Monforte AD, Friis-Moller N, Kirk O, Fontas E, Weller I, Phillips A, Lundgren J. Risk of Myocardial Infarction in Patients with HIV Infection Exposed to Specific Individual Antiretroviral Drugs from the 3 Major Drug Classes: The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study. J INFECT DIS, 2010. 201:318-330. I.F.:5,87. transversAL research groups Clinical pharmacology 4 Worm SW, Friis-Moller N, Bruyand M, Monforte AD, Rickenbach M, Reiss P, El-Sadr W, Phillips A, Lundgren J, Sabin C. High prevalence of the metabolic syndrome in HIV-infected patients: impact of different definitions of the metabolic syndrome. AIDS, 2010. 24:427-435. I.F.:4,91. 5 Weber R, Sabin C, Reiss P, DeWit S, Worm SW, Law M, Dabis F, Monforte AD, Fontas E, El-Sadr W, Kirk O, Rickenbach M, Phillips A, Ledergerber B, Lundgren J. HBV or HCV coinfections and risk of myocardial infarction in HIV-infected individuals: the D:A:D Cohort Study. ANTIVIR THER, 2010. 15:1077-1086. I.F.:4,32. Grants for research in progress Trilla A. European Network for Highly Infectious Diseases. Sponsored by: European Commission, 2006205. Amount: 5.644,34 euros. Duration: 01/07/2007-30/06/2010. Carne X. Estudio observacional, controlado en pacientes hipertensos tratados con iecas para valorar riesgo genético de hipersensibilidad pulmonar (tos seca). Sponsored by: Ministerio Sanidad y Consumo, EC07/90239. Amount: 141.812,00 euros. Duration: 29/10/2007-30/12/2010. Vilella A. Planes de actuación frente a una pandemia de gripe: Análisis sistemático de los actualmente vigentes en España y desarrollo de un ejercicio de simulación para evaluar localmente su factibilidad. Sponsored by: Ministerio Sanidad y Consumo, PI070184. Amount: 32.186,00 euros. Duration: 26/11/2007-30/12/2010. Carne X. European Clinical Research Infrastructures Network and biotherapy facilities: Preparation Phase for the InfrastructureCentre coordinador: INSERM. Sponsored by: INSERM - DRCT Institut Thématique Santé Publique, 211738. Amount: 336.074,00 euros. Duration: 01/03/200828/02/2011. Arnaiz JA. Fixed Dose Combination drugs for Secondary Cardiovascular Prevention. Sponsored by: CNICCENTRO NAC. INVEST. C.CARLOS III, 241559. Amount: 482.878,00 euros. Duration: 01/07/201030/06/2013. Calvo G. Estudio de cohortes para evaluar la seguridad y la efectividad del programa de vacunación frente a la gripe A (H1N1) en el área de cobertura sanitaria de un hospital de tercer nivel. Sponsored by: MINISTERIO DE SANIDAD, POLITICA SOCIAL E IGUALDAD, TRA-063. Amount: 120.478,32 euros. Duration: 01/01/2010-31/12/2011. Calvo G. Servicios de asesoramiento en evaluación clínica de solicitudes de autorización y comercialización de medicamentos de uso humano autorizados por procedimiento centralizado. Sponsored by: Agencia Española de Medicamentos y Productos Farmacéuticos, 48/227.06/09. Amount: 29.902.699,00 euros. Duration: 09/02/2010-08/02/2012. Thesis Codina C. Acontecimientos adversos producidos por medicamentos en pacientes hospitalizados: Influencia de las estrategias de actuación en su detección y prevención. PhD student: Carolina Berga Cullere. Calvo G. Estudio prospectivo multicéntrico de la incidencia, relevancia clínica, factores de riesgo y preventibilidad del ingreso hospitalario por fracaso renal agudo asociado al uso de fármacos inhibidores del sistema renina-angiotensina.. Sponsored by: INSTITUTO DE SALUD CARLOS III, EC08/00173. Amount: 43.318,00 euros. Duration: 01/01/200930/12/2011. Calvo G. Servicio Técnico para la emisión de informes de validación de modificacioens de importancia mayor de medicamentos de uso humano. Nº Procedimiento 48/227.06/09. Sponsored by: Agencia Española Medicamento AEMPS, 09/484. Amount: 148.747,14 euros. Duration: 08/02/2010-31/12/8900. 301 transversal research groups TransversAL group for research in primary care Strategic Objectives Group Members TEAM LEADER Antoni Sisó Almirall (GESCLÍNIC) Tel.: 93 227 99 24 Fax: 93 227 55 97 E-mail: asiso@clinic.ub.es IDIBAPS Members: Lluisa Benito Serrano (GESCLINIC) Marta Catalán Adell (CAPSE) Zoe Herreras Pérez (CAPSE) Imma Garrell Lluís (CAPSE) Joan Gené Badia (CAPSE) Imma Grau Corral (Hospital Clínic) Pilar Navarrete Duran (CAPSE) Marta Navarro González (CAPSE) Jacinto Ortiz Molina (GESCLINIC) Ignacio Menacho (GESCLINIC) Antoni Salvà Riquer (CAPSE) Núria Sánchez Ruano (CAPSE) Laura Sebastián Montal (GESCLINIC) Ethel Sequeira Aymar (CAPSE) Josep Miquel Sotoca (Hospital Clínic) Marina Rovira (CAPSE) Lluís González de Paz (GESCLINIC) Elisenda Sant Arderiu (CAPSE) Research Fellows: Emma Marianela Morales Espinoza (GESCLINIC) Norma Nely Nardi (Hospital Clínic) Staticians: Belchin Adriyanov Kostov (Fundació Clínic) Nursing Staff: Narly Benachi Sandoval (CAPSE) Noemí García (CAPSE) Rosa Segarra (CAPSE) Esther Blat (GESCLINIC) 302 Collaborators: Sílvia Canivell Fusté (IDIBAPS) Jaume Benavent Àreu (Institut Català de la Salut) Primary care is the point of patient entry to the healthcare system, and the primary care centers are where most of the population health problems are dealt with. It is in this setting where the relationship between the patient and reference primary care physician and nurse is a key factor in preventing and healing diseases, and in promoting healthy habits. In the research context, the multidisciplinary and transverse nature of the activities of the primary care professional favors a biological, psychological and social approach to the patients and their illnesses, in both the consulting office and in the home. The integral approach to the individual and longitudinal care over the full course of the life of the patient makes it possible to conduct proprietary and/or collaborative studies targeted at knowledge of the characteristics of the population, people and their illnesses. Primary care aims to carry out research inherent to its nature, integrating within the existing investigational networks and groups, and working in a coordinated manner with other consolidated research teams from different perspectives: • Conduction of population-based studies (both descriptive and evaluating interventions and follow-up), in an accessible and well defined population of subjects, taking advantage of the computer-based filing of clinical data. • Conduction of research into healthcare results or outcomes. • Description of the natural history of the patient and disease from a biological, psychological and social perspective. transversAL research groups Transversal group for research in primary care • Conduction of studies of risk factors and preventive medicine. • Analysis of the morbidity and mortality of the most prevalent disorders. • Development of collaborative studies with the administration and research entities or groups allowing the implementation of translation research. In the year 2010, Research in Primary Care has been organized around the CAPSE-GESCLINIC Research Unit, integrated by Dr. Antoni Sisó (Director of the CAPSE_GESCLINIC Unit), Dr. Laura Sebastián (Manager of CAPSE-GESCLINIC), Dr. Anna Pereira (Management adjunct to the CAPSE), Lluís González (DUEGESCLINIC), Elena Mañes (DUE-CAPSE), and Narly Benachi (DUE-Clinical TrialsCAPSE). Main Lines of Research • Healthcare continuity and management of chronic diseases. • Use of healthcare services. • The fragility – geriatrics – dependency – home care axis. • Use of medicines. • Primary care and autoimmunity. • Atherogenesis, risk factors and cardiovascular diseases. • Chronic pain. • Mental health, smoking and other addictions. • Respiratory diseases. • Digestive and liver diseases. • HIV infection – AIDS and other infectious diseases. • 2.0. Health. For further information: www.forumclinic.org PUBLICATIONS originals I.F.: 49,85 1 Soto-Cardenas MJ, Perez-De-Lis M, Bove A, Navarro C, Brito-Zeron P, Diaz-Lagares C, Gandia M, Akasbi M, Siso A, Ballester E, Torres A, Ramos-Casals M. Bronchiectasis in primary Sjogren’s syndrome: prevalence and clinical significance. CLIN EXP RHEUMATOL. 28:647-653. I.F.:2,40. 2 Perez-De-Lis M, Akasbi M, Siso A, Diez-Cascon P, Brito-Zeron P, DiazLagares C, Ortiz J, Perez-Alvarez R, Ramos-Casals M, Coca A. Cardiovascular risk factors in primary Sjogren’s syndrome: a case-control study in 624 patients. LUPUS. 19:941-948. I.F.:2,59. 3 Ramos-Casals M, Brito-Zeron P, Perez-De-Lis M, Diaz-Lagares C, Bove A, Soto MJ, Jimenez I, Belenguer R, Siso A, Muxi A, Pons F. Clinical and Prognostic Significance of Parotid Scintigraphy in 405 Patients with Primary Sjogren’s Syndrome. J RHEUMATOL. 37:585-590. I.F.:3,85. 4 Siso A, Ramos-Casals M, Bove A, Brito-Zeron P, Soria N, Nardi N, Testi A, Perez-De-Lis M, Diaz-Lagares C, Darnell A, Sentis J, Coca A. Outcomes in Biopsy-Proven Lupus Nephritis Evaluation of 190 White Patients From a Single Center. MEDICINE. 89:300-307. I.F.:5,05. 5 Ramos-Casals M, Brito-Zeron P, Perez-De-Lis M, Jimenez I, Blanco MJ, Bove A, Soto MJ, Akasbi M, Diaz C, Sentis J, Siso A. Sjogren Syndrome or Sjogren Disease? The Histological and Immunological Bias Caused by the 2002 Criteria. CLIN REV ALLERG IMMU. 38:178-185. I.F.:2,60. 6 Ramos-Casals M, Tzioufas AG, Stone JH, Siso A, Bosch X. Treatment of Primary Sjogren Syndrome A Systematic Review. JAMA-J AM MED ASSOC. 304:452-460. I.F.:28,90. 7 Zambon D, Quintana M, Mata P, Alonso R, Benavent J, Cruz-Sanchez F, Gich J, Pocovi M, Civeira F, Capurro S, Bachman D, Sambamurti K, Nicholas J, Pappolla MA. Higher Incidence of Mild Cognitive Impairment in Familial Hypercholesterolemia. AM J MED. 123:267-274. I.F.:4,47. Grants for research in progress Grau I. Desarrollo y coorganización del proyecto ForumClinic. Programa interactiu per a pacients adreçat a què aquests augmentin el seu grau d’autonomia respecte a la seva salut utilitzant les oportunitats de les noves tecnologies. Sponsored by: Fundación BBVA, 0000. Amount: 0,00 euros. Duration: 01/01/2009-31/12/2012. Juan C. Identificació de grups de pacients amb requeriments similars de temps de cures d’infermeria en un programa d’atenció domiciliària urbà en l’àmbit de l’atenció primària. Sponsored by: FIS, PI060337. Amount: 0,00 euros. Duration: 01/01/2008-31/12/2010. Siso A. Multilingual OrganiK Information management in the medical domain (Projecte MORMED). Sponsored by: Comission Europea, 250534. Amount: 0,00 euros. Duration: 01/03/201031/08/2012. Siso A. Usefulness of the VScan in Primary Care (PC) daily practice as complementary to physical examination. Sponsored by: General Electrics Healthcare, 10/503. Amount: 0,00 euros. Duration: 16/07/2010-31/12/2012. 303 transversal research groups TransversAL group for research in primary care Morales EN. Prevalencia, gasto sanitario y morbimortalidad cardiovascular del dolor crónico no oncológico en Atención Primaria. Sponsored by: CAPSE-GESCLINIC, 10/503. Amount: 0,00 euros. Duration: 01/06/201001/06/2011. Thesis Serrat M. Intervenció social sobre la implantació de grups terapèutics per a cuidadors de pacients amb malaltia d’Alzheimer. Sponsored by: Fundació Pasqual Maragall i Obra Social de La Caixa, 10/503. Amount: 0,00 euros. Duration: 01/01/2010-31/12/2010. Siso A, Navarro D. Vigència de la Carta de Drets i Deures dels ciutadans en relació a la Salut i l’Atenció Sanitària entre els usuaris dels serveis d’Atenció Primària de Salut. PhD student: Lluís González de Paz, Universitat de Barcelona. Erdozain MA. Impacte del tractament del Dolor amb Acupuntura a l’Atenció Primària. Sponsored by: CAPSE, 10/503. Amount: 0,00 euros. Duration: 01/01/2009-31/12/2010. 304 Siso A. Anàlisis de prevalença, despesa sanitària i morbimortalitat cardiovascular del dolor crònic nooncológic a l’atenció primària. PhD student: Morales, Emma M. transversal research groups Research in nursing Strategic Objectives Group Members TEAM LEADER Adelaida Zabalegui (Hospital Clínic) Tel.: 93 227 54 24 Fax: 93 227 17 77 E-mail: azabaleg@clinic.ub.es Collaborators: Mercè Piazuelo i Pont (Hospital Clínic) Amèlia Pérez González (Hospital Clínic) Miquel Sanz Moncosi (Hospital Clínic) Mª Teresa Hospital Vidal (Hospital Clínic) Mercè Comes Forastero (Hospital Clínic) Felip Burgos Rincón (Hospital Clínic) Dolors Robles Antúnez (Hospital Clínic) Montserrat Amigó Tandin (Hospital Clínic) Luis González de Paz (Gesclínic) Research in nursing is essential for responding to the healing demands of the current healthcare system. Its complexity in the hospital setting is derived from the associated increase in patient severity upon admission, the reduction in hospital stay, the incorporation of new technologies, the aging of the population, patient requests for information, social change, and the global crisis. Main Lines of Research Internationally, research activity in nursing is improving thanks to the definition of priorities, the identification of groups and the focusing of their research lines, increased funding, and integration of the results obtained in the clinical practice setting. Accordingly, an increase is being observed in the number of publications in international journals, documented in the Cumulative Index to Nursing and Allied Health Literature (CINAH) and the Medline database, affording credibility and acknowledgement to our research activities. This improved scientific production has been achieved through the competitive funding of projects and the development of research training programs on the part of the professional and government organizations, and the generalized application of anonymous and rigorous peer review of the results of the investigations made. Research in nursing presents differential paradigmatic elements with respect to other types of research in the health sciences, such as its particular patient focus (rather than disease-based focus), and the study of physiological, psychological, sociocultural and/or spiritual aspects of the individual, with a view to improving healing. The effort to secure this unique approach has resulted in the definition of priority research areas in nursing, which in this country comprise the following: evaluation of the efficacy of nursing interventions; the promotion of health and the development of strategies designed to implicate patients in their own healing; 305 transversal research groups Research in nursing PUBLICATIONS healing based on evidence; the implementation and evaluation of results in clinical practice; and measurement of the quality of nursing care. In Spain, research in nursing is still an emergent activity. Its consolidation will be facilitated by the recent introduction of degree programs, masters and doctorate courses specifically targeted at nursing, with the participation of professionals accredited for teaching in research. For the first time, nurses following a doctorate program will be able to access extensive and rigorous training in the scientific method, to ensure the quality of their scientific production in the field of nursing care. Our present challenge is application to the healthcare setting: nurses should understand research as a driving force in their professional development and in the improvement of their care of patients and their families – incorporating it into their daily clinical practice. We are aware of the enormous task awaiting us. In this context, we are inspired by the brilliant trajectory of research in nursing in the United States or Europe (United kingdom, Sweden, Finland, the Netherlands, etc.) – countries where nursing has been capable of attracting financial support, gaining access to mentors, and consolidating its lines of research. Nursing in the Clinic Hospital can lead the process of incorporating research to clinical practice, based on a solid institutional reference and a strongly-rooted scientific culture. The recent creation of the Nursing Research Committee aims to visualize and reinforce this activity. We already have competitive projects financed by national and European agencies, and have ambitious plans for improvement that should result in an increase in the number and relevance of our publications. In sum, our hospital has the motivation and scientific leadership needed to face the challenge of research in nursing. 306 Originals I.F.: 22,63 1 Sastre S, Popescu D, Nunez M, Pomes J, Tomas X, Peidro L. Doublebundle versus single-bundle ACL reconstruction using the horizontal femoral position: a prospective, randomized study. KNEE SURG SPORT TR A, 2010. 18:32-36. I.F.:1,67. 2 Popescu D, Sastre S, Caballero M, Lee JWK, Claret I, Nunez M, Lozano L. Meniscal repair using the FasT-Fix device in patients with chronic meniscal lesions. KNEE SURG SPORT TR A, 2010. 18:546-550. I.F.:1,67. 3 Jansa M, Hernandez C, Vidal M, Nunez M, Bertran MJ, Sanz S, Castell C, Sanz G. Multidimensional analysis of treatment adherence in patients with multiple chronic conditions. A crosssectional study in a tertiary hospital. PATIENT EDUC COUNS, 2010. 81:161168. I.F.:1,98. 4 Rodriguez-Blanco T, FernandezSan-Martin I, Balague-Corbella M, Berenguera A, Moix J, Montiel-Morillo E, Nunez-Juarez E, Gonzalez-Moneo MJ, Pie-Oncins M, Martin-Penacoba R, Roura-Olivan M, Nunez-Juarez M, Pujol-Ribera E. Study protocol of effectiveness of a biopsychosocial multidisciplinary intervention in the evolution of non-speficic sub-acute low back pain in the working population: cluster randomised trial. BMC HEALTH SERV RES, 2010. 10:-. I.F.:1,66. 5 Amigo M, Nogue S, Miro O. Use of activated charcoal in acute poisonings: Clinical safety and factors associated with adverse reactions in 575 cases. MED CLIN-BARCELONA, 2010. 135:243-249. I.F.:1,23. 6 Pozo-Rodriguez F, Alvarez CJ, CastroAcosta A, Moreno CM, Capelastegui A, Esteban C, Carcereny CH, Lopez-Campos JL, Alonso JLI, Quilez AL, Agusti A. Clinical Audit of Patients Admitted to Hospital in Spain due to Exacerbation of COPD (AUDIPOC Study): Method and Organisation. ARCH BRONCONEUMOL, 2010. 46:349-357. I.F.:2,17. 7 Gonzalo V, Lozano JJ, Munoz J, Balaguer F, Pellise M, DeMiguel CR, Andreu M, Jover R, Llor X, Giraldez MD, Ocana T, Serradesanferm A, Alonso-Espinaco V, Jimeno M, Cuatrecasas M, Sendino O, Castellvi-Bel S, Castells A. Aberrant Gene Promoter Methylation Associated with Sporadic Multiple Colorectal Cancer. PLOS ONE, 2010. 5:-. I.F.:4,35. 8 Valldeoriola F, Regidor I, MinguezCastellanos A, Lezcano E, Garcia-Ruiz P, Rojo A, Salvador A, Castro A, Grandas F, Kulisevsky J, Marti MJ, Martinez-Martin P, Relova L, Rumia J, Camara A, Burguera JA, Linazasoro G, DeVal JL, Obeso J, Rodriguez-Oroz MC, Tolosa E. Efficacy and safety of pallidal stimulation in primary dystonia: results of the Spanish multicentric study. J NEUROL NEUROSUR PS, 2010. 81:65-69. I.F.:4,87. 9 Rosa AR, Reinares M, Michalak EE, Bonnin CM, Sole B, Franco C, Comes M, Torrent C, Kapczinski F, Vieta E. Functional Impairment and Disability across Mood States in Bipolar Disorder. VALUE HEALTH, 2010. 13:984-988. I.F.:3,03. transversAL research groups Research in nursing Reviews I.F.: 1,234 1 Valldeoriola F, Camara A. Intraduodenal infusion of levodopa. REV NEUROLOGIA, 2010. 51:41-48. I.F.:1,23. Editorials I.F.: 5,527 1 Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, VanDerGrinten C, Gustafsson P, Jensen R, Macintyre N, Mckay RT, Pedersen OF, Pellegrino R, Viegi G, Wanger J. Standardisation of lung function testing: the authors’ replies to readers’ comments. EUR RESPIR J, 2010. 36:14961498. I.F.:5,53. Grants for research in progress Zabalegui A. Patrones de afrontamiento al cuidado oncológico paliativo. Sponsored by: Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias, PI061269. Amount: 24.623,50 euros. Duration: 12/11/2006-30/06/2010. Zabalegui A. Grup de recerca reconegut com consolidat de Catalunya al “Grup de Cures a la Gent Gran Dependent”. Sponsored by: Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR), 2009 SGR 916. Amount: 0,00 euros. Duration: 03/07/2009-31/12/2012. Zabalegui A. Estudio experimental sobre la eficacia de una intervención innovadora de información, formación y apoyo social “INFOSA” a cuidadores principales de personas mayores dependientes. Sponsored by: INSTITUTO DE SALUD CARLOS III, PI09/0111. Amount: 62.315,00 euros. Duration: 17/02/201031/12/2012. Burgos F. Estudio Europeo de Salud Respiratoria: Seguimiento de la población española a los 18 años de su inicio. Sponsored by: FIS, 2009 ECRHS III. Amount: 77.440,00 euros. Duration: 01/01/2009-31/12/2011. Zabalegui A. Improving health services for European citizens with dementia: Development of best practice strategies for the transition from ambulatory to institutional long-trem care facilities (RightTimePlaceCare). Sponsored by: European Commission, 2421153. Amount: 249.075,00 euros. Duration: 01/01/2010-30/06/2013. 307 Team leader index A L Àlvar Agustí.............................. 138 Jordi Alberch............................ 218 Antonio Alcaraz........................ 140 Vicente Arroyo.......................... 157 Francisco Lozano........................ 89 B Oriol Bachs............................... 290 Juan Balasch............................ 144 Joan Albert Barberà.................. 131 Miguel Bernardo....................... 221 Jaume Bosch........................... 164 Josep Brugada......................... 109 Jordi Bruix................................ 161 C Josep Mª Campistol................. 114 Elías Campo Güerri................... 250 Xavier Carné............................. 298 Josep Carreras......................... 153 Antoni Castells......................... 182 Francisco Cervantes................. 272 Ricard Cervera............................ 73 Daniel Closa............................. 100 Dolors Colomer........................ 279 Cristóbal Mezquita.................... 260 Guadalupe Mengod.................. 198 Montserrat Milà........................ 262 Oscar Miró Andreu..................... 97 Rafael Molina........................... 248 P Julián Panés............................. 169 Albert Parés............................. 172 César Picado............................ 134 Anna M. Planas........................ 203 Francesca Pons........................ 256 Susana Puig............................. 265 R Antonia Ribes........................... 186 Antoni Rimola........................... 178 Emili Ros.................................. 118 S Ginés Escolar........................... 282 Manel Sabaté........................... 104 Maria Victoria Sánchez............. 236 Raimon Sanmartí........................ 72 Antoni Sisó Almirall.................. 302 F T Ramon Farré............................. 122 José Carlos Fernández-Checa... 175 Jorge Ferrer............................. 189 Joaquim Forés i Viñeta............... 92 Xavier Forns............................. 154 Eduardo Tolosa......................... 206 Antoni Torres............................ 125 Ramon Trullàs........................... 244 E G Pere Gascón Vilaplana.............. 286 Josep M. Gatell.......................... 79 Ramon Gomis........................... 191 Eduard Gratacós....................... 148 Francesc Graus........................ 240 Núria Guanyabens.................... 172 308 M U Álvaro Urbano-Ispizúa............... 268 Álvaro Urbano Márquez............ 212 V Josep Valls Solé....................... 211 Y Jordi Yagüe................................. 95 J Z Carme Junqué.......................... 233 Adelaida Zabalegui.................... 305 Roselló, 149-153 08036 Barcelona www.idibaps.org Your gateway to IDIBAPS. A portal open to medical professionals, scientists and biomedicine enthusiasts where you will find information about the institution and its activities