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42 results on '"Maastricht University [Maastricht]-Maastricht University [Maastricht]"'

1. Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion

Author: Lebrun, Lorène J, Lenaerts, Kaatje, Kiers, Dorien, Pais de Barros, Jean-Paul, Le Guern, Naïg, Plesnik, Jiri, Thomas, Charles, Bourgeois, Thibaut, Dejong, Cornelis H.C., Kox, Matthijs, Hundscheid, Inca H.R., Khan, Naim Akhtar, Mandard, Stéphane, Deckert, Valérie, Pickkers, Peter, Drucker, Daniel, Lagrost, Laurent, Grober, Jacques, Surgery, RS: NUTRIM - R2 - Liver and digestive health, RS: NUTRIM - R2 - Gut-liver homeostasis, MUMC+: MA Heelkunde (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Promovendi NTM, MUMC+: DA Pat AIOS (9), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Department of Surgery [Maastricht, the Netherlands], NUTRIM School of Nutrition and Translational Research in Metabolism [Maastricht, The Netherlands]-Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Department of Intensive Care Medicine [Nijmegen, the Netherlands], Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands]-Radboud Institute for Health Sciences [Nijmegen, the Netherlands]-Radboud Center for Infectious Diseases [Nijmegen, the Netherlands]-Radboud University Medical Center [Nijmegen], Equipe NuTox (LNC - U1231) (NUTOX), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Department of Medicine [Toronto, Canada], Mt. Sinai Hospital [Toronto, Canada]-Lunenfeld-Tanenbaum Research Institute [Toronto, Canada]-University of Toronto [Canada], This work was supported by the INSERM, Centre de Recherches UMR 1231, the University Bourgogne Franche-Comte´ , a French government grant managed by the French National Research Agency under the program ‘‘Investissements d’Avenir’’ with reference ANR-11 LABX-0021, the FEDER, and the Regional Council of Bourgogne Franche-Comte´ . D.J.D. is supported by the Canada Research Chairs program, CIHR grant 154321, and the Banting & Best Diabetes Centre-Novo Nordisk Chair in Incretin Biology., ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011), Mandard, Stéphane, Laboratoires d'excellence - Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer - - Lipstic2011 - ANR-11-LABX-0021 - LABX - VALID, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht]-NUTRIM School of Nutrition and Translational Research in Metabolism [Maastricht, The Netherlands], Radboud University Medical Center [Nijmegen]-Radboud Institute for Health Sciences [Nijmegen, the Netherlands]-Radboud Center for Infectious Diseases [Nijmegen, the Netherlands]-Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands], Mt. Sinai Hospital [Toronto, Canada]-University of Toronto [Canada]-Lunenfeld-Tanenbaum Research Institute [Toronto, Canada], ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer(2011), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), NUTRIM School of Nutrition and Translational Research in Metabolism [Maastricht, The Netherlands]-Maastricht University Medical Center [the Netherlands], Equipe NuTox (LNC - U1231) ( NUTOX ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Lunenfeld-Tanenbaum Research Institute [Toronto, ON, Canada]-Mt. Sinai Hospital [Toronto, Canada]-University of Toronto [Canada], ANR-11-LABX-0021/11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du ( 2011 ), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, endocrine system, Adolescent, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], LIPOPOLYSACCHARIDE, Proglucagon, INSULIN-SECRETION, DISEASE, Young Adult, gut injury, INFLAMMATION, Ileum, Animals, Humans, Calcium Signaling, TLR4, PERMEABILITY, PHYSIOLOGY, lcsh:QH301-705.5, Cells, Cultured, Aged, Aged, 80 and over, GLUCAGON-LIKE PEPTIDE-1, enteroendocrine cells, Interleukin-6, Dextran Sulfate, digestive, oral, and skin physiology, Middle Aged, Colitis, lipopolysaccharides, RECEPTOR AGONISTS, glucagon-like peptide 1, Mice, Inbred C57BL, Toll-Like Receptor 4, MODEL, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MICE, Proprotein Convertase 1, lcsh:Biology (General), intestinal ischemia, Reperfusion Injury, Cytokines, Myristic Acids, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, hormones, hormone substitutes, and hormone antagonists
Abstract: Summary: Glucagon-like peptide 1 (GLP-1) is a hormone released from enteroendocrine L cells. Although first described as a glucoregulatory incretin hormone, GLP-1 also suppresses inflammation and promotes mucosal integrity. Here, we demonstrate that plasma GLP-1 levels are rapidly increased by lipopolysaccharide (LPS) administration in mice via a Toll-like receptor 4 (TLR4)-dependent mechanism. Experimental manipulation of gut barrier integrity after dextran sodium sulfate treatment, or via ischemia/reperfusion experiments in mice, triggered a rapid rise in circulating GLP-1. This phenomenon was detected prior to measurable changes in inflammatory status and plasma cytokine and LPS levels. In human subjects, LPS administration also induced GLP-1 secretion. Furthermore, GLP-1 levels were rapidly increased following the induction of ischemia in the human intestine. These findings expand traditional concepts of enteroendocrine L cell biology to encompass the sensing of inflammatory stimuli and compromised mucosal integrity, linking glucagon-like peptide secretion to gut inflammation. : Lebrun et al. demonstrate that enteroendocrine L cells sense lipopolysaccharides (pro-inflammatory bacterial compounds) after gut injury and respond by secreting glucagon-like peptide 1. These findings expand concepts of L cell function to include roles as both a nutrient and pathogen sensor, linking glucagon-like peptide secretion to gut inflammation. Keywords: glucagon-like peptide 1, lipopolysaccharides, enteroendocrine cells, TLR4, gut injury, intestinal ischemia, inflammation
Published: 2017

2. OBEDIS Core Variables Project: European Expert Guidelines on a Minimal Core Set of Variables to Include in Randomized, Controlled Clinical Trials of Obesity Interventions

Author: António L. Palmeira, Thorkild I. A. Sørensen, Martin Neovius, Martine Laville, Mikael Rydén, Andrea Natali, Maud Alligier, Romain Barrès, Kristina Campbell, David Jacobi, I. Sadaf Farooqi, Jean-Michel Oppert, Helen M. Roche, André Scheen, Karine Clément, Ellen E. Blaak, Yves Boirie, Gijs H. Goossens, Jason C.G. Halford, Luc Tappy, Nathalie Farpour-Lambert, Hannele Yki-Järvinen, Uberto Pagotto, Chantal Simon, Jörg Hager, Jildau Bouwman, Paul Brunault, Gema Frühbeck, Dominique Langin, Olivier Ziegler, Chantal Julia, Hans Hauner, Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), University of Copenhagen = Københavns Universitet (KU), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], CHU Clermont-Ferrand, Netherlands Organization for Applied Scientific Research (TNO), TNO Science and Industry, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), KC Microbiome Communications Group, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University of Cambridge [UK] (CAM), Université de Genève (UNIGE), Geneva University Hospitals and Geneva University, Clínica Universidad de Navarra [Pamplona], Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], University of Liverpool, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Klinikums rechts der Isar, Centre National de la Recherche Scientifique (CNRS), Université de Nantes (UN), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pisa - Università di Pisa, Karolinska Institutet [Stockholm], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Alma Mater Studiorum University of Bologna (UNIBO), Université de Lisbonne, University College Dublin [Dublin] (UCD), Centre Hospitalier Universitaire de Liège (CHU-Liège), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Lausanne (UNIL), Minerva Foundation Institute for Medical Research, University of Helsinki, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Joint Programming Initiative Heathy Diet for Healthy Life, Alligier M., Barres R., Blaak E.E., Boirie Y., Bouwman J., Brunault P., Campbell K., Clement K., Farooqi I.S., Farpour-Lambert N.J., Fruhbeck G., Goossens G.H., Hager J., Halford J.C.G., Hauner H., Jacobi D., Julia C., Langin D., Natali A., Neovius M., Oppert J.M., Pagotto U., Palmeira A.L., Roche H., Ryden M., Scheen A.J., Simon C., Sorensen T.I.A., Tappy L., Yki-Jarvinen H., Ziegler O., Laville M., FCRIN/FORCE Network, Centre de Recherche en Nutrition Humaine Rhône-Alpes, Novo Nordisk, Department of Human Biology, Maastricht University Medical Center (MUMC), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Nutrition clinique, Centre Hospitalier Universitaire Gabriel Montpied, TNO,Netherlands Organisation for Applied Scientific Research, UMR U 1253, Université de Tours, Nutrition et obésité : approches systémiques, Sorbonne Université, Wellcome-MRC Institute of Metabolic Science and NIHR Biomedical Research Centre, University of Cambridge, Service of Therapeutic Education for Chronic Diseases, Department of Community Health, Primary Care and Emergency, Geneva University Hospitals, Department of Endocrinology and Nutrition, Navarra Public Health Institute, Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición - Biomedical Research Center in Red-Physiopathology of Obesity and Nutrition (CIBEROBN), University of Navarra, University of Cape Town, Metabolic Phenotyping, Nestlé Institute of Health Sciences, Psychological Sciences, University of Liverpool (University of Liverpool), Institut für Ernährungsmedizin des Klinikums Rechts der Isar, Technical University of Munich (TUM), Institut du Thorax, Centre Hospitalier Universitaire de Nantes, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Université Toulouse III - Paul Sabatier, Centre Hospitalier Universitaire de Toulouse, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Department of Medicine (Solna), Nutrition, Institut de Cardiométabolisme et Nutrition (ICAN), CHU Pitié-Salpêtrière [APHP], Department of Medical and Surgical Sciences, Universita degli Studi di Padova, CIPER, PANO-SR, Faculty of Human Kinetics, University of Lisbon, UCD Institute of Food and Health, University College Dublin (UCD), Department of Medicine, The University of Sydney, Diabètes, Nutrition et maladies métaboliques, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Physiologie, Université de Picardie Jules Verne (UPJV), Helsinki University Central Hospital, Endocrinologie, Diabetes et Nutrition, Hôpital Brabois, Maastricht University [Maastricht]-Maastricht University [Maastricht], Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, ProdInra, Archive Ouverte, Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), University of Copenhagen = Københavns Universitet (UCPH), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Université de Genève = University of Geneva (UNIGE), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lausanne = University of Lausanne (UNIL), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, HUS Internal Medicine and Rehabilitation, Humane Biologie, and RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health
Subjects: 0301 basic medicine, Research design, Gerontology, Health (social science), Psychological intervention, Choice Behavior, 0302 clinical medicine, QUALITY-OF-LIFE, OBSTRUCTIVE SLEEP-APNEA, Medicine, Medical History Taking, lcsh:RC620-627, Interventions, METABOLIC SYNDROME, Randomized Controlled Trials as Topic, ddc:616, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Precision medicine, Prognosis, C-REACTIVE PROTEIN, 3. Good health, Europe, lcsh:Nutritional diseases. Deficiency diseases, CARDIOVASCULAR-DISEASE, Research Design, Variable, lcsh:Nutrition. Foods and food supply, Human, Prognosi, education, WEIGHT-LOSS, lcsh:TX341-641, Intervention, 030209 endocrinology & metabolism, GASTRIC BYPASS-SURGERY, Guidelines, Patient care, 03 medical and health sciences, Variables, Physiology (medical), Humans, CORONARY-HEART-DISEASE, Obesity, Expert Testimony, Core set, 030109 nutrition & dietetics, business.industry, Stratification, medicine.disease, Diet, BODY-MASS INDEX, Clinical trial, PHYSICAL-ACTIVITY, Biological Variation, Population, 3121 General medicine, internal medicine and other clinical medicine, Metabolic syndrome, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes. © 2020 The Author(s) Published by S. Karger AG, Basel.
Published: 2020

3. Innovative devices for actinic keratoses: a hot‐button issue

Author: Nicole W.J. Kelleners-Smeets, Mahtab Samimi, Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de dermatologie (Maastricht), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Dermatologie, MUMC+: MA Dermatologie (9), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: medicine.medical_specialty, Keratosis, business.industry, [SDV]Life Sciences [q-bio], Dermatology, Actinic keratoses, medicine.disease, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience
Published: 2020

4. A Novel Framework for Noninvasive Analysis of Short-Term Atrial Activity Dynamics During Persistent Atrial Fibrillation

Author: Ulrich Schotten, Harry J.G.M. Crijns, Joël Karel, Theo Lankveld, Olivier Meste, Pietro Bonizzi, Ralf Peeters, Stef Zeemering, Department of data science and Knowledge Engineering [Maastricht], Maastricht University [Maastricht], Laboratoire d'Informatique, Signaux, et Systèmes de Sophia-Antipolis (I3S) / Equipe SIGNAL, Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Department of Physiology, Maastricht University, Department of Physiology, Maastricht University [Maastricht]-Maastricht University [Maastricht], DKE Scientific staff, RS: FSE DACS, RS: FSE DACS Mathematics Centre Maastricht, RS: Carim - H08 Experimental atrial fibrillation, Fysiologie, MUMC+: MA Med Staf Artsass Cardiologie (9), Cardiologie, RS: Carim - H01 Clinical atrial fibrillation, MUMC+: MA Cardiologie (9), and RS: FSE MaCSBio
Subjects: medicine.medical_specialty, Databases, Factual, Recurrence analysis, Biomedical Engineering, Electric Countershock, 030204 cardiovascular system & hematology, ELECTROCARDIOGRAM, Signal, 03 medical and health sciences, Electrocardiography, 0302 clinical medicine, Spatio-Temporal Analysis, Atrial fibrillation progression, Recurrence, Internal medicine, Atrial Fibrillation, medicine, Waveform, Humans, Heart Atria, Propagation patterns, Physics, medicine.diagnostic_test, Dynamics (mechanics), Body Surface Potential Mapping, Atrial fibrillation substrate complexity, Models, Cardiovascular, Atrial fibrillation, Signal Processing, Computer-Assisted, STANDARDIZATION, medicine.disease, Computer Science Applications, Term (time), Electrical cardioversion, Persistent atrial fibrillation, Cardiology, Original Article, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, 030217 neurology & neurosurgery
Abstract: International audience; ECG-based representation of atrial fibrillation (AF) progression is currently limited. We propose a novel framework for a more sensitive noninvasive characterization of the AF substrate during persistent AF. An atrial activity (AA) recurrence signal is computed from body surface potential map (BSPM) recordings, and a set of characteristic indices is derived from it which captures the short- and long-term recurrent behaviour in the AA patterns. A novel measure of short- and long-term spatial variability of AA propagation is introduced, to provide an interpretation of the above indices, and to test the hypothesis that the variability in the oscillatory content of AA is due mainly to a spatially uncoordinated propagation of the AF waveforms. A simple model of atrial signal dynamics is proposed to confirm this hypothesis, and to investigate a possible influence of the AF substrate on the short-term recurrent behaviour of AA propagation. Results confirm the hypothesis, with the model also revealing the above influence. Once the characteristic indices are normalized to remove this influence, they show to be significantly associated with AF recurrence 4 to 6 weeks after electrical cardioversion. Therefore, the proposed framework improves noninvasive AF substrate characterization in patients with a very similar substrate. Graphical Abstract Schematic representation of the proposed framework for the noninvasive characterization of short-term atrial signal dynamics during persistent AF. The proposed framework shows that the faster the AA is propagating, the more stable its propagation paths are in the short-term (larger values of Speed in the bottom right plot should be interpreted as lower speed of propagation of the corresponding AA propagation patters).
Published: 2020

5. Decoding the sound of hand-object interactions in primary somatosensory cortex

Author: Bailey, Kerri, Giordano, Bruno, Kaas, Amanda, Smith, Fraser, University of East Anglia [Norwich] (UEA), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Department of Cognitive Neuroscience [Maastricht, Pays-Bas], Faculty of Psychology and Neuroscience [Maastricht, Pays-Bas], and Maastricht University [Maastricht]-Maastricht University [Maastricht]
Subjects: [SCCO.NEUR]Cognitive science/Neuroscience
Published: 2020

6. Comparison of SMS-EPI and 3D-EPI at 7T in an fMRI localizer study with matched spatiotemporal resolution and homogenized excitation profiles

Author: Le Ster, Caroline, Moreno, Antonio, Mauconduit, Franck, Gras, Vincent, Stirnberg, Ruediger, Poser, Benedikt A., Vignaud, Alexandre, Eger, Evelyn, Dehaene, Stanislas, Meyniel, Florent, Boulant, Nicolas, IFR49 - Neurospin - CEA, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de la Santé et de la Recherche Médicale (INSERM), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Department of Cognitive Neuroscience [Maastricht, Pays-Bas], Faculty of Psychology and Neuroscience [Maastricht, Pays-Bas], Maastricht University [Maastricht]-Maastricht University [Maastricht], Collège de France - Chaire Psychologie cognitive expérimentale, Collège de France (CdF (institution)), This work was supported by European Research Council, Proof of Concept #700812 (https://erc.europa.eu/funding/proofconcept)., Chaire Psychologie cognitive expérimentale, MRI, RS: FPN CN 5, and Bodescot, Myriam
Subjects: Central Nervous System, Male, Physiology, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Sensory Physiology, Social Sciences, Signal-To-Noise Ratio, Biochemistry, Nervous System, methods [Echo-Planar Imaging], Diagnostic Radiology, Fats, Database and Informatics Methods, methods [Brain Mapping], methods [Magnetic Resonance Imaging], Functional Magnetic Resonance Imaging, Medicine and Health Sciences, Image Processing, Computer-Assisted, Psychology, 3 T, Language, TESLA, Brain Mapping, Echo-Planar Imaging, Radiology and Imaging, Physics, Brain, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, TEMPORAL RESOLUTION, Magnetic Resonance Imaging, Lipids, Physical Sciences, Medicine, Female, PARALLEL, Anatomy, Sequence Analysis, Research Article, Adult, Imaging Techniques, Bioinformatics, TRANSMISSION, Science, Sequence Databases, Neuroimaging, Research and Analysis Methods, Sensitivity and Specificity, Young Adult, physiology [Brain], Diagnostic Medicine, Acoustic Signals, Humans, WHOLE-BRAIN, ddc:610, 2D, Cognitive Psychology, Biology and Life Sciences, Acoustics, PHYSIOLOGICAL NOISE, RF PULSES, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Biological Databases, ROC Curve, STATE FUNCTIONAL MRI, Cognitive Science, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Neuroscience
Abstract: International audience; The simultaneous multi-slice EPI (SMS-EPI, a.k.a. MB-EPI) sequence has met immense popularity recently in functional neuroimaging. A still less common alternative is the use of 3D-EPI, which offers similar acceleration capabilities. The aim of this work was to compare the SMS-EPI and the 3D-EPI sequences in terms of sampling strategies for the detection of task-evoked activations at 7T using detection theory. To this end, the spatial and temporal resolutions of the sequences were matched (1.6 mm isotropic resolution, TR = 1200 ms) and their excitation profiles were homogenized by means of calibration-free parallel-transmission (Universal Pulses). We used a fast-event "localizer" paradigm of 5:20 min in order to probe sensorimotor functions (visual, auditory and motor tasks) as well as higher level functions (language comprehension, mental calculation), where results from a previous large-scale study at 3T (N = 81) served as ground-truth reference for the brain areas implicated in each cognitive function. In the current study, ten subjects were scanned while their activation maps were generated for each cognitive function with the GLM analysis. The SMS-EPI and 3D-EPI sequences were compared in terms of raw tSNR, t-score testing for the mean signal, activation strength and accuracy of the robust sensorimotor functions. To this end, the sensitivity and specificity of these contrasts were computed by comparing their activation maps to the reference brain areas obtained in the 3T study. Estimated flip angle distributions in the brain reported a normalized root mean square deviation from the target value below 10% for both sequences. The analysis of the t-score testing for the mean signal revealed temporal noise correlations, suggesting the use of this metric instead of the traditional tSNR for testing fMRI sequences. The SMS-EPI and 3D-EPI thereby yielded similar performance from a detection theory perspective.
Published: 2019

7. Homeostasis of the gut barrier and potential biomarkers

Author: Agnes Meheust, Muriel Derrien, Patrice D. Cani, Freddy J. Troost, Thomas T. MacDonald, Vassilia Theodorou, Jerry M. Wells, Robert-Jan M. Brummer, Annick Mercenier, Willem M. de Vos, Jan Dekker, Clara Lucia Garcia-Rodenas, Arjen Nauta, Animal Sciences, Host-Microbe Interactomics, Wageningen University and Research Center (WUR), School of Medicine and Health, Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Centre Daniel Carasso, Danone Nutricia Research, Barts and The London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London (QMUL), University Hospital Maastricht, Department of Internal Medicine, Division of Gastroenterology-Hepatology, Maastricht University Medical Center (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Metabolism and Nutrition Research Group, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), Louvain Drug Research Institute, Université Catholique de Louvain, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Groupe Danone, Laboratory of Microbiology, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institute of Nutritional Science, Nestlé Research Center, FrieslandCampina, Wageningen University and Research [Wageningen] (WUR), Maastricht University Medical Centre (MUMC), Université Catholique de Louvain = Catholic University of Louvain (UCL), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, UCL - SSS/LDRI - Louvain Drug Research Institute, and Wells, Jerry M.
Subjects: 0301 basic medicine, IRRITABLE-BOWEL-SYNDROME, Gastrointestinal Diseases, Physiology, epithelial permeability, Segmented filamentous bacteria, [SDV]Life Sciences [q-bio], BACTERICIDAL/PERMEABILITY-INCREASING PROTEIN, toxicologie alimentaire, microbiote digestif, POLYMERIC IMMUNOGLOBULIN RECEPTOR, Review, human health, peptide antimicrobien, antimicrobial peptides, Epithelial permeability, Microbiologie, Gut barrier, TIGHT JUNCTION PERMEABILITY, Homeostasis, IGA MONOCLONAL-ANTIBODIES, biology, Microbiota, Gastroenterology, Pattern recognition receptor, santé humaine, 3. Good health, INNATE IMMUNE-RESPONSE, trouble gastrointestinal, perméabilité intestinale, Antimicrobial peptides, moyen de prévention, Microbiology, 03 medical and health sciences, Immune system, Physiology (medical), medicine, microbiota, Animals, Humans, Host-Microbe Interactomics, REGULATORY T-CELLS, gut barrier, VLAG, TOLL-LIKE RECEPTORS, Innate immune system, Hepatology, barrière intestinale, medicine.disease, Bactericidal/permeability-increasing protein, Mucus, Gastrointestinal Tract, SEGMENTED FILAMENTOUS BACTERIA, 030104 developmental biology, Immunology, biology.protein, WIAS, INTESTINAL EPITHELIAL-CELLS, Dysbiosis
Abstract: The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions through the production of short-chain fatty acids (SCFAs) and interactions with innate pattern recognition receptors in the mucosa, driving the steady-state expression of mucus and antimicrobial factors. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability, and dysbiosis of the microbiota, which are recognized to play a role in the pathophysiology of a variety of gastrointestinal disorders. Additionally, gut-brain signaling may be affected by prolonged mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the hypothalamus-pituitary-adrenal axis and both mast cell-dependent and mast cell-independent mechanisms. The modulation of gut barrier function through nutritional interventions, including strategies to manipulate the microbiota, is considered a relevant target for novel therapeutic and preventive treatments against a range of diseases. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases, but there remains a need to explore their use in assessing the effect of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of available biomarkers and their predictive value for gut health in human cohorts.
Published: 2017

8. Implicit learning of artificial grammatical structures after inferior frontal cortex lesions

Author: Sonja A. Kotz, Tatiana Jarret, Anika Stockert, Barbara Tillmann, Section Neuropsychology, RS: FPN NPPP I, Auditory Cognition and Psychoacoustics Team [Lyon], Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Language and Aphasia Laboratory [Leipzig, Allemagne], Department of Neurology [Leipzig, Allemagne], Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Department of Neuropsychology [Leipzig, Allemagne], Max Planck Institute for Human Cognitive and Brain Sciences [Leipzig] (IMPNSC), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Department of Neuropsychology [Maastricht, Pays-Bas], Faculty of Psychology and Neuroscience [Maastricht, Pays-Bas], Maastricht University [Maastricht]-Maastricht University [Maastricht], Department of Psychopharmacology [Maastricht, Pays-Bas], This research was supported by a grant from EBRAMUS ITN to BT and SAK (Europe BRAin and MUSic) (Grant Agreement number 238157). The team 'Auditory cognition and psychoacoustics' is part of the LabEx CeLyA ('Centre Lyonnais d’Acoustique', grant ANR-10-LABX-60 to BT)., ANR-10-LABX-0060,CeLyA,Lyon Acoustics Centre(2010), Bodescot, Myriam, Lyon Acoustics Centre - - CeLyA2010 - ANR-10-LABX-0060 - LABX - VALID, Auditory Cognition and Psychoacoustics (CAP), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, NEURAL BASIS, Physiology, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Social Sciences, LANGUAGE, Pathology and Laboratory Medicine, 0302 clinical medicine, Cognition, Learning and Memory, BASAL GANGLIA, COGNITIVE CONTROL, Medicine and Health Sciences, Psychology, Evoked Potentials, Clinical Neurophysiology, Cognitive Impairment, Grammar, Brain Mapping, BRAIN BASIS, Multidisciplinary, CHUNK STRENGTH, Learning Disabilities, Cognitive Neurology, 05 social sciences, SYNTAX, Electroencephalography, Middle Aged, Language acquisition, Frontal Lobe, Electrophysiology, Bioassays and Physiological Analysis, Categorization, Brain Electrophysiology, Neurology, Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, psychological phenomena and processes, ERP, Cognitive psychology, Research Article, Artificial grammar learning, Imaging Techniques, Science, Cognitive Neuroscience, education, Prefrontal Cortex, Neurophysiology, Context (language use), Neuroimaging, EVENT-RELATED POTENTIALS, Cognitive neuroscience, Research and Analysis Methods, behavioral disciplines and activities, 050105 experimental psychology, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, BROCAS AREA, Humans, Learning, 0501 psychology and cognitive sciences, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, Language Acquisition, Language Disorders, Electrophysiological Techniques, Cognitive Psychology, Biology and Life Sciences, Linguistics, Syntax, Implicit learning, Broca Area, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Case-Control Studies, Lesions, Cognitive Science, Clinical Medicine, 030217 neurology & neurosurgery, Neuroscience
Abstract: Objective Previous research associated the left inferior frontal cortex with implicit structure learning. The present study tested patients with lesions encompassing the left inferior frontal gyrus (LIFG; including Brodmann areas 44 and 45) to further investigate this cognitive function, notably by using non-verbal material, implicit investigation methods, and by enhancing potential remaining function via dynamic attending. Patients and healthy matched controls were exposed to an artificial pitch grammar in an implicit learning paradigm to circumvent the potential influence of impaired language processing. Methods Patients and healthy controls listened to pitch sequences generated within a finite-state grammar (exposure phase) and then performed a categorization task on new pitch sequences (test phase). Participants were not informed about the underlying grammar in either the exposure phase or the test phase. Furthermore, the pitch structures were presented in a highly regular temporal context as the beneficial impact of temporal regularity (e.g. meter) in learning and perception has been previously reported. Based on the Dynamic Attending Theory (DAT), we hypothesized that a temporally regular context helps developing temporal expectations that, in turn, facilitate event perception, and thus benefit artificial grammar learning. Results Electroencephalography results suggest preserved artificial grammar learning of pitch structures in patients and healthy controls. For both groups, analyses of event-related potentials revealed a larger early negativity (100–200 msec post-stimulus onset) in response to ungrammatical than grammatical pitch sequence events. Conclusions These findings suggest that (i) the LIFG does not play an exclusive role in the implicit learning of artificial pitch grammars, and (ii) the use of non-verbal material and an implicit task reveals cognitive capacities that remain intact despite lesions to the LIFG. These results provide grounds for training and rehabilitation, that is, learning of non-verbal grammars that may impact the relearning of verbal grammars. © 2019 Jarret et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Published: 2019

9. 2018 Joint European consensus document on the management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous cardiovascular interventions:a joint consensus document of the European Heart Rhythm Association (EHRA), European Society of Cardiology Working Group on Thrombosis, European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA)

Author: Fauchier, Laurent, Cinaud, Alexandre, Brigadeau, François, Lepillier, Antoine, Pierre, Bertrand, Abbey, Selim, Fatemi, Marjaneh, Franceschi, Frederic, Guedeney, Paul, Jacon, Peggy, Paziaud, Olivier, Venier, Sandrine, Deharo, Jean Claude, Gras, Daniel, Klug, Didier, Mansourati, Jacques, Montalescot, Gilles, Piot, Olivier, Defaye, Pascal, Lip, Gregory, Collet, Jean-Phillippe, Haude, Michael, Byrne, Robert, Chung, Eugene, Halvorsen, Sigrun, Lau, Dennis, Lopez-Cabanillas, Nestor, Lettino, Maddalena, Marin, Francisco, Obel, Israel, Rubboli, Andrea, Storey, Robert, Valgimigli, Marco, Huber, Kurt, Potpara, Tatjana, Blomström Lundqvist, Carina, Crijns, Harry, Steffel, Jan, Heidbüchel, Hein, Stankovic, Goran, Airaksinen, Juhani, ten Berg, Jurrien, Capodanno, Davide, James, Stefan, Bueno, Hector, Morais, Joao, Sibbing, Dirk, Rocca, Bianca, Hsieh, Ming-Hsiung, Akoum, Nazem, Lockwood, Deborah, Gomez Flores, Jorge Rafael, Jardine, Ronald, Fysiologie, MUMC+: MA Cardiologie (9), Cardiologie, RS: CARIM - R2.01 - Clinical atrial fibrillation, RS: Carim - H01 Clinical atrial fibrillation, Éducation Éthique Santé EA 7505 (EES), Université de Tours (UT), Université Paris Descartes - Paris 5 (UPD5), Hôtel-Dieu, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre cardiologique du Nord (CCN), Griset SA, Diehl - Griset, Nouvelles Cliniques Nantaises, Service de Cardiologie (BREST - Cardio), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de cardiologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Grenoble, Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques (DS-ACI / UMR MD2), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Cardiologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Optimisation des régulations physiologiques (ORPHY (EA 4324)), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Cardiac Stimulation and Rhythmology, University of Liverpool, Aalborg University [Denmark] (AAU), Lukaskrankenhaus, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Universidad Nacional de Córdoba [Argentina], San Gerardo Hospital of Monza, Universidad de Murcia, S. Maria delle Croci Hospital, University of Sheffield [Sheffield], University of Bern, Sigmund Freud University (SFU), University of Belgrade [Belgrade], Department of Physiology, Maastricht University, Department of Physiology, Maastricht University [Maastricht]-Maastricht University [Maastricht], University hospital of Zurich [Zurich], and ESC Sci Document Grp
Subjects: Cardiac Catheterization, medicine.medical_treatment, Heart Valve Diseases, ELUTING STENT IMPLANTATION, 030204 cardiovascular system & hematology, VITAMIN-K ANTAGONIST, Left atrial appendage occlusion, Coronary artery disease, [SHS]Humanities and Social Sciences, Percutaneous coronary intervention, 0302 clinical medicine, HAS-BLED SCORES, Risk Factors, Stent, ST-SEGMENT ELEVATION, Position paper, 030212 general & internal medicine, Myocardial infarction, Consensus document, 610 Medicine & health, Stroke, ComputingMilieux_MISCELLANEOUS, BARE-METAL STENTS, European Heart Rhythm Association, AORTIC-VALVE IMPLANTATION, Low molecular weight heparin, Antiplatelet agents, DUAL ANTIPLATELET THERAPY, Atrial fibrillation, Acute coronary syndrome, Anticoagulation, Antithrombotic therapy, Bleeding, Non-Vitamin K antagonist oral anticoagulants, Parenteral anticoagulants, Thromboembolism, Thrombosis, Vitamin K antagonists, Cardiology and Cardiovascular Medicine, Physiology (medical), BLEEDING RISK SCORES, Treatment Outcome, UNINTERRUPTED ORAL ANTICOAGULATION, ACUTE MYOCARDIAL-INFARCTION, medicine.medical_specialty, Consensus, Settore BIO/14 - FARMACOLOGIA, medicine.drug_class, Hemorrhage, Risk Assessment, 03 medical and health sciences, Fibrinolytic Agents, medicine, Humans, Intensive care medicine, business.industry, Anticoagulants, ta3121, medicine.disease, Non-vitamin K antagonist oral anticoagulants, Human medicine, business, Platelet Aggregation Inhibitors
Abstract: In 2014, a joint consensus document dealing with the management of antithrombotic therapy in atrial fibrillation (AF) patients presenting with acute coronary syndrome (ACS) and/or undergoing percutaneous coronary or valve interventions was published, which represented an effort of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). Since publication of this document, additional data from observational cohorts, randomized controlled trials, and percutaneous interventions as well as new guidelines have been published. Moreover, new drugs and devices/interventions are also available, with an increasing evidence base. The approach to managing AF has also evolved towards a more integrated or holistic approach. In recognizing these advances since the last consensus document, EHRA, WG Thrombosis, EAPCI, and ACCA, with additional contributions from HRS, APHRS, Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA), proposed a focused update, to include the new data, with the remit of comprehensively reviewing the available evidence and publishing a focused update consensus document on the management of antithrombotic therapy in AF patients presenting with ACS and/or undergoing percutaneous coronary or valve interventions, and providing up-to-date consensus recommendations for use in clinical practice.
Published: 2019

10. ADHERE: randomized controlled trial comparing renal function in de novo kidney transplant recipients receiving prolonged-release tacrolimus plus mycophenolate mofetil or sirolimus

Author: Rummo, Oleg O., Carmellini, Mario, Rostaing, Lionel, Oberbauer, Rainer, Christiaans, Maarten H. L., Mousson, Christiane, Langer, Robert M., Citterio, Franco, Charpentier, Bernard, Brown, Malcolm, Kazeem, Gbenga, Lehner, Frank, Heer, Munish, Lim, Wai, Mühlbacher, Ferdinand, Pratschke, Johann, Bonvoisin, Cathérine, Kuypers, Dirk, Dedochova, Jarmila, Kuman, Milan, Le Meur, Yann, Deteix, Patrice, Frimat, Luc, Lang, Philippe, Lebranchu, Yvon, Legendre, Christophe, Westeel, Pierre Francois, Schenker, Peter, Hilgers, Karl-Friedrich, Witzke, Oliver, Hauser, Ingeborg, Kliem, Volker, Zeier, Martin, Kunzendorf, Ulrich, Bartels, Michael, Jonas, Sven, Guba, Markus, Wolters, Heiner H., Chan, Tak-Mao, Caputo, Flavia, Sparacino, Vito, Nowicki, Michal, Glyda, Maciej, Kim, Yu Seun, Jongwon, Ha, Kim, Chan Duck, Han, Duck Jong, Kim, Yeong Hoon, Perlin, Dmitry, Sal'Mayer, Alexander, Semchenko, Sergey B., Nesterenko, Igor, Franco, Antonio, Grinyó, Josep, Inza, Ainhoa, Ruiz, Juan Carlos, Chiang, Yang-Jen, Lee, Po-Chang, Suleymanlar, Gultekin, Sevmis, Sinasi, Kacar, Serdar, Republican Scientific and Practical Center (RSPC) for organ and Tissue Transplantation, Minsk, Republican Scientific and Practical Center (RSPC) for Organ and Transplantation, Department of Medical, Surgical and Neuroscience, University of Siena, Policlinico 'Santa Maria alle Scotte', Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Department of Internal Medicine III, Medizinische Universität Wien = Medical University of Vienna, Department of Internal Medicine/Division of Nephrology, Maastrich, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Department of Chemical Engineering (DCE-MIT), Massachusetts Institute of Technology (MIT), Department of Surgery , Renal Transplantation, Rome, Catholic University, Rome, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Internal Medicine, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Astellas Pharma Europe Ltd, Chertsey, Universität Bern [Bern], Universidad de Cantabria, Kuypers, Dirk, RS: NUTRIM - R3 - Respiratory & Age-related Health, MUMC+: MA Nefrologie (9), Interne Geneeskunde, and RS: NUTRIM - R3 - Chronic inflammatory disease and wasting
Subjects: Graft Rejection, Male, Time Factors, Settore MED/18 - CHIRURGIA GENERALE, MULTICENTER, 030232 urology & nephrology, 030230 surgery, Kidney Function Tests, GLOMERULAR-FILTRATION-RATE, Kidney Failure, 0302 clinical medicine, Adrenal Cortex Hormones, Clinical endpoint, Medicine, calcineurin antagonists, Chronic, Kidney transplantation, ComputingMilieux_MISCELLANEOUS, OUTCOMES, immunosuppression, Graft Survival, Middle Aged, 3. Good health, kidney clinical, Treatment Outcome, surgical procedures, operative, REJECTION, Tolerability, ALLOGRAFT RECIPIENTS, outcome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, WITHDRAWAL, Immunosuppressive Agents, Glomerular Filtration Rate, medicine.drug, Adult, medicine.medical_specialty, Urology, Renal function, Tacrolimus, Mycophenolic acid, 03 medical and health sciences, Transplantation, Humans, EXPOSURE, COMBINATION, Aged, Sirolimus, business.industry, Mycophenolic Acid, medicine.disease, Kidney Failure, Chronic, Transplant Recipients, Kidney Transplantation, Surgery, Discontinuation, INHIBITORS, business
Abstract: ADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 postkidney transplant, in patients who received prolonged-release tacrolimus-based immunosuppressive regimens. On Days 0-27, patients received prolonged-release tacrolimus (initially 0.2 mg/kg/day), corticosteroids, and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolonged-release tacrolimus (≥25% dose reduction on Day 42) plus sirolimus (Arm 2). The primary endpoint was glomerular filtration rate by iohexol clearance (mGFR) at Week 52. Secondary endpoints included eGFR, creatinine clearance (CrCl), efficacy failure (patient withdrawal or graft loss), and patient/graft survival. Tolerability was analyzed. The full-analysis set comprised 569 patients (Arm 1: 287; Arm 2: 282). Week 52 mean mGFR was similar in Arm 1 versus Arm 2 (40.73 vs. 41.75 ml/min/1.73 m(2) ; P = 0.405), as were the secondary endpoints, except composite efficacy failure, which was higher in Arm 2 versus 1 (18.2% vs. 11.5%; P = 0.002) owing to a higher postrandomization withdrawal rate due to adverse events (AEs) (14.4% vs. 5.2%). Results from this study show comparable renal function between arms at Week 52, with fewer AEs leading to study discontinuation with prolonged-release tacrolimus plus MMF (Arm 1) versus lower dose prolonged-release tacrolimus plus sirolimus (Arm 2). ispartof: Transplant International vol:30 issue:1 pages:83-95 ispartof: location:Switzerland status: published
Published: 2017

11. Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study

Author: Eléonore Tollard, Christel Depienne, Carola G.M. van Berkel, Graziella Uziel, Céline Dupuits, Maarten Kamermans, Truus E.M. Abbink, Suzanna G.M. Frints, Nienke L. Postma, Alexis Brice, Adeline Vanderver, Christine E. M. de Die-Smulders, Emiel Polder, Marjo S. van der Knaap, Nicole I. Wolf, Frédéric Sedel, Marianna Bugiani, Damien Galanaud, J. S. H. Vles, Vera M. Kalscheuer, Valerie Touitou, Jan Klooster, Frédéric Darios, Cengiz Yalcinkaya, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pathology Department, VU University Medical Center [Amsterdam], Child Neurology Department, Fondazione IRCCS Istituto Neurologico, Service de Neuroradiologie [CHU Pitié-Salpêtrière], Neurologie, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Radiologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Department of Clinical Genetics [Maastricht], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Department of Child Neurology [Maastricht], Department of Neurology, Children's National Medical Center, Unit of Child Neurology, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Division of Child Neurology, Istanbul University -Cerrahpasa Medical School, Department Human Molecular Genetics [MPIMG Berlin], Max Planck Institute for Molecular Genetics (MPIMG), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Department of Retinal Signal Processing, Netherlands Institute for Neuroscience-KNAW, Department of Neurogenetics, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), ELA, APHP, INSERM, Pathology, Pediatric surgery, NCA - Brain mechanisms in health and disease, Cerrahpasa Medical School-Istanbul University, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), Genetica & Celbiologie, RS: MHeNs School for Mental Health and Neuroscience, RS: GROW - School for Oncology and Reproduction, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, UF Neurométabolique Bioclinique et Génétique [CHU Pitié-Salpêtrière], Algorithms, models and methods for images and signals of the human brain (ARAMIS), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Service d'ophtalmologie [CHU Pitié-Salpêtrière], Maastricht University [Maastricht], Cerrahpasa Faculty of Medicine, Istanbul University, Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), University of Amsterdam [Amsterdam] (UvA), Service de neurologie 1 [CHU Pitié-Salpétrière], Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Depienne, Christel, Other departments, ANS - Amsterdam Neuroscience, and Genome Analysis
Subjects: Male, Pathology, Candidate gene, Brain Edema, [SDV.GEN] Life Sciences [q-bio]/Genetics, Polymerase Chain Reaction, Leukoencephalopathy, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Leukoencephalopathies, Image Processing, Computer-Assisted, Exome, Age of Onset, 10. No inequality, Child, Exome sequencing, Myelin Sheath, media_common, Neurologic Examination, 0303 health sciences, education.field_of_study, biology, Homozygote, Brain, Genetic Diseases, X-Linked, SDG 10 - Reduced Inequalities, Middle Aged, Immunohistochemistry, Magnetic Resonance Imaging, 3. Good health, medicine.anatomical_structure, Connexin 32, Female, medicine.symptom, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Signal Transduction, Adult, medicine.medical_specialty, Adolescent, Cerebellar Ataxia, White matter, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Chloride Channels, medicine, media_common.cataloged_instance, Humans, RNA, Messenger, European union, education, 030304 developmental biology, Aged, CLCN2, [SDV.GEN]Life Sciences [q-bio]/Genetics, Cerebellar ataxia, Fibroblasts, medicine.disease, CLC-2 Chloride Channels, biology.protein, Neurology (clinical), 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND: Mutant mouse models suggest that the chloride channel ClC-2 has functions in ion and water homoeostasis, but this has not been confirmed in human beings. We aimed to define novel disorders characterised by distinct patterns of MRI abnormalities in patients with leukoencephalopathies of unknown origin, and to identify the genes mutated in these disorders. We were specifically interested in leukoencephalopathies characterised by white matter oedema, suggesting a defect in ion and water homoeostasis. METHODS: In this observational analytical study, we recruited patients with leukoencephalopathies characterised by MRI signal abnormalities in the posterior limbs of the internal capsules, midbrain cerebral peduncles, and middle cerebellar peduncles from our databases of patients with leukoencephalopathies of unknown origin. We used exome sequencing to identify the gene involved. We screened the candidate gene in additional patients by Sanger sequencing and mRNA analysis, and investigated the functional effects of the mutations. We assessed the localisation of ClC-2 with immunohistochemistry and electron microscopy in post-mortem human brains of individuals without neurological disorders. FINDINGS: Seven patients met our inclusion criteria, three with adult-onset disease and four with childhood-onset disease. We identified homozygous or compound-heterozygous mutations in CLCN2 in three adult and three paediatric patients. We found evidence that the CLCN2 mutations result in loss of function of ClC-2. The remaining paediatric patient had an X-linked family history and a mutation in GJB1, encoding connexin 32. Clinical features were variable and included cerebellar ataxia, spasticity, chorioretinopathy with visual field defects, optic neuropathy, cognitive defects, and headaches. MRI showed restricted diffusion suggesting myelin vacuolation that was confined to the specified white matter structures in adult patients, and more diffusely involved the brain white matter in paediatric patients. We detected ClC-2 in all components of the panglial syncytium, enriched in astrocytic endfeet at the perivascular basal lamina, in the glia limitans, and in ependymal cells. INTERPRETATION: Our observations substantiate the concept that ClC-2 is involved in brain ion and water homoeostasis. Autosomal-recessive CLCN2 mutations cause a leukoencephalopathy that belongs to an emerging group of disorders affecting brain ion and water homoeostasis and characterised by intramyelinic oedema. FUNDING: European Leukodystrophies Association, INSERM and Assistance Publique-Hôpitaux de Paris, Dutch Organisation for Scientific Research (ZonMw), E-Rare, Hersenstichting, Optimix Foundation for Scientific Research, Myelin Disorders Bioregistry Project, National Institute of Neurological Disorders and Stroke, and Genetic and Epigenetic Networks in Cognitive Dysfunction (GENCODYS) Project (funded by the European Union Framework Programme 7).
Published: 2013

12. Analyses of single nucleotide polymorphisms in selected nutrient-sensitive genes in weight-regain prevention: the DIOGENES study

Author: Lesli H. Larsen, Marie Kunešová, Arne Astrup, Dominique Langin, Marleen A. van Baak, J. Alfredo Martínez, Susan A. Jebb, Wim H. M. Saris, Karani Santhanakrishnan Vimaleswaran, Andreas Pfeiffer, Claus Holst, Teodora Handjieva-Darlenska, Nathalie Viguerie, Angeliki Papadaki, Jorg Hager, Lars Ängquist, Thomas Larsen, Thorkild I. A. Sørensen, Ruth J. F. Loos, Department of Human Nutrition, Faculty of Life Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Institute of Preventive Medicine, Copenhagen University Hospitals, MRC Epidemiology Unit, Addenbrooke's Hospital-Institute of Metabolic Science, Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Metabolic Science, MRC, Department of Nutrition, Dietetics and Metabolic Diseases, National Transport Hospital, MRC Human Nutrition Research, Elsie Widdowson Laboratory, Institute of Endocrinology, Obesity Management Center, Department of Physiology and Nutrition, Universidad de Navarra [Pamplona] (UNAV), Department of Social Medicine, University of Crete [Heraklion] (UOC), Department of Endocrinology, Diabetes & Nutrition, German Institute of Human Nutrition-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism-Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Simon, Marie Francoise, Humane Biologie, and RS: NUTRIM - R1 - Metabolic Syndrome
Subjects: Male, 030309 nutrition & dietetics, BEHAVIOR INTERACTIONS, MESH: Dietary Proteins, PROTEIN, Medicine (miscellaneous), MESH: Food Habits, Weight Gain, Body Mass Index, MESH: Genotype, 0302 clinical medicine, Weight loss, MESH: Obesity, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 2. Zero hunger, 0303 health sciences, Nutrition and Dietetics, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH: DNA, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, Glycemic index, OBESITY, MESH: Waist Circumference, MESH: Weight Gain, DIETS, Female, Dietary Proteins, Waist Circumference, medicine.symptom, Adult, medicine.medical_specialty, Waist, Genotype, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, LOSS MAINTENANCE, Biology, Polymorphism, Single Nucleotide, MESH: Genetic Loci, MESH: Body Mass Index, 03 medical and health sciences, MESH: Weight Loss, Internal medicine, Weight Loss, medicine, Humans, Caloric Restriction, Glycemic, MESH: Caloric Restriction, MESH: Humans, MESH: Adult, DNA, Feeding Behavior, medicine.disease, Obesity, MESH: Male, Endocrinology, Genetic Loci, MESH: Glycemic Index, GLYCEMIC INDEX, Body mass index, Weight gain, MESH: Female
Abstract: International audience; BACKGROUND: Differences in the interindividual response to dietary intervention could be modified by genetic variation in nutrient-sensitive genes. OBJECTIVE: This study examined single nucleotide polymorphisms (SNPs) in presumed nutrient-sensitive candidate genes for obesity and obesity-related diseases for main and dietary interaction effects on weight, waist circumference, and fat mass regain over 6 mo. DESIGN: In total, 742 participants who had lost ≥ 8% of their initial body weight were randomly assigned to follow 1 of 5 different ad libitum diets with different glycemic indexes and contents of dietary protein. The SNP main and SNP-diet interaction effects were analyzed by using linear regression models, corrected for multiple testing by using Bonferroni correction and evaluated by using quantile-quantile (Q-Q) plots. RESULTS: After correction for multiple testing, none of the SNPs were significantly associated with weight, waist circumference, or fat mass regain. Q-Q plots showed that ALOX5AP rs4769873 showed a higher observed than predicted P value for the association with less waist circumference regain over 6 mo (-3.1 cm/allele; 95% CI: -4.6, -1.6; P/Bonferroni-corrected P = 0.000039/0.076), independently of diet. Additional associations were identified by using Q-Q plots for SNPs in ALOX5AP, TNF, and KCNJ11 for main effects; in LPL and TUB for glycemic index interaction effects on waist circumference regain; in GHRL, CCK, MLXIPL, and LEPR on weight; in PPARC1A, PCK2, ALOX5AP, PYY, and ADRB3 on waist circumference; and in PPARD, FABP1, PLAUR, and LPIN1 on fat mass regain for dietary protein interaction. CONCLUSION: The observed effects of SNP-diet interactions on weight, waist, and fat mass regain suggest that genetic variation in nutrient-sensitive genes can modify the response to diet. This trial was registered at clinicaltrials.gov as NCT00390637.
Published: 2016

13. Slow septal conduction is key in LBBB patient-specific models

Author: Sánchez, Carlos, Potse, Mark, D'Ambrosio, Gabriele, Illner, Annekatrin, Regoli, François, Caputo, Maria Luce, Conte, Giulio, Moccetti, Tiziano, Caiani, Enrico G., Prinzen, Frits W., Krause, Rolf, Auricchio, Angelo, Center for Computational Medicine in Cardiology [Lugano], Università della Svizzera italiana = University of Italian Switzerland (USI), Cardiocentro Ticino [Lugano], Universität Zürich [Zürich] = University of Zurich (UZH), Dipartimento di Elettronica, Informazione e Bioingegneria (DEIB), Politecnico di Milano [Milan] (POLIMI), Department of Physiology, Maastricht University, Department of Physiology, and Maastricht University [Maastricht]-Maastricht University [Maastricht]
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, cardiovascular diseases
Abstract: International audience; PURPOSE: Left-bundle-branch block (LBBB) is a heterogeneous ventricular electrical disorder. Patient-specific models were created to characterize myocardial electrical properties in heart failure patients with LBBB.METHODS: The database consisted of 10 patients diagnosed with LBBB with no scars as detected by cardiac magnetic resonance imaging (CMR). The ECG criteria proposed by Strauss et al. were used for LBBB diagnosis. Realistic individual anatomical models were created from CMR images. Properties such as early activation sites, tissue conductivity, and ionic current dynamics in ventricular cells were tuned to match both clinically recorded ECG and intracardiac ventricular activation sequence. Electrical activity in the ventricles was simulated using a reaction-diffusion equation. The Ten Tusscher-Panfilov 2006 model was used to simulate cell electrophysiology. Intracardiac electrograms and 12-lead ECGs were computed by solving the bidomain equation.SUMMARY: Left ventricular endocardial activation was completed in about 80-90 ms. In order to match the recorded electrical activation sequence and the QRS morphology, the conduction velocity needed to be increased slightly in some of the models. Most of the 10 patient-specific models presented similarities in their tuning: reduction of cell surface-to-volume ratio to mimic hypertrophy and increase conduction velocity, and reduction of potassium currents and heterogeneous distribution of their densities to match the T wave. Specific regional properties in the septum of very slow conduction, particularly in the cross-fiber direction (see example in the Figure), were essential to simulate the prolonged trans-septal delay from the right to the left ventricle in some LBBB patients.CONCLUSION: Despite notable prolongation of trans-septal time in LBBB patients, conduction velocity in the working myocardium is not impaired in all patients. Patient-specific simulation may help in characterizing myocardial properties, and possibly in patient selection for the most appropriate electrical or biological therapy.
Published: 2016

14. Analysis of RET promoter CpG island methylation using methylation-specific PCR (MSP), pyrosequencing, and methylation-sensitive high-resolution melting (MS-HRM): impact on stage II colon cancer patient outcome

Author: Chantal Ramaekers, Manon van Engeland, Caroline Chapusot, Benjamin Tournier, Veerle Melotte, Martijn Vervoort, Matty P. Weijenberg, Kim M. Smits, Valérie Jooste, Muriel X. G. Draht, Department of patholgy [School of Oncology and Developmental Biology - Maastricht], School for Oncology and Developmental Biology [Maastricht] ( GROW ), Maastricht University [Maastricht]-Maastricht University Medical Center-Maastricht University [Maastricht]-Maastricht University Medical Center, Department of radiotherapy [School of Oncology and Developmental Biology - Maastricht], Registre Bourguignon des Cancers Digestifs, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Zuyd University of Applied Sciences (Heerlen, Pays-Bas), Chemelot Innovation and Learning Labs (Geleen, Pays-Bas), Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University [Maastricht], Pathologie, RS: GROW - R2 - Basic and Translational Cancer Biology, Promovendi ODB, Epidemiologie, RS: GROW - R1 - Prevention, Radiotherapie, School for Oncology and Developmental Biology [Maastricht] (GROW), Maastricht University [Maastricht]-Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht]-Maastricht University Medical Centre (MUMC), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: Male, 0301 basic medicine, MESH: Sequence Analysis, DNA, Bisulfite sequencing, Analytic sensitivity, MS-HRM, MESH : Aged, MESH : Promoter Regions, Genetic, Polymerase Chain Reaction, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH: DNA Methylation, MESH : Female, MESH : Proto-Oncogene Proteins c-ret, Promoter Regions, Genetic, MESH: CpG Islands, MESH : Polymerase Chain Reaction, Genetics (clinical), MESH: Aged, DNA methylation, MESH : Prognosis, Methylation, MESH : CpG Islands, Prognosis, pyrosequencing, 030220 oncology & carcinogenesis, MESH: Survival Analysis, Female, MESH : Colorectal Neoplasms, MESH : Sensitivity and Specificity, Colorectal Neoplasms, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Sensitivity and Specificity, MESH: Proto-Oncogene Proteins c-ret, High Resolution Melt, MESH: Prognosis, 03 medical and health sciences, MESH: Promoter Regions, Genetic, Genetics, Humans, Molecular Biology, Aged, MESH: Humans, Research, MSP, Proto-Oncogene Proteins c-ret, MESH : Humans, MESH: Polymerase Chain Reaction, Sequence Analysis, DNA, Survival Analysis, Molecular biology, MESH: Sensitivity and Specificity, MESH: Male, 030104 developmental biology, Pyrosequencing, Illumina Methylation Assay, CpG Islands, Cancer biomarkers, Clinical sensitivity, Primer (molecular biology), MESH : Survival Analysis, RET, MESH: Female, MESH : DNA Methylation, MESH: Colorectal Neoplasms, Developmental Biology, MESH : Sequence Analysis, DNA
Abstract: Background Already since the 1990s, promoter CpG island methylation markers have been considered promising diagnostic, prognostic, and predictive cancer biomarkers. However, so far, only a limited number of DNA methylation markers have been introduced into clinical practice. One reason why the vast majority of methylation markers do not translate into clinical applications is lack of independent validation of methylation markers, often caused by differences in methylation analysis techniques. We recently described RET promoter CpG island methylation as a potential prognostic marker in stage II colorectal cancer (CRC) patients of two independent series. Methods In the current study, we analyzed the RET promoter CpG island methylation of 241 stage II colon cancer patients by direct methylation-specific PCR (MSP), nested-MSP, pyrosequencing, and methylation-sensitive high-resolution melting (MS-HRM). All primers were designed as close as possible to the same genomic region. In order to investigate the effect of different DNA methylation assays on patient outcome, we assessed the clinical sensitivity and specificity as well as the association of RET methylation with overall survival for three and five years of follow-up. Results Using direct-MSP and nested-MSP, 12.0 % (25/209) and 29.6 % (71/240) of the patients showed RET promoter CpG island methylation. Methylation frequencies detected by pyrosequencing were related to the threshold for positivity that defined RET methylation. Methylation frequencies obtained by pyrosequencing (threshold for positivity at 20 %) and MS-HRM were 13.3 % (32/240) and 13.8 % (33/239), respectively. The pyrosequencing threshold for positivity of 20 % showed the best correlation with MS-HRM and direct-MSP results. Nested-MSP detected RET promoter CpG island methylation in deceased patients with a higher sensitivity (33.1 %) compared to direct-MSP (10.7 %), pyrosequencing (14.4 %), and MS-HRM (15.4 %). While RET methylation frequencies detected by nested-MSP, pyrosequencing, and MS-HRM varied, the prognostic effect seemed similar (HR 1.74, 95 % CI 0.97–3.15; HR 1.85, 95 % CI 0.93–3.86; HR 1.83, 95 % CI 0.92–3.65, respectively). Conclusions Our results show that upon optimizing and aligning four RET methylation assays with regard to primer location and sensitivity, differences in methylation frequencies and clinical sensitivities are observed; however, the effect on the marker’s prognostic outcome is minimal. Electronic supplementary material The online version of this article (doi:10.1186/s13148-016-0211-8) contains supplementary material, which is available to authorized users.
Published: 2016

15. In vivo EP studies in transgenic short QT syndrome type 1 rabbits reveal shortened atrial and ventricular refractory periods and higher atrial and ventricular tachyarrhythmia inducibility

Author: Steinfurt, Johannes, Brunner, Michael, Franke, Gerlind, Perez-Feliz, Stefanie, Bodi, Ilona, Pantulu, Naga Deepa, Lang, Corinna Nadine, Ziupa, David, Zehender, Manfred, Zur Hausen, Axel, Jolivet, Genevieve, Bode, Christoph, Odening, Katja E., Heart Center, Department of Cardiology and Angiology, University of Freiburg, Department of Pathology, University of Alabama at Birmingham [ Birmingham] (UAB), Department of patohology, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), German Cardiac Society. DEU., Maastricht University Medical Center (MUMC), Biologie du développement et reproduction (BDR), and École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], arythmie, in vitro study, cardiac dysrhythmia, rabbit, ventricule, heart, étude in vitro, transgenic mouse, cœur, cardiovascular system, animal transgénique, cardiovascular diseases, lapin, Autre (Sciences du Vivant)
Abstract: In vivo EP studies in transgenic short QT syndrome type 1 rabbits reveal shortened atrial and ventricular refractory periods and higher atrial and ventricular tachyarrhythmia inducibility. 82. Annual Meeting of the German Cardiac Society
Published: 2016

16. Circulating ACE is a predictor of weight loss maintenance not only in overweight and obese women, but also in men

Author: Wang, P., Holst, C., Wodzig, W. K. W. H., Andersen, M. R., Astrup, A., Van Baak, M. A., Larsen, T. M., Jebb, S. A., Kafatos, A., Pfeiffer, A. F. H., Martinez, J. A., Handjieva-Darlenska, T., Kunesova, M., Viguerie, N., Langin, D., Saris, W. H. M., Mariman, E. C. M., Diogenes, Consortium, Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism-Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Institute of Preventive Medicine / Institut for Sygdomsforebyggelse, Copenhagen University Hospital-Frederiksberg Hospital Hovedvejen, Department of Clinical Chemistry, Maastricht University Medical Centre (MUMC), Department of Clinical Biochemistry, Copenhagen University Hospital, Department of Human Nutrition, Faculty of Life Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Elsie Widdowson Laboratory, MRC Human Nutrition Research, Department of Social Medicine, Preventive Medicine and Nutrition Clinic, University of Crete [Heraklion] (UOC), Department of Clinical Nutrition, German Institute of Human Nutrition, Department of Endocrinology, Diabetes and Nutrition, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Physiology and Nutrition, Universidad de Navarra [Pamplona] (UNAV), Department of Nutrition, Dietetics and Metabolic Diseases, National Multiprofile Transport Hospital, Obesity Management Centre, Institute of Endocrinology, Obesity Research Laboratory, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Department of Human Biology Nutrition and Toxicology Research (Diogenes), Maastricht University [Maastricht]-Institute Maastricht (NUTRIM), Humane Biologie, MUMC+: DA CDL Algemeen (9), RS: NUTRIM - R4 - Gene-environment interaction, RS: NUTRIM - R1 - Metabolic Syndrome, Simon, Marie Francoise, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Cross-sectional study, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), MESH: Energy Intake, 030204 cardiovascular system & hematology, Overweight, Weight Gain, 0302 clinical medicine, Weight loss, MESH: Obesity, 2. Zero hunger, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Diet, Reducing, 0303 health sciences, Nutrition and Dietetics, MESH: Middle Aged, MESH: Sex Distribution, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Predictive Value of Tests, 3. Good health, MESH: Weight Gain, Female, medicine.symptom, Adult, medicine.medical_specialty, Diet, Reducing, Peptidyl-Dipeptidase A, 03 medical and health sciences, MESH: Weight Loss, MESH: Cross-Sectional Studies, Predictive Value of Tests, Internal medicine, Weight Loss, medicine, Humans, Obesity, Sex Distribution, 030304 developmental biology, MESH: Humans, business.industry, MESH: Biological Markers, MESH: Adult, Odds ratio, Anthropometry, Confidence interval, MESH: Male, MESH: Peptidyl-Dipeptidase A, Endocrinology, Cross-Sectional Studies, business, Energy Intake, Weight gain, Body mass index, MESH: Female, Biomarkers
Abstract: BACKGROUND:Circulating angiotensin-converting enzyme (ACE) was identified as a predictor of weight loss maintenance in overweight/obese women of the Diogenes project.OBJECTIVE:To investigate whether ACE acted also as a predictor in men of the Diogenes study and to compare it with that in women.DESIGN:Subjects, who lost >/=8% of body weight induced by low-caloric diet in an 8-week weight loss period, were assigned to weight loss maintenance with dietary intervention for 6 months.SUBJECTS:125 overweight/obese healthy men from eight European countries who completed whole intervention.MEASUREMENTS:Concentrations and activity of serum ACE at baseline and after the 8-week weight loss, in addition to anthropometric and physiological parameters.RESULTS:Serum ACE concentration decreased by 11.3+/-10.6% during the weight loss period in men. A greater reduction is associated with less body weight regain during the maintenance period (r=0.227, P=0.012). ACE change was able to predict a weight regain
Published: 2012

17. Implementation of trastuzumab in conjunction with adjuvant chemotherapy in the treatment of non-metastatic breast cancer in the Netherlands

Author: L. de Munck, Phb Willemse, Michael Schaapveld, Jelle Wesseling, Sabine Siesling, Renée Otter, Adri C. Voogd, Vivianne C. G. Tjan-Heijnen, Epidemiologie, Interne Geneeskunde, RS: CAPHRI School for Public Health and Primary Care, RS: GROW - School for Oncology and Reproduction, Department of Research, Comprehensive Cancer Centre North East, Department of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Department of Health Technology & Services Research, University of Twente [Netherlands], Department of Pathology, Department of Epidemiology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Comprehensive Cancer Centre South (CCCS), Division of Medical Oncology, Department of Internal Medicine, GROW - School for Oncology and Developmental Biology, Department of Medical Oncology, University Medical Centre Groningen, and Faculty of Behavioural, Management and Social Sciences
Subjects: Adult, Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, Adjuvant chemotherapy, IR-77770, medicine.medical_treatment, Antineoplastic Agents, Breast Neoplasms, Disease, ONCOGENE, Guideline, Antibodies, Monoclonal, Humanized, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Trastuzumab, Internal medicine, HER2, medicine, Humans, Non metastatic, 030212 general & internal medicine, skin and connective tissue diseases, neoplasms, Adjuvant, Aged, Netherlands, Aged, 80 and over, business.industry, Antibodies, Monoclonal, Middle Aged, medicine.disease, 3. Good health, Cancer registry, Chemotherapy, Adjuvant, HER-2, 030220 oncology & carcinogenesis, Female, METIS-277775, business, medicine.drug
Abstract: International audience; Trastuzumab in conjunction with adjuvant chemotherapy markedly improves outcome. In the Netherlands, a national guideline was released in September 2005 stating that trastuzumab should be given in conjunction with adjuvant chemotherapy in women with HER2-positive breast cancer. Aim of this study was to identify the number of women with HER2-positive breast cancer and to evaluate the level of implementation of adjuvant trastuzumab in clinical practice nationwide. Women diagnosed with primary breast cancer between September 2005 and January 2007 were selected from the Netherlands Cancer Registry (NCR). HER2 status, adjuvant treatment and reasons to withhold trastuzumab were registered. 14,934 Breast cancer patients were diagnosed in this period of whom 1,928 (13%) had a HER2-positive tumour. Of all HER2-positive women receiving adjuvant chemotherapy, 66 (6%) did not receive trastuzumab. This percentage decreased from 10% at the time of introduction of the guideline to 4% in the study period September 2005-December 2006. Most common reasons to withhold trastuzumab were cardiovascular disease (29%) and patient refusal (21%). Of all HER2-positive patients who received adjuvant chemotherapy, 94% received trastuzumab. The implementation of trastuzumab in clinical practice was realized within 8 months after introduction of the new guideline.
Published: 2011

18. MLL2 Mutation Spectrum in 45 Patients with Kabuki Syndrome

Author: Marinus J. Blok, Joep P.M. Geraedts, Thomy de Ravel, Demis Tserpelis, Aimee D C Paulussen, Raoul C.M. Hennekam, Eric Smeets, Constance T.R.M. Schrander-Stumpel, Maaike Vreeburg, Hubert J T Smeets, Irene Stolte-Dijkstra, Wilhelmina S. Kerstjens-Frederikse, Marie José H. Van Den Boogaard, J. J. P. Schrander, Grazia M.S. Mancini, Jean-Pierre Fryns, Annemieke M. A. Wagemans, Marja W. Wessels, Y. Detisch, Koenraad Devriendt, Arie van Haeringen, Alexander P.A. Stegmann, Crool Posma-Velter, Jasper J. van der Smagt, Amsterdam Neuroscience, Amsterdam Public Health, Paediatrics, Family Medicine, Kindergeneeskunde, RS: GROW - School for Oncology and Reproduction, Klinische Genetica, Clinical Genetics, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], School for Oncology & Developmental Biology (GROW), Department of Clinical Genetics, Department of Paediatrics, Department of Medical Genetics, University Medical Center [Utrecht], Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), Department of Genetics, University Medical Center Groningen [Groningen] (UMCG), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Human Genetics, Erasmus University Rotterdam, Department of Pediatrics, Academic Medical Center, University of Amsterdam [Amsterdam] (UvA), Center for Human Genetics, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Clinical sciences, Medical Genetics, and Pediatrics
Subjects: Male, Hematologic Diseases/genetics, Biology, medicine.disease_cause, PROTEIN LYSINE METHYLTRANSFERASES, Frameshift mutation, Exon, Neoplasm Proteins/genetics, EARS, Abnormalities, Multiple/genetics, Genetics, medicine, Missense mutation, Humans, Abnormalities, Multiple, histone methyl transferase, Epigenetics, Gene, Genetics (clinical), Mutation, Kabuki syndrome, Life Sciences, MAKE-UP-SYNDROME, Face/abnormalities, medicine.disease, Molecular biology, Hematologic Diseases, GENE, Vestibular Diseases/genetics, Neoplasm Proteins, DNA-Binding Proteins, Vestibular Diseases, KS, Histone methyltransferase, Face, MLL2, GROWTH, Female, DNA-Binding Proteins/genetics, MENTAL-RETARDATION
Abstract: Kabuki Syndrome (KS) is a rare syndrome characterized by intellectual disability and multiple congenital abnormalities, in particular a distinct dysmorphic facial appearance. KS is caused by mutations in the MLL2 gene, encoding an H3K4 histone methyl transferase which acts as an epigenetic transcriptional activator during growth and development. Direct sequencing of all 54 exons of the MLL2 gene in 45 clinically well-defined KS patients identified 34 (75.6%) different mutations. One mutation has been described previously, all others are novel. Clinically, all KS patients were sporadic, and mutations were de novo for all 27 families for which both parents were available. We detected nonsense (n=11), frameshift (n=17), splice site (n=4) and missense (n=2) mutations, predicting a high frequency of absent or non-functional MLL2 protein. Interestingly, both missense mutations located in the C-terminal conserved functional domains of the protein. Phenotypically our study indicated a statistically significant difference in the presence of a distinct facial appearance (p=0.0143) and growth retardation (p=0.0040) when comparing KS patients with an MLL2 mutation compared to patients without a mutation. Our data double the number of MLL2 mutations in KS reported so far and widen the spectrum of MLL2 mutations and disease mechanisms in KS.© 2010 Wiley-Liss, Inc. PMID: 21280141 [PubMed - in process]
Published: 2011

19. Computer-aided detection in full-field digital mammography in a clinical population: performance of radiologist and technologists

Author: Carla Boetes, Jos M. A. van Engelshoven, Alphons G.H. Kessels, Karin Flobbe, Frank J.H.M. van den Biggelaar, Department of Radiology, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Department of Clinical Epidemiology and Medical Technology Assessment, Beeldvorming, Epidemiologie, MUMC+: KIO Kemta (9), and RS: GROW - School for Oncology and Reproduction
Subjects: Adult, Cancer Research, medicine.medical_specialty, Digital mammography, Health Personnel, Performance, Population, CAD, Breast Neoplasms, Sensitivity and Specificity, Young Adult, Breast cancer, Sensitivity, medicine, Mammography, Humans, False Positive Reactions, cardiovascular diseases, education, Aged, Aged, 80 and over, Computer-aided detection, education.field_of_study, medicine.diagnostic_test, business.industry, Middle Aged, medicine.disease, Cad system, Full field digital mammography, Computer aided detection, Oncology, Radiologist, Specificity, Radiographic Image Interpretation, Computer-Assisted, Female, Radiology, business, Software, Technologist
Abstract: International audience; The purpose of the study was to evaluate the impact of a computer-aided detection (CAD) system on the performance of mammogram readers in interpreting digital mammograms in a clinical population. Furthermore, the ability of a CAD system to detect breast cancer in digital mammography was studied in comparison to the performance of radiologists and technologists as mammogram readers. Digital mammograms of 1,048 consecutive patients were evaluated by a radiologist and three technologists. Abnormalities were recorded and an imaging conclusion was given as a BI-RADS score before and after CAD analysis. Pathology results during 12 months follow up were used as a reference standard for breast cancer. Fifty-one malignancies were found in 50 patients. Sensitivity and specificity were computed before and after CAD analysis and provided with 95% CIs. In order to assess the detection rate of malignancies by CAD and the observers, the pathological locations of these 51 breast cancers were matched with the locations of the CAD marks and the mammographic locations that were considered to be suspicious by the observers. For all observers, the sensitivity rates did not change after application of CAD. A mean sensitivity of 92% was found for all technologists and 84% for the radiologist. For two technologists, the specificity decreased (from 84 to 83% and from 77 to 75%). For the radiologist and one technologist, the application of CAD did not have any impact on the specificity rates (95 and 83%, respectively). CAD detected 78% of all malignancies. Five malignancies were indicated by CAD without being noticed as suspicious by the observers. In conclusion, the results show that systematic application of CAD in a clinical patient population failed to improve the overall sensitivity of mammogram interpretation by the readers and was associated with an increase in false-positive results. However, CAD marked five malignancies that were missed by the different readers.
Published: 2010

20. Physical activity and the risk of breast cancer in BRCA1/2 mutation carriers

Author: Senno Verhoef, Christi J. van Asperen, Charlotte J. Dommering, Peggy Manders, J. Margriet Collée, Flora E. van Leeuwen, Matti A. Rookus, Anouk Pijpe, Margreet G. E. M. Ausems, Hans F. A. Vasen, Richard M. Brohet, Encarna B. Gomez-Garcia, Laura J. van't Veer, Cora M. Aalfs, Nicoline Hoogerbrugge, Human Genetics, Department of Epidemiology, Netherlands Cancer Institute, Department of Human Genetics, Radboud University Medical Center [Nijmegen], Department of Research and Education, Spaarne hospital, Department of Clinical Genetics, Rotterdam Family Cancer Clinic, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Family Cancer Clinic, The Netherlands Foundation for the Detection of Hereditary Tumours, Department of Clinical Genetics, Leiden University Medical Center (LUMC), Department of Clinical Genetics and Human Genetics, VU University Medical Center [Amsterdam], Department of Medical Genetics, University Medical Center [Utrecht], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Department of Pathology, Human genetics, Epidemiology and Data Science, EMGO - Quality of care, Klinische Genetica, Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Clinical Genetics, and Internal Medicine
Subjects: Adult, Cancer Research, medicine.medical_specialty, Heterozygote, Genetics and epigenetic pathways of disease [NCMLS 6], Epidemiology, Population, Genes, BRCA2, Genes, BRCA1, Physical exercise, Breast Neoplasms, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, Risk Factors, BRCA1/2, Internal medicine, medicine, Humans, Risk factor, education, Exercise, HEBON, 030304 developmental biology, Gynecology, 0303 health sciences, education.field_of_study, Hereditary cancer and cancer-related syndromes [ONCOL 1], business.industry, Physical activity, Cancer, Retrospective cohort study, Middle Aged, medicine.disease, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Mutation, Female, Breast disease, business, Cohort study
Abstract: Contains fulltext : 89737.pdf (Publisher’s version ) (Closed access) BRCA1/2 mutation carriers have a high lifetime risk of developing breast cancer. Differences in penetrance indicate that this risk may be influenced by lifestyle factors. Because physical activity is one of the few modifiable risk factors, it may provide a target to add to breast cancer prevention in this high-risk population. We examined the association between self-reported lifetime sports activity and breast cancer risk in a nationwide retrospective cohort study, including 725 carriers, of whom 218 had been diagnosed with breast cancer within 10 years prior to questionnaire completion. We found a nonsignificantly decreased risk for ever engaging in sports activity (HR = 0.84, 95%CI = 0.57-1.24). Among women who had participated in sports, a medium versus low level of intensity and duration (i.e., between 11.0 and 22.7 mean MET hours/week averaged over a lifetime) reduced the risk of breast cancer (HR = 0.59, 95%CI = 0.36-0.95); no dose-response trend was observed. For mean hours/week of sports activity, a nonsignificant trend was observed (HR(low versus never) = 0.93, 95%CI = 0.60-1.43; HR(medium versus never) = 0.81, 95%CI = 0.51-1.29; HR(high versus never) = 0.78, 95%CI = 0.48-1.29; p (trend overall) = 0.272; p (trend active women) = 0.487). For number of years of sports activity no significant associations were found. Among women active in sports before age 30, mean MET hours/week showed the strongest inverse association of all activity measures (HR(medium versus low) = 0.60, 95%CI = 0.38-0.96; HR(high versus low) = 0.58, 95%CI = 0.35-0.94; p (trend) = 0.053). Engaging in sports activity after age 30 was also inversely associated with breast cancer risk (HR = 0.63, 95%CI = 0.44-0.91). Our results indicate that sports activity may reduce the risk of breast cancer in BRCA1/2 mutation carriers. 01 februari 2010
Published: 2010

21. In primary breast cancer the mitotic activity yields similar prognostic information as the histological grade: a study with long-term follow-up

Author: Huub Straatman, André L. M. Verbeek, Louk V.A.M. Beex, Peter Bult, Vivianne C. G. Tjan-Heijnen, Jan Willem H. Leer, Peggy Manders, J. Hendriks, Roland Holland, Department of Pathology, Radboud University Medical Center [Nijmegen], Department of Chemical Endocrinology, Department of Medical Oncology, Department of Human Genetics, Department of Epidemiology & Biostatistics, PHARMO, Institute for Drug Outcome Research, Division of Medical Oncology, Department of Internal Medicine, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], National Expert and Training Centre for Breast Cancer Screening, Department of Radiotherapy, Interne Geneeskunde, Kindergeneeskunde, and RS: GROW - School for Oncology and Reproduction
Subjects: Adult, Chemical and physical biology [NCMLS 7], Cancer Research, medicine.medical_specialty, Prognostic variable, Mitotic index, medicine.medical_treatment, Breast Neoplasms, Kaplan-Meier Estimate, Aetiology, screening and detection [ONCOL 5], Gastroenterology, Molecular epidemiology [NCEBP 1], Breast cancer, Risk Factors, Translational research [ONCOL 3], Internal medicine, Mitotic Index, Humans, Medicine, Histological grade, Aged, Netherlands, Proportional Hazards Models, Retrospective Studies, Aged, 80 and over, Gynecology, business.industry, Carcinoma, Carcinoma, Ductal, Breast, Breast cancer mortality, Hazard ratio, Cancer, Histology, Middle Aged, Prognosis, medicine.disease, Mitotic activity, Oncology, Evaluation of complex medical interventions [NCEBP 2], Female, Breast disease, business, Adjuvant, Follow-Up Studies
Abstract: Contains fulltext : 88107.pdf (Publisher’s version ) (Closed access) We evaluated with long-term follow-up, the prognostic value of the mitotic activity index (MAI) and the volume corrected mitotic index (M/V-index) compared with that of the histological grade in breast cancer patients not treated with adjuvant systemic therapy. Of 739 consecutive patients living in the city of Nijmegen, the Netherlands, 477 patients with primary unilateral breast cancer were not treated with adjuvant systemic therapy and eligible for the study. In multivariate survival analyses the MAI and M/V-index showed similar hazard ratios (HRs) compared to HRs of histological grade for overall survival (OS) (HR: 1.45, 1.48, and grade II versus grade I (GII/GI) 1.34, grade III versus grade I (GIII/GI) 1.53, respectively) and for breast cancer specific survival (BCSS) (HR: 1.27, 1.57, and (GII/GI) 1.57 (GIII/GI) 2.32, respectively). Other independent prognostic variables for OS and BCSS were age at diagnosis, tumour size, and number of positive lymph nodes. In the present study with long term follow-up, we compared the prognostic value of mitotic activity with that of histological grade and found no advantage for the mitotic activity in predicting either BCSS or OS and concluded that histological grade and the mitotic activity were equally informative in predicting patient outcome. As histological grade is a well established and widely used prognosticator we do not have arguments to replace the histological grade by the mitotic indices MAI or M/V-index. 01 juli 2010
Published: 2009

22. Patient-specific modelling of cardiac electrophysiology in heart-failure patients

Author: Stefano Muzzarelli, Mark Potse, Angelo Auricchio, Romina Murzilli, Frits W. Prinzen, Enrico G. Caiani, Rolf Krause, Wilco Kroon, François Regoli, Dorian Krause, University of Zurich, Potse, Mark, Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Center for Computational Medicine in Cardiology (CCMC), Università della Svizzera italiana = University of Italian Switzerland (USI), Institute of Computational Science, Cardiocentro Ticino [Lugano], Universität Zürich [Zürich] = University of Zurich (UZH), Department of Bioengineering [Politecnico Milano], Politecnico di Milano [Milan] (POLIMI), Department of Physiology, Maastricht University, Department of Physiology, Maastricht University [Maastricht]-Maastricht University [Maastricht], Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Fysiologie, and RS: CARIM - R2 - Cardiac function and failure
Subjects: Male, Action Potentials, 02 engineering and technology, 030204 cardiovascular system & hematology, Ventricular Function, Left, Electrocardiography, 0302 clinical medicine, 2737 Physiology (medical), Heart Rate, medicine.diagnostic_test, Cardiac electrophysiology, Left bundle branch block, Models, Cardiovascular, Articles, Left bundle-branch block, Cardiology, Female, Electrical conduction system of the heart, Electrophysiologic Techniques, Cardiac, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Bundle-Branch Block, 0206 medical engineering, 610 Medicine & health, 11171 Cardiocentro Ticino, 2705 Cardiology and Cardiovascular Medicine, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart Conduction System, Predictive Value of Tests, Physiology (medical), Internal medicine, Heart rate, medicine, Humans, Computer Simulation, cardiovascular diseases, Endocardium, Aged, Heart Failure, Bundle branch block, business.industry, Computer models, Numerical Analysis, Computer-Assisted, medicine.disease, 020601 biomedical engineering, Heart failure, business, Conduction disorders
Abstract: Aims Left-ventricular (LV) conduction disturbances are common in heart-failure patients and a left bundle-branch block (LBBB) electrocardiogram (ECG) type is often seen. The precise cause of this pattern is uncertain and is probably variable between patients, ranging from proximal interruption of the left bundle branch to diffuse distal conduction disease in the working myocardium. Using realistic numerical simulation methods and patient-tailored model anatomies, we investigated different hypotheses to explain the observed activation order on the LV endocardium, electrogram morphologies, and ECG features in two patients with heart failure and LBBB ECG. Methods and results Ventricular electrical activity was simulated using reaction-diffusion models with patient-specific anatomies. From the simulated action potentials, ECGs and cardiac electrograms were computed by solving the bidomain equation. Model parameters such as earliest activation sites, tissue conductivity, and densities of ionic currents were tuned to reproduce the measured signals. Electrocardiogram morphology and activation order could be matched simultaneously. Local electrograms matched well at some sites, but overall the measured waveforms had deeper S-waves than the simulated waveforms. Conclusion Tuning a reaction-diffusion model of the human heart to reproduce measured ECGs and electrograms is feasible and may provide insights in individual disease characteristics that cannot be obtained by other means.
Published: 2014

23. MAX Mutations Cause Hereditary and Sporadic Pheochromocytoma and Paraganglioma

Author: Patricia L. M. Dahia, Maurizio Castellano, Nicole Reisch, Carli M. J. Tops, N. Abermil, Marta Barontini, Graeme Eisenhofer, Sandra Bernaldo de Quirós, Salud Borrego, Álvaro Gómez-Graña, Nelly Burnichon, M. Giacchè, Mercedes Robledo, Emiliano Honrado, Giuseppe Opocher, Francesca Schiavi, Xavier Girerd, Elena Rapizzi, Lucía Inglada-Pérez, Esther Korpershoek, Henri J L M Timmers, Massimo Mannelli, Encarna B. Gomez-Garcia, Elisa Taschin, María-Dolores Chiara, Sara Bobisse, Alberto Cascón, Peggy Pierre, Carlos Suárez, Alexander P.A. Stegmann, Arjen R. Mensenkamp, Felix Beuschlein, Luigi Mori, Iñaki Comino-Méndez, Marinus J. Blok, Laurence Amar, Arnaud Murat, Macarena Ruiz-Ferrer, Ronald R. de Krijger, F Schillo, Frederik J. Hes, Karel Pacak, Nicole Paes Morales, Tonino Ercolino, Jacques W.M. Lenders, Rocío Letón, Miguel Urioste, Eleonora P M Corssmit, Isabelle Guilhem, Nan Qin, Anne-Paule Gimenez-Roqueplo, Giovanna Roncador, Pierre-François Plouin, Tamara Prodanov, Yves-Jean Bignon, Victoria M. Raymond, Jérôme Bertherat, Miguel Quesada-Charneco, Anna Merlo, Aguirre A. de Cubas, Philippe Chanson, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centro de Investigaciones Endocrinológicas, Hospital de Niños R. Gutiérrez, Service d'Endocrinologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre de Référence pour les Maladies Rares, Laboratoire de diagnostic génétique et moléculaire, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Equipe de recherche sur les traitements individualisés des cancers (ERTICa), Université d'Auvergne - Clermont-Ferrand I (UdA), Clinical Genetics, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], School for Oncology & Developmental Biology (GROW), Department of Genetics, Reproduction and Fetal Medicine, Universidad de Sevilla / University of Sevilla-Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío [Sevilla], Centre for Biomedical Network Research on Rare Diseases (CIBERER), Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Departments of Pathology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre Hospitalier Universitaire [Rennes], Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Beijing Genomics Institute [Shenzhen] (BGI), Monoclonal antibodies unit, Centro Nacional de Investigaciones Oncológicas, Group of Human Genetics, Spanish National Cancer Research Center (CNIO), Familial Cancer Clinic, Veneto Institute of Oncology, IRCCS & Department of Medical and Surgical Sciences, Università degli Studi di Padova = University of Padua (Unipd), Carl Gustav Carus University Hospital, Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, MUMC+: DA KG Lab Centraal Lab (9), Klinische Genetica, Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Centre de Référence pour les Maladies Rares, Centre Jean Perrin, Maastricht University Medical Center (MUMC), Universidad de Sevilla-Hospital Universitario Virgen del Rocío [Sevilla]-Institute of Biomedicine of Seville (IBIS), Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), Universita degli Studi di Padova, Centro Nacional de Investigaciones Oncológicas, CNIO, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Pathology, Pediatrics, Clinical sciences, Medical Genetics, Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Paris Descartes - Paris 5 ( UPD5 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Centre de Référence pour les Maladies Rares, Equipe de recherche sur les traitements individualisés des cancers ( ERTICa ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), Maastricht University Medical Center (MUMC+), Universidad de Sevilla-University Hospital Virgen del Rocio-Institute of Biomedicine of Seville (IBIS), Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Erasmus MC-University Medical Center, Laboratoire de Neurosciences Cognitives [Marseille] ( LNC ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Beijing Genomics Institute [Shenzhen] ( BGI ), and Beijing Genomics Institute
Subjects: Male, Pheochromocytoma, Genetics, Cancer Research, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics, MESH : Germ-Line Mutation, Somatic cell, MESH: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, MESH : Aged, Adrenal Gland Neoplasms, MESH : Child, Preschool, medicine.disease_cause, Germline, MESH : Pheochromocytoma, 0302 clinical medicine, MESH: Aged, 80 and over, MESH : Child, Paraganglioma, MESH: Child, MESH: Germ-Line Mutation, MESH : Female, Child, Aged, 80 and over, MESH: Aged, 0303 health sciences, Mutation, MESH: Middle Aged, Cardiovascular diseases [NCEBP 14], Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, MESH: Genetic Predisposition to Disease, MESH : Adult, Middle Aged, MESH : Paraganglioma, Phenotype, 3. Good health, Oncology, MESH: Young Adult, 030220 oncology & carcinogenesis, Child, Preschool, Female, MESH : Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Adult, MESH: Paraganglioma, Adolescent, MESH : Adrenal Gland Neoplasms, MESH : Male, MESH : Young Adult, Biology, 03 medical and health sciences, Young Adult, Germline mutation, SDG 3 - Good Health and Well-being, MESH : Adolescent, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Adrenal Gland Neoplasms/genetics, Humans, MESH : Middle Aged, Genetic Predisposition to Disease, MESH: Pheochromocytoma, MESH : Aged, 80 and over, Germ-Line Mutation, 030304 developmental biology, Aged, MESH: Adolescent, MESH: Humans, Paraganglioma/genetics, Genetic heterogeneity, Translational research Genomic disorders and inherited multi-system disorders [ONCOL 3], MESH : Humans, Hormonal regulation [IGMD 6], MESH: Child, Preschool, MESH: Adult, medicine.disease, MESH: Adrenal Gland Neoplasms, MESH: Male, Pheochromocytoma/genetics, Cancer research, MESH : Genetic Predisposition to Disease, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: 11 pages, 2 figures, 2 tables.-- Burnichón, Nelly et al., Purpose: Pheochromocytomas (PCC) and paragangliomas (PGL) are genetically heterogeneous neural crest-derived neoplasms. Recently we identified germline mutations in a new tumor suppressor susceptibility gene, MAX (MYC-associated factor X), which predisposes carriers to PCC. How MAX mutations contribute to PCC/PGL and associated phenotypes remain unclear. This study aimed to examine the prevalence and associated phenotypic features of germline and somatic MAX mutations in PCC/PGL., Design: We sequenced MAX in 1,694 patients with PCC or PGL (without mutations in other major susceptibility genes) from 17 independent referral centers. We screened for large deletions/duplications in 1,535 patients using a multiplex PCR-based method. Somatic mutations were searched for in tumors from an additional 245 patients. The frequency and type of MAX mutation was assessed overall and by clinical characteristics., Results: Sixteen MAX pathogenic mutations were identified in 23 index patients. All had adrenal tumors, including 13 bilateral or multiple PCCs within the same gland (P < 0.001), 15.8% developed additional tumors at thoracoabdominal sites, and 37% had familial antecedents. Age at diagnosis was lower (P = 0.001) in MAX mutation carriers compared with nonmutated cases. Two patients (10.5%) developed metastatic disease. A mutation affecting MAX was found in five tumors, four of them confirmed as somatic (1.65%). MAX tumors were characterized by substantial increases in normetanephrine, associated with normal or minor increases in metanephrine., Conclusions: Germline mutations in MAX are responsible for 1.12% of PCC/PGL in patients without evidence of other known mutations and should be considered in the genetic work-up of these patients. ©2012 AACR.
Published: 2012

24. Multiple effects of a short-term dexamethasone treatment in human skeletal muscle and adipose tissue

Author: Flora Picard, Carine Valle, P. Barbe, Jason S. Iacovoni, Nathalie Viguerie, Balbine Roussel, Wim H. M. Saris, Gabby B. Hul, Dominique Langin, Simon, Marie Francoise, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées, Department of Human Biology, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Humane Biologie, RS: NUTRIM - R1 - Metabolic Syndrome, Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]
Subjects: Male, MESH: Serum Amyloid A Protein, Physiology, Adipose tissue, Dexamethasone, ACTIVATION, 0302 clinical medicine, Mineralocorticoid receptor, Longitudinal Studies, MESH: Longitudinal Studies, GENE-EXPRESSION, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, MESH: Muscle, Skeletal, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, C-Reactive Protein, medicine.anatomical_structure, Adipose Tissue, MESH: Dexamethasone, medicine.symptom, Glucocorticoid, MESH: Adipose Tissue, medicine.drug, Adult, medicine.medical_specialty, Adipose tissue macrophages, 030209 endocrinology & metabolism, Inflammation, Biology, METABOLISM, 03 medical and health sciences, Downregulation and upregulation, MICROARRAY, INFLAMMATION, Internal medicine, MESH: C-Reactive Protein, Genetics, medicine, gene expression profiling, Humans, GLUCOCORTICOIDS, Muscle, Skeletal, 030304 developmental biology, Serum Amyloid A Protein, MESH: Humans, Skeletal muscle, 3T3-L1 ADIPOCYTES, MESH: Adult, INSULIN-RESISTANT MICE, MESH: Male, Endocrinology, healthy volunteers, SERUM-AMYLOID-A, CELLS, glucocorticoid, MESH: Glucocorticoids
Abstract: Viguerie N, Picard F, Hul G, Roussel B, Barbe P, Iacovoni JS, Valle C, Langin D, Saris WHM. Multiple effects of a short-term dexamethasone treatment in human skeletal muscle and adipose tissue. Physiol Genomics 44: 141-151, 2012. First published November 22, 2011; doi:10.1152/physiolgenomics.00032.2011.-Glucocorticoids are frequently prescribed drugs with important side-effects such as glucose intolerance and tissue remodeling. The goal was to explore the molecular basis of the response of skeletal muscle and adipose tissue during a short-term dexamethasone treatment to better understand the induction of side-effects of glucocorticoids on these metabolic tissues. Fifteen healthy male subjects were assigned to a 4-day treatment with dexamethasone at 4 mg/day. The primary outcome measures were changes in gene expression profiling of subcutaneous skeletal muscle and adipose tissue. Urinary cortisol, plasma, and metabolic biochemistry were also assessed. In both tissues the prominent observation was a response to stress and increased inflammatory responses. An upregulation of the serum amyloid A was detected in skeletal muscle, adipose tissue, and plasma, whereas circulating levels of C reactive protein, another acute phase protein, decreased along with a worsened insulin sensitivity index. As tissue-specific features, tissue remodeling was shown in skeletal muscle while the adipose tissue exhibited a decreased energy metabolism. Several limitations might be raised due to the small number of subjects investigated: a possible cross talk with the mineralocorticoid receptor, and a single time point may not identify regulations occurring during longitudinal treatment. In line with the known physiological effect of glucocorticoids the early modulation of stress response genes was observed. An unexpected feature was the upregulation of the inflammatory and immune pathways. The identification of novel impact on two glucocorticoid target tissues provides a molecular basis for the design of more specific glucocorticoids devoid of adverse effects.
Published: 2012

25. Mycophenolate mofetil: role in autoimmune hepatitis and overlap syndromes

Author: Baven-Pronk, Martine A.M.C., Coenraad, Minneke J., Van Buuren, Henk, De Man, Robert A, Van Erpecum, Karel J, Lamers, Mieke M.H., Drenth, Joost, Van Den Berg, Aad A.P., Beuers, Ulrich, Den Ouden, Jannie, Koek, Ger H., Van Nieuwkerk, Carin M.J., Bouma, Gerd, Brouwer, Johannes T., Van Hoek, Bart, Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Gastroenterology, University Medical Center [Utrecht], Radboud University Medical Center [Nijmegen], University Medical Center Groningen [Groningen] (UMCG), Department of Gastroenterology & Hepatology, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), HAGA Hospital, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Free University Medical Center [Amsterdam], and Reinier de Graaf Gasthuis
Subjects: Medicine
Abstract: International audience; Background and Aims: Treatment failure occurs in 20% of autoimmune hepatitis patients on prednisolone and azathioprine (AZA). There is no established second line treatment. This retrospective observational study was conducted to assess the efficacy of mycophenolate mofetil as second line treatment after AZA-intolerance or AZA-nonresponse in autoimmune hepatitis and overlap syndromes. Methods: Consecutive patients from the Dutch Autoimmune Hepatitis Group cohort, consisting of 661 patients , with autoimmune hepatitis or overlap syndromes, AZA-intolerance or AZA-nonresponse, and past or present use of mycophenolate mofetil were included. Primary endpoint of mycophenolate mofetil treatment was biochemical remission. Secondary endpoints were biochemical response (without remission), treatment failure and prevention of disease progression. Results: Forty-five patients treated with mycophenolate mofetil were included. In autoimmune hepatitis remission or response was achieved in 13% and 27% in the AZA-nonresponse group compared to 67% and 0% in the AZA-intolerance group (P = 0.008). In overlap-syndromes remission or response was reached in 57% and 14% in the AZA-nonresponse group and 63% and 25% of the AZA-intolerance group (NS). 33% had side-effects and 13% discontinued mycophenolate mofetil. Overall 38% had treatment failure; this was 60% in the autoimmune hepatitis AZA-nonresponse group. Decompensated liver cirrhosis, liver transplantations and death were only seen in the autoimmune hepatitis AZA-nonresponse group (P < 0.001). Conclusion: Mycophenolate mofetil induced response or remission in a majority of patients with autoimmune hepatitis and azathioprine-intolerance and with overlap syndromes, irrespective of intolerance or nonresponse for azathioprine. In autoimmune hepatitis with azathioprine nonresponse mycophenolate mofetil is less often efective.
Published: 2011

26. Effectiveness of involving a nurse specialist for patients with urinary incontinence in primary care: results of a pragmatic multicentre randomised controlled trial

Author: Albers-Heitner, Pytha, Lagro-Janssen, Toine, Joore, Manuela, Berghmans, Bary, Nieman, Fred, Venema, Pieter, Severens, Johan, Winkens, Ron, Department of Integrated Care, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Department of Primary and Community Care, Radboud University Medical Center [Nijmegen], Department of Clinical Epidemiology and Medical Technology Assessment, Department of Health Organisation, Policy, and Economics, Pelvic care Centre Maastricht (PcCM), Poliklinisch Continentie Centrum, HAGA Hospital, Institute of Health Policy and Management, Erasmus University Rotterdam, and Department of General Practice
Subjects: Medicine
Abstract: International audience; Abstract Background Urinary incontinence (UI) primary care management is substandard, offering care rather than cure despite the existence of guidelines that help to improve cure. Involving nurse specialists on incontinence in general practice could be a way to improve care for UI patients. Aims We studied whether involving nurse specialists on UI in general practice reduced severity and impact of UI. Methods Between 2005 and 2008 a pragmatic multicentre randomised controlled trial was performed comparing a one-year intervention by trained nurse specialists with care-as-usual after initial diagnosis and assessment by general practitioners in adult patients with stress, urgency or mixed UI in four Dutch regions (Maastricht, Nijmegen, Helmond, The Hague). Simple randomisation was computer-generated with allocation concealment. Analysis was done by intention-to-treat principles. Main outcome measure was the International Consultation on Incontinence Questionnaire Short Form (ICIQ-UI SF) severity sum score. Results 186 patients followed the intervention and 198 received care-as-usual. Patients in both study groups improved significantly in UI severity and impact on health-related quality of life. After correction for effect modifiers (type of UI, Body Mass Index) we found significant differences between groups in favour of the intervention group at three months (p = 0.04); no differences were found in the one-year linear trend (p = 0.15). Patients in the intervention group without baseline anxiety/depression improved significantly better compared to care-as-usual after one year (p = 0.03). Conclusion Involving nurse specialists in care for UI patients supplementary to general practitioners can improve severity and impact of UI, after correction for effect modifiers. This is also the case in specific situations such as anxiety/depression.
Published: 2011

27. Nuclear translocation of β-catenin and decreased expression of E-cadherin in HPV-positive tonsillar cancer: An early event in HPV-related tumor progression?

Author: Stenner, Markus, Yosef, Basima, Huebbers, Christian U, Preuss, Simon Florian, Dienes, Hans Peter, Speel, Ernst-Jan M, Odenthal, Margarete, Klussmann, Jens Peter, ENT, University of Cologne, Pathology, Jean-Uhrmacher-Institute, Molecular Cell Biology, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], and Justus-Liebig-Universität Gießen (JLU)
Subjects: Medicine
Abstract: International audience; Aims: High-risk human papillomaviruses (HPV) seem to be an important risk factor for tonsillar cancer. However, only few data exist concerning molecular changes during metastasis. Methods and Results: We examined 48 primary tonsillar carcinoma samples (25 HPV-16 DNA positive, 23 HPV-16 DNA negative) and their respective lymph node metastases for their HPV status and for the expression of p16, E-cadherin, β-catenin and vimentin. A positive HPV-specific PCR correlated significantly with p16 overexpression in both the primary tumor and metastasis (p
Published: 2011

28. Body weight and risk of breast cancer in BRCA1/2 mutation carriers

Author: Manders, P., Pijpe, A., Hooning, M.J., Kluijt, I., Vasen, H.F., Hoogerbrugge, N., Asperen, C.J. van, Meijers-Heijboer, H., Ausems, M.G., Os, T.A. van, Gomez-Garcia, E.B., Brohet, R.M., Leeuwen, F.E. van, Rookus, M.A., Ligtenberg, M.J.L., Clinical Genetics, Medical Oncology, Internal Medicine, Human genetics, VU University medical center, EMGO - Quality of care, CCA - Innovative therapy, Klinische Genetica, RS: GROW - School for Oncology and Reproduction, Department of Epidemiology, Netherlands Cancer Institute, Department of Human Genetics, Radboud University Medical Center [Nijmegen], Department of Medical Oncology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Family Cancer Clinic, The Netherlands Foundation for the Detection of Hereditary Tumours, Poortgebouw Zuid, Department of Clinical Genetics, Leiden University Medical Center (LUMC), Department of Clinical Genetics and Human Genetics, VU University Medical Center [Amsterdam], Department of Medical Genetics, University Medical Center [Utrecht], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Department of Research and Education, Spaarne hospital, University of Groningen, and Human Genetics
Subjects: Cancer Research, Epidemiology, Overweight, SUSCEPTIBILITY, Weight Gain, Polymerase Chain Reaction, Body Mass Index, Cohort Studies, 0302 clinical medicine, Breast cancer, Risk Factors, Netherlands, 2. Zero hunger, 0303 health sciences, education.field_of_study, Obstetrics, BRCA1 Protein, Genetic Carrier Screening, WOMEN, DNA, Neoplasm, Middle Aged, Prognosis, 3. Good health, Postmenopause, Survival Rate, Oncology, 030220 oncology & carcinogenesis, OBESITY, Female, LIFE-STYLE, Breast disease, medicine.symptom, Adult, medicine.medical_specialty, Population, Hereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1], Breast Neoplasms, Body weight Breast cancer BRCA1/2 HEBON Epidemiology ovarian-cancer estrogen-receptor physical-activity life-style mass index geo-hebon obesity cohort women susceptibility, OVARIAN-CANCER, 03 medical and health sciences, Young Adult, MASS INDEX, SDG 3 - Good Health and Well-being, BRCA1/2, medicine, Humans, COHORT, Risk factor, education, HEBON, 030304 developmental biology, Retrospective Studies, Gynecology, BRCA2 Protein, Hereditary cancer and cancer-related syndromes [ONCOL 1], business.industry, Cancer, Body weight, medicine.disease, ESTROGEN-RECEPTOR, PHYSICAL-ACTIVITY, Premenopause, GEO-HEBON, Case-Control Studies, Mutation, Hereditary cancer and cancer-related syndromes Genomic disorders and inherited multi-system disorders [ONCOL 1], business, Weight gain, Body mass index
Abstract: Contains fulltext : 95679.pdf (Publisher’s version ) (Closed access) Obesity is an established risk factor for postmenopausal breast cancer in the general population. However, it is still unclear whether this association also exists in BRCA1/2 mutation carriers. We investigated the association between self-reported anthropometric measures and breast cancer risk in a nationwide retrospective cohort study, including 719 BRCA1/2 carriers, of whom 218 had been diagnosed with breast cancer within 10 years prior to questionnaire completion. All time-varying Cox proportional hazards analyses were stratified by menopausal status. For premenopausal breast cancer, no statistically significant associations were observed for any of the anthropometric measures. The association between body mass index (BMI) at age 18 and premenopausal breast cancer risk suggested a trend of decreasing risk with increasing BMI (HR(22.50-24.99 vs. 18.50-22.49) = 0.83, 95% CI = 0.47-1.44 and HR(>/= 25.00 vs. 18.50-22.49) = 0.41, 95% CI = 0.13-1.27). For postmenopausal breast cancer, being 1.67 m and taller increased the risk 1.7-fold (HR = 1.67, 95% CI = 1.01-2.74) when compared to a height /= 72 kg increased the risk of postmenopausal breast cancer 2.1-fold (95% CI = 1.23-3.59). A current BMI of >/= 25.0 kg/m(2), an adult weight gain of 5 kg or more, and a relative adult weight gain of 20% or more were all non-significantly associated with a 50-60% increased risk of postmenopausal breast cancer [HR = 1.46 (0.86-2.51), HR = 1.56 (95% CI = 0.85-2.87), and HR = 1.60 (95% CI = 0.97-2.63), respectively], when compared with having a healthy or stable weight. No associations for body weight or BMI at age 18 were observed. In conclusion, menopausal status seemed to modify the association between body weight and breast cancer risk among BRCA1/2 carriers. We observed no clear association between body weight and premenopausal breast cancer, while overweight and weight gain increased postmenopausal breast cancer risk. Carriers may reduce their risk of postmenopausal breast cancer by maintaining a healthy body weight throughout life.
Published: 2011

29. Review article: Clinical relevance of transient lower esophageal sphincter relaxations (TLESR) in gastroesophageal reflux disease

Author: Kessing, Boudewijn Floris, Conchillo, Jose M, Bredenoord, Albert J, Smout, André J P M, Masclee, Ad A., Gastroenterology and Hepatology, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Maastricht University Medical Centre (MUMC), and Maastricht University [Maastricht]-Maastricht University [Maastricht]
Subjects: digestive, oral, and skin physiology, Medicine
Abstract: International audience; Background Transient lower esophageal sphincter relaxations (TLESR) are considered the physiological mechanism which enables venting of gas from the stomach and appear as sphincter relaxations which are not induced by swallowing. It has become increasingly clear that most reflux episodes occur during TLESRs and therefore play a key role in gastroesophageal reflux disease (GERD). Aim The aim of this study is to describe the current knowledge about TLESRs and its clinical implications. Methods Search of the literature published in English using the PubMed database and relevant abstracts presented at international conventions. Results Several factors influence the rate of TLESRs including anti-reflux surgery, meal, body position, nutrition, lifestyle and a wide array of neurotransmitters. Ongoing insights in the neurotransmitters responsible for the modulation of TLESRs, as well as the neural pathways involved in TLESR induction, have lead to novel therapeutic targets. These therapeutic targets can serve as an add on therapy in patients with an unsatisfactory response to PPI by inhibiting TLESRs and its associated reflux events. However, the TLESR-inhibiting drugs that are currently available still have significant side effects. Conclusions It is likely that in the future, selected GERD patients may benefit from TLESR inhibition when a compound is found without significant side effects.
Published: 2011

30. Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer

Author: Maxwell, C.A., Benitez, J., Gomez-Baldo, L., Osorio, A., Bonifaci, N., Fernandez-Ramires, R., Costes, S.V., Guino, E., Chen, H., Evans, G.J.R., Mohan, P., Catala, I., Petit, A., Aguilar, H., Villanueva, A., Aytes, A., Serra-Musach, J., Rennert, G., Lejbkowicz, F., Peterlongo, P., Manoukian, S., Peissel, B., Ripamonti, C.B., Bonanni, B., Viel, A., Allavena, A., Bernard, L., Radice, P., Friedman, E., Kaufman, B., Laitman, Y., Dubrovsky, M., Milgrom, R., Jakubowska, A., Cybulski, C., Gorski, B., Jaworska, K., Durda, K., Sukiennicki, G., Lubinski, J., Shugart, Y.Y., Domchek, S.M., Letrero, R., Weber, B.L., Hogervorst, F.B.L., Rookus, M.A., Collee, J.M., Devilee, P., Ligtenberg, M.J., Luijt, R.B. van der, Aalfs, C.M., Waisfisz, Q., Wijnen, J., Roozendaal, C.E.P. van, Easton, D.F., Peock, S., Cook, M., Oliver, C., Frost, D., Harrington, P., Evans, D.G., Lalloo, F., Eeles, R., Izatt, L., Chu, C., Eccles, D., Douglas, F., Brewer, C., Nevanlinna, H., Heikkinen, T., Couch, F.J., Lindor, N.M., Wang, X.S., Godwin, A.K., Caligo, M.A., Lombardi, G., Loman, N., Karlsson, P., Ehrencrona, H., Wachenfeldt, A. von, Barkardottir, R.B., Hamann, U., Rashid, M.U., Lasa, A., Caldes, T., Andres, R., Schmitt, M., Assmann, V., Stevens, K., Offit, K., Curado, J., Tilgner, H., Guigo, R., Aiza, G., Brunet, J., Castellsague, J., Martrat, G., Urruticoechea, A., Blanco, I., Tihomirova, L., Goldgar, D.E., Buys, S., John, E.M., Miron, A., Southey, M., Daly, M.B., Schmutzler, R.K., Wappenschmidt, B., Meindl, A., Arnold, N., Deissler, H., Varon-Mateeva, R., Sutter, C., Niederacher, D., Imyamitov, E., Sinilnikova, O.M., Stoppa-Lyonne, D., Mazoyer, S., Verny-Pierre, C., Castera, L., Pauw, A. de, Bignon, Y.J., Uhrhammer, N., Peyrat, J.P., Vennin, P., Ferrer, S.F., Collonge-Rame, M.A., Mortemousque, I., Spurdle, A.B., Beesley, J., Chen, X.Q., Healey, S., Barcellos-Hoff, M.H., Vidal, M., Gruber, S.B., Lazaro, C., Capella, G., McGuffog, L., Nathanson, K.L., Antoniou, A.C., Chenevix-Trench, G., Fleisch, M.C., Moreno, V., Pujana, M.A., HEBON, EMBRACE, SWE-BRCA, BCFR, GEMO Study Collaborators, kConFab, Human genetics, CCA - Innovative therapy, Universitat de Barcelona, Faculteit der Geneeskunde, Translational Research Laboratory, Catalan Institute of Oncology-Bellvitge Institute for Biomedical Research, Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), Catalan Institute of Oncology, Human Genetics Group, Spanish National Cancer Research Centre, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Biomarkers and Susceptibility Unit, Life Science Division [LBNL Berkeley], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Child and Family Research Institute, Department of Pathology, University Hospital of Bellvitge, Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare, Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Division of Cancer Prevention and Genetics, Unit of Experimental Oncology 1, Centro di Riferimento Oncologico, Department of Genetics, Biology and Biochemistry, University of Turin, Department of Experimental Oncology, Istituto Europeo di Oncologia-Consortium for Genomics Technology (Cogentech), The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Department of Genetics and Pathology, Pomeranian Medical University-International Hereditary Cancer Centre, Unit of Statistical Genetics, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health, Abramson Cancer Center, University of Pennsylvania [Philadelphia], Family Cancer Clinic, Netherlands Cancer Institute, Department of Epidemiology, Department of Clinical Genetics, Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Department of Genetic Epidemiology, Leiden University Medical Center (LUMC), Department of Human Genetics, Radboud university [Nijmegen], Department of Clinical Molecular Genetics, University Medical Center [Utrecht], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), VU University Medical Center [Amsterdam], Center for Human and Clinical Genetics, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Department of Oncology, Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, Yorkshire Regional Genetics Service, St James's hospital, Wessex Clinical Genetics Service, Princess Anne Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Royal Devon & Exeter Hospital, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Laboratory Medicine and Pathology, Mayo Clinic, Department of Medical Genetics, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Lawrence], Section of Genetic Oncology, Pisa University Hospital-University of Pisa - Università di Pisa, Lund University Hospital, Sahlgrenska University Hospital [Gothenburg], Departament of Genetics and Pathology, Uppsala University-Rudbeck Laboratory, Karolinska University Hospital [Stockholm], Landspitali-University Hospital, Molecular Genetics of Breast Cancer, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Deutsches Krebsforschungszentrum, Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Servicio de Genética, Hospital de la Santa Creu i Sant Pau, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Medical Oncology Division, Hospital Clínico de Zaragoza, Department of Internal Medicine III, University of Rostock, Center for Experimental Medicine, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE)-Institute of Tumor Biology, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Bioinformatics and Genomics Group, Centre for Genomic Regulation (CRG), Genetic Counseling and Hereditary Cancer Programme, Latvian Biomedical Research and Study Centre [Rīga], Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Department of Internal Medicine, Huntsman Cancer Institute, Cancer Prevention Institute of California, Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Department of Surgery, Harvard Medical School [Boston] (HMS), entre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne, Division of Population Science, Fox Chase Cancer Center, Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU), Universitätsklinikum Ulm - University Hospital of Ulm, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Heidelberg University Hospital [Heidelberg], University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], N. N. Petrov Institute of Oncology, Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Génétique moléculaire, signalisation et cancer (GMSC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Pathologie moléculaire des cancers, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Oncogénétique, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Laboratoire d'Oncologie Moléculaire Humaine, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Consultation d'Oncogénétique, Laboratoire de Génétique Chromosomique, Hôtel-Dieu-CH Chambéry, Département de Génétique et Reproduction, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Queensland Institute of Medical Research, Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute [Boston]-Department of Cancer Biology, Department of Genetics [Boston], Department of Internal Medicine, Epidemiology, Human Genetics, Department of Obstetrics and Gynaecologie, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], This work was funded by the Spanish Ministries of Health, and Science ane Innovation (CB07/02/2005, FIS 08/1120, 08/1359, 08/1635, and 09/02483, RTICCC RD06/0020/1060 and RD06/0020/0028, Transversal Action Against Cancer, the Spanish Biomedical Research Centre Networks for Epidemiology and Public Health, and Rare Diseases, and the 'Ramón y Cajal' Young Investigator Program), the Spanish National Society of Medical Oncology (2010), the Spanish Association Against Cancer (AECC 2010), the AGAUR Catalan Government Agency (2009SGR1489 and 2009SGR293, and the Beatriu Pinós Postdoctoral Program), the Ramón Areces Foundation (XV), the 'Roses Contra el Càncer' Foundation, the Michael Cuccione Foundation for Childhood Cancer Research, Cancer Research-UK (C490/A10119, C1287/A8874, C1287/A10118, C5047/A8385, and C8197/A10123), the National Institute for Health Research (UK), the Association for International Cancer Research (AICR-07-0454), the Ligue National Contre le Cancer (France), the Association 'Le cancer du sein, parlons-en!', the Dutch Cancer Society (NKI 1998-1854, 2004-3088, and 2007-3756), the Fondazione Italiana per la Ricerca sul Cancro ('Hereditary Tumors'), the Associazione Italiana per la Ricerca sul Cancro (4017), the Italian Ministero della Salute (RFPS-2006-3-340203 and 'Progetto Tumori Femminili'), the Italian Ministero dell'Universita' e Ricerca (RBLAO3-BETH), the Fondazione IRCCS Istituto Nazionale Tumori (INT '5×1000'), the Fondazione Cassa di Risparmio di Pisa (Istituto Toscano Tumori), the National Breast Cancer Foundation (Australia), the Australian National Health and Medical Research Council (145684, 288704, and 454508), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, the Cancer Foundation of Western Australia, the German Cancer Aid (107054), the Center for Molecular Medicine Cologne (TV93), the National Cancer Institute (USA, CA128978 and CA122340), National Institutes of Health (RFA-CA-06-503, BCFR U01 CA69398, CA69417, CA69446, CA69467, CA69631, and CA69638), the Research Triangle Institute Informatics Support Center (RFP N02PC45022-46), the Specialized Program of Research Excellence (SPORE P50 CA83638 and CA113916), the Department of Defense Breast Cancer Research Program (05/0612), the Eileen Stein Jacoby Fund, the Breast Cancer Research Foundation, the Marianne and Robert MacDonald Foundation, the Komen Foundation, the Helsinki University Central Hospital Research Fund, the Academy of Finland (110663), the Finnish Cancer Society, the Sigrid Juselius Foundation, and the EU FP7 (223175, HEALTH-F2-2009-223175)., HEBON, EMBRACE, SWE-BRCA, BCFR, GEMO Study Collaborators, kConFab, Human Genetics, Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Università degli studi di Torino = University of Turin (UNITO), Tel Aviv University (TAU), International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), University of Pennsylvania, Universiteit Leiden-Universiteit Leiden, Radboud University [Nijmegen], University of Kansas Medical Center [Kansas City, KS, USA], Uppsala University, Université de Lille-UNICANCER-Université de Lille-UNICANCER, Autard, Delphine, Neurology, and Pathology
Subjects: Mama -- Càncer -- Aspectes genètics, MESH: Extracellular Matrix Proteins, endocrine system diseases, Cellular differentiation, Genes, BRCA2, Genes, BRCA1, Microtubules, MESH: Genotype, 0302 clinical medicine, Breast cancer, Aurora Kinases, MESH: Genetic Variation, Biology (General), skin and connective tissue diseases, 0303 health sciences, Extracellular Matrix Proteins, Tumor, MESH: Microtubules, Cancer Risk Factors, 3. Good health, Hyaluronan Receptors, Oncology, Receptors, Estrogen, MESH: Epithelial Cells, 030220 oncology & carcinogenesis, MESH: Receptors, Estrogen, Medicine, General Agricultural and Biological Sciences, Genotype, QH301-705.5, MESH: Antigens, CD44, General Biochemistry, Genetics and Molecular Biology, MESH: Protein-Serine-Threonine Kinases, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Genetics, Cancer Genetics, Humans, Progenitor cell, Biology, MESH: BRCA1 Protein, MESH: Humans, CD44, Genetic Variation, Epithelial Cells, Oncogenes, medicine.disease, BRCA1, BRCA2, Genes, Carcinogenesis, MESH: Genes, BRCA1, MESH: Female, MESH: Genes, BRCA2, Population Genetics, HeLa Cells, Epithelial cells, medicine.disease_cause, MESH: BRCA2 Protein, Cell polarity, Basic Cancer Research, Receptors, Breast, MESH: Breast, MESH: Heterozygote, Aurora Kinase A, Cèl·lules epitelials, biology, BRCA1 Protein, General Neuroscience, MESH: Genetic Predisposition to Disease, Cell Polarity, Biological Sciences, BRCA2 Protein, Mama -- Càncer -- Aspectes moleculars, Protein-Serine-Threonine Kinases, Female, Stem cell, MESH: Cell Polarity, Research Article, Oncogens, Heterozygote, MESH: Cell Line, Tumor, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Protein Serine-Threonine Kinases, Cell Line, Càncer de mama, Cell Line, Tumor, Regulació genètica, medicine, Genetic Predisposition to Disease, Antigens, 030304 developmental biology, General Immunology and Microbiology, Human Genetics, Estrogen, MESH: HeLa Cells, Genetics of Disease, biology.protein, Cancer research, Gene Function, MESH: Breast Neoplasms
Abstract: Genetic analysis identifies the HMMR gene as a modifier of the breast cancer risk associated with BRCA1 gene mutation, while cell biological analysis of the protein product suggests a function in regulating development of the mammary gland., Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio (wHR) = 1.09 (95% CI 1.02–1.16), ptrend = 0.017; and n = 3,965, wHR = 1.04 (95% CI 0.94–1.16), ptrend = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM., Author Summary Mutations in two genes that were initially identified as predisposing carriers to early-onset breast cancer, BRCA1 and BRCA2, cause similar perturbations in cellular responses to DNA damage but predispose carriers to distinct tumor types. Thus, the two genes may trigger different carcinogenic processes. We have used genetic analyses of affected families to uncover additional genetic variation that is linked to the risk of developing cancer for carriers of BRCA1 mutations. This variation falls within a centrosomal gene, named HMMR. The protein product of HMMR, which is called RHAMM, works in concert with BRCA1 to regulate the structure of normal breast cells as they grow and become polarized. This polarization process depends upon a balance between the activities of BRCA1 and the Aurora kinase A, with the kinase opposing BRCA1 function and promoting growth. Our findings provide new insights into the mechanism through which BRCA1 may promote commitment of initially bipotent mammary cells towards the luminal lineage, and how loss of this function may predispose cells to become breast tumors of a basal-like type.
Published: 2011

31. Expression of aberrantly glycosylated Mucin-1 in ovarian cancer

Author: Van Elssen, Catharina H.M.J., Frings, Peter W.H., Bot, Freek J., Van De Vijver, Koen K, Huls, Mariska B, Meek, Bob, Hupperets, Pierre, Germeraad, Wilfred T.V., Bos, Gerard M.J., Promovendi ODB, Pathologie, Interne Geneeskunde, RS: GROW - School for Oncology and Reproduction, Internal medicine, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Pathology, and Intenal medicine, oncology
Subjects: ovarian adenocarcinoma, STn, endocrine system diseases, Tn, Medicine, Mucin 1 and glycosylation, tumour-associated antigen, digestive system diseases, female genital diseases and pregnancy complications
Abstract: International audience; Aims: Mucin 1 (MUC1) is an important tumour-associated antigen (TAA), both over-expressed and aberrantly glycosylated in adenocarcinomas. The objective of this study was to examine the MUC1-glycosylation status in primary ovarian adenocarcinomas and metastatic lesions. Methods and results: Paraffin-embedded tissue sections of 37 primary ovarian adenocarcinomas representing all histotypes (22 serous, 5 mucinous, 2 clear cell, 8 endometrioid), 4 serous borderline tumours with intraepithelial carcinoma, 7 sections of ovarian endometriosis and 13 metastatic lesions were analysed by immuno-histochemistry. Non-neoplastic ovarian surface epithelium and serous cystadenomas were used as controls. All epithelia expressed MUC1 protein. Of primary tumours, 76% expressed the differentiation-dependent glycoform and 84% the cancer-associated glycoform (Tn/Sialyl-Tn-epitopes). In metastatic lesions this was 77% and 85%, respectively. Notably, in 57% of ovarian endometriosis and 75% of intraepithelial lesions, the cancer-associated MUC1 epitopes were expressed, whereas normal ovarian surface epithelium and serous cystadenomas did not express these epitopes. Conclusions: The underglycosylated MUC1 epitopes are expressed by all histotypes of primary ovarian adenocarcinomas, by the vast majority of metastatic lesions and by ovarian cancer precursor lesions, whereas not by normal ovarian tissue. These results indicate that MUC1-associated Tn/STn-epitopes are important targets for immunotherapy and diagnostic imaging in ovarian cancer patients.
Published: 2010

32. Skeletal muscle lipase content and activity in obesity and type 2 diabetes

Author: Aline Mairal, Luc J. C. van Loon, Ellen E. Blaak, Dominique Hansen, Matthijs K. C. Hesselink, Gijs H. Goossens, Cedric Moro, Dominique Langin, Johan W. E. Jocken, Department of Human Biology, Maastricht University [Maastricht], Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Jessa Hospital and Rehabilitation and Healthcare Research Center, Provinciale Hogeschool Limburg University College, Department of Human Movement Sciences, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise, Humane Biologie, Nutrition and Movement Sciences, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, and RS: NUTRIM - R1 - Metabolic Syndrome
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Arbitrary unit, Lipolysis, Clinical Biochemistry, Triacylglycerol lipase, Context (language use), Biochemistry, MESH: Lipase, Endocrinology, Insulin resistance, Thinness, Reference Values, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, MESH: Obesity, Humans, MESH: Lipolysis, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, Lipase, Muscle, Skeletal, MESH: Muscle, Skeletal, MESH: Sterol Esterase, MESH: Thinness, MESH: Humans, biology, Biochemistry (medical), MESH: Reference Values, Skeletal muscle, Sterol Esterase, medicine.disease, MESH: Case-Control Studies, MESH: Male, MESH: Insulin Resistance, Lipoprotein Lipase, medicine.anatomical_structure, Diabetes Mellitus, Type 2, Case-Control Studies, Adipose triglyceride lipase, biology.protein, Insulin Resistance, MESH: Diabetes Mellitus, Type 2, MESH: Lipoprotein Lipase
Abstract: Context: The obese insulin-resistant state is characterized by elevated lipid storage in skeletal muscle tissue. Objective: We tested whether differences in muscle triacylglycerol (TAG) and diacylglycerol (DAG) lipase content and activity are associated with incomplete in vivo lipolysis and lipid accumulation. Design and Patients: Two case-control studies were conducted on skeletal muscle biopsies from lean (n = 13) and obese (n = 10) men (study 1) and from 11 nonobese type 2 diabetic (T2D), obese T2D, and healthy normoglycemic men (study 2). Main Outcome Measures: Skeletal muscle lipase protein content and activity and muscle lipid content (TAG and DAG) were determined. Results: Skeletal muscle hormone-sensitive lipase protein content was lower (0.39 +/- 0.07 vs. 1.00 +/- 0.19 arbitrary units; P = 0.004) and adipose triglyceride lipase protein content was higher in obese men compared with lean controls (2.17 +/- 0.40 vs. 0.42 +/- 0.23 arbitrary units; P = 0.008). This apparent difference in lipase content was accompanied by a 60% lower ratio of DAG to TAG hydrolase activity in the obese men (11.4 +/- 2.3 vs. 26.5 +/- 7.3 nmol/h . mg; P = 0.045), implying incomplete lipolysis. Lower hormone-sensitive lipase and higher adipose triglyceride lipase content was confined to obesity per se, because it was observed solely in obese T2D men but not in healthy normoglycemic controls and nonobese T2D men. Muscle total DAG content was not higher in obese men but was even lower (6.2 +/- 0.7 vs. 9.4 +/- 0.9 mumol/mg dry weight; P = 0.017). TAG content did not differ between groups (84.7 +/- 18.9 vs. 70.4 +/- 12.4 mumol/mg dry weight; P = 0.543). Conclusions: Our data do not support an important role of total muscle DAG content in the development of insulin resistance in obese men.
Published: 2010

33. Proton pump inhibitor use is associated with an increased risk for microscopic colitis: a case-control study

Author: Keszthelyi, Daniel, Jansen, Sita V, Schouten, Gerben A, De Kort, Sander, Scholtes, Brian, Engels, Leopold GJB, Masclee, Ad A., Gastroenterology and Hepatology, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Internal Medicine, and Orbis Medical Concern
Subjects: Medicine
Abstract: International audience; Background: Microscopic colitis (MC) causes chronic watery diarrhea. Recent studies have suggested an etiological role for various medications, including proton pump inhibitors, in the pathogenesis of MC. Aim: To determine whether an association exists between microscopic colitis and proton pump inhibitor use in patients with documented microscopic colitis versus age and sex-matched controls. Methods: In this retrospective case-control study. Cases of microscopic colitis from a secondary and tertiary referral medical center diagnosed in the last 5 years were reviewed. Demographic characteristics, clinical, histological and endoscopic records, as well as exposure to PPIs and NSAIDs were assessed. Controls from the population were matched to cases by gender and by age. Results: During the investigated period, 136 cases were identified in both hospitals. Of these, 95 cases of MC were retrieved for detailed analysis. Exposure to proton pump inhibitors at the time of the histological diagnosis was significantly higher in MC patients than in controls (38% vs 11%, p
Published: 2010

34. Variation in management of early breast cancer in the Netherlands, 2003-2006

Author: J.W.W. Coebergh, M.L.E.A. Jansen-Landheer, Henk Struikmans, Michel W.J.M. Wouters, Vivianne C. G. Tjan-Heijnen, L.V. van de Poll-Franse, C.J.H. van de Velde, L.N. van Steenbergen, Interne Geneeskunde, RS: GROW - School for Oncology and Reproduction, Public Health, Medical and Clinical Psychology, Comprehensive Cancer Centre South, Tilburg University [Tilburg], Netspar, Dept. of Surgery, Antoni van Leeuwenhoek Hospital, Comprehensive Cancer Centre Amsterdam, Dept. of Public Health, Erasmus University Medical Centre, Dept. of Radiotherapy, Leiden University Medical Center (LUMC), Medical Centre Haaglanden, Dept. of Internal Medicine, Maastricht University Medical Centre (MUMC), and Maastricht University [Maastricht]-Maastricht University [Maastricht]
Subjects: sentinel lymph node procedure, medicine.medical_treatment, Segmental, Mastectomy, Segmental, Breast-conserving surgery, Registries, Non-U.S. Gov't, Mastectomy, Adjuvant, Netherlands, Research Support, Non-U.S. Gov't, General Medicine, Sentinel node, Middle Aged, Combined Modality Therapy, Hospitals, Treatment Outcome, Oncology, Lymphatic Metastasis, Female, Adult, medicine.medical_specialty, Breast surgery, Antineoplastic Agents, Breast Neoplasms, Research Support, breast conserving surgery, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Journal Article, Humans, early breast cancer, axillary lymph node dissection, Aged, Neoplasm Staging, Gynecology, Radiotherapy, business.industry, Sentinel Lymph Node Biopsy, Axillary Lymph Node Dissection, medicine.disease, Cancer registry, Radiation therapy, Logistic Models, Axilla, Lymph Node Excision, Surgery, Radiotherapy, Adjuvant, adjuvant systemic therapy, business
Abstract: BACKGROUND: To describe variation in staging and primary treatment by hospital characteristics including type and volume and region in patients with early breast cancer (BC) in the Netherlands, 2003-2006 after completion of national guidelines in 2002.METHODS: All patients newly diagnosed with invasive BC in 2003-2006 and recorded in the Netherlands Cancer Registry were included (n = 51 354). Multivariable logistic regression analyses examined the influence of patient and hospital characteristics, also by region, on type of breast surgery, axillary lymph node dissection (ALND), sentinel node procedure (SNP), and adjuvant irradiation and/or systemic treatment.RESULTS: Patients CONCLUSION: With detailed evidence-based national guidelines since 2002 the considerable regional and hospital variation in staging procedures and primary treatment among newly diagnosed patients with early breast cancer in the Netherlands decreased markedly, suggesting the presence of late adaptors rather than specific hospital characteristics.
Published: 2010

35. Are breast conservation and mastectomy equally effective in the treatment of young women with early breast cancer? Long-term results of a population-based cohort of 1,451 patients aged ≤40 years

Author: Grard A. P. Nieuwenhuijzen, M. Cathelijne B. J. E. Tutein Nolthenius-Puylaert, Rudi M. H. Roumen, Maurice J.C. van der Sangen, Adri C. Voogd, Philip Poortmans, Fenneke M. M. van de Wiel, Miranda F. Ernst, Vivianne C. G. Tjan-Heijnen, Department of Radiotherapy, Catharina Hospital, Faculty of Health, Medicine and Life Sciences, Maastricht University [Maastricht], Dr. Bernard Verbeeten Institute, Division of Medical Oncology, Department of Internal Medicine, Research Institute Growth and Development (GROW), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Department of Surgery, Máxima Medical Centre, Jeroen Bosch Hospital, Department of Pathology, Elkerliek Hospital, Department of Epidemiology, Research Institute Growth and Development (GROW), and Eindhoven Cancer Registry
Subjects: Adult, Cancer Research, medicine.medical_specialty, Survival, medicine.medical_treatment, Breast carcinoma, Breast Neoplasms, Systemic treatment, Mastectomy, Segmental, Cohort Studies, Young Adult, Breast cancer, Recurrence, Internal medicine, medicine, Humans, Young adult, Mastectomy, Neoplasm Staging, business.industry, Age Factors, Cancer, Breast conservation, medicine.disease, Prognosis, Combined Modality Therapy, Survival Analysis, Confidence interval, Surgery, Oncology, Local control, Female, Breast disease, business, Cohort study
Abstract: International audience; To compare the effectiveness of breast-conserving therapy (BCT) and mastectomy, all women aged ≤40 years, treated for early-stage breast cancer in the southern part of the Netherlands between 1988 and 2005, were identified. A total of 562 patients underwent mastectomy and 889 patients received BCT. During follow-up, 23 patients treated with mastectomy and 135 patients treated with BCT developed a local relapse without previous or simultaneous evidence of distant disease. The local relapse risk for patients treated with mastectomy was 4.4% (95% confidence interval (CI) 2.4-6.4) at 5 years and reached a plateau after 6 years at 6.0% (95% CI 3.5-8.5). After BCT, the 5-, 10- and 15-year risks were 8.3% (95% CI 6.3-10.5), 18.4% (95% CI 15.0-21.8) and 28.2% (95% CI 23.0-33.4), respectively (
Published: 2010

36. Safety of avoiding routine use of axillary dissection in early stage breast cancer: a systematic review

Author: Maaike de Boer, Vivianne C. G. Tjan-Heijnen, George F. Borm, Paul J. van Diest, J.H.M.J. Vestjens, Marjolein L. Smidt, Manon J. Pepels, RS: NUTRIM - R2 - Gut-liver homeostasis, Interne Geneeskunde, Surgery, RS: GROW - School for Oncology and Reproduction, Division of Medical Oncology, Department of Internal Medicine, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Department of Medical Oncology, Radboud University Medical Center [Nijmegen], Department of Surgery, GROW--School for Oncology and Developmental Biology, University Medical Centre Utrecht, University Medical Center [Utrecht], and Department of Epidemiology, Biostatistics and HTA
Subjects: Cancer Research, medicine.medical_specialty, Survival, SENTINEL-LYMPH-NODE, LONG-TERM, SURGERY, medicine.medical_treatment, Sentinel lymph node, Quality of nursing and allied health care [NCEBP 6], Breast Neoplasms, Axillary recurrence, Breast cancer, Axillary lymph node dissection, Clinical endpoint, Medicine, Humans, Survival rate, Radical mastectomy, Neoplasm Staging, 25-YEAR FOLLOW-UP, RECURRENCE RATE, business.industry, Sentinel Lymph Node Biopsy, Axillary Lymph Node Dissection, medicine.disease, Prognosis, REGIONAL RECURRENCE, Surgery, RANDOMIZED CLINICAL-TRIAL, Survival Rate, Oncology, Sentinel node, Evaluation of complex medical interventions [NCEBP 2], Lymphatic Metastasis, RADICAL-MASTECTOMY, BIOPSY, Lymph Node Excision, Lymphadenectomy, Female, Breast disease, Neoplasm Recurrence, Local, business
Abstract: Item does not contain fulltext Physicians are moving away from routine axillary lymph node dissection (ALND) in clinically node-negative breast cancer. We conducted a systemic review on the safety of this policy. Pubmed and Cochrane library were searched for. Sixty-eight studies were included: studies of clinically node-negative patients in the pre-sentinel node (SN) era; observational studies of SN-negative patients, without ALND; comparative studies of SN-negative patients, with a non-ALND and an ALND group; SN-positive studies, of patients without ALND. Primary endpoint was the pooled axillary recurrence rate (ARR) of each category; secondary endpoint was overall survival (OS) rate. In pre-SN studies, with larger tumors and less systemic therapy, ARR without ALND after 5-10 years follow-up was 12-18%, with 5% reduced OS. In the observational SN-negative studies, with median follow-up of 36 months, the pooled ARR was 0.6% (95% CI 0.6-0.8). In the comparative SN-negative studies, pooled ARR was 0.4% (95% CI 0.2-0.6) without ALND versus 0.3% (95% CI 0.1-0.6) with ALND at 31 and 47 months, respectively, and no survival disadvantage. In SN-positive studies, ARR was up to 1.7% (95% CI 1.0-2.7) at 30 months. For patients with an H&E positive SN the ARR without ALND was 5% after 23 months, which may imply rates as high as 13 and 18% after 5 and 8 years. In conclusion, this systematic review confirms the safety of omitting ALND in SN-negative patients. There is a potential role for avoiding ALND in selected SN-positive patients, but eligibility criteria and the role of systemic therapy need further to be elucidated.
Published: 2010

37. Childhood and adolescent energy restriction and subsequent colorectal cancer risk: results from the Netherlands Cohort Study

Author: R Alexandra Goldbohm, Anton F.P.M. de Goeij, Laura A. E. Hughes, Adriaan P. de Bruïne, Piet A. van den Brandt, Manon van Engeland, Matty P. Weijenberg, Promovendi ODB, Epidemiologie, Pathologie, RS: CAPHRI School for Public Health and Primary Care, RS: GROW - School for Oncology and Reproduction, Epidemiology, Maastricht University [Maastricht], Department of Epidemiology, Prevention and Health, TNO Quality of Life, Pathology, Maastricht University Medical Centre (MUMC), and Maastricht University [Maastricht]-Maastricht University [Maastricht]
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Epidemiology, Colorectal cancer, Hunger, Lower risk, Young Adult, cohort studies, Residence Characteristics, Risk Factors, medicine, Humans, Body Weights and Measures, Prospective Studies, Risk factor, Prospective cohort study, Child, Exercise, Aged, Netherlands, business.industry, Smoking, starvation, General Medicine, Middle Aged, medicine.disease, Surgery, Diet, Socioeconomic Factors, Cohort, Medicine, adolescence, Female, caloric restriction, Risk assessment, business, Colorectal Neoplasms, Energy Intake, Cohort study, Demography
Abstract: Background: Energy restriction during childhood and adolescence is suggested to lower colorectal cancer (CRC) risk. We investigated this in the Netherlands Cohort Study. Methods: Information on diet and other risk factors was collected by a baseline questionnaire in 1986 when cohort members were 55-69 years of age (n = 120 852). Three indicators of early life exposure to energy restriction were assessed: father's employment status during the Economic Depression (1932-40), place of residence during Second World War years (1940-44) and the 'Hunger Winter' (1944-45), a severe famine. Using the case-cohort approach, incidence rate ratios (RRs) and 95% confidence intervals (CIs) were calculated for total colorectal, proximal colon, distal colon, rectosigmoid and rectal cancers, according to the three time periods of energy restriction. After 16.3 years of follow-up, 2573 cases were available for multivariate analyses. Results: Men who lived in a western city during the Hunger Winter and therefore exposed to the highest degree of energy restriction, had a lower risk of developing CRC (RR: 0.81, 95% CI: 0.68-0.98), and tumours of the proximal colon (RR: 0.72, 95% CI: 0.54-0.96) and rectum (RR: 0.71, 95% CI: 0.53-0.96). In women, non-statistically significant inverse associations were observed for tumours of the distal colon, rectosigmoid and rectum. Inverse associations were also observed between the other two exposure times and studied endpoints, though not statistically significant. Conclusions: This unique observational evidence suggests that severe energy restriction during childhood and adolescence may lower CRC risk, especially in men, thus providing insight regarding the role of energy intake during early life in CRC development. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2010; all rights reserved.
Published: 2010

38. Assessment of false-negative cases of breast MR imaging in women with a familial or genetic predisposition

Author: Jan G. M. Klijn, Claudette E. Loo, Theo Kok, E. Bergers, Adriana J. Rijnsburger, Inge-Marie Obdeijn, Martin N. J. M. Wasser, Carla Boetes, Department of Radiology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Radiology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Family Cancer Clinic, Leiden University Medical Center (LUMC), VU University Medical Center [Amsterdam], Groningen University Medical Center, Radboud University Medical Center [Nijmegen], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Beeldvorming, RS: FHML non-thematic output, Radiology & Nuclear Medicine, Medical Oncology, Radiology and nuclear medicine, and CCA - Innovative therapy
Subjects: Cancer Research, Breast cancer, Risk Factors, Mass Screening, skin and connective tissue diseases, False Negative Reactions, ULTRASOUND, Netherlands, medicine.diagnostic_test, BRCA1 Protein, Middle Aged, RESONANCE, Magnetic Resonance Imaging, CANCER, Pedigree, Gene Expression Regulation, Neoplastic, Hereditary, Oncology, CARCINOMA IN-SITU, Screening, Female, Radiology, Breast disease, Breast cancer MRI Screening Hereditary carcinoma in-situ high-risk diagnostic-accuracy mutation carriers brca2 mutations cancer mammography resonance surveillance ultrasound, MRI, Adult, medicine.medical_specialty, Breast Neoplasms, MUTATION CARRIERS, Malignancy, Risk Assessment, MAMMOGRAPHY, SDG 3 - Good Health and Well-being, Predictive Value of Tests, SURVEILLANCE, medicine, Genetic predisposition, Humans, Mammography, Genetic Predisposition to Disease, DIAGNOSTIC-ACCURACY, BRCA2 MUTATIONS, Retrospective Studies, BRCA2 Protein, business.industry, Carcinoma in situ, Cancer, Ductal carcinoma, medicine.disease, Surgery, HIGH-RISK, Carcinoma, Intraductal, Noninfiltrating, Mutation, Apoptosis Regulatory Proteins, business
Abstract: International audience; In order to assess the characteristics of malignant breast lesions those were not detected during screening by MR imaging. In the Dutch MRI screening study (MRISC), a non-randomized prospective multicenter study, women with high familial risk or a genetic predisposition for breast cancer were screened once a year by mammography and MRI and every 6 months with a clinical breast examination (CBE). The false-negative MR examinations were subject of this study and were retrospectively reviewed by two experienced radiologists. From November 1999 until March 2006, 2,157 women were eligible for study analyses. Ninety-seven malignant breast tumors were detected, including 19 DCIS (20%). In 22 patients with a malignant lesion, the MRI was assessed as BI-RADS 1 or 2. One patient was excluded because the examinations were not available for review. Forty-three percent (9/21) of the false-negative MR cases concerned pure ductal carcinoma in situ (DCIS) or DCIS with invasive foci, in eight of them no enhancement was seen at the review. In six patients the features of malignancy were missed or misinterpreted. Small lesion size ( = 3), extensive diffuse contrast enhancement of the breast parenchyma ( = 2), and a technically inadequate examination ( = 1) were other causes of the missed diagnosis. A major part of the false-negative MR diagnoses concerned non-enhancing DCIS, underlining the necessity of screening not only with MRI but also with mammography. Improvement of MRI scanning protocols may increase the detection rate of DCIS. The missed and misinterpreted cases are reflecting the learning curve of a multicenter study.
Published: 2009

39. The impact of preoperative breast MRI on the re-excision rate in invasive lobular carcinoma of the breast

Author: Peter Bult, Ritse M. Mann, Carla Boetes, Theo Wobbes, Claudette E. Loo, Kenneth G. A. Gilhuijs, Jelle O. Barentsz, Beeldvorming, RS: GROW - School for Oncology and Reproduction, Department of Radiology, Radboud University Medical Center [Nijmegen], The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Department of Surgery, Department of Pathology, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], School for Oncology and Developmental Biology [Maastricht] (GROW), Maastricht University [Maastricht]-Maastricht University Medical Centre (MUMC), and Maastricht University [Maastricht]
Subjects: Adult, Reoperation, Cancer Research, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Breast Neoplasms, Aetiology, screening and detection [ONCOL 5], Mastectomy, Segmental, Preoperative care, Risk Assessment, Breast cancer, Translational research [ONCOL 3], Predictive Value of Tests, Breast conserving surgery, Preoperative Care, Breast-conserving surgery, Odds Ratio, Medicine, Breast MRI, Humans, Neoplasm Invasiveness, skin and connective tissue diseases, Mastectomy, Aged, Netherlands, Retrospective Studies, Aged, 80 and over, medicine.diagnostic_test, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Invasive lobular carcinoma, Magnetic Resonance Imaging, Surgery, Carcinoma, Lobular, Treatment Outcome, Oncology, Female, Breast disease, Radiology, business, Re-excision rate
Abstract: Contains fulltext : 87794.pdf (Publisher’s version ) (Closed access) Re-excision rates after breast conserving surgery(BCS) of invasive lobular carcinoma (ILC) are high.Preoperative breast MRI has the potential to reduce re-excision rates, but may lead to an increased rate of mastectomies. Hence, we assessed the influence of preoperative breast MRI on the re-excision rate and the rate of mastectomies. We performed a retrospective cohort study of a consecutive series of patients with ILC who presented in one of two dedicated tertiary cancer centers between 1993 and 2005. We assessed the initial type of surgery(BCS or mastectomy), the re-excision rate and the final type of surgery. Patients were stratified into two groups:those who received preoperative MRI (MR? group) and those who did not (MR- group). In the MR- group, 27%of the patients underwent a re-excision after initial BCS. In the MR? group, this rate was significantly lower at 9%.The odds ratio was 3.64 (95% CI: 1.30-10.20, P = 0.010).There was a trend towards a lower final mastectomy rate in the MR? group compared to the MR- group (48 vs. 59%,P = 0.098). In conclusion, preoperative MRI in patients with ILC can reduce re-excision rates without increasing the rate of mastectomies. 01 januari 2010
Published: 2009

40. Local recurrence in rectal cancer can be predicted by histopathological factors

Author: Regina G. H. Beets-Tan, R.C. Dresen, H.J.T. Rutten, Iris D. Nagtegaal, Grard A. P. Nieuwenhuijzen, J.H.J.M. van Krieken, T.B.J. Demeyere, Esther Peters, A. J. C. Van Den Brule, Alfons G. H. Kessels, Department of Surgery, Catharina Hospital Eindhoven, Department of Radiology, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Department of Pathology, Radboud University Medical Center [Nijmegen], Department of pathology, and Department of Epidemiology
Subjects: Adult, Male, medicine.medical_specialty, Age-related aspects of cancer [ONCOL 2], Genetics and epigenetic pathways of disease [NCMLS 6], Lymphovascular invasion, Colorectal cancer, lymphovascular invasion, Protective factor, Aetiology, screening and detection [ONCOL 5], Logistic regression, Gastroenterology, Translational research [ONCOL 3], Internal medicine, Adjuvant therapy, Medicine, Humans, Neoplasm Invasiveness, rectal cancer, extramural venous invasion, Aged, Netherlands, Gynecology, Aged, 80 and over, Hereditary cancer and cancer-related syndromes [ONCOL 1], integumentary system, business.industry, Rectal Neoplasms, Incidence (epidemiology), Incidence, fungi, Case-control study, food and beverages, General Medicine, Middle Aged, medicine.disease, Prognosis, Combined Modality Therapy, Logistic Models, Oncology, Case-Control Studies, histopathology, Surgery, Histopathology, Female, Neoplasm Recurrence, Local, local recurrence, business
Abstract: Contains fulltext : 79958.pdf (Publisher’s version ) (Closed access) AIM: The main cause of local recurrence (LR) in rectal cancer is involvement of the circumferential resection margin (CRM). However, patients with a negative CRM can also develop LR, suggesting that additional factors are important for LR. The aim of this study was to identify histopathological factors predictive for the development of LR after primary rectal cancer treatment. METHODS: T x N x M0 patients treated for locally recurrent rectal cancer at the Catharina hospital from 1994 to 2006 (n=92) were matched with a control group of patients who did not develop LR after primary rectal cancer treatment for at least 2 years (n=185) based on the type of neoadjuvant treatment in a 1:2 ratio. The pathology of all primary rectal cancers was reviewed. Patient, treatment and histopathological characteristics were studied in relation to the development of LR with logistic regression. RESULTS: Logistic regression indicated the presence of lymphovascular invasion (LVI, OR 4.66, P
Published: 2009

41. Noninvasive Characterisation of Short-and Long-Term Recurrence of Atrial Signals During Persistent Atrial Fibrillation

Author: Olivier Meste, Harry J.G.M. Crijns, Theo Lankveld, Muhammad Haziq Kamarul Azman, Ulrich Schotten, Joël Karel, Stef Zeemering, Pietro Bonizzi, Ralf Peeters, Department of data science and Knowledge Engineering [Maastricht], Maastricht University [Maastricht], Department of Physiology [Maastricht], Laboratoire d'Informatique, Signaux, et Systèmes de Sophia-Antipolis (I3S) / Equipe SIGNAL, Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Department of Cardiology, Cardiovascular Research Institute Maastricht, Department of Physiology, Maastricht University, Department of Physiology, Maastricht University [Maastricht]-Maastricht University [Maastricht], DKE Scientific staff, RS: FSE DACS BMI, Fysiologie, RS: CARIM - R2.11 - Experimental atrial fibrillation, Cardiologie, MUMC+: MA Cardiologie (9), RS: CARIM - R2.01 - Clinical atrial fibrillation, and RS: FSE MaCSBio
Subjects: Therapy Outcome, medicine.medical_specialty, business.industry, 0206 medical engineering, 020206 networking & telecommunications, Atrial fibrillation, 02 engineering and technology, Mutually exclusive events, medicine.disease, 020601 biomedical engineering, Term (time), Internal medicine, Persistent atrial fibrillation, 0202 electrical engineering, electronic engineering, information engineering, medicine, Cardiology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract: International audience; Propagation of electrical atrial activity (AA) during atrial fibrillation (AF) is a process characterized by different short-and long-term recurrence behaviours. Two anti-thetical (not mutually exclusive) hypotheses are proposed to noninvasively describe this nonstationary behaviour. The first hypothesis (H1) assumes a process with stationary spatial properties of AA propagation, but time-varying frequency properties, and vice versa for the second (H2). Based on H1 and H2, two phenomenological models were proposed, both able to replicate observations on AF patients, and a novel measure was introduced to assess the spatial variability of AA propagation (SVAAP) over short and long AA segments. Validity of the models was tested by looking at the relation between SVAAP-long and SVAAP-short on real observations from AF patients (high-density body surface potential maps recorded in 75 patients affected by persistent AF). H1 is confirmed if SVAAP-short is approximately equal to SVAAP-long. H2 if SVAAP-short is less than SVAAP-long. Results confirmed H2, showing that AA propagation during AF has strong nonstationary spatial properties. This could suggest new parameters to characterise AF sub-strate and predict therapy outcome.

42. Noninvasive recurrence quantification analysis predicts atrial fibrillation recurrence in persistent patients undergoing electrical cardioversion

Author: Olivier Meste, Theo Lankveld, Ulrich Schotten, Harry J.G.M. Crijns, Pietro Bonizzi, Joël Karel, Ralf Peeters, Stef Zeemering, Fysiologie, DKE Scientific staff, RS: FSE DACS BMI, Promovendi CD, Cardiologie, RS: CARIM - R2.11 - Experimental atrial fibrillation, MUMC+: MA Cardiologie (9), RS: CARIM - R2.01 - Clinical atrial fibrillation, RS: FSE MaCSBio, Meste, Olivier, Laboratoire d'Informatique, Signaux, et Systèmes de Sophia-Antipolis (I3S) / Equipe SIGNAL, Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Department of Physiology, Maastricht University, Department of Physiology, Maastricht University [Maastricht]-Maastricht University [Maastricht], Department of data science and Knowledge Engineering [Maastricht], and Maastricht University [Maastricht]
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, medicine.medical_specialty, COMPLEXITY, business.industry, 020206 networking & telecommunications, Atrial fibrillation, 02 engineering and technology, 030204 cardiovascular system & hematology, medicine.disease, Electrical cardioversion, 03 medical and health sciences, 0302 clinical medicine, Recurrence quantification analysis, Internal medicine, 0202 electrical engineering, electronic engineering, information engineering, medicine, Cardiology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, In patient, Temporal organization, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing
Abstract: International audience; This study proposes a novel noninvasive ECG-based approach to accurately quantify differences in the atrial activity (AA) signals of atrial fibrillation (AF) patients characterized by very similar global AF organization. High-density body surface potential maps were recorded in 63 patients in persistent AF prior to electrical car-dioversion (32 recurrences occurred after 4-6 weeks). AF substrate complexity was quantified as the degree of overall temporal organization of the AA pattern, determined from multi-variable unthresholded recurrence plots (RP). Results showed that non-recurrent patients were characterized by temporally more stable propagation patterns than recurrent patients, suggesting a lower complexity of the AF substrate in the former. This was used to discriminate between recurrent and non-recurrent AF patients following electrical cardioversion with an accuracy of 72%. Noninvasive assessment of AF substrate complexity in patients characterized by very similar levels of AF progression was improved by applying RP-based analysis on extracted AA signals. The proposed approach may help improving AF treatment selection and success.

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