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1. An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity

Author: Volta U, Bardella MT, Calabrò A, Troncone R, Corazza GR, Study Group for Non Celiac Gluten S.e.n.s.i.t.i.v.i.t.y. Authors’ contributions UV: Study design, clinical evaluation, enrollment of patients, data analysis, writing of the manuscript, final s.u.p.e.r.v.i.s.i.o.n. MTB: Study design, final supervision of the m.a.n.u.s.c.r.i.p.t. AC, RT: Study design, final supervision of the m.a.n.u.s.c.r.i.p.t. GRC: Study design, final supervision of the m.a.n.u.s.c.r.i.p.t. All authors read, approved the final m.a.n.u.s.c.r.i.p.t. The Study Group for Non Celiac Gluten Sensitivity, included Carmela Bagnato, Claudio Belcari, Antonella Bellantoni, Giacomo Caio, Francesca Calella, Maria Cappello, Carolina Ciacci, Cinzia D’Agate, Italo De Vitis, Antonio Di Sabatino, Gianmarco Fava, Maria Rita Frau, Alessandro Fugazza, Stefano Andrea Grassi, Giuseppina Larcinese, Giovanni Latella, Adriano Lauri, Angelo Lauria, Nicoletta Lenoci, Norma Beatriz Lopez Rios, Donatella Macchia, Mauro Minelli, Beba Molinari, Olivia Morelli, Maria Gloria Mumolo, Giovanni Niccoli, Caterina Pacenza, Francesco Pallone, Fabrizio Parente, Raffaella Pulitanò, Rossella Pumpo, Antonio Rispo, Flavio Romolo Rispoli, Francesco Tedone, Flavio Valiante, Giovanni Viviani, Paolo Usai S.a.t.t.a. All these authors performed clinical evaluation, as well as final supervision of the manuscript, RIEGLER, Gabriele, DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE, Da definire, Volta U, Bardella MT, Calabrò A, Troncone R, Corazza GR, Study Group for Non-Celiac Gluten Sensitivity, Volta, U, Bardella, Mt, Calabrò, A, Troncone, R, Corazza, Gr, Authors’ contributions UV: Study design, Study Group for Non Celiac Gluten S. e. n. s. i. t. i. v. i. t. y., Clinical, Evaluation, enrollment of, Patient, Data, Analysi, writing of the, Manuscript, MTB: Study design, final s. u. p. e. r. v. i. s. i. o. n., final supervision of the m. a. n. u. s. c. r. i. p. t., Ac, RT: Study, Design, GRC: Study design, final supervision of the m. a. n. u. s. c. r. i. p. t., All authors read, final supervision of the m. a. n. u. s. c. r. i. p. t., The Study Group for Non Celiac Gluten Sensitivity, approved the final m. a. n. u. s. c. r. i. p. t., included Carmela, Bagnato, Claudio, Belcari, Antonella, Bellantoni, Giacomo, Caio, Francesca, Calella, Maria, Cappello, Carolina, Ciacci, Cinzia, D’Agate, Italo De, Viti, Antonio Di, Sabatino, Gianmarco, Fava, Maria Rita, Frau, Alessandro, Fugazza, Stefano Andrea, Grassi, Giuseppina, Larcinese, Giovanni, Latella, Adriano, Lauri, Angelo, Lauria, Nicoletta, Lenoci, Norma Beatriz Lopez, Rio, Donatella, Macchia, Mauro, Minelli, Beba, Molinari, Olivia, Morelli, Maria Gloria, Mumolo, Giovanni, Niccoli, Caterina, Pacenza, Francesco, Pallone, Fabrizio, Parente, Raffaella, Pulitanò, Rossella, Pumpo, Riegler, Gabriele, Antonio, Rispo, Flavio Romolo, Rispoli, Francesco, Tedone, Flavio, Valiante, Giovanni, Viviani, All these authors performed clinical evaluation, Paolo Usai S. a. t. t. a., as well as final supervision of the, Manuscript, and The Study Group for Non-Celiac Gluten, Sensitivity
Subjects: Male, Abdominal pain, Constipation, Gastrointestinal Diseases, Non-celiac gluten sensitivity, FODMAP, prospective survey, Intestinal mucosa, Anti-gliadin antibodies, Celiac disease, Clinical picture, Duodenal biopsy, Prospective survey, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Celiac Disease, Child, Child, Preschool, Diet, Gluten-Free, Female, Food Hypersensitivity, Glutens, HLA-DQ Antigens, Humans, Intestinal Mucosa, Italy, Middle Aged, Prevalence, Prospective Studies, Sex Factors, Surveys and Questionnaires, Young Adult, Medicine (all), Diagnosis, 80 and over, Irritable bowel syndrome, Medicine(all), biology, General Medicine, Multicenter study, Gluten-free diet, medicine.symptom, medicine.medical_specialty, CELIAC DISEASE, celiac disease, gluten, non celiac gluten sensitivity, digestive system, NO, Bloating, Internal medicine, medicine, Preschool, business.industry, nutritional and metabolic diseases, medicine.disease, digestive system diseases, Diet, Food intolerance, Immunology, biology.protein, Commentary, Gluten-Free, Gluten free, business, Gluten
Abstract: none 6 no Background: Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. Methods: From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. Results: In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial lymphocytes (31%). The ratio between suspected NCGS and new CD diagnoses, assessed in 28 of the participating centers, was 1.15 to 1. Conclusions: This prospective survey shows that NCGS has a strong correlation with female gender and adult age. Based on our results, the prevalence of NCGS seems to be only slightly higher than that of celiac disease. none Volta U;Bardella MT;Calabrò A;Troncone R;Corazza GR;Study Group for Non-Celiac Gluten Sensitivity Volta U;Bardella MT;Calabrò A;Troncone R;Corazza GR;Study Group for Non-Celiac Gluten Sensitivity
Published: 2014

2. Atopy modifies the association between inhaled corticosteroid use and lung function decline in patients with asthma

Author: Isabelle Pin, Isa Cerveri, Lucia Cazzoletti, Andrei Malinovschi, Josep M. Antó, Simone Accordini, Deborah Jarvis, David Gislason, Ane Johannessen, Bénédicte Leynaert, Pierpaolo Marchetti, Diogenes S. Ferreira, Nicole Probst-Hensch, Alessandro Marcon, Christer Janson, Rain Jögi, Judith Garcia-Aymerich, Angelo Corsico, Joachim Heinrich, Joost Weyler, Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 2610, 4350 97/0035-01, 99/0034-01, 99/0034-02 97/0035, 97/0035-02, 99/0034-04, 99/0034-06, 99/0034-07, 99/350 90MR/10, 91AF/6 SEPAR R01 HL62633-01 018996 911631 Russell Sage Foundation, RSF ResMed Foundation AstraZeneca GlaxoSmithKline, GSK Novartis U.S. Public Health Service, USPHS: R01 HL62633-01 Chiesi Farmaceutici, Chiesi Faculty of Arts and Sciences, Harvard University, FAS Boehringer Ingelheim VÃ¥rdalstiftelsen Freiwillige Akademische Gesellschaft, FAG Commercial Aircraft of China, COMAC Wellcome Trust, WT: WT 084703MA Horizon 2020 Framework Programme, H2020: 633212 Growing Spine Foundation, GSF Gobierno del Principado de Asturias Blond McIndoe Research Foundation, BMRF Asthma and Allergy Foundation of America, AAFA Ministerio de Sanidad, Consumo y Bienestar Social, MISAN Union Chimique Belge, UCB Medical Research Council, MRC: 92091, G0901214 National Institute for Health Research, NIHR British Lung Foundation, BLF European Commission, EC: EU-PEAL PL01237 National Health and Medical Research Council, NHMRC: G.0402.00 Asthma Foundation of Victoria Deutsche Forschungsgemeinschaft, DFG: FR1526/1-1, HE 3294/10-1, MA 711/4-1, MA 711/6-1, NO 262/7-1 Agence Nationale de la Recherche, ANR Schweizerischer Nationalfonds zur FÃ¶rderung der Wissenschaftlichen Forschung, SNSF: 3100-059302, 3200-042532, 3200-052720, 3247-065896, 3247BO-104283, 3247BO-104284, 3247BO-104288, 33CSCO-108796, 33CSCO-134276/1, 4026-028099, 4026-28099 Eesti Teadusfondi, ETF: 1088 ForskningsrÃ¥det fÃ¶r Arbetsliv och Socialvetenskap, FAS Eesti Teadusagentuur: 562 Bundesamt für Gesundheit, BAG Belgian Federal Science Policy Office, BELSPO Generalitat de Catalunya Consell CatalÃ de Recerca i InnovaciÃ³: 1999SGR 00241 Haridus- ja Teadusministeerium: SF0180060s09 HjÃ¤rt-Lungfonden Consiglio Nazionale delle Ricerche, CNR Instituto de Salud Carlos III, ISCIII: C03/011, C03/09 HÃ¡skÃ³li Ãslands, HI Norges ForskningsrÃ¥d: 101422/310, 214123 Medicinska ForskningsrÃ¥det, MFR Cancéropôle Ile de France Russian Science Foundation, RSF: 381/05.93 Ministeriet Sundhed Forebyggelse SUVA Sociedad Española de Neumología y Cirugía Torácica, SEPAR: FIS 09/01511, FIS PS09/00716, FIS PS09/02185, FIS PS09/03190, SEPAR 1001/2010 Horizon 2020 Universiteit Antwerpen ComitÃ© des Maladies Respiratoires de l'IsÃ¨re ComissiÃ³ Interdepartamental de Recerca i InnovaciÃ³ TecnolÃ²gica, CIRIT: 1997 SGR 00079, 1999 SGR 00214 Servicio Murciano de Salud Regione del Veneto Regione Piemonte Astma- och AllergifÃ¶rbundet Centre Hospitalier Universitaire de Bordeaux, CHU de Bordeaux Office FÃ©dÃ©ral de l'Education et de la Science, OFES Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie, BMBWF Helmholtz Zentrum MÃ¼nchen Lungenliga Schweiz Ministerio de Medio Ambiente y Medio Rural y Marino, MARM: G03/176 Ministère des Solidarités et de la Santé INCLIVA Instituto de Investigación Sanitaria: 91/0016-060-05/E, 92/0319, 93/0393, PS09/00716, PS09/01511, PS09/02185, PS09/02457, PS09/03190 Fundació Autònoma Solidària, FAS Servicio Andaluz de Salud, SAS, The ALEC study is funded by the European Union's Horizon 2020 Research and Innovation programme under grant agreement number 633212. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. National funders who supported data collection in the original studies are listed in Appendix E4 in this article's Online Repository at www.jaci-inpractice.org. The funders had no role in the writing of the manuscript or the decision to submit it for publication.Conflicts of interest: D. S. Ferreira reports grants from the Asthma Foundation of Victoria, Allen and Hanburys, National Health and Medical Research Council. I. Pin reports travel grants and honoraria from Novartis, Zambon, and AstraZeneca, and nonfinancial support from AGIR?dom. R. J?gi reports grants from Estonian Research Council Personal Research (grant no. 562), and consultancy, lecture, and travel fees from GlaxoSmithKline, Boehringer, and Novartis. The rest of the authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work.Financial support for ECRHS I: The coordination of this work was supported by the European Commission, and the authors and participants are grateful to the late C. Baya and M. Hallen for their help during the study and K. Vuylsteek and the members of the COMAC for their support. The following grants helped to fund the local studies: Australia: Asthma Foundation of Victoria, Allen and Hanbury's, Belgium: Belgian Science Policy Office, National Fund for Scientific Research, Estonia: Estonian Science Foundation (grant no. 1088), France: Minist?re de la Sant?, Glaxo France, Institut Pneumologique d'Aquitaine, Contrat de Plan Etat-R?gion Languedoc-Rousillon, Caisse nationale de l'assurance maladie des travailleurs salari?s, Comit? national contre les maladies respiratoires et la tuberculose (90MR/10, 91AF/6), Ministre delegu? de la sant?, R?seau national de sant? publique, France, Germany: Helmholtz Zentrum Munich and Bundesminister f?r Forschung und Technologie, Italy: Ministero dell'Universit? e della Ricerca Scientifica e Tecnologica, Consiglio Nazionale delle Ricerche, Regione Veneto (grant RSF no. 381/05.93), Norway: Norwegian Research Council project no. 101422/310, Portugal: Glaxo Farmac?utica Lda, Sandoz Portugesa, Spain: Fondo de Investigaci?n Sanitaria (nos. 91/0016-060-05/E, 92/0319, and 93/0393), Hospital General de Albacete, Hospital General Juan Ram?n Jim?nez, Direcci?n Regional de Salud P?blica (Consejer?a de Sanidad del Principado de Asturias), Consell Interdepartamental de Recerca i Innovaci? Tecnol?gica (1997 SGR 00079), and Servicio Andaluz de Salud, Sweden: The Swedish Medical Research Council, the Swedish Heart-Lung Foundation, the Swedish Association against Asthma and Allergy, Switzerland: Swiss National Science Foundation (grant no. 4026-28099), and UK: National Asthma Campaign, British Lung Foundation, Department of Health, South Thames Regional Health Authority.Financial support for ECRHS II: Australia: National Health and Medical Research Council, Belgium: Antwerp: Fund for Scientific Research (grant code G.0402.00), University of Antwerp, and Flemish Health Ministry, Estonia: Tartu: Estonian Science Foundation (grant no. 4350), France: (All) Programme Hospitalier de Recherche Clinique?Direction de la Recherche Clinique de Grenoble 2000 number 2610, Ministry of Health, Minist?re de l'Emploi et de la Solidarit?, Direction G?nerale de la Sant?, Centre Hospitalier Universitaire de Grenoble, Bordeaux: Institut Pneumologique d'Aquitaine, Grenoble: Comite des Maladies Respiratoires de l'Isere, Montpellier: Aventis (France), Direction Regionale des Affaires Sanitaires et Sociales Languedoc-Roussillon, Paris: Union Chimique Belge-Pharma (France), Aventis (France), Glaxo France, Germany: Erfurt: GSF?National Research Centre for Environment and Health, Deutsche Forschungsgemeinschaft (grant code FR1526/1-1), Hamburg: GSF?National Research Centre for Environment and Health, Deutsche Forschungsgemeinschaft (grant code MA 711/4-1), Iceland: Reykjavik: Icelandic Research Council and Icelandic University Hospital Fund, Italy: Pavia: GlaxoSmithKline Italy, Italian Ministry of University and Scientific and Technological Research (MURST), and Local University Funding for Research 1998 and 1999, Turin: Azienda Sanitaria Locale 4 Regione Piemonte (Italy), Azienda Ospedaliera Centro Traumatologico Ospedaliero/Centro Traumatologico Ortopedico?Istituto Clinico Ortopedico Regina Maria Adelaide Regione Piemonte, Verona: Ministero dell'Universit? e della Ricerca Scientifica (MURST), Glaxo Wellcome s.p.a., Norway: Bergen: Norwegian Research Council, Norwegian Asthma and Allergy Association, Glaxo Wellcome AS, and Norway Research Fund, Spain: Fondo de Investigacion Santarias (grant codes 97/0035-01, 99/0034-01, and 99/0034-02), Hospital Universitario de Albacete, Consejeria de Sanidad, Barcelona: Sociedad Espanola de Neumolog?a y Cirug?a Toracica, Public Health Service (grant code R01 HL62633-01), Fondo de Investigaciones Santarias (grant codes 97/0035-01, 99/0034-01, and 99/0034-02), Consell Interdepartamentalde Recerca i Innovaci? Tecnol?gica (grant code 1999SGR 00241), Instituto de Salud Carlos III, Red de Centros de Epidemiolog?a y Salud P?blica, C03/09, Red de Bases moleculares y fisiol?gicas de las Enfermedades Respiratorias, C03/011 and Red de Grupos Infancia y Medio Ambiente G03/176, Huelva: Fondo de Investigaciones Santarias (grant codes 97/0035-01, 99/0034-01, and 99/0034-02), Galdakao: Basque Health Department, Oviedo: Fondo de Investigaciones Sanitaria (97/0035-02, 97/0035, 99/0034-01, 99/0034-02, 99/0034-04, 99/0034-06, 99/350, and 99/0034-07), European Commission (EU-PEAL PL01237), Generalitat de Catalunya (CIRIT 1999 SGR 00214), Hospital Universitario de Albacete, Sociedad Espa?ola de Neumolog?a y Cirug?a Tor?cica (SEPAR R01 HL62633-01), Red de Centros de Epidemiolog?a y Salud P?blica (C03/09), Red de Bases moleculares y fisiol?gicas de las Enfermedades Respiratorias (C03/011), and Red de Grupos Infancia y Medio Ambiente (G03/176, 97/0035-01, 99/0034-01, and 99/0034-02), Sweden: G?teborg, Umea, AND Uppsala: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences and Allergy Research, Swedish Asthma and Allergy Foundation, Swedish Cancer and Allergy Foundation, and Swedish Council for Working Life and Social Research (FAS), Switzerland: Basel: Swiss National Science Foundation, Swiss Federal Office for Education and Science, and Swiss National Accident Insurance Fund, UK: Ipswich and Norwich: Asthma UK (formerly known as National Asthma Campaign).Financial support for ECRHS III: Australia: National Health and Medical Research Council, Belgium: Antwerp: South and Antwerp City: Research Foundation Flanders (grant code G.0.410.08.N.10), Estonia: Tartu: the Estonian Ministry of Education (SF0180060s09), France: (All): Minist?re de la Sant?, Programme Hospitalier de Recherche Clinique national 2010, Bordeaux: INSERM U897 Universit? Bordeaux segalen, Grenoble: Comite Scientifique AGIRadom 2011, and Paris: Agence Nationale de la Sant?, R?gion Ile de France, domaine d'int?r?t majeur, Germany: Erfurt: German Research Foundation (HE 3294/10-1), Hamburg: German Research Foundation (MA 711/6-1, NO 262/7-1), Iceland: Reykjavik: The Landspitali University Hospital Research Fund, University of Iceland Research Fund, ResMed Foundation, California, USA, Orkuveita Reykjavikur (Geothermal plant), and Vegager?in (The Icelandic Road Administration, Italy: All Italian centers were funded by the Italian Ministry of Health, Chiesi Farmaceutici SpA, in addition, Verona was funded by Cariverona Foundation and Education Ministry (Ministero dell'Istruzione, dell'Universit? e della Ricerca), Norway: Norwegian Research Council (grant no. 214123), Western Norway Regional Health Authorities (grant no. 911631), and Blond McIndoe Research Foundation, Spain: Fondo de Investigaci?n Sanitaria (PS09/02457, PS09/00716, PS09/01511, PS09/02185, PS09/03190), Servicio Andaluz de Salud, Sociedad Espa?ola de Neumolog?a y Cirurg?a Tor?cica (SEPAR 1001/2010), Fondo de Investigaci?n Sanitaria (PS09/02457), Barcelona: Fondo de Investigaci?n Sanitaria (FIS PS09/00716), Galdakao: Fondo de Investigaci?n Sanitaria (FIS 09/01511), Huelva: Fondo de Investigaci?n Sanitaria (FIS PS09/02185) and Servicio Andaluz de Salud, Oviedo: Fondo de Investigaci?n Sanitaria (FIS PS09/03190), Sweden: All centers were funded by The Swedish Heart and Lung Foundation, The Swedish Asthma and Allergy Association, The Swedish Association against Lung and Heart Disease, Swedish Research Council for health, working life and welfare, G?teborg: also received further funding from the Swedish Council for Working Life and Social Research. Umea: also received funding from Vasterbotten Country Council ALF grant, Switzerland: The Swiss National Science Foundation (grants nos. 33CSCO-134276/1, 33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, and 4026-028099), The Federal Office for Forest, Environment and Landscape, The Federal Office of Public Health, The Federal Office of Roads and Transport, the canton's government of Aargan, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Z?rich, the Swiss Lung League, the canton's Lung League of Basel-Stadt/Basel, Landschaft, Geneva, Ticino, Valais, and Zurich, SUVA, Freiwillige Akademische Gesellschaft, UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics, European Commission 018996 (GABRIEL), Wellcome Trust WT 084703MA, and UK: Medical Research Council (grant no.92091), support also provided by the National Institute for Health Research through the Primary Care Research Network., Financial support for ECRHS III: Australia: National Health and Medical Research Council, Estonia: Tartu: the Estonian Ministry of Education ( SF0180060s09 ), France: (All): Ministère de la Santé, Programme Hospitalier de Recherche Clinique national 2010, Bordeaux: INSERM U897 Université Bordeaux segalen, and Paris: Agence Nationale de la Santé, Région Ile de France, domaine d'intérêt majeur, Germany: Erfurt: German Research Foundation ( HE 3294/10-1 ), Hamburg: German Research Foundation ( MA 711/6-1 , NO 262/7-1 ), Iceland: Reykjavik: The Landspitali University Hospital Research Fund, University of Iceland Research Fund, ResMed Foundation , California, USA , Orkuveita Reykjavikur (Geothermal plant), and Vegagerðin (The Icelandic Road Administration, Italy: All Italian centers were funded by the Italian Ministry of Health , Chiesi Farmaceutici SpA, in addition, Verona was funded by Cariverona Foundation and Education Ministry (Ministero dell'Istruzione, dell'Università e della Ricerca), Norway: Norwegian Research Council (grant no. 214123 ), Western Norway Regional Health Authorities (grant no. 911631 ), and Blond McIndoe Research Foundation, Spain: Fondo de Investigación Sanitaria (PS09/02457, PS09/00716, PS09/01511, PS09/02185, PS09/03190), Servicio Andaluz de Salud, Sociedad Española de Neumología y Cirurgía Torácica ( SEPAR 1001/2010), Fondo de Investigación Sanitaria (PS09/02457), Barcelona: Fondo de Investigación Sanitaria (FIS PS09/00716), Galdakao: Fondo de Investigación Sanitaria (FIS 09/01511), Huelva: Fondo de Investigación Sanitaria (FIS PS09/02185) and Servicio Andaluz de Salud, Oviedo: Fondo de Investigación Sanitaria (FIS PS09/03190), Sweden: All centers were funded by The Swedish Heart and Lung Foundation, The Swedish Asthma and Allergy Association , The Swedish Association against Lung and Heart Disease , Swedish Research Council for health, working life and welfare, Göteborg: also received further funding from the Swedish Council for Working Life and Social Research . Umea: also received funding from Vasterbotten Country Council ALF grant, Switzerland: The Swiss National Science Foundation (grants nos. 33CSCO-134276/1 , 33CSCO-108796 , 3247BO-104283 , 3247BO-104288 , 3247BO-104284 , 3247-065896 , 3100-059302 , 3200-052720 , 3200-042532 , and 4026-028099 ), The Federal Office for Forest, Environment and Landscape, The Federal Office of Public Health, The Federal Office of Roads and Transport, the canton's government of Aargan, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Zürich, the Swiss Lung League , the canton's Lung League of Basel-Stadt/Basel, Landschaft, Geneva, Ticino, Valais, and Zurich, SUVA, Freiwillige Akademische Gesellschaft , UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics , European Commission 018996 (GABRIEL), Wellcome Trust WT 084703MA, and UK: Medical Research Council (grant no. 92091 ), support also provided by the National Institute for Health Research through the Primary Care Research Network ., Conflicts of interest: D. S. Ferreira reports grants from the Asthma Foundation of Victoria , Allen and Hanburys , National Health and Medical Research Council . I. Pin reports travel grants and honoraria from Novartis , Zambon , and AstraZeneca , and nonfinancial support from AGIRàdom. R. Jõgi reports grants from Estonian Research Council Personal Research (grant no. 562 ), and consultancy, lecture, and travel fees from GlaxoSmithKline, Boehringer, and Novartis. The rest of the authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work., Financial support for ECRHS II: Australia: National Health and Medical Research Council, Belgium: Antwerp: Fund for Scientific Research (grant code G.0402.00 ), University of Antwerp , and Flemish Health Ministry, Estonia: Tartu: Estonian Science Foundation (grant no. 4350 ), France: (All) Programme Hospitalier de Recherche Clinique—Direction de la Recherche Clinique de Grenoble 2000 number 2610, Ministry of Health , Ministère de l’Emploi et de la Solidarité, Direction Génerale de la Santé, Centre Hospitalier Universitaire de Grenoble, Bordeaux: Institut Pneumologique d’Aquitaine, Grenoble: Comite des Maladies Respiratoires de l’Isere, Germany: Erfurt: GSF— National Research Centre for Environment and Health , Deutsche Forschungsgemeinschaft (grant code FR1526/1-1 ), Hamburg: GSF— National Research Centre for Environment and Health , Deutsche Forschungsgemeinschaft (grant code MA 711/4-1 ), Turin: Azienda Sanitaria Locale 4 Regione Piemonte (Italy), Azienda Ospedaliera Centro Traumatologico Ospedaliero/Centro Traumatologico Ortopedico—Istituto Clinico Ortopedico Regina Maria Adelaide Regione Piemonte, Verona: Ministero dell’Università e della Ricerca Scientifica (MURST), Glaxo Wellcome s.p.a., Norway: Bergen: Norwegian Research Council , Norwegian Asthma and Allergy Association , Glaxo Wellcome AS , and Norway Research Fund, Spain: Fondo de Investigacion Santarias (grant codes 97/0035-01 , 99/0034-01 , and 99/0034-02 ), Hospital Universitario de Albacete, Consejeria de Sanidad, Barcelona: Sociedad Espanola de Neumología y Cirugía Toracica, Public Health Service (grant code R01 HL62633-01 ), Fondo de Investigaciones Santarias (grant codes 97/0035-01 , 99/0034-01 , and 99/0034-02 ), Consell Interdepartamentalde Recerca i Innovació Tecnológica (grant code 1999SGR 00241 ), Instituto de Salud Carlos III, Red de Centros de Epidemiología y Salud Pública, C03/09, Red de Bases moleculares y fisiológicas de las Enfermedades Respiratorias, C03/011 and Red de Grupos Infancia y Medio Ambiente G03/176, Huelva: Fondo de Investigaciones Santarias (grant codes 97/0035-01 , 99/0034-01 , and 99/0034-02 ), Oviedo: Fondo de Investigaciones Sanitaria ( 97/0035-02 , 97/0035 , 99/0034-01 , 99/0034-02 , 99/0034-04 , 99/0034-06 , 99/350 , and 99/0034-07 ), European Commission ( EU-PEAL PL01237 ), Generalitat de Catalunya ( CIRIT 1999 SGR 00214), Hospital Universitario de Albacete, Sociedad Española de Neumología y Cirugía Torácica ( SEPAR R01 HL62633-01 ), Red de Centros de Epidemiología y Salud Pública (C03/09), Red de Bases moleculares y fisiológicas de las Enfermedades Respiratorias (C03/011), and Red de Grupos Infancia y Medio Ambiente (G03/176, Sweden: Göteborg, Umea, AND Uppsala: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences and Allergy Research , Swedish Asthma and Allergy Foundation , Swedish Cancer and Allergy Foundation , and Swedish Council for Working Life and Social Research ( FAS ), Switzerland: Basel: Swiss National Science Foundation , Swiss Federal Office for Education and Science , and Swiss National Accident Insurance Fund, UK: Ipswich and Norwich: Asthma UK (formerly known as National Asthma Campaign)., Financial support for ECRHS I: The coordination of this work was supported by the European Commission , and the authors and participants are grateful to the late C. Baya and M. Hallen for their help during the study and K. Vuylsteek and the members of the COMAC for their support. The following grants helped to fund the local studies: Australia: Asthma Foundation of Victoria , Allen and Hanbury's, Belgium: Belgian Science Policy Office , National Fund for Scientific Research, Estonia: Estonian Science Foundation (grant no. 1088 ), France: Ministère de la Santé, Glaxo France , Institut Pneumologique d'Aquitaine , Contrat de Plan Etat-Région Languedoc-Rousillon , Caisse nationale de l'assurance maladie des travailleurs salariés, Comité national contre les maladies respiratoires et la tuberculose (90MR/10, 91AF/6), Ministre delegué de la santé, Réseau national de santé publique, France, Germany: Helmholtz Zentrum Munich and Bundesminister für Forschung und Technologie, Italy: Ministero dell'Università e della Ricerca Scientifica e Tecnologica, Consiglio Nazionale delle Ricerche, Regione Veneto (grant RSF no. 381/05.93 ), Portugal: Glaxo Farmacêutica Lda, Sandoz Portugesa, Spain: Fondo de Investigación Sanitaria (nos. 91/0016-060-05/E , 92/0319 , and 93/0393 ), Hospital General de Albacete, Hospital General Juan Ramón Jiménez, Dirección Regional de Salud Pública (Consejería de Sanidad del Principado de Asturias), Consell Interdepartamental de Recerca i Innovació Tecnològica (1997 SGR 00079), and Servicio Andaluz de Salud, Sweden: The Swedish Medical Research Council , the Swedish Heart-Lung Foundation , the Swedish Association against Asthma and Allergy, Switzerland: Swiss National Science Foundation (grant no. 4026-28099 ), and UK: National Asthma Campaign , British Lung Foundation , Department of Health , South Thames Regional Health Authority ., The ALEC study is funded by the European Union’s Horizon 2020 Research and Innovation programme under grant agreement number 633212. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. National funders who supported data collection in the original studies are listed in Appendix E4 in this article's Online Repository at www.jaci-inpractice.org . The funders had no role in the writing of the manuscript or the decision to submit it for publication., Commission of the European Communities, Medical Research Council (MRC), and Ageing Lungs European Cohorts ALEC
Subjects: Allergy, Epidemiology, Respiratory Medicine and Allergy, Cohort Studies, Atopy, Allergic sensitization, 0302 clinical medicine, Adrenal Cortex Hormones, Immunology and Allergy, Medicine, 030212 general & internal medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Lung, Sensitization, Lungmedicin och allergi, biology, Inhaled corticosteroids, Lung function decline, Pyroglyphidae, Precision medicine, 3. Good health, PROPENSITY SCORE, medicine.anatomical_structure, IgE, Cohort study, Life Sciences & Biomedicine, Response to corticosteroids, Asthma, Adult, medicine.medical_specialty, Immunology, Allergic inflammation, 03 medical and health sciences, FEV1/FVC ratio, Internal medicine, Administration, Inhalation, Animals, Humans, House dust mite, Science & Technology, business.industry, Ageing Lungs in European Cohorts (ALEC) study, medicine.disease, biology.organism_classification, 030228 respiratory system, Cats, Human medicine, business
Abstract: BACKGROUND: Inhaled corticosteroids (ICSs) are the mainstay of asthma treatment, but response to medication is variable. Patients with allergic inflammation generally show a better short-term response to ICSs; however, studies on predictors of long-term response are few. OBJECTIVE: To assess whether allergic sensitization can modify the association between ICS use and lung function decline over 20 years in adult asthma. METHODS: We used data from the 3 clinical examinations of the European Community Respiratory Health Survey. We measured ICS use (no use, and use for 8 years) and FEV1 decline among subjects with asthma over the 2 periods between consecutive examinations. We conducted a cohort study combining data of the 2 periods (906 observations from 745 subjects) to assess whether the association between ICS use and FEV1 decline was modified by allergic sensitization (IgE > 0.35 kU/L for any of house-dust mite, timothy grass, cat, or Cladosporium). RESULTS: FEV1 decline was similar for non-ICS users, as well as ICS users for less than 1.3 years, with and without allergic sensitization. However, among subjects on ICSs for a longer period, sensitization was associated with an attenuated decline (P-interaction = .006): in the group treated for more than 8 years, FEV1 decline was on average 27 mL/y (95% CIBonferroni-adjusted, 11-42) lower for subjects with sensitization compared with nonsensitized subjects. CONCLUSIONS: Our study suggests that biomarkers of atopy can predict a more favorable long-term response to ICSs. Randomized controlled studies are needed to confirm these findings. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.
Published: 2020
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3. Atezolizumab with or without bevacizumab and platinum-pemetrexed in patients with stage IIIB/IV non-squamous non-small cell lung cancer with EGFR mutation, ALK rearrangement or ROS1 fusion progressing after targeted therapies: A multicentre phase II open-label non-randomised study GFPC 06-2018

Author: Olivier Bylicki, Pascale Tomasini, Gervais Radj, Florian Guisier, Isabelle Monnet, Charles Ricordel, Laurence Bigay-Game, Margaux Geier, Christos Chouaid, Catherine Daniel, Aurelie Swalduz, Anne-Claire Toffart, Helene Doubre, Jean-Michel Peloni, Diane Moreau, Fabien Subtil, Jean-Michel Grellard, Marie Castera, Benedicte Clarisse, Pedro-Henrique Martins-Lavinas, Chantal Decroisette, Laurent Greillier, Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire d'Informatique, du Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHI Créteil, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Curie [Paris], Centre Léon Bérard [Lyon], CHU Grenoble, Hôpital Foch [Suresnes], Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), and This trial was granted by financial support and drug supply (atezolizumab, bevacizumab) from Roche S.A.S which was not involved in the design and conduct of the study, nor in the collection, management, analysis and interpretation of the data. It was not involved in the writing of the manuscript.
Subjects: Cancer Research, Oncology, Non-small cell lung cancer, Resistance, [SDV.CAN]Life Sciences [q-bio]/Cancer, Immunotherapy, EGFR-mutation
Abstract: International audience; Background: Previous reports showed limited efficacy of immune checkpoint inhibitors as single-agent treatment for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation or ALK/ROS1 fusion. We aimed at evaluating the efficacy and safety of immune checkpoint inhibitor combined with chemotherapy and bevacizumab (when eligible) in this patient subgroup.Methods: We conducted a French national open-label multicentre non-randomised non-comparative phase II study in patients with stage IIIB/IV NSCLC, oncogenic addiction (EGFR mutation or ALK/ROS1 fusion), with disease progression after tyrosine kinase inhibitor and no prior chemotherapy. Patients received platinum, pemetrexed, atezolizumab, bevacizumab (PPAB cohort) or, if not eligible to bevacizumab, platinum-pemetrexed-atezolizumab (PPA cohort). The primary end-point was the objective response rate (RECIST v1.1) after 12 weeks, evaluated by blind independent central review.Results: 71 patients were included in PPAB cohort and 78 in PPA cohort (mean age, 60.4/66.1 years; women 69.0%/51.3%; EGFR mutation, 87.3%/89.7%; ALK rearrangement, 12.7%/5.1%; ROS1 fusion, 0%/6.4%, respectively). After 12 weeks, objective response rate was 58.2% (90% confidence interval [CI], 47.4-68.4) in PPAB cohort and 46.5% (90% CI, 36.3-56.9) in PPA cohort. Median progression-free survival and overall survival were 7.3 (95% CI 6.9-9.0) months and 17.2 (95% CI 13.7-NA) months in PPAB cohort and 7.2 (95% CI 5.7-9.2) months and 16.8 (95% CI 13.5-NA) months in PPA cohort, respectively. Grade 3-4 adverse events occurred in 69.1% of patients in PPAB cohort and 51.4% in PPA cohort; Grade 3-4 atezolizumab-related adverse events occurred in 27.9% and 15.3%, respectively.Conclusion: Combination approach with atezolizumab with or without bevacizumab and platinum-pemetrexed achieved promising activity in metastatic EGFR-mutated or ALK/ROS1-rearranged NSCLC after tyrosine kinase inhibitor failure, with acceptable safety profile.
Published: 2023
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4. Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

Author: Amanda J. Cross, Petra H.M. Peeters, Pietro Ferrari, Françoise Clavel-Chapelon, Salvatore Panico, Augustin Scalbert, Anja Olsen, José María Huerta, Paolo Vineis, Gianluca Severi, Eva Ardanaz, H. Bas Bueno-de-Mesquita, Ruth C. Travis, Bénédicte Elena-Herrmann, Nicholas J. Wareham, Pagona Lagiou, Talita Duarte-Salles, Christina Bamia, Anne Tjønneland, Rudolf Kaaks, Bodil Ohlsson, Magdalena Stepien, Antonio Agudo, Krasimira Aleksandrova, Heiner Boeing, Isabelle Romieu, Kay-Tee Khaw, Veronika Fedirko, Domenico Palli, Julie A. Schmidt, Anne Fages, Rosario Tumino, Valeria Pala, Anna Floegel, Dimitrios Trichopoulos, Miren Dorronsoro, Marc J. Gunter, Klas Sjöberg, Clément Pontoizeau, Marie-Christine Boutron-Ruault, Elisabete Weiderpass, Tilman Kühn, Elio Riboli, Mazda Jenab, Antonia Trichopoulou, Esther Molina-Montes, Fages, Anne, Duarte Salles, Talita, Stepien, Magdalena, Ferrari, Pietro, Fedirko, Veronika, Pontoizeau, Clément, Trichopoulou, Antonia, Aleksandrova, Krasimira, Tjønneland, Anne, Olsen, Anja, Clavel Chapelon, Françoise, Boutron Ruault, Marie Christine, Severi, Gianluca, Kaaks, Rudolf, Kuhn, Tilman, Floegel, Anna, Boeing, Heiner, Lagiou, Pagona, Bamia, Christina, Trichopoulos, Dimitrio, Palli, Domenico, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Vineis, Paolo, Bueno de Mesquita, H. Ba, Peeters, Petra H, Weiderpass, Elisabete, Agudo, Antonio, Molina Montes, Esther, Huerta, José María, Ardanaz, Eva, Dorronsoro, Miren, Sjöberg, Kla, Ohlsson, Bodil, Khaw, Kay Tee, Wareham, Nick, Travis, Ruth C, Schmidt, Julie A, Cross, Amanda, Gunter, Marc, Riboli, Elio, Scalbert, Augustin, Romieu, Isabelle, Elena Herrmann, Benedicte, Jenab, Mazda, ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), ISA - Centre de RMN à très hauts champs, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), parent, International Agency for Cancer Research (IACR), Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Department of Epidemiology, Deutsches Institut für Ernahrungsforschung Potsdam-Rehbrücke (DIFE), Institute of Cancer Epidemiology, Danish Cancer Society, Department of Food Science [Copenhagen] (UCPH FOOD), Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Gustave Roussy (IGR), Human Genetics Foundation (HuGeF), Università degli studi di Torino (UNITO), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Thermo Fisher Scientific, Thermo Fisher Scientific Inc., German Institute of Human Nutrition Potsdam-Rehbruecke, German Institute of Human Nutrition, Harvard School of Public Health, WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Nutritional Epidemiology Unit, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-IRCCS Foundation, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Julius Center for Health Sciences and Primary Care, VU University Medical Center [Amsterdam], Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Community Medicine, University of Tromsø (UiT), Department of Research, Cancer Registry of Norway-Samfundet Folkhälsan, Helsinki, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet [Stockholm], Institut Català d'Oncologia, Spain Institute of Oncology, Andalusian School of Public Health [Granada], Consortium for Biomedical Research in Epidemiology and Public Health, CIBER de Epidemiología y Salud Pública (CIBERESP), Danish Cancer Society Research Center, Murcia Regional Health Council, Sección de Epidemiología de Enfermedades No Transmisibles, Navarre Public Health Institute, Epidemiology and Health Information, Public Health Department of Gipuzkoa, Volvo, VOLVO-VOLVO, Skane University Hospital [Lund], University of Cambridge School of Clinical Medicine, MRC epidemiology Unit, Addenbrooke's Hospital, Cancer Epidemiology Unit, University of Oxford [Oxford], Laboratoire d'informatique Fondamentale de Marseille (LIF), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), School of Public Health [London, UK] (Faculty of Medicine), Imperial College London, Department of Chemistry, University of Cambridge [UK] (CAM), Nutrition and Metabolism Section, Biomarkers Group, Nutrition and Metabolism Section, This work was supported by the French National Cancer Institute (L'Institut National du Cancer, INCA, grant number 2009-139, PI: M. Jenab). AF received financial support (BDI fellowship) from the Centre National de la Recherche Scientifique (CNRS) and Bruker Biospin. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, and Institut National de la Sante et de la Recherche Medicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands), European Research Council (ERC, grant number ERC-2009-AdG 232997) and Nordforsk, and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skane and Vasterbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). The funders had no role in the study design, data collection, analysis, and interpretation presented in this article. They were neither involved in the writing of the manuscript, nor in the decision to submit it for publication., Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Centre Européen de Résonance Magnétique Nucléaire à Très Hauts Champs (CERMNTHC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 'Civile M. P. Arezzo' Hospital, Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), [Fages,A, Pontoizeau,C, Elena-Herrmann,B] Institut des Sciences Analytiques, Centre de RMN à très hauts champs, CNRS/ENS Lyon/UCB Lyon-1, Université de Lyon, Villeurbanne, France. [Duarte-Salles,T, Stepien,M, Ferrari,P, Scalbert,A, Romieu,I, Jenab,M] International Agency for Research on Cancer (IARC-WHO), Lyon, France. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, USA. [Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Aleksandrova,K, Floegel,A, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany. [Tjønneland,A, Olsen,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Clavel-Chapelon,F, Boutron-Ruault,M] INSERM, Centre for Research in Epidemiology and Population Health (CESP), nutrition, Hormones and Women’s Health Team, Villejuif, France. Université Paris Sud, Villejuif, France. Institut Gustave Roussy, Villejuif, France. [Severi,G, Vineis,P] Human Genetics Foundation (HuGeF), Torino, Italy. [Kaaks,R, Kuhn,T] Department of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Lagiou,P, Bamia,C] Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Goudi, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.P. Arezzo' Hospital, Ragusa, Italy. [Vineis,P, Peeters,PH] MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Bueno-de-Mesquita,HB, Cross,A, Gunter,M, RibolI,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Peeters,PH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland. [Agudo,A] Unit of Nutrition and Cancer, IDIBELL, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain. [Molina-Montes,E] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Molina-Montes,E, Huerta,JM, Ardanaz, E] CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Ardanaz,E] Navarre Public Health Institute, Pamplona, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia CIBERESP, Basque Regional Health Department, San Sebastian, Spain. [Sjöberg,K] Department of Clinical Sciences, Lund University, Malmö, Sweden. Department of Gastroenterology and Nutrition, Skåne University Hospital, Malmö, Sweden. [Ohlsson,B] Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Lund University, Malmö, Sweden. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Addenbrooke’s Hospital, Cambridge, UK. [Wareham,N] MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. [Travis,RC, Schmidt,JA] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., This work was supported by the French National Cancer Institute (L’Institut National du Cancer, Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). The funders had no role in the study design, data collection, analysis, and interpretation presented in this article. They were neither involved in the writing of the manuscript, nor in the decision to submit it for publication, Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Torino = University of Turin (UNITO), University of Naples Federico II = Università degli studi di Napoli Federico II, and University of Oxford
Subjects: Oncology, Male, Neoplasias Hepáticas, Cirrhosis, Magnetic Resonance Spectroscopy, Epidemiology, Hepatocellular carcinoma, Nuclear magnetic resonance, Cohort Studies, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, Hepatocellular [Medical Subject Headings], 0302 clinical medicine, Risk Factors, Prospective Studies, Prospective cohort study, CIRRHOSIS, Early Detection of Cancer, Medicine(all), 0303 health sciences, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver Neoplasms [Medical Subject Headings], Liver Neoplasms, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Metabolomics [Medical Subject Headings], Metabolómica, Estudios Prospectivos, General Medicine, Middle Aged, CANCER, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Liver Neoplasm, 030220 oncology & carcinogenesis, Female, Liver cancer, Case-Control Studie, Life Sciences & Biomedicine, Metabolomics, Carcinoma Hepatocelular, Research Article, Human, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], TISSUE METABOLOMICS, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], Metabolomic, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus [Medical Subject Headings], Càncer de fetge, 03 medical and health sciences, Medicine, General & Internal, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, IDENTIFY SERUM BIOMARKERS, Internal medicine, General & Internal Medicine, medicine, Humans, Obesity, Epidemiologia, 030304 developmental biology, FATTY LIVER-DISEASE, Aged, Hepatitis, Science & Technology, business.industry, Case-control study, METABONOMICS, Cancer, MASS-SPECTROMETRY, medicine.disease, NMR, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Prospective Studie, Case-Control Studies, DISCOVERY, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], Immunology, RISK-FACTORS, Cohort Studie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers. Methods: To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort. Results: A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis. Conclusion: Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer., This work was supported by the French National Cancer Institute (L’Institut National du Cancer; INCA; grant number 2009-139; PI: M. Jenab). AF received financial support (BDI fellowship) from the Centre National de la Recherche Scientifique (CNRS) and Bruker Biospin. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands); European Research Council (ERC; grant number ERC-2009-AdG 232997) and Nordforsk, and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK).
Published: 2015
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5. Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism

Author: Pretzsch, Charlotte, Floris, Dorothea, Schäfer, Tim, Bletsch, Anke, Gurr, Caroline, Lombardo, Michael, Chatham, Chris, Tillmann, Julian, Charman, Tony, Arenella, Martina, Jones, Emily, Ambrosino, Sara, Bourgeron, Thomas, Dumas, Guillaume, Cliquet, Freddy, Leblond, Claire, Loth, Eva, Oakley, Bethany, Buitelaar, Jan, Baron-Cohen, Simon, Beckmann, Christian, Persico, Antonio, Banaschewski, Tobias, Durston, Sarah, Freitag, Christine, Murphy, Declan, Ecker, Christine, King‘s College London, Universität Zürich [Zürich] = University of Zurich (UZH), Radboud University Medical Center [Nijmegen], Goethe-Universität Frankfurt am Main, Istituto Italiano di Tecnologia (IIT), F. Hoffmann-La Roche [Basel], University of London [London], Utrecht University [Utrecht], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Montréal (UdeM), University of Cambridge [UK] (CAM), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Universität Heidelberg [Heidelberg] = Heidelberg University, The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union’s Horizon-2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. (The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.) Any views expressed are those of the author(s) and not necessarily those of the funders (IHI-JU2). This work was further supported by the European Union Horizon-2020 programme CANDY (Grant Agreement No. 847818). CMF acknowledges support from the European Union and the German Research Association (DFG). DGM acknowledges support from the NIHR Maudsley Biomedical Research Centre., and European Project: 777394,H2020-JTI-IMI2-2016-10-two-stage,AIMS-2-TRIALS(2018)
Subjects: [SCCO.NEUR]Cognitive science/Neuroscience
Abstract: International audience; Individuals with autism spectrum disorder (henceforth referred to as autism) display significant variation in clinical outcome. For instance, across age, some individuals’ adaptive skills naturally improve or remain stable, while others’ decrease. To pave the way for ‘precision-medicine’ approaches, it is crucial to identify the cross-sectional and, given the developmental nature of autism, longitudinal neurobiological (including neuroanatomical and linked genetic) correlates of this variation. We conducted a longitudinal follow-up study of 333 individuals (161 autistic and 172 neurotypical individuals, aged 6–30 years), with two assessment time points separated by ~12–24 months. We collected behavioural (Vineland Adaptive Behaviour Scale-II, VABS-II) and neuroanatomical (structural magnetic resonance imaging) data. Autistic participants were grouped into clinically meaningful “Increasers”, “No-changers”, and “Decreasers” in adaptive behaviour (based on VABS-II scores). We compared each clinical subgroup’s neuroanatomy (surface area and cortical thickness at T1, ∆T (intra-individual change) and T2) to that of the neurotypicals. Next, we explored the neuroanatomical differences’ potential genomic associates using the Allen Human Brain Atlas. Clinical subgroups had distinct neuroanatomical profiles in surface area and cortical thickness at baseline, neuroanatomical development, and follow-up. These profiles were enriched for genes previously associated with autism and for genes previously linked to neurobiological pathways implicated in autism (e.g. excitation-inhibition systems). Our findings suggest that distinct clinical outcomes (i.e. intra-individual change in clinical profiles) linked to autism core symptoms are associated with atypical cross-sectional and longitudinal, i.e. developmental, neurobiological profiles. If validated, our findings may advance the development of interventions, e.g. targeting mechanisms linked to relatively poorer outcomes.
Published: 2023
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6. Excitatory/inhibitory imbalance in autism: the role of glutamate and GABA gene-sets in symptoms and cortical brain structure

Author: Hollestein, Viola, Poelmans, Geert, Forde, Natalie J, Beckmann, Christian F, Ecker, Christine, Mann, Caroline, Schäfer, Tim, Moessnang, Carolin, Baumeister, Sarah, Banaschewski, Tobias, Bourgeron, Thomas, Loth, Eva, Dell'Acqua, Flavio, Murphy, Declan GM, Puts, Nicolaas A, Tillmann, Julian, Charman, Tony, Jones, Emily JH, Mason, Luke, Ambrosino, Sara, Holt, Rosemary, Bölte, Sven, Buitelaar, Jan K, Naaijen, Jilly, Hollestein, Viola [0000-0002-6326-4172], Poelmans, Geert [0000-0001-7039-6985], Banaschewski, Tobias [0000-0003-4595-1144], Loth, Eva [0000-0001-9458-9167], Murphy, Declan GM [0000-0002-6664-7451], Puts, Nicolaas A [0000-0003-1024-1927], Charman, Tony [0000-0003-1993-6549], Bölte, Sven [0000-0002-4579-4970], Buitelaar, Jan K [0000-0001-8288-7757], Apollo - University of Cambridge Repository, Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Radboud University Medical Center [Nijmegen], Goethe-Universität Frankfurt am Main, King‘s College London, Universität Heidelberg [Heidelberg] = Heidelberg University, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Sackler Institute of Translational Neurodevelopment [London], F. Hoffmann-La Roche [Basel], University of London [London], Utrecht University [Utrecht], University of Cambridge [UK] (CAM), Karolinska Institutet [Stockholm], Curtin University [Perth], Planning and Transport Research Centre (PATREC), Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], This work has been supported by the EU-AIMS (European Autism Interventions) and AIMS-2-TRIALS programmes which receive support from Innovative Medicines Initiative Joint Undertaking Grant No. 115300 and 777394, the resources of which are composed of financial contributions from the European Union’s FP7 and Horizon2020 Programmes, and from the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies’ in-kind contributions, and AUTISM SPEAKS, Autistica and SFARI, by the Horizon2020 supported programme CANDY Grant No. 847818 and a Veni grant from the Netherlands organization for scientific research (NWO) under grant number VI.Veni.194.032 awarded to JN. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. Any views expressed are those of the authors and not necessarily those of the funders., European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), European Project: 777394,H2020-JTI-IMI2-2016-10-two-stage,AIMS-2-TRIALS(2018), and European Project: 101069276,CANDY
Subjects: Adult, Male, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Adolescent, Autism Spectrum Disorder, article, Glutamic Acid, Brain, 692/699/476/1373, Cellular and Molecular Neuroscience, Psychiatry and Mental health, All institutes and research themes of the Radboud University Medical Center, 692/53, 59/57, Humans, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Autistic Disorder, 631/378, Transcriptome, gamma-Aminobutyric Acid, Biological Psychiatry
Abstract: Funder: AIMS-2TRIALS/EU-AIMS which receive support from Innovative Medicines Initiative Joint Undertaking grant numbers 115300 and 777394, Funder: Horizon2020 CANDY programme grant number 847818, Funder: Dutch NWO Veni grant grant number VI.Veni.194.032, The excitatory/inhibitory (E/I) imbalance hypothesis posits that imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms underlies the behavioral characteristics of autism. However, how E/I imbalance arises and how it may differ across autism symptomatology and brain regions is not well understood. We used innovative analysis methods-combining competitive gene-set analysis and gene-expression profiles in relation to cortical thickness (CT) to investigate relationships between genetic variance, brain structure and autism symptomatology of participants from the AIMS-2-TRIALS LEAP cohort (autism = 359, male/female = 258/101; neurotypical control participants = 279, male/female = 178/101) aged 6-30 years. Using competitive gene-set analyses, we investigated whether aggregated genetic variation in glutamate and GABA gene-sets could be associated with behavioral measures of autism symptoms and brain structural variation. Further, using the same gene-sets, we corelated expression profiles throughout the cortex with differences in CT between autistic and neurotypical control participants, as well as in separate sensory subgroups. The glutamate gene-set was associated with all autism symptom severity scores on the Autism Diagnostic Observation Schedule-2 (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R) within the autistic group. In adolescents and adults, brain regions with greater gene-expression of glutamate and GABA genes showed greater differences in CT between autistic and neurotypical control participants although in opposing directions. Additionally, the gene expression profiles were associated with CT profiles in separate sensory subgroups. Our results suggest complex relationships between E/I related genetics and autism symptom profiles as well as brain structure alterations, where there may be differential roles for glutamate and GABA.
Published: 2023
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7. Association between reported work in cold environments and stroke occurrence in the CONSTANCES cohort: a prospective study

Author: Marc Fadel, Grace Sembajwe, Dominique Tripodi, Vincent Bonneterre, Annette Leclerc, Yves Roquelaure, Audrey Petit, Alexis Descatha, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hofstra University [Hempstead], Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Nantes Université - UFR Lettres et Langages (Nantes Univ - UFR LL), Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), UMS 011, Institut National de la Santé et de la Recherche Médicale (INSERM), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), The study was funded by the Interuniversity Institution of Occupational Health of Paris Ile-de-France, which had no role in the collection of data, analyses and the writing of the manuscript. The CONSTANCES Cohort Study was supported and funded by the Caisse Nationale d’Assurance Maladie, it is an ‘Infrastructure Nationale en Biologie et Santé’ and benefits from ANR (ANR-11-INBS-0002) grant funding. CONSTANCES is also partly funded by MSD, AstraZeneca and Lundbeck., and ANR-11-INBS-0002,CONSTANCES,La cohorte CONSTANCES - Infrastructure épidémiologique ouverte pour la recherche et la surveillance(2011)
Subjects: Cohort Studies, Stroke, Risk Factors, [SDV]Life Sciences [q-bio], Incidence, Humans, General Medicine, Prospective Studies
Abstract: ObjectiveCold environments are a potential risk factor for stroke. The aim of this study was to investigate the association between performing work tasks in cold environments and the occurrence of a first stroke event.MethodsFrom the French population-based cohort CONSTANCES (‘Cohorte des consultants des Centres d'examens de santé’ in French), we collected data from baseline questionnaires along with medical interviews on cardiovascular risk factors and reported exposure to cold temperatures (ResultsThere were 160 782 participants and 224 strokes (168 ischaemic and 76 haemorrhagic) included in our study. No significant increase in stroke was found for working in cold environments; the adjusted OR for often or almost always exposed was 1.14 (95% CI 0.46 to 2.84).ConclusionsThis study did not reveal a significant excess risk of stroke for occupational exposures to low temperatures. Further studies are needed to better assess the effect of preventive measures and very low temperature on occurrence of cardiovascular diseases.
Published: 2022
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8. The association between ambient UVB dose and ANCA-associated vasculitis relapse and onset

Author: Scott, Jennifer, Havyarimana, Enock, Navarro-Gallinad, Albert, White, Arthur, Wyse, Jason, van Geffen, Jos, van Weele, Michiel, Buettner, Antonia, Wanigasekera, Tamara, Walsh, Cathal, Aslett, Louis, Kelleher, John D., Power, Julie, Ng, James, O’Sullivan, Declan, Hederman, Lucy, Basu, Neil, Little, Mark A., Zgaga, Lina, Little, Mark, Lavin, Peter, Wall, Catherine, Mellotte, George, Fitzgerald, Ted, O’Keefe, Hannah, Dilworth, Rachel, O’Neill, Pamela, Carr, Vicki, Conlon, Niall, Griffin, Brenda, Sexton, Donal, Kosgei, Caroline, O’Meara, Yvonne, White, Eoghan, Mahony, Stephen, Molloy, Eamonn, Holian, John, Griffin, Matt, Lappin, David, Judge, Conor, Cormican, Sarah, O’Connell, Blathnaid, Clince, Michelle, Casserly, Liam, Clarkson, Michael, O’Shaughnessy, Michelle, Verrelli, Alyssa, Stoeman, Sinead, Daly, Fergus, Slattery, Laura, Murphy, Aisling, De Freitas, Declan, Conlon, Peter, Denton, Mark, Treanor, Carol, Magee, Colm, Seaghdha, Conall O., O’Hara, Paul, McGrath, Susan, Moloney, Brona, Moore, Dean, Kelly, Dearbhla, McCarthy, Mary, Obilana, Ayanfeoluwa, Kennedy, Claire, Connaughton, Dervla, Canney, Mark, Wong, Limy, Moran, Sarah, and Dr. Jennifer Scott is a Wellcome-HRB Irish Clinical Academic Training (ICAT) Fellow, and this work was performed within the Irish Clinical Academic Training (ICAT) Programme, supported by the Wellcome Trust and the Health Research Board (Grant Number 203930/B/16/Z), the Health Service Executive, National Doctors Training and Planning and the Health and Social Care, Research and Development Division, Northern Ireland. MAL received funding from Health Research Board/Irish Nephrology Society (MRCG-2016-12) and Science Foundation Ireland (13/RC/2106_P2 and 11/YI/B2093). ANG and EH received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 813545. The funders were not involved in any part of the study design, analysis or writing of the manuscript.
Subjects: Geoepidemiology, integumentary system, Ultraviolet Rays, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Environment, Vitamin D Deficiency, Recurrence, Chronic Disease, Medicine and Health Sciences, Humans, Ultraviolet B (UVB) radiation, Computer Engineering, Vitamin D, ANCA-associated vasculitis
Abstract: Background The aetiology of ANCA-associated vasculitis (AAV) and triggers of relapse are poorly understood. Vitamin D (vitD) is an important immunomodulator, potentially responsible for the observed latitudinal differences between granulomatous and non-granulomatous AAV phenotypes. A narrow ultraviolet B spectrum induces vitD synthesis (vitD-UVB) via the skin. We hypothesised that prolonged periods of low ambient UVB (and by extension vitD deficiency) are associated with the granulomatous form of the disease and an increased risk of AAV relapse. Methods Patients with AAV recruited to the Irish Rare Kidney Disease (RKD) (n = 439) and UKIVAS (n = 1961) registries were studied. Exposure variables comprised latitude and measures of ambient vitD-UVB, including cumulative weighted UVB dose (CW-D-UVB), a well-validated vitD proxy. An n-of-1 study design was used to examine the relapse risk using only the RKD dataset. Multi-level models and logistic regression were used to examine the effect of predictors on AAV relapse risk, phenotype and serotype. Results Residential latitude was positively correlated (OR 1.41, 95% CI 1.14–1.74, p = 0.002) and average vitD-UVB negatively correlated (0.82, 0.70–0.99, p = 0.04) with relapse risk, with a stronger effect when restricting to winter measurements (0.71, 0.57–0.89, p = 0.002). However, these associations were not restricted to granulomatous phenotypes. We observed no clear relationship between latitude, vitD-UVB or CW-D-UVB and AAV phenotype or serotype. Conclusion Our findings suggest that low winter ambient UVB and prolonged vitD status contribute to AAV relapse risk across all phenotypes. However, the development of a granulomatous phenotype does not appear to be directly vitD-mediated. Further research is needed to determine whether sufficient vitD status would reduce relapse propensity in AAV.
Published: 2022
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9. Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19

Author: Aiwei Zhu, Fernando Real, Claude Capron, Arielle R. Rosenberg, Aymeric Silvin, Garett Dunsmore, Jaja Zhu, Andréa Cottoignies-Callamarte, Jean-Marc Massé, Pierre Moine, Simon Bessis, Mathieu Godement, Guillaume Geri, Jean-Daniel Chiche, Silvana Valdebenito, Sandrine Belouzard, Jean Dubuisson, Geoffroy Lorin de la Grandmaison, Sylvie Chevret, Florent Ginhoux, Eliseo A. Eugenin, Djillali Annane, Elisabeth Cramer Bordé, Morgane Bomsel, Institut Cochin [IC UM3 (UMR 8104 / U1016)], Université de Versailles Saint-Quentin-en-Yvelines [UVSQ], Hôpital Ambroise Paré [AP-HP], Hôpital Cochin [AP-HP], Immunologie anti-tumorale et immunothérapie des cancers [ITIC], Institut Gustave Roussy [IGR], Infection et inflammation [2I], The University of Texas Medical Branch [UTMB], Institut Pasteur de Lille, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Hôpital Raymond Poincaré [Garches], Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) [SBIM], Singapore Immunology Network [SIgN], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service d'Hématologie et d'Immunologie [AP-HP Hôpital Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Institut Gustave Roussy (IGR), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation médicale polyvalente [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], The University of Texas Medical Branch (UTMB), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP), Université de Lille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Agency for science, technology and research [Singapore] (A*STAR), ANR-20-COVI-0024,MUCOLUNG,Rôle des cellules pulmonaires infectées par le SRAS-CoV-2 et réponse humoral dans l' évolution du COVID-19: de la physiopathologie au test de médicaments candidats dans les modèles de cellules muqueuses(2020), Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), School of Medicine [Shanghai Jiaotong University], Shanghai Jiaotong University, Accident Compensation Corporation, ACC, Fondation pour la Recherche Médicale, FRM, China Scholarship Council, CSC, The authors thank Professor John F. Martin (University College of London, UK) for fruitful advice and discussion on the role of NRP1 receptor and VEGF in COVID19 and resultant therapeutical implications, and for English editing. The authors greatly acknowledge Karine Bailly and Muriel Andrieu of the Cochin Cytometry and Immunobiology Facility for cytokine analyses, as well as Thomas Guilbert from the Imag’IC facility for instruction on the IXplore Spin Confocal Imaging Microscope System (Olympus) and Livine Duban from Luminex corp for instruction on the Guava easyCyte 12HT base system (Millipore) during the COVID-19 confinement period. We also thank also Dr. Nicolas Chapuis (Hôpital Cochin, Paris, France) and Pr. Nicholas Heming (Hôpital Raymond Poincaré, Garches, France) for helpful discussion., Joint funding by the Agence Nationale de la Recherche (France) and Fondation pour la Recherche Médicale (France): Flash COVID ANR-FRM: ANR-20-COVI-0024. Funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript. AZ was supported by the China Scholarship Council and ACC by the Fondation pour la Recherche Médicale., and REAL, Fernando
Subjects: Blood Platelets, Pharmacology, Platelets, SARS-CoV-2, Macrophages, [SDV]Life Sciences [q-bio], Membrane Proteins, RNA-Binding Proteins, COVID-19, Thrombosis, Cell Biology, [SDV] Life Sciences [q-bio], Lung, Megakaryocytes, Cellular and Molecular Neuroscience, Humans, Molecular Medicine, Molecular Biology
Abstract: SARS-CoV-2, although not being a circulatory virus, spread from the respiratory tract resulting in multiorgan failures and thrombotic complications, the hallmarks of fatal COVID-19. A convergent contributor could be platelets that beyond hemostatic functions can carry infectious viruses. Here, we profiled 52 patients with severe COVID-19 and demonstrated that circulating platelets of 19 out 20 non-survivor patients contain SARS-CoV-2 in robust correlation with fatal outcome. Platelets containing SARS-CoV-2 might originate from bone marrow and lung megakaryocytes (MKs), the platelet precursors, which were found infected by SARS-CoV-2 in COVID-19 autopsies. Accordingly, MKs undergoing shortened differentiation and expressing anti-viral IFITM1 and IFITM3 RNA as a sign of viral sensing were enriched in the circulation of deadly COVID-19. Infected MKs reach the lung concomitant with a specific MK-related cytokine storm rich in VEGF, PDGF and inflammatory molecules, anticipating fatal outcome. Lung macrophages capture SARS-CoV-2-containing platelets in vivo. The virus contained by platelets is infectious as capture of platelets carrying SARS-CoV-2 propagates infection to macrophages in vitro, in a process blocked by an anti-GPIIbIIIa drug. Altogether, platelets containing infectious SARS-CoV-2 alter COVID-19 pathogenesis and provide a powerful fatality marker. Clinical targeting of platelets might prevent viral spread, thrombus formation and exacerbated inflammation at once and increase survival in COVID-19.
Published: 2022
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10. Patient healthcare trajectories of intrahepatic cholangiocarcinoma in France: A nationwide retrospective analysis

Author: Cindy Neuzillet, Corinne Emery, Clément Teissier, Stéphane Bouée, Astrid Lièvre, Institut Curie [Paris], Biostatistics, CEMKA, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], This study was sponsored by Incyte Biosciences International Sàrl., Geneva, Switzerland. INCYTE validated the design of the study, the analysis, the interpretation of data and the writing of the manuscript which was first written by the 2 experts and CEMKA., and Jonchère, Laurent
Subjects: French PMSI database, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, Epidemiology, Health Policy, Patterns of care, Real life, Internal Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Public aspects of medicine, RA1-1270, Intrahepatic cholangiocarcinoma
Abstract: International audience; BACKGROUND: Little is known about the epidemiology and patterns of care of intrahepatic cholangiocarcinoma (iCCA) in daily clinical practice. The aims of this study were to estimate the number of declared cases during the study period 2014-2015 in France from a hospitalization database and to describe the healthcare trajectories of these patients. METHODS: A retrospective analysis was carried out using the French nationwide prospective hospitalization database. All pts with a new diagnosis of "carcinoma of the intrahepatic bile duct" who had a first hospital stay in the Medicine, Surgery and Obstetrics departments (MSO) between 2014 and 2015 with a 2-year follow-up were included. Data related to the first identified stay (S1) in the MSO and on all subsequent stays in the MSO, aftercare and rehabilitation or home hospitalization were analysed. FINDINGS: A total of 3650 new iCCA cases were identified. At S1 (admission via emergency room (ER) in 28%), the median age of the patients was 73 years, 57% were male and 35% had metastases. Jaundice/anaemia/ascites/cholangitis were reported in 17%/16%/12%/7% of patients, respectively. The care of patients at S1 was mainly provided in general hospitals (CHG, 60%). A total of 896 (24%) patients died during S1. They were more frequently hospitalized via the ER (48% vs 23%), metastatic (52% vs 35%) and symptomatic. Subsequent stays were identified for 2507 (69%) patients. Three healthcare pathways were defined: surgery (n = 519; 14%), chemotherapy (CT) without surgery (n = 812; 22%) and best supportive care (BSC) (n = 2319; 63%). CT, surgery and BSC were most frequently performed in the cancer centres, university hospitals and CHG, respectively. INTERPRETATION: This medico administrative study reveals a higher number of iCCA cases than that previously reported by registries and highlights the severity of this disease. FUNDING: This study was sponsored by Incyte Biosciences International Sàrl., Geneva, Switzerland. INCYTE validated the design of the study, the analysis, the interpretation of data and the writing of the manuscript which was first written by the 2 experts and CEMKA.
Published: 2022
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11. DNA methylation in infants with low and high body fatness

Author: Elisabet Forsum, Patrick Müller, Signe Altmäe, Colm E Nestor, Pontus Henriksson, David Brodin, Antonio Lentini, Marie Löf, [Henriksson,P, Löf,M] Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden. [Lentini,A, Nestor,CE] Crown Princess Victoria Children’s Hospital, and Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden. [Altmäe,S] Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Granada, Granada, Spain. [Altmäe,S] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Brodin,D, Müller,P, Löf,M] Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden. [Forsum,E] Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden., and The study was funded by Formas (data collection) and a grant from Bo and Vera Ax:son Johnsons Foundation (data analysis) (both ML). CEN was supported by grants from the Swedish Research Council (2015–03495) and the Swedish Cancer Society (CAN 2017/625). SA was supported by grants from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and European Regional Development Fund (FEDER) grants: RYC-2016-21199 and ENDORE SAF2017–87526. The funding body had no role in the design of the study, data collection, analysis and interpretation of data, writing of the manuscript and the decision to publish. Open Access funding provided by Linköping University Library.
Subjects: genetic structures, Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weight::Birth Weight [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Morphogenesis::Embryonic and Fetal Development::Fetal Development [Medical Subject Headings], Buccal swab, Obesidad, Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose [Medical Subject Headings], Physiology, Índice de masa corporal, Body composition, Body Mass Index, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Methylation [Medical Subject Headings], Birth Weight, Peso al nacer, Body mass index, 0303 health sciences, Persons::Persons::Age Groups::Infant [Medical Subject Headings], Epigenetic, Anatomy::Tissues::Connective Tissue::Adipose Tissue [Medical Subject Headings], Adipose Tissue, 030220 oncology & carcinogenesis, DNA methylation, Body Composition, Anatomy::Tissues::Membranes::Mucous Membrane::Mouth Mucosa [Medical Subject Headings], DNA microarray, Medical Genetics, psychological phenomena and processes, Biotechnology, Research Article, Metilación de ADN, lcsh:QH426-470, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Plethysmography [Medical Subject Headings], Birth weight, lcsh:Biotechnology, Carbohydrate metabolism, Biology, Health outcomes, 03 medical and health sciences, lcsh:TP248.13-248.65, Genetics, Humans, Epigenetics, Obesity, Composición corporal, 030304 developmental biology, Medicinsk genetik, Body fatness, Mouth Mucosa, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic [Medical Subject Headings], Infant, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Body Composition [Medical Subject Headings], DNA Methylation, lcsh:Genetics, Epigenómica, Persons::Persons::Parents [Medical Subject Headings]
Abstract: The authors gratefully thank the parents and children that participated in the PATHOS study., Background: Birth weight is determined by the interplay between infant genetics and the intrauterine environment and is associated with several health outcomes in later life. Many studies have reported an association between birth weight and DNA methylation in infants and suggest that altered epigenetics may underlie birthweight-associated health outcomes. However, birth weight is a relatively nonspecific measure of fetal growth and consists of fat mass and fat-free mass which may have different effects on health outcomes which motivates studies of infant body composition and DNA methylation. Here, we combined genome-wide DNA methylation profiling of buccal cells from 47 full-term one-week old infants with accurate measurements of infant fat mass and fat-free mass using air-displacement plethysmography. Results: No significant association was found between DNA methylation in infant buccal cells and infant body composition. Moreover, no association between infant DNA methylation and parental body composition or indicators of maternal glucose metabolism were found. Conclusions: Despite accurate measures of body composition, we did not identify any associations between infant body fatness and DNA methylation. These results are consistent with recent studies that generally have identified only weak associations between DNA methylation and birthweight. Although our results should be confirmed by additional larger studies, our findings may suggest that differences in DNA methylation between individuals with low and high body fatness may be established later in childhood., Swedish Research Council Formas, Swedish Research Council 2015-03495, Swedish Cancer Society CAN 2017/625, Spanish Ministry of Economy, Industry and Competitiveness (MINE CO), European Union (EU) RYC-2016-21199 ENDORE SAF2017-87526, Linkoping University Library, Bo and Vera Ax:son Johnsons Foundation
Published: 2020
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12. Metabolic Disorders in Patients with Chronic Hepatitis B Virus Infection: Coffee as a Panacea? (ANRS CO22 Hepather Cohort)

Author: Tangui, Barré, Hélène, Fontaine, Stanislas, Pol, Clémence, Ramier, Vincent, Di Beo, Camelia, Protopopescu, Fabienne, Marcellin, Morgane, Bureau, Marc, Bourlière, Céline, Dorival, Ventzislava, Petrov-Sanchez, Tarik, Asselah, Elisabeth, Delarocque-Astagneau, Dominique, Larrey, Jean-Charles, Duclos-Vallée, Fabrice, Carrat, Patrizia, Carrieri, On Behalf Of The Anrs/Afef Hepather Study Group, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Joseph [Marseille], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Beaujon [AP-HP], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Raymond Poincaré [AP-HP], Laboratoire de biochimie Saint-Eloi, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Paul Brousse, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gilead Sciences, Meso Scale Diagnostics, MSD, Janssen Pharmaceuticals, Agence Nationale de la Recherche, ANR, Association Française pour l'Etude du Foie, AFEF, The Hepather cohort is funded by INSERM-ANRS MIE (France REcherche Nord&sud Sida-vih Hepatites|Maladies Infectieuses Emergentes), ANR Equipex and Cohort (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé) and MSD, Janssen, Gilead, Abbvie, BMS, Roche. These funding sources had no role in the writing of the manuscript, or in the decision to submit it for publication., Acknowledgments: We would like to thank the participating patients and clinicians at each site. We also thank INSERM-ANRS MIE for sponsoring, funding and conducting the ANRS CO22 Hepather cohort in collaboration with the French Association for the Study of the Liver (Association Française pour l'Etude du Foie: AFEF). Finally, our thanks to Jude Sweeney (Milan, Italy) for the English revision and copyediting of our manuscript, and HAL UVSQ, Équipe
Subjects: Polyphenol, [SDV] Life Sciences [q-bio], Dyslipidemia, Tea, [SDV]Life Sciences [q-bio], Hypertension, Hepatitis B, Coffee, Metabolic syndrome
Abstract: International audience; People living with chronic hepatitis B virus (HBV) infection are at high risk of liver disease progression, which is positively associated with metabolic disorders, but inversely associated with dyslipidemia. Diet, including dietary antioxidants, is a lever of metabolic disorder management. In particular, elevated coffee consumption is associated with different metabolic outcomes in the general population. We aimed to test whether such associations occur in HBV-infected people. Based on cross-sectional data from the ANRS CO22 Hepather cohort, we performed logistic regression models with (i) dyslipidemia, (ii) hypertension, and (iii) diabetes as outcomes, and with demographic, clinical, and socio-behavioral (including coffee consumption) data as explanatory variables. Among 4746 HBV-infected patients, drinking ≥3 cups of coffee per day was associated with a higher risk of dyslipidemia (adjusted odds ratio [95% confidence interval] 1.49 [1.10–2.00], p = 0.009) and a lower risk of hypertension (0.64 [0.50–0.82], p = 0.001). It was not associated with diabetes. Elevated coffee consumption was associated with a higher risk of dyslipidemia and a lower risk of hypertension in HBV-infected patients, two effects expected to be associated with favorable clinical outcomes. Further studies should test whether such metabolic benefits translate into reduced mortality risk in this population.
Published: 2022
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13. The anti-androgenic fungicide triticonazole induces region-specific transcriptional changes in the developing rat perineum and phallus

Author: Monica Kam Draskau, Camilla Lindgren Schwartz, Bertrand Evrard, Aurélie Lardenois, Andrew Pask, Frédéric Chalmel, Terje Svingen, National Food Institute [Lyngby] (Forside), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), University of Melbourne, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), and This work was funded by the Danish Environmental Protection Agency (DEPA) as a project under the Centre on Endocrine Disrupters (CeHoS). The funding body (DEPA) was not involved in study design, interpretation of data, or in writing of the manuscript.
Subjects: Male, Conazoles, Environmental Engineering, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Genital tubercle, Public Health, Environmental and Occupational Health, Androgen Antagonists, BRB-Seq, General Medicine, General Chemistry, Cyclopentanes, Triazoles, Perineum, Pollution, Anogenital distance, Fungicides, Industrial, Rats, Environmental Chemistry, Animals, Endocrine disruptors, Biomarkers, Fungicides
Abstract: International audience; Intrauterine exposure to endocrine disrupting chemicals can interfere with male reproductive development. This can lead to male reproductive disorders such as hypospadias, cryptorchidism and reduced fertility, as well as shorter anogenital distance (AGD) - a biomarker for incomplete androgen-dependent fetal masculinization. However, it remains challenging to predict adverse in vivo outcomes based on in vitro effect patterns for many chemicals. This is a challenge for modern toxicology, which aims to reduce animal testing for chemical safety assessments. To enable the transition towards higher reliance on alternative test methods, we need to better map underlying mechanisms leading to adverse effects. Herein, we have analyzed the transcriptome of the perineum and phallus of male fetal rats and defined the impacts of exposure to an anti-androgenic fungicide, triticonazole. Previously we have shown that developmental exposure to triticonazole can induce short male AGD, but without a marked effect on the transcriptome of the fetal testes. In contrast, we report here significant changes to the transcriptional landscape of the perineum and phallus, including regional differences between these adjacent tissues. This highlights the importance of analyzing the correct tissue when characterizing mechanisms of complex in vivo effect outcomes. Our results provide a rich resource for the spatiotemporal gene networks that are involved in the development of male external genitalia, and that can be disrupted upon exposure to chemicals that prevent normal masculinization of the perineum and phallus. Such data will be critical in the development of novel alternative test methods to determine the endocrine disrupting potential of existing and emerging chemicals.
Published: 2022
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14. Impact of procedural success on clinical outcome after MitraClip: Results from the MITRA-FR trial

Author: Messika-Zeitoun, David, Attias, David, Piriou, Nicolas, Iung, Bernard, Armoiry, Xavier, Trochu, Jean-Noël, Donal, Erwan, Habib, Gilbert, Cormier, Bertrand, Guerin, Patrice, Lefèvre, Thierry, Maucort-Boulch, Delphine, Boutitie, Florent, Vahanian, Alec, Riche, Benjamin, Obadia, Jean-François, University of Ottawa [Ottawa], Centre cardiologique du Nord (CCN), Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Assistance Publique - Hôpitaux de Marseille (APHM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Privé Jacques Cartier [Massy], Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR Odontologie (Nantes Univ – UFR Odonto), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hôpital Louis Pradel [CHU - HCL], This trial was funded by the French Ministry of Health and Research National Programme and Abbott Vascular. Abbott Vascular provided the devices and the support for the investigators’ meetings. Neither Abbott Vascular nor any other commercial entity had a role in trial design, participating centre selection, centre monitoring and oversight, data collection, patient enrolment, patient management, data storage, data analysis, data interpretation, the writing of the manuscript or the decision to submit the manuscript., and Service de Biostatistiques [Lyon]
Subjects: Heart Valve Prosthesis Implantation, Heart Failure, Mitral Valve Insufficiency, Stroke Volume, General Medicine, Outcomes, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Ventricular Function, Left, Treatment Outcome, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, Transcatheter mitral valve therapy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cardiology and Cardiovascular Medicine, Mitral regurgitation
Abstract: International audience; BACKGROUND: Differences in procedural success rates have been proposed to explain the divergent results between the MITRA-FR trial (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) and the COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation). AIM: To examine whether MITRA-FR patients who had successful clip implantation achieved a better outcome than the control group.METHODS: Based on the per protocol population of MITRA-FR, we compared the outcome in 71 patients in whom optimal clip implantation was achieved (group 1: mitral regurgitation grade ≤ 1 + at discharge) with that in 23 patients with non-optimal clip implantation (group 2: mitral regurgitation grade ≥ 2 + at discharge) and that in 137 patients in the control group (group 3). The primary endpoint was all-cause death or unplanned hospitalization for heart failure at 24 months.RESULTS: Event-free survival was not different across the groups (42±6% in group 1, 30±10% in group 2 and 31±4% in group 3; log-rank P=0.32). In multivariable analyses, after adjustment for age, sex, rhythm, aetiology, left ventricular ejection fraction and mitral regurgitation severity, group was not associated with variations in outcome: using Group 3 as reference, hazard ratio 0.86, 95% confidence interval 0.58-1.27 (P=0.43) in group 1; and hazard ratio 0.98 95% confidence interval 0.54-1.76 (P=0.94) in group 2.CONCLUSIONS: The clinical outcome of patients in whom optimal procedural result was achieved at discharge was not different compared with the control group. Our results do not support the hypothesis that the differences in rates of residual mitral regurgitation at discharge between MITRA-FR and COAPT explain the divergent results between the two trials.
Published: 2021
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15. PFOS disrupts key developmental pathways during hiPSC-derived cardiomyocyte differentiation in vitro

Author: Nichlas Davidsen, Louise Ramhøj, Indusha Kugathas, Bertrand Evrard, Thomas A. Darde, Frédéric Chalmel, Terje Svingen, Anna Kjerstine Rosenmai, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), National Food Institute [Lyngby] (Forside), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), SciLicium, The project was funded by the Ministry of Foods, Agriculture and Fisheries of Denmark, project FEMINIX. The funding sources had no involvement in the study design, data collection and analysis, or in the writing of this manuscript., and Jonchère, Laurent
Subjects: Epidermal Growth Factor, [SDV]Life Sciences [q-bio], Induced Pluripotent Stem Cells, Cell Differentiation, General Medicine, Development, Toxicology, Perfluorooctanesulfonic acid, [SDV] Life Sciences [q-bio], [SDV.TOX] Life Sciences [q-bio]/Toxicology, In vitro, SDG 3 - Good Health and Well-being, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Humans, Myocytes, Cardiac, Spheroids
Abstract: International audience; Exposure to perfluorooctanesulfonic acid (PFOS) has been associated with congenital heart disease (CHD) and decreased birth weight. PFOS exposure can disrupt signaling pathways relevant for cardiac development in stem cell-derived cardiomyocyte assays, such as the PluriBeat assay, where spheroids of human induced pluripotent stem cells (hiPSCs) differentiate into contracting cardiomyocytes. Notably, cell line origin can also affect how the assay responds to chemical exposure. Herein, we examined the effect of PFOS on cardiomyocyte differentiation by transcriptomics profiling of two different hiPSC lines to see if they exhibit a common pattern of disruption. Two stages of differentiation were investigated: the cardiac progenitor stage and the cardiomyocyte stage. Many differentially expressed genes (DEGs) were observed between cell lines independent of exposure. However, 135 DEGs were identified as common between the two cell lines. Of these, 10 DEGs were associated with GO-terms related to the heart. PFOS exposure disrupted multiple signaling pathways relevant to cardiac development, including WNT, TGF, HH, and EGF. Of these pathways, genes related to the non-canonical WNTCa(2+) signaling was particularly affected. PFOS thus has the capacity to disrupt pathways important for cardiac development and function.
Published: 2022
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16. Standardised Outcomes in Nephrology – Chronic Kidney Disease (SONG-CKD): a protocol for establishing a core outcome set for adults with chronic kidney disease who do not require kidney replacement therapy

Author: Andrew S. Levey, Armando Teixeira-Pinto, Samuel Fung, Nicole Scholes-Robertson, Gloria Ashuntantang, Laura Cortés Sanabria, Samaya Anumudu, Amelie Bernier-Jean, Martin Howell, Louese Dunn, Tim Usherwood, Eduardo Lorca, Martin Wilkie, Andrea Matus Gonzalez, Magdalena Madero, Ikechi G. Okpechi, Daniel Gallego, Jonathan C. Craig, Adeera Levin, Allison Tong, Patrick Rossignol, Katherine Widders, Yeoungjee Cho, Ian H. de Boer, Andrea K. Viecelli, David C. Wheeler, Nicole Evangelidis, Bénédicte Sautenet, Laura Sola, Chandana Guha, The University of Sydney, Westmead Hospital [Sydney], MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Instituto Nacional de Cardiologia Ignacio Chavez, Université de Yaoundé I, Hospital Universitario de Guadalajara, Department of Medicine, Kidney Research Institute, University of Washington, Kidney Research Institute [Seattle] (KRI), Princess Margaret Hospital, Hong Kong, Federacion Nacional ALCER (Spanish Kidney Patient's Federation), Tufts University School of Medicine [Boston], University of British Columbia (UBC), Hospital Salvador, University of Cape Town, University of Alberta, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Dialysis Unit, CASMU-IAMPP, Montevideo, University of New South Wales [Sydney] (UNSW), Centre for Nephrology, UCL Medical School, Translational Research Institute, University College of London [London] (UCL), University of Queensland [Brisbane], Princess Alexandra Hospital, Brisbane, Baylor College of Medecine, Sheffield Children's NHS Foundation Trust, Flinders University [Adelaide, Australia], This project is supported by the National Health and Medical Research Council (NHMRC) Program Grant 1092597. NE is supported by the National Health and Medical Research Council (NHMRC) Program Grant 1092597. AT is supported by The University of Sydney Robinson Fellowship. YC is supported by the NHMRC Early Career Fellowship 1126256. AV is supported by a Jacquot Research Establishment Fellowship. The funding bodies do not have a role in the design, collection, analysis, and interpretation of data, in the writing of the manuscript, and in the decision to submit the manuscript for publication., Division of Nephrology and Hypertension, Faculty of Health Sciences, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, and BOZEC, Erwan
Subjects: Nephrology, Medicine (General), Delphi Technique, 030232 urology & nephrology, Medicine (miscellaneous), urologic and male genital diseases, MESH: Delphi Technique, law.invention, Study Protocol, Clinical trials, 0302 clinical medicine, Randomized controlled trial, law, Chronic kidney disease, Outcome Assessment, Health Care, Pharmacology (medical), 030212 general & internal medicine, MESH: Treatment Outcome, MESH: Research Design, MESH: Nephrology, female genital diseases and pregnancy complications, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Renal Replacement Therapy, Treatment Outcome, Research Design, Outcomes research, Adult, medicine.medical_specialty, MESH: Renal Insufficiency, Chronic, 03 medical and health sciences, R5-920, Quality of life (healthcare), [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Renal Insufficiency, Chronic, MESH: Outcome Assessment, Health Care, Intensive care medicine, MESH: Humans, business.industry, Core outcome set, MESH: Quality of Life, MESH: Adult, medicine.disease, Transplantation, Clinical trial, Quality of Life, MESH: Renal Replacement Therapy, Patient-centred outcomes, MESH: Systematic Reviews as Topic, business, Systematic Reviews as Topic, Kidney disease, Qualitative research
Abstract: Background Globally, over 1.2 million people die from chronic kidney disease (CKD) every year. Patients with CKD are up to 10 times more likely to die prematurely than progress to kidney failure requiring kidney replacement therapy. The burden of symptoms and impaired quality of life in CKD may be compounded by comorbidities and treatment side effects. However, patient-important outcomes remain inconsistently and infrequently reported in trials in patients with CKD, which can limit evidence-informed decision-making. The Standardised Outcomes in Nephrology – Chronic Kidney Disease (SONG-CKD) aims to establish a consensus-based core outcome set for trials in patients with CKD not yet requiring kidney replacement therapy to ensure outcomes of relevance to patients, caregivers and health professionals are consistently reported in trials. Methods SONG-CKD involves four phases: a systematic review to identify outcomes (domains and measures) that have been reported in randomised controlled trials involving adults with CKD who do not require kidney replacement therapy; stakeholder key informant interviews with health professionals involved in the care of adults with CKD to ascertain their views on establishing core outcomes in CKD; an international two-round online Delphi survey with patients, caregivers, clinicians, researchers, policy makers and industry representatives to obtain consensus on critically important outcome domains; and stakeholder consensus workshops to review and finalise the set of core outcome domains for trials in CKD. Discussion Establishing a core outcome set to be reported in trials in patients with CKD will enhance the relevance, transparency and impact of research to improve the lives of people with CKD. Trial registration Not applicable. This study is registered with the Core Outcome Measures in Effectiveness Trials (COMET) database: http://www.comet-initiative.org/Studies/Details/1653.
Published: 2021
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17. Assessing Prevalence and Factors Related to Frailty in Community-Dwelling Older Adults: A Multinomial Logistic Analysis

Author: Maria Rosa García-Merino, Encarnación Blanco-Reina, Gabriel Ariza-Zafra, Jenifer Valdellós, Inmaculada Bellido-Estevez, Lorena Aguilar-Cano, Ricardo Ocaña-Riola, [Blanco-Reina,E, Bellido-Estévez,I] Pharmacology and Therapeutics Department, Instituto de Investigación Biomédica de Málaga-IBIMA, School of Medicine, University of Málaga, Málaga, Spain. [Aguilar-Cano,L] Physical Medicine and Rehabilitation Department, Hospital Regional Universitario, Málaga, Spain. [García-Merino,MR, Valdellós,J] Health District of Málaga-Guadalhorce, Málaga, Spain. [Ocaña-Riola,R] Escuela Andaluza de Salud Pública, Granada, Spain. [Ocaña-Riola,R] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Ariza-Zafra,G] Geriatrics Department, Complejo Hospitalario Universitario, Albacete, Spain., This research was funded by the Fundación Pública Andaluza Progreso y Salud, Consejería de Salud, Junta de Andalucía, through the Programme Proyectos de Investigación Biomédica (Grant number PI 0234/14). The APC was funded by the University of Málaga. The funders had no role in the design of the study, in the collection, analyses or interpretation of data, and in the writing of the manuscript or in the decision to publish the results.
Subjects: Gerontology, Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], Activities of daily living, Persons::Persons::Age Groups::Adult::Aged::Frail Elderly [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Polypharmacy [Medical Subject Headings], Psychiatry and Psychology::Mental Disorders [Medical Subject Headings], Diseases::Musculoskeletal Diseases::Rheumatic Diseases::Osteoarthritis [Medical Subject Headings], frailty, osteoarticular pathology, Article, primary care, Pharmacotherapy, Atención primaria de salud, Intervention (counseling), Medicine, older adults, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Polypharmacy, Anthropology, Education, Sociology and Social Phenomena::Human Activities::Activities of Daily Living [Medical Subject Headings], business.industry, Stressor, Anthropology, Education, Sociology and Social Phenomena::Human Activities::Activities of Daily Living::Independent Living [Medical Subject Headings], General Medicine, Psicopatología, psychopathology, Health Care::Health Services Administration::Patient Care Management::Comprehensive Health Care::Primary Health Care [Medical Subject Headings], Polimedicación, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], Fragilidad, Artropatías, Information Science::Information Science::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings], Logistic analysis, Multinomial distribution, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Behavioral Symptoms::Depression [Medical Subject Headings], business, polymedication, Personas mayores frágiles, Psychopathology
Abstract: Frailty is an age-related clinical condition that typically involves a deterioration in the physiological capacity of various organ systems and heightens the patient’s susceptibility to stressors. For this reason, one of the main research goals currently being addressed is that of characterising the impact of frailty in different settings. The main aim of this study is to determine the prevalence of Fried’s frailty phenotype among community-dwelling older people and to analyse the factors associated with frailty. In this research study, 582 persons aged 65 years or more participated in this cross-sectional study that was conducted at primary healthcare centres in Málaga, Spain. Sociodemographic, clinical, functional and comprehensive drug therapy data were compiled. The relationship between the independent variables and the different states of frailty was analysed by using a multinomial logistic regression model. Frailty was present in 24.1% of the study sample (95% CI = 20.7–27.6) of whom 54.3% were found to be pre-frail and 21.6% were non-frail. The study variable most strongly associated with frailty was the female gender (OR = 20.54, 95% CI = 9.10–46.3). Other factors found to be associated with the state of frailty included age, dependence for the instrumental activities of daily living (IADL), polymedication, osteoarticular pathology and psychopathology. This study confirms the high prevalence of frailty among community-dwelling older people. Frailty may be associated with many factors. Some of these associated factors may be preventable or modifiable and, thus, provide clinically relevant targets for intervention. This is particularly the case for depressive symptoms, the clinical control of osteoarthritis and the use of polypharmacy.
Published: 2021

18. Diagnosis and Management of Heart Failure in Elderly Patients from Hospital Admission to Discharge: Position Paper

Author: Patrice Cacoub, Gilles Berrut, Olivier Hanon, Tahar Chouihed, Nicholas Lamblin, Nicholas Delarche, Emmanuel Andrès, Patrick Henry, Thibaud Damy, CHU Henri Mondor, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre hospitalier de Pau, Pôle hospitalo-universitaire de gérontologie clinique [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Immunologie [CHU Pitié-Salpétrière], 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), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, CHU Strasbourg, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Université de Paris (UP), Novartis provided financial support for logistic management but was not involved in the writing of the manuscript., CHU Henri Mondor [Créteil], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université Paris Cité (UPCité), and Gestionnaire, HAL Sorbonne Université 5
Subjects: medicine.medical_specialty, Hospital setting, Management of heart failure, Review, 030204 cardiovascular system & hematology, elderly, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Multidisciplinary approach, Community health care, medicine, Transitional care, 030212 general & internal medicine, Intensive care medicine, heart failure management, business.industry, General Medicine, medicine.disease, practical guidance, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Heart failure, Hospital admission, Medicine, Position paper, business
Abstract: International audience; Multidisciplinary management of worsening heart failure (HF) in the elderly improves survival. To ensure patients have access to adequate care, the current HF and French health authority guidelines advise establishing a clearly defined HF patient pathway. This pathway involves coordinating multiple disciplines to manage decompensating HF. Yet, recent registry data indicate that insufficient numbers of patients receive specialised cardiology care, which increases the risk of rehospitalisation and mortality. The patient pathway in France involves three key stages: presentation with decompensated HF, stabilisation within a hospital setting and transitional care back out into the community. In each of these three phases, HF diagnosis, severity and precipitating factors need to be promptly identified and managed. This is particularly pertinent in older, frail patients who may present with atypical symptoms or coexisting comorbidities and for whom geriatric evaluation may be needed or specific geriatric syndrome management implemented. In the transition phase, multi-professional post-discharge management must be coordinated with community health care professionals. When the patient is discharged, HF medication must be optimised, and patients educated about self-care and monitoring symptoms. This review provides practical guidance to clinicians managing worsening HF in the elderly.
Published: 2021
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19. Shell tools and productive strategies of hunter-gatherer groups: Some reflections from a use-wear analysis at the Balma del Gai site (Barcelona, Spain)

Author: Pilar García-Argüelles, Lluís Lloveras, Jordi Nadal, Ignacio Clemente-Conte, David Cuenca-Solana, Centre de Recherche en Archéologie, Archéosciences, Histoire (CReAAH), Le Mans Université (UM)-Université de Rennes (UR)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR Histoire, Histoire de l'Art et Archéologie (UFR HHAA), Université de Nantes (UN)-Université de Nantes (UN)-Ministère de la Culture (MC), Universidad de Cantabria [Santander], Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Universitat de Barcelona (UB), While carrying out the analyses making up this research DCS was financed by thes Fyssen Foundation through a postdoctoral grant from UMR 6566 CReAAH. During the period of writing of the manuscript DCS was financed by the Ministerio de Ciencia, Innovación y Universidades through the Juan de la Cierva Research Programme - Incorporación (IJCI-2014-20590). Ll. Lloveras was financed by a postdoctoral contract (BP-B00140-2014) from the Departament d’Universitats, Recerca i Societat de la Informació de la Generalitat de Catalunya and the COFUND programme (Marie Curie Actions). We are also grateful for the finance received for the projects HAR2017-86509 and SGR2017-00011., Université de Nantes (UN)-Le Mans Université (UM)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Universidad de Cantabria, Université de Nantes - UFR Histoire, Histoire de l'Art et Archéologie (UFR HHAA), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Le Mans Université (UM), Le Mans Université (UM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), and Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC)-Nantes Université (NU)
Subjects: 010506 paleontology, Archeology, Adornment, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Context (language use), Perishable materials, Use-wear analysis, 01 natural sciences, Mediterranean coast, 0601 history and archaeology, 14. Life underwater, Sea level, Hunter-gatherer, 0105 earth and related environmental sciences, Shell tools, Glycymeris, 060102 archaeology, biology, Epipalaeolithic, Excavation, 06 humanities and the arts, biology.organism_classification, Archaeology, Geography, Hunter-gatherers, Rock shelter
Abstract: Balma del Gai site is a small rock shelter situated in the municipality of Moià (Barcelona, Spain) at an altitude of 760 m above sea level and 50 km from the current coastline. The levels of occupation in this context are dated between 13,442 cal BP and 9,552 cal BP, being related to the so-denominated “Epimagdalenian” and “Microlaminar Sauveterroid” complexes. The excavations have provided important mollusc samples, both terrestrial and marine, which have been studied and considered alimentary and adornment resources. In this article, we present the results of the use-wear analyses of the shell tools of Mytilus galloprovincialis Lamarck, 1819 and Glycymeris glycymeris (Linnaeus, 1758). The results of these analyses and their comparison with analytical experimentation demonstrate that some of these shells were used as tools for developing diverse productive activities related to the processing of materials of animal, mineral and vegetal origin. In this way, this research contributes to: 1) broaden the technological spectrum registered in this context and in a wider sense for Epipalaeolithic hunter-gatherers (beyond the traditional technological elements), 2) demonstrate a diversified use of the shells as adornments, food and tools in the site; an aspect of great interest especially bearing in mind the distance from the coast.
Published: 2021
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20. Hypophosphatasia: A Unique Disorder of Bone Mineralization

Author: Villa-Suárez, Juan Miguel, García-Fontana, Cristina, Andújar-Vera, Francisco, González-Salvatierra, Sheila, de Haro-Muñoz, Tomás, Contreras-Bolívar, Victoria, García-Fontana, Beatriz, Muñoz-Torres, Manuel, [Villa-Suárez,JM, de Haro-Muñoz,T] Clinical Analysis Unit, University Hospital Clínico San Cecilio, Granada, Spain. [Villa-Suárez,JM, García-Fontana,C, Andújar-Vera,F, González-Salvatierra,S, Contreras-Bolívar,V, García-Fontana,B, Muñoz-Torres,M] Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain. [García-Fontana,C, Muñoz-Torres,M] Endocrinology and Nutrition Unit, University Hospital Clínico San Cecilio, Granada, Spain. [García-Fontana,C, Muñoz-Torres,M] CIBERFES, Institute of Health Carlos III, Granada, Spain. [González-Salvatierra,S, Muñoz-Torres,M] Department of Medicine, University of Granada, Granada, Spain., This research was funded by the Institute of Health Carlos III grants (PI18-00803 and PI18-01235), co-funded by the European Regional Development Fund (FEDER). In addition, JM.V-S and C.G-F are funded by predoctoral and postdoctoral fellowships, respectively, from the Institute of Health Carlos III (CM19/00188, CD20/00022). The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, and in the writing of the manuscript, or in the decision to publish the results.
Subjects: Fosfato de piridoxal, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Phosphoric Monoester Hydrolases::Alkaline Phosphatase [Medical Subject Headings], Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Metal Metabolism, Inborn Errors::Hypophosphatasia [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], Mutación, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Enzyme Therapy::Enzyme Replacement Therapy [Medical Subject Headings], Pyridoxal-5′-phosphate, Hypophosphatasia, Genotype-phenotype, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Asfotase alfa, TNSALP, Hipofosfatasia, Fosfatasa alcalina, Terapia de reemplazo enzimático
Abstract: Hypophosphatasia (HPP) is a rare genetic disease characterized by a decrease in the activity of tissue non-specific alkaline phosphatase (TNSALP). TNSALP is encoded by the ALPL gene, which is abundantly expressed in the skeleton, liver, kidney, and developing teeth. HPP exhibits high clinical variability largely due to the high allelic heterogeneity of the ALPL gene. HPP is characterized by multisystemic complications, although the most common clinical manifestations are those that occur in the skeleton, muscles, and teeth. These complications are mainly due to the accumulation of inorganic pyrophosphate (PPi) and pyridoxal-50-phosphate (PLP). It has been observed that the prevalence of mild forms of the disease is more than 40 times the prevalence of severe forms. Patients with HPP present at least one mutation in the ALPL gene. However, it is known that there are other causes that lead to decreased alkaline phosphatase (ALP) levels without mutations in the ALPL gene. Although the phenotype can be correlated with the genotype in HPP, the prediction of the phenotype from the genotype cannot be made with complete certainty. The availability of a specific enzyme replacement therapy for HPP undoubtedly represents an advance in therapeutic strategy, especially in severe forms of the disease in pediatric patients. Yes
Published: 2021

21. The role of organization of care in GPs' prevention practice

Author: Raphaëlle Delpech, Isabelle Pendola-Luchel, Pascaline Mourey, Mathilde Baumhauer, Arnaud Gautier, Henri Panjo, Rissane Ourabah, Lorraine Poncet, L. Rigal, Virginie Ringa, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, This project was funded by the French Research Institute in Public Health (IReSP). The funder had no role in the creation of the research question, design of the study, data collection, analysis, interpretation, or in the writing of this manuscript., Santé publique France - French National Public Health Agency [Saint-Maurice, France], Institut national d'études démographiques (INED), Université Paris-Saclay, and HAL UVSQ, Équipe
Subjects: Typology, medicine.medical_specialty, Attitude of Health Personnel, media_common.quotation_subject, [SDV]Life Sciences [q-bio], General Practice, MEDLINE, 03 medical and health sciences, 0302 clinical medicine, Negatively associated, General Practitioners, Surveys and Questionnaires, Health care, Medicine, Humans, 030212 general & internal medicine, Practice Patterns, Physicians', Care Planning, Socioeconomic status, media_common, 030505 public health, business.industry, Addiction, Public Health, Environmental and Occupational Health, Social environment, 3. Good health, [SDV] Life Sciences [q-bio], Family medicine, Global Positioning System, 0305 other medical science, business, Family Practice, Research Article
Abstract: Background: General practitioners (GPs) do not systematically include preventive recommendations in their practice, and some characteristics of health care organization are associated with more systematic prevention. But the characteristics of health care organization may act in a nonuniform manner depending on the type of preventive care. Thus, one characteristic can be positively associated with one type of preventive care and negatively associated with another. Our aim was to investigate the association between health care organization in general practice and different areas of preventive care (immunization and addiction prevention), in search of nonuniform associations. Methods: We used a representative survey of 1,813 French GPs conducted in 2009. Four preventive care practices were studied: immunization through flu and HPV vaccination, and prevention of addictive behaviors concerning tobacco and alcohol use. Characteristics of GPs’ health care organization and the social context of their practice were collected (spatial accessibility to GPs and socioeconomic level of the area of practice). We constructed mixed models to study associations and interactions between the organization variables and preventive care. Results: Four out of five characteristics of GPs’ organization have uneven impacts on different types of preventive care (p-interaction < 10-4). For example, number of daily consultations is associated with better immunization prevention but with poorer prevention counseling in addictive behaviors. In contrast, working with digital medical files is uniformly associated with both types of preventive care (OR = 1.29 [1.15–1.45]; P < 10-4). Conclusion: An approach centered on specific types of preventive care should help deepen our understanding of prevention and possibly help to identify a new typology for preventive care.
Published: 2021
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22. Watch out for a second SNP: focus on multi-nucleotide variants in coding regions and rescued stop-gained

Author: Fabien Degalez, Frédéric Jehl, Kévin Muret, Maria Bernard, Frédéric Lecerf, Laetitia Lagoutte, Colette Désert, Frédérique Pitel, Christophe Klopp, Sandrine Lagarrigue, Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Système d'Information des GENomes des Animaux d'Elevage (SIGENAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique Animale et Biologie Intégrative (GABI), Université Paris-Saclay-AgroParisTech-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French institutions Institut Agro (AGROCAMPUS OUEST) and INRAE [Fr-AgENCODE project (2015–2017) and ELASTICe project (2012)]. FJ, FD, and KM were Ph.D. fellows supported by the Brittany region (France) and the INRAE Animal Genetics division. These funding bodies had no role in the design of the study, in the collection, analysis, and interpretation of data, or in the writing of the manuscript., ANR-11-BSV7-0004,FatInteger,Recherche de régulateurs clefs de la plasticité lipidique chez deux espèces monogastriques majeures (porc et poule) en combinant des données haut débit et des approches statistique, bioinformatique et phylogénique.(2011), ANR-13-ADAP-0014,ChickStress,Mécanismes d'adaptation à la chaleur et à un aliment suboptimal chez la poule pondeuse(2013), ANR-09-GENM-0004,EpiBird,Analyse Epigénétique chez les Oiseaux(2009), European Project: 633531,H2020,H2020-SFS-2014-2,Feed-a-Gene(2015), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: SNP, MNV, Single-nucleotide polymorphism, Computational biology, QH426-470, Biology, 03 medical and health sciences, 0302 clinical medicine, FATP4, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], SLC27A4, rescued stop-gained, Genetics, Coding region, Missense mutation, Gene, Genetics (clinical), Original Research, 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, multi-nucleotide variants (MNV), Potential effect, Molecular Medicine, variation, 030217 neurology & neurosurgery
Abstract: Most single-nucleotide polymorphisms (SNPs) are located in non-coding regions, but the fraction usually studied is harbored in protein-coding regions because potential impacts on proteins are relatively easy to predict by popular tools such as the Variant Effect Predictor. These tools annotate variants independently without considering the potential effect of grouped or haplotypic variations, often called “multi-nucleotide variants” (MNVs). Here, we used a large RNA-seq dataset to survey MNVs, comprising 382 chicken samples originating from 11 populations analyzed in the companion paper in which 9.5M SNPs— including 3.3M SNPs with reliable genotypes—were detected. We focused our study on in-codon MNVs and evaluate their potential mis-annotation. Using GATK HaplotypeCaller read-based phasing results, we identified 2,965 MNVs observed in at least five individuals located in 1,792 genes. We found 41.1% of them showing a novel impact when compared to the effect of their constituent SNPs analyzed separately. The biggest impact variation flux concerns the originally annotated stop-gained consequences, for which around 95% were rescued; this flux is followed by the missense consequences for which 37% were reannotated with a different amino acid. We then present in more depth the rescued stop-gained MNVs and give an illustration in the SLC27A4 gene. As previously shown in human datasets, our results in chicken demonstrate the value of haplotype-aware variant annotation, and the interest to consider MNVs in the coding region, particularly when searching for severe functional consequence such as stop-gained variants.
Published: 2021
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23. Molecular Mimicry: a Paradigm of Host-Microbe Coevolution Illustrated by Legionella

Author: Silke Schmidt, Carmen Buchrieser, Sonia Mondino, Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Work in the C.B. laboratory is financed by the Institut Pasteur, and funding has been received from the French Government (grants ANR-10-LABX-62-IBEID and ANR-15-CE17-0014-03 to C.B.) and the Fondation de la Recherche Médicale (grant EQU201903007847 to C.B.). S.S. is a scholar in the Pasteur-Paris University (PPU) international Ph.D. program and received a stipend from the Institut Pasteur., S.M., S.S., and C.B. contributed to the conception and the design of the minireview. S.M. and S.S. researched and wrote the paper. C.B. directed and contributed to the writing of the manuscript., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-15-CE17-0014,ProgLegio,Biomarqueurs bactériens et humains d'intérêt pronostic pour les légionelloses sévères(2015), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Collège Doctoral
Subjects: Virulence Factors, Legionella, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Computational biology, medicine.disease_cause, Microbiology, Legionella pneumophila, Genome, Host-Microbe Biology, Biological Coevolution, 03 medical and health sciences, Bacterial Proteins, Virology, medicine, Humans, host-pathogen interactions, molecular mimicry, Gene, Coevolution, 030304 developmental biology, 0303 health sciences, Host Microbial Interactions, biology, 030306 microbiology, Host (biology), biology.organism_classification, eukaryotic-like proteins, QR1-502, Molecular mimicry, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, amoeba-resistant bacteria, Identification (biology), Minireview, Genome, Bacterial, Function (biology)
Abstract: Through coevolution with host cells, microorganisms have acquired mechanisms to avoid the detection by the host surveillance system and to use the cell’s supplies to establish themselves. Indeed, certain pathogens have evolved proteins that imitate specific eukaryotic cell proteins, allowing them to manipulate host pathways, a phenomenon termed molecular mimicry. Bacterial “eukaryotic-like proteins” are a remarkable example of molecular mimicry. They are defined as proteins that strongly resemble eukaryotic proteins or that carry domains that are predominantly present in eukaryotes and that are generally absent from prokaryotes., Through coevolution with host cells, microorganisms have acquired mechanisms to avoid the detection by the host surveillance system and to use the cell’s supplies to establish themselves. Indeed, certain pathogens have evolved proteins that imitate specific eukaryotic cell proteins, allowing them to manipulate host pathways, a phenomenon termed molecular mimicry. Bacterial “eukaryotic-like proteins” are a remarkable example of molecular mimicry. They are defined as proteins that strongly resemble eukaryotic proteins or that carry domains that are predominantly present in eukaryotes and that are generally absent from prokaryotes. The widest diversity of eukaryotic-like proteins known to date can be found in members of the bacterial genus Legionella, some of which cause a severe pneumonia in humans. The characterization of a number of these proteins shed light on their importance during infection. The subsequent identification of eukaryotic-like genes in the genomes of other amoeba-associated bacteria and bacterial symbionts suggested that eukaryotic-like proteins are a common means of bacterial evasion and communication, shaped by the continuous interactions between bacteria and their protozoan hosts. In this review, we discuss the concept of molecular mimicry using Legionella as an example and show that eukaryotic-like proteins effectively manipulate host cell pathways. The study of the function and evolution of such proteins is an exciting field of research that is leading us toward a better understanding of the complex world of bacterium-host interactions. Ultimately, this knowledge will teach us how host pathways are manipulated and how infections may possibly be tackled.
Published: 2020
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24. Use of mental health supports by civilians exposed to the November 2015 terrorist attacks in Paris

Author: Stéphanie Vandentorren, Yvon Motreff, Maude Marillier, Gabrielle Rabet, Thierry Baubet, Cécile Vuillermoz, Lise Eilin Stene, Antoine Messiah, Philippe Pirard, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ministère des Affaires Sociales et de la Santé PIA ANR-10-EQPX-0021-01 Norges Forskningsråd: 288321, and This study was performed by Santé publique France as part of its remit. Santé publique France is funded by the French Ministry of Health. The ESPA 13 November survey is part of EQUIPEX Matrice’s '13 November' transdisciplinary research programme which is funded by the French General Secretariat for investment (SGPI) via the National Research Agency (ANR) and its 'Programme d’Investissement pour l’Avenir' (PIA ANR-10-EQPX-0021-01). PP, YM, GR, MM and SV are employees of Santé publique France. AM and TB are employees of the 'Institut National de la Santé et de la Recherche Médicale'. The contributions from LES and CV were funded by The Research Council of Norway (p.nr. 288321). The funding bodies had no role in the design of the study, data collection, data analysis, data interpretation or in the writing of the manuscript. Acknowledgments
Subjects: Adult, Male, medicine.medical_specialty, Paris, Referral, Health care use, Anxiety, Hospital Anxiety and Depression Scale, Health administration, Stress Disorders, Post-Traumatic, 03 medical and health sciences, 0302 clinical medicine, General Practitioners, Health service research, medicine, Humans, 030212 general & internal medicine, Psychiatry, Depression (differential diagnoses), Psychiatric Status Rating Scales, business.industry, Depression, lcsh:Public aspects of medicine, Health Policy, Public health, Post-traumatic, lcsh:RA1-1270, Middle Aged, Mental health, Stress disorders, Psychological first aid, Checklist, Mental health outreach, 3. Good health, 030227 psychiatry, Mental health services, Disaster medicine, Terrorist attacks, Female, Terrorism, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, Specialization, Research Article
Abstract: BackgroundThe use of mental health supports by populations exposed to terrorist attacks is rarely studied despite their need for psychotrauma care. This article focuses on civilians exposed to the November 2015 terrorist attacks in Paris and describes the different combinations of mental health supports (MHSu) used in the following year according to type of exposure and type of mental health disorder (MHD).MethodsSanté publique Franceconducted a web-based survey of civilians 8–11 months after their exposure to the November 2015 terrorist attacks in Paris. All 454 respondents met criterion A of the DSM-5 definition of post-traumatic stress disorder (PTSD). MHD (anxiety, depression, PTSD) were assessed using the PCL-5 checklist and the Hospital Anxiety and Depression Scale. MHSu provided were grouped under outreach psychological support, visits for psychological difficulties to a victims’ or victim support association, consultation with a general practitioner (GP), consultation with a psychiatrist or psychologist (specialist), and initiation of regular mental health treatment (RMHT). Chi-squared tests highlighted differences in MHSu use according to type of exposure (directly threatened, witnessed, indirectly exposed) and MHD. Phi coefficients and joint tabulations were employed to analyse combinations of MHSu use.ResultsTwo-thirds of respondents used MHSu in the months following the attacks. Visits to a specialist and RMHT were more frequent than visits to a GP (respectively, 39, 33, 17%). These were the three MHSu most frequently used among people with PTSD (46,46,23%), with depression (52,39,20%), or with both (56,58, 33%). Witnesses with PTSD were more likely not to have RMHT than those directly threatened (respectively, 65,35%). Outreach support (35%) and visiting an association (16%) were both associated with RMHT (Phi = 0.20 and 0.38, respectively). Very few (1%) respondents initiated RMHT directly. Those who indirectly initiated it (32%) had taken one or more intermediate steps. Visiting a specialist, not a GP, was the most frequent of these steps.ConclusionOur results highlight possibilities for greater coordination of mental health care after exposure to terrorist attacks including involving GP for screening and referral, and associations to promote targeted RMHT. They also indicate that greater efforts should be made to follow witnesses.
Published: 2020
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25. Nocturia in patients with cognitive dysfunction: a systematic review of the literature

Author: Véronique Phé, Charles Joussain, Karel Everaert, Rebecca Haddad, Thomas F. Monaghan, G. Robain, Saskia Roggeman, Wendy Bower, Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine physique et réadaptation [CHU Raymond-Poincaré], Hôpital Raymond Poincaré [AP-HP], Sorbonne Université - Département de neurologie 2 - Mazarin, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), SociÃ©tÃ© FranÃ§aise de MÃ©decine Vasculaire, SFMV, and RH reports grants from, Fonds de dotation Renaitre, Société Française de Médecine Physique et de Réadaptation with the institutional support of Merz Pharma France and Société Interdisciplinaire Francophone d’UroDynamique et de Pelvi Périnéologie. Authors independently conceptualized the design, methods, data collection, analysis and writing of the manuscript and grants did not influence the content.
Subjects: medicine.medical_specialty, Epidemiology, IMPACT, medicine.medical_treatment, 030232 urology & nephrology, MEDLINE, lcsh:Geriatrics, urologic and male genital diseases, FREQUENCY, 03 medical and health sciences, 0302 clinical medicine, Cognitive dysfunction, Lower urinary tract symptoms, Medicine and Health Sciences, medicine, QUALITY, Nocturia, TERMINOLOGY, RISK, Rehabilitation, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, MORTALITY, Confounding, Cognition, STANDARDIZATION, medicine.disease, SLEEP, female genital diseases and pregnancy complications, OVERACTIVE BLADDER, PREVALENCE, 3. Good health, lcsh:RC952-954.6, Systematic review, Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery, Research Article, Clinical psychology
Abstract: Background The objective of this study is to evaluate current literature on the association between cognitive dysfunction and nocturia. Methods A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was conducted through MEDLINE, EMBASE and COCHRANE databases and completed in November 2019. Randomized and non-randomized studies were included if they assessed the association between cognitive dysfunction and nocturia in older participants with or without neurological diseases. The quality of included studies was evaluated using the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS). Results A total of 8 cross-sectional studies conducted in older patient populations met the criteria for inclusion. A statistically significant association was identified in 6 studies on univariate analysis, which persisted in 2 studies after controlling for confounding factors. The association between cognitive dysfunction and nocturia was positive for all 6 significant analyses. The overall risk of bias was unclear. Conclusion A significant positive association between cognitive dysfunction and nocturia was identified. However, research has been limited to cross-sectional studies, which precludes identification of causality between cognitive dysfunction and nocturia. Heightened awareness of the complex interplay between cognition and nocturia would allow professionals involved in the care of cognitively impaired patients with concomitant nocturia to more effectively manage these symptoms.
Published: 2020
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26. The I-MICRO trial, Ilomedin for treatment of septic shock with persistent microperfusion defects: a double-blind, randomized controlled trial-study protocol for a randomized controlled trial

Author: Marc Leone, Jacques Duranteau, Eric Vicaut, François Dépret, Daniel De Backer, Matthieu Legrand, Bruno Levy, Patrick Rossignol, Hafid Ait Oufella, Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of California [San Francisco] (UCSF), University of California, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Interrégional Edith Cavell (CHIREC), Hôpitaux Universitaires Paris Sud, Hôpital Nord AP‐MM Marseille, France (AP‐MM Marseille), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The study is funded by a grant from the Programme Hospitalier de Recherche Clinique - PHRC National 2017 from the French Minister of Health. The funding body has no role in the design of the study, collection, analysis, and interpretation of the data, and writing of the manuscript., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of California [San Francisco] (UC San Francisco), University of California (UC), Service d'Anesthésie réanimation [CHU Saint-Antoine], CHU Saint-Antoine [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), Université libre de Bruxelles (ULB), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Assistance Publique - Hôpitaux de Marseille (APHM), Université de Lorraine (UL), and BOZEC, Erwan
Subjects: Inotrope, Resuscitation, Organ Dysfunction Scores, Vasodilator Agents, Medicine (miscellaneous), Cardiorespiratory Medicine and Haematology, Pharmacologie, Capillary refill time, law.invention, Prostacyclin, Study Protocol, 0302 clinical medicine, Randomized controlled trial, law, Vasodilator, Multicenter Studies as Topic, Pharmacology (medical), 030212 general & internal medicine, Prospective Studies, Infusions, Intravenous, Randomized Controlled Trials as Topic, Outcome, lcsh:R5-920, Shock, Hematology, Sciences bio-médicales et agricoles, Shock, Septic, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Phase III as Topic, Treatment Outcome, Anesthesia, 6.1 Pharmaceuticals, SOFA score, France, medicine.symptom, I-MICRO trial investigators, Intravenous, lcsh:Medicine (General), Infusions, Randomization, Clinical Trials and Supportive Activities, Clinical Sciences, Skin mottling, Sepsis, 03 medical and health sciences, Double-Blind Method, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Clinical Research, General & Internal Medicine, medicine, Humans, Clinical Trials, Iloprost, Septic shock, business.industry, Septic, Microcirculation, Organ dysfunction, Hemodynamics, Evaluation of treatments and therapeutic interventions, 030208 emergency & critical care medicine, medicine.disease, Clinical Trials, Phase III as Topic, Cardiovascular System & Hematology, business
Abstract: Background: Septic shock remains a significant cause of death in critically ill patients. During septic shock, some patients will retain microcirculatory disorders despite optimal hemodynamic support (i.e. fluid resuscitation, vasopressors, inotropes). Alterations in the microcirculation are a key pathophysiological factor of organ dysfunction and death in septic shock patients. Ilomedin is a prostacyclin analog with vasodilatory effect and anti-Thrombotic properties (i.e. inhibition of platelet aggregation) preferentially at the microcirculatory level. We hypothesize that early utilization of intravenous Ilomedin in septic shock patients with clinical persistence of microperfusion disorders would improve the recovery of organ dysfunction. Methods: The I-MICRO trial is a multicenter, prospective, randomized, double-blinded, placebo-controlled study. We plan to recruit 236 adult patients with septic shock and persistent microcirculatory disorders (i.e. skin mottling or increased capillary refill time) despite hemodynamic support. Participants will be randomized to receive a 48-h intravenous infusion of either Ilomedin or placebo starting at the earliest 6 h and later 24 h after septic shock. The primary outcome will be the change (delta) of sequential organ failure assessment (SOFA) score between randomization and day 7. Secondary outcomes will include mean SOFA score during the first 7 days after randomization, mortality at day 28 post-randomization, number of ventilation-free survival days in the 28 days post-randomization, number of renal replacement therapy-free survival days in the 28 days post-randomization, number of vasopressor-free survival days in the 28 days post-randomization, and mottling score at day 1 after randomization. Discussion: The trial aims to provide evidence on the efficacy and safety of Ilomedin in patients with septic shock and persistent microcirculatory disorders. Trial registration: NCT NCT03788837. Registered on 28 December 2018, SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2020
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27. Klebsiella pneumoniae carriage in low-income countries: antimicrobial resistance, genomic diversity and risk factors

Author: Jean-Marc Collard, Perlinot Herindrainy, Raymond Bercion, Didier Guillemot, Maria Pardos de la Gandara, Andriniaina Rakotondrasoa, Benoit Garin, Elisabeth Delarocque-Astagneau, Agathe de Lauzanne, Melanie Hennart, Sylvain Brisse, Carla Rodrigues, Virginie Passet, Thierno Abdoulaye Diallo, Muriel Vray, Bich-Tram Huynh, Alexandra Kerleguer, Laurence Borand, Abdoulaye Seck, Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris], Unité de Bactériologie Expérimentale [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur du Cambodge, Institut Pasteur de Bangui, Centre National de Référence - National Reference Center Escherichia coli, Shigella et Salmonella (CNR-ESS), This work was supported by the Institut Pasteur programme Action Concertee Inter-Pasteurienne (Grant A-14-2014) and by the French government’s Investissement d’Avenir program Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant ANR-10-LABX-62-IBEID). Support to the BIRDY project was provided by the Total Foundation, MSDAVENIR and the Monaco Department of International Cooperation. CR was supported financially by the MedVetKlebs project, a component of European Joint Programme One Health EJP, which has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 773830. The funders had no role in study design, data collection and analysis, interpretation, or writing of the manuscript., We thank all collaborators of the BIRDY program: Rasoanaivo Fanjalalaina Vololonirina, Andrianonimiadana Lova Maminirina, Rabearitiana Lydos, Rasoloson Dimitri, Randrianirina Frédérique, Ratsima Hariniaina Elisoa, Volahasina Antsa Tanjona, Volahasina Antso Fenitra, Randriamamonjiarison Aina Nirina, Andrianirina Zafitsara Zo, Andriatahina Todisoa, Vincent Richard, Awa Ndir, Amy Gassama Sow, Balla Sy, Marguerite Diatta, Pape Samba Dieye, Jean Baptiste Diouf, Joseph Faye, Abibatou Ndiaye, Bouya Ndao, Thida Chon, Veronique Ngo, Arnaud Tarantola, Sok Touch, Patrice Piola, Sophie Goyet, Siyin Lach, Elsa Kermorvant-Duchemin, Michael Padget, Laurence Watier, and Abdou Armya Youssouf. We thank all physicians, laboratory staff, field interviewers, and community workers involved in the project. We thank Leonardo Panunzi for assistance with genomic analyses of resistance genes, and the 'Plateforme de Microbiologie Mutualisée' of Institut Pasteur for genomic sequencing. We are grateful to all women participating in the BIRDY program., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health EJP)(2018), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health)(2018), Moulherat, Isabelle, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and Klebsiella pneumoniae: from ecology to source attribution and transmission control - MedVetKlebs (a component of European Joint Programme One Health) - - H2020-SFS-2017-12018-01-01 - 2019-12-31 - 773830 - VALID
Subjects: 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, antibiotic resistance, Klebsiella pneumoniae, media_common.quotation_subject, Developing country, RC799-869, Biology, Microbiology, genomic diversity, 03 medical and health sciences, 0302 clinical medicine, Antibiotic resistance, low-income countries, medicine, media_common, carriage, 2. Zero hunger, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Public health, Gastroenterology, Diseases of the digestive system. Gastroenterology, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Multiple drug resistance, 030104 developmental biology, Infectious Diseases, Carriage, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Research Paper/Report, community, 030211 gastroenterology & hepatology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Diversity (politics), Research Article
Abstract: The genomic sequencing data were deposited in the NCBI/ENA/DDBJ databases and are accessible via the BioProject PRJEB29143; International audience; Klebsiella pneumoniae (hereafter, Kp) is a major public health threat responsible for high levels of multidrug resistant (MDR) human infections. Besides, Kp also causes severe infections in the community, especially in Asia and Africa. Although most Kp infections are caused by endogenous intestinal carriage, little is known about the prevalence and microbiological characteristics of Kp in asymptomatic human carriage, and attached risk factors including environmental sources exposure. Here, 911 pregnant women from communities in Madagascar, Cambodia, and Senegal were screened for gut colonization by Kp. Characteristics of Kp strains (antimicrobial susceptibility, genomic diversity, virulence, and resistance genes) were defined, and associated risk factors were investigated.Kp carriage rate was 55.9%, and Kp populations were highly heterogeneous (6 phylogroups, 325 sequence types, Simpson index 99.6%). One third of Kp isolates had acquired antimicrobial resistance genes. MDR-Kp (11.7% to 39.7%) and extended spectrum beta-lactamase (ESBL)-producing Kp (0.7% to 14.7%) varied among countries. Isolates with virulence genes were detected (14.5%). Environmental exposure factors including food, animal contacts, or hospitalization of household members were associated with carriage of Kp, antimicrobial resistance and hypervirulence. However, risk factors were country-specific and Kp subpopulation-specific.This large-scale multicenter study uncovers the huge diversity of Kp in human gut carriage, demonstrates that antimicrobial resistance is widespread in communities of three low-income countries, and underlines the challenges posed by Kp colonization to the control of antimicrobial
Published: 2020
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28. Adherence to the Mediterranean Lifestyle and Desired Body Weight Loss in a Mediterranean Adult Population with Overweight: A PREDIMED-Plus Study

Author: Josep A. Tur, Itziar Abete, José J. Gaforio, Jordi Salas-Salvadó, Nerea Becerra-Tomás, Francisco J. Tinahones, Albert Goday, Xavier Pintó, Maria Dolors Zomeño, Julia Wärnberg, Alejandro Oncina-Canovas, Carmen Saiz, Jessica Pérez-López, Dolores Corella, Clotilde Vázquez, Lucas Tojal-Sierra, Leyre Notario-Barandiaran, Marga Morey, Lidia Daimiel, Aurora Bueno-Cavanillas, José Manuel Santos-Lozano, José Lapetra, F. Javier Basterra-Gortari, Julia Muñoz, Alicia Julibert, Marian Martín, M. Rosa Bernal-Lopez, Sara Castro-Barquero, Ana Galera, Josep Vidal, Vicente Martín-Sánchez, Miguel Ruiz-Canela, Maria C Belló-Mora, Emilio Ros, Ignacio M. Gimenez-Alba, Antonio García Ríos, Tamara Casañas-Quintana, Ángel M. Alonso-Gómez, Jesús García-Gavilán, Josep Basora, Jesús Vioque, Ramon Estruch, Dora Romaguera, Luis Serra-Majem, Cesar I Fernandez-Lazaro, Pilar Matía-Martín, Escarlata Angullo-Martinez, Cristina Bouzas, Carmen Sayón-Orea, J. Alfredo Martínez, Olga Castañer, Maria del Mar Bibiloni, [Bouzas,C, Bibiloni,MM, Julibert,A, Ruiz-Canela,M, Salas-Salvadó,J, Corella,D, Zomeño,MD, Romaguera,D, Alonso-Gómez,ÁM, Wärnberg,J, Martínez,JA, Serra-Majem,L, Estruch,R, Tinahones,FJ, Lapetra,J, Pintó,X, García Ríos,A, Vázquez,C, Ros,E, Fernandez-Lázaro,CI, Becerra-Tomás,N, Gimenez-Alba,IM, Muñoz,J, Morey,M, Pérez-López,J, Abete,I, Casañas-Quintana,T, Castro-Barquero,S, Bernal-López,MR, Santos-Lozano,JM, Galera,A, Angullo-Martinez,E, Basterra-Gortari,FJ, Basora,J, Saiz,C, Castañer,O, Martín,M, Belló-Mora,MC, Sayón-Orea,C, García-Gavilán,J, Goday,A, Tur,JA] CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Bouzas,C, Tojal-Sierra,L, Tur,JA] Research Group on Community Nutrition & Oxidative Stress, University of Balearic Islands, Guillem Colom Bldg, Campus, Palma de Mallorca, Spain. [Bouzas,C, Tur,JA] Health Research Institute of the Balearic Islands (IdISBa), Palma de Mallorca, Spain. [Ruiz-Canela,M, Sayón-Orea,C] Department of Preventive Medicine and Public Health, IdISNA, University of Navarra, Pamplona, Spain. [Salas-Salvadó,J, García-Gavilán,J] Universitat Rovira i Virgili, Department of Biochemistry and Biotechnology, Human Nutrition Unit, Reus, Spain. [Salas-Salvadó,J] Institut d’Investigació Sanitària Pere Virgili (IISPV), Reus, Spain. [Corella,D, Saiz,C] Department of Preventive Medicine, University of Valencia, Valencia, Spain. [Zomeño,MD, Goday,A] Unit of Cardiovascular Risk and Nutrition, Institut Hospital del Mar de Investigaciones Médicas Municipal d’Investigació Mèdica (IMIM), Barcelona, Spain. [Zomeño,MD] Blanquerna School of Health Sciences, Universitat Ramon Llull, Barcelona, Spain. [Vioque,J, Oncina-Canovas,A, Notario-Barandiarán,L] Unit of Nutritional Epidemiology, Miguel Hernández University, ISABIAL-UMH, Alicante, Spain. [Vioque,J, Bueno-Cavanillas,A, Gaforio,JJ, Notario-Barandiarán,L] CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Alonso-Gómez,ÁM, Belló-Mora,MC] Bioaraba Health Research Institute, Osakidetza Basque Health Service, Araba University Hospital, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain. [Wärnberg,J, Pérez-López,J] Department of Nursing, School of Health Sciences, University of Málaga-IBIMA, Málaga, Spain. [Martínez,JA] Precision Nutrition Program, IMDEA Food, CEI UAM + CSIC, Madrid, Spain. [Martínez,JA, Abete,I] Department of Nutrition, Food Sciences, and Physiology, Center for Nutrition Research, University of Navarra, Pamplona, Spain. [Serra-Majem,L, Casañas-Quintana,T] Institute for Biomedical Research, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain. [Estruch,R, Castro-Barquero,S] Department of Internal Medicine, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain. [Tinahones,FJ, Bernal-López,MR] Virgen de la Victoria Hospital, Department of Endocrinology, Biomedical Research Institute of Málaga (IBIMA), University of Málaga, Málaga, Spain. [Lapetra,J, Santos-Lozano,JM] Department of Family Medicine, Research Unit, Distrito Sanitario Atención Primaria Sevilla, Sevilla, Spain. [Pintó,X, Galera,A] Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain. [García Ríos,A] Lipids and Atherosclerosis Unit, Department of Internal Medicine, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. [Bueno-Cavanillas,A] Department of Preventive Medicine, University of Granada, Granada, Spain. [Gaforio,JJ] Department of Health Sciences, Centro de Estudios Avanzados en Olivar y Aceites de Oliva, University of Jaen, Jaen, Spain. [Matía-Martín,P] Department of Endocrinology and Nutrition, Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC), Madrid, Spain. [Daimiel,L] Nutritional Genomics and Epigenomics Group, IMDEA Food, CEI UAM + CSIC, Madrid, Spain. [Martín-Sánchez,V] CIBER Diabetes y Enfermedades Metabólicas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Martín-Sánchez,V] Institute of Biomedicine (IBIOMED), University of León, León, Spain. [Vidal,J] Department of Endocrinology, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain. [Vázquez,C] Department of Endocrinology, Fundación Jiménez-Díaz, Madrid, Spain. [Ros,E] Lipid Clinic, Department of Endocrinology and Nutrition, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain. [Angullo-Martinez,E] Escola Graduada Primary Health Care Center, IBSalut, Palma de Mallorca, Spain. [Basterra-Gortari,FJ, Sayón-Orea,C] Servicio Navarro de Salud, Osasunbidea, Pamplona, Spain., The PREDIMED-Plus trial was supported by the official funding agency for biomedical research of the Spanish government, ISCIII, through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (five coordinated FIS projects led by J.S.-S. and J.Vidal, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, and PI19/01332, the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to J.S.-S., the European Research Council (Advanced Research Grant 2013–2018, 340918) to Miguel Ángel Martínez-González, the Recercaixa Grant to J.S.-S. (2013ACUP00194), Grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018), a Grant from the Generalitat Valenciana (PROMETEO/2017/017), a SEMERGEN Grant, EU-COST Action CA16112, a Grant of support to research groups no. 35/2011 from the Balearic Islands Government, Grants from Balearic Islands Health Research Institute (IDISBA), funds from the European Regional Development Fund (CIBEROBN CB06/03 and CB12/03) and from the European Commission (EAT2BENICE_H2020_SFS2016). M. Rosa Bernal-López was supported by 'Miguel Servet Type I' program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the European Regional Development Fund. Jordi Salas-Salvadó is partially supported by ICREA under the ICREA Academia programme. Cristina Bouzas received a Fernando Tarongí Bauzà PhD Grant. I.M Gimenez-Alba received a grant FPU from the Ministry of Science, Innovation and Univesities (reference FPU 18/01703). The funding sponsors had no role in the design of the study, in the collection, analyses, or interpretation of the data, and in the writing of the manuscript, and in the decision to publish the results.
Subjects: Male, Mediterranean diet, Obesidad, ejercicio físico, Body Mass Index, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Surveys and Questionnaires, Antineoplastic Combined Chemotherapy Protocols, Medicine, mediana edad, education.field_of_study, anciano, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Age Factors [Medical Subject Headings], dieta, protocolos de quimioterapia antineoplásica combinada, 3. Good health, Older adults, metotrexato, programas de reducción de peso, Obesitat, lcsh:Nutrition. Foods and food supply, Personas mayores frágiles, Ideal weight, Lifestyles, Check Tags::Male [Medical Subject Headings], lcsh:TX341-641, Article, Estilo de vida, 03 medical and health sciences, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Size::Body Weight::Overweight [Medical Subject Headings], Anthropology, Education, Sociology and Social Phenomena::Human Activities::Exercise [Medical Subject Headings], ifosfamida, Humans, cisplatino, Ifosfamide, education, Exercise, Aged, conducta alimentaria, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Metabolic Syndrome X [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], PREDIMED-Plus, medicine.disease, Obesity, Methotrexate, Check Tags::Female [Medical Subject Headings], Desired weight loss, Metabolic syndrome, Cisplatin, Body mass index, Demography, obesity, cumplimiento del paciente, humanos, Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Ideal Body Weight, desired weight loss, Health Care::Health Care Facilities, Manpower, and Services::Health Promotion::Weight Reduction Programs [Medical Subject Headings], Overweight, Diet, Mediterranean, Mediterranean lifestyle, Health Care::Health Care Facilities, Manpower, and Services::Health Services::Preventive Health Services::Health Promotion::Healthy People Programs [Medical Subject Headings], Weight loss, 030212 general & internal medicine, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Health Behavior::Patient Compliance [Medical Subject Headings], Abdominal obesity, older adults, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], 2. Zero hunger, Nutrition and Dietetics, mediterranean lifestyle, sobrepeso, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Nutrition Therapy::Diet Therapy::Diet, Mediterranean [Medical Subject Headings], Age Factors, ideal weight, Middle Aged, Peso corporal ideal, Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weight::Ideal Body Weight [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], Weight Reduction Programs, Body image, Female, medicine.symptom, peso corporal ideal, Estils de vida, doxorrubicina, body image, Population, Imagen corporal, 030209 endocrinology & metabolism, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Feeding Behavior [Medical Subject Headings], overweight, Healthy Lifestyle, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, índice de masa corporal, Feeding Behavior, Dieta mediterránea, Diet, Doxorubicin, Sobrepeso, Patient Compliance, Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Perception::Body Image [Medical Subject Headings], business, Food Science
Abstract: Background. Body weight dissatisfaction is a hindrance to following a healthy lifestyle and it has been associated with weight concerns. Objectives. The aim of this study was to assess the association between the adherence to the Mediterranean lifestyle (diet and exercise) and the desired body weight loss in an adult Mediterranean population with overweight. Methods. Cross-sectional analysis in 6355 participants (3268 men; 3087 women) with metabolic syndrome and BMI (Body mass index) between 27.0 and 40.0 kg/m2 (55–75 years old) from the PREDIMED-Plus trial. Desired weight loss was the percentage of weight that participants wished to lose. It was categorized into four cut-offs of this percentage (Q1, European Research Council (ERC) 340918, Recercaixa Grant 2013ACUP00194, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, Generalitat Valenciana PROMETEO/2017/017, SEMERGEN Grant, European Union (EU) European Cooperation in Science and Technology (COST) CA16112, Balearic Islands Government 35/2011, Balearic Islands Health Research Institute (IDISBA), European Union (EU) CIBEROBN CB06/03 CB12/03 PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056, European Commission Joint Research Centre EAT2BENICE_H2020_SFS2016, "Miguel Servet Type I" program from the ISCIII-Madrid (Spain) CP15/00028, ICREA under the ICREA Academia programme, Fernando Tarongi Bauza PhD Grant, FPU from the Ministry of Science, Innovation and Univesities FPU 18/01703, Spanish government, ISCIII, through the Fondo de Investigacion para la Salud (FIS), Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332
Published: 2020

29. Gene expression regulated by abatacept associated with methotrexate and correlation with disease activity in rheumatoid arthritis

Author: Gaelle Dzangue-Tchoupou, Olivier Vittecoq, Céline Derambure, Maria Antonietta D'Agostino, Thierry Lequerré, Bodescot, Myriam, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré [AP-HP], Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), The APPRAISE trial was funded by Bristol-Myers Squibb and this ancillary study was funded by Bristol-Myers Squibb which was involved in the design of the study as well as in the collection of clinical data and biological samples, in the interpretation of data, in the writing of this manuscript and in the decision to submit the manuscript for publication. This does not alter our adherence to PLOS ONE policies on sharing data and materials., and Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Male, 0301 basic medicine, Oncology, Cell signaling, Settore MED/16 - REUMATOLOGIA, Gene Expression, Arthritis, Apoptosis, Signal transduction, medicine.disease_cause, Biochemistry, Autoimmunity, Arthritis, Rheumatoid, White Blood Cells, 0302 clinical medicine, Animal Cells, Rheumatoid, Medicine and Health Sciences, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Multidisciplinary, TCR signaling cascade, Cell Death, T Cells, Signaling cascades, CD28, Middle Aged, C-Reactive Proteins, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Cell Processes, Antirheumatic Agents, Rheumatoid arthritis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Medicine, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Cellular Types, Research Article, medicine.drug, musculoskeletal diseases, medicine.medical_specialty, Science, Immune Cells, T cell, Immunology, Motor Proteins, Cytotoxic T cells, Rheumatoid Arthritis, Autoimmune Diseases, Abatacept, 03 medical and health sciences, Rheumatology, Molecular Motors, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, medicine, Humans, 030203 arthritis & rheumatology, Blood Cells, business.industry, Biology and Life Sciences, Proteins, Cell Biology, medicine.disease, Methotrexate, 030104 developmental biology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Clinical Immunology, Clinical Medicine, Transcriptome, business, CD80
Abstract: International audience; Objectives: Abatacept acts as a competitive inhibitor of the CD28/(CD80/86) costimulation signal required for T cell activation. Mechanisms of action of abatacept have not been fully investigated. The objective of this study was to provide detailed insight into the mode of action of Abatacept based on gene expression data. Methods: In this ancillary study from the APPRAISE trial, we investigated the global molecular effects of Abatacept in whole blood samples collected prospectively in biologic naive rheumatoid arthritis patients (n = 19) at baseline and 6 months after the initiation of Abatacept therapy concomitant with methotrexate. Whole human genome microarrays (4x44K) were performed on both baseline and 6-month samples from responders and non-responders patients categorized according to EULAR criteria. T-test with Benjamini-Hochberg correction was performed to identify significant gene expression changes. Gene Ontology and Single Experiment Analysis tools allowed us to highlight specific biological mechanisms involved in methotrexate/Abatacept. Results: In methotrexate/Abatacept responders, 672 genes were significantly (q
Published: 2020
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30. Potential Therapeutic Effects of the Neural Stem Cell-Targeting Antibody Nilo1 in Patient-Derived Glioblastoma Stem Cells

Author: Rackov G., Iegiani G., Uribe D., Quezada C., Belda-Iniesta C., Escobedo-Lucea C., Silva A., Puig P., González-Rumayor V., Ayuso-Sacido Á. and We thank Rafael Samaniego from the Confocal Microscopy Unit (Instituto de Investigaci?n Sanitaria Gregorio Mara?on, Madrid, Spain) and Josefa Carri?n-Navarro for technical help. Funding. This work was funded by the Spanish Ministry of Economy, Industry and Competitivity (RTC-2015-3846-1) grant to ?A-S and VG-R, ?Fondo de Investigaciones Sanitarias? (FIS) (PI17-01489), and the Miguel Servet program (CP11/00147 and CPII16/00056) from the Instituto de Salud Carlos III to ?A-S. GR holds postdoctoral Juan de la Cierva Fellowship. GI was funded by Erasmus program. DU holds Doctorado Nacional CONICYT fellowship. CQ was funded by FONDECYT (N? 1160777). None of the funding institutions had the role in the design of the study and collection, analysis and interpretation of the data, and writing of the manuscript.
Published: 2020

31. The effect of an online exercise programme on bone health in paediatric cancer survivors (iBoneFIT): study protocol of a multi-centre randomized controlled trial

Author: Francisco Jesus Llorente-Cantarero, Manuel Arroyo-Morales, Maria C. Vicho-González, Maria J. Ortega-Acosta, Francisco B. Ortega, Luis Gracia-Marco, Dimitris Vlachopoulos, Vicente Martínez-Vizcaíno, Ana I. Benito-Bernal, Manuel Muñoz-Torres, Esther Ubago-Guisado, Idoia Labayen, Jonatan R. Ruiz, Juan F. Pascual-Gázquez, Maria Elena Mateos, Maria J. Sánchez, Jose J. Gil-Cosano, Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa. ISFOOD - Institute for Innovation and Sustainable Development in Food Chain, Universidad Pública de Navarra. Departamento de Ciencias de la Salud, Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila, [Gil-Cosano,JJ, Ubago-Guisado,E, Ortega,FB, Ruiz,JR, Gracia-Marco,L] PROFITH 'PROmoting FITness and Health through Physical Activity' Research Group, Sport and Health University Research Institute (iMUDS), Department of Physical Education and Sports, Faculty of Sport Sciences, University of Granada, Granada, Spain. [Sánchez,MJ] Andalusian School of Health (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria Ibs.GRANADA, Granada, Spain. [Sánchez,MJ] CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Sánchez,MJ] Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain. [Ortega-Acosta,MJ, Pascual-Gázquez,JF] Servicio de Pediatría y Oncohematología Pediátricas, Hospital Universitario Virgen de las Nieves, Granada, Spain. [Mateos,ME, Vicho-González,MC] Pediatric Oncology Unit, Department of Pediatrics, Reina Sofia University Hospital, Córdoba, Spain. [Mateos,ME, Llorente-Cantarero,FJ] Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Córdoba, Spain. [Benito-Bernal,AI] Hospital Infantil Universitario Niño Jesús, Madrid, Spain. [Llorente-Cantarero,FJ] CIBEROBN, (Physiopathology of Obesity and Nutrition) Institute of Health Carlos III (ISCIII), Madrid, Spain. [Llorente-Cantarero,FJ] Department of Specific Didactics, Faculty of Education, University of Córdoba, Córdoba, Spain. [Labayen,I] Institute for Innovation and Sustainable Development in Food Chain (IS-FOOD), Navarra’s Health Research Institute (IdiSNA), Department of Health Sciences, Public University of Navarra, Pamplona, Navarra, Spain. [Martinez-Vizcaino,V] Universidad de Castilla-La Mancha, Health and Social Research Center, Cuenca, Spain. [Martinez-Vizcaino,V] Faculty of Health Sciences, Universidad Autónoma de Chile, Talca, Chile. [Vlachopoulos,D] Children’s Health and Exercise Research Centre, Sport and Health Sciences, University of Exeter, Exeter, UK. [Arroyo-Morales, M] Biohealth Research Institute in Granada (ibs.GRANADA), Granada, Spain. [Arroyo-Morales, M] Department of Physiotherapy, University of Granada, Granada, Spain. [Arroyo-Morales, M] 'Cuídate' Support Unit for Oncology Patients (UAPO), Sport and Health University Research Institute (iMUDS), Granada, Spain. [Muñoz-Torres,M] Bone Metabolic Unit, Endocrinology and Nutrition Division, Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria de Granada (Ibs.GRANADA), Granada, Spain. [Muñoz-Torres,M] CIBERFES, Instituto de Salud Carlos III, Madrid, Spain. [Muñoz-Torres,M] Department of Medicine, Universidad de Granada, Granada, Spain., The iBoneFIT project is funded by a fellowship from 'la Caixa' Foundation (ID 100010434). The fellowship code is LCF/BQ/PR19/11700007. This study has been partially supported by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence, and Unit of Excellence on Exercise and Health (UCEES), and by the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and European Regional Development Fund (ERDF), ref. SOMM17/6107/UGR. The funders had no role in the design of this study, in the collection, analyses or interpretation of the data, in the writing of the manuscript or in the decision to submit the manuscript for publication.
Subjects: Male, Calidad de vida, Physical fitness, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Methods::Research Design [Medical Subject Headings], law.invention, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Study Protocol, 0302 clinical medicine, Quality of life, Randomized controlled trial, Cancer Survivors, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Physical Therapy Modalities::Exercise Therapy::Plyometric Exercise [Medical Subject Headings], law, Bone Density, Huesos, Child, Cancer, Anatomy::Musculoskeletal System::Skeleton::Bone and Bones [Medical Subject Headings], education.field_of_study, lcsh:Public aspects of medicine, Pediatría, Telemedicina, Diseases::Neoplasms [Medical Subject Headings], Neoplasias, Telemedicine, Exercise Therapy, Research Design, Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Quality of Life [Medical Subject Headings], Female, Persons::Persons::Patients::Survivors [Medical Subject Headings], Survivor, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Physical Therapy Modalities::Exercise Therapy [Medical Subject Headings], Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Program Evaluation [Medical Subject Headings], Plyometric exercise, medicine.medical_specialty, Adolescent, Population, Check Tags::Male [Medical Subject Headings], 030209 endocrinology & metabolism, Persons::Persons::Age Groups::Adolescent [Medical Subject Headings], Sobrevivientes, Information Science::Information Science::Communications Media::Telecommunications::Telemedicine [Medical Subject Headings], 03 medical and health sciences, Trabecular bone score, medicine, Humans, Persons::Persons::Age Groups::Child [Medical Subject Headings], education, Bone, Ejercicio pliométrico, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Bone Density [Medical Subject Headings], business.industry, Public health, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Paediatrics, 030229 sport sciences, Anthropometry, Mental health, Check Tags::Female [Medical Subject Headings], Physical therapy, business, Program Evaluation
Abstract: Background: New approaches on paediatric cancer treatment aim to maintain long-term health. As a result of radiotherapy, chemotherapy or surgery, paediatric cancer survivors tend to suffer from any chronic health condition. Endocrine dysfunction represents one of the most common issues and affects bone health. Exercise is key for bone mass accrual during growth, specifically plyometric jump training. The iBoneFIT study will investigate the effect of a 9-month online exercise programme on bone health in paediatric cancer survivors. This study will also examine the effect of the intervention on body composition, physical fitness, physical activity, calcium intake, vitamin D, blood samples quality of life and mental health. Methods: A minimum of 116 participants aged 6 to 18 years will be randomized into an intervention (n = 58) or control group (n = 58). The intervention group will receive an online exercise programme and diet counselling on calcium and vitamin D. In addition, five behaviour change techniques and a gamification design will be implemented in order to increase the interest of this non-game programme. The control group will only receive diet counselling. Participants will be assessed on 3 occasions: 1) at baseline; 2) after the 9 months of the intervention; 3) 4 months following the intervention. The primary outcome will be determined by dual energy X-ray absorptiometry (DXA) and the hip structural analysis, trabecular bone score and 3D-DXA softwares. Secondary outcomes will include anthropometry, body composition, physical fitness, physical activity, calcium and vitamin D intake, blood samples, quality of life and mental health., La Caixa Foundation 100010434 LCF/BQ/PR19/11700007, University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES), Junta de Andalucía SOMM17/6107/UGR, European Union (EU) SOMM17/6107/UGR
Published: 2020

32. Efficacy, cost-utility and physiological effects of Acceptance and Commitment Therapy (ACT) and Behavioural Activation Treatment for Depression (BATD) in patients with chronic low back pain and depression: study protocol of a randomised, controlled trial including mobile-technology-based ecological momentary assessment (IMPACT study)

Author: Carlos Suso-Ribera, Francesco D'Amico, Antonio Cuesta-Vargas, Juan P. Sanabria-Mazo, Antoni Sanz, Juan R. Castaño-Asins, Pere Estivill-Rodríguez, Paula Cristóbal-Narváez, Albert Feliu-Soler, Adrián Pérez-Aranda, Grasa Mm, Antonio Montes-Pérez, Azucena García-Palacios, Lance M. McCracken, Carlos G. Forero, Michael Maes, Araceli Rosa, Xavier Borrás, Juan V. Luciano, Ariadna Colomer-Carbonell, Bernat Carreras-Marcos, Laura Andrés-Rodríguez, Silvia Edo, Olga Comps-Vicente, Montserrat Esteve, This study has been funded by the Institute of Health Carlos III (ISCIII, and PI19/00112 & PI16/00165 have been cofinanced with European Union ERDF funds). JVL has a 'Miguel Servet Type II' contract from the ISCIII (CPII19/00003). ISCIII did not have any role in the analysis and interpretation of data, in the writing of the manuscript and in the decision to submit the paper for publication.
Subjects: Technology, General Practice, lcsh:Medicine, Impact study, Chronic pain, R Medicine (General), Acceptance and commitment therapy, law.invention, Clinical trials, Randomized controlled trial, Terapia de aceptación y compromiso, law, Depresión, Tratamiento breve de activación conductual para la depresión, Dolor persistente, Persistent pain, Medicine, Multicenter Studies as Topic, Depressió psíquica, Depression (differential diagnoses), Applied Psychology, Randomized Controlled Trials as Topic, Ecology, Depression, Teràpia racional emotiva conductual, General Medicine, Dolor crònic, Chronic low back pain, Mental depression, Rational emotive behavior therapy, BF Psychology, Ecological Momentary Assessment, Clinical trials, Depression & mood disorders, pain management, Brief behavioral activation treatment for depression, 159.9, Health Economics, Dolor lumbar crónico, Humans, Tractament breu d’activació conductual per a la depressió, Acceptance and Commitment Therapy, Protocol (science), Dolor lumbar crònic, business.industry, lcsh:R, Teràpia d’acceptació i compromís, Dolor persistent, Tillämpad psykologi, Pain management, Clinical trial, Allmänmedicin, pain management, Spain, Depression & mood disorders, Economic evaluation, Depressió, business, Low Back Pain
Abstract: IntroductionThe IMPACT study focuses on chronic low back pain (CLBP) and depression symptoms, a prevalent and complex problem that represents a challenge for health professionals. Acceptance and Commitment Therapy (ACT) and Brief Behavioural Activation Treatment for Depression (BATD) are effective treatments for patients with persistent pain and depression, respectively. The objectives of this 12 month, multicentre, randomised, controlled trial (RCT) are (i) to examine the efficacy and cost-utility of adding a group-based form of ACT or BATD to treatment-as-usual (TAU) for patients with CLBP and moderate to severe levels of depressive symptoms; (ii) identify pre–post differences in levels of some physiological variables and (iii) analyse the role of polymorphisms in the FKBP5 gene, psychological process measures and physiological variables as mediators or moderators of long-term clinical changes.Methods and analysisParticipants will be 225 patients with CLBP and moderate to severe depression symptoms recruited at Parc Sanitari Sant Joan de Déu (St. Boi de Llobregat, Spain) and Hospital del Mar (Barcelona, Spain), randomly allocated to one of the three study arms: TAU vs TAU+ACT versus TAU+BATD. A comprehensive assessment to collect clinical variables and costs will be conducted pretreatment, post-treatment and at 12 months follow-up, being pain interference the primary outcome measure. The following physiological variables will be considered at pretreatment and post-treatment assessments in 50% of the sample: immune-inflammatory markers, hair cortisol and cortisone, serum cortisol, corticosteroid-binding globulin and vitamin D. Polymorphisms in the FKBP5 gene (rs3800373, rs9296158, rs1360780, rs9470080 and rs4713916) will be analysed at baseline assessment. Moreover, we will include mobile-technology-based ecological momentary assessment, through the Pain Monitor app, to track ongoing clinical status during ACT and BATD treatments. Linear mixed-effects models using restricted maximum likelihood, and a full economic evaluation applying bootstrapping techniques, acceptability curves and sensitivity analyses will be computed.Ethics and disseminationThis study has been approved by the Ethics Committee of the Fundació Sant Joan de Déu and Hospital del Mar. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media and various community engagement activities.Trial registration numberNCT04140838
Published: 2020

33. Low serum DHEA-S is associated with impaired lung function in women

Author: Thorarinn Gislason, Isabelle Pin, Nicole Probst-Hensch, Jesús Martínez-Moratalla, Bénédicte Leynaert, Alessandro Marcon, Judith Garcia-Aymerich, Sandra Dorado-Arenas, Pascal Demoly, Rain Jõgi, Deborah Jarvis, Joachim Heinrich, Torben Sigsgaard, Josep M. Antó, Eva Lindberg, Jose Antonio Gullón-Blanco, Elisabeth Zemp, Dennis Nowak, Chantal Raherison, Kai Triebner, Shyamali C. Dharmage, Diana A van der Plaat, José Luis Sánchez-Ramos, Kjell Torén, Bertil Forsberg, Giancarlo Pesce, Steinar Hustad, Francisco Gómez-Real, Dominique Courbon, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Bergen (UiB), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Aarhus University Hospital, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), IMIM-Hospital del Mar, Generalitat de Catalunya, Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), BrainTech Laboratory [CHU Grenoble Alpes - Inserm U1205] (Brain Tech Lab ), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Sahlgrenska Academy at University of Gothenburg [Göteborg], Umeå University, Uppsala University Hospital, University of Basel (Unibas), Imperial College London, Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Agence Nationale de la Recherche, ANR 633212 ComitÃ© des Maladies Respiratoires de l'IsÃ¨re European Commission, EC: QLK4-CT-1999–01237 Norges ForskningsrÃ¥d: 228174 Institut National de la SantÃ© et de la Recherche MÃ©dicale, Inserm: U700 Agence Nationale de la Recherche, ANR Medical Research Council, MRC: 92091 Composites Innovation Centre, CIC Eesti Teadusagentuur: 562, The current study is part of the Ageing for Lungs in European Cohorts (ALEC) study ( www.alecstudy.org ), ALEC has received funding from the European Union's Horizon 2020 research and innovation program [grant agreement No. 633212]. The coordination of the ECRHS was supported by the European Commission [grant agreement no. QLK4-CT-1999–01237] and the Medical Research Council [grant agreement no. 92091]. The hormones measures at ECRHS III were funded by the Norwegian Research Council [grant agreement no. 228174]. Hormones measures at ECRHS II were funded by the local budget of the ECRHS Paris team, INSERM U700, Epidemiology, with further support from the Comité National contre les Maladies Respiratoires (CNMR), the centre d'Investigation Clinique (CIC), Bichat Hospital, and the French Agence Nationale de la Recherche (ANR). Bodies funding the local studies are listed in the Online Supplement. The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication., Dr Demoly reports presentation honoraria from Stallergène Greer, ALK, Mylan, Astra Zeneca, Bausch&Lomb and personal fees as board advisor from Chiesi, Sanofi, Thermo Fisher Scientific, outside the submitted work. Dr Jogi reports personal grants from the Estonian Research Council [personal research grant no.562], and reports travel grants and presentation honoraria from GSK, Novartis, Boehringer, outside the submitted work. Dr Pin reports travel grants and presentation honoraria from GSK, Novartis, Astra Zeneca, Zambon Pharma, outside the submitted work. All the authors declare no competing interests., European Project: 633212,H2020,H2020-PHC-2014-two-stage,ALEC(2015), Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: Research paper, Respiratory Medicine and Allergy, [SDV]Life Sciences [q-bio], Population, Physiology, Dehydroepiandrosterone, Endocrinology and Diabetes, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dehydroepiandrosterone sulfate, Karlhormónar, Medicine, Airflow obstruction, Sex hormones, 030212 general & internal medicine, 0101 mathematics, education, Kynhormónar, Testosterone, Lungmedicin och allergi, 2. Zero hunger, lcsh:R5-920, education.field_of_study, business.industry, Incidence (epidemiology), Öndunarfæri, 010102 general mathematics, EPICENE, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, 3. Good health, Airflow Obstruction, Androgens, Cohort Studies, Sex Hormones, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, chemistry, Endokrinologi och diabetes, Cohort studies, lcsh:Medicine (General), business, Body mass index, hormones, hormone substitutes, and hormone antagonists, Cohort study, Hormone
Abstract: Publisher's version (útgefin grein), Background: Emerging evidence suggests that androgens and estrogens have a role in respiratory health, but it is largely unknown whether levels of these hormones can affect lung function in adults from the general population. This study investigated whether serum dehydroepiandrosterone sulfate (DHEA-S), a key precursor of both androgens and estrogens in peripheral tissues, was related to lung function in adult women participating in the European Community Respiratory Health Survey (ECRHS). Methods: Lung function and serum DHEA-S concentrations were measured in n = 2,045 and n = 1,725 women in 1999–2002 and in 2010–2013, respectively. Cross-sectional associations of DHEA-S levels (expressed as age-adjusted z-score) with spirometric outcomes were investigated, adjusting for smoking habits, body mass index, menopausal status, and use of corticosteroids. Longitudinal associations of DHEA-S levels in 1999–2002 with incidence of restrictive pattern and airflow limitation in 2010–2013 were also assessed. Findings: Women with low DHEA-S (z-score, The current study is part of the Ageing for Lungs in European Cohorts (ALEC) study ( www.alecstudy.org ), ALEC has received funding from the European Union's Horizon 2020 research and innovation program [grant agreement No. 633212]. The coordination of the ECRHS was supported by the European Commission [grant agreement no. QLK4-CT-1999–01237] and the Medical Research Council [grant agreement no. 92091]. The hormones measures at ECRHS III were funded by the Norwegian Research Council [grant agreement no. 228174]. Hormones measures at ECRHS II were funded by the local budget of the ECRHS Paris team, INSERM U700, Epidemiology, with further support from the Comité National contre les Maladies Respiratoires (CNMR), the centre d'Investigation Clinique (CIC), Bichat Hospital, and the French Agence Nationale de la Recherche (ANR). Bodies funding the local studies are listed in the Online Supplement. The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Published: 2020
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34. Cannabis use is associated with a lower risk of diabetes in chronic hepatitis C-infected patients (ANRS CO22 Hepather cohort)

Author: Barré, Tangui, Nishimwe, Marie Libérée, Protopopescu, Camelia, Marcellin, Fabienne, Carrat, Fabrice, Dorival, Céline, Delarocque-Astagneau, Elisabeth, Larrey, Dominique G., Bourlière, Marc, Petrov-Sanchez, Ventzislava, Simony, Mélanie, Pol, Stanislas, Fontaine, Hélène, Carrieri, Patrizia Maria, Pageaux, Georges Philippe, HAL UVSQ, Équipe, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Merck Sharp and Dohme, MSD Agence Nationale de la Recherche, ANR AbbVie Bristol-Myers Squibb, BMS AbbVie Association Française pour l'Etude du Foie, AFEF Roche Gilead Sciences Shionogi Cilag MSD France, FC reports grants from INSERM-ANRS, during the conduct of the study, and personal fees from Imaxio, outside the submitted work. MB reports grants and personal fees from AbbVie and Gilead, outside the submitted work, and personal fees from MSD, Janssen, Boehringher Ingelheim, Intercept, and Bristol-Myers Squibb, outside the submitted work. SP has received consulting and lecturing fees from Bristol-Myers Squibb, Janssen, Gilead, Roche, MSD, MYR-Pharma, Shionogi, Biotest and Abbvie, as well as grants from Bristol-Myers Squibb, Gilead, Roche and MSD. HF reports personal fees and invitations for medical meetings from Gilead, AbbVie, Bristol-Myers Squibb, MSD, and Janssen, outside the submitted work. Other authors declare no financial support. The cohort received financial support from the INSERM-ANRS (France Recherche Nord & Sud Sida-HIV H?patites), the French ANR (Agence Nationale de la Recherche), the French DGS (Direction Générale de la Santé), Merck Sharp and Dohme, Janssen-Cilag, Gilead, Abbvie, Bristol-Myers Squibb, and Roche. Those funding sources had no role in the writing of the manuscript or the decision to submit it for publication. We thank the study participants and the participating clinicians at each site. We also thank the INSERM-ANRS for sponsoring, funding and conducting the ANRS CO22 Hepather cohort in collaboration with the French Association for the Study of the Liver (Association Fran?aise pour l'Etude du Foie: AFEF). Finally, our thanks to Jude Sweeney for the English revision and editing of our manuscript., On behalf of the ANRS/AFEF Hepather study group : Delphine Bonnet, Virginie Sicart (CHU Purpan, Toulouse, France), François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig‐Lavie, Marianne Maynard (Hospices Civils de Lyon, Lyon, France), Morane Cavellec, Marjorie Cheraud‐Carpentier, François Raffi, Florian Vivrel (Hôpital Hôtel‐Dieu, Nantes, France), Jaouad Benhida, Jérôme Boursier, Paul Calès, Françoise Lunel, Frédéric Oberti (CHU Angers, Angers, France), Nathalie Boyer, Audrey Gilibert, Nathalie Giuily (Hôpital Beaujon, Clichy, France), Giovanna Scoazec (Hôpital Beaujon, Clichy, France and Hôpital Henri Mondor, Créteil, France), Sandrine Fernandes, Sylvie Keser, Philippe Sultanik, Anaïs Vallet‐Pichard (Hôpital Cochin, Paris, France), Juliette Foucher, Jean‐Baptiste Hiriart, Aurore Mathias, Julien Vergniol (Hôpital Haut‐Lévêque, Pessac, Bordeaux, France), Chrystelle Ansaldi, Laëtitia Chouquet, Emilie De Luca, Valérie Oules (Hôpital Saint Joseph, Marseille, France), Rodolphe Anty, Eve Gelsi, Régine Truchi (CHU de Nice, Nice, France), Elena Luckina, Nadia Messaoudi, Joseph Moussali, (Groupe Hospitalier Pitié‐Salpétrière, Paris, France), Barbara De Dieuleveult, Damien Labarriere, Pascal Poter, Si Nafa Si Ahmed (CHR La Source, Orléans, France), Nathalie Ganne‐Carrié, Véronique Grando‐Lemaire, Pierre Nahon, Alan Peltier, Judith Ung (Hôpital Jean Verdier, Bondy, France), Mariette Gougeon, Anne Guillygomarch, Caroline Jezequel (CHU Rennes, Rennes, France), Romain Moirand, Thomas F. Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo‐Noumbissie (Hôpitaux Universitaires de Strasbourg, Strasbourg, France), Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani‐Nani (CHU de Nancy, Vandoeuvre‐lès‐Nancy, France), Marie‐Albertine Bernard (CHU de Nancy, Vandoeuvre‐lès‐Nancy, France and Centre Hospitalier Régional, Metz, France), Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Georges‐Philippe Pageaux, Marie Pierre Ripault (Hôpital Saint Eloi, Montpellier, France), Karl Barange, Christophe Bureau, Jean Marie Peron, Marie Angèle Robic, Léa Tarallo (CHU Purpan, Toulouse, France), Marine Faure, Bruno Froissart, Marie‐Noelle Hilleret, Vincent Leroy (CHU de Grenoble, Grenoble, France), Odile Goria, Victorien Grard, Hélène Montialoux (CHU Charles Nicolle, Rouen, France), Muriel François, Christian Ouedraogo, Christelle Pauleau, Anne Varault (Hôpital Henri Mondor, Créteil, France), Tony Andreani, Bénédicte Angoulevant, Azeline Chevance, Lawrence Serfaty (Hôpital Saint‐Antoine, Paris, France), Teresa Antonini, Audrey Coilly, Jean‐Charles Duclos Vallée, Mariagrazia Tateo (Hôpital Paul Brousse, Villejuif, France), Armand Abergel, Corinne Bonny, Chanteranne Brigitte, Géraldine Lamblin, Léon Muti (Hôpital Estaing, Clermont‐Ferrand, France), Abdenour Babouri, Virginie Filipe (Centre Hospitalier Régional, Metz, France), Camille Barrault, Laurent Costes, Hervé Hagège, Soraya Merbah (Centre Hospitalier Intercommunal, Créteil, France), Paul Carrier, Maryline Debette‐Gratien, Jérémie Jacques (CHU Limoges, Limoges, France), Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet (CHRU Claude Huriez, Lille, France), Marc Bardou, Donya Da Costa Souhiel, Patrick Hillon, Marianne Latournerie (Dijon University Hospital, Dijon, France), Yannick Bacq, Didier Barbereau, Charlotte Nicolas (CHU Trousseau, 37044 Tours, France), Nisserine Ben Amara, Danièle Botta‐Fridlund, Isabelle Portal (CHU Timone, Marseille, France), Moana Gelu‐Simeon, Marie‐Josée Lafrance (CHU de Pointe‐à‐Pitre, Pointe‐à‐Pitre, Guadeloupe)., Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Eloi, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Liver Cirrhosis, cannabis, medicine.medical_specialty, Population, HIV Infections, 030209 endocrinology & metabolism, marijuana smoking, Lower risk, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Diabetes mellitus, Internal medicine, medicine, Humans, Risk factor, education, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, education.field_of_study, Hepatology, biology, business.industry, 1. No poverty, Hepatitis C, Hepatitis C, Chronic, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, biology.organism_classification, 3. Good health, chronic, Cross-Sectional Studies, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, diabetes mellitus, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030211 gastroenterology & hepatology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cannabis, France, business
Abstract: International audience; Chronic hepatitis C virus (HCV) infection is a risk factor of insulin resistance, and HCV-infected patients are at a high risk of developing diabetes. In the general population, research has shown the potential benefit of cannabis use for the prevention of diabetes and related metabolic disorders. We aimed to test whether cannabis use is associated with a lower risk of diabetes in chronic HCV-infected patients. Chronic HCV-infected patients (n = 10 445) were selected from the French national, multicenter, observational ANRS CO22 Hepather cohort. Cross-sectional data collected at cohort enrollment were used to assess the association between patients’ clinical and behavioural characteristics and the risk of diabetes. Logistic regression model was performed with cannabis use as the main independent variable and a significance level set at 5%. A similar model stratified by the presence of advanced liver fibrosis (FIB-4 > 3.25) was also run. After multivariable adjustment, current (AOR [95%CI]: 0.49 [0.38-0.63]) and former (0.81 [0.67-0.98], P
Published: 2020
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35. High Prevalence of Leptospira spp. in Rodents in an Urban Setting in Madagascar

Author: Minoarisoa Rajerison, Benoit Garin, Soanandrasana Rahelinirina, Fehivola Andriamiaramanana, Pascale Bourhy, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Biologie des Spirochètes / Biology of Spirochetes, Institut Pasteur [Paris], CHU Pointe-à-Pitre/Abymes [Guadeloupe], We would like to thank the staff of the Plague Unit, Institut Pasteur Madagascar for field and technical assistance, and the team of the Centre National de Référence de la Leptospirose, Institut Pasteur, Paris for technical assistance genotyping isolates. We thank D. Wagner for improving the English writing in the manuscript., and Institut Pasteur [Paris] (IP)
Subjects: MESH: Leptospira interrogans, Veterinary medicine, [SDV]Life Sciences [q-bio], animal diseases, 030231 tropical medicine, MESH: Rodentia, MESH: Leptospira, law.invention, MESH: Madagascar, 03 medical and health sciences, 0302 clinical medicine, law, Leptospira, Virology, MESH: Cities, medicine, MESH: Animals, 030212 general & internal medicine, MESH: Prevalence, Polymerase chain reaction, High prevalence, Bacterial disease, biology, MESH: Kidney, MESH: Leptospirosis, bacterial infections and mycoses, biology.organism_classification, medicine.disease, MESH: DNA, Bacterial, Leptospirosis, 3. Good health, Leptospira borgpetersenii, Infectious Diseases, Capital city, bacteria, Parasitology, MESH: Rodent Diseases, Leptospira interrogans
Abstract: International audience; Leptospirosis is a neglected zoonotic bacterial disease caused by pathogenic Leptospira spp. Only limited studies have been conducted on the presence of Leptospira spp. in rats in Antananarivo, the capital city of Madagascar. We assessed Leptospira prevalence in small mammals in urban areas of Antananarivo where sanitation is inadequate and there is risk of flooding during the rainy season. We captured rodents and shrews at two sites and examined kidney samples from 114 animals using culture and a real-time polymerase chain reaction (PCR) assay specific to pathogenic Leptospira spp. We identified 23 positive samples containing Leptospira interrogans and Leptospira borgpetersenii, with a high prevalence in Rattus norvegicus (44.9%). Our results indicate that small mammals, in particular R. norvegicus, present a major public health risk for acquiring leptospirosis in Antananarivo.
Published: 2019
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36. Effectiveness of a Mindfulness and Self-Compassion Standard Training Program versus an Abbreviated Training Program on Stress in Tutors and Resident Intern Specialists of Family and Community Medicine and Nursing in Spain

Author: Juan Carlos, Verdes-Montenegro-Atalaya, Luis Ángel, Pérula-de Torres, Norberto, Lietor-Villajos, Cruz, Bartolomé-Moreno, Herminia, Moreno-Martos, Luis Alberto, Rodríguez, Teresa, Grande-Grande, Rocío, Pardo-Hernández, Benito, León-Del-Barco, Mirian, Santamaría-Peláez, Luis A, Mínguez, Josefa, González-Santos, Raúl, Soto-Cámara, Jerónimo J, González-Bernal, On Behalf Of The Minduudd Collaborative Study Group, On Behalf Of The Minduudd Collaborative Study Group, [Verdes-Montenegro-Atalaya,JC, Grande-Grande,T] Family and Community Medicine Teaching Department of Burgos, Burgos, Spain. [Pérula-de Torres,LÁ] Multi-Professional Teaching Unit for Family and Community Care of Cordoba, Healthcare District of Cordoba and Guadalquivir, Institute Maimonides Research Institute Cordoba (IMIBIC), Reina Sofía University Hospital, University of Cordoba, Cordoba, Spain. [Lietor-Villajos,N] Family and Community Medicine Teaching Department of Jaen, Jaen, Spain. [Bartolomé-Moreno,C] Family and Community Medicine Teaching Department of Zaragoza Sector 1, Zaragoza, Spain. [Moreno-Martos,H] Multi-Professional Teaching Unit for Family and Community Care of Almería, Almería, Spain. [Rodríguez,LA] Family and Community Medicine Teaching Department of Ponferrada, León, Spain. [Pardo-Hernández,R, Santamaría-Peláez,M, González-Santos,J, Soto-Cámara,R, González-Bernal,JJ] Department of Health Sciences, University of Burgos, Burgos, Spain. [León-Del-Barco,B] Department of Psychology, Faculty of Teacher Training College, University of Extremadura, Caceres, Spain. [Mínguez,LA] Department of Educational Sciences, University of Burgos, Burgos, Spain., and This project has received an 'Isabel Fernández, 2017' scholarship from the Andalusian Society of Family and Community Medicine (SAMFyC, Ref. 153/17). On the other hand, it has received funding in the call for research and innovation projects in the field of Primary Care of the Andalusian Health Service (Ref. AP-0155-2018). The funding source had no influence on the design of the study, data collection and analysis, or the writing of the manuscript.
Subjects: mindfulness, Mindfulness, Health, Toxicology and Mutagenesis, España, MBSR, Stress level, law.invention, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], stress, Randomized controlled trial, law, Surveys and Questionnaires, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Behavioral Symptoms::Stress, Psychological [Medical Subject Headings], Stress (linguistics), media_common, Estudiantes del area de la salud, PSQ, Primary care, Resident intern specialists, Encuestas y Cuestionarios, Tutors, Estrés fisiológico, Community Medicine, Atención plena, tutors, Medicine, Training program, Psychology, Self-compassion, Atención primaria de la salud, media_common.quotation_subject, education, Psychiatry and Psychology::Behavioral Disciplines and Activities::Psychotherapy::Behavior Therapy::Cognitive Therapy::Mindfulness [Medical Subject Headings], Empathy, Stress, Article, Information Science::Information Science::Data Collection::Questionnaires [Medical Subject Headings], primary care, Nursing, Intervention (counseling), Humans, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Disciplines and Occupations::Health Occupations::Medicine::Community Medicine [Medical Subject Headings], Public Health, Environmental and Occupational Health, resident intern specialists, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Personality::Empathy [Medical Subject Headings], Spain, Stress, Psychological
Abstract: Stress is one of the most common problems among healthcare professionals, as they are exposed to potentially stressful and emotionally challenging situations in the workplace. Mindfulness-based stress reduction (MBSR) training programs have been shown to decrease stress. The objective of this study was to compare the effectiveness of an abbreviated 4-weeks MBSR training program in relation to a standard 8-weeks one on the stress levels. A controlled and randomized clinical trial was designed, in which 112 tutors and resident intern specialists in Family and Community Medicine and Nursing of six Spanish National Health System teaching units (TUs) participated. Participants included in the experimental groups (EGs) received a MBRS training program (standard or abbreviated), while control group (CG) participants did not receive any intervention. The stress levels were assessed by the Perceived Stress Questionnaire (PSQ) in three different moments during the study: before, immediately after, and 3 months after the intervention. Adjusted covariance analysis (ANCOVA), using pretest scores as the covariate, showed a significant reduction in stress (F(2,91) = 5.165, p = 0.008, η2 = 0.102) in the post-test visit, attributable to the implementation of the standard training program, but without the maintenance of its effects over time. No significant impact of the abbreviated training program on stress levels was observed in the intergroup comparison. A standard 8-weeks MBSR training program aimed at tutors and resident intern specialists in Family and Community Medicine and Nursing produces significant improvements in stress levels compared with the abbreviated intervention and no intervention. New studies about abbreviated training programs are needed to provide effective treatments which improve well-being of these professionals.
Published: 2021
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37. An Immunodominant and Conserved B-Cell Epitope in the Envelope of Simian Foamy Virus Recognized by Humans Infected with Zoonotic Strains from Apes

Author: Damien Batalie, Thomas Montange, Richard Njouom, Edouard Betsem, Caroline Lambert, Antoine Gessain, Augustin Mouinga-Ondémé, Florence Buseyne, Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Cellule Pasteur, PRES Sorbonne Paris Cité-Université Paris Diderot - Paris 7 (UPD7), Université de Yaoundé I [Yaoundé], Centre international de recherches médicales de Franceville (CIRMF), Organisation Mondiale de la Santé (OMS), Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), C.L. was personally supported by a doctoral grant from the French government program Investissement d’Avenir, Laboratory of Excellence, Integrative Biology of Emerging Infectious Diseases (LabEx IBEID). This study was supported by the Institut Pasteur in Paris, France, the Program Transversal de Recherche from the Institut Pasteur (PTR#437), and the Agence Nationale de la Recherche (grant ANR-10-LABX-62-IBEID, REEMFOAMY project, ANR 15-CE-15-0008-01). The funding agencies had no role in the study design, generation of results, or writing of the manuscript., We thank M. Bourgine for her helpful advice on the ELISAs. We thank members of the Unité d’Épidémiologie et Physiopathologie des Virus Oncogènes for discussions and technical advice. The text has been edited by a native English speaker., ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), ANR-15-CE15-0008,REEMFOAMY,L'infection humaine par les virus foamy simiens zoonotiques : rôle des facteurs virologiques et immunologiques dans la restrcition de l'emergence virale(2015), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Université de Yaoundé I, Centre International de Recherches Médicales de Franceville (CIRMF), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]
Subjects: Male, viruses, Simian foamy virus, Simian, Antibodies, Viral, Epitope, Retrovirus, Viral Envelope Proteins, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Zoonoses, antibody, Cameroon, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, Zoonotic Infection, virus diseases, Hominidae, Middle Aged, zoonotic infections, 3. Good health, retrovirus, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Epitopes, B-Lymphocyte, Antibody, Adult, Pan troglodytes, Immunology, Cercopithecus, Microbiology, Virus, 03 medical and health sciences, Virology, Animals, Humans, emergence, Gabon, Tropism, 030304 developmental biology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Gorilla gorilla, 030306 microbiology, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Insect Science, DNA, Viral, biology.protein, Pathogenesis and Immunity, Spumavirus, Retroviridae Infections
Abstract: International audience; Cross-species transmission of simian foamy viruses (SFVs) from nonhu-man primates (NHPs) to humans is currently ongoing. These zoonotic retroviruses establish lifelong persistent infection in their human hosts. SFV are apparently non-pathogenic in vivo, with ubiquitous in vitro tropism. Here, we aimed to identify envelope B-cell epitopes that are recognized following a zoonotic SFV infection. We screened a library of 169 peptides covering the external portion of the envelope from the prototype foamy virus (SFVpsc_huHSRV.13) for recognition by samples from 52 Central African hunters (16 uninfected and 36 infected with chimpanzee, gorilla, or Cercopithecus SFV). We demonstrate the specific recognition of peptide N 96-V 110 located in the leader peptide, gp18 LP. Forty-three variant peptides with truncations, alanine substitutions, or amino acid changes found in other SFV species were tested. We mapped the epitope between positions 98 and 108 and defined six amino acids essential for recognition. Most plasma samples from SFV-infected humans cross-reacted with sequences from apes and Old World monkey SFV species. The magnitude of binding to peptide N 96-V 110 was significantly higher for samples of individuals infected with a chimpanzee or gorilla SFV than those infected with a Cercopithecus SFV. In conclusion, we have been the first to define an immunodomi-nant B-cell epitope recognized by humans following zoonotic SFV infection. IMPORTANCE Foamy viruses are the oldest known retroviruses and have been mostly described to be nonpathogenic in their natural animal hosts. SFVs can be transmitted to humans, in whom they establish persistent infection, like the simian lenti-and deltaviruses that led to the emergence of two major human pathogens, human immunodeficiency virus type 1 and human T-lymphotropic virus type 1. This is the first identification of an SFV-specific B-cell epitope recognized by human plasma samples. The immunodominant epitope lies in gp18 LP , probably at the base of the envelope trimers. The NHP species the most genetically related to humans transmitted SFV strains that induced the strongest antibody responses. Importantly, this epitope is well conserved across SFV species that infect African and Asian NHPs.
Published: 2019
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38. Incorporating individual historical controls and aggregate treatment effect estimates into a Bayesian survival trial: a simulation study

Author: Lisa V. Hampson, Marie-Cécile Le Deley, Caroline Brard, Nathalie Gaspar, Gwénaël Le Teuff, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Statistical Methodology [Bâle, Suisse], Novartis Pharma AG, Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Unité de Méthodologie et de Biostatistique [Lille] (UMB), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, We acknowledge for the design, analysis, interpretation of the simulation study, and for the writing of the manuscript, funding from – PhD grant from doctoral school of public health, Paris-Sud, Paris-Saclay – Lisa Hampson’s contribution to the paper was partly funded by the UK Medical Research Council (grant MR/M013510/1) and was completed while she was an employee of Lancaster University – Ligue contre le cancer, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, and Bodescot, Myriam
Subjects: Simulation study, Epidemiology, Computer science, Bayesian probability, Health Informatics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Power prior, law.invention, 03 medical and health sciences, 0302 clinical medicine, Adjuvants, Immunologic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Randomized controlled trial, law, Statistics, Prior probability, Humans, Computer Simulation, 030212 general & internal medicine, Set (psychology), Baseline (configuration management), Bayesian randomised survival trial, Randomized Controlled Trials as Topic, Weibull distribution, Osteosarcoma, lcsh:R5-920, Phosphatidylethanolamines, 030503 health policy & services, Aggregate (data warehouse), Bayes Theorem, Variance (accounting), Models, Theoretical, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Control Groups, Mixture prior, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Research Design, Sample Size, Individual control data, 0305 other medical science, lcsh:Medicine (General), Aggregate treatment effect, Acetylmuramyl-Alanyl-Isoglutamine, Rare disease, Algorithms, Research Article
Abstract: Background Performing well-powered randomised controlled trials (RCTs) of new treatments for rare diseases is often infeasible. However, with the increasing availability of historical data, incorporating existing information into trials with small sample sizes is appealing in order to increase the power. Bayesian approaches enable one to incorporate historical data into a trial’s analysis through a prior distribution. Methods Motivated by a RCT intended to evaluate the impact on event-free survival of mifamurtide in patients with osteosarcoma, we performed a simulation study to evaluate the impact on trial operating characteristics of incorporating historical individual control data and aggregate treatment effect estimates. We used power priors derived from historical individual control data for baseline parameters of Weibull and piecewise exponential models, while we used a mixture prior to summarise aggregate information obtained on the relative treatment effect. The impact of prior-data conflicts, both with respect to the parameters and survival models, was evaluated for a set of pre-specified weights assigned to the historical information in the prior distributions. Results The operating characteristics varied according to the weights assigned to each source of historical information, the variance of the informative and vague component of the mixture prior and the level of commensurability between the historical and new data. When historical and new controls follow different survival distributions, we did not observe any advantage of choosing a piecewise exponential model compared to a Weibull model for the new trial analysis. However, we think that it remains appealing given the uncertainty that will often surround the shape of the survival distribution of the new data. Conclusion In the setting of Sarcome-13 trial, and other similar studies in rare diseases, the gains in power and accuracy made possible by incorporating different types of historical information commensurate with the new trial data have to be balanced against the risk of biased estimates and a possible loss in power if data are not commensurate. The weights allocated to the historical data have to be carefully chosen based on this trade-off. Further simulation studies investigating methods for incorporating historical data are required to generalise the findings. Electronic supplementary material The online version of this article (10.1186/s12874-019-0714-z) contains supplementary material, which is available to authorized users.
Published: 2019
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39. Full Statistics of Conjugated Thermodynamic Ensembles in Chains of Bistable Units

Author: Stefano Giordano, Manon Benedito, Fabio Manca, Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Acoustique Impulsionnelle & Magnéto-Acoustique Non linéaire - Fluides, Interfaces Liquides & Micro-Systèmes - IEMN (AIMAN-FILMS - IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Laboratoire de Physique Statistique de l'ENS (LPS), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Funding: This research was funded by region Hauts de France through the project MEPOFIB (MEchanics of POlymers and FIBers)., Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study, in the analyses of the problem, in the writing of the manuscript, or in the decision to publish the results., Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Acoustique Impulsionnelle & Magnéto-Acoustique Non linéaire - Fluides, Interfaces Liquides & Micro-Systèmes - IEMN (AIMAN-FILMS-IEMN), Institut d’Électronique, de Microélectronique et de Nanotechnologie - Département Opto-Acousto-Électronique - UMR 8520 (IEMN-DOAE), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France)-Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), and Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France)
Subjects: Bistability, bistability, lcsh:Engineering machinery, tools, and implements, Thermodynamic equilibrium, Probability density function, 02 engineering and technology, 01 natural sciences, polymer chain, symbols.namesake, 0103 physical sciences, ensembles equivalence, Statistical physics, [NLIN]Nonlinear Sciences [physics], lcsh:Technological innovations. Automation, 010306 general physics, Canonical ensemble, Physics, [PHYS]Physics [physics], Gibbs and Helmholtz ensembles, lcsh:HD45-45.2, General Engineering, Statistical mechanics, [PHYS.MECA]Physics [physics]/Mechanics [physics], 021001 nanoscience & nanotechnology, Potential energy, Helmholtz free energy, Thermodynamic limit, symbols, lcsh:TA213-215, 0210 nano-technology, small systems thermodynamics
Abstract: International audience; The statistical mechanics and the thermodynamics of small systems are characterized by 1 the non-equivalence of the statistical ensembles. Concerning a polymer chain or an arbitrary chain 2 of independent units, this concept leads to different force-extension responses for the isotensional 3 (Gibbs) and the isometric (Helmholtz) thermodynamic ensembles for a limited number of units 4 (far from the thermodynamic limit). While the average force-extension response has been largely 5 investigated in both Gibbs and Helmholtz ensembles, the full statistical characterization of this 6 thermo-mechanical behavior has not been approached by evaluating the corresponding probability 7 densities. Therefore, we elaborate in this paper a technique for obtaining the probability density of the 8 extension when the force is applied (Gibbs ensemble) and the probability density of the force when the 9 extension is prescribed (Helmholtz ensemble). This methodology, here developed at thermodynamic 10 equilibrium, is applied to a specific chain composed of units characterized by a bistable potential 11 energy, which is able to mimic the folding and unfolding of several macromolecules of biological 12 origin. 13
Published: 2019
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40. Efficacy of the In2Care® auto-dissemination device for reducing dengue transmission: study protocol for a parallel, two-armed cluster randomised trial in the Philippines

Author: Ariza Aguila, Marianette T. Inobaya, Ava Kristy Sy, Edward K. Thomsen, Jason R. Angeles, Michael J. Bangs, Ferdinand V. Salazar, Richard Paul, Tom Toner, Research Institute for Tropical Medicine [Muntinlupa City, Philippines], Liverpool School of Tropical Medicine (LSTM), Kasetsart University - KU (THAILAND), Kasetsart University (KU), PT Freeport Indonesia/International SOS, Génétique fonctionnelle des maladies infectieuses - Functional Genetics of Infectious Diseases, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Génomique évolutive, modélisation et santé (CNRS-UMR2000), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This study was funded by the Agence Française de Développement in the context of the Ecomore 2 programme ( www.ecomore.org/ ). The funding body did not have any role in project design or in the writing of this manuscript. The trial sponsor is Institut Pasteur, Paris, France., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Génomique évolutive, modélisation et santé (GEMS)
Subjects: Male, Insecticides, Mosquito Control, Time Factors, MESH: Philippines, Pyridines, Philippines, Medicine (miscellaneous), MESH: Dengue, Dengue virus, medicine.disease_cause, MESH: Dengue Virus, Dengue fever, law.invention, Dengue, Study Protocol, 0302 clinical medicine, Aedes aegypti, law, Aedes, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, Medicine, MESH: Pest Control, Biological, Pharmacology (medical), MESH: Animals, 030212 general & internal medicine, Chikungunya, MESH: Incidence, Child, MESH: Beauveria, Randomized Controlled Trials as Topic, MESH: Mosquito Control, lcsh:R5-920, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, Incidence, MESH: Aedes, 3. Good health, Mosquito control, Transmission (mechanics), Host-Pathogen Interactions, Female, MESH: Mosquito Vectors, lcsh:Medicine (General), Adolescent, Context (language use), Mosquito Vectors, 03 medical and health sciences, Environmental health, Animals, Humans, Beauveria, Pest Control, Biological, MESH: Adolescent, Beauvaria, MESH: Humans, business.industry, MESH: Host-Pathogen Interactions, MESH: Pyridines, MESH: Time Factors, Dengue Virus, medicine.disease, biology.organism_classification, MESH: Male, MESH: Insecticides, MESH: Randomized Controlled Trials as Topic, Pyriproxyfen, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Auto-dissemination, business, MESH: Female, 030217 neurology & neurosurgery
Abstract: Background Mosquito-borne viruses are imposing an ever increasing health burden worldwide. In addition to the recent Zika and chikungunya virus epidemics, dengue viruses have become the fastest growing problem with a 40-fold increase in the number of reported cases over the past five decades. Current mosquito control techniques involving larval source reduction, larviciding, and space spray of adulticides are costly, laborious, and of debatable efficacy. There remains an urgent need for the development of intervention methods that can be reasonably implemented in the context of modern day urbanisation. Auto-dissemination (AD) of insecticide by adult mosquitoes offers a potentially practical and useful tool in an integrated vector control programme. Recently, an immediately employable AD device, the In2Care® mosquito trap, has been commercialised and shows promise as an effective tool. However, there remains a lack of demonstration of epidemiological efficacy. Methods/design This trial aims to assess the extent to which implementation of In2Care® mosquito traps can reduce vector Aedes (Stegomyia) spp. adult mosquito densities and dengue virus transmission as measured by sequential sero-conversion rates in children 6–16 years of age in a dengue endemic location: Lipa City, Philippines. To achieve this, we will carry out a parallel, two-armed cluster randomised trial evaluating AD efficacy for reducing the incidence of dengue over a 2-year period with 4 consecutive months of vector control during peak dengue transmission each year. Discussion For decades, it has been commonly accepted that an integrated approach to mosquito control is required. The World Health Organization (WHO) Global Strategic Framework for Integrated Vector Management recommends a range of interventions, in combination, to increase control impact to reduce transmission. This efficacy trial of the first commercial product using the AD approach will be informative in assessing the general utility of AD in reducing not only adult vector densities but, more importantly, reducing the incidence of dengue. The AD technique may complement source reduction and larviciding campaigns by more efficiently targeting the most productive containers and those beyond human reach. If successful, this mosquito control strategy could prove an invaluable tool in the fight against urban mosquito vectors and a reduction in the burden of associated disease. Trial registration ISRCTN44272773. Registered on 31 January 2019. Electronic supplementary material The online version of this article (10.1186/s13063-019-3376-6) contains supplementary material, which is available to authorized users.
Published: 2019
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41. Blood lead level in infants and subsequent risk of malaria : a prospective cohort study in Benin, Sub-Saharan Africa

Author: Jacqueline Milet, Michel Cot, André Garcia, Florence Bodeau-Livinec, Amanda Garrison, David Courtin, Pierre Ayotte, Achille Massougbodji, Babak Khoshnood, Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), 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)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Institut de Recherche Clinique du Bénin [Abomey-Calavi, Bénin] (IRCB), Institut National de Santé Publique du Québec [Canada] (INSPQ), École des Hautes Études en Santé Publique [EHESP] (EHESP), The Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD) funded the TOVI study, grant R21-HD060524. The MiPPAD trial (NCT00811421) was co-funded by the European and Developing Countries Clinical Trials Partnership (EDCTP-IP.07.31080.002). The 'Anaemia in Pregnancy: Etiologies and Consequences' (APEC) study received funding from a grant from the Bill and Melinda Gates Foundation. The TOLIMMUNPAL project was funded by the French ANR (Agence Nationale de la Recherche) and coordinated by Dr André Garcia (IRD, UMR 216). Amanda Garrison received funding from PRINCEPS (Université Sorbonne Paris Cité) during the writing of this manuscript., ANR-10-PRSP-0012,TOLIMMUNPAL(2010), Bodescot, Myriam, PROGRAMME DE RECHERCHE EN SANTE PUBLIQUE - - TOLIMMUNPAL2010 - ANR-10-PRSP-0012 - PRSP - VALID, 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 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), and Mère et enfant face aux infections tropicales (MERIT - UMR_D 216)
Subjects: Male, Multivariate statistics, Pediatrics, Epidemiology, Health, Toxicology and Mutagenesis, 010501 environmental sciences, Biochemistry, 01 natural sciences, Geographical Locations, Families, Mathematical and Statistical Techniques, 0302 clinical medicine, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, Benin, 030212 general & internal medicine, Prospective cohort study, Children, Protozoans, Global and Planetary Change, Multidisciplinary, medicine.diagnostic_test, Incidence, Nutritional Deficiencies, Statistics, Eukaryota, Pollution, 3. Good health, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Chemistry, Quartile, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Physical Sciences, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Regression Analysis, Medicine, Female, medicine.symptom, Research Article, Chemical Elements, medicine.medical_specialty, Blood chemistry, Science, Protective factor, Research and Analysis Methods, Risk Assessment, Asymptomatic, 03 medical and health sciences, Malarial parasites, parasitic diseases, Parasitic Diseases, medicine, Metallic lead, Humans, Statistical Methods, Africa South of the Sahara, Nutrition, 0105 earth and related environmental sciences, business.industry, Iron deficiency, Organisms, Public Health, Environmental and Occupational Health, Univariate, Infant, Biology and Life Sciences, Tropical Diseases, medicine.disease, Parasitic Protozoans, Malaria, Lead, Age Groups, People and Places, Africa, Population Groupings, Blood lead level, business, Linear regression analysis, Mathematics, Follow-Up Studies
Abstract: International audience; Lead and malaria both present significant health risks to children in Sub-Saharan Africa. Previous studies have shown that high blood lead levels in children act as a protective factor against subsequent malaria incidence. The main objective of this study was to investigate associations between blood lead level and malaria outcomes prospectively in Beninese children from 12 to 24 months of age. Two-hundred and four children were assessed for lead at 12 months and closely followed until 24 months for malaria; when symptoms and parasite density were also recorded. Univariate and multivariate negative binomial and linear regression models tested associations between blood lead level quartile and total episodes of malaria (total symptomatic and asymptomatic episodes) and parasite density, respectively. Median blood lead level among children measured at 12 months was 56.50 (4.81-578) μg/L. During the 12-month follow-up, 172 (84.31%) children had at least one malaria episode. Univariate and multivariate negative binomial and linear regressions did not reveal significant associations between blood lead level quartile and malaria outcomes. Iron deficiency was not found to be an effect modifier. Results from this prospective child-cohort study investigating associations between blood lead level and malaria did not confirm results from previous cross-sectional studies. Further research is needed to further explore this relationship and other co-morbidities due to malaria and lead.
Published: 2019
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42. Enhanced emergence of antibiotic-resistant pathogenic bacteria after in vitro induction with cancer chemotherapy drugs

Author: Marion Richard, Didier Hocquet, Didier Mazel, Christine Fagnoni-Legat, Virginie Nerich, Alexandre Meunier, Xavier Bertrand, Olivier Adotevi, Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de pharmacologie, Plasticité du Génome Bactérien - Bacterial Genome Plasticity (PGB), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), This work was supported by the University Hospital of Besançon, France (Grant RAPACE - APICHU 2016). The study sponsor had no role in the design of the study, the collection, analysis and interpretation of the data, the writing of the manuscript or the decision to submit the manuscript for publication, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Service de pharmacie, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), and Plasticité du Génome Bactérien
Subjects: 0301 basic medicine, Microbiology (medical), Staphylococcus aureus, medicine.drug_class, 030106 microbiology, Antibiotics, Antineoplastic Agents, Drug resistance, Microbial Sensitivity Tests, Biology, medicine.disease_cause, Microbiology, 03 medical and health sciences, SOS Response (Genetics), 0302 clinical medicine, Antibiotic resistance, Drug Resistance, Bacterial, Enterobacter cloacae, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Mutation frequency, SOS response, SOS Response, Genetics, Pharmacology, Pathogenic bacteria, Chemotherapy regimen, 3. Good health, Anti-Bacterial Agents, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Pseudomonas aeruginosa
Abstract: International audience; BACKGROUND:Infections with antibiotic-resistant pathogens in cancer patients are a leading cause of mortality. Cancer patients are treated with compounds that can damage bacterial DNA, potentially triggering the SOS response, which in turn enhances the bacterial mutation rate. Antibiotic resistance readily occurs after mutation of bacterial core genes. Thus, we tested whether cancer chemotherapy drugs enhance the emergence of resistant mutants in commensal bacteria.METHODS:Induction of the SOS response was tested after the incubation of Escherichia coli biosensors with 39 chemotherapeutic drugs at therapeutic concentrations. The mutation frequency was assessed after induction with the SOS-inducing chemotherapeutic drugs. We then tested the ability of the three most highly inducing drugs to drive the emergence of resistant mutants of major bacterial pathogens to first-line antibiotics.RESULTS:Ten chemotherapeutic drugs activated the SOS response. Among them, eight accelerated the evolution of the major commensal E. coli, mostly through activation of the SOS response, with dacarbazine, azacitidine and streptozotocin enhancing the mutation rate 21.3-fold (P
Published: 2018
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43. Modeling and parameter retrieving in time domain spectroscopy of material and metamaterial

Author: Mathias Vanwolleghem, Jean-Francois Lampin, Sergey Mitryukovskiy, Martin Mičica, Romain Peretti, Kevin Froberger, S. Eliet, Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Photonique THz - IEMN (PHOTONIQUE THz - IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), ACKNOWLEDGMENTDuring the writing of this manuscript, we realized how much our humble work mention the foundational works of many great scientists from the past in both physics and mathematics communities. We hope that we did not forget anybody and apologies if we did. This work was partially supported by : i) the international chair of excellence 'ThOTroV' from region 'Hauts-de-France' ii) the French government through the National Research Agency (ANR) under programs PIA EQUIPEX LEAF ANR-11-EQPX-0025 and ExCELSiOR ANR 11-EQPX-0015 and iii) the 'Welcome Talent' grant 'NeFiSToV' from 'Métropole Européenne de Lille'. All the authors are grateful to Jean-Michel Malet for the help to set up the purge aquarium in the TDS set-up., ANR-11-EQPX-0025,LEAF,Plateforme de traitement laser pour l'électronique flexible multifonctionnelle(2011), ANR-11-EQPX-0015,Excelsior,Centre expérimental pour l'étude des propriétés des nanodispositifs dans un large spectre du DC au moyen Infra-rouge.(2011), and Photonique THz - IEMN (PHOTONIQ THz - IEMN)
Subjects: Time-domain spectroscopy, [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], Materials science, refractive index, TeraHertz, business.industry, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Metamaterial, modeling, 02 engineering and technology, 01 natural sciences, 010309 optics, 020210 optoelectronics & photonics, 0103 physical sciences, 0202 electrical engineering, electronic engineering, information engineering, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, Optoelectronics, Time domain, business, Spectroscopy, optimization, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; AbstractIn this proceeding, we present a software Fit@TDS that enables to retrieve the refractive index of a sample from a timedomain spectroscopy experiment. The software include commonly used methods where the refractive index is extracted from frequency domain data. This method has limitations when the signal is too noisy or when the absorption peak saturates the absorption. Thus, the software includes as well a new method where the refractive index are directly fitted using a model (the Drude-Lorentz for example) in the time domain. This method uses an optimization algorithm that retrieves the parameters of the model corresponding to the studied material. In this proceeding, we explain the methods and test them on fictitious samples to probe the feasibility and reliability of the proposed model.
Published: 2018
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44. The 17β-Estradiol induced upregulation of the Adhesion G-protein coupled receptor (ADGRG7) is modulated by ESRα and SP1 complex

Author: Samira Benhadjeba, André Tremblay, Mathieu Lévesque, Shunmoogum A. Patten, Florina Moldovan, Edward T. Bagu, Isabelle Villemure, Amani Hassan, Lydia Edjekouane, CHU Sainte Justine [Montréal], University of South Dakota [Vermillion] (USD), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), École Polytechnique de Montréal (EPM), Université de Montréal (UdeM), This work was supported by the Fondation Yves Cotrel-Institut de France by grants to F.M., and S.A.P., The Faculty of Dentistry, Université de Montréal, Fonds Ernest- Charron and The Network for Oral and Bone Health Research by grants to F.M., We thank the MEDITIS program for the salary support (A.H.) and FRQS to S.A.P., and The authors would like to thank Heather Yampolsky for help in editing and writing of the manuscript. We would like also to thank Dr Stefan Parent, Madam Soraya Barchi and Mr Francois Cyril for providing osteoblasts that were used in the study. We are also grateful for the lab of Dr Santos for providing Huh-7 cells.
Subjects: 0301 basic medicine, QH301-705.5, medicine.drug_class, [SDV]Life Sciences [q-bio], ADGRG7, Science, Estrogen receptor, Biology, Estradiol (E2), General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Downregulation and upregulation, medicine, GPR128, Biology (General), Binding site, Receptor, Adhesion G-protein coupled receptor, G protein-coupled receptor, Regulation of gene expression, Osteoblasts, AIS, Estrogen, Gene regulation, Cell biology, 030104 developmental biology, General Agricultural and Biological Sciences, Gastrointestinal function, Research Article
Abstract: The physiological role and the regulation of ADGRG7 are not yet elucidated. The functional involvement of this receptor was linked with different physiological process such as reduced body weight, gastrointestinal function and recently, a gene variant in ADGRG7 was observed in patients with adolescent idiopathic scoliosis. Here, we identify the ADGRG7 as an estrogen-responsive gene under the regulation of estrogen receptor ERα in scoliotic osteoblasts and other cells lines. We found that ADGRG7 expression was upregulated in response to estrogen (E2) in adolescent idiopathic scoliosis (AIS) cells. ADGRG7 promoter studies indicate the presence of an ERα response half site in close vicinity of a specificity protein 1 (SP1) binding site. Mutation of the SP1 site completely abrogated the response to E2, indicating its essential requirement. ChIP confirmed the binding of SP1 and ERα to the ADGRG7 promoter. Our results identify the ADGRG7 gene as an estrogen-responsive gene under the control of ERα and SP1 tethered actions, suggesting a possible role of estrogens in the regulation of ADGRG7. This article has an associated First Person interview with the first author of the paper., Summary: Estrogen plays a significant role in AIS and studying the regulation of ADGRG7 by E2 in AIS cells is essential for understanding molecular mechanisms underlying AIS pathogenesis.
Published: 2018
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45. Gene flow and adaptive potential in a generalist ectoparasite

Author: Anaïs Appelgren, Blandine Doligez, Heinz Richner, Karen D. McCoy, Verena Saladin, Evolution, adaptation et comportement, Département écologie évolutive [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institute of Ecology & Evolution (IEE), University of Bern, Evolution of host-microbe communities (MIVEGEC-EVCO), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), and The study was financially supported by the French Ministry of Higher Education and Research, the Swiss National Science Foundation, the RégionRhône-Alpes (Explora’doc student mobility grant) and the French National Center for Scientific Research (CNRS). Funding agencies did not participate in or influence study design, data collection, analysis and interpretation, nor writing of the manuscript.
Subjects: 0106 biological sciences, 0301 basic medicine, Population genetics, Generalist and specialist species, 01 natural sciences, Songbirds, Evolutionsbiologi, Parus major, Ceratophyllus gallinae, Principal Component Analysis, education.field_of_study, Geography, biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, Discriminant Analysis, Adaptation, Physiological, Siphonaptera, Habitat fragmentation, Research Article, Gene Flow, Genetic Markers, Evolution, Local adaptation, Population, Zoology, Ficedula albicollis, 010603 evolutionary biology, Host Specificity, Host-Parasite Interactions, 03 medical and health sciences, QH359-425, Animals, Parasites, Ecological specialization, education, Ecology, Evolution, Behavior and Systematics, Isolation by distance, Parus, Evolutionary Biology, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Spatial scale, Genetic Variation, Dispersal, biology.organism_classification, Multi-host system, Genetics, Population, 030104 developmental biology, Genetic Loci, Biological dispersal, Chickens, Microsatellite Repeats, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Background In host-parasite systems, relative dispersal rates condition genetic novelty within populations and thus their adaptive potential. Knowledge of host and parasite dispersal rates can therefore help us to understand current interaction patterns in wild populations and why these patterns shift over time and space. For generalist parasites however, estimates of dispersal rates depend on both host range and the considered spatial scale. Here, we assess the relative contribution of these factors by studying the population genetic structure of a common avian ectoparasite, the hen flea Ceratophyllus gallinae, exploiting two hosts that are sympatric in our study population, the great tit Parus major and the collared flycatcher Ficedula albicollis. Previous experimental studies have indicated that the hen flea is both locally maladapted to great tit populations and composed of subpopulations specialized on the two host species, suggesting limited parasite dispersal in space and among hosts, and a potential interaction between these two structuring factors. Results C. gallinae fleas were sampled from old nests of the two passerine species in three replicate wood patches and were genotyped at microsatellite markers to assess population genetic structure at different scales (among individuals within a nest, among nests and between host species within a patch and among patches). As expected, significant structure was found at all spatial scales and between host species, supporting the hypothesis of limited dispersal in this parasite. Clustering analyses and estimates of relatedness further suggested that inbreeding regularly occurs within nests. Patterns of isolation by distance within wood patches indicated that flea dispersal likely occurs in a stepwise manner among neighboring nests. From these data, we estimated that gene flow in the hen flea is approximately half that previously described for its great tit hosts. Conclusion Our results fall in line with predictions based on observed patterns of adaptation in this host-parasite system, suggesting that parasite dispersal is limited and impacts its adaptive potential with respect to its hosts. More generally, this study sheds light on the complex interaction between parasite gene flow, local adaptation and host specialization within a single host-parasite system. Electronic supplementary material The online version of this article (10.1186/s12862-018-1205-2) contains supplementary material, which is available to authorized users.
Published: 2018
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46. The use of FDI criteria in clinical trials on direct dental restorations: A scoping review

Author: Brigitte Grosgogeat, Thomas Marquillier, M Pérard, Florence Chemla, Pierre Millet, Justine Le Clerc, Jean-Christophe Maurin, Sophie Doméjean, Kerstin Gritsch, Elisabeth Dursun, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche en Odontologie Clinique - Clermont Auvergne (CROC), Université Clermont Auvergne (UCA), Université de Rennes 1 - UFR d'Odontologie (UR1 Odontologie), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Faculté de Chirurgie Dentaire (UPD5 Odontologie), Université Paris Descartes - Paris 5 (UPD5), Laboratoire des Multimatériaux et Interfaces (LMI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université des Sciences et de la Technologie Houari Boumediene [Alger] (USTHB), Centre Hospitalier Universitaire de Reims (CHU Reims), Unité de Recherche Biomatériaux Innovants et Interfaces (URB2i - EA 4462), Université Paris Descartes - Paris 5 (UPD5)-Université Paris 13 (UP13), To the DECAT collaborative group, especially the team of Pr Gueyffier (coordination) and the Hospices Civils of Lyon (sponsor).This review is in relation with the DECAT study (DEep Caries Treatment). This clinical trial received a PHRC grant (which is a French funding source for hospital clinical trial) from the ministry of health (DGOS). This funding source had neither involvement in the study design, in the analysis, collection and interpretation of data nor in the writing of this manuscript. Tothe corresponding authors of the included studies, whoanswered the questionnaire. To Maxime Faure, who contributed to this publication as part of his end-of-studies thesis in Dental Surgery (University Lyon 1, France). To Misha Dhuper (University of Ottawa), who reviewed the English language in this manuscript.., Centre de Recherche en Odontologie Clinique (CROC), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), UFR d’Odontologie, Université de Lyon, Hospices Civils de Lyon (HCL), Université Paris 13 (UP13)-Université Paris Descartes - Paris 5 (UPD5), Université de Rennes - UFR d'Odontologie (UR Odontologie), Université de Rennes (UR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université des Sciences et de la Technologie Houari Boumediene = University of Sciences and Technology Houari Boumediene [Alger] (USTHB), Université de Reims Champagne-Ardenne (URCA), and Institut de Thermique, Mécanique, Matériaux (ITheMM)
Subjects: Databases, Factual, Surface Properties, Direct dental restorations, Clinical assessment, MEDLINE, Color, Dentistry, Dental Caries, Composite Resins, 03 medical and health sciences, 0302 clinical medicine, Usphs criteria, Humans, Medicine, Tooth Erosion, Clinical significance, Dental Restoration Failure, 030212 general & internal medicine, Dental Restoration, Permanent, Restorative dentistry, General Dentistry, Clinical Trials as Topic, FDI criteria, business.industry, Retrospective cohort study, 030206 dentistry, Dental Marginal Adaptation, Dentin Sensitivity, Clinical judgment, Clinical trial, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: OBJECTIVES: A scoping review was conducted to explore the use of FDI criteria 10 years after their introduction. The first aim was to compare the amount of studies using the FDI and/or the modified USPHS criteria. The second aim was to analyse the use of the FDI criteria in clinical trials evaluating direct dental restorations. DATA: Listing of studies using FDI and/or USPHS criteria per year since 2007. Clinical studies related to the assessment of direct restorations using FDI criteria. SOURCE: Two systematic searches - regarding the use of FDI and modified USPHS criteria - were carried out on Medline/Pubmed in order to identify the studies published between 2007 and 2017. Authors of the included articles were contacted to clarify their choice of FDI criteria in their studies. ClinicalTrials.gov database was also queried for the on-going studies that use FDI and modified USPHS criteria. STUDY SELECTION: In the first review, all the clinical trials (randomized/non-randomized, controlled, prospective/retrospective studies) that used FDI criteria to evaluate direct restorations on primary or permanent teeth were included. CONCLUSIONS: 16.3% of the studies used FDI criteria. The percentage of studies using them increased from 4.5% in 2010 to 50.0% in 2016. In average, 8.5 FDI criteria were used. The most employed criteria were: marginal adaptation (96.7%), staining (90.0%), fracture of material and retention (90.0%), recurrence of caries/erosion/abfraction (90.0%), post-operative sensitivity/tooth vitality (86.7%) and surface luster (60.0%). In addition, among the 27 on-going studies from ClinicalTrials.gov database, 51.9% use FDI criteria (including 87.5% with an open recruitment status). CLINICAL SIGNIFICANCE: FDI criteria were reported as practical (various and freely selectable), relevant (sensitive as well as appropriate to current restorative materials and clinical studies design), standardized (making comparisons between investigations easier). Investigators should go on using them for a better standardization of their clinical judgment, allowing comparisons with other studies.
Published: 2018
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47. Auditory cortex interneuron development requires cadherins operating hair-cell mechanoelectrical transduction

Author: Libé-Philippot, Baptiste, Vittot, Michel, Boutet de Monvel, Jacques, Le Gal, Sébastien, Dupont, Typhaine, Avan, Paul, Métin, Christine, Michalski, Nicolas, Petit, Christine, Collège de France - Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Equipe Biophysique Neurosensorielle [Neuro-Dol], Neuro-Dol (Neuro-Dol), Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de la Vision, 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), This work was supported by PhD funding from the French Ministry of Research allocated by the Ecole Normale Supérieure (Paris) (to B.L.-P.), the Prix Emergence and the SEIZEAR grant of the Agir Pour l’Audition foundation (to N.M.), and by grants from the ANR as part of the second Investissements d’Avenir program LIGHT4DEAF (ANR-15-RHUS-0001) and LabEx LIFESENSES (ANR-10-LABX-65), the European Research Council (ERC-2011-ADG_294570 to C.P.), BNP Paribas Foundation, FAUN-Stiftung, and LHW-Stiftung., We thank M. Bosch Grau, S. Chardenoux, A. Emptoz, C. Leclech, D. Oficjalska, M. Pedraza Boti, E. Pepermans, C. Trébeau, and D. Weil for assistance with this project, and J.-P. Hardelin for his important contribution to the writing of the manuscript. We thank S. Etienne-Manneville (Institut Pasteur, Paris) and S. Garel (Ecole Normale Supérieure, Paris) for advice. We thank G. Lepousez (Institut Pasteur, Paris) and N. Renier (Institut du Cerveau et de la Moelle Epinière, Paris) for critical reading of the manuscript. We thank C. Dehay (PrimaLyon Platform, Institut Cellule Souche et Cerveau, INSERM, Bron, France), N. Kessaris (University College London, London), and M. Sato (University of Fukui, Fukui, Japan) for sharing brain sections from macaque embryos, Nkx2.1-cre:Rosa-tdTomato mice, and Adgrv1tm1Msat mice, respectively. We acknowledge the Imagopole/Citech facility (Institut Pasteur, Paris), which is part of the France BioImaging infrastructure supported by the French Agence Nationale pour la Recherche (ANR-10-INSB-04-01, Investissements d’Avenir program), for the use of its microscopes, ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), ANR-15-RHUS-0001,LIGHT4DEAF,ECLAIRER LA SURDITÉ : UNE APPROCHE HOLISTIQUE DU SYNDROME D'USHER(2015), European Project: 294570,EC:FP7:ERC,ERC-2011-ADG_20110310,HAIRBUNDLE(2012), Chaire Génétique et physiologie cellulaire, michalski, nicolas, Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID, ECLAIRER LA SURDITÉ : UNE APPROCHE HOLISTIQUE DU SYNDROME D'USHER - - LIGHT4DEAF2015 - ANR-15-RHUS-0001 - RHUS - VALID, and Assembling the puzzle of the operating auditory hair bundle - HAIRBUNDLE - - EC:FP7:ERC2012-12-01 - 2017-11-30 - 294570 - VALID
Subjects: Auditory Cortex, Male, neuronal migration, tip links, Cadherin Related Proteins, Cell Polarity, Biological Sciences, Cadherins, Mechanotransduction, Cellular, Receptors, G-Protein-Coupled, Mice, adhesion code, nervous system, parvalbumin interneurons, Interneurons, deafness, Animals, Macaca, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Protein Precursors
Abstract: International audience; Many genetic forms of congenital deafness affect the sound reception antenna of cochlear sensory cells, the hair bundle. The resulting sensory deprivation jeopardizes auditory cortex (AC) maturation. Early prosthetic intervention should revive this process. Nevertheless, this view assumes that no intrinsic AC deficits coexist with the cochlear ones, a possibility as yet unexplored. We show here that many GABAergic interneurons, from their generation in the medial ganglionic eminence up to their settlement in the AC, express two cadherin-related (cdhr) proteins, cdhr23 and cdhr15, that form the hair bundle tip links gating the mechanoelectrical transduction channels. Mutant mice lacking either protein showed a major decrease in the number of parvalbumin interneurons specifically in the AC, and displayed audiogenic reflex seizures. Cdhr15- and Cdhr23-expressing interneuron precursors in Cdhr23(-/-) and Cdhr15(-/-) mouse embryos, respectively, failed to enter the embryonic cortex and were scattered throughout the subpallium, consistent with the cell polarity abnormalities we observed in vitro. In the absence of adhesion G protein-coupled receptor V1 (adgrv1), another hair bundle link protein, the entry of Cdhr23- and Cdhr15-expressing interneuron precursors into the embryonic cortex was also impaired. Our results demonstrate that a population of newborn interneurons is endowed with specific cdhr proteins necessary for these cells to reach the developing AC. We suggest that an "early adhesion code" targets populations of interneuron precursors to restricted neocortical regions belonging to the same functional area. These findings open up new perspectives for auditory rehabilitation and cortical therapies in patients.
Published: 2017
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48. Roussouly's sagittal spino-pelvic morphotypes as determinants of gait in asymptomatic adult subjects

Author: Ziad Bakouny, Abir Massaad, Ismat Ghanem, Wafa Skalli, Gaby Kreichati, Elie Saghbini, Ayman Assi, Virginie Lafage, Université Saint-Joseph de Beyrouth (USJ), Institut de Biomécanique Humaine Georges Charpak (IBHGC), Université Sorbonne Paris Nord-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), This study was supported by the research council of the University of Saint-Joseph (grant number: FM189). The study sponsors were involved in neither the study design, collection, analysis and interpretation of data nor in the writing of the manuscript, and nor in the decision to submit the manuscript for publication.
Subjects: Pelvic tilt, Adult, Male, Pelvic incidence, Kinematics, Adolescent, Posture, Biophysics, Roussouly classification, Osteoarthritis, Walking, Asymptomatic, Sagittal alignment, Pelvis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Image Interpretation, Computer-Assisted, medicine, Humans, Orthopedics and Sports Medicine, Lumbar lordosis, Gait, Femoroacetabular impingement, 030222 orthopedics, business.industry, Rehabilitation, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Anatomy, medicine.disease, Sagittal plane, Spine, Biomechanical Phenomena, medicine.anatomical_structure, Cross-Sectional Studies, Gait analysis, Sciences du vivant, Female, Ankle, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Sagittal alignment is known to greatly vary between asymptomatic adult subjects; however, there are no studies on the possible effect of these differences on gait. The aim of this study is to investigate whether asymptomatic adults with different Roussouly sagittal alignment morphotypes walk differently. Ninety-one asymptomatic young adults (46M & 45W), aged 21.6±2.2years underwent 3D gait analysis and full body biplanar X-rays with three-dimensional (3D) reconstructions of their spines and pelvises and generation of sagittal alignment parameters. Subjects were divided according to Roussouly's sagittal alignment classification. Sagittal alignment and kinematic parameters were compared between Roussouly types. 17 subjects were classified as type 2, 47 as type 3, 26 as type 4 but only 1 as type 1. Type 2 subjects had significantly more mean pelvic retroversion (less mean pelvic tilt) during gait compared to type 3 and 4 subjects (type 2: 8.2°; type 3:11.2°, type 4: 11.3°) and significantly larger ROM pelvic obliquity compared to type 4 subjects (type 2: 11.0°; type 4: 9.1°). Type 2 subjects also had significantly larger maximal hip extension during stance compared to subjects of types 3 and 4 (type 2: -11.9°; type 3: -8.8°; type 4: -7.9°) and a larger ROM of ankle plantar/dorsiflexion compared to type 4 subjects (type 2: 31.1°; type 4: 27.9°). Subjects with type 2 sagittal alignment were shown to have a gait pattern involving both increased hip extension and pelvic retroversion which could predispose to posterior femoroacetabular impingement and consequently osteoarthritis. This study was supported by the research council of the University of Saint-Joseph (grant number: FM189). The study sponsors were involved in neither the study design, collection, analysis and interpretation of data nor in the writing of the manuscript; nor in the decision to submit the manuscript for publication.
Published: 2017
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49. Expression and epigenomic landscape of the sex chromosomes in mouse post-meiotic male germ cells

Author: Charlotte Moretti, Daniel Vaiman, Frédéric Tores, Julie Cocquet, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Plateforme de génomique [SFR Necker], Structure Fédérative de Recherche Necker ( SFR Necker - UMS 3633 / US24 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), This work was supported by Inserm (Institut National de la Sante et de la Recherche Medicale), Cnrs (Centre National de la Recherche Scientifique), Université Paris Descartes, the Agence Nationale de la Recherche program ANR-12–JSV2-0005–01 (to J.C.) and a Marie Curie fellowship FP7-PEOPLE-2010-IEF-273143 (to J.C.). The funding bodies did not have any role in the design of the study, the collection, analysis, and interpretation of data nor in the writing of the manuscript., Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), BMC, BMC, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Epigenomics, Male, 0301 basic medicine, X Chromosome, Mouse, [SDV]Life Sciences [q-bio], Spermiogenesis, Biology, Crotonylation, Y chromosome, Genome, H3K9me3, Histones, Mice, 03 medical and health sciences, Meiosis, Y Chromosome, Genetics, Animals, Spermatogenesis, Molecular Biology, Autosome, MSCI, [ SDV ] Life Sciences [q-bio], Sequence Analysis, RNA, Research, High-Throughput Nucleotide Sequencing, Chromosome, Sex chromosomes, H3K4me3, H3K27ac, Chromosome 14, Spermatids, Chromatin, [SDV] Life Sciences [q-bio], Germ Cells, 030104 developmental biology, Microscopy, Fluorescence, Post-meiotic sex chromatin
Abstract: Background During meiosis, the X and Y chromosomes are transcriptionally silenced. The persistence of repressive chromatin marks on the sex chromatin after meiosis initially led to the assumption that XY gene silencing persists to some extent in spermatids. Considering the many reports of XY-linked genes expressed and needed in the post-meiotic phase of mouse spermatogenesis, it is still unclear whether or not the mouse sex chromatin is a repressive or permissive environment, after meiosis. Results To determine the transcriptional and chromatin state of the sex chromosomes after meiosis, we re-analyzed ten ChIP-Seq datasets performed on mouse round spermatids and four RNA-seq datasets from male germ cells purified at different stages of spermatogenesis. For this, we used the last version of the genome (mm10/GRCm38) and included reads that map to several genomic locations in order to properly interpret the high proportion of sex chromosome-encoded multicopy genes. Our study shows that coverage of active epigenetic marks H3K4me3 and Kcr is similar on the sex chromosomes and on autosomes. The post-meiotic sex chromatin nevertheless differs from autosomal chromatin in its enrichment in H3K9me3 and its depletion in H3K27me3 and H4 acetylation. We also identified a posttranslational modification, H3K27ac, which specifically accumulates on the Y chromosome. In parallel, we found that the X and Y chromosomes are enriched in genes expressed post-meiotically and display a higher proportion of spermatid-specific genes compared to autosomes. Finally, we observed that portions of chromosome 14 and of the sex chromosomes share specific features, such as enrichment in H3K9me3 and the presence of multicopy genes that are specifically expressed in round spermatids, suggesting that parts of chromosome 14 are under the same evolutionary constraints than the sex chromosomes. Conclusions Based on our expression and epigenomic studies, we conclude that, after meiosis, the mouse sex chromosomes are no longer silenced but are nevertheless regulated differently than autosomes and accumulate different chromatin marks. We propose that post-meiotic selective constraints are at the basis of the enrichment of spermatid-specific genes and of the peculiar chromatin composition of the sex chromosomes and of parts of chromosome 14. Electronic supplementary material The online version of this article (doi:10.1186/s13072-016-0099-8) contains supplementary material, which is available to authorized users.
Published: 2016
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50. Evaluation of the performances of six commercial kits designed for dengue NS1 and anti-dengue IgM, IgG and IgA detection in urine and saliva clinical specimens

Author: Anne-Claire Andries, Anavaj Sakuntabhai, Veasna Duong, Sivuth Ong, Philippe Dussart, Paul F. Horwood, Philippe Buchy, Sopheaktra Ros, Unité de Virologie / Virology Unit [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), The study was supported by Standard Diagnostics, Inc. The funders had no role in study design, in the collection, analysis and interpretation of data, in writing of the manuscript, or in the decision to submit the article for publication. This research also received funding from the European Union Seventh Framework Programme (FP7/2007/2011) under Grant Agreement n°282 378., European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
Subjects: 0301 basic medicine, Immunoglobulin A, Saliva, MESH: Reagent Kits, Diagnostic, NS1, Urine, Rapid diagnostic test, MESH: Dengue, Viral Nonstructural Proteins, Dengue virus, medicine.disease_cause, MESH: Dengue Virus, Immunoglobulin G, Dengue fever, Dengue, 0302 clinical medicine, Medicine, MESH: Immunoglobulin G, biology, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Case-Control Studies, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Immunoglobulin M, 3. Good health, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Research Article, 030231 tropical medicine, 030106 microbiology, Enzyme-Linked Immunosorbent Assay, Sensitivity and Specificity, Antibodies, 03 medical and health sciences, parasitic diseases, Humans, MESH: Saliva, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Diagnostic, MESH: Immunoglobulin A, MESH: Humans, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], business.industry, Dengue Virus, medicine.disease, MESH: Sensitivity and Specificity, Immunoglobulin M, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Case-Control Studies, Immunology, biology.protein, MESH: Viral Nonstructural Proteins, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Reagent Kits, Diagnostic, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business
Abstract: Background Rapid diagnostic tests (RDTs) have been commercialized in order to help physicians in dengue diagnosis. Until recently, only blood samples were used for those tests but it has been shown in several studies that urine and saliva can also be employed for dengue diagnosis. RDTs for the detection of NS1 antigen and anti-dengue IgG, IgM and IgA in urine and saliva specimens have thus been developed by Standard Diagnostics. The aim of this study was to evaluate the performances these new commercial assays. Methods Two panels of clinical specimens were used: one for the evaluation of the NS1-detection devices and the second for the evaluation of the antibody-detection kits. Each panel consisted of urine and saliva specimens collected sequentially from 86 patients with a confirmed dengue infection. A total of 291 saliva and 440 urine samples were included in the NS1-evaluation panel and 530 saliva and 528 urine specimens constituted the antibody-evaluation panel. All samples were tested in parallel by in-house ELISAs and by the commercial RDTs. Results The RDTs demonstrated an overall sensitivity of 15.5 %/27.9 %/10.7 % for NS1/IgG/IgA detection in urine samples and 20.4 %/ 34.8 %/11 %/6.2 % for NS1/IgG/IgM/IgA detection in saliva samples. Compared to the in-house NS1 ELISA, the results obtained with the NS1 RDT demonstrated a good correlation with urine samples (kappa coefficient: 0.88) but not with saliva specimens (kappa coefficient: 0.28). RDTs designed for antibody detection in saliva and urine were extremely specific (100 %), but less sensitive than the in-house ELISAs (i.e., reduction of the overall sensitivity by 12.2 % for the RDT designed for IgG detection in urine and by 23.7 % for the RDT detecting anti-DENV IgM in saliva). IgM were not detected in urine, either by RDT or ELISA. Conclusions Although the RDTs evaluated here offer an apparently attractive approach for dengue diagnosis, this study suggests that these new commercial kits would require further improvement to increase the sensitivity. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1551-x) contains supplementary material, which is available to authorized users.
Published: 2016
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