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1. 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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2. 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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3. 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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4. 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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5. 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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6. 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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7. 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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8. 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), Société Française de Médecine 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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9. 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

10. 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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11. 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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12. 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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13. 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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14. Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis

Author

C Rodríguez-Martin, Bella Pajares, Manuel Ruiz-Borrego, Ana Lluch, MC Cámara, Miguel Martin, Eva Carrasco, Marina Pollán, Antonio Antón, Manuel Ramos, Miguel Ángel Seguí, John R. Mackey, Tadeusz Pienkowski, Olivier Tredan, Charles L. Vogel, Joaquín Gavilá, Emilio Alba, Lourdes Calvo, Álvaro Rodríguez-Lescure, Grupo Español de Investigación de Cáncer de Mama, Sanofi, Bristol-Myers Squibb, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Spanish Breast Cancer Research Group, GEICAM, [Pajares,B, Alba,E] Medical Oncology Department, Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain. [Pollán,M] Epidemiology Nacional Center, Instituto de Salud Carlos III, Madrid, Spain. [Martín,M] Medical Oncology Department, Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain. [Mackey,J] Medical Oncology Department, Medical Cross Cancer Institute, Edmonton, AB, Canada. [Lluch,A] Hematology-Oncology Department, Hospital Clínico Universitario de Valencia- INCLIVA Health Research Institute, University of Valencia, Valencia, Spain. [Gavila,J] Medical Oncology Department, Instituto Valenciano de Oncología, Valencia, Spain. [Vogel,Ch] Medical Oncology Department, Sylvester Comprehensive Cancer at Deerfield, Miller School of Medicine, Univ. of Miami- Deerfield Bch, Miami, FL, USA. [Ruiz-Borrego,M] Medical Oncology Department, Hospital Virgen del Rocío, Sevilla, Spain. [Calvo,L] Medical Oncology Department, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain. [Pienkowski,T] Medical Oncology Department, European Health Center, Otwock, Poland. [Rodríguez-Lescure,A] Medical Oncology Department, Hospital General Universitario de Elche, Alicante, Spain. [Seguí,MA] Medical Oncology Department, Corporación Sanitaria Parc Taulí, Sabadell, Spain. [Trendan,O] Medical Oncology Department, Centre Léon Bérard, Lyon, France. [Antón,A] Medical Oncology Department, Hospital Miguel Servet, Zaragoza, Spain. [Ramos,M] Medical Oncology Department, Centro Oncológico de Galicia, A Coruña, Spain. [Cámara,MdC, Rodríguez-Martín,C, Carrasco,E] Spanish Breast Cancer Research Group, GEICAM, Madrid, Spain., and This work was supported by the Spanish Breast Cancer Research Group (Grupo Español de Investigación de Cáncer de Mama) (GEICAM). No funding was received for the data analyses or the writing of this manuscript. Clinical trials GEICAM/9805 and BCIRG 001 were funded by Sanofi Aventis. GEICAM/9906 and GEICAM/2003-02 were partially funded by Bristol-Myers Squibb. These funding bodies were not involved in the collection and interpretation of the data or in the decision to publish. EA and MM were also supported by FEDER (RECTICC-RD12/0036/0076)

Subjects
Índice de Masa Corporal, Oncology, Receptor, ErbB-2, medicine.medical_treatment, Obesidad, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis [Medical Subject Headings], Supervivencia sin Enfermedad, Body Mass Index, Antineoplastic Combined Chemotherapy Protocols, Medicine, Anthracyclines, Young adult, Medicine(all), Hazard ratio, Neoplasias de la Mama, Pronóstico, Femenino, Middle Aged, Prognosis, Chemotherapy regimen, Treatment Outcome, Female, Taxoids, Mastectomy, Research Article, Adult, medicine.medical_specialty, Análisis de Supervivencia, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Breast Neoplasms, Disease-Free Survival, Young Adult, Breast cancer, Internal medicine, Adjuvant therapy, Humans, Obesity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Disease-Free Survival [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Gynecology, Dose-Response Relationship, Drug, business.industry, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [Medical Subject Headings], Retrospective cohort study, Antineoplásicos, medicine.disease, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Multivariate Analysis, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], Neoplasm Recurrence, Local, business, Body mass index
Abstract

Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification. METHODS: We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003-02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype. RESULTS: Multivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype. CONCLUSIONS: Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes. This work was supported by the Spanish Breast Cancer Research Group (Grupo Español de Investigación de Cáncer de Mama) (GEICAM). No funding was received for the data analyses or the writing of this manuscript. Clinical trials GEICAM/9805 and BCIRG 001 were funded by Sanofi Aventis. GEICAM/9906 and GEICAM/2003-02 were partially funded by Bristol-Myers Squibb. These funding bodies were not involved in the collection and interpretation of the data or in the decision to publish. EA and MM were also supported by FEDER (RECTICC-RD12/0036/0076). We thank all the participating patients, clinicians, GEICAM and local research staff. We thank Hosanna Soler Vila, PhD, who provided medical writing services on behalf of GEICAM. Sí

Published
2013

15. Oral verrucous hyperplasia due to repetitive chewing on lips

Author

Richard Alweis, Stephen Melnick, Salik Nazir, Noelle Juliano, Priya Rajagopalan, and SN, PR, SM & NJ were involved in overall drafting, design and writing of the manuscript. RA was involved in patient care, diagnosis and overall design of the manuscript. All authors have read and agreed with the final manuscript

Subjects
lcsh:Internal medicine, medicine.medical_specialty, business.industry, Verrucous carcinoma, 030206 dentistry, medicine.disease, Dermatology, Community hospital, Verrucous hyperplasia, 03 medical and health sciences, Premalignant lesions, verrucous hyperplasia, verrucous carcinoma, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal Medicine, Medicine, lcsh:RC31-1245, business, Imaging Column
Abstract

No abstract available. (Published: 6 July 2016) Citation: Journal of Community Hospital Internal Medicine Perspectives 2016, 6 : 31595 - http://dx.doi.org/10.3402/jchimp.v6.31595

Published
2016
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