Descriptor: "Human health and pathology" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

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189 results on '"Human health and pathology"'

1. Paclitaxel induces lymphatic endothelial cells autophagy to promote metastasis

Author: Anne-Catherine Prats, Barbara Garmy-Susini, Melinda Alves, Laurent O. Martinez, Charlotte Vaysse, Souad Najib, Anne Gomez-Brouchet, Julie Guillermet-Guibert, Eric Lacazette, Nicole Therville, Charlotte Chollet, Florence Tatin, Camille Franchet, Audrey Zamora, Tiffany Fougeray, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Garmy-Susini, Barbara, ProdInra, Migration, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cancer Research, medicine.medical_treatment, Metastasis, chemistry.chemical_compound, Breast cancer, 0302 clinical medicine, Cell Movement, Cancer, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, lcsh:Cytology, Chloroquine, 3. Good health, Endothelial stem cell, Lymphatic Endothelium, Lymphatic system, medicine.anatomical_structure, Paclitaxel, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Female, Lymph, Sentinel Lymph Node, Endothelium, Cell Survival, government.form_of_government, Immunology, Médecine humaine et pathologie, Breast Neoplasms, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cell Line, Tumor, Autophagy, Cell Adhesion, medicine, Humans, lcsh:QH573-671, Cell Proliferation, 030304 developmental biology, Chemotherapy, business.industry, Endothelial Cells, Cell Biology, medicine.disease, chemistry, Drug Resistance, Neoplasm, government, Cancer research, Human health and pathology, Lysosomes, business, Proto-Oncogene Proteins c-akt, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Cytotoxic therapy for breast cancer inhibits the growth of primary tumors, but promotes metastasis to the sentinel lymph nodes through the lymphatic system. However, the effect of first-line chemotherapy on the lymphatic endothelium has been poorly investigated. In this study, we determined that paclitaxel, the anti-cancer drug approved for the treatment of metastatic or locally advanced breast cancer, induces lymphatic endothelial cell (LEC) autophagy to increase metastases. While paclitaxel treatment was largely efficacious in inhibiting LEC adhesion, it had no effect on cell survival. Paclitaxel inhibited LEC migration and branch point formation by inducing an autophagy mechanism independent of Akt phosphorylation. In vivo, paclitaxel mediated a higher permeability of lymphatic endothelium to tumor cells and this effect was reversed by chloroquine, an autophagy-lysosome inhibitor. Despite a strong effect on reducing tumor size, paclitaxel significantly increased metastasis to the sentinel lymph nodes. This effect was restricted to a lymphatic dissemination, as chemotherapy did not affect the blood endothelium. Taken together, our findings suggest that the lymphatic system resists to chemotherapy through an autophagy mechanism to promote malignant progression and metastatic lesions. This study paves the way for new combinative therapies aimed at reducing the number of metastases.
Published: 2019

2. Whey protein isolate modulates beta-carotene bioaccessibility depending on gastro-intestinal digestion conditions

Author: Torsten Bohn, Yvan Larondelle, Charles Desmarchelier, Giulia Dingeo, Patrick Borel, Celal Degerli, Thomas Schleeh, Mohammed Iddir, Luxembourg Institute of Health (LIH), Centre recherche en CardioVasculaire et Nutrition (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Luxembourg Institute of Science and Technology (LIST), Institut des Sciences de la Vie, Université Catholique de Louvain (UCL), Faculté de Médecine et Médecine Dentaire [UCLouvain], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Université Catholique de Louvain = Catholic University of Louvain (UCL), Grant No. C16/BM/11320230, EU-COST actions EUROCAROTEN (CA15136) and POSITIVE (FA 1403), Prémilleux, Annick, and UCL - SST/LIBST - Louvain Institute of Biomolecular Science and Technology
Subjects: micellisation, [SDV]Life Sciences [q-bio], 01 natural sciences, Analytical Chemistry, Whey protein isolate, Pepsin, Bile, activité gastrointestinale, Food science, Carotenoid, Micelles, bioaccessibilité, ComputingMilieux_MISCELLANEOUS, onde péristaltique, 2. Zero hunger, chemistry.chemical_classification, biology, Chemistry, Emulsion, food and beverages, Micellization, 04 agricultural and veterinary sciences, General Medicine, beta Carotene, 040401 food science, [SDV] Life Sciences [q-bio], Spectrophotometry, protéine, gouttelette lipidique, Digestion, émulsion, Biological Availability, Médecine humaine et pathologie, Absorption (skin), In Vitro Techniques, carotenoide, 0404 agricultural biotechnology, beta-Carotene, Humans, Proteins, Carotenoids, Lipid droplets, Peristalsis, beta carotène, cinétique de digestion, 010401 analytical chemistry, Pepsin A, 0104 chemical sciences, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, isolat protéique, Whey Proteins, Enzyme, Pancreatin, Digestive enzyme, biology.protein, Human health and pathology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract: International audience; Carotenoids are lipophilic phytochemicals; their intake has been associated with reduced chronic diseases. However, their absorption depends on emulsification during digestion and incorporation into mixed micelles, requiring digestive enzymes, gastric peristalsis, bile, and dietary lipids. In this study, we investigated whether whey-protein-isolate (WPI), a commonly consumed protein source, can modulate β-carotene bioaccessibility in vitro, especially under incomplete digestive conditions, i.e. under low digestive enzyme concentrations. Thus, amounts of pepsin, pancreatin, bile, co-digested lipids and kinetic energy and gastric digestion time were modified, and WPI at concentrations equivalent to 0/25/50% of the protein recommended dietary allowance (approx. 60 g/d) were added to β-carotene dissolved in oil. WPI enhanced bioaccessibility by up to 20% (p
Published: 2019

3. Increased levels of the megakaryocyte and platelet expressed cysteine proteases stefin A and cystatin A prevent thrombosis

Author: Marie-Christine Alessi, Anna Mezzapesa, Marie Maraninchi, Delphine Bastelica, Christophe Dubois, Lydie Crescence, Michel Grino, Marjorie Poggi, Jean-Claude Bordet, Annabelle Dupont, Laurence Panicot-Dubois, Franck Peiretti, René Valéro, Matthias Canault, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, 'Fondation de France' (grant 00056841) and the Société Francophone du Diabète, Centre recherche en CardioVasculaire et Nutrition (C2VN), Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), and Prémilleux, Annick
Subjects: 0301 basic medicine, Male, Platelet Aggregation, [SDV]Life Sciences [q-bio], lcsh:Medicine, cathepsine, Cathepsin B, Mice, 0302 clinical medicine, Megakaryocyte, mégacaryocyte, Platelet, thrombose, Receptor, lcsh:Science, Mice, Knockout, Multidisciplinary, Chemistry, analyse de l'expression génique, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Megakaryocytes, Blood Platelets, Platelets, Médecine humaine et pathologie, Article, Diabetes Mellitus, Experimental, 03 medical and health sciences, Downregulation and upregulation, medicine, Animals, Humans, Cystatin A, Platelet activation, Calcium Signaling, Obesity, Thrombus, Rats, Wistar, protéase à cystéine, lcsh:R, Thrombosis, medicine.disease, Platelet Activation, Molecular biology, Rats, Mice, Inbred C57BL, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, Human health and pathology, lcsh:Q, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery
Abstract: Increased platelet activity occurs in type 2 diabetes mellitus (T2DM) and such platelet dysregulation likely originates from altered megakaryopoiesis. We initiated identification of dysregulated pathways in megakaryocytes in the setting of T2DM. We evaluated through transcriptomic analysis, differential gene expressions in megakaryocytes from leptin receptor-deficient mice (db/db), exhibiting features of human T2DM, and control mice (db/+). Functional gene analysis revealed an upregulation of transcripts related to calcium signaling, coagulation cascade and platelet receptors in diabetic mouse megakaryocytes. We also evidenced an upregulation (7- to 9.7-fold) of genes encoding stefin A (StfA), the human ortholog of Cystatin A (CSTA), inhibitor of cathepsin B, H and L. StfA/CSTA was present in megakaryocytes and platelets and its expression increased during obesity and diabetes in rats and humans. StfA/CSTA was primarily localized at platelet membranes and granules and was released upon agonist stimulation and clot formation through a metalloprotease-dependent mechanism. StfA/CSTA did not affect platelet aggregation, but reduced platelet accumulation on immobilized collagen from flowing whole blood (1200 s−1). In-vivo, upon laser-induced vascular injury, platelet recruitment and thrombus formation were markedly reduced in StfA1-overexpressing mice without affecting bleeding time. The presence of CA-074Me, a cathepsin B specific inhibitor significantly reduced thrombus formation in-vitro and in-vivo in human and mouse, respectively. Our study identifies StfA/CSTA as a key contributor of platelet-dependent thrombus formation in both rodents and humans.
Published: 2019

4. Comprehensive clinical profiling of the Gauting locoregional lung adenocarcinoma donors

Author: Serge Guyétant, Jürgen Behr, Yves Courty, Kristina A. M. Arendt, Agnès Petit-Courty, Sylvain Marchand-Adam, Valérie Gissot, Anne-Sophie Lamort, Ina Koch, Jan‐Christian Kaiser, Georgios T. Stathopoulos, Ioanna Giopanou, Maria Oplopoiou, Michael Lindner, Ioannis Lilis, Martin E. Eichhorn, Rudolf Hatz, Giannoula Ntaliarda, Mario A.A. Pepe, Laura V. Klotz, Anja Stowasser, Alicia Morresi-Hauf, Sabine J. Behrend, Ludwig Maximilians University of Munich, German Center for Lung Research, Comprehensive pneumology center, Partenaires INRAE, University Hospital, German Centre for Lung Research, Institut National de la Santé et de la Recherche Médicale (INSERM), University-Hospital Munich-Großhadern [München], Heidelberg University, University of Patras, Alexander Fleming Biomedical Sciences Research Center, Asklepios Medical Center, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours), Asklepios Lung Clinic Gauting, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Ludwig-Maximilians University [Munich] (LMU), and ProdInra, Migration
Subjects: 0301 basic medicine, Research design, Male, Cancer Research, Lung Neoplasms, Death risk, Pneumologie et système respiratoire, LADC, lung adenocarcinoma, obstruction, smoking, survival, Pulmonary Surgical Procedures, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, Recurrence, Germany, Medicine, Prospective Studies, Cancer, Original Research, Curative intent, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, résection, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cohort, Adenocarcinoma, Female, Lung resection, medicine.medical_specialty, adénocarcinome, Médecine humaine et pathologie, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma of Lung, lcsh:RC254-282, Time-to-Treatment, 03 medical and health sciences, FEV1/FVC ratio, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Humans, tabagisme, Radiology, Nuclear Medicine and imaging, Mortality, Pulmonology and respiratory tract, Aged, Neoplasm Staging, Lung, business.industry, Clinical Cancer Research, medicine.disease, 030104 developmental biology, poumon, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Human health and pathology, Ladc, Lung Adenocarcinoma, Obstruction, Smoking, Survival, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; A comprehensive characterization of lung adenocarcinoma (LADC) clinical features is currently missing. We prospectively evaluated Caucasian patients with early-stage LADC. Patients with LADC diagnosed between 2011 and 2015 were prospectively assessed for lung resection with curative intent. Fifty clinical, pathologic, radiologic, and molecular variables were recorded. Patients were followed till death/study conclusion. The main findings were compared to a separate cohort from France. Of 1943 patients evaluated, 366 were enrolled (18.8%; 181 female; 75 never-smokers; 28% of registered Bavarian cases over the study period). Smoking and obstruction were significantly more prevalent in GLAD compared with adult Bavarians (P < 0.0001). Ever-smoker tumors were preferentially localized to the upper lobes. We observed 120 relapses and 74 deaths over 704 cumulative follow-up years. Median overall and disease-free survival were >7.5 and 3.6 years, respectively. Patients aged 65 years, resected >60 days postdiagnosis, with abnormal FVC/DLCO VA , N2/N3 stage, or solid histology had significantly decreased survival estimates. These were fit into a weighted locoregional LADC death risk score that outperformed pTNM7 in predicting survival in the GLAD and in our second cohort. We define the clinical gestalt of locoregional LADC and provide a new clinical tool to predict survival, findings that may aid future management and research design
Published: 2019

5. Effectiveness and costs of non-invasive foetal RHD genotyping in rhesus-D negative mothers: a French multicentric two-arm study of 850 women

Author: Meryl Darlington, Bruno Carbonne, Agnès Mailloux, Yves Brossard, Annie Levy-Mozziconacci, Anne Cortey, Hassani Maoulida, Tabassome Simon, Alexandra Rousseau, Isabelle Durand-Zaleski, the GENIFERH1 Study Group, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], CHU Saint-Antoine [APHP], Service de Gynécologie et Obstétrique [Marseille], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), CHU Trousseau [APHP], Littoral, Environnement : Méthodes et Outils Numériques (LEMON), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), and colin, yves
Subjects: Genotyping Techniques, Cost effectiveness, Cost-Benefit Analysis, Rho(D) Immune Globulin, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, 0302 clinical medicine, Pregnancy, Prenatal Diagnosis, Rh-Hr Blood-Group System, 030219 obstetrics & reproductive medicine, Anti-D immunoglobulin, Obstetrics, Cost evaluation, Cost-effectiveness, Non-invasive foetal RHD genotyping, Pregnancy Outcome, Obstetrics and Gynecology, Prenatal Care, 3. Good health, [SDV] Life Sciences [q-bio], Gynécologie et obstétrique, Santé publique et épidémiologie, Gestation, Female, France, Research Article, medicine.medical_specialty, Genotype, Reproductive medicine, Médecine humaine et pathologie, Rh Isoimmunization, lcsh:Gynecology and obstetrics, 03 medical and health sciences, Fetus, medicine, Humans, Immunologic Factors, Genotyping, lcsh:RG1-991, business.industry, Gynecology and obstetrics, medicine.disease, Rhesus d, Clinical trial, Human health and pathology, business, Postpartum period
Abstract: Background The determination of foetal Rhesus D (RHD) status allows appropriate use of IgRh prophylaxis by restricting its use to cases of RHD feto-maternal incompatibilities. There is a degree of uncertainty about the cost-effectiveness of foetal RHD determination, yet screening programs are being introduced into clinical practice in many countries. This paper evaluates the impact of non-invasive foetal Rhesus D (RHD) status determination on the costs of managing RHD-negative pregnant women and on the appropriate use of anti-D prophylaxis in a large sample of RHD-negative pregnant women using individual prospectively collected clinical and economic data. Methods A prospective two-armed trial of RHD negative pregnant women was performed in 11 French Obstetric Departments. Non-invasive foetal RHD genotyping was performed before 26 weeks' gestation in the experimental arm whereas the control arm participants received usual care. The costs associated with patient management in relation to their RHD negative status (biological tests, anti-D prophylaxis and visits) were calculated from inclusion to the end of the postpartum period. The costs of hospital admissions during pregnancy and delivery were also determined. Results A total of 949 patients were included by 11 centres between 2009 and 2012, and 850 completed follow-up, including medical and biological monitoring. Patients were separated into two groups: the genotyping group (n=515) and the control group (n=335). The cost of the genotyping was estimated at 140 euros per test. The total mean cost per patient was estimated at €3,259 (SD ± 1,120) and €3,004 (SD ± 1,004) in the genotyping and control groups respectively. The cost of delivery represented three quarters of the total cost in both groups. The performance of managing appropriately RHD negative anti-D prophylaxis was 88% in the genotyping group, versus 65% in the control group. Using the costs related to RHD status (biological tests, anti-D immunoglobulin injections and visits) the incremental cost-effectiveness ratio (ICER) was calculated to be €578 for each percentage gain in women receiving appropriate management. Conclusion Early knowledge of the RHD status of the foetus using non-invasive foetal RHD genotyping significantly improved the management of RHD negative pregnancies with a small increase in cost. Trial registration Clinical trials registry-NCT00832962–13 January 2009 - retrospectively registered. Electronic supplementary material The online version of this article (10.1186/s12884-018-2114-5) contains supplementary material, which is available to authorized users.
Published: 2018

6. Evaluating the cost-consequence of a standardized strategy for the etiological diagnosis of uveitis (ULISSE study)

Author: de Parisot, Audrey, Jamilloux, Yvan, Kodjikian, Laurent, Errera, Marie-Hélène, Sedira, Neila, Heron, Emmanuel, Perard, Laurent, Cornut, Pierre-Loic, Schneider, Christelle, Rivière, Sophie, Ollé, Priscille, Pugnet, Grégory, Cathebras, Pascal, Manoli, Pierre, Bodaghi, Bahram, Saadoun, David, Baillif, Stéphanie, Tieulié, Nathalie, André, Marc, Chiambaretta, Fédéric, BONIN, Nicolas, Bielefeld, Philip, Bron, Alain, Mouriaux, Frédéric, Bienvenu, Boris, Amamra, Nassira, Guerre, Pascale, Decullier, Evelyne, Sève, Pascal, ULISSE, ., Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sève, Pascal, Hospices Civils de Lyon (HCL), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Equipe mobile de Gériatrie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Pierre-Paul Riquet Hospital, Poison Control Center, Toulouse-Purpan University Hospital, Toulouse, France., Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Desgenettes Hospital, Partenaires INRAE, CHU Limoges, CHU Rouen, Normandie Université (NU), La Conception, Bicêtre Hospital, South Hospital, Rabelais Center, Hôpital Montchanin, Centre Hospitalier Universitaire [Rennes], Hôpital Chalon-sur-Saône, Hôpital Nantes, and The French Ministry of Health (PHRC 2009).
Subjects: Male, Bacterial Diseases, Pediatrics, Organes des sens, Pathology and Laboratory Medicine, Treponematoses, law.invention, Diagnostic Radiology, 0302 clinical medicine, Randomized controlled trial, law, Medicine and Health Sciences, Prospective Studies, Practice Patterns, Physicians', Prospective cohort study, health care economics and organizations, ComputingMilieux_MISCELLANEOUS, Serodiagnosis, Multidisciplinary, Ophthalmologists, Radiology and Imaging, Middle Aged, Magnetic Resonance Imaging, 3. Good health, Serology, Infectious Diseases, Radiological weapon, Medicine, Female, France, Uveitis, Research Article, Neglected Tropical Diseases, Adult, medicine.medical_specialty, Imaging Techniques, Science, Urology, Sensory Organs, MEDLINE, Sexually Transmitted Diseases, Tuberculin, Médecine humaine et pathologie, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Diagnostic Medicine, Virology, medicine, Humans, Syphilis, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 030203 arthritis & rheumatology, business.industry, Genitourinary Infections, Biology and Life Sciences, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Tropical Diseases, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Ophthalmology, Viral Disease Diagnosis, 030221 ophthalmology & optometry, Etiology, Human health and pathology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; MAIN OBJECTIVE: To prospectively assess the cost-consequence of a standardized diagnostic strategy as to compared to an open one for the etiological diagnosis of uveitis. DESIGN: This was a prospective, non-inferiority, multicentre, randomized controlled trial. METHODS: We included all consecutive patients with uveitis who had visited at least one of the Departments of Ophthalmology. In the standardized group, patients had a minimal work-up regardless of the type of uveitis (including evaluation of the CBC, ESR, C-reactive protein, tuberculin skin test, syphilis serology and chest X-ray). Depending on ophthalmological findings, further investigations could be performed. In the open strategy, ophthalmologists were free to order any kind of investigation. The main outcome was the mean cost per patient of each strategy. RESULTS: 903 uveitis patients were included from January, 2010 to May, 2013. The mean cost per patient of the standardized strategy was 182.97 euros [CI 95% (173.14; 192.80)], and the mean cost per patient of the open strategy was 251.75 euros [CI 95% (229.24; 274.25)]. Therefore, the mean cost per patient of the standardized strategy was significantly lower than the mean cost per patient of the open strategy (p
Published: 2020

7. Influence of cardiac hemodynamic variables on retinal vessel density measurement on optical coherence tomography angiography in patients with myocardial infarction

Author: Florian Baudin, Pierre-Henry Gabrielle, Marianne Zeller, Louis Arnould, Alain M. Bron, Catherine Creuzot-Garcher, Yves Cottin, T. Pommier, Stéphane Pitois, Charles Guenancia, Creuzot Garcher, Catherine, ProdInra, Migration, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Male, Cardiac output, Longitudinal study, retina, Organes des sens, medicine.medical_treatment, Hemodynamics, Cell Count, Pilot Projects, law.invention, chemistry.chemical_compound, 0302 clinical medicine, oct angiography, law, cardiovascular disease, Longitudinal Studies, Prospective Studies, Myocardial infarction, Fluorescein Angiography, Ejection fraction, Rehabilitation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Heart, Middle Aged, Intensive care unit, 3. Good health, myocardial infarction, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Cardiology, cardiovascular system, Female, Tomography, Optical Coherence, medicine.medical_specialty, Sensory Organs, Médecine humaine et pathologie, 03 medical and health sciences, Internal medicine, medicine, Humans, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Aged, business.industry, Retinal Vessels, Stroke Volume, Retinal, medicine.disease, Ophthalmology, chemistry, 030221 ophthalmology & optometry, Human health and pathology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: INTRODUCTION: Quantitative measurements of retinal microvasculature by optical coherence tomography angiography (OCT-A) have been used to assess cardiovascular risk profile. However, to date, there are no studies focusing on OCT-A imaging in the setting of the altered hemodynamic status found in high-risk cardiovascular patients. METHODS: To determine the potential association between retinal vascular density on OCT-A and a comprehensive battery of hemodynamic variables in patients with myocardial infarction (MI) using data from the acute phase and at 3 months follow-up after cardiac rehabilitation. This prospective longitudinal study included patients who presented with MI in the cardiology intensive care unit at Dijon University Hospital. Main outcomes and measurements were retinal vessel density on OCT-A, hemodynamic status based on left ventricular ejection fraction (LVEF), and indexed cardiac output during the acute phase of myocardial infarction and at 3 months follow-up. RESULTS: Overall, 30 patients were included in this pilot study. The median (IQR) age was 64 years (55-71) with 87% men. At admission, the mean (SD) LVEF was 53% (11), and the mean indexed cardiac output was 2.70 (0.83) L/min/m(2). On OCT-A, the mean inner retinal vascular density was 19.09 (2.80) mm(-1). No significant association was found between retinal vascular density and hemodynamic variables. CONCLUSION: We found no significant association between retinal vascular density on OCT-A and hemodynamic variables in the acute phase of a myocardial infarction or after 3 months of cardiac rehabilitation. Therefore, OCT-A findings do not seem to be influenced by the hemodynamic changes associated with myocardial infarction., Introduction : Les caractéristiques quantitatives de la microvascularisation rétinienne en tomographie par cohérence optique angiographie (OCT-A) ont été utilisées pour évaluer le profil de risque cardiovasculaire. Cependant à ce jour, aucune étude ne s’est intéressée à la description microvasculaire en OCT-A dans un contexte d’une altération de l’état hémodynamique chez des patients présentant un risque cardiovasculaire élevé. Méthodes : Déterminer l’association potentielle entre la densité vasculaire rétinienne en OCT-A et un ensemble exhaustif de variables hémodynamiques chez des patients atteints d’un infarctus du myocarde en utilisant les données de la phase aiguë et du suivi à 3 mois, après une rééducation cardiaque. Cette étude longitudinale prospective a inclus des patients présentant un infarctus du myocarde dans l’unité de soins intensifs cardiologique du centre hospitalier universitaire de Dijon. Les critères principaux étaient la densité vasculaire rétinienne en OCT-A, la fraction d’éjection ventriculaire gauche (FEVG) et le débit cardiaque indexé à la phase aiguë de l’infarctus du myocarde et lors du suivi à 3 mois. Résultats : Au total, 30 patients ont été inclus dans cette étude pilote. L’âge médian (écart interquartile) était de 64 ans (55–71) avec 87 % d’hommes. À l’admission, la FEVG moyenne (écart type) était de 53 % (11) et le débit cardiaque indexé moyen était de 2,70 (0,83) L/min/m2. De plus, la densité vasculaire rétinienne interne moyenne était de 19,09 (2,80) mm−1. Aucune association significative n’a été trouvée entre la densité vasculaire rétinienne et les variables hémodynamiques. Conclusion : Nous n’avons pas trouvé d’association significative entre la densité vasculaire rétinienne en OCT-A et les variables hémodynamiques ni à la phase aiguë de l’infarctus du myocarde ni après 3 mois de réadaptation cardiaque. Par conséquent, les résultats quantitatifs de l’OCT-A ne semblent pas être influencés par les variations hémodynamiques chez des patients ayant présenté un infarctus du myocarde.
Published: 2020

8. Role of the interferons in CD64 and CD169 expressions in whole blood: Relevance in the balance between viral- or bacterial-oriented immune responses

Author: Fabrice Malergue, Pénélope Bourgoin, Géraldine Biéchelé, Inès Ait Belkacem, Pierre-Emmanuel Morange, ProdInra, Migration, Aix Marseille Université (AMU), Beckman Coulter SA, Partenaires INRAE, Faculté des sciences de Luminy, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 2016/1368, and 2018/1212
Subjects: lcsh:Immunologic diseases. Allergy, Adult, 0301 basic medicine, Neutrophils, Sialic Acid Binding Ig-like Lectin 1, Immunology, pathways, Médecine humaine et pathologie, Biology, Monocytes, Flow cytometry, 03 medical and health sciences, Transduction (genetics), 0302 clinical medicine, Immune system, medicine, Humans, Immunology and Allergy, CD64, Original Research, Whole blood, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, Activator (genetics), flow cytometry, Receptors, IgG, Interleukin, Bacterial Infections, CD169, interferons, 3. Good health, 030104 developmental biology, Virus Diseases, Human health and pathology, lcsh:RC581-607, Janus kinase, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: Introduction CD64 expression increases on neutrophils during bacterial infections. Recently an increase in CD169 expression has been discovered on monocytes during viral infections. Generally, interferons α (IFNsα) and IFNsγ are key drivers of the infectious host immune response. The purpose of this study was to explore if a link exists between these IFNs and both biomarkers. Methods Whole blood samples from healthy volunteers were stimulated with either IFNs, interleukins, or infectious extracts, to mimic an infectious state. Expressions of CD64 and CD169 were assessed in these samples by multiple flow cytometry methods, over precise kinetics. Results The expression of CD64 was statistically higher in samples stimulated with IFNγ, and CD169 in those stimulated with IFNα (and all other type I IFNs). Surface expressions are directly induced by their respective IFNs via Janus kinase/signal transducer and activator of transduction pathways within 6 to 8 hours of incubation. Mixing both types of IFNs seemed to indicate that they partially inhibit each other. Conclusions The induction of CD169 on monocytes and CD164 on neutrophils by type I and type II IFNs confirms the relevance of these markers for assessing between a viral‐ vs bacterial‐oriented immune response., CD64 and CD169 are expressed in samples stimulated with interferon γ (IFNγ) and IFNα, indicating relevance for discriminating infections.
Published: 2020

9. Effect of Diet in Chronic Spontaneous Urticaria: A Systematic Review

Author: Stéphane Munck, Annabel Maruani, Marie-Hélène Jegou, Bach-Nga Pham, Bruno Giraudeau, Mahtab Samimi, Hélène Cornillier, Olivier Chosidow, Annie-Pierre Jonville-Béra, Florence Hacard, Gwenaëlle d'Acremont, Service de dermatologie, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut National de la Santé et de la Recherche Médicale (INSERM), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Département d'Enseignement et de Recherche en Médecine Générale (DERGM), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre Hospitalier Universitaire de Lyon, Service de Pharmacologie Clinique, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Médecin Dermatologue, Partenaires INRAE, Médecin Pédiatre, Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Henri Mondor, Centre de Preuves en Dermatologie, France, Cornillier, Hélène, Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), and ProdInra, Migration
Subjects: medicine.medical_specialty, Urticaria, Provocation test, Population, MEDLINE, Médecine humaine et pathologie, Dermatology, chronic urticaria, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, allergological tests, Risk Factors, Internal medicine, Fish Products, diet, food, spontaneous urticaria, lcsh:Dermatology, Humans, Medicine, education, maladie inflammatoire, Chronic urticaria, Dermatologie, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, maladie de la peau, Remission Induction, Complete remission, General Medicine, Evidence-based medicine, Allergens, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, lcsh:RL1-803, 3. Good health, régime alimentaire, Treatment Outcome, 030228 respiratory system, Chronic Disease, Human health and pathology, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Histamine
Abstract: International audience; Strategies for diets in chronic spontaneous urticaria (CSU) are controversial. This systematic review assessed the interest in diet for managing CSU. We searched for original reports in MEDLINE, EMBASE, CENTRAL and LILACS. Among the 278 reports screened, 20 were included, involving 1,734 patients. Reports described 3 types of systematic diet: pseudoallergen-free diet (n = 1,555 patients), low-histamine diet (n = 223) and diet without fish products (n = 47), which induced complete remission in 4.8%, 11.7% and 10.6% of patients, respectively, and partial remission in 37.0%, 43.9% and 4.3%. Eight reports described personalized exclusion diets (66 patients) adapted to symptoms/allergological test results and led to complete remission in 74.6% of patients, although the diagnosis of CSU was doubtful. No comparative randomized studies of diets were available. The only randomized studies were based on oral provocation tests with the suspected responsible diet. Population and outcomes were heterogeneous. In conclusion, there is evidence for the benefit of diets in CSU only in individual patients with clinical symptoms. However, the level of evidence is low for the benefit of systematic diets in CSU because systematic double-blind controlled trials of diet are lacking.
Published: 2018

10. Efficacy of two vitamin E formulations in patients with abetalipoproteinemia and chylomicron retention disease

Author: Philippe Moulin, Jocelyne Drai, Emmanuelle Reboul, Emile Levy, Charlotte Cuerq, Lioara Restier, Noël Peretti, Mathilde Di Filippo, Marie-Caroline Michalski, Alain Lachaux, Emilie Blond, Pierre Poinsot, Agnès Sassolas, Sybil Charrière, Cyrielle Caussy, Christian Laveille, Christophe Marçais, Emilie Henin, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire de Mécanique des Systèmes et des Procédés (LMSP), Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Université de Montréal (UdeM), Centre recherche en CardioVasculaire et Nutrition (C2VN), and ProdInra, Migration
Subjects: Male, 0301 basic medicine, apoprotein-b, [SDV]Life Sciences [q-bio], medicine.medical_treatment, tissu adipeux, métabolisme des lipides, Anderson disease, adipose-tissue, Biochemistry, Gastroenterology, Hypobetalipoproteinemias, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, liquid-chromatography, Vitamin E, chronic cholestasis, triglyceride transfer protein, Research Articles, Vitamin E Acetate, lipoprotéine, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, chylomicron, Middle Aged, tocopherol, metabolic disease, Abetalipoproteinemia, adipose tissue, 3. Good health, lipid and lipoprotein metabolism, absorption, hypocholesterolemia, Female, 030211 gastroenterology & hepatology, Vitamin E deficiency, Safety, Chylomicron retention disease, Adult, Biochemistry & Molecular Biology, medicine.medical_specialty, Drug Compounding, Drug Storage, Médecine humaine et pathologie, Biological Availability, andersons disease, QD415-436, Tocofersolan, 03 medical and health sciences, Malabsorption Syndromes, alpha-tocopherol, Internal medicine, abetalipoproteinémie, medicine, Humans, hypocholestérolemie, adipose, business.industry, tissue, Cell Biology, fatty-acids, maladie métabolique, mutations, medicine.disease, 030104 developmental biology, Fat-Soluble Vitamin, Intestinal Absorption, chemistry, Case-Control Studies, Human health and pathology, business, alpha-Tocopherol, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, lipid-metabolism
Abstract: International audience; Abetalipoproteinemia (ABL) and chylomicron retention disease (CMRD) are extremely rare recessive forms of hypobetalipoproteinemia characterized by intestinal lipid malabsorption and severe vitamin E deficiency. Vitamin E is often supplemented in the form of fat-soluble vitamin E acetate, but fat malabsorption considerably limits correction of the deficiency. In this crossover study, we administered two different forms of vitamin E, tocofersolan (a water-soluble derivative of RRR-alpha-tocopherol) and alpha-tocopherol acetate, to three patients with ABL and four patients with CMRD. The aims of this study were to evaluate the intestinal absorption characteristics of tocofersolan versus alpha-tocopherol acetate by measuring the plasma concentrations of alpha-tocopherol over time after a single oral load and to compare efficacy by evaluating the ability of each formulation to restore vitamin E storage after 4 months of treatment. In patients with ABL, tocofersolan and alpha-tocopherol acetate bioavailabilities were extremely low (2.8% and 3.1%, respectively). In contrast, bioavailabilities were higher in patients with CMRD (tocofersolan, 24.7%; alpha-tocopherol acetate, 11.4%). Plasma concentrations of alpha-tocopherol at 4 months were not significantly different by formulation type in ABL or CMRD. This study provides new insights about vitamin E status in ABL and CMRD and suggests the potential of different formulations as treatment options.
Published: 2018

11. Shift in skin microbiota of Western European women across aging

Author: R. Jugé, P. Rouaud-Tinguely, K. Servaes, C. Grimaldi, H. Coppin, J. Breugnot, M.-P. Roth, B. Closs, R & D Department, SILAB, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-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-Institut National de la Santé et de la Recherche Médicale (INSERM), ProdInra, Migration, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT)
Subjects: 0301 basic medicine, Aging, Western European women, Corynebacterium, Beta diversity, Applied Microbiology and Biotechnology, 030207 dermatology & venereal diseases, Taxonomic composition, 0302 clinical medicine, Alpha diversity, propionibacterium, Young adult, 16S rRNA gene sequencing, Skin, Dermatologie, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, integumentary system, biology, Microbiota, Age-related changes, actinobacteria, épiderme, vieillissement, General Medicine, Middle Aged, communauté bactérienne, 3. Good health, Europe, 16s rrna gene sequencing, Female, Proteobacteria, Biotechnology, Adult, protéobactérie, Médecine humaine et pathologie, Dermatology, personne âgée, Young Adult, 03 medical and health sciences, taxonomie bactérienne, Age groups, Humans, Microbiote cutané, Aged, Bacteria, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, biology.organism_classification, 030104 developmental biology, Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract: International audience; Aims : The objective of our study was to compare the microbiota diversity between two different age groups of Western European women. Methods and Results : Skin‐swab samples were collected directly on the forehead of 34 healthy Western European women: 17 younger (21‐31 years old) and 17 older individuals (54‐69 years old). Bacterial communities were evaluated using the 16S rRNA gene sequencing. Data revealed a higher alpha diversity on the skin of older individuals compared with younger ones. Overall microbiota structure was different between the two age groups, as demonstrated by beta diversity analysis, which also highlighted a high interpersonal variation within older individuals. Furthermore, taxonomic composition analysis showed both an increase in Proteobacteria and a decrease in Actinobacteria on the older skin. At the genus level, older skin exhibited a significant increase in Corynebacterium and a decrease in Propionibacterium relative abundance. Conclusions : Our study revealed a shift in the distribution of skin microbiota during chronological aging in Western European women. Significance and Impact of Study: Altogether these results could become the basis to develop new approaches aiming to rebalance the skin microbiota, which is modified during the aging process.
Published: 2018

12. Perioperative management of adult diabetic patients. Postoperative period

Author: Gaëlle Cheisson, Sophie Jacqueminet, Emmanuel Cosson, Carole Ichai, Anne-Marie Leguerrier, Bogdan Nicolescu-Catargi, Alexandre Ouattara, Igor Tauveron, Paul Valensi, Dan Benhamou, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (COMUE) (USPC), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Pontchaillou [Rennes], CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Service d'Endocrinologie-Diabétologie, CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Gabriel Montpied [Clermont-Ferrand], ProdInra, Migration, and Benhamou, Dan
Subjects: Diabetes, Perioperative, Basal-bolus, Insulin pump, Hypoglycaemia, Hyperglycaemia, endocrine system diseases, Médecine humaine et pathologie, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Diabetes Mellitus, Humans, Hypoglycemic Agents, Insulin, Postoperative Period, 030212 general & internal medicine, Postoperative Care, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, nutritional and metabolic diseases, 030208 emergency & critical care medicine, General Medicine, 3. Good health, Anesthesiology and Pain Medicine, Hyperglycemia, Human health and pathology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Working party approved by the French Society of Anaesthesia and Intensive Care Medicine (SFAR) and the French Society for the study of Diabetes (SFD); International audience; Follow on from continuous intravenous administration of insulin with an electronic syringe (IVES) is an important element in the postoperative management of a diabetic patient. The basal-bolus scheme is the most suitable taking into account the nutritional supply and variable needs for insulin, reproducing the physiology of a normal pancreas: (i) slow (long-acting) insulin (= basal) which should immediately take over from IVES insulin simulating basal secretion; (ii) ultra-rapid insulin to simulate prandial secretion (= bolus for the meal); and (iii) correction of possible hyperglycaemia with an additional ultra-rapid insulin bolus dose. A number of schemes are proposed to help calculate the dosages for the change from IV insulin to subcutaneous insulin and for the basal-bolus scheme. Postoperative resumption of an insulin pump requires the patient to be autonomous. If this is not the case, then it is mandatory to establish a basal-bolus scheme immediately after stopping IV insulin. Monitoring of blood sugar levels should be continued postoperatively. Hypoglycaemia and severe hyperglycaemia should be investigated. Faced with hypoglycaemia < 3.3 mmol/L (0.6 g/L), glucose should be administered immediately. Faced with hyperglycaemia > 16.5 mmol/L (3 g/L) in a T1D or T2D patient treated with insulin, investigations for ketosis should be undertaken systematically. In T2D patients, unequivocal hyperglycaemia should also call to mind the possibility of diabetic hyperosmolarity (hyperosmolar coma). Finally, the modalities of recommencing previous treatments are described according to the type of hyperglycaemia, renal function and diabetic control preoperatively and during hospitalisation.
Published: 2018

13. Perioperative management of adult diabetic patients. Intraoperative period

Author: Alexandre Ouattara, Igor Tauveron, Emmanuel Cosson, Dan Benhamou, Gaëlle Cheisson, Sophie Jacqueminet, Paul Valensi, Carole Ichai, Anne-Marie Leguerrier, Bogdan Nicolescu-Catargi, Benhamou, Dan, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (COMUE) (USPC), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Pontchaillou [Rennes], CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), CHU Clermont-Ferrand, Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Gabriel Montpied [Clermont-Ferrand], and ProdInra, Migration
Subjects: Insulin pump, medicine.medical_treatment, Médecine humaine et pathologie, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Sudden death, Diabetic nephropathy, Intraoperative Period, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Diabetic cardiomyopathy, Diabetes mellitus, Glycaemic control, Diabetes Mellitus, medicine, Humans, Hypoglycemic Agents, Insulin, Perioperative, 030212 general & internal medicine, Intraoperative Care, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Diabetes, General Medicine, medicine.disease, Insulin therapy, 3. Good health, Anesthesiology and Pain Medicine, Anesthesia, Human health and pathology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: In diabetic patients undergoing surgery, we recommend assessing glycaemic control preoperatively by assessing glycated haemoglobin (HbA1c) levels and recent capillary blood sugar (glucose) levels, and to adjust any treatments accordingly before surgery, paying particular attention to specific complications of diabetes. Gastroparesis creates a risk of stasis and aspiration of gastric content at induction of anaesthesia requiring the use of a rapid sequence induction technique. Cardiac involvement can be divided into several types. Coronary disease is characterised by silent myocardial ischaemia, present in 30-50% of T2D patients. Diabetic cardiomyopathy is a real cause of heart failure. Finally, cardiac autonomic neuropathy (CAN), although rarely symptomatic, should be investigated because it causes an increased risk of cardiovascular events and a risk of sudden death. Several signs are suggestive of CAN, and confirmation calls for close perioperative surveillance. Chronic diabetic kidney disease (diabetic nephropathy) aggravates the risk of perioperative acute renal failure, and we recommend measurement of the glomerular filtration rate preoperatively. The final step of the consultation concerns the management of antidiabetic therapy. Preoperative glucose infusion is not necessary if the patient is not receiving insulin. Non-insulin drugs are not administered on the morning of the intervention except for metformin, which is not administered from the evening before. The insulins are injected at the usual dose the evening before. The insulin pump is maintained until the patient arrives in the surgical unit. It should be remembered that insulin deficiency in a T1D patient leads to ketoacidosis within a few hours.
Published: 2018

14. Kinetics of plasma apolipoprotein E isoforms by LC-MS/MS: a pilot study

Author: Blanchard, Valentin, Ramin-Mangata, Stéphane, Billon-Crossouard, Stephanie, Aguesse, Audrey, Durand, Manon, Chemello, Kevin, Nativel, Brice, Flet, Laurent, Chetiveaux, Maud, Jacobi, David, Bard, Jean-Marie, Ouguerram, Khadija, Lambert, Gilles, Krempf, Michel, Croyal, Mikael, Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Nutrition Humaine Ouest (CRNH Ouest), Université de Nantes (UN), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Pharmacie, Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), FR 3473 Institut universitaire Mer et Littoral (IUML), Université de Bretagne Sud (UBS)-Le Mans Université (UM)-Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Nantes (UN)-École Centrale de Nantes (ECN), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre de recherche en nutrition humaine Ouest, Nutrition périnatale [Nantes] (Centres de Recherche en Nutrition Humaine - CRNH), Centre de Recherche en Nutrition Humaine - Ouest, INRA: UMR1280 Physiologie des adaptations (UMR1280), Institut National de la Recherche Agronomique (INRA), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS), Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), UMR 1280 Physiologie des Adaptations Nutritionnelles, and Institut de Cancérologie de l'Ouest
Subjects: Male, Apolipoprotein E2, [SDV]Life Sciences [q-bio], Apolipoprotein E4, Apolipoprotein E3, Médecine humaine et pathologie, lipoprotein/metabolism, Pilot Projects, QD415-436, apolipoprotein E isoforms, Biochemistry, Lipoproteins/Kinetics, tandem mass spectrometry, Humans, Protein Isoforms, Food and Nutrition, liquid chromatography, lipoprotein/kinetics, Chromatography, High Pressure Liquid, peptide, stable isotope tracers, Middle Aged, Kinetics, Lipoproteins/Metabolism, Alimentation et Nutrition, Human health and pathology, lipids (amino acids, peptides, and proteins), Patient-Oriented and Epidemiological Research
Abstract: International audience; Human apolipoprotein E (apoE) exhibits three major isoforms (apoE2, apoE3, and apoE4) corresponding to polymorphism in theAPOEgene. Total plasma apoE concentrations are closely related to these isoforms but the underlying mechanisms are unknown. We aimed to describe the kinetics of apoE individual isoforms to explore the mechanisms for variable total apoE plasma concentrations. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to discriminate between isoforms by identifying specific peptide sequences in subjects (3 E2/E3, 3 E3/E3 and 3 E3/E4 phenotypes) who received a primed constant infusion of2H3-leucine for 14 hours. ApoE concentrations and leucine enrichments were measured hourly in plasma. Concentrations of apoE2 were higher than apoE3, and concentrations of apoE4 were lower than apoE3. There was no difference between apoE3 and apoE4 catabolic rates and between apoE2 and apoE3 production rates, but apoE2 catabolic rates and apoE4 production rates were lower. Then, the mechanisms leading to the difference in total plasma apoE concentrations are related to contrasted kinetics of the isoforms. Production or catabolic rates are differently affected according to the specific isoforms. From these grounds, studies on the regulation of the involved biochemical pathways and the impact of pathological environments are now warranted.
Published: 2018

15. Rational design of adjuvants targeting the C-type lectin Mincle

Author: Eric Perouzel, Alain Vercellone, Jacques Prandi, Martine Gilleron, Sandro Silva-Gomes, David Sancho, Jérôme Nigou, Francisco J. Cueto, Gérard Tiraby, Thierry Lioux, Sophie Barbe, Alexiane Decout, Daniel Drocourt, Isabelle André, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Research Department, InvivoGen, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Association Nationale de la Recherche et de la Technologie (ANRT), Nigou, Jérôme, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: mycobacteria, glycolipid, innate immunity, 0301 basic medicine, vaccin, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Mannose, immunogenicity, Adaptive Immunity, approche pharmacologique, Mice, chemistry.chemical_compound, 0302 clinical medicine, glycolipide, Cell Wall, C-type lectin, vaccine, immunogenicite, mycobactérie, Receptors, Immunologic, Multidisciplinary, Immunogenicity, Biological Sciences, 3. Good health, Process Engineering, Biochemistry, Vaccines, Subunit, Cord Factors, paroi cellulaire, Adjuvant, cytokine anti inflammatoire, vaccine adjuvants, Médecine humaine et pathologie, Molecular Dynamics Simulation, Biology, Mycobacterium, 03 medical and health sciences, Glycolipid, Immune system, adjuvant, Adjuvants, Immunologic, medicine, Animals, Humans, Tuberculosis, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Lectins, C-Type, Génie des procédés, Rational design, Lectin, 030104 developmental biology, chemistry, Mutagenesis, biology.protein, Human health and pathology, immunité, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: Adresse actuelle Decout Alexiane : GLYcoDiag, Res Dept, F-45067 Orléans 2, France; The advances in subunit vaccines development have intensified the search for potent adjuvants, particularly adjuvants inducing cell-mediated immune responses. Identification of the C-type lectin Mincle as one of the receptors underlying the remarkable immunogenicity of the mycobacterial cell wall, via recognition of trehalose-6,6'-dimycolate (TDM), has opened avenues for the rational design of such molecules. Using a combination of chemical synthesis, biological evaluation, molecular dynamics simulations, and protein mutagenesis, we gained insight into the molecular bases of glycolipid recognition by Mincle. Unexpectedly, the fine structure of the fatty acids was found to play a key role in the binding of a glycolipid to the carbohydrate recognition domain of the lectin. Glucose and mannose esterified at O-6 by a synthetic alpha-ramified 32-carbon fatty acid showed agonist activity similar to that of TDM, despite their much simpler structure. Moreover, they were seen to stimulate proinflammatory cytokine production in primary human and murine cells in a Mincle-dependent fashion. Finally, they were found to induce strong Th1 and Th17 immune responses in vivo in immunization experiments in mice and conferred protection in a murine model of Mycobacterium tuberculosis infection. Here we describe the rational development of new molecules with powerful adjuvant properties.
Published: 2017

16. Dietary exposure to pesticide residues and associated health risks in infants and young children - Results of the French infant total diet study

Author: Renwei Hu, Paule Vasseur, Véronique Sirot, Marion Hulin, Alexandre Nougadère, Cyril Feidt, Jean-Pierre Cravedi, Julien Jean, Xavier Sarda, Richard J. Fussell, Mathilde Merlo, Jean-Charles Leblanc, Gilles Rivière, European Food Safety Authority (EFSA), Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Terre et Environnement de Lorraine (OTELo), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherches Animal et Fonctionnalités des Produits Animaux (URAFPA), Université de Lorraine (UL)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), (ex Food and Environment Research Agency), Fera Science Limited, INOVALYS, Laboratoire de sécurité des aliments de Maisons-Alfort (LSAl), Direction de l'évaluation des produits réglementés (DEPR), The infant TDS was supported by the French Ministry for food, agriculture and fisheries, the French Ministry for health, the French Ministry for ecology and sustainable development and ANSES., and Nougadère, Alexandre
Subjects: [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, Piperonyl butoxide, Insecticides, 010504 meteorology & atmospheric sciences, [SDV]Life Sciences [q-bio], food safety, infants and young children, pesticide residues, total diet study, exposure assessment, risk characterization, Médecine humaine et pathologie, Food Contamination, 010501 environmental sciences, Biology, Toxicology, 01 natural sciences, Food safety, Baby food, Dietary Exposure, chemistry.chemical_compound, Dieldrin, Humans, Pesticides, Child, Toxicologie, Captan, lcsh:Environmental sciences, 0105 earth and related environmental sciences, General Environmental Science, 2. Zero hunger, lcsh:GE1-350, Pesticide residue, business.industry, Pesticide Residues, Risk characterization, Infant, Pesticide, 3. Good health, Diet, Santé publique et épidémiologie, chemistry, 13. Climate action, Child, Preschool, Total diet study, Exposure assessment, Human health and pathology, Infants and young children, business, Lindane
Abstract: A total diet study (TDS) was undertaken to estimate the chronic dietary exposure to pesticide residues and health risks for the French infants and young children below 3 years old. As a whole, 516 pesticides and metabolites were analysed in 309 food composite samples including 219 manufactured baby foods and 90 common foods, which cover 97% of infants and young children's diet. These composite samples were prepared using 5,484 food products purchased during all seasons from 2011 to 2012 and processed as consumed. Pesticide residues were detected in 67% of the samples and quantified in 27% of the baby food samples and in 60% of the common foods. Seventy-eight different pesticides were detected and 37 of these quantified at levels ranging from 0.02 to 594 µg/kg. The most frequently detected pesticides (greater than 5% samples) were (1) the fungicides 2-phenylphenol, azoxystrobin, boscalid, captan and its metabolite tetrahydrophthalimide, carbendazim, cyprodinil, difenoconazole, dodine, imazalil, metalaxyl, tebuconazole, thiabendazole, (2) the insecticides acetamiprid, pirimiphos-methyl and thiacloprid, (3) the herbicide metribuzin and (4) the synergist piperonyl butoxide. Dietary intakes were estimated for each of the 705 individuals studied and for 431 pesticides incl. 281 with a toxicological reference value (TRV). In the lower-bound scenario, which tends to underestimate the exposure, the TRV were never exceeded. In the upper-bound scenario that overestimates exposure, the estimated intakes exceeded the TRV for dieldrin and lindane (two persistent organic pollutants) and propylene thiourea, a metabolite of propineb. For these three substances, more sensitive analyses are needed to refine the assessment. For 17 other detected and/or prioritised pesticides, the risk could not be characterised due to the lack of a valid TRV, of certain food analyses or the absence of analytical standards for their metabolites. Keywords: Food safety, Infants and young children, Pesticide residues, Total diet study, Exposure assessment, Risk characterization
Published: 2019

17. High prevalence of kaolin consumption in migrant women living in a major urban area of France: A cross-sectional investigation

Author: Pascal Caillet, Véronique Carton, Edouard Marchal, Marie Grall-Bronnec, Caroline Victorri-Vigneau, Catherine Pintas, Alain Pineau, Norbert Winer, Pascale Jolliet, Maud Poirier, Department of Clinical Pharmacology [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Gynecology and Obstetrics [Nantes], Department of Addictology and Psychiatry [Nantes], MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-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), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Institut des maladies de l'appareil digestif [Nantes] (IMAD), This work was supported by the University Hospital of Nantes., Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Bodescot, Myriam, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Caillet, Pascal
Subjects: Urban Population, Cross-sectional study, Economics, Maternal Health, Immigration, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Social Sciences, 010501 environmental sciences, Logistic regression, 01 natural sciences, Geographical Locations, Families, 0302 clinical medicine, Medicine and Health Sciences, Prevalence, Medicine, Psychology, heavy-metals, Public and Occupational Health, 030212 general & internal medicine, 10. No inequality, Kaolin, Children, media_common, risk, Transients and Migrants, Multidisciplinary, pica, Obstetrics and Gynecology, Hematology, anemia, Gynécologie et obstétrique, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Alimentation et Nutrition, Physical Sciences, Female, France, pregnancy, Psychosocial, Research Article, Chemical Elements, Adult, Substance-Related Disorders, Science, media_common.quotation_subject, Iron, Intoxication, Médecine humaine et pathologie, Addiction, geohelminths, iron-deficiency, 03 medical and health sciences, Environmental health, Mental Health and Psychiatry, geophagy, Food and Nutrition, Humans, Iron Deficiency Anemia, health implications, Geophagia, 0105 earth and related environmental sciences, Consumption (economics), business.industry, Biology and Life Sciences, Odds ratio, Gynecology and obstetrics, Confidence interval, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Age Groups, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, People and Places, Africa, Women's Health, Human health and pathology, Population Groupings, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Finance
Abstract: International audience; Geophagia is a feeding behavior involving the regular intake of soil, including clay-like kaolin. Frequent in Africa, kaolin consumption is associated with heavy metal intoxication, iron and other micronutrient deficiencies, geohelminth infection and inactivation of concomitantly taken drugs. It is expected that this practice would be imported into an asylum country during the immigration process. To confirm this hypothesis, a single center, cross-sectional study was conducted at the University Hospital of Nantes, France, whose main objective was to assess whether the prevalence of kaolin consumers was high in a migrant population living in a large French metropolitan area (the city of Nantes). Each woman consulting for the first time at the Medical and Psychosocial Gynecology Obstetric Unit during the inclusion period ranging from January 1, 2017, to July 1, 2017, was asked for consent to be included in the study. The main outcome was the proportion of positive answers regarding consumption of kaolin within the last twelve months, with its 95% confidence interval (CI). A logistic regression was performed to identify drivers of consumption, and a clustering approach was conducted to identify profiles of consumers. A total of 284 women were included in the study, of whom 110 (38.7%) were pregnant. Our main finding was a 14.1% (95% CI: 10.5-18.6) prevalence of clay consumers. Second, the characteristic most strongly associated with consumption was Central or West Africa origin (adjusted Odds Ratio (aOR) = 52.7; 95% CI: 13.7-202.2). Finally, 60% of consumers showed signs of addictive-like phenomena, and three profiles were identified, depicting a continuum of patients in regard to their control over their kaolin consumption. Our results suggest that kaolin consumption is frequent in particular subpopulations of migrants. This warrants further study of the clinical consequences of kaolin consumption and its associated addictive-like symptoms.
Published: 2019

18. The introduction of new hosts with human trade shapes the extant distribution of Toxoplasma gondii lineages

Author: Carine Brouat, Azra Hamidović, Aurélien Mercier, Daniel Ajzenberg, Thomas Cuny, Marie-Laure Dardé, M. Diagne, Nicolas Plault, Mamoudou Diallo, Mbacké Sembène, Amedine Sarr, Aliou Sow, Lokman Galal, Fatoumata Coulibaly, Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Faculté des Sciences et Techniques (FST), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Faculty of Sciences and Technique, Department of Geology, LCPM, Laboratoire de Chimie et Physique des Matériaux, Service de Parasitologie Mycologie [CHU Limoges], CHU Limoges, ANR-17-CE35-0004,IntroTox,PHENOMÈNES D'INTROGRESSIONS DANS L'ÉTUDE DE LA DIVERSITÉ GÉNÉTIQUE DU TOXOPLASME ENTRE LA FRANCE ET L'AFRIQUE DE L'OUEST ET CENTRALE : DES INFLUENCES HUMAINES ET ENVIRONEMENTALES(2017), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), and 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)
Subjects: 0301 basic medicine, RC955-962, Population Dynamics, médecine humaine, Population genetics, House mouse, Toxoplasma Gondii, Geographical Locations, Mice, 0302 clinical medicine, Arctic medicine. Tropical medicine, Genotype, Phylogeny, Animal biology, Protozoans, education.field_of_study, Geography, Virulence, Commerce, Eukaryota, Senegal, Europe, Phylogeography, Africa, Western, Infectious Diseases, Biogeography, Public aspects of medicine, RA1-1270, Toxoplasma, Polymorphism, Restriction Fragment Length, Research Article, Lineage (genetic), Animal Types, 030231 tropical medicine, Population, Médecine humaine et pathologie, Zoology, Biology, 03 medical and health sciences, Biologie animale, Genetic variation, parasitic diseases, Genetics, Animals, Humans, Domestic Animals, education, Alleles, Poultry Diseases, Disease Reservoirs, Evolutionary Biology, Population Biology, Ecology and Environmental Sciences, Public Health, Environmental and Occupational Health, Organisms, Toxoplasma gondii, Biology and Life Sciences, Genetic Variation, sénégal, biology.organism_classification, Parasitic Protozoans, Geographic Distribution, 030104 developmental biology, Genetics, Population, Toxoplasmosis, Animal, People and Places, Africa, Earth Sciences, Human health and pathology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Chickens, Population Genetics, Microsatellite Repeats
Abstract: Toxoplasma gondii is a zoonotic protozoan with a worldwide occurrence, but the determinants of the current pattern in the geographical distribution of T. gondii lineages and strains remain poorly understood. To test the influence of human trade on T. gondii populations, we conducted a population genetic study of 72 T. gondii animal isolates from Senegal, a West African country in which the ongoing inland progress of invasive murine hosts (introduced in port cities of Senegal since the 16th century by European sailors) is well described. Isolates were mainly collected on free-range poultry, which are considered as relevant bioindicators of T. gondii strain diversity in the domestic environment. Sampling was conducted in two port cities of Senegal (Dakar and Saint-Louis) and in one inland region (Kedougou). Population genetic analyses using 15 microsatellite markers revealed different patterns between port cities where lineages non-virulent for mice (type II, type III, and Africa 4) were predominant, and Kedougou where the mouse-virulent Africa 1 lineage was the most common. By considering the current spatial pattern in the inland progress of invasive rodents in Senegal, our results suggest that the invasive house mouse Mus musculus domesticus counter-selects the Africa 1 lineage in the invaded areas. The comparison of the microsatellite alleles of type II strains from Senegal to type II strains from other areas in Africa and Western Europe, using discriminant analysis of principal components and Network analysis, point to a mainly Western European origin of the type II lineage in Senegal. Collectively, these findings suggest that human-mediated intercontinental migrations of murine hosts are important vectors of T. gondii strains. Differential susceptibility of endemic and introduced murine hosts to various T. gondii strains probably determines the persistence of these strains in the environment, and therefore their availability for human and animal infection., Author summary Toxoplasma gondii is a zoonotic protozoan with a worldwide distribution and which can infects virtually all warm-blooded species, including human. Clinical expression of human toxoplasmosis, as well as T. gondii strains diversity, exhibit contrasting patterns across geographic regions. The determinants of this geographical structure are poorly understood, but a growing body of evidence supports an important role of human-mediated migrations of T. gondii hosts in the intercontinental dissemination of some parasite lineages. The results of our study conducted in Senegal suggest that the invasive house mouse—which was introduced in the port cities of this country through maritime trade since colonial times—has a dramatic influence on the T. gondii populations of invaded areas. This important T. gondii reservoir seems to be a vector for the intercontinental migrations of T. gondii. In addition, it may have a role in the selection (or the counter-selection) of local T. gondii populations found in invaded areas. This study provides insights into the mechanisms shaping T. gondii populations, thereby determining which strains will be available for human and animal infection.
Published: 2019

19. Neonatal growth velocity of preterm infants: The weight Z-score change versus Patel exponential model

Author: Anne Frondas-Chauty, Matthieu Hanf, Simon Nusinovici, Dominique Darmaun, Géraldine Gascoin, Cyril Flamant, Laure Simon, Jean-Christophe Rozé, Valérie Rouger, Department of Neonatal Medicine [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Épidémiologie Clinique [Nantes], Centre d'Investigation Clinique [Nantes] (CIC004), Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Réseau Grandir Ensemble [Nantes], Department of Neonatal Medicine [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Simon, Laure, and Bodescot, Myriam
Subjects: Male, Physiology, Maternal Health, population, Blood Pressure, Weight Gain, Vascular Medicine, methods, children, Families, 0302 clinical medicine, Child Development, Mathematical and Statistical Techniques, Pregnancy, Medicine and Health Sciences, Birth Weight, 030212 general & internal medicine, Growth Charts, Children, education.field_of_study, Multidisciplinary, Obstetrics, Statistics, Gestational age, Obstetrics and Gynecology, Regression analysis, Hospitals, Exponential function, Hospitalization, Physiological Parameters, Alimentation et Nutrition, Physical Sciences, Hypertension, Medicine, Regression Analysis, Female, medicine.symptom, Infants, Infant, Premature, Research Article, medicine.medical_specialty, Birth weight, Science, Population, Médecine humaine et pathologie, Gestational Age, Standard score, Research and Analysis Methods, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Hypertensive Disorders in Pregnancy, 030225 pediatrics, Linear regression, medicine, Food and Nutrition, Humans, Statistical Methods, education, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Body Weight, Infant, Newborn, Infant, Biology and Life Sciences, Neonates, Health Care, Age Groups, Health Care Facilities, People and Places, Women's Health, Human health and pathology, Population Groupings, business, Weight gain, Mathematics, Developmental Biology
Abstract: International audience; BACKGROUND: Different methods are used to assess the growth of preterm infants during neonatal hospital stay. The primary objective was to compare two methods for assessing growth velocity: g/kg/d according to the Patel exponential model (EM) and change in weight z-score (ZS) according to Fenton curves. The secondary objective was to highlight factors influencing the level of agreement between the two methods.METHODS: Preterm infants born before 33 weeks were included. Growth velocity was computed by EM and ZS methods and linear regression was used to predict what growth velocity by EM method would be obtained using the ZS method. Differences between EM growth velocity and EM growth velocity predicted by ZS method were then used to assess the level of agreement between the two methods. A difference between -2 and +2 g/kg/day was considered as fair agreement, greater than ± 4 g/kg/day as poor agreement, and as disagreement otherwise.RESULTS: Among the 3954 children included, we observe a fair agreement in 2471 children (62.5%), a poor agreement in 1278 (32.3%) and a disagreement in 205 children (5.2%). Birth weight and gestational age explained 31% and 25%, respectively, of the variance in the difference between the two methods.CONCLUSIONS: In more than a third of enrolled children, the two methods for measuring growth velocity disagreed substantially. As variation of weight Z-score takes into account infant gestational age and gender, it could be more suitable to analyze a population of preterm infants with a wide range of gestational age.
Published: 2019

20. Retinal Vascular Density as A Novel Biomarker of Acute Renal Injury after Acute Coronary Syndrome

Author: Guillaume Alan, Maud Maza, Alain M. Bron, A. Azemar, Florence Bichat, Louis Arnould, Marianne Zeller, Pierre-Henri Gabrielle, Catherine Creuzot-Garcher, Stéphane Pitois, Charles Guenancia, Yves Cottin, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration, and Guenancia, Charles
Subjects: Male, 0301 basic medicine, Organes des sens, Computed Tomography Angiography, Contrast Media, Coronary Angiography, Kidney, 0302 clinical medicine, Natriuretic Peptide, Brain, Prospective Studies, Prospective cohort study, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, Acute kidney injury, Acute Kidney Injury, Middle Aged, Intensive Care Units, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Predictive value of tests, Alimentation et Nutrition, Cardiology, Medicine, Biomarker (medicine), Female, Interventional cardiology, Tomography, Optical Coherence, Acute coronary syndrome, medicine.medical_specialty, Science, Sensory Organs, Médecine humaine et pathologie, Predictive markers, Risk Assessment, Article, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Food and Nutrition, Humans, Acute Coronary Syndrome, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Aged, business.industry, Reproducibility of Results, Retinal Vessels, medicine.disease, Peptide Fragments, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, Microvessels, Coronary care unit, Feasibility Studies, Human health and pathology, business, Complication, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Kidney disease
Abstract: Iodinated contrast agent (ICA)-induced acute kidney injury (AKI) following acute coronary syndrome (ACS) is a frequent complication, which may lead to chronic kidney disease and increased mortality. Optical coherence tomography angiography (OCT-A) of the retina is new tool delivering a rapid and noninvasive assessment of systemic microvascularization, which is potentially involved in the occurrence of ICA-induced AKI. Between October 2016 and March 2017, 452 ACS patients were admitted to our cardiac intensive care unit. OCT-A was performed within 48 h after the ICA injection. Patients with a history of retinal disease were excluded. The patients included were divided into two groups depending on whether or not AKI occurred after injection of ICA, according to KDIGO criteria. Of the 216 patients included, 21 (10%) presented AKI. AKI was significantly associated with age, Mehran score, GRACE score, and NT-proBNP. AKI patients had significantly lower retinal vascular density (RVD)) and had more frequent low RVD (81% vs 45%, P = 0.002). Adding low RVD to the Mehran score and the NT-proBNP, or to the GRACE score and the NT-proBNP, significantly improved their predictive values, suggesting that systemic microvascular involvement remains incompletely addressed by either standard risk scores or factors known to be associated with ICA-induced AKI.
Published: 2019

21. Alteration of erythrocyte membrane polyunsaturated fatty acids in preterm newborns with retinopathy of prematurity

Author: Stéphane Grégoire, Niyazi Acar, Denis S. Semama, Julie Mazzocco, Ninon Ternoy, Charlotte Pallot, Cyril Meillon, Lionel Bretillon, Catherine Creuzot-Garcher, Corinne Chantegret, Alain M. Bron, Delphine Martin, Aurélie Donier, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Université Bourgogne Franche-Comté [COMUE] (UBFC), This work has been funded by the Regional Council of Burgundy France (PARI Agral 1), FEDER (European Funding for Regional Economical Development), Association Nationale Recherche Technologie, Fondation de France/Fondation de l’Oeil, Agence Nationale de la Recherche [ANR-11-LABEX-0021]., and Acar, Niyazi
Subjects: 0301 basic medicine, Organes des sens, prémature, lcsh:Medicine, fatty acids, retinopathy of prematury, chemistry.chemical_compound, 0302 clinical medicine, Prospective Studies, lcsh:Science, Prospective cohort study, chemistry.chemical_classification, Multidisciplinary, Gestational age, Retinopathy of prematurity, 3. Good health, Docosahexaenoic acid, In utero, Alimentation et Nutrition, Fatty Acids, Unsaturated, Female, lipids (amino acids, peptides, and proteins), Arachidonic acid, Animal studies, Infant, Premature, Polyunsaturated fatty acid, medicine.medical_specialty, rétine, Sensory Organs, Médecine humaine et pathologie, Gestational Age, Article, 03 medical and health sciences, Fatty Acids, Omega-6, Internal medicine, Fatty Acids, Omega-3, medicine, Food and Nutrition, Humans, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Fatty acids, acide gras oméga 6, business.industry, lcsh:R, Erythrocyte Membrane, Infant, Newborn, acide gras oméga 3, medicine.disease, eye diseases, 030104 developmental biology, Endocrinology, chemistry, lcsh:Q, Human health and pathology, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Extremely preterm infants are at high risk for retinopathy of prematurity (ROP), a potentially blinding disease characterized by abnormalities in retinal vascularization. Whereas animal studies revealed that n-3 polyunsaturated fatty acids (PUFAs) may be of benefit in preventing ROP, human studies conducted on preterm infants during the 1st weeks of life showed no association between blood n-3 PUFA bioavailability and ROP incidence and/or severity, probably because of the influence of nutrition on the lipid status of infants. In the OmegaROP prospective cohort study, we characterized the erythrocyte concentrations of PUFAs in preterm infants aged less than 29 weeks gestational age (GA) without any nutritional influence. We show that GA is positively associated with the erythrocyte n-6 to n-3 PUFA ratio, and particularly with the ratio of arachidonic acid (AA) to docosahexaenoic acid (DHA), in infants with ROP. A time-dependent accumulation of AA at the expense of DHA seems to occur in utero in erythrocytes of preterm infants who will develop ROP, thus reinforcing previous data on the beneficial properties of DHA on this disease. In addition, preliminary data on maternal erythrocyte membrane lipid concentrations suggest modifications in placental transfer of fatty acids. Documenting the erythrocyte AA to DHA ratio at birth in larger cohorts might be useful to set up new prognostic factors for ROP.
Published: 2019

22. Vitreomacular Interface Abnormalities and Glaucoma in an Elderly Population (The MONTRACHET Study)

Author: Alassane Seydou, Catherine Creuzot-Garcher, Alain M. Bron, Cyril Meillon, Julie Blanc, Inès Ben Ghezala, Christine Binquet, Clémence Deschasse, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Institut National de la Santé et de la Recherche Médicale (INSERM), Supported by an interregional grant titled 'Programme Hospitalier de Recherche Clinique' and the regional Council of Burgundy., ProdInra, Migration, and Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Retinal Ganglion Cells, Multivariate analysis, Organes des sens, genetic structures, Visual Acuity, Glaucoma, Comorbidity, 0302 clinical medicine, Nerve Fibers, domaine spectral, Prospective Studies, Aged, 80 and over, Univariate analysis, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, tomographie, 3. Good health, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, population-based study, spectral-domain optical coherence tomography, Optic nerve, Female, France, Tomography, Optical Coherence, medicine.medical_specialty, Sensory Organs, Population, Médecine humaine et pathologie, glaucoma, vitreomacular interface, 03 medical and health sciences, Retinal Diseases, Ophthalmology, Elderly population, medicine, Humans, donnée optique, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, étude de population, education, Intraocular Pressure, Aged, business.industry, medicine.disease, Neurovascular bundle, eye diseases, glaucome, 030221 ophthalmology & optometry, Maculopathy, Human health and pathology, sense organs, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: International audience; Purpose: To investigate the prevalence of vitreomacular interface abnormalities (VMIAs) in a French elderly glaucomatous population. Methods: Using a population-based study, the MONTRACHET (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases) study conducted in Dijon from 2009 to 2013 in individuals older than 75 years, the prevalence of VMIAs was estimated on glaucoma patients. Results: A total of 1130 participants (2225 eyes) were included in the study. The mean age of participants was 82.3 +/- 3.8 years, and 62.74% were women. Regarding the frequency of all VMIAs, there was no statistical difference between glaucoma patients and nonglaucoma participants (51.85% vs. 53.92%, respectively, P = 0.372). In univariate analysis, vitreomacular adherences were more frequent in nonglaucoma participants (18.39% vs. 10.78%, P = 0.036). Epiretinal membranes were more frequent in the glaucomatous population (47.06% vs. 38.13%, P = 0.018). The prevalence of macular cysts was comparable in the two groups (7.84% vs. 5.64%, P = 0.262). Macular cysts were more frequent in eyes treated with preservative-free, IOP-lowering eye drops when compared with the eyes of nonglaucomatous participants treated with IOP-lowering eye drops containing a preservative (26.67% vs. 3.37% and 5.76%, respectively, P < 0.001). In multivariate analysis, these results were no longer significant. Conclusions: The prevalence of VMIAs was high in this elderly population and similar in both glaucomatous and nonglaucomatous participants. The information provided by macular optical coherence tomography scans should be considered with caution when used for glaucoma management in elderly patients.
Published: 2019

23. Validation of intracardiac shunt using thoracic bioimpedance and inert gas rebreathing in adults before and after percutaneous closure of atrial septal defect in a cardiology research unit: study protocol

Author: Bruno Pereira, Jean-René Lusson, Frédéric Costes, Aurélie Chalard, Romain Trésorier, Hélène Perrault, Laura Filaire, Ruddy Richard, Claire Dauphin, Thoracic and Endocrine Surgery, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Cardiology and Vascular Department, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Faculty of Health Sciences, University of Ottawa [Ottawa], Respiratory and Epidemiology Clinical Research Unit, Montreal Chest Institute, McGill University Health Center [Montreal] (MUHC)-McGill University Health Center [Montreal] (MUHC), MCGill University Health Centre, Biostatistiques, Danone Research, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), médecine du sport et explorations fonctionnelles, Centre Jean Perrin, Centre Hospitalier Universitaire Gabriel Montpied, University of Ottawa [Ottawa] (uOttawa), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), and Richard, Ruddy
Subjects: atrial septal defect (ASD), cardiac output, inert gas rebreathing, shunt quantification, thoracic bioimpedance, medicine.medical_specialty, Cardiac output, Percutaneous, Médecine humaine et pathologie, Cardiologie et système cardiovasculaire, Doppler echocardiography, Cardiovascular Medicine, Cardiography, Impedance, Noble Gases, Intracardiac injection, Heart Septal Defects, Atrial, 03 medical and health sciences, 0302 clinical medicine, Oxygen Consumption, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Protocol, Medicine, Humans, 030212 general & internal medicine, Independent research, medicine.diagnostic_test, business.industry, General Medicine, Echocardiography, Doppler, 3. Good health, Clinical trial, Cardiology and cardiovascular system, Treatment Outcome, Breath Tests, Cardiology, Human health and pathology, Inert gas rebreathing, business, 030217 neurology & neurosurgery, Shunt (electrical), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IntroductionIntrathoracic shunt quantification is a major factor for appropriate clinical management of heart and pulmonary diseases. Intracardiac shunts quantified by pulmonary to systemic output ratio (Qp/Qs) are generally assessed by Doppler echocardiography, MRI or catheterisation. Recently, some authors have suggested the concomitant use of thoracic bioimpedance (TB) and inert gas rebreathing (IGR) techniques for shunt quantification. The purpose of this study is to validate the use of this approach under conditions where shunt fraction is directly quantified such as in patients with isolated atrial septal defect (ASD).Methods and analysisThis trial is a prospective, observational single-centre, non-blinded study of adults seen for percutaneous closure of ASD. Qp/Qs ratio will be directly measured by Doppler echocardiography and direct Fick. IGR and TB will be used simultaneously to measure the cardiac output before and after closure: the ratio of outputs measured by IGR and TB reflecting the shunt fraction. The primary outcome will be the comparison of shunt values measured by TB-IGR and Doppler echocardiography.Ethics and disseminationThe study has been approved by an independent Research Ethics Committee (2017-A03149-44 Fr) and registered as an official clinical trial. The results will be published in a peer-reviewed journal.Trial registration numberNCT03437148; Pre-results.
Published: 2019

24. Letter to the editor: clarifying some aspects and the terminology of individualized human milk fortification

Author: Jean-Charles Picaud, Clair-Yves Boquien, Caroline King, Paola Tonetto, Sertac Arslanoglu, Barbara Królak-Olejnik, Delphine Lamireau, Working Group on Human Milk Fortification [Milan, Italie], European Milk Bank Association [Milan, Italie] (EMBA), Division of Neonatology [Istanbul, Turquie], Department of Pediatrics [Istanbul, Turquie], Istanbul Medeniyet University [Istanbul, Turquie] (IMU)-Istanbul Medeniyet University [Istanbul, Turquie] (IMU), Department of Nutrition & Dietetics [Londres, Royaume-Uni], Imperial College Healthcare NHS Trust [Londres, Royaume-Uni], Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Lactariums de Bordeaux-Marmande [Bordeaux], Pôle pédiatrique [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux]-CHU de Bordeaux Pellegrin [Bordeaux], Neonatal Unit [Turin, Italie], University of Turin, Division of Neonatology [Wrocław, Pologne], Wroclaw Medical University [Wrocław, Pologne], Division of Neonatology [Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Institut National de la Recherche Agronomique (INRA)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Bodescot, Myriam, Università degli studi di Torino = University of Turin (UNITO), Wrocław Medical University, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Arslanoglu, Sertac
Subjects: Adjustable fortification, Blood urea nitrogen, Enteral nutrition, Human milk fortification, Individualized fortification, Preterm infant feeding, Preterm infants, Targeted fortification, Supplementation, Enteral feeding, Terminology, Plasma, 0302 clinical medicine, fluids and secretions, Pregnancy, Very low birth weight infant, Medicine, Birth Weight, Urea, 030212 general & internal medicine, lcsh:RJ1-570, food and beverages, Protein intake, Urea concentration, Alimentation et Nutrition, Food, Fortified, Female, Research Article, Letter to the editor, Fortification, Médecine humaine et pathologie, Protein supply, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 030225 pediatrics, Environmental health, Food and Nutrition, Humans, Nutrition, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Milk, Human, business.industry, Infant, Newborn, Infant, lcsh:Pediatrics, Infant, premature, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Pediatrics, Perinatology and Child Health, Human health and pathology, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Background Feeding breast milk is associated with reduced morbidity and mortality, as well as improved neurodevelopmental outcome but does not meet the high nutritional requirements of preterm infants. Both plasma and urinary urea concentrations represent amino acid oxidation and low concentrations may indicate insufficient protein supply. This study assesses the effect of different levels of enteral protein on plasma and urinary urea concentrations and determines if the urinary urea-creatinine ratio provides reliable information about the protein status of preterm infants. Methods Sixty preterm infants (birthweight
Published: 2019

25. Muscle wasting in patients with end‐stage renal disease or early‐stage lung cancer: common mechanisms at work

Author: Stéphane Boisgard, Cécile Polge, Carole Philipponnet, Lydie Combaret, Julien Aniort, E. Rosset, Daniel Béchet, Odile Burlet-Schiltz, Anne-Elisabeth Heng, Alexandre Stella, A. Poyet, Daniel Taillandier, Didier Attaix, Agnès Claustre, Marc Filaire, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Néphrologie, Centre Hospitalier Universitaire (CHU), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Université Clermont Auvergne (UCA)-Institut National de la Recherche Agronomique (INRA), Université Clermont Auvergne (UCA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de nutrition cellulaire et moléculaire, Institut National de la Recherche Agronomique (INRA), Institut de Chimie de Clermont-Ferrand - Clermont Auvergne (ICCF), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Sigma CLERMONT (Sigma CLERMONT), CHU Clermont-Ferrand, Service de Chirurgie vasculaire, Unité de nutrition et métabolisme protéique, Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service d’Orthopédie Traumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Chirurgie Vasculaire, CHU Clermont-Ferrand, Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Service de Chirurgie Orthopédique et Traumatologique Hôpital Gabriel Montpied, Centre Hospitalier Universitaire de Clermont-Ferrand, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Aniort, Julien, Stella, Alexandre, Philipponnet, Carole, Poyet, Anaïs, Polge, Cécile, Claustre, Agnes, Combaret, Lydie, Béchet, Daniel, Attaix, Didier, Boisgard, Stéphane, Rosset, Eugenio, Burlet-Schiltz, Odile, Heng, Anne-Elisabeth, and Taillandier, Daniel
Subjects: Male, Proteomics, 0301 basic medicine, lcsh:Diseases of the musculoskeletal system, Lung Neoplasms, Cytoskeleton organization, Biopsy, [SDV]Life Sciences [q-bio], Skeletal muscle, Physiology, 0302 clinical medicine, Orthopedics and Sports Medicine, Wasting, Geriatry and gerontology, Cancer, lcsh:Human anatomy, Middle Aged, 3. Good health, Muscular Atrophy, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Original Article, medicine.symptom, Signal Transduction, Muscle contraction, Proteasome Endopeptidase Complex, Renal failure, Frailty syndrome, Proteasome, Autophagy, Médecine humaine et pathologie, Hemolysis, lcsh:QM1-695, End stage renal disease, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Physiology (medical), medicine, Humans, Muscle, Skeletal, Lung cancer, Aged, business.industry, Computational Biology, Original Articles, medicine.disease, 030104 developmental biology, Proteolysis, Gériatrie et gérontologie, Kidney Failure, Chronic, Human health and pathology, lcsh:RC925-935, Energy Metabolism, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background Loss of muscle mass worsens many diseases such as cancer and renal failure, contributes to the frailty syndrome , and is associated with an increased risk of death. Studies conducted on animal models have revealed the preponderant role of muscle proteolysis and in particular the activation of the ubiquitin proteasome system (UPS). Studies conducted in humans remain scarce, especially within renal deficiency. Whether a shared atrophying programme exists independently of the nature of the disease remains to be established. The aim of this work was to identify common modifications at the transcriptomic level or the proteomic level in atrophying skeletal muscles from cancer and renal failure patients. Methods Muscle biopsies were performed during scheduled interventions in early-stage (no treatment and no detectable muscle loss) lung cancer (LC), chronic haemodialysis (HD), or healthy (CT) patients (n = 7 per group; 86% male; 69.6 ± 11.4, 67.9 ± 8.6, and 70.2 ± 7.9 years P > 0.9 for the CT, LC, and HD groups, respectively). Gene expression of members of the UPS, autophagy, and apoptotic systems was measured by quantitative real-time PCR. A global analysis of the soluble muscle proteome was conducted by shotgun proteomics for investigating the processes altered. Results We found an increased expression of several UPS and autophagy-related enzymes in both LC and HD patients. The E3 ligases MuRF1 (+56 to 78%, P < 0.01), MAFbx (+68 to 84%, P = 0.02), Hdm2 (+37 to 59%, P = 0.02), and MUSA1/Fbxo30 (+47 to 106%, P = 0.01) and the autophagy-related genes CTPL (+33 to 47%, P = 0.03) and SQSTM1 (+47 to 137%, P < 0.01) were overexpressed. Mass spectrometry identified >1700 proteins, and principal component analysis revealed three differential proteomes that matched to the three groups of patients. Orthogonal partial least square discriminant analysis created a model, which distinguished the muscles of diseased patients (LC or HD) from those of CT subjects. Proteins that most contributed to the model were selected. Functional analysis revealed up to 238 proteins belonging to nine metabolic processes (inflammatory response, proteolysis, cytoskeleton organization, glucose metabolism, muscle contraction, oxidant detoxifica-tion, energy metabolism, fatty acid metabolism, and extracellular matrix) involved in and/or altered by the atrophying programme in both LC and HD patients. This was confirmed by a co-expression network analysis. Conclusions We were able to identify highly similar modifications of several metabolic pathways in patients exhibiting diseases with different aetiologies (early-stage LC vs. long-term renal failure). This strongly suggests that a common atrophying programme exists independently of the disease in human.
Published: 2019

26. Satellite cells fail to contribute to muscle repair but are functional in Pompe disease (glycogenosis type II)

Author: Salwa Soussi, Carine Ciron, Thibaut Larcher, Lydie Lagalice, Johan Deniaud, Sylvie Durand, Isabelle Leroux, Karl Rouger, Francesca Franzoso, Laurence Dubreil, Julien Pichon, Marie-Anne Colle, Eliot Gougeon, Mireille Ledevin, Virginie Maurier, Développement et Pathologie du Tissu Musculaire (DPTM), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Nantes, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), and Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Cell, Skeletal muscle, lcsh:RC346-429, Dystrophin, Mice, chemistry.chemical_compound, 0302 clinical medicine, Muscle regeneration, [SDV.IDA]Life Sciences [q-bio]/Food engineering, satellite cell, Myocyte, Longitudinal Studies, Glycogen, Glycogen Storage Disease Type II, Glycogen overload, Age Factors, Pompe disease, Lysosome, Pathophysiology, Cell biology, maladie de Pompe, medicine.anatomical_structure, Collagen, Microtubule-Associated Proteins, GAA KO 6neo/6neo mice, Satellite Cells, Skeletal Muscle, education, Médecine humaine et pathologie, Mice, Transgenic, Cardiotoxins, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, Satellite cell, Splitting, In vivo, cellule satellite, Autophagy, medicine, Animals, Humans, Regeneration, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Muscle, Skeletal, lcsh:Neurology. Diseases of the nervous system, business.industry, Research, Mice, Inbred C57BL, Disease Models, Animal, Ki-67 Antigen, 030104 developmental biology, Gene Expression Regulation, chemistry, Human health and pathology, Laminin, Neurology (clinical), Glucan 1,4-alpha-Glucosidase, Lysosomes, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Pompe disease, which is due to acid alpha-glucosidase deficiency, is characterized by skeletal muscle dysfunction attributed to the accumulation of glycogen-filled lysosomes and autophagic buildup. Despite the extensive tissue damages, a failure of satellite cell (SC) activation and lack of muscle regeneration have been reported in patients. However, the origin of this defective program is unknown. Additionally, whether these deficits occur gradually over the disease course is unclear. Using a longitudinal pathophysiological study of two muscles in a Pompe mouse model, here, we report that the enzymatic defect results in a premature saturating glycogen overload and a high number of enlarged lysosomes. The muscles gradually display profound remodeling as the number of autophagic vesicles, centronucleated fibers, and split fibers increases and larger fibers are lost. Only a few regenerated fibers were observed regardless of age, although the SC pool was preserved. Except for the early age, during which higher numbers of activated SCs and myoblasts were observed, no myogenic commitment was observed in response to the damage. Following in vivo injury, we established that muscle retains regenerative potential, demonstrating that the failure of SC participation in repair is related to an activation signal defect. Altogether, our findings provide new insight into the pathophysiology of Pompe disease and highlight that the activation signal defect of SCs compromises muscle repair, which could be related to the abnormal energetic supply following autophagic flux impairment.
Published: 2019

27. Real-world outcomes of observation and treatment in diabetic macular edema with very good visual acuity: the OBTAIN study

Author: Jay Chhablani, Jan Darius Unterlauft, Zafer Cebeci, Dinah Zur, Matias Iglicki, Inês Laíns, Mali Okada, Anna Sala-Puigdollers, Catharina Busch, Anat Loewenstein, Voraporn Chaikitmongkol, Ana Rita Santos, Marco Lupidi, Paradee Kunavisarut, Patricio J. Rodríguez-Valdés, Matus Rehak, Samantha Fraser-Bell, Adrian T. Fung, Pierre-Henry Gabrielle, Assaf Hilely, Małgorzata Ozimek, Ermete Giancipoli, Laboratoire LTEE, University of Sydney, Tel-Aviv Sourasky Medical Center, Tecnológico de Monterrey (ITESM), Istanbul University, Università degli Studi di Perugia (UNIPG), Westmead Hospital [Sydney], Macquarie University, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bourgogne Franche-Comté [COMUE] (UBFC), Università degli Studi di Sassari, Chiang Mai University (CMU), Royal Melbourne Hospital, Universidade de Coimbra, Association for Innovation and Biomedical Research on Light and Image (AIBILI), Harvard Medical School [Boston] (HMS), Polytechnic Institute of Porto, Hospital Clínic de Barcelona, L.V. Prasad Eye Institute, Partenaires INRAE, Medical University in Lublin, National University of Central Buenos Aires, Retina Australia, Retina Pigmentosa ASBL, Retina Brazil, The Foundation Fighting Blindness, Retina Ry / Retina Finland, Association RETINA France, PRO RETINA Deutschland e. V., Hellenic Retina Society, Hong Kong, For Our Sight Foundation, Blindrafélagið, Icelandic Association of the visually impaired (BIAVI) (Retina Iceland), Blindrafelagid – Retina Iceland, Fighting Blindness, Certo Clav, Retina Itialia, Japanese Retinitis Pigmentosa Society, Patientengroep Retina, Retina New Zealand Inc., Retinitis Pigmentosa Foreningen i Norge, Pakistan Foundation Fighting Blindness, ARP (Portuguese Association of RP), Retina South Africa, Svenska RP-Föreningen, RETINITIS PIGMENTOSA TAIPEI, RP Fighting Blindness, Foundation Fighting Blindness, Repositório Científico do Instituto Politécnico do Porto, and Busch, Catharina
Subjects: Male, Visual acuity, genetic structures, patient diabétique, Endocrinology, Diabetes and Metabolism, Visual Acuity, Angiogenesis Inhibitors, Observation, oedème maculaire, 030204 cardiovascular system & hematology, Cohort Studies, 0302 clinical medicine, Endocrinology, Good visual acuity, Diabetic macular edema, acuité visuelle, Real world outcomes, General Medicine, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, Bevacizumab, Treatment Outcome, Intravitreal Injections, Endocrinologie et métabolisme, Female, Original Article, medicine.symptom, Tomography, Optical Coherence, Cohort study, medicine.medical_specialty, Vision Disorders, Médecine humaine et pathologie, 030209 endocrinology & metabolism, Macular Edema, 03 medical and health sciences, Macular laser, Ophthalmology, Diabetes mellitus, Internal Medicine, medicine, Humans, Anti-VEGF therapy, Aged, Retrospective Studies, Endocrinology and metabolism, Diabetic Retinopathy, Dose-Response Relationship, Drug, business.industry, Intravitreal therapy, medicine.disease, eye diseases, laser, Human health and pathology, sense organs, Subretinal fluid, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, thérapie
Abstract: Aims To describe and compare the functional and anatomical outcomes of untreated and treated diabetic macular edema (DME) in eyes with very good baseline visual acuity (VA) in a real-world setting. Methods A 12-month, retrospective, multicenter, observational cohort study, including DME patients with baseline visual acuity (VA) ≤ 0.1 logMAR (≥ 20/25 Snellen) and central subfield thickness (CST) > 250 µm with intra- and/or subretinal fluid seen on optical coherence tomography. Results A total of 249 eyes were included, of which 155 were treated and 94 were non-treated during follow-up. Most eyes maintained vision (VA gain or VA loss
Published: 2019

28. Clinical Profile of Methotrexate-resistant Juvenile Localised Scleroderma

Author: Hardy, Juliette, Boralevi, Franck, Mallet, Stephanie, Cabrera, Natalia, Belot, Alexandre, Phan, Alice, Barbarot, Sébastien, Duriez-Lasek, Audrey, Chiaverini, Christine, Hubiche, Thomas, Mahe, Emmanuel, Begon, Edouard, Bourrat, Emmanuelle, Boccara, Olivia, Aubert, Hélène, Lerosey, Martine Grall, Droitcourt, Catherine, Piram, Maryam, Mazereeuw-Hautier, Juliette, Research Group of the French Society of Paediatric Dermatology (SDFP in French), ., Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Université de Bordeaux (UB), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Femme Mère Enfant, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Vincent de Paul, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Intercommunal, Hôpital d'Argenteuil, Université de Cergy Pontoise (UCP), Université Paris-Seine, AP-HP Hôpital universitaire Robert-Debré [Paris], CHU Necker - Enfants Malades [AP-HP], CHU Rouen, Normandie Université (NU), CHU Pontchaillou [Rennes], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), and Hardy, Juliette
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Adolescent, morphea, Drug Resistance, Médecine humaine et pathologie, Dermatology, Scleroderma, 03 medical and health sciences, Localised scleroderma, Scleroderma, Localized, 0302 clinical medicine, Internal medicine, lcsh:Dermatology, medicine, Juvenile, Humans, scleroderma, Localized Scleroderma, Paediatric dermatology, Child, Retrospective Studies, Dermatologie, 030203 arthritis & rheumatology, localized scleroderma, methotrexate, treatment, business.industry, Infant, General Medicine, lcsh:RL1-803, medicine.disease, Rheumatology, 3. Good health, 030104 developmental biology, Methotrexate, Child, Preschool, Human health and pathology, Female, Dermatologic Agents, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Morphea, medicine.drug
Abstract: International audience; Methotrexate has demonstrated its efficiency for the treatment of juvenile localized scleroderma but some patients may be resistant. The aim of our study was to define the profile of such patients. We performed an observational retrospective multicenter study between 2007 and 2016 and included all children seen in the French Paediatric Dermatology and Rheumatology departments with active localized scleroderma treated by methotrexate for a minimum of 4 months. Metho-trexate efficacy was assessed clinically and/or by imaging between the fourth to twelfth months of treatment. A total of 57 patients were included. Metho-trexate dosage ranged from 7 to 15 mg/m2/week. Only 4 patients were resistant. No common features could be identified between these 4 patients. Children with localized scleroderma are rarely resistant to metho-trexate and we did not identify a clinical profile for those resistant patients.
Published: 2019

29. Risk factors for carbapenem-resistant Enterobacteriaceae infections: a French case-control-control study

Author: Marie-Hélène Nicolas-Chanoine, Jérôme Robert, Marie Vigan, Cédric Laouénan, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Education and Research on Macromolecules, Université de Liège, Service de Microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC epidémiologie clinique/ essais cliniques, Hôpital Bichat - Claude Bernard, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Team E13, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Bactériologie et d'Hygiène Hospitalière [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), grant (NI12025) from the National Ministry of Health Hospital Clinical Research Program (PHRC2012), 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 Diderot - Paris 7 (UPD7), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire Jean Perrin (LJP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Gestionnaire, Hal Sorbonne Université, Centre d'Immunologie et des Maladies Infectieuses (CIMI), and Nicolas-Chanoine, Marie-Hélène
Subjects: Male, 0301 basic medicine, Multivariate analysis, résistance aux antibiotiques, Carbapenem-resistant enterobacteriaceae, Carbapenem-resistant Enterobacteriaceae (CRE), Carbapenemase-producing Enterobacteriaceae (CPE), Case-control-control study, Multicentre study, Risk factors, 0302 clinical medicine, Medical microbiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Univariate analysis, Microbiology and Parasitology, Enterobacteriaceae Infections, General Medicine, Middle Aged, Microbiologie et Parasitologie, Anti-Bacterial Agents, 3. Good health, [STAT]Statistics [stat], facteur de risque, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, Adult, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Médecine humaine et pathologie, Microbial Sensitivity Tests, beta-Lactamases, 03 medical and health sciences, Bacterial Proteins, Enterobacteriaceae, Internal medicine, medicine, entérobacteriaceae, Humans, Medical history, Male gender, Aged, business.industry, infection bactérienne, biochemical phenomena, metabolism, and nutrition, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Carbapenem-Resistant Enterobacteriaceae, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Human health and pathology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Electronic supplementary material : The online version of this article ( https://doi.org/10.1007/s10096-018-3438-9) contains supplementary material, which is available to authorized users.; International audience; This study aimed to assess characteristics associated with infections due to carbapenem-resistant Enterobacteriaceae (CRE), producing (CPE) or not producing (non-CPE) carbapenemase, among hospitalised patients in 2014-2016 in France. Case-patients with CRE were compared to two control populations. In multivariate analysis comparing 160 CRE cases to 160 controls C1 (patients with a clinical sample positive for carbapenem-susceptible Enterobacteriaceae), five characteristics were linked to CRE: male gender (OR = 1.9; 95% CI = 1.3-3.4), travel in Asia (OR = 10.0; 95% CI = 1.1-91.2) and hospitalisation in (OR = 2.4; 95% CI = 1.3-4.4) or out of (OR = 4.4; 95% CI = 0.8-24.1) France in the preceding 12 months, infection in the preceding 3 months (OR = 3.0; 95% CI = 1.5-5.9), and antibiotic receipt between admission and inclusion (OR = 1.9; 95% CI = 1.0-3.3). In multivariate analysis comparing 148 CRE cases to 148 controls C2 [patients with culture-negative sample(s)], four characteristics were identified: prior infection (OR = 3.3; 95% CI = 1.6-6.8), urine drainage (OR = 3.0; 95% CI = 1.5-6.1) and mechanical ventilation (OR = 3.7; 95% CI = 1.1-13.0) during the current hospitalisation, and antibiotic receipt between admission and inclusion (OR = 6.6; 95% CI = 2.8-15.5). Univariate analyses comparing separately CPE cases to controls (39 CPE vs C1 and 36 CPE vs C2) and non-CPE cases to controls (121 non-CPE vs C1 and 112 non-CPE vs C2), concomitantly with comparison of CPE to non-CPE cases showed that only CPE cases were at risk of previous travel and hospitalisation abroad. This study shows that, among CRE, risk factors are different for CPE and non-CPE infection, and suggests that question patients about their medical history and lifestyle should help for early identification of patients at risk of CPE among patients with CRE.
Published: 2019

30. Staphylococcus aureus induces DNA damage in host cell

Author: Deplanche, Martine, Mouhali, Nassim, Nguyen, Minh-Thu, Cauty, Chantal, Ezan, Frederic, Diot, Alan, Raulin, Lesly, Dutertre, Stephanie, Langouët, Sophie, Legembre, Patrick, Taieb, Frederic, Otto, Michael, Laurent, Frédéric, Goetz, Friedrich, Le Loir, Yves, Berkova, Nadia, Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, 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), Centre National de Reference des Staphylocoques, Université de Lyon, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biosit : biologie, santé, innovation technologique (SFR UMS CNRS 3480 - INSERM 018), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Eugène Marquis (CRLCC), Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institutes of Health [Bethesda] (NIH), French National Institute for Agricultural Research (INRA), LONGhealth - MP-P10573 (to N.B. and M.D), Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), U.S. National Institutes of Health (NIH), Grant Number 1 ZIA AI000904 (to M.O.), the Deutsche Forschungsgemeinschaft (DFG) SFB766 (to F.G. and M.T.), Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), U.S. National Institutes of Health (NIH) [1 ZIA AI000904], Deutsche Forschungsgemeinschaft (DFG) [SFB766], 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), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 ), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Eberhard Karls Universität Tübingen, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Jonchère, Laurent
Subjects: host cell, DNA Repair, lcsh:Medicine, human health, Histones, Phosphorylation, lcsh:Science, Osteitis, Etoposide, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, santé animale, Microbiology and Parasitology, santé humaine, Staphylococcal Infections, Microbiologie et Parasitologie, G2 Phase Cell Cycle Checkpoints, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Mechanisms of disease, Alimentation et Nutrition, Host-Pathogen Interactions, adn génomique, Infection, Staphylococcus aureus, Guanine, Genomic Islands, Lipoproteins, Bacterial Toxins, Médecine humaine et pathologie, Double-strand DNA breaks, Article, Cell Line, Tumor, Food and Nutrition, Humans, Cellular microbiology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Arthritis, Infectious, Osteoblasts, animal health, infection bactérienne, lcsh:R, cellule hôte, Acetylcysteine, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Oxidative Stress, staphylococcus aureus, infection, Human health and pathology, lcsh:Q, Reactive Oxygen Species, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Protein Processing, Post-Translational, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, DNA Damage, HeLa Cells
Abstract: International audience; Staphylococcus aureus causes serious medical problems in human and animals. Here we show thatS. aureus can compromise host genomic integrity as indicated by bacteria-induced histone H2AXphosphorylation, a marker of DNA double strand breaks (DSBs), in human cervix cancer HeLa andosteoblast-like MG-63 cells. This DNA damage is mediated by alpha phenol-soluble modulins (PSMα1–4),while a specific class of lipoproteins (Lpls), encoded on a pathogenicity island in S. aureus, dampens theH2AX phosphorylation thus counteracting the DNA damage. This DNA damage is mediated by reactiveoxygen species (ROS), which promotes oxidation of guanine forming 7,8-dihydro-8-oxoguanine (8-oxoG). DNA damage is followed by the induction of DNA repair that involves the ATM kinase-signalingpathway. An examination of S. aureus strains, isolated from the same patient during acute initial andrecurrent bone and joint infections (BJI), showed that recurrent strains produce lower amounts of Lpls,induce stronger DNA-damage and prompt the G2/M transition delay to a greater extent that suggest aninvolvement of these mechanisms in adaptive processes of bacteria during chronicization. Our findingsredefine our understanding of mechanisms of S. aureus-host interaction and suggest that the balancebetween the levels of PSMα and Lpls expression impacts the persistence of the infection.
Published: 2019

31. Subretinal drusenoid deposits in the elderly in a population-based study (the Montrachet study)

Author: Florian Baudin, Alassane Seydou, Pierre-Henry Gabrielle, Catherine Creuzot-Garcher, Inès Ben Ghezala, Christine Binquet, Niyazi Acar, Alain M. Bron, Louis Arnould, Hervé Devilliers, ProdInra, Migration, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Santé et de la Recherche Médicale (INSERM), INRA, CNRS, Université de Bourgogne, Regional Council of Burgundy France (PARI Agrale 1), FEDER (European Funding for Regional Economic Development), French National Research Agency (ANR) under the 'Investissements d'Avenir' program, ANR-11-LABX-0021-01-LipSTIC Labex., and Creuzot Garcher, Catherine
Subjects: Male, Multivariate analysis, Organes des sens, medicine.medical_treatment, 0302 clinical medicine, Epidemiology, Photography, Prevalence, Vitamin E, Medicine, Aged, 80 and over, 0303 health sciences, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, Age Factors, 3. Good health, medicine.anatomical_structure, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Alimentation et Nutrition, Female, France, Tomography, Optical Coherence, medicine.medical_specialty, Sensory Organs, Population, Médecine humaine et pathologie, Retinal Drusen, 03 medical and health sciences, Sex Factors, Zeaxanthins, Ophthalmology, Humans, Food and Nutrition, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, education, Aged, 030304 developmental biology, business.industry, Lutein, Fundus photography, Macular degeneration, medicine.disease, eye diseases, Population based study, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030221 ophthalmology & optometry, Human health and pathology, Choroid, sense organs, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Purpose: The aim of this study was to investigate the prevalence of subretinal drusenoid deposits (SDD) and to identify associated factors in an elderly population. Methods: The participants of the population-based Montrachet study underwent an exhaustive ophthalmologic examination, including color fundus photography and macular spectral domain-optical coherence tomography (SD-OCT), coupled with infrared reflectance imaging. The presence of SDD and other age-related macular degeneration lesions, according to the European Eye Epidemiology SD-OCT classification of macular diseases, and subfoveal choroidal thickness were recorded. Moreover, the association of SDD and both clinical and demographic factors as well as plasma levels of vitamin E and lutein/zeaxanthin (L/Z) were analyzed. Results: The mean age of patients was 82.3 ± 3.8 years and 62.7% were female. The prevalence of SDD was 18.1% (n = 205) in the subjects with at least one eye interpretable (n = 1135). In multivariate analysis, SDD was positively associated with increasing age (OR, 4.6; 95% CI, 2.8–7.7; P < 0.001 for subjects aged >85 years), female sex (OR, 1.7; 95% CI, 1.2–2.4; P = 0.005), and plasma L/Z level (OR, 1.2; 95% CI, 1.0–1.5; P = 0.039), and negatively associated with lipid-lowering drugs use (OR, 0.5; 95% CI, 0.3–0.9; P = 0.014 for statin medications) and subfoveal choroidal thickness (OR, 0.8; 95% CI, 0.7–0.9; P = 0.002). Conclusions: The prevalence of SDD was high in subjects older than 75 years, more frequent in women, and was associated with a thinner choroid. The association with lipid-lowering drugs deserves further investigation.
Published: 2019

32. Baseline microbiota composition modulates antibiotic-mediated effects on the gut microbiota and host

Author: Aonghus Lavelle, Hang-Phuong Pham, Eric Guédon, Philippe Langella, Thomas W. Hoffmann, Harry Sokol, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, ILTOO Pharma, Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-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), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Syndifrais-CNIEL (Paris, France) for their financial support with the project Exibam. Aonghus Lavelle has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n. PCOFUND-GA-2013-609102, through the PRESTIGE programme coordinated by Campus France., Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), ProdInra, Archive Ouverte, Sorbonne Université, Saint-Antoine Research Center (CRSA), Institut National de la Santé et de la Recherche Médicale (INSERM), 1Sorbonne Université, Saint-Antoine Research Center (CRSA) Paris, Department of Gastroenterology, Saint Antoine Hospital, Assistance Publique – Hopitaux de Paris, and Sorbonne Universités
Subjects: Male, Antibiotics, microbiome, Gut flora, human health, Transcriptome, antibiotique, Feces, Mice, Medical microbiology, antibiotic, Prevotella, Gut, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Microbiota, Microbiology and Parasitology, santé humaine, Fecal Microbiota Transplantation, Microbiologie et Parasitologie, Anti-Bacterial Agents, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, lcsh:QR100-130, intestin, transcriptome, expression des gènes, Microbiology (medical), medicine.medical_specialty, Colon, medicine.drug_class, Médecine humaine et pathologie, Biology, Amoxicillin-Potassium Clavulanate Combination, Bacterial Physiological Phenomena, Microbiology, lcsh:Microbial ecology, 03 medical and health sciences, Microbial ecology, medicine, Animals, Germ-Free Life, Humans, Microbiome, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, intestine, 030304 developmental biology, Bacteria, 030306 microbiology, Research, Gene Expression Profiling, biology.organism_classification, Gastrointestinal Microbiome, Immunology, Human health and pathology, Bacteroides, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Normal mammalian development and homeostasis are dependent upon the gut microbiota. Antibiotics, essential for the treatment and prophylaxis of bacterial infections, can have collateral effects on the gut microbiota composition, which can in turn have far-reaching and potentially deleterious consequences for the host. However, the magnitude and duration of such collateral effects appear to vary between individuals. Furthermore, the degree to which such perturbations affect the host response is currently unclear. We aimed to test the hypothesis that different human microbiomes have different responses to a commonly prescribed antibiotic and that these differences may impact the host response. Methods Germ-free mice (n = 30) humanized with the microbiota of two unrelated donors (A and B) were subjected to a 7-day antibiotic challenge with amoxicillin-clavulanate (“co-amoxiclav”). Microbiome and colonic transcriptome analysis was performed, pre (day 0) and post antibiotics (day 8) and subsequently into recovery (days 11 and 18). Results Unique community profiles were evident depending upon the donor, with donor A recipient mice being dominated by Prevotella and Faecalibacterium and donor B recipient mice dominated by Bacteroides and Parabacteroides. Donor A mice underwent a marked destabilization of their microbiota following antibiotic treatment, while donor B mice maintained a more stable profile. Dramatic and overlapping alterations in the host transcriptome were apparent following antibiotic challenge in both groups. Despite this overlap, donor A mice experienced a more significant alteration in gene expression and uniquely showed correlations between host pathways and key microbial genera. Conclusions Germ-free mice humanized by different donor microbiotas maintain distinct microbiome profiles, which respond in distinct ways to antibiotic challenge and evince host responses that parallel microbiome disequilibrium. These results suggest that inter-individual variation in the gut microbiota may contribute to personalized host responses following microbiota perturbation. Electronic supplementary material The online version of this article (10.1186/s40168-019-0725-3) contains supplementary material, which is available to authorized users.
Published: 2019

33. Educational and health outcomes associated with bronchopulmonary dysplasia in 15-year-olds born preterm

Author: Catherine Arnaud, Christophe Delacourt, Marie Mittaine, Pierre-Yves Ancel, Didier Pinquier, Marie Vestraete, Laure Couderc, Stéphane Marret, Alice Hadchouel, David Drummond, Adèle Bellino, Héloïse Torchin, Jean-Christophe Rozé, Jessica Rousseau, Paediatric Pulmonology, Ghent University Hospital, Université Paris Descartes - Paris 5 (UPD5), Hopital port Royal, Partenaires INRAE, Université de Nantes (UN), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Purpan (CHU Purpan), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (COMUE) (USPC), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], ProdInra, Migration, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), and Drummond, David
Subjects: Male, Pediatrics, European People, Social Sciences, Logistic regression, Adolescents, Pathology and Laboratory Medicine, Vascular Medicine, Cohort Studies, Families, 0302 clinical medicine, Sociology, Pregnancy, Medicine and Health Sciences, Ethnicities, 030212 general & internal medicine, French People, Children, Bronchopulmonary Dysplasia, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Academic Success, Schools, Organic Compounds, maternity, Chemistry, ventilatory, Cohort, Physical Sciences, Premature Birth, Medicine, Female, Steroids, France, Cohort study, Research Article, medicine.medical_specialty, Dysplasia, Adolescent, Pédiatrie, Science, xygen, Médecine humaine et pathologie, Special needs, Hemorrhage, behavioral disciplines and activities, Education, neonatal, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Signs and Symptoms, Diagnostic Medicine, 030225 pediatrics, mental disorders, medicine, Humans, Full Term, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Organic Chemistry, Infant, Newborn, Chemical Compounds, Biology and Life Sciences, Neonates, Patient Acceptance of Health Care, medicine.disease, Bronchopulmonary dysplasia, Age Groups, People and Places, Human health and pathology, Population Groupings, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Developmental Biology
Abstract: IntroductionTo evaluate the consequences of bronchopulmonary dysplasia (BPD) on academic outcomes and healthcare use in adolescents born very preterm.MethodsThis cohort study included 15-year-old adolescents born very preterm (< 32 weeks) between 2011 and 2013, with and without BPD, and controls born full term. Data regarding academic performance, current medical follow-up, and family characteristics were collected. Multivariate logistic regression was used to quantify relationships between academic outcomes and BPD.ResultsFrom the 1341 children included in the initial cohort, 985 adolescents were eligible and 351 included (55 preterms with a history of BPD, 249 without, and 47 controls). Among adolescents born very preterm, a history of BPD was associated with a higher risk to attend a school for children with special needs (p < 0.05) and to have repeated a grade (p = 0.01). It was also associated with an increased number of medical and paramedical consultations. A history of BPD was not associated with the parents' employment status, family structure, or the presence of younger siblings.ConclusionThis study highlights that a history of BPD is associated with poorer academic outcomes and high healthcare use in adolescence.
Published: 2019

34. TNF blockade contributes to restore lipid oxidation during exercise in children with juvenile idiopathic arthritis

Author: Emmanuelle Rochette, Pierre Bourdier, Anthony Birat, Etienne Merlin, Bruno Pereira, Eric Doré, Pascale Duché, Sébastien Ratel, Stéphane Echaubard, Pédiatrie, Centre Hospitalier National Pédiatrique Charles de Gaulle (CHNP-CDG), Unité CRECHE, Centre d’Investigation Clinique 1405 (CIC), Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche en Nutrition Humaine, Délégation de la Recherche Clinique et Innovations, CHU Clermont-Ferrand, Impact de l'Activité Physique sur la Santé (IAPS), Université de Toulon (UTLN), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Rochette, Emmanuelle
Subjects: Male, lcsh:Diseases of the musculoskeletal system, Arthritis, physical activity, Pediatrics, Incremental exercise, 0302 clinical medicine, Immunology and Allergy, 030212 general & internal medicine, Child, ComputingMilieux_MISCELLANEOUS, education.field_of_study, lcsh:RJ1-570, fat oxidation, Carbohydrate Metabolism, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, Oxidation-Reduction, Research Article, medicine.medical_specialty, Adolescent, Pédiatrie, Population, Médecine humaine et pathologie, Inflammation, Carbohydrate metabolism, 03 medical and health sciences, Oxygen Consumption, Rheumatology, Lipid oxidation, Internal medicine, medicine, Humans, education, Exercise, 030203 arthritis & rheumatology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Tumor Necrosis Factor-alpha, Lipid metabolism, Calorimetry, Indirect, lcsh:Pediatrics, medicine.disease, Lipid Metabolism, Arthritis, Juvenile, Endocrinology, pediatric, inflammation, Case-Control Studies, Pediatrics, Perinatology and Child Health, Exercise Test, Tumor Necrosis Factor Inhibitors, Human health and pathology, lcsh:RC925-935, metabolism, business, Energy Metabolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Children with juvenile idiopathic arthritis (JIA) have impaired physical abilities. TNF-α plays a crucial role in this pathogenesis, but it is also involved in the use of lipids and muscle health. Objective of this study was to explore substrate oxidation and impact of TNF blockade on energy metabolism in children with JIA as compared to healthy children. Methods Fifteen non-TNF-blockaded and 15 TNF-blockaded children with JIA and 15 healthy controls were matched by sex, age, and Tanner stage. Participants completed a submaximal incremental exercise test on ergocycle to determine fat and carbohydrate oxidation rates by indirect calorimetry. Results The maximal fat oxidation rate during exercise was lower in JIA children untreated by TNF blockade (134.3 ± 45.2 mg.min− 1) when compared to the controls (225.3 ± 92.9 mg.min− 1, p = 0.007); but was higher in JIA children under TNF blockade (163.2 ± 59.0 mg.min− 1, p = 0.31) when compared to JIA children untreated by TNF blockade. At the same relative exercise intensities, there was no difference in carbohydrate oxidation rate between three groups. Conclusions Lipid metabolism during exercise was found to be impaired in children with JIA. However, TNF treatment seems to improve the fat oxidation rate in this population. Trial registration In ClinicalTrials.gov, reference number NCT02977416, registered on 30 November 2016.
Published: 2019

35. Serum levels of miR-126 and miR-223 and outcomes in chronic kidney disease patients

Author: Fourdinier, Ophélie, Schepers, Eva, Metzinger-Le Meuth, Valérie, Glorieux, Griet, Liabeuf, Sophie, Verbeke, Francis, Vanholder, Raymond, Brigant, Benjamin, Pletinck, Anneleen, Diouf, Momar, Burtey, Stéphane, Choukroun, Gabriel, Massy, Ziad A., Metzinger, Laurent, Argiles, Angel, Beige, Joachim, Brunet, Philippe, Cohen, Gerald, Deif, Omar Abou, Evenepoel, Pieter, Fliser, Danilo, Fridolin, Ivo, Gmerek, Andreas, Jankowski, Joachim, Jankowski, Vera, Masereeuw, Roos, Mischak, Harald, Ortiz, Alberto, Perna, Alessandra, Rodriguez-Portillo, Juan Mariano, Schanstra, Joost, Spasovski, Goce, Stamatialis, Dimitrios, Steppan, Sonja, Storr, Markus, Stegmayr, Bernd G., Stenvinkel, Peter, Thornalley, Paul J., Wiecek, Andrej, Biomaterials Science and Technology, INSERM U-1088, Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, Ghent University Hospital, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire Ambroise Paré (CHU Ambroise Paré), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), ProdInra, Migration, Fourdinier, Ophélie, Schepers, Eva, Metzinger-Le Meuth, Valérie, Glorieux, Griet, Liabeuf, Sophie, Verbeke, Franci, Vanholder, Raymond, Brigant, Benjamin, Pletinck, Anneleen, Diouf, Momar, Burtey, Stéphane, Choukroun, Gabriel, Massy, Ziad A., Metzinger, Laurent, Argiles, Angel, Beige, Joachim, Brunet, Philippe, Cohen, Gerald, Deif, Omar Abou, Evenepoel, Pieter, Fliser, Danilo, Fridolin, Ivo, Gmerek, Andrea, Jankowski, Joachim, Jankowski, Vera, Masereeuw, Roo, Mischak, Harald, Ortiz, Alberto, Perna, Alessandra, Rodriguez-Portillo, Juan Mariano, Schanstra, Joost, Spasovski, Goce, Stamatialis, Dimitrio, Steppan, Sonja, Storr, Marku, Stegmayr, Bernd G., Stenvinkel, Peter, Thornalley, Paul J., and Wiecek, Andrej
Subjects: insuffisance rénale, 0301 basic medicine, Nephrology, Male, medicine.medical_treatment, SMOOTH-MUSCLE-CELLS, lcsh:Medicine, urologic and male genital diseases, Gastroenterology, Severity of Illness Index, 0302 clinical medicine, Medicine and Health Sciences, Medicine, lcsh:Science, POPULATION, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, PLASMA, PROLIFERATION, microarn articielle, activité sérique, Middle Aged, Prognosis, CANCER, Pathophysiology, female genital diseases and pregnancy complications, 3. Good health, European Uremic Toxin Work Group-EUTox, Female, INJURY MOLECULE-1, Adult, EXPRESSION, medicine.medical_specialty, Endpoint Determination, Population, Médecine humaine et pathologie, Down-Regulation, PREDICTS PROGRESSION, Article, End stage renal disease, 03 medical and health sciences, CIRCULATING MICRORNAS, Internal medicine, Humans, Renal replacement therapy, Renal Insufficiency, Chronic, General, education, Survival rate, Aged, business.industry, lcsh:R, Cancer, QUANTIFICATION, medicine.disease, Survival Analysis, accident cardiovasculaire, MicroRNAs, 030104 developmental biology, Case-Control Studies, néphropathie, Human health and pathology, lcsh:Q, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Kidney disease
Abstract: Several microRNAs (miRNAs) have been linked to chronic kidney disease (CKD) mortality, cardiovascular (CV) complications and kidney disease progression. However, their association with clinical outcomes remains poorly evaluated. We used real-time qPCR to measure serum levels of miR-126 and miR-223 in a large cohort of 601 CKD patients (CKD stage G1 to G5 patients or on renal replacement therapy - CKD G5D) from Ghent University Hospital and 31 healthy controls. All-cause mortality and cardiovascular and renal events were registered as endpoints over a 6 year follow-up period. miR-126 levels were significantly lower from CKD stage G2 on, compared to controls. The serum levels of miR-223 were significantly lower from CKD stage G3B on. When considering overall mortality, patients with levels of either miR-126 or miR-223 below the median had a lower survival rate. Similar results were observed for CV and renal events. The observed link between the two miRNAs' seric levels and mortality, cardiovascular events or renal events in CKD appears to depend on eGFR. However, this does not preclude their potential role in the pathophysiology of CKD. In conclusion, CKD is associated with a decrease in circulating miR-223 and miR-126 levels. ispartof: Sci Rep vol:9 issue:1 pages:4477- ispartof: location:England status: Published online
Published: 2019

36. Pre-transplantation assessment of BK virus serostatus: Significance, current methods, and obstacles

Author: Haidar Akl, Fatima Dakroub, Antoine Touzé, Etienne Brochot, Brochot, Etienne, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Université Libanaise, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), CHU Amiens-Picardie, and Institut National de la Recherche Agronomique (INRA)-Université de Tours
Subjects: Graft Rejection, 0301 basic medicine, medicine.medical_treatment, Virologie, lcsh:QR1-502, BK virus serology, Review, 030230 surgery, medicine.disease_cause, lcsh:Microbiology, Serology, 0302 clinical medicine, serological technique, Kidney transplantation, Predictive marker, Immunosuppression, santé humaine, 3. Good health, BK virus, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, kidney transplantation, polyomavirus, Médecine humaine et pathologie, Structure type, antigène viral, 03 medical and health sciences, Virology, medicine, Humans, Serologic Tests, Viremia, immunodétection, Retrospective Studies, Immunosuppression Therapy, transplantation rénale, business.industry, medicine.disease, Transplant Recipients, Transplantation, Tumor Virus Infections, 030104 developmental biology, DNA, Viral, Immunology, Human health and pathology, business, Serostatus, sérologie, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The immunosuppression required for graft tolerance in kidney transplant patients can trigger latent BK polyomavirus (BKPyV) reactivation, and the infection can progress to nephropathy and graft rejection. It has been suggested that pre-transplantation BKPyV serostatus in donors and recipients is a predictive marker for post-transplantation BKPyV replication. The fact that research laboratories have used many different assay techniques to determine BKPyV serostatus complicates these data analysis. Even studies based on the same technique differed in their standard controls choice, the antigenic structure type used for detection, and the cut-off for seropositivity. Here, we review the different BKPyV VP1 antigens types used for detection and consider the various BKPyV serostatus assay techniques' advantages and disadvantages. Lastly, we highlight the obstacles in the implementation of a consensual BKPyV serologic assay in clinics (e.g., the guidelines absence in this field).
Published: 2019

37. Subfoveal Choroidal Thickness, Cardiovascular History, and Risk Factors in the Elderly: The Montrachet Study

Author: Youssef El Alami, Abderrahmane Bourredjem, Alain M. Bron, Charles Guenancia, Alassane Seydou, Pierre-Henry Gabrielle, Christine Binquet, Christophe Tzourio, Vincent Daien, Louis Arnould, Catherine Creuzot-Garcher, Creuzot Garcher, Catherine, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), 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), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Supported by an interregional grant (Programme Hospitalier de Recherche Clinique) and the Regional Council of Burgundy, by INRA, CNRS, Université de Bourgogne, Regional Council of Burgundy France (PARI Agrale 1), FEDER (European Funding for Regional Economic Development), and a French government grant managed by the French National Research Agency (ANR) under the ‘‘Investissements d'Avenir' program, ANR-11-LABX-0021-01-LipSTIC Labex., and ProdInra, Migration
Subjects: Male, retina, Organes des sens, Heart disease, 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, cardiovascular disease, Aged, 80 and over, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Framingham Risk Score, Age Factors, Organ Size, Axial length, 3. Good health, Axial Length, Eye, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Cardiovascular Diseases, population-based study, Biomarker (medicine), Female, France, Tomography, Optical Coherence, medicine.medical_specialty, Sensory Organs, Population, Médecine humaine et pathologie, subfoveal choroidal thickness, elderly, 03 medical and health sciences, Heart Score, Montrachet study, choroid, Ophthalmology, medicine, Humans, Medical history, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, education, Aged, Cardiovascular History, business.industry, medicine.disease, 030221 ophthalmology & optometry, Maculopathy, Human health and pathology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Purpose: To measure subfoveal choroidal thickness (SFCT) in the elderly and to determine the associations among SFCT, cardiovascular history, and the 10-year risk of fatal cardiovascular disease (CVD). Methods: We conducted a population-based study, the Montrachet (Maculopathy Optic Nerve, nuTRition neurovAsCular, and HEarT disease) study, in subjects older than 75 years. SFCT was measured with spectral-domain optical coherence tomography (SD-OCT) with enhanced-depth mode imaging. Participants underwent a comprehensive eye examination. The history of CVD, CVD risk factors, and a score-based estimation of their 10-year risk of cardiovascular mortality (Heart Score) were collected. Results: Overall, 764 participants were retained for analysis. The mean SFCT was 206.4 +/- 83.0 mum. The mean age was 81.9 +/- 3.6 years. After a multivariable analysis, older age (beta = -32.56 mum, P < 0.001) and longer axial length (beta = -20.71 mum, P < 0.001) were independently associated with thinner SFCT. SFCT was not significantly associated with sex, cardiovascular history, classical CVD risk factors, or prognostic risk score. Conclusions: This study confirms that longer axial length and older age are associated with thinner SFCT. However, SFCT does not appear to be a biomarker for cardiovascular history in this study.
Published: 2019

38. Evolutionarily conserved susceptibility of the mitochondrial respiratory chain to SDHI pesticides and its consequence on the impact of SDHIs on human cultured cells

Author: Pierre Rustin, Agathe Kahn, Judith Favier, Paule Bénit, Pierre Gressens, D Chretien, Sylvie Bortoli, Anne Paule Gimenez-Roqueplo, Laurence Huc, Malgorzata Rak, Manuel Schiff, Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Contaminants & Stress Cellulaire (ToxAlim-COMICS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Service de neurologie pédiatrique et maladies métaboliques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), No specific funding was initially provided for this work. After the work realization, PB and PR received a specific support grant from the French Association POLLINIS (https://www.pollinis.org/). General expenses were covered by grants from AAJI (Association pour l’Aide aux Jeunes Infirmes & aux Personnes Handicapées), AFAF (Association Française de l’Ataxie de Friedreich), Association OLY (Ouvrir Les Yeux), ANR MITOXDRUGS (ANR-16-CE18-0010)., ANR-16-CE18-0010,MITOXDRUGS,Toxicité mitochondriale des médicaments et stéatose hépatique. Généralisation de la relation causale pour le développement de nouveaux tests prédictifs.(2016), 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) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Rustin, Pierre, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Bodescot, Myriam, and Toxicité mitochondriale des médicaments et stéatose hépatique. Généralisation de la relation causale pour le développement de nouveaux tests prédictifs. - - MITOXDRUGS2016 - ANR-16-CE18-0010 - AAPG2016 - VALID
Subjects: 0301 basic medicine, Glutamine, Respiratory chain, Mitochondrion, Toxicology, Biochemistry, Antioxidants, Database and Informatics Methods, 0302 clinical medicine, Animal Cells, Medicine and Health Sciences, Glycolysis, Annelids, Amino Acids, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Energy-Producing Organelles, Cells, Cultured, Connective Tissue Cells, Multidisciplinary, biology, Organic Compounds, Succinate dehydrogenase, Monosaccharides, Acidic Amino Acids, Quinones, Eukaryota, Neurodegenerative Diseases, Bees, Mitochondria, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Insects, Succinate Dehydrogenase, Chemistry, Mitochondrial respiratory chain, [SDV.TOX.TVM] Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, Connective Tissue, Physical Sciences, Mitochondrial Membranes, Medicine, Cellular Structures and Organelles, Cellular Types, Anatomy, Honey Bees, Sequence Analysis, Research Article, Arthropoda, Bioinformatics, Science, Carbohydrates, Médecine humaine et pathologie, [SDV.TOX.TVM]Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, Oxidative phosphorylation, Bioenergetics, Research and Analysis Methods, Electron Transport, Fungal Proteins, 03 medical and health sciences, Drug Resistance, Fungal, Animals, Earthworms, Humans, Oligochaeta, Pesticides, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Toxicologie, Organic Chemistry, Chemical Compounds, Organisms, Fungi, Biology and Life Sciences, Proteins, Cell Biology, Fibroblasts, Invertebrates, Hymenoptera, Biological Tissue, Glucose, 030104 developmental biology, Cell culture, biology.protein, Human health and pathology, Sequence Alignment, 030217 neurology & neurosurgery
Abstract: International audience; Succinate dehydrogenase (SDH) inhibitors (SDHIs) are used worldwide to limit the proliferation of molds on plants and plant products. However, as SDH, also known as respiratory chain (RC) complex II, is a universal component of mitochondria from living organisms, highly conserved through evolution, the specificity of these inhibitors toward fungi warrants investigation. We first establish that the human, honeybee, earthworm and fungal SDHs are all sensitive to the eight SDHIs tested, albeit with varying IC50 values, generally in the micromolar range. In addition to SDH, we observed that five of the SDHIs, mostly from the latest generation, inhibit the activity of RC complex III. Finally, we show that the provision of glucose ad libitum in the cell culture medium, while simultaneously providing sufficient ATP and reducing power for antioxidant enzymes through glycolysis, allows the growth of RC-deficient cells, fully masking the deleterious effect of SDHIs. As a result, when glutamine is the major carbon source, the presence of SDHIs leads to time-dependent cell death. This process is significantly accelerated in fibroblasts derived from patients with neurological or neurodegenerative diseases due to RC impairment (encephalopathy originating from a partial SDH defect) and/or hypersensitivity to oxidative insults (Friedreich ataxia, familial Alzheimer's disease).
Published: 2019

39. Prebiotics: mechanisms and preventive effects in allergy

Author: Sébastien Barbarot, Carole Brosseau, Susan L. Prescott, Debra J. Palmer, Amandine Selle, Marie Bodinier, Bodinier, Marie, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Telethon KIDS Institute, The University of Western Australia (UWA), University of Western Australia, Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), and Université de Nantes (UN)
Subjects: 0301 basic medicine, Allergy, Allergy prevention, medicine.medical_treatment, Médecine humaine et pathologie, lcsh:TX341-641, Review, Biology, 03 medical and health sciences, 0302 clinical medicine, Immune system, allergy, clinical studies, epithelial barrier, immune system, mechanisms, microbiota, prebiotics, preclinical studies, Hypersensitivity, medicine, Humans, Food and Nutrition, Microbiome, Barrier function, Epithelial barrier, Nutrition and Dietetics, Prebiotic, Fatty Acids, Volatile, medicine.disease, Early life, 3. Good health, Gastrointestinal Tract, 030104 developmental biology, 030228 respiratory system, Immunology, Alimentation et Nutrition, Human health and pathology, lcsh:Nutrition. Foods and food supply, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Food Science
Abstract: International audience; Allergic diseases now affect over 30% of individuals in many communities, particularly young children, underscoring the need for effective prevention strategies in early life. These allergic conditions have been linked to environmental and lifestyle changes driving the dysfunction of three interdependent biological systems: microbiota, epithelial barrier and immune system. While this is multifactorial, dietary changes are of particular interest in the altered establishment and maturation of the microbiome, including the associated profile of metabolites that modulate immune development and barrier function. Prebiotics are non-digestible food ingredients that beneficially influence the health of the host by 1) acting as a fermentable substrate for some specific commensal host bacteria leading to the release of short-chain fatty acids in the gut intestinal tract influencing many molecular and cellular processes; 2) acting directly on several compartments and specifically on different patterns of cells (epithelial and immune cells). Nutrients with prebiotic properties are therefore of central interest in allergy prevention for their potential to promote a more tolerogenic environment through these multiple pathways. Both observational studies and experimental models lend further credence to this hypothesis. In this review, we describe both the mechanisms and the therapeutic evidence from preclinical and clinical studies exploring the role of prebiotics in allergy prevention.
Published: 2019

40. Parathyroid hormone initiates dynamic NHERF1 phosphorylation cycling and conformational changes that regulate NPT2A-dependent phosphate transport

Author: Rima Al-awar, David Uehling, Babu Joseph, Sheng Li, Jose M. Paredes, Tatyana Mamonova, Angel Orte, Kunhong Xiao, W. Bruce Sneddon, Qiangmin Zhang, Peter A. Friedman, Jennifer McGarvey, Hongda Liu, Frederic Jean-Alphonse, Dawei Wang, University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Universidad de Granada (UGR), Department of Medicine, University of California [San Diego] (UC San Diego), University of California-University of California, Department of Drug Discovery, Alnylam Pharmaceuticals, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Department of Structural Biology, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Supported by National Institutes of Health Awards DK105811 and DK111427 (to P. A. F.), Spanish Ministry of Economy and Competitiveness Grant CTQ2014-56370-R, the Agencia Estatal de Investigacion (AEI), and the European Regional Development Fund (ERDF) (to A. O.)., Universidad de Los Andes [Venezuela] (ULA), Sun Yat-Sen University [Guangzhou] (SYSU), Chinese Academy of Sciences [Beijing] (CAS), and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Protein Conformation, Parathyroid hormone, phosphoprotéine, biochimie structurale, Crystallography, X-Ray, Biochemistry, protein-protein interaction, chemistry.chemical_compound, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Serine, structural biology, Protein phosphorylation, Phosphorylation, deuterium, phosphoprotein phosphatase 1 (PP1), Chemistry, Kinase, PDZ domain, protein phosphorylation, hydrogen-deuterium exchange, NHERF1, NPT2A, phosphate transport, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], hydrogène, Lipids, transfert de phosphate, Cell biology, Parathyroid Hormone, Protein Structure and Folding, Sodium-Hydrogen Exchangers, Phosphatase, Médecine humaine et pathologie, Sodium-Phosphate Cotransporter Proteins, Type IIa, Phosphates, phosphatase, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, Dephosphorylation, 03 medical and health sciences, Humans, Amino Acid Sequence, Furans, Molecular Biology, Ion Transport, hormone thyroïdienne, 030102 biochemistry & molecular biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, Phosphoproteins, Phosphate, Receptors, Neuropeptide Y, HEK293 Cells, 030104 developmental biology, Phosphoprotein, transporteur de phosphate, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Human health and pathology, phosphorylation des protéines, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Na+-H+ exchanger regulatory factor-1 (NHERF1) is a PDZ protein that scaffolds membrane proteins, including sodium-phosphate co-transport protein 2A (NPT2A) at the plasma membrane. NHERF1 is a phosphoprotein with 40 Ser and Thr residues. Here, using tandem MS analysis, we characterized the sites of parathyroid hormone (PTH)-induced NHERF1 phosphorylation and identified 10 high-confidence phosphorylation sites. Ala replacement at Ser(46), Ser(162), Ser(181), Ser(269), Ser(280), Ser(291), Thr(293), Ser(299), and Ser(302) did not affect phosphate uptake, but S290A substitution abolished PTH-dependent phosphate transport. Unexpectedly, Ser(290) was rapidly dephosphorylated and rephosphorylated after PTH stimulation, and we found that protein phosphatase 1 (PP1), which binds NHERF1 through a conserved VxF/W PP1 motif, dephosphorylates Ser(290). Mutating (VPF259)-V-257 eliminated PP1 binding and blunted dephosphorylation. Tautomycetin blocked PP1 activity and abrogated PTH-sensitive phosphate transport. Using fluorescence lifetime imaging (FLIM), we observed that PTH paradoxically and transiently elevates intracellular phosphate. Added phosphate blocked PP1-mediated Ser(290) dephosphorylation of recombinant NHERF1. Hydrogen-deuterium exchange MS revealed that -sheets in NHERF1's PDZ2 domain display lower deuterium uptake than those in the structurally similar PDZ1, implying that PDZ1 is more cloistered. Dephosphorylated NHERF1 exhibited faster exchange at C-terminal residues suggesting that NHERF1 dephosphorylation precedes Ser(290) rephosphorylation. Our results show that PP1 and NHERF1 form a holoenzyme and that a multiprotein kinase cascade involving G protein-coupled receptor kinase 6A controls the Ser(290) phosphorylation status of NHERF1 and regulates PTH-sensitive, NPT2A-mediated phosphate uptake. These findings reveal how reversible phosphorylation modifies protein conformation and function and the biochemical mechanisms underlying PTH control of phosphate transport.
Published: 2019

41. Depression and obesity, data from a national administrative database study: Geographic evidence for an epidemiological overlap

Author: J.-C. Chauvet-Gelinier, Catherine Quantin, Adrien Roussot, Jean-Michel Petit, Bruno Vergès, Marie-Claude Brindisi, Jonathan Cottenet, Bernard Bonin, Service de psychiatrie générale et addictologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Laboratoire de psychologie : dynamiques relationnelles et processus identitaires [Dijon] (PSY-DREPI), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC), 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), The authors received no specific funding for this work., Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), université de Bourgogne, LNC, and Chauvet-Gelinier, Jean-Christophe
Subjects: Male, Multivariate analysis, Spatial Epidemiology, Databases, Factual, Physiology, Epidemiology, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Social Sciences, Comorbidity, Geographical locations, dépression, 0302 clinical medicine, Rurality, Risk Factors, Medicine and Health Sciences, Prevalence, 030212 general & internal medicine, Depression (differential diagnoses), Geographic Areas, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Multidisciplinary, Geography, Depression, Spatial epidemiology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, 3. Good health, Europe, Santé publique et épidémiologie, obésité, Physiological Parameters, épidémiologie, Medicine, Female, France, Research Article, Urban Areas, Adult, medicine.medical_specialty, Science, Médecine humaine et pathologie, zone rurale, 030209 endocrinology & metabolism, Human Geography, Urban Geography, 03 medical and health sciences, Mental Health and Psychiatry, medicine, Humans, Obesity, European Union, Aged, Depressive Disorder, Major, business.industry, Mood Disorders, Body Weight, Biology and Life Sciences, développement épidémiologique, environnement urbain, medicine.disease, Rural Areas, zone urbaine, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Multivariate Analysis, Earth Sciences, Human health and pathology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Rural area, People and places, business, Demography
Abstract: BackgroundDepression and obesity are two major conditions with both psychological and somatic burdens. Some data suggest strong connections between depression and obesity and more particularly associated prevalence of both disorders. However, little is known about the geographical distribution of these two diseases. This study aimed to determine if there is spatial overlap between obesity and depression using data from the entire French territory.MethodsData for 5,627 geographic codes for metropolitan France were collected from the two national hospital databases (PMSI-MCO and RIM-P) for the year 2016. We identified people who were depressed, obese or both registered in the two public medico-administrative databases, and we assessed their location. In addition, a multivariable analysis was performed in order to determine geographic interactions between obesity and depression after controlling for age, sex, environmental and socio-economic factors (social/material deprivation, urbanicity/rurality).Results1,045,682 people aged 18 years and older were identified. The mapping analysis showed several cold and hot regional clusters of coinciding obesity and depression. The multivariable analysis demonstrated significant geographic interactions, with an increasing probability of finding a high prevalence of obesity in regions with major depression (OR 1.29 95% CI 1.13-1.49, p = 0.0002) and an increased probability of finding a high prevalence of depression in regions with a high ration of obesity (OR 1.32, 95% CI 1.15-1.52, pConclusionOur study confirms the significant bidirectional relationships between obesity and depression at a group level. French geographic patterns reveal a partial overlap between obesity and depression, suggesting these two diseases can be included in a common approach. Further studies should be done to increase the understanding of this complex comorbidity.
Published: 2019

42. Minor allele of the factor V K858R variant protects from venous thrombosis only in non-carriers of factor V Leiden mutation

Author: Céline Derbois, Noémie Saut, Philippe Amouyel, Stéphanie Debette, Louisa Goumidi, Elisabetta Castoldi, Manal Ibrahim-Kosta, David M. Smadja, Marine Germain, P. van Doorn, Pierre Morange, Etienne Patin, Marie-Christine Alessi, Pierre Suchon, Robert Olaso, David A. Tregouet, Francis Couturaud, Jean-François Deleuze, Florian Thibord, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'hématologie biologique [Hôpital de la Timone - Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Innovations thérapeutiques en hémostase (IThEM - U1140), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie biologique [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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), Sorbonne Université (SU), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, 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 Recherche en Génomique Humaine (CNRGH), Maastricht University [Maastricht], Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génétique Evolutive Humaine - Human Evolutionary Genetics, The authors would like to thank three research programs managed by the National Research Agency (ANR) as part of the French Investment for the Future initiative genetic investigations: the GENMED Laboratory of Excellence on Medical Genomics (ANR-10-LABX-0013), the French Clinical Research Infrastructure Network on Venous Thrombo-Embolism (F-CRIN INNOVTE) and the ICAN Institute for Cardiometabolism and Nutrition (ANR-10-IAHU-05) who partially supported performing genetic investigations in the MARTHA GWAS, MARTHA12, EDITH and FARIVE studies. TF was financially supported by a PhD grant from the GENMED Laboratory of Excellence on Medical Genomics (ANR-10-LABX-0013). vDP was supported by grant nr. 2014-1 from the Dutch Thrombosis Foundation. The present project was supported by a grant from CSL Behring., ANR-10-LABX-0013,GENMED,Medical Genomics(2010), ANR-10-INBS-0003,F-CRIN,Plateforme Nationale d'Infrastructures de Recherche Clinique(2010), ANR-10-IAHU-0005,ICAN,Institut de Cardiologie-Métabolisme-Nutrition(2010), Biochemie, RS: CARIM - R1 - Thrombosis and haemostasis, RS: CARIM - R1.01 - Blood proteins & engineering, RS: Carim - B01 Blood proteins & engineering, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre recherche en CardioVasculaire et Nutrition (C2VN), Université de Brest (UBO), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), ANR: PREFI-10-LABX-13/10-LABX-0013,GENMED,Medical Genomics(2010), ANR-10-INBS-03-01/10-INBS-0003,F-CRIN,Plateforme Nationale d'Infrastructures de Recherche Clinique(2010), ANR-10-IAHU-0005/10-IAHU-0005,ICAN,ICAN(2010), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: 0301 basic medicine, Male, lcsh:Medicine, Genome-wide association study, polymorphisme, PATHWAY, 0302 clinical medicine, COAGULATION-FACTOR-V, lcsh:Science, Venous Thrombosis, RISK, Multidisciplinary, biology, Factor V, DEFECTS, Venous thrombosis, Female, France, medicine.drug, medicine.medical_specialty, Heterozygote, B-DOMAIN, Médecine humaine et pathologie, Article, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Factor V Leiden, Humans, Allele, GENOME-WIDE ASSOCIATION, coagulation, facteur viii, Alleles, Genetic Association Studies, business.industry, lcsh:R, allèle, medicine.disease, GENE, Minor allele frequency, 030104 developmental biology, Endocrinology, Amino Acid Substitution, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Case-Control Studies, biology.protein, lcsh:Q, Human health and pathology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Activated protein C resistance, business, 030217 neurology & neurosurgery, Protein C, RESISTANCE, thrombose veineuse
Abstract: Factor V serves an important role in the regulation of blood coagulation. The rs6025 (R534Q) and rs4524 (K858R) polymorphisms in the F5 gene, are known to influence the risk of venous thrombosis. While the rare Q534 (factor V Leiden) allele is associated with an increased risk of venous thrombosis, the minor R858 allele is associated with a lower risk of disease. However, no study has deeply examined the cumulative impact of these two variations on venous thrombosis risk. We study the association of these polymorphisms with the risk of venous thrombosis in 4 French case-control populations comprising 3719 patients and 4086 controls. We demonstrate that the Q534 allele has a dominant effect over R858. Besides, we show that in individuals not carrying the Q534 allele, the protective effect of the R858 allele acts in a dominant mode. Thrombin generation-based normalized activated protein C sensitivity ratio was lower in the 858R/R homozygotes than in the 858K/K homozygotes (1.92 ± 1.61 vs 2.81 ± 1.57, p = 0.025). We demonstrate that the R858 allele of the F5 rs4524 variant protects from venous thrombosis only in non-carriers of the Q534 allele of the F5 rs6025. Its protective effect is mediated by reduced factor VIII levels and reduced activated protein C resistance.
Published: 2019

43. MicroRNAs in Obesity and Related Metabolic Disorders

Author: Jean-François Landrier, Adel Derghal, Lourdes Mounien, Prémilleux, Annick, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Aix-Marseille University, INRA INSERM andBenjamin Delessert foundation, and Centre recherche en CardioVasculaire et Nutrition (C2VN)
Subjects: 0301 basic medicine, Untranslated region, micro-RNA, obesity, diabetes, adipose tissue, pancreas, inflammation, leptin, [SDV]Life Sciences [q-bio], Médecine humaine et pathologie, tissu adipeux, pancréas, 030209 endocrinology & metabolism, Type 2 diabetes, Review, Biology, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Metabolic Diseases, Diabetes mellitus, microRNA, medicine, Animals, Humans, Epigenetics, lcsh:QH301-705.5, Gene, Leptin, General Medicine, medicine.disease, Obesity, 3. Good health, [SDV] Life Sciences [q-bio], obésité, MicroRNAs, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, trouble métabolique, lcsh:Biology (General), leptine, micro arn, Human health and pathology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, diabète
Abstract: International audience; Metabolic disorders are characterized by the inability to properly use and/or store energy. The burdens of metabolic disease, such as obesity or diabetes, are believed to arise through a complex interplay between genetics and epigenetics predisposition, environment and nutrition. Therefore, understanding the molecular mechanisms for the onset of metabolic disease will provide new insights for prevention and treatment. There is growing concern about the dysregulation of micro-RNAs (miRNAs) in metabolic diseases. MiRNAs are short non-coding RNA molecules that post-transcriptionally repress the expression of genes by binding to untranslated regions and coding sequences of the target mRNAs. This review aims to provide recent data about the potential involvement of miRNAs in metabolic diseases, particularly obesity and type 2 diabetes.
Published: 2019

44. Effectiveness of an antenatal maternal supplementation with prebiotics for preventing atopic dermatitis in high-risk children (the PREGRALL study): protocol for a randomised controlled trial

Author: Linda Lassel, Marion Boivin, Lucie Planche, Sébastien Barbarot, Vincent Dochez, Bertrand Kaeffer, Virginie Badon, Martine Tching-Sin, Clémentine Cabridain, Catherine Droitcourt, Marie Bodinier, Norbert Winer, Annabel Maruani, Franck Perrotin, David Riochet, Elodie Faurel-Paul, Hélène Aubert, Natasha K Rogers, Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), University of Nottingham, UK (UON), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Agence Nationale de la RechercheAgence Nationale de la Recherche, Ministère des Affaires Sociales et de la SantéMinistère des Affaires Sociales et de la Santé, Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CIC Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), and Jonchère, Laurent
Subjects: Male, Pediatrics, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Psychological intervention, law.invention, 0302 clinical medicine, Randomized controlled trial, Quality of life, Pregnancy, law, Protocol, Multicenter Studies as Topic, 030212 general & internal medicine, Randomized Controlled Trials as Topic, Prenatal Care, General Medicine, Atopic dermatitis, 3. Good health, [SDV] Life Sciences [q-bio], dermatology, Treatment Outcome, Alimentation et Nutrition, Gestation, eczema, paediatric dermatology, Female, medicine.medical_specialty, Médecine humaine et pathologie, Placebo, Dermatitis, Atopic, 03 medical and health sciences, Double-Blind Method, medicine, Humans, Food and Nutrition, business.industry, Prebiotic, Infant, Newborn, Infant, Maternal Nutritional Physiological Phenomena, medicine.disease, Clinical trial, Prebiotics, Dietary Supplements, Human health and pathology, Pregnant Women, business, 030217 neurology & neurosurgery
Abstract: IntroductionAtopic dermatitis (AD) is a chronic inflammatory disease affecting 10%–15% of children in Europe. There is a need for new primary preventive therapeutic strategies in at-risk populations. Recent research has indicated that atopic diseases are associated with a disrupted gut microbial ‘balance’ in early life raising the possibility that interventions which yield optimal patterns of microflora could improve host’s health. Prebiotics, sugars with immunomodulatory properties that stimulate the diversity of the digestive microbiota, are ideal candidates for such research. So far, most clinical trials have focused on improving infant gut colonisation postnatally. However, prenatal life is a crucial period during which different tolerance mechanisms are put in place. We aim to determine whether antenatal prebiotics supplementation prevents AD in high-risk children.Methods and analysisThis is a randomised, multicentre, double-blind, trial to evaluate the effectiveness of antenatal prebiotic maternal supplementation (galacto-oligosaccharide/inulin) in pregnant women versus placebo on the occurrence of AD at 1 year of age in at-risk children (defined as having a maternal history of atopic disease). Participating women will be randomised to daily ingestion of a prebiotics or placebo (maltodextrin) from 20 weeks’ gestation until delivery. The primary outcome is the prevalence of AD at 1 year of age, using the version of the UK Working Party Diagnostic Criteria optimised for preventive studies. Key secondary endpoints are AD severity, quality of life and prebiotics tolerance. The target sample size is 376 women (188 patients per group) which will provide 80% power to detect a 33% reduction of the risk of AD in the verum group (α=0.05). The primary analysis will be based on the intention-to-treat principle.Ethics and disseminationResults will be presented in peer-reviewed journals and at international conferences. Ethics approval for the study was obtained from the institutional ethical review board of ‘Comité de Protection des Personnes Sud Ouest—Outre-Mer III’ of the University Hospital Centre of Bordeaux (2017/13).Trial registration numberNCT03183440; Pre-results.
Published: 2019

45. Exploiting vulnerabilities of cancer by targeting nuclear receptors of stromal cells in tumor microenvironment

Author: Nguan Soon Tan, Hong Sheng Cheng, Jeannie Xue Ting Lee, Walter Wahli, Cheng, Hong Sheng, School of Biological Sciences, Nanyang Technological University (NTU), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Université de Lausanne (UNIL), Singapore Ministry of Education [2014-T2-1-012, 2017-T1-002-103, 2015-T1-001-034], Lee Kong Chian School of Medicine, Nanyang Technological University Start-up Grant, and Lee Kong Chian School of Medicine (LKCMedicine)
Subjects: 0301 basic medicine, Cancer Research, Stromal cell, Angiogenesis, Cancer-associated fibroblast, Nuclear Receptors, Médecine humaine et pathologie, Receptors, Cytoplasmic and Nuclear, Antineoplastic Agents, Tumor-associated macrophage, Review, Biology, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Immune system, Nuclear receptors, Neoplasms, Tumor Microenvironment, Animals, Humans, Receptor, Tumor microenvironment, Myeloid-derived suppressor cells, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Science::Biological sciences [DRNTU], 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Myeloid-derived Suppressor Cell, Cancer research, Molecular Medicine, Human health and pathology, Signal transduction, Stromal Cells, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction
Abstract: The tumor microenvironment is a complex and dynamic cellular community comprising the tumor epithelium and various tumor-supporting cells such as immune cells, fibroblasts, immunosuppressive cells, adipose cells, endothelial cells, and pericytes. The interplay between the tumor microenvironment and tumor cells represents a key contributor to immune evasiveness, physiological hardiness and the local and systemic invasiveness of malignant cells. Nuclear receptors are master regulators of physiological processes and are known to play pro−/anti-oncogenic activities in tumor cells. However, the actions of nuclear receptors in tumor-supporting cells have not been widely studied. Given the excellent druggability and extensive regulatory effects of nuclear receptors, understanding their biological functionality in the tumor microenvironment is of utmost importance. Therefore, the present review aims to summarize recent evidence about the roles of nuclear receptors in tumor-supporting cells and their implications for malignant processes such as tumor proliferation, evasion of immune surveillance, angiogenesis, chemotherapeutic resistance, and metastasis. Based on findings derived mostly from cell culture studies and a few in vivo animal cancer models, the functions of VDR, PPARs, AR, ER and GR in tumor-supporting cells are relatively well-characterized. Evidence for other receptors, such as RARβ, RORγ, and FXR, is limited yet promising. Hence, the nuclear receptor signature in the tumor microenvironment may harbor prognostic value. The clinical prospects of a tumor microenvironment-oriented cancer therapy exploiting the nuclear receptors in different tumor-supporting cells are also encouraging. The major challenge, however, lies in the ability to develop a highly specific drug delivery system to facilitate precision medicine in cancer therapy. MOE (Min. of Education, S’pore) Published version
Published: 2018

46. Stem cell properties of peripheral blood endothelial progenitors are stimulated by soluble CD146 via miR-21: potential use in autologous cell therapy

Author: Benjamin Guillet, Aurélie S. Leroyer, Anaïs Moyon, Jimmy Stalin, Richard Bachelier, Stéphanie Simoncini, Alexandrine Bertaud, Nathalie Bardin, Marie Nollet, Marcel Blot-Chabaud, Laure Balasse, Françoise Dignat-George, Gabrielle Sarlon, Amel Essaadi, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre recherche en CardioVasculaire et Nutrition (C2VN), Centre National de la Recherche Scientifique (CNRS)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-École Centrale de Marseille (ECM)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), and DIGNAT-GEORGE, Françoise
Subjects: 0301 basic medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Cell, Cell- and Tissue-Based Therapy, lcsh:Medicine, Mice, Ischemia, ischémie, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, medicine.diagnostic_test, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells, thérapie cellulaire, Flow Cytometry, 3. Good health, Hindlimb, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, CD146, effet thérapeutique, Stem cell, Adult, Adolescent, Blotting, Western, Médecine humaine et pathologie, Mice, Nude, CD146 Antigen, Article, Flow cytometry, 03 medical and health sciences, Young Adult, cellule souche, medicine, Animals, Humans, Progenitor cell, Cell Proliferation, business.industry, Growth factor, lcsh:R, Endothelial Cells, medicine.disease, Embryonic stem cell, MicroRNAs, 030104 developmental biology, Cancer research, Human health and pathology, lcsh:Q, business, cellule endotheliale
Abstract: Cell-based therapies constitute a real hope for the treatment of ischaemic diseases. One of the sources of endothelial progenitors for autologous cell therapy is Endothelial Colony Forming Cells (ECFC) that can be isolated from peripheral blood. However, their use is limited by their low number in the bloodstream and the loss of their stem cell phenotype associated with the acquisition of a senescent phenotype in culture. We hypothesized that adding soluble CD146, a novel endothelial growth factor with angiogenic properties, during the isolation and growth procedures could improve their number and therapeutic potential. Soluble CD146 increased the number of isolated peripheral blood ECFC colonies and lowered their onset time. It prevented cellular senescence, induced a partial mesenchymal phenotype and maintained a stem cell phenotype by stimulating the expression of embryonic transcription factors. These different effects were mediated through the induction of mature miR-21. When injected in an animal model of hindlimb ischaemia, sCD146-primed ECFC isolated from 40 ml of blood from patients with peripheral arterial disease were able to generate new blood vessels and restore blood flow. Treatment with sCD146 could thus constitute a promising strategy to improve the use of autologous cells for the treatment of ischaemic diseases.
Published: 2018

47. Minimal change nephrotic syndrome in patients infected with human immunodeficiency virus: a retrospective study of 8 cases

Author: Romain Arrestier, Vincent Audard, Anissa Moktefi, Philippe Gatault, Nathalie Dejucq-Rainsford, Guillaume Canaud, Dil Sahali, Flavia Vocila, Quentin Raimbourg, Hélène François, Anne-Pascale Satie, Anne-Elisabeth Heng, Isabelle Brocheriou, Corinne Isnard-Bagnis, David Buob, Shao-yu Zhang, Emmanuelle Plaisier, Marie Matignon, Néphrologie Transplantation, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris (AP-HP), 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 de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 ), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre de Référence Maladies Rares « Syndrome Néphrotique Idiopathique de l’Enfant et de l’Adulte », CHU Pitié-Salpêtrière [AP-HP], service de Néphrologie, Hôpital Bretonneau, Hôpital Bichat - Claude Bernard, Assistance Publique - Hôpitaux de Paris (AP-HP), Service Néphrologie, Centre Hospitalier de Cannes, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service Néphrologie Dialyse Transplantation, CHU Clermont-Ferrand, service de Médecine Interne et d'Immunologie Clinique, Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris (AP-HP), service Anatomie et Cytologie Pathologique, 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 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Tenon, Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital La Pitie Salpetriere, service d'Anatomie et de Cytologie Pathologiques, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Clermont-Ferrand, Hôpital Universitaire Pitié Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP - HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, 0301 basic medicine, Nephrology, 030232 urology & nephrology, HIV Infections, lcsh:RC870-923, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, C-mip, Medicine, ComputingMilieux_MISCELLANEOUS, Urologie et Néphrologie, Podocytes, Acute kidney injury, Aids, Albuminuria, HIV infection, Minimal change nephrotic syndrome, Rituximab, Middle Aged, 3. Good health, Female, Viral load, Research Article, medicine.drug, Adult, medicine.medical_specialty, Médecine humaine et pathologie, Context (language use), Nephropathy, Young Adult, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Humans, Urology and Nephrology, Aged, Retrospective Studies, business.industry, Nephrosis, Lipoid, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, 030104 developmental biology, Human health and pathology, business, Nephrotic syndrome, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: International audience; BACKGROUND: Human immunodeficiency virus (HIV) is associated with diverse glomerular diseases. Characteristics of minimal change nephrotic syndrome (MCNS) in this setting have been little studied, and the specific features of this uncommon association remain to be determined. METHODS: We conduct a retrospective study. Clinical, biological and pathological characteristics of patients with MCNS and HIV infection were assessed. We evaluated HIV infection by in situ hybridization and CMIP expression by immunochemistry on kidney biopsies and compared it to HIV-associated nephropathy (HIVAN) and idiopathic MCNS. RESULTS: Eight patients were identifies. In all but one of these cases, MCNS occurred after HIV diagnosis (mean of 9.5 years). Acute kidney injury was detected in three cases. Mean CD4(+) lymphocyte count was 733/mm(3) and three patients had a detectable HIV viral load. In situ hybridization for HIV-1 RNA detection yielded a positive signal in a few tubular cells in the renal parenchyma in two of four patients with HIV infection associated with MCNS. Podocytes of these patients presented strong positive immunostaining for CMIP (4/4). Three patients suffered steroid-dependent nephrotic syndrome, and another two patients had at least one relapse. Rituximab treatment was initiated in four cases. After a median follow-up of 20 months, all patients were in remission (complete in 5 cases). CONCLUSIONS: In patients with MCNS occurring in a context of HIV infection, podocyte injury seems to be associated with CMIP induction rather than renal HIV infection but further studies are needed to determine the molecular link between these two conditions.
Published: 2018

48. Usefulness of maximal oxygen pulse in timing of pulmonary valve replacement in patients with isolated pulmonary regurgitation

Author: Damien Bonnet, Magalie Ladouceur, Olivier Grenier, Marc Dufour, Jean-Philippe Jais, Antoine Legendre, Florence Pontnau, Elie Mousseaux, Ruddy Richard, Laurence Iserin, CHU Necker - Enfants Malades [AP-HP], cardiologie congénitale adulte, Hôpital Européen Georges Pompidou, Assistance Publique – Hôpitaux de Paris (AP-HP), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Medecine du sport et explorations fonctionnelles, Centre Hospitalier Universitaire de Clermont-Ferrand, Laboratoire de Biostatistique et d'Informatique Médicale, Université Paris Descartes - Paris 5 (UPD5), Département de Cardiologie, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), radiologie cardiovasculaire, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Unité de Nutrition Humaine (UNH), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), CHU Clermont-Ferrand, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Hôpital Européen Georges Pompidou, Assistance Publique – Hôpitaux de Paris ( AP-HP ), Unité de Nutrition Humaine - Clermont Auvergne ( UNH ), Université Clermont Auvergne ( UCA ) -Institut national de la recherche agronomique [Auvergne/Rhône-Alpes] ( INRA Auvergne/Rhône-Alpes ), Université Paris Descartes - Paris 5 ( UPD5 ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), U 970, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Sorbonne Paris Cité ( USPC ), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 030204 cardiovascular system & hematology, 0302 clinical medicine, Pulmonary Valve Replacement, 030212 general & internal medicine, Child, Stroke, Tetralogy of Fallot, Heart Valve Prosthesis Implantation, education.field_of_study, pulmonary valve replacement, CHD, cardiopulmonary exercise test, oxygen pulse, regurgitation, General Medicine, Middle Aged, Magnetic Resonance Imaging, 3. Good health, medicine.anatomical_structure, valve pulmonaire, Cardiology, Female, France, Cardiology and Cardiovascular Medicine, consommation d'oxygène, Adult, medicine.medical_specialty, Adolescent, Population, Oxygen pulse, Médecine humaine et pathologie, ventricule, Young Adult, 03 medical and health sciences, chirurgie cardiaque, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, Pulmonary regurgitation, medicine, Humans, In patient, education, Pulmonary Valve, business.industry, Stroke Volume, medicine.disease, Pulmonary Valve Insufficiency, Oxygen, Ventricle, Pediatrics, Perinatology and Child Health, Exercise Test, Ventricular Function, Right, Human health and pathology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Patients with pulmonary regurgitation after tetralogy of Fallot repair have impaired aerobic capacity; one of the reasons is the decreasing global ventricular performance at exercise, reflected by decreasing peak oxygen pulse. The aims of our study were to evaluate the impact of pulmonary valve replacement on peak oxygen pulse in a population with pure pulmonary regurgitation and with different degrees of right ventricular dilatation and to determine the predictors of peak oxygen pulse after pulmonary valve replacement.The mean and median age at pulmonary valve replacement was 27 years. Mean pre-procedural right ventricular end-diastolic volume was 182 ml/m2. Out of 24 patients, 15 had abnormal peak oxygen pulse before pulmonary valve replacement. We did not observe a significant increase in peak oxygen pulse after pulmonary valve replacement (p=0.76). Among cardiopulmonary test/MRI/historical pre-procedural parameters, peak oxygen pulse appeared to be the best predictor of peak oxygen pulse after pulmonary valve replacement (positive and negative predictive values, respectively, 0.94 and 1). After pulmonary valve replacement, peak oxygen pulse was well correlated with left ventricular stroke and end-diastolic volumes (r=0.67 and 0.68, respectively).Our study confirms the absence of an effect of pulmonary valve replacement on peak oxygen pulse whatever the initial right ventricular volume, reflecting possible irreversible right and/or left ventricle lesions. Pre-procedural peak oxygen pulse seemed to well predict post-procedural peak oxygen pulse. These results encourage discussions on pulmonary valve replacement in patients showing any decrease in peak oxygen pulse during their follow-up.
Published: 2015

49. Acute Tetraplegia Caused by Rat Bite Fever in Snake Keeper and Transmission of Streptobacillus moniliformis

Author: Werner Nicklas, Simon Poignant, Christa Ewers, Antoine Guillon, Tobias Eisenberg, Youenn Jouan, Ahmad Fawzy, Laurent Mereghetti, Hessian State Laboratory, Partenaires INRAE, Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours), Justus-Liebig-Universität Gießen (JLU), Cairo University, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Guillon, Antoine, and Institut National de la Recherche Agronomique (INRA)-Université de Tours
Subjects: Male, 0301 basic medicine, Pathology, Streptobacillus, Epidemiology, rat bite fever, lcsh:Medicine, Streptobacillus moniliformis, 0302 clinical medicine, Rat-Bite Fever, rat, 030212 general & internal medicine, Animal Husbandry, bacteria, Tetraplegia, biology, Transmission (medicine), variable number tandem repeat analysis, Microbiology and Parasitology, transmission, Snakes, Middle Aged, Microbiologie et Parasitologie, Anti-Bacterial Agents, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, PCR, Infectious Diseases, paralysie, France, Nucleic Acid Amplification Techniques, zoonose, Microbiology (medical), medicine.medical_specialty, acute tetraplegia, morsure, Rat-bite fever, 030106 microbiology, Médecine humaine et pathologie, multilocus variant analysis, rats, reptiles, snake keeper, snakes, species specificity, zoonoses, Amoxicillin-Potassium Clavulanate Combination, Quadriplegia, lcsh:Infectious and parasitic diseases, Microbiology, 03 medical and health sciences, Research Letter, medicine, Animals, Humans, lcsh:RC109-216, infection bactérienne, lcsh:R, Acute Tetraplegia Caused by Rat Bite Fever in Snake Keeper and Transmission of Streptobacillus moniliformis, Nucleic acid amplification technique, biology.organism_classification, medicine.disease, Rats, Human health and pathology, humain, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; We report acute tetraplegia caused by rat bite fever in a 59-year old man (snake keeper) and transmission of Streptobacillus moniliformis. We found an identical characteristic bacterial pattern in rat and human samples, which validated genotyping-based evidence for infection with the same strain, and identified diagnostic difficulties concerning infection with this microorganism.
Published: 2017

50. Bisphenol S Impaired Human Granulosa Cell Steroidogenesis in Vitro

Author: Marlène Z. Lacroix, Ophélie Téteau, Pascal Papillier, Alice Desmarchais, Aurélien Binet, Virginie Maillard, F. Guerif, Sarah Amar, Sébastien Elis, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours), Innovations Thérapeutiques et Résistances (InTheRes), Institut National de la Recherche Agronomique (INRA)-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, Projet Région Centre Val de Loire BEMOL APR IR 2017Projet Agence de la BioMédecine 2018 FertiPhénol, ANR-18-CE34-0011,MAMBO,Impact du métabolisme sur les effets ovariens du bisphenol S(2018), and Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]
Subjects: 0301 basic medicine, steroidogenesis, Bisphenol S, 010501 environmental sciences, urologic and male genital diseases, 01 natural sciences, lcsh:Chemistry, chemistry.chemical_compound, Gene expression, Follicular phase, Sulfones, lcsh:QH301-705.5, endocrine disruptors, women, granulosa cells, proliferation, Cells, Cultured, Progesterone, Spectroscopy, perturbateur endocrinien, General Medicine, Progesterone secretion, 3. Good health, Computer Science Applications, Endocrine disruptor, bisphénol s, Female, hormones, hormone substitutes, and hormone antagonists, endocrine system, Granulosa cell, Médecine humaine et pathologie, In Vitro Techniques, Article, Catalysis, Inorganic Chemistry, Andrology, 03 medical and health sciences, Phenols, cellule de la granulosa, steroidogénèse, Humans, Cholesterol Side-Chain Cleavage Enzyme, Physical and Theoretical Chemistry, Molecular Biology, 0105 earth and related environmental sciences, Cholesterol side-chain cleavage enzyme, Organic Chemistry, Follicular Fluid, 030104 developmental biology, Gene Expression Regulation, lcsh:Biology (General), lcsh:QD1-999, chemistry, HSD3B1, Human health and pathology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Bisphenol S (BPS) is a structural analog of the endocrine disruptor bisphenol A (BPA), it is the main BPA replacement in the plastics industry. Previous studies have shown that BPA and BPS exhibit similar effects on reproduction in fish and rodent species. BPS reportedly alters steroidogenesis in bovine granulosa cells. Luteinised granulosa cells collected from 59 women who were undergoing an in vitro fertilization procedure were cultured for 48 h in the presence or absence of BPS (10 nM, 100 nM, 1 &micro, M, 10 &micro, M or 50 &micro, M). BPS exposure was investigated by assessing follicular fluids from these 59 women for their BPS content. Culture medium, cells, total messenger RNA (mRNA) and total protein extracted from the luteinised granulosa cells were examined for oestradiol and progesterone secretion, cellular proliferation, viability, gene expression, steroidogenic enzyme expression and cell signaling. BPS was measured in follicular fluids using mass spectrometry. Exposure of granulosa cells to 10 or 50 &micro, M BPS for 48 h induced a 16% (p = 0.0059) and 64% (p &lt, 0.0001) decrease, respectively, in progesterone secretion, 50 &micro, M BPS decreased oestradiol secretion by 46% (p &lt, 0.0001). Ten &micro, M BPS also tended to reduce CYP11A1 protein expression by 37% (p = 0.0947) without affecting HSD3B1 and CYP19A1 expression. Fifty &micro, M BPS increased ERRg expression. Environmental levels of BPS (nanomolar range) did not induce changes in steroidogenesis in human granulosa cells. The effects of BPS were observed after only 48 h of BPS exposure. These acute effects might be similar to chronic effects of physiological BPS levels.
Published: 2020

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