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51. Collaboration between academics, small pharmaceutical company and patient organizations in the development of a new formulation of cysteamine in nephropathic cystinosis: A successful story

Author: Cécile Acquaviva-Bourdain, Catherine Cornu, Fabien Subtil, Patrice Nony, Catherine Mercier, Christine Vianey-Saban, Denis Morin, Georges Deschênes, Aurélia Bertholet-Thomas, Ségolène Gaillard, Behrouz Kassai, Pierre Cochat, Laurent Roche, EPICIME-CIC 1407 de Lyon, Inserm, Service de Pharmacologie Clinique, Hospices Civils de Lyon, 69677 Bron, France, parent, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hôpital Robert Debré Paris, Hôpital Robert Debré, Structural Impact Laboratory (SIMLab), Centre for Research-based Innovation (CRI), Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU)-Norwegian University of Science and Technology (NTNU), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), 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), Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal [CHU Lyon] (Centre de Biologie et Pathologie Est), Hospices Civils de Lyon (HCL)-Groupement Hospitalier Est, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon, Hospices Civils de Lyon (HCL), Service de néphrologie, rhumatologie et dermatologie pédiatriques [Hôpital Femme Mère Enfant, HCL], Hospices Civils de Lyon (HCL)-Hôpital Mère Enfant, Centre de référence des maladies rénales rares Néphrogones [CHU-HCL, Lyon], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Motricité, interactions, performance EA 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), Université de Nantes (UN)-Université de Nantes (UN), EPICIME-CIC 1407 de Lyon, Inserm, Service de Pharmacologie Clinique, CHU-Lyon, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CCSD, Accord Elsevier
Subjects: [SDV]Life Sciences [q-bio], Population, Disease, 030226 pharmacology & pharmacy, Patient advocacy, Nephropathic cystinosis, Clinical research, 03 medical and health sciences, 0302 clinical medicine, Nursing, Multidisciplinary approach, Nephropathic Cystinosis, Medicine, Pharmacology (medical), education, [SDV.IB] Life Sciences [q-bio]/Bioengineering, education.field_of_study, business.industry, 3. Good health, Rare diseases, Clinical trial, [SDV] Life Sciences [q-bio], [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business, Rare disease
Abstract: International audience; Rare diseases usually concern small and disseminated population. Implementing clinical research with the right design, outcomes measures and the recruitment of patients are challenges. Collaborations, training and multidisciplinary approach are often required. In this article, we provide an overview of a successful collaboration in nephropathic cystinosis (NC), focusing on what was the key of success, the interactions between academics, the pharmaceutical company and patients organizations. NC is considered as a very rare disease. In 2010, a new formulation of cysteamine, the only available treatment to improve renal outcome of the disease, was proposed by a small American company. Studies were implemented in France under the coordination of an expert of the disease and the clinical investigation center of Lyon. The collaboration resulted in a good recruitment and retention of the patients in the study and most of all in the availability of the new formulation in France. Patients could have facilitated the research by being involved in the early stages of the studies. Involving patients and public early in the process is particularly important in rare diseases as the patient is a great source of knowledge and has his own expectations. Priorities of research, design, conduct and reporting of clinical trials can be defined in collaboration with adults but also with young patients or public, the first concerned in rare diseases. This concept is still to be developed and improved especially with paediatric patients.
Published: 2020
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52. Dihydroceramides in Triglyceride-Enriched VLDL Are Associated with Nonalcoholic Fatty Liver Disease Severity in Type 2 Diabetes

Author: Carlier, Aurélie, Phan, Franck, Szpigel, Anaïs, Hajduch, Eric, Salem, Joe-Elie, Gautheron, Jérémie, Le Goff, Wilfried, Guerin, Maryse, Lachkar, Floriane, Ratziu, Vlad, Hartemann, Agnès, Ferré, Pascal, Foufelle, Fabienne, Bourron, Olivier, Service de diabétologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], 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), Service de Diabétologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), HAL-SU, Gestionnaire, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, sphingolipids, Lipoproteins, VLDL, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Ceramides, liver, Article, lipoproteins, dihydroceramide, Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease, NAFLD, diabetes mellitus, Humans, biomarker, lipids (amino acids, peptides, and proteins), Insulin Resistance, VLDL, Triglycerides
Abstract: Summary Plasma dihydroceramides are predictors of type 2 diabetes and related to metabolic dysfunctions, but the underlying mechanisms are not characterized. We compare the relationships between plasma dihydroceramides and biochemical and hepatic parameters in two cohorts of diabetic patients. Hepatic steatosis, steatohepatitis, and fibrosis are assessed by their plasma biomarkers. Plasma lipoprotein sphingolipids are studied in a sub-group of diabetic patients. Liver biopsies from subjects with suspected non-alcoholic fatty liver disease are analyzed for sphingolipid synthesis enzyme expression. Dihydroceramides, contained in triglyceride-rich very-low-density lipoprotein (VLDL), are associated with steatosis and steatohepatitis. Expression of sphingolipid synthesis enzymes is correlated with histological steatosis and inflammation grades. In conclusion, association of plasma dihydroceramides with nonalcoholic fatty liver might explain their predictive character for type 2 diabetes. Our results suggest a relationship between hepatic sphingolipid metabolism and steatohepatitis and an involvement of dihydroceramides in the synthesis/secretion of triglyceride-rich VLDL, a hallmark of NAFLD and type 2 diabetes dyslipidemia., Graphical Abstract, Highlights Plasma dihydroceramides are associated with NAFLD severity in type 2 diabetic patients Plasma dihydroceramides are found in triglyceride-enriched VLDL A role for dihydroceramide in triglyceride-rich VLDL synthesis/secretion is suggested Expression of enzymes of hepatic sphingolipid synthesis increases with NAFLD severity, Plasma dihydroceramides are long-term predictors of type 2 diabetes onset. Carlier et al. discovered that plasma dihydroceramides are associated with non-alcoholic fatty liver disease severity in diabetic patients and are found in triglyceride-enriched VLDL. It strongly suggests that dysregulated hepatic fat metabolism is an early and major component of diabetes onset.
Published: 2020
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53. Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes

Author: Franck Phan, Anne-Caroline Jeannin, Carole E. Aubert, Ziad A. Massy, Agnès Hartemann, Joe-Elie Salem, M. Halbron, Chloé Amouyal, Christian Funck-Brentano, Olivier Bourron, Cees Vemeer, Sorbonne Université (SU), Service de Diabétologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC Paris Est, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Bern, Maastricht University [Maastricht], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), This work was supported by a fund from the Lilly Company. The research activities of C.E.A. were supported by a doctoral research scholarship from the University of Lausanne. A.C.J received a grant from Ministère français des Affaires Sociales et de la Santé (Bourse année recherche 2017/2018)., RS: Carim - B02 Vascular aspects thrombosis and Haemostasis, Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Bodescot, Myriam, Service de diabétologie [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Vitamin K, Diabetic neuropathy, diagnosis, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Organic chemistry, Type 2 diabetes, Biochemistry, BONE MORPHOGENETIC PROTEIN-2, Endocrinology, 0302 clinical medicine, Matrix gla protein, Medicine and Health Sciences, Diabetes diagnosis and management, Insulin, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Multidisciplinary, biology, Vitamins, nerve-conduction, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Type 2 Diabetes, 3. Good health, Physical sciences, Chemistry, Neurology, Optical Equipment, Engineering and Technology, Biomarker (medicine), Medicine, Research Article, Retinopathy, cardiovascular risk, medicine.medical_specialty, HbA1c, alpha, Endocrine Disorders, B vitamins, Science, prevalence, INHIBITION, Equipment, 610 Medicine & health, 030209 endocrinology & metabolism, Chemical compounds, 03 medical and health sciences, 360 Social problems & social services, Diabetes mellitus, Internal medicine, Organic compounds, Diabetes Mellitus, medicine, Hemoglobin, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Peripheral Neuropathy, Diabetic Endocrinology, Biology and life sciences, criteria, RECEPTOR, business.industry, Lasers, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Proteins, medicine.disease, Diagnostic medicine, Hormones, Neuropathy, Peripheral neuropathy, Metabolic Disorders, biology.protein, RISK-FACTORS, business, 030217 neurology & neurosurgery
Abstract: International audience; AIMS/HYPOTHESIS:Diabetic peripheral neuropathy is a frequent and severe complication of diabetes. As Matrix-gla-protein (MGP) is expressed in several components of the nervous system and is involved in some neurological disease, MGP could play a role in peripheral nervous system homeostasis. The aim of this study was to evaluate factors associated with sensitive diabetic neuropathy in Type 2 Diabetes, and, in particular, dephospho-uncarboxylated MGP (dp-ucMGP), the inactive form of MGP.METHODS:198 patients with Type 2 Diabetes were included. Presence of sensitive diabetic neuropathy was defined by a neuropathy disability score (NDS) ≥6. Plasma levels of dp-ucMGP were measured by ELISA.RESULTS:In this cohort, the mean age was 64+/-8.4 years old, and 80% of patients were men. Peripheral neuropathy was present in 15.7% of the patients and was significantly associated (r = 0.51, p
Published: 2020
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54. Repeated 5-day cycles of low dose aldesleukin in amyotrophic lateral sclerosis (IMODALS): A phase 2a randomised, double-blind, placebo-controlled trial

Author: Raul Juntas-Morales, Marius Mickunas, Massimo Locati, Timothy Tree, Nicolas Pageot, John De Vos, Jean-Luc Veyrune, P. Nigel Leigh, William Camu, Ulf Andreasson, Christine Payan, Janine Kirby, Pamela J. Shaw, Ammar Al-Chalabi, Christophe Masseguin, Safa Saker, Carey M. Suehs, Cecilia Garlanda, Henrik Zetterberg, Andrea Malaspina, Gilbert Bensimon, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Immunobiology, King‘s College London, Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, BESPIM, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Humanitas University [Milan] (Hunimed), University of Milan, Barts & The London School of Medicine and Dentistry, University of Gothenburg (GU), Department of Neuroscience, Academic Neurology Unit, University of Sheffield, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Généthon, Dementia Research Centre [London] (DRC), University College of London [London] (UCL), Institute of Psychiatry, Psychology & Neuroscience, King's College London, Brighton and Sussex Medical School (BSMS), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Milano = University of Milan (UNIMI), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Gestionnaire, HAL Sorbonne Université 5
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Placebo-controlled study, Antineoplastic Agents, Placebo, T-Lymphocytes, Regulatory, General Biochemistry, Genetics and Molecular Biology, Randomised clinical trial, Immunophenotyping, Double blind, 03 medical and health sciences, 0302 clinical medicine, Aldesleukin, T-Lymphocyte Subsets, Internal medicine, Medicine, Humans, Amyotrophic lateral sclerosis, Adverse effect, Aged, Aged, 80 and over, business.industry, Low dose, Amyotrophic Lateral Sclerosis, Low dose interleukin-2, General Medicine, Regulatory T cells, Middle Aged, medicine.disease, Recombinant Proteins, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Treatment Outcome, Neuro-inflammation, 030220 oncology & carcinogenesis, Pharmacodynamics, Cytokines, Interleukin-2, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Chemokines, business, Biomarkers, Research Paper
Abstract: Background\ud \ud Low-dose interleukin-2 (ld-IL-2) enhances regulatory T-cell (Treg) function in auto-inflammatory conditions. Neuroinflammation being a pathogenic feature of amyotrophic lateral sclerosis (ALS), we evaluated the pharmacodynamics and safety of ld-IL-2 in ALS subjects.\ud \ud \ud Methods\ud \ud We performed a single centre, parallel three-arm, randomised, double-blind, placebo-controlled study. Eligibility criteria included age < 75 years, disease duration < 5 years, riluzole treatment > 3 months, and a slow vital capacity ≥ 70% of normal. Patients were randomised (1:1:1) to aldesleukin 2 MIU, 1 MIU, or placebo once daily for 5 days every 4 weeks for 3 cycles. Primary outcome was change from baseline in Treg percentage of CD4+ T cells (%Tregs) following a first cycle. Secondary laboratory outcomes included: %Treg and Treg number following repeated cycles, and plasma CCL2 and neurofilament light chain protein (NFL) concentrations as surrogate markers of efficacy. Safety outcomes included motor-function (ALSFRS-R), slow vital capacity (SVC), and adverse event reports. This trial is registered with ClinicalTrials.gov, NCT02059759.\ud \ud \ud Findings\ud \ud All randomised patients (12 per group), recruited from October 2015 to December 2015, were alive at the end of follow-up and included in the intent-to-treat (ITT) analysis. No drug-related serious adverse event was observed. Non-serious adverse events occurred more frequently with the 1 and 2 MIU IL-2 doses compared to placebo, including injection site reactions and flu-like symptoms. Primary outcome analysis showed a significant increase (p < 0·0001) in %Tregs in the 2 MIU and 1 MIU arms (mean [SD]: 2 MIU: +6·2% [2·2]; 1 MIU: +3·9% [1·2]) as compared to placebo (mean [SD]: -0·49% [1·3]). Effect sizes (ES) were large in treated groups: 2 MIU ES=3·7 (IC95%: 2·3–4·9) and 1 MIU ES=3·5 (IC95%: 2·1–4·6). Secondary outcomes showed a significant increase in %Tregs following repeated cycles (p < 0·0001) as compared to placebo, and a dose-dependent decrease in plasma CCL2 (p = 0·0049). There were no significant differences amongst the three groups on plasma NFL levels.\ud \ud \ud Interpretation\ud \ud Ld-IL-2 is well tolerated and immunologically effective in subjects with ALS. These results warrant further investigation into their eventual therapeutic impact on slowing ALS disease progression.\ud \ud \ud Funding\ud \ud : The French Health Ministry (PHRC-I-14-056), EU H2020 (grant #633413), and the Association pour la Recherche sur la SLA (ARSLA).
Published: 2020
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55. The Effect of the Food Matrix on the In Vitro Bio‐Accessibility and IgE Reactivity of Peanut Allergens

Author: Aida Semic-Jusufagic, Hervé Bernard, Karine Adel-Patient, E. N. Clare Mills, Rebekah Sayers, Frances Smith, Philip J. Padfield, Angela Simpson, Ivona Baricevic, Wentong Xue, Anuhradha Balasundaram, Carol Ann Costello, Huan Rao, Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], China Agricultural University (CAU), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, UK Research & Innovation (UKRI) : Biotechnology and Biological Sciences Research Council (BBSRC)BB/1006109/1BB/K501608/1, China Scholarship Council, Newton fund project placement grant, European Project: 312147,EC:FP7:KBBE,FP7-KBBE-2012-6-singlestage,IFAAM(2013), Service de Pharmacologie et Immunoanalyse (SPI), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA))
Subjects: 0301 basic medicine, Arachis, in vitro digestion, Protein digestion, Food Handling, medicine.medical_treatment, Biological Availability, medicine.disease_cause, Ige reactivity, 03 medical and health sciences, Allergen, Antacid, bio-accessibility, medicine, Humans, Peanut Hypersensitivity, allergens, peanuts, Food science, Plant Proteins, 2. Zero hunger, Gastrointestinal tract, 030109 nutrition & dietetics, medicine.diagnostic_test, Chemistry, Membrane Proteins, food and beverages, Antigens, Plant, Hydrogen-Ion Concentration, Immunoglobulin E, In vitro, 030104 developmental biology, Immunoassay, Digestion, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, food matrix, Food Science, Biotechnology, 2S Albumins, Plant
Abstract: International audience; Scope: Factors such as food processing, the food matrix, and antacid medication may affect the bio-accessibility of proteins in the gastrointestinal tract and hence their allergenic activity. However, at present they are poorly understood. Methods and Results: Roasted peanut flour was incorporated into either a chocolate dessert or cookie matrix and bio-accessibility were assessed using an in vitro digestion system comprising a model chew and simulated gastric and duodenal digestion. Protein digestion was monitored by SDS-PAGE and immunoreactivity analyzed by immunoblotting and immunoassay. IgE reactivity was assessed by immunoassay using serum panels from peanut-allergic subjects. Roasted peanut flour proteins proved highly digestible following gastro-duodenal digestion even when incurred into a food matrix, with only low molecular weight polypeptides of Mr < 8 kDa remaining. When gastric digestion was performed at pH 6.5 (simulating the effect of antacid medication), peanut proteins are not digested; subsequent duodenal digestion is also limited. IgE reactivity of the major peanut allergens Ara h 1, Ara h 2, and Ara h 6, although reduced, was retained after oral-gastro-duodenal digestion irrespective of digestion conditions employed.Conclusion: Peanut allergen bio-accessibility is unaffected by the dessert or cookie matrices whilst high intra-gastric pH conditions render allergens more resistant to digestion.
Published: 2020
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56. Improvement of the Immunochromatographic NG-Test Carba 5 Assay for the Detection of IMP Variants Previously Undetected

Author: Saoussen Oueslati, Marine Laguide, Stéphanie Simon, Hervé Volland, Virginie Paris, Laurent Dortet, Camille Gonzalez, Thierry Naas, Maxime Laroche, Delphine Girlich, Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Structure, Dynamique, Fonction Et Expression Des Beta-Lactamases À Large Spectre, Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11)-Université Paris-Sud - Paris 11 (UP11)-Centre National de Référence de la Résistance aux Antibiotiques (CNR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Ecologie et Evolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Sud Orsay-Centre National de la Recherche Scientifique (CNRS), NG Biotec, French National Reference Center for Antibiotic Resistance: Carbapenemase producing Enterobacteriaceae [Le Kremlin-Bicêtre], Bacteriology-Hygiene unit [Le Kremlin-Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), University Paris-Sud, France., ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université Paris-Sud - Paris 11 (UP11)-Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio], detection, NDM, Microbial Sensitivity Tests, Biology, medicine.disease_cause, beta-Lactamases, Microbiology, 03 medical and health sciences, Enterobacterales, Bacterial Proteins, Mechanisms of Resistance, medicine, polycyclic compounds, Pharmacology (medical), OXA-48, 030304 developmental biology, Pharmacology, Immunoassay, 0303 health sciences, Acinetobacter, 030306 microbiology, Pseudomonas aeruginosa, IMP, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, LFIA, 3. Good health, KPC, enzymes and coenzymes (carbohydrates), Infectious Diseases, VIM, CPEs, bacteria, rapid diagnostic
Abstract: International audience; Here, we evaluated the immunochromatographic assay NG-Test Carba 5v2 (NG-Biotech), with improved IMP variant detection on 31 IMP producers, representing the different branches of the IMP phylogeny, including 32 OXA-48, 19 KPC, 12 VIM, 14 NDM, and 13 multiple carbapenemase producers (CPs), 13 CPs that were not targeted, and 13 carbapenemase-negative isolates. All tested IMP variants were accurately detected without impairing detection of the other carbapenemases. Thus, NG-Test Carba 5v2 is now well adapted to countries with high IMP prevalence and to the epidemiology of CP-Pseudomonas aeruginosa, where IMPs are most frequently detected.
Published: 2019
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57. Coupling caging and proteomics on the European flounder (Platichthys flesus) to assess the estuarine water quality at micro scale

Author: Jean Armengaud, Grégory Charrier, Elodie Borcier, Justine Receveur, Baghdad Ouddane, Mamadou Diop, Jean Laroche, Jean-Charles Gaillard, Rachid Amara, Jérôme Couteau, Sébastien Artigaud, Vianney Pichereau, Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Biochimie des Systèmes Perturbés (LBSP), TOXEM, Laboratoire de Spectrochimie Infrarouge et Raman - UMR 8516 (LASIR), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en économie et management (CREM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Innovations technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de documentation de recherche et d'expérimentations sur les pollutions accidentelles des eaux (Cedre), Cedre, Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement - UMR 8516 (LASIRE), Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire d’Océanologie et de Géosciences (LOG) - UMR 8187 (LOG), Institut national des sciences de l'Univers (INSU - CNRS)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Nord]), Région Bretagne, Seine Aval 6 –HQFish, Agence Française pour la Biodiversité –POPEST, Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille Institut (CLIL), and Centre National de la Recherche Scientifique (CNRS)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut national des sciences de l'Univers (INSU - CNRS)
Subjects: Environmental Engineering, 010504 meteorology & atmospheric sciences, Proteome, Zoology, Flounder, 010501 environmental sciences, Ecotoxicology, 01 natural sciences, Estuary water quality, Condition index, Caging, Fish physiology, [SDU.STU.GC]Sciences of the Universe [physics]/Earth Sciences/Geochemistry, Water Quality, Shotgun proteomics, Environmental Chemistry, Animals, 14. Life underwater, EUROPEAN FLOUNDER, Waste Management and Disposal, 0105 earth and related environmental sciences, Pollutant, geography, geography.geographical_feature_category, biology, ACL, Estuary, biology.organism_classification, Suess, Caging Stress, Pollution, Platichthys, 13. Climate action, Water quality, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Estuaries, Water Pollutants, Chemical, Environmental Monitoring
Abstract: International audience; Estuaries are important areas highly vulnerable to anthropogenic pollutions. Therefore, the assessment of estuarine water quality is a major ecological issue. In this study, we sampled juveniles of the European flounder in the “pristine” Canche estuary, and caged them in Canche and in two polluted sites of the Seine estuary, Rouen and Fosse Nord. After one month, the metal and organic pollutants in these sites were assessed, and we evaluated several phenotypic indicators (condition index, RNA/DNA ratios and genotoxicity), and extracted the proteins in fish livers for analysis using a shotgun proteomics approach.The results showed strong modifications in the fish caged in both sites of the Seine estuary, as compared to those caged in Canche. In particular, many proteins involved in phase I and phase II detoxification reactions were accumulated in the liver of fish caged in the site showing the highest pollution, Rouen. In addition, we observed a general disruption of metabolism, in particular an increase in lipid synthesis and carbohydrate degradation in Rouen, and a decrease in the abundance of proteins associated to translational activity in Fosse Nord. At both sites, several stress proteins were decreased.The proteomic impact of the encagement by itself was also evaluated, by comparing the liver proteome of fish caged in Canche to that of fish stayed in natura during the same time. The results showed proteomic signatures of exposure to stressful conditions (particularly heat stress), most probably related to the micro-habitat in which the cages were placed. In conclusion, the caging technique is of great interest for ecotoxicological assessment of estuarine waters, but should consider that the results are representative of the micro-habitat around the cages, which does not necessarily represent the overall heterogeneity of the estuarine environment.
Published: 2019
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58. High plasma level of S100A8/S100A9 and S100A12 at admission indicates a higher risk of death in septic shock patients

Author: Dubois, Christelle, Marcé, Dominique, Faivre, Valérie, Lukaszewicz, Anne-Claire, Junot, Christophe, Fenaille, François, Simon, Stéphanie, Becher, François, Morel, Nathalie, Payen, Didier, Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Anesthesiology & Critical Care, Hôpital Lariboisière, Hôpital Lariboisière, 'Bourse CIFRE' (Convention Industrielle de Formation pour la REcherche) by ANRT (Association Nationale de la Recherche et de la Technologie) BertinTechnologies, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Lallemant, Christopher
Subjects: Adult, Male, Risk, [SPI] Engineering Sciences [physics], lcsh:Medicine, Article, Prognostic markers, [SPI]Engineering Sciences [physics], Patient Admission, Sepsis, Calgranulin B, Humans, Calgranulin A, Disease, lcsh:Science, Aged, lcsh:R, S100A12 Protein, Proteins, Middle Aged, Prognosis, Shock, Septic, Survival Analysis, lcsh:Q, Female, ELISA, Leukocyte L1 Antigen Complex
Abstract: International audience; Biomarkers in sepsis for severity, prediction of outcome or reversibility of organ dysfunction are warranted. Measurements of plasma DAMP levels at admission can reflect the severity of cellular damage in septic shock, which might predict the prognosis and reduce the risk of overtreating patients with costly therapies. We measured plasma levels of two DAMPs, S100A8/S100A9 and S100A12 during the first 24 h of admission of septic shock patients. Forty-nine septic shock patients with a similar SOFA scores were selected from our sepsis database to compare a similar proportion of survivors and non-survivors. Plasma levels of S100A8/S100A9 and S100A12 were compared with healthy volunteers using in-house ELISA. Plasma levels of S100A8/S100A9 and S100A12 (5.71 [2.60-13.63] mu g/mL and 0.48 [0.22-1.05] mu g/mL) were higher in septic shock patients than in healthy volunteers (1.18 [0.74-1.93] mu g/mL and 0.09 [0.02-0.39] mu g/mL) (P < 0.0001 and P = 0.0030). Levels of S100A8/S100A9 and S100A12 in non-survivors at day 28 (11.70 [2.85-24.36] mu g/mL and 0.62 [0.30-1.64] mu g/mL) were significantly higher than in survivors (4.59 [2.16-7.47] mu g/mL and 0.30 [0.20-0.49] mu g/mL) (P = 0.0420 and P = 0.0248) and correlated well (Spearman r = 0.879, P < 0.0001). The high level of plasma calgranulins at admission in septic shock, were higher in non-survivors compared to survivors. These markers could indicate a higher risk of death when SOFA scores are similar and help the stratification of patients for improved care and therapy selection.
Published: 2019
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59. Proof-of-Concept Study of Drug Brain Permeability Between in Vivo Human Brain and an in Vitro iPSCs-Human Blood-Brain Barrier Model

Author: Anne-Cécile Guyot, Serena Pavoni, Frank Yates, Oliver Langer, Jean-Philippe Deslys, Frédéric Théodoro, Yulia Kiyan, Narciso Costa, Ferid Nassor, Gwenaëlle Le Roux, Nicolas Tournier, Rafika Jarray, Alain Pruvost, Aloïse Mabondzo, Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service d'Etude des Prions et des Infections Atypiques, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Sup'Biotech, Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medizinische Hochschule Hannover (MHH), Department of Clinical Pharmacology, Medizinische Universität Wien = Medical University of Vienna, Preclinical Molecular Imaging, AIT Austrian Institute of Technology GmbH, French National Research Agency (ANR), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Lallemant, Christopher
Subjects: 0301 basic medicine, Drug Evaluation, Preclinical, lcsh:Medicine, Pharmacology, Positron-emission-tomography, Mice, [SPI]Engineering Sciences [physics], 0302 clinical medicine, Endothelial-cells, Medicine, Abcb1, lcsh:Science, Induced pluripotent stem cell, Cells, Cultured, media_common, Inhibition, Multidisciplinary, Brain, Cell Differentiation, Human brain, medicine.anatomical_structure, Drug development, Blood-Brain Barrier, Abcg2, Strategies, Neuroglia, Delivery, Drug, [SPI] Engineering Sciences [physics], media_common.quotation_subject, Induced Pluripotent Stem Cells, Central nervous system, Transport, Models, Biological, Proof of Concept Study, Permeability, Article, 03 medical and health sciences, Pharmacokinetics, In vivo, Animals, Humans, business.industry, lcsh:R, In vitro, Rats, 030104 developmental biology, Pet, Positron-Emission Tomography, lcsh:Q, business, 030217 neurology & neurosurgery
Abstract: The development of effective central nervous system (CNS) drugs has been hampered by the lack of robust strategies to mimic the blood-brain barrier (BBB) and cerebrovascular impairments in vitro. Recent technological advancements in BBB modeling using induced pluripotent stem cells (iPSCs) allowed to overcome some of these obstacles, nonetheless the pertinence for their use in drug permeation study remains to be established. This mandatory information requires a cross comparison of in vitro and in vivo pharmacokinetic data in the same species to avoid failure in late clinical drug development. Here, we measured the BBB permeabilities of 8 clinical positron emission tomography (PET) radioligands with known pharmacokinetic parameters in human brain in vivo with a newly developed in vitro iPSC-based human BBB (iPSC-hBBB) model. Our findings showed a good correlation between in vitro and in vivo drug brain permeability (R2 = 0.83; P = 0.008) which contrasted with the limited correlation between in vitro apparent permeability for a set of 18 CNS/non-CNS compounds using the in vitro iPSCs-hBBB model and drug physicochemical properties. Our data suggest that the iPSC-hBBB model can be integrated in a flow scheme of CNS drug screening and potentially used to study species differences in BBB permeation.
Published: 2019
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60. Lean body weight is the best scale for venous thromboprophylaxis algorithm in severely obese patients undergoing bariatric surgery

Author: Stéphane Berdah, Thierry Bege, Anne Dutour, Corinne Frere, Sandrine Boullu, C. Vincentelli, Bénédicte Gaborit, Joe-Elie Salem, Pierre-Emmanuel Morange, Olivier Emungania, Pierre-Antoine Moulin, Assistance Publique - Hôpitaux de Marseille (APHM), 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 (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), 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), Assistance Publique-Hôpitaux de Marseille (AP-HM), Aix Marseille Université (AMU), Service de pharmacologie biologique [CHU Pitié-Salpâtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CIC Paris Est, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Sorbonne Université (SU), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service d'Hématologie clinique [CHU Pitié-Salpêtrière]
Subjects: Adult, Dalteparin, Male, medicine.medical_specialty, Multivariate analysis, Lean body weight, medicine.drug_class, [SDV]Life Sciences [q-bio], Ideal Body Weight, Bariatric Surgery, Low molecular weight heparin, Renal function, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Weight Loss, medicine, Humans, Mass index, Prospective Studies, Low-molecular-weight heparin, 2. Zero hunger, Pharmacology, Univariate analysis, business.industry, Body Weight, Anticoagulants, Venous Thromboembolism, Middle Aged, Anti-Xa activity, Obesity, Morbid, 3. Good health, Surgery, Regimen, Lean body mass, Female, Median body, Glomerular filtration rate, Severe obesity, business
Abstract: International audience; Severely obese patients undergoing bariatric surgery (BS) are at increased risk for venous thromboembolism (VTE). How standard low molecular weight heparin (LMWH) regimen should be adapted to provide both sufficient efficacy and safety in this setting is unclear. We aimed to compare the influence of four body size descriptors (BSD) on peak anti-Xa levels in BS obese patients receiving LMWH fixed doses to identify which one had the greatest impact. One hundred and thirteen BS obese patients [median body mass index (BMI), 43.3 kg/m(2) (IQR, 40.6-48.7 kg/m(2))] receiving subcutaneous dalteparin 5000 IU twice daily were included in this prospective monocenter study. Peak steady-state anti-Xa levels were measured peri-operatively following thromboprophylaxis initiation. Only 48% of patients achieved target anti-Xa levels (0.2-0.5 IU/ml). In univariate analysis, age, gender, total body-weight (TBW), lean body-weight (LBW), ideal body-weight (IBW), BMI and estimated glomerural filtration rate (eGFR) were associated with anti-Xa levels. The strongest negative association was observed with LBW (r=-0.56, p55.8 kg) had the highest sensitivity (73%) and specificity (69%) to predict sub-prophylactic anti-Xa levels. In multivariate analysis, LBW and eGFR remained associated with anti-Xa levels (beta=-0.47 +/- 0.08, p
Published: 2018
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61. Efficacy and safety of a T-type calcium channel blocker in patients with neuropathic pain: A proof-of-concept, randomized, double-blind and controlled trial

Author: Christian Lucas, Claude Dubray, Noémie Delage, Christelle Créac’h, G. Mick, M. Letellier, E. Serra, Damien Richard, Pascale Picard, A. Hamdani, Alain Eschalier, S. Soriot‐Thomas, P. Arcagni, Pascale Vergne-Salle, V. Martinez, Michel Lantéri-Minet, D. Delbrouck, E. Bozzolo, C. Maindet, C. Dualé, Christian Gov, H. Alchaar, Nicolas Kerckhove, Bruno Pereira, D. Lefebvre‐Kuntz, Céline Lambert, S. Romettino, L. Balp, N. Leroux‐Bromberg, E. Piquet, C. Brosse, Christophe Mallet, Lise Bernard, F. Marcaillou, Y. Perier, V.S. Hieng, B. Lietar, R. Deleens, M. Navez, D. Gillet, E. Kuhn, Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche & Innovation Gaz et Energies Nouvelles - GDF Suez (CRIGEN), Gaz de France Suez (GDF Suez), Institut de recherche sur la biologie de l'insecte UMR7261 (IRBI), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Advanced Technologies R&D, STMicroelectronics, Qualité des eaux et prévention des pollutions (UR QELY), Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF), Space Science and Astrobiology Division at Ames, NASA Ames Research Center (ARC), Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Pharmacologie Médicale [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre d’Investigation Clinique (CIC), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Neuro-Dol - Clermont Auvergne (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Bureau International des Poids et Mesures (BIPM), Centre de Recherche sur la Matière Divisée (CRMD), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Department of Chemistry and Institute for Nanoscale Physics and chemistry (INPAC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Département d'Ingenierie et d'Etudes des Protéines, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Erosion torrentielle neige et avalanches (UR ETGR (ETNA)), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Méthodes d'Analyses pour le Traitement d'Images et la Stéréorestitution (MATIS), Laboratoire des Sciences et Technologies de l'Information Géographique (LaSTIG), École nationale des sciences géographiques (ENSG), Institut National de l'Information Géographique et Forestière [IGN] (IGN)-Institut National de l'Information Géographique et Forestière [IGN] (IGN)-École nationale des sciences géographiques (ENSG), Institut National de l'Information Géographique et Forestière [IGN] (IGN)-Institut National de l'Information Géographique et Forestière [IGN] (IGN), Institut National d'Horticulture, CHU Gabriel Montpied (CHU), CHU Clermont-Ferrand, CIC Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Pharmacologie Clinique-CHU Gabriel-Montpied, Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie de Clermont-Ferrand - Clermont Auvergne (ICCF), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Service de Pharmacologie Médicale [Clermont-Ferrand], and Département d'Ingenierie et d'Etudes des Protéines (DIEP)
Subjects: Adult, Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, Analgesic, Proof of Concept Study, law.invention, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Randomized controlled trial, law, medicine, Humans, education, Adverse effect, ComputingMilieux_MISCELLANEOUS, Aged, Analgesics, education.field_of_study, business.industry, Chronic pain, Middle Aged, Calcium Channel Blockers, medicine.disease, Interim analysis, 3. Good health, 030104 developmental biology, Anesthesiology and Pain Medicine, Anticonvulsant, Anesthesia, Neuropathic pain, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Ethosuximide, Neuralgia, Anticonvulsants, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Chronic Pain, business, 030217 neurology & neurosurgery
Abstract: Background T‐type calcium channels have been shown to play an important role in the initiation and maintenance of neuropathic pain and represent a promising therapeutic target for new analgesic treatments. Ethosuximide (ETX), an anticonvulsant and a T‐type channel blocker has shown analgesic effect in several chronic pain models but has not yet been evaluated in patients with neuropathic pain. Methods This proof‐of‐concept, multicentre, double‐blind, controlled and randomized trial compared the efficacy and safety of ETX (given as add‐on therapy) to an inactive control (IC) in 114 patients with non‐diabetic peripheral neuropathic pain. After a 7‐day run‐in period, eligible patients aged over 18 years were randomly assigned (1:1) to ETX or IC for 6 weeks. The primary outcome was the difference between groups in the pain intensity (% of change from the baseline to end of treatment) assessed in the intention‐to‐treat population. This study is registered with EudraCT (2013‐004801‐26) and ClinicalTrials.gov (NCT02100046). Results The study was stopped during the interim analysis due to the high number of adverse events in the active treatment group. ETX failed to reduce total pain and showed a poor tolerance in comparison to IC. In the per‐protocol analysis, ETX significantly reduced pain intensity by 15.6% (95% CI −25.8; −5.4) from baseline compared to IC (−7.8%, 95% CI −14.3; −1.3; p = 0.033), but this result must be interpreted with caution because of a small subgroup of patients. Conclusion Ethosuximide did not reduce the severity of neuropathic pain and induces, at the doses used, many adverse events. Significance This article shows that ETX is not effective to treat neuropathic pain. Nevertheless, per‐protocol analysis suggests a possible analgesic effect of ETX. Thus, our work adds significant knowledge to preclinical and clinical data on the benefits of T‐type calcium channel inhibition for the treatment of neuropathic pain.
Published: 2018
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62. Exposure of livestock to GM feeds : Detectability and measurement

Author: Alain Paris, Gijs Kleter, Sarah McFarland, Anna Nadal, Maria Pla, Mònica Toldrà, Jean-Michel Wal, Marzia De Giacomo, Jeroen P. van Dijk, R. Onori, Ralf Einspanier, Esther J. Kok, University Hospital of Girona, Istituto Superiore di Sanità (ISS), Freie Universität Berlin, Wageningen University and Research Centre (WUR), Molécules de Communication et Adaptation des Micro-Organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Wageningen Univ & Res, RIKILT, Akkermaalsbos 2, NL-6708 WB Wageningen, Netherlands, Partenaires INRAE, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Project: 312031,EC:FP7:KBBE,FP7-KBBE-2012-6-singlestage,MARLON(2012), Istituto Superiore di Sanità, Service de Pharmacologie et d'Immunoanalyse (SPI), and Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
Subjects: 0301 basic medicine, Novel Foods & Agrochains, [SDV]Life Sciences [q-bio], Genetically modified crops, Toxicology, Novel Foods & Agroketens, 01 natural sciences, Polymerase Chain Reaction, Animal tissue, law.invention, law, Tissue Distribution, BU Toxicology, Novel Foods & Agrochains, Polymerase chain reaction, media_common, Plant Proteins, BU Toxicology, High-Throughput Nucleotide Sequencing, General Medicine, Plants, Genetically Modified, Genetically modified organism, BU Toxicologie, Novel Foods & Agroketens, Livestock, Traceability, DNA, Plant, Animal feed, BU Toxicologie, Biology, 03 medical and health sciences, Multiplex polymerase chain reaction, media_common.cataloged_instance, Animals, Humans, European Union, European union, VLAG, business.industry, DNA and protein transfer, 010401 analytical chemistry, Animal Feed, 0104 chemical sciences, Biotechnology, 030104 developmental biology, Genetically modified organism (GMO), 13. Climate action, Exposure assessment, business, Multiplex Polymerase Chain Reaction, Biomarkers, Food Science
Abstract: International audience; This review explores the possibilities to determine livestock consumption of genetically modified (GM) feeds ingredients including detection of genetically modified organism (GMO)-related DNA or proteins in animal samples, and the documentary system that is in place for GM feeds under EU legislation. The presence and level of GMO-related DNA and proteins can generally be readily measured in feeds, using established analytical methods such as polymerase chain reaction and immuno-assays, respectively. Various technical challenges remain, such as the simultaneous detection of multiple GMOs and the identification of unauthorized GMOs for which incomplete data on the inserted DNA may exist. Given that transfer of specific GMO-related DNA or protein from consumed feed to the animal had seldom been observed, this cannot serve as an indicator of the individual animal's prior exposure to GM feeds. To explore whether common practices, information exchange and the specific GM feed traceability system in the EU would allow to record GM feed consumption, the dairy chain in Catalonia, where GM maize is widely grown, was taken as an example. It was thus found that this system would neither enable determination of an animal's consumption of specific GM crops, nor would it allow for quantitation of the exposure.
Published: 2018
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63. A multiplex lateral flow immunoassay for the rapid identification of NDM-, KPC-, IMP- and VIM-type and OXA-48-like carbapenemase-producing Enterobacteriaceae

Author: Sandrine Bernabeu, Karine Devilliers, Stéphanie Simon, Agnès B Jousset, Thierry Naas, Elodie Creton, Saoussen Oueslati, Hervé Volland, Garence Cotellon, Anaïs Vogel, Marc Plaisance, Laurent Dortet, Hervé Boutal, Volland, Herve, Institut National de la Recherche Agronomique (INRA), Université Paris Saclay (COmUE), Centre National de Référence de la Résistance aux Antibiotiques (CNR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Assistance Publique-Hopitaux de Paris (AP-HP), University Paris-Sud, Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), French National Research Agency [ANR-10-LABX-33], Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) DesInMBL [ANR-14-JAMR-002], Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: carba np test, desorption ionization-time, flight mass-spectrometry, k-set assay, immunochromatographic test, multicenter evaluation, cultured bacteria, beta-lactamase, pcr, 0301 basic medicine, Microbiology (medical), Carbapenemase-Producing Enterobacteriaceae, food.ingredient, Time Factors, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030106 microbiology, Cross Reactions, Sensitivity and Specificity, beta-Lactamases, Microbiology, 03 medical and health sciences, food, Bacterial Proteins, medicine, polycyclic compounds, Agar, Pharmacology (medical), Multiplex, Original Research, Pharmacology, Immunoassay, biology, Enterobacteriaceae Infections, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Enterobacteriaceae, Rapid identification, Clinical microbiology, 030104 developmental biology, Infectious Diseases, Carbapenem-Resistant Enterobacteriaceae, Beta-lactamase, Lateral flow immunoassay
Abstract: International audience; Objectives: The global spread of carbapenemase-producing Enterobacteriaceae represents a substantial challenge in clinical practice and rapid and reliable detection of these organisms is essential. The aim of this study was to develop and validate a lateral flow immunoassay (Carba5) for the detection of the five main carbapenemases (KPC-, NDM-, VIM-and IMP-type and OXA-48-like). Methods: Carba5 was retrospectively and prospectively evaluated using 296 enterobacterial isolates from agar culture. An isolated colony was suspended in extraction buffer and then loaded on the manufactured Carba5. Results: All 185 isolates expressing a carbapenemase related to one of the Carba5 targets were correctly and unambiguously detected in
Published: 2018
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64. Financial incentives for smoking cessation in pregnancy: multicentre randomised controlled trial

Author: Noémi Berlin, Ivan Berlin, Martine Breton, Léontine Goldzahl, Marie Malecot, Florence Jusot, Service de Pharmacologie médicale [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), EconomiX, Université Paris Nanterre (UPN)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Saint Joseph - Saint Luc [Lyon], Hôpital Morvan - CHRU de Brest (CHU - BREST ), Laboratoire d'Economie de Dauphine (LEDa), Institut de Recherche pour le Développement (IRD)-Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), EDHEC Business School (EDHEC), Université catholique de Lille (UCL), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], École des hautes études commerciales du Nord (EDHEC), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, medicine.medical_specialty, medicine.medical_treatment, Birth weight, media_common.quotation_subject, Health Behavior, Corrections, 01 natural sciences, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Reward, Randomized controlled trial, Pregnancy, law, medicine, Birth Weight, Humans, Single-Blind Method, 030212 general & internal medicine, 0101 mathematics, media_common, Motivation, Obstetrics, business.industry, Research, 010102 general mathematics, Pregnancy Outcome, Obstetrics and Gynecology, Gestational age, Prenatal Care, General Medicine, Odds ratio, Abstinence, medicine.disease, 3. Good health, Smoking cessation, Female, Smoking Cessation, Apgar score, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objective To evaluate the efficacy of financial incentives dependent on continuous smoking abstinence on smoking cessation and birth outcomes among pregnant smokers. Design Single blind, randomised controlled trial. Setting Financial Incentive for Smoking Cessation in Pregnancy (FISCP) trial in 18 maternity wards in France. Participants 460 pregnant smokers aged at least 18 years who smoked ≥5 cigarettes/day or ≥3 roll-your-own cigarettes/day and had a pregnancy gestation of Interventions Participants in the financial incentives group received a voucher equivalent to €20 (£17; $23), and further progressively increasing vouchers at each study visit if they remained abstinent. Participants in the control group received no financial incentive for abstinence. All participants received a €20 show-up fee at each of six visits. Main outcome measures The main outcome measure was continuous smoking abstinence from the first post-quit date visit to visit 6, before delivery. Secondary outcomes in the mothers were point prevalence abstinence, time to smoking relapse, withdrawal symptoms, blood pressure, and alcohol and cannabis use in past 30 days. Secondary outcomes in the babies were gestational age at birth, birth characteristics (birth weight, length, head circumference, Apgar score), and a poor neonatal outcome—a composite measure of transfer to the neonatal unit, congenital malformation, convulsions, or perinatal death. Results Mean age was 29 years. In the financial incentives and control groups, respectively, 137 (59%) and 148 (65%) were employed, 163 (71%) and 171 (75%) were in a relationship, and 41 (18%) and 31 (13%) were married. The participants had smoked a median of 60 cigarettes in the past seven days. The continuous abstinence rate was significantly higher in the financial incentives group (16%, 38/231) than control group (7%, 17/229): odds ratio 2.45 (95% confidence interval 1.34 to 4.49), P=0.004). The point prevalence abstinence rate was higher (4.61, 1.41 to 15.01, P=0.011), the median time to relapse was longer (visit 5 (interquartile range 3-6) and visit 4 (3-6), P Conclusions Financial incentives to reward smoking abstinence compared with no financial incentives were associated with an increased abstinence rate in pregnant smokers. Financial incentives dependent on smoking abstinence could be implemented as a safe and effective intervention to help pregnant smokers quit smoking. Trial registration ClinicalTrials.gov NCT02606227 .
Published: 2021
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65. Effectiveness of heart rate control on hemodynamics in critically ill patients with atrial tachyarrhythmias managed by amiodarone

Author: Christophe Faisy, Jean-Sébastien Hulot, Nadia Aissaoui, Pauline Dureau, Saik Urien, Christian Funck-Brentano, Joe-Elie Salem, Maria El-Aissaoui, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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), CIC - Mère Enfant Necker Cochin Paris Centre (CIC 1419), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], HAL-UPMC, Gestionnaire, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Service de pharmacologie biologique [CHU Pitié-Salpâtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP], Hôpital Européen Georges Pompidou [APHP] ( HEGP ), CIC - Mère Enfant Necker Cochin Paris Centre ( CIC 1419 ), and CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Male, Mean arterial pressure, medicine.medical_specialty, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, medicine.drug_class, Critical Illness, medicine.medical_treatment, Heart rate, Amiodarone, Hemodynamics, 030204 cardiovascular system & hematology, law.invention, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, law, Tachycardia, Internal medicine, medicine, Humans, Heart Atria, 030212 general & internal medicine, Renal replacement therapy, Aged, Aged, 80 and over, Pharmacology, Atrial tachyarrhythmia, business.industry, [ SDV.SP.MED ] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Shock, Middle Aged, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Intensive care unit, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Epinephrine, Anesthesia, Sedative, Cardiology, Female, sense organs, business, Anti-Arrhythmia Agents, medicine.drug
Abstract: Atrial tachyarrhythmias (AT) are common in intensive care unit (ICU) patients and might contribute to hemodynamic instability if heart rate (HR) is persistently too rapid. We aimed to assess if HR control below 115 or 130bpm with amiodarone improves hemodynamics in ICU patients with AT. This observational study included 73 ICU patients with disabling AT receiving amiodarone for HR control. A total of 525 changes (mainly within 4-8h) in mean arterial pressure (MAP) and 167 changes in plasma lactate in response to HR variations above 115 or 130bpm were analyzed. Epinephrine, sedative drugs, fluid loading, use of diuretics, continuous renal replacement therapy and amiodarone dosing were among covariables assessed. Univariable analysis showed that HR variations above 115bpm were poorly correlated to change in MAP (r=0.11, p
Published: 2017
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66. B- and T-cell subpopulations in patients with severe idiopathic membranous nephropathy may predict an early response to rituximab

Author: Karine Dahan, Tabassome Simon, Eva Languille, Michelle Rosenzwajg, Joana Hygino, Hanna Debiec, Pierre Ronco, David Klatzmann, Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de néphrologie et de transplantation rénale [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], Service de Pharmacologie médicale = service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], HAL-UPMC, Gestionnaire, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, 0301 basic medicine, Chemokine, Time Factors, 030232 urology & nephrology, Glomerulonephritis, Membranous, Severity of Illness Index, T-Lymphocytes, Regulatory, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, regulatory T cells, Podocyte, rituximab, 0302 clinical medicine, natural killer cells, biology, Middle Aged, CD56 Antigen, 3. Good health, Killer Cells, Natural, Phenotype, Treatment Outcome, medicine.anatomical_structure, Nephrology, Female, Rituximab, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Antibody, Immunosuppressive Agents, medicine.drug, Adult, Paris, T cell, B-Lymphocyte Subsets, GPI-Linked Proteins, Immunophenotyping, 03 medical and health sciences, Membranous nephropathy, Predictive Value of Tests, memory B cells, medicine, Humans, In patient, Aged, Autoantibodies, Tumor Necrosis Factor-alpha, business.industry, Receptors, IgG, Interleukin-2 Receptor alpha Subunit, membranous nephropathy, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, CD4 Lymphocyte Count, 030104 developmental biology, Supportive psychotherapy, TNF-α, Immunology, biology.protein, Interleukin-5, business, Biomarkers
Abstract: International audience; Primary membranous nephropathy (PMN) is characterized by antibodies to the podocyte, but little is known about B- and T-cell populations and their response to rituximab is controversial. To help resolve this we compared 33 lymphocyte subpopulations and 27 cytokines/chemokines in 25 patients with severe PMN and 27 age-matched healthy individuals. At baseline, patients had a significantly increased percentage of naive B-cells with significantly decreased switched and non-switched memory B-cells. There was a significantly decreased percentage of natural killer (NK) cells with an increase in the CD56brightCD16-/lo NK subset. There were a significantly decreased percentage of regulatory T cells, together with an increased plasma concentration of TNF-alpha, IL-5 and IL-2RA. We then investigated 16 patients at eight days and three and six months after treatment with rituximab added to supportive therapy compared to nine patients with supportive therapy alone. After rituximab, B-cell recovery was still incomplete at six months, with persistent alterations of B-cell subsets, a significant increase of both T-regulatory (Treg) cells and NK cells, and a significant decrease of both the CD56brightCD16-/lo NK subset and TNF-alpha levels. The patients who clinically responded to rituximab had a significantly lower percentage of Tregs at baseline compared to non-responders and a significantly increased percentage at day eight. Tregs remained unchanged in non-responders and in patients treated with supportive therapy alone. Thus, evaluation of Tregs might be useful for predicting early response to rituximab.
Published: 2017
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67. In vitro cytotoxic effects of DEHP-alternative plasticizers and their primary metabolites on a L929 cell line

Author: Teuta Eljezi, Pierre Pinta, Marie-Christine Chagnon, Damien Richard, Jean-Michel Chezal, Jérémy Pinguet, Valérie Sautou, Gaël Grimandi, Emmanuel Moreau, Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne ( IMoST ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ), CHU Clermont-Ferrand, Laboratoire d'ingénierie osteo-articulaire et dentaire ( LIOAD ), Université de Nantes ( UN ) -IFR26-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Pharmacologie Médicale [Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], Equipe NuTox (LNC - U1231) ( NUTOX ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Caractérisation et sécurité biologique des surfaces nanostructurées ( C-BIOSENSS ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), Matériaux d'intérêt biologique, Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service Pharmacie [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Louise Michel [Clermont-Ferrand], Laboratoire d'ingénierie osteo-articulaire et dentaire (LIOAD), Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Gestion et en Economie (IREGE), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Service de Pharmacologie Médicale [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Caractérisation et sécurité biologique des surfaces nanostructurées (C-BIOSENSS), Université d'Auvergne - Clermont-Ferrand I (UdA), Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-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), Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), and Jehan, Frederic
Subjects: 0301 basic medicine, Environmental Engineering, Metabolite synthesis, Biocompatibility, Cell Survival, Cytotoxicity, Health, Toxicology and Mutagenesis, Metabolite, Phthalic Acids, In Vitro Techniques, DEHP-alternative plasticizers, 010501 environmental sciences, 01 natural sciences, [ SDE ] Environmental Sciences, Mice, 03 medical and health sciences, chemistry.chemical_compound, Phthalates, Plasticizers, In vivo, Diethylhexyl Phthalate, Animals, Environmental Chemistry, Organic chemistry, Polyvinyl Chloride, Cells, Cultured, 0105 earth and related environmental sciences, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Chromatography, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Public Health, Environmental and Occupational Health, Plasticizer, Primary metabolite, Esters, General Medicine, General Chemistry, Fibroblasts, Pollution, In vitro, 3. Good health, Phthalic acid, 030104 developmental biology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, chemistry
Abstract: IF 4.208; International audience; Phthalic acid esters have been widely used to improve the plasticity of PVC medical devices. They carry a high exposure risk for both humans and the environment in clinical situations. Our study focuses on the cytotoxicity of alternative plasticizers. Postulated primary metabolites were synthesized, not being commercially available. Cytotoxicity assays were performed on L929 murine cells according to the ISO-EN 10993-5 standard design for the biocompatibility of medical devices. The tested concentrations of plasticizers (0.01, 0.05 and 0.1 mg/ml) covered the range likely to be found in biological fluids coming into direct contact with the medical devices. DEHP, DINP and DINCH were cytotoxic at the highest concentration (0.1 mg/ml) for 7 days of exposure. Their corresponding metabolites were found to be more cytotoxic, for the same concentration. By contrast, TOTM and its corresponding metabolite MOTM were not found to be cytotoxic. DEHA showed no cytotoxicity, but its corresponding monoester (MEHA) produced a cytotoxic effect at 0.05 mg/ml. In clinical situations, medical devices can release plasticizers, which can come into contact with patients. In vivo, the plasticizers are quickly transformed into primary metabolites. It is therefore important to measure the effects of both the plasticizers and their corresponding metabolites. Standard first-line cytotoxicity assays should be performed to ensure biocompatibility.
Published: 2017
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68. P47. Proteomic analysis of the Radiation-Induced Bystander Effects between low-dose irradiated Chondrosarcoma cells and Bystander Chondrocytes

Author: Lepleux, Charlotte, Rofidal, Valerie, Hem, Sonia, Almunia, Christine, Armengaud, J., Chevalier, François, Accueil et Recherche en Radiobiologie des Ions Accélérés (ARIA), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU), Biochimie et Physiologie Moléculaire des Plantes (BPMP), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), 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), Laboratoire Innovations technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Chevalier, Francois
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SDV.BV] Life Sciences [q-bio]/Vegetal Biology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

69. Reply to J. Heinrich

Author: Camille Davisse-Paturet, Blandine de Lauzon-Guillain, Amandine Divaret-Chauveau, Chantal Raherison, Karine Adel-Patient, Sandrine Lioret, Marie-Noëlle Dufourg, Marie-Aline Charles, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), 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), Cancer environnement (EPICENE ), 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)-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), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Unité d'Allergologie Pédiatrique, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), EFS-Institut national d'études démographiques (INED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: business.industry, Incidence, Immunology, Eczema, Infant, EPICENE, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Child, Preschool, Pediatrics, Perinatology and Child Health, Immunology and Allergy, Medicine, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030212 general & internal medicine, Theology, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Hypersensitivity
Published: 2019
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70. Androgenic Effects on Ventricular Repolarization

Author: Salem, Joe-Elie, Yang, Tao, Moslehi, Javid, Waintraub, Xavier, Gandjbakhch, Estelle, Bachelot, Anne, Hidden-Lucet, Françoise, Hulot, Jean-Sébastien, Knollmann, Bjorn, Lebrun-Vignes, Bénédicte, Funck-Brentano, Christian, Glazer, Andrew, Roden, Dan, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Cardiologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Centre de référence des maladies endocriniennes rares de la croissance et du développement [CHU Pitié-Salpêtrière], Centre des Pathologies gynécologiques Rares [CHU Pitié-Salpêtrière], Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de pharmacologie biologique [CHU Pitié-Salpâtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre de référence des maladies endocriniennes rares de la croissance [CHU Pitié-Salpêtrière], Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV]Life Sciences [q-bio], testosterone, long QT syndrome, hypogonadism, torsades de pointes, androgen antagonists
Abstract: International audience; BACKGROUND:Male hypogonadism, arising from a range of etiologies including androgen-deprivation therapies (ADTs), has been reported as a risk factor for acquired long-QT syndrome (aLQTS) and torsades de pointes (TdP). A full description of the clinical features of aLQTS associated with ADT and of underlying mechanisms is lacking.METHODS:We searched the international pharmacovigilance database VigiBase for men (n=6 560 565 individual case safety reports) presenting with aLQTS, TdP, or sudden death associated with ADT. In cardiomyocytes derived from induced pluripotent stem cells from men, we studied electrophysiological effects of ADT and dihydrotestosterone.RESULTS:Among subjects receiving ADT in VigiBase, we identified 184 cases of aLQTS (n=168) and/or TdP (n=68; 11% fatal), and 99 with sudden death. Of the 10 ADT drugs examined, 7 had a disproportional association (reporting odds ratio=1.4-4.7; P
Published: 2019
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71. Evaluation of Sample Preparation Methods for Fast Proteotyping of Microorganisms by Tandem Mass Spectrometry

Author: Karim Hayoun, Olivier Pible, Duarte Gouveia, Lucia Grenga, Béatrice Alpha-Bazin, Jean Armengaud, Institut National de la Recherche Agronomique (INRA), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Region OccitanieRegion Occitanie, ANR program 'Phylopeptidomics'French National Research Agency (ANR) [ANR-17-CE18-0023-01], French joint ministerial program of R&D against CBRNE threats, Armengaud, Jean, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and ANR-17-CE18-0023,Phylopeptidomics,Identification rapide de bactéries pathogènes et résistances aux antibiotiques(2017)
Subjects: Microbiology (medical), detection, identification, mass spectrometry, proteotyping, sample preparation, shotgun proteomics, microorganisms, Lysis, Microorganism, [SDV]Life Sciences [q-bio], lcsh:QR1-502, Peptide, Tandem mass spectrometry, Mass spectrometry, Microbiology, lcsh:Microbiology, 03 medical and health sciences, Sample preparation, Shotgun proteomics, 030304 developmental biology, Original Research, chemistry.chemical_classification, 0303 health sciences, Chromatography, 030306 microbiology, Chemistry, Gel electrophoresis of proteins
Abstract: International audience; Tandem mass spectrometry-based proteotyping allows characterizing microorganisms in terms of taxonomy and is becoming an important tool for investigating microbial diversity from several ecosystems. Fast and automatable sample preparation for obtaining peptide pools amenable to tandem mass spectrometry is necessary for enabling proteotyping as a high-throughput method. First, the protocol to increase the yield of lysis of several representative bacterial and eukaryotic microorganisms was optimized by using a long and drastic bead-beating setting with 0.1 mm silica beads, 0.1 and 0.5 mm glass beads, in presence of detergents. Then, three different methods to obtain greater digestion yield from these extracts were tested and optimized for improve efficiency and reduce application time: denaturing electrophoresis of proteins and in-gel proteolysis, suspension-trapping filter-based approach (S-Trap) and, solidphase-enhanced sample preparation named SP3. The latter method outperforms the other two in terms of speed and delivers also more peptides and proteins than with the in-gel proteolysis (2.2 fold for both) and S-trap approaches (1.3 and 1.2 fold, respectively). Thus, SP3 directly improves tandem mass spectrometry proteotyping.
Published: 2019
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72. Use of partially hydrolysed formula in infancy and incidence of eczema, respiratory symptoms or food allergies in toddlers from the ELFE cohort

Author: Sandrine Lioret, Blandine de Lauzon-Guillain, Karine Adel-Patient, Marie-Aline Charles, Corinne Bois, Marie-Noëlle Dufourg, Amandine Divaret-Chauveau, Camille Davisse-Paturet, Chantal Raherison, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), 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), CHU Bordeaux [Bordeaux], 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), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), EFS-Institut national d'études démographiques (INED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 6 : ORCHAD - Origines précoces de la santé du développement de l'enfant (CRESS - U1153), 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)-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), The ELFE survey is a joint project between INED (Institut National d'Etudes Démographiques), INSERM (Institut National de la Santé et de la Recherche Médicale), EFS (Etablissement Français du Sang), InVS (Institut de Veille Sanitaire), INSEE (Institut National de la Statistique et des Etudes Economiques), the Ministry of Health (DGS, Direction Générale de la Santé), the Ministry of Environment (DGPR, Direction Générale de la Prévention des Risques), the Ministry of Health and Employment (DREES, Direction de la Recherche, des Etudes, de l'Evaluation et des Statistiques), and the CNAF (Caisse Nationale des Allocations Familiales), with the support of the Ministry of Research and CCDSHS (Comité de Concertation pour les Données en Sciences Humaines et Sociales) and the Ministry of Culture (DEPS, Département des études, de la prospective et des statistiques). As part of the RECONAI platform, the study received state funding from the ANR within the framework of the 'Future Investments' program (reference: ANR-11- EQPX-0038)., ANR-11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), 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), Service de Pharmacologie et Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Biologie et de Technologies du CEA Saclay, Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-11-EQPX-0038/11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), de Lauzon-Guillain, Blandine, Equipements d'excellence - Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance - - RE-CO-NAI2011 - ANR-11-EQPX-0038 - EQPX - VALID, Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Pediatrics, medicine.medical_specialty, breastfeeding, Immunology, Population, Breastfeeding, formula feeding, Breast milk, Lower risk, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, partially hydrolyzed formula, medicine, Immunology and Allergy, 030212 general & internal medicine, infancy, education, Asthma, 2. Zero hunger, education.field_of_study, food allergy, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, wheezing, Incidence (epidemiology), asthma, medicine.disease, 3. Good health, 030228 respiratory system, Infant formula, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Pediatrics, Perinatology and Child Health, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, eczema, business
Abstract: International audience; BACKGROUND AND OBJECTIVES:Partially hydrolyzed formulas (pHF) are recommended in non-breastfed infants with familial history of allergy to prevent allergy development. However, recent meta-analysis does not provide strong support for their protective effect. The present work assesses the links between 2-month infant formula use and the incidence of eczema, respiratory symptoms, or food allergies (FA) up to 2 years of age.METHODS:The nationwide ELFE birth cohort is a population-based study from mainland France. Infant feeding (breast milk only, partially hydrolyzed formula with [pHF-HA] or without a hypoallergenic label [pHF-non-HA], and non-hydrolyzed formula [Nhf]) was reported at 2 months. Eczema, FA, and respiratory symptoms such as wheezing and asthma were reported at 2 months, 1 year, and 2 years. Infants with prior FA at 2 months were excluded from analyses.RESULTS:Among 11 720 infants, those who received only breast milk at 2 months were at lower risk of eczema at 1 year than those who received nHF (OR[95% CI] = 0.78[0.65-0.94] in non-at-risk infants; 0.86[0.75-0.98] in at-risk infants). The use of pHF-HA, compared with nHF, at 2 months was related to higher risk of wheezing at 1 year in at-risk infants (1.68[1.24-2.28]) and higher risk of FA at 2 years both in non-at-risk infants (3.78[1.52-9.41]) and in at-risk infants (2.31[1.36-3.94]).CONCLUSIONS:In this nationwide study, pHF-HA use was not associated with a lower risk of any of the studied outcomes. Quite the reverse, it was associated with a higher risk of wheezing and FA. This should be confirmed in further studies.
Published: 2019
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73. Breastfeeding Status and Duration and Infections, Hospitalizations for Infections and Antibiotic Use in the First Two Years of Life in the ELFE Cohort

Author: Davisse-Paturet, Camille, Adel-Patient, Karine, Divaret-Chauveau, Amandine, Pierson, Juliette, Lioret, Sandrine, Cheminat, Marie, Dufourg, Marie-Noëlle, Charles, Marie-Aline, De Lauzon-Guillain, Blandine, 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), Service de Pharmacologie et Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Biologie et de Technologies du CEA Saclay, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), The ELFE survey is a joint project between the French Institute for Demographic Studies (INED) and the National Institute of Health and Medical Research (INSERM), in partnership with the French blood transfusion service (Etablissement français du sang, EFS), Santé publique France, the National Institute for Statistics and Economic Studies (INSEE), the Direction générale de la santé (DGS, part of the Ministry of Health and Social Affairs), the Direction générale de la prévention des risques (DGPR, Ministry for the Environment), the Direction de la recherche, des études, de l’évaluation et des statistiques (DREES, Ministry of Health and Social Affairs), the Département des études, de la prospective et des statistiques (DEPS, Ministry of Culture), and the Caisse nationale des allocations familiales (CNAF), with the support of the Ministry of Higher Education and Research and the Institut national de la jeunesse et de l’éducation populaire (INJEP). Via the RECONAI platform, it received a government grant managed by the National Research Agency under the 'Investissements d’avenir' program (ANR-11-EQPX-0038)., ANR-11-EQPX-0038/11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), de Lauzon-Guillain, Blandine, Equipements d'excellence - Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance - - RE-CO-NAI2011 - ANR-11-EQPX-0038 - EQPX - VALID, Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, ANR-11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Adult, Male, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, breastfeeding, Infant, lcsh:TX341-641, birth cohort, Article, Anti-Bacterial Agents, Cohort Studies, Hospitalization, antibiotic use, Breast Feeding, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Communicable Disease Control, Humans, Female, Infant Food, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, infections, hospitalizations, lcsh:Nutrition. Foods and food supply
Abstract: In low- and middle-income countries, the protective effect of breastfeeding against infections is well established, but in high-income countries, the effect could be weakened by higher hygienic conditions. We aimed to examine the association between breastfeeding and infections in the first 2 years of life, in a high-income country with relatively short breastfeeding duration. Among 10,349 young children from the nationwide Etude Longitudinale Française depuis l’Enfance (ELFE) birth cohort, breastfeeding and parent-reported hospitalizations, bronchiolitis and otitis events, and antibiotic use were prospectively collected up to 2 years. Never-breastfed infants were used as reference group. Any breastfeeding for
Published: 2019
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74. Very Early Blood Diffusion of the Active Lethal and Edema Factors of Bacillus anthracis After Intranasal Infection

Author: Pierre L. Goossens, François Becher, Clémence Rougeaux, Jean-Nicolas Tournier, Unité de Biothérapies anti-Infectieuses et Immunité [Brétigny-sur-Orge], Institut de Recherche Biomédicale des Armées (IRBA), Pathogénie des Toxi-infections bactériennes, Institut Pasteur [Paris], Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, École du Val de Grâce (EVDG), Service de Santé des Armées, National Reference Center for Anthrax [Brétigny-sur-Orge] (CNR-LE Charbon), This work was funded by the Joint Ministerial Program of R&D against CBRNE risks (NRBC H1.11)., Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Pasteur [Paris] (IP), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, Pathogenesis and Host Response, [SDV]Life Sciences [q-bio], inhalational anthrax, Bacteremia, MESH: Virulence, MESH: Animals, Outbred Strains, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Edema, Immunology and Allergy, MESH: Animals, MESH: Bacteremia, bacteria, biology, Virulence, toxins, 3. Good health, Bacillus anthracis, MESH: Bacillus anthracis, Infectious Diseases, medicine.anatomical_structure, Female, medicine.symptom, Nasal Absorption, MESH: Enzyme Activation, mice, Virulence Factors, Anthrax toxin, 030106 microbiology, Bacterial Toxins, Spleen, Microbiology, Anthrax, 03 medical and health sciences, Major Articles and Brief Reports, Antigen, MESH: Enzyme Assays, blood, medicine, MESH: Anthrax, Animals, Outbred Strains, Animals, MESH: Mice, MESH: Virulence Factors, Enzyme Assays, Antigens, Bacterial, business.industry, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Enzyme Activation, Disease Models, Animal, 030104 developmental biology, MESH: Bacterial Toxins, MESH: Nasal Absorption, MESH: Biomarkers, Nasal administration, MESH: Disease Models, Animal, business, MESH: Female, MESH: Antigens, Bacterial, Biomarkers
Abstract: Background Lethal and edema toxins are critical virulence factors of Bacillus anthracis. Few data are available on their presence in the early stage of intranasal infection. Methods To investigate the diffusion of edema factor (EF) and lethal factor (LF), we use sensitive quantitative methods to measure their enzymatic activities in mice intranasally challenged with a wild-type B anthracis strain or with an isogenic mutant deficient for the protective antigen. Results One hour after mouse challenge, although only 7% of mice presented bacteremia, LF and EF were detected in the blood of 100% and 42% of mice, respectively. Protective antigen facilitated the diffusion of LF and EF into the blood compartment. Toxins played a significant role in the systemic dissemination of B anthracis in the blood, spleen, and liver. A mouse model of intoxination further confirmed that LT and ET could diffuse rapidly in the circulation, independently of bacteria. Conclusions In this inhalational model, toxins have disseminated rapidly in the blood, playing a significant and novel role in the early systemic diffusion of bacteria, demonstrating that they may represent a very early target for the diagnosis and the treatment of anthrax., The enzymatically active components of B anthracis toxins and bacteria can diffuse very early in the blood during inhalational anthrax model, paving the way for an ultra-precocious diagnosis and the setup of an early and effective treatment.
Published: 2019
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75. Abatacept for Severe Immune Checkpoint Inhibitor–Associated Myocarditis

Author: Johnson, Douglas, Salem, Joe-Elie, Allenbach, Yves, Vozy, Aurore, Brechot, Nicolas, Douglas, Johnson, B., Javid, Moslehi, Javid, Kerneis, Mathieu, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de référence des maladies rares neuromusculaires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), NOAA Earth System Research Laboratory (ESRL), National Oceanic and Atmospheric Administration (NOAA), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Gestionnaire, HAL Sorbonne Université 5, Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: musculoskeletal diseases, Autoimmune myocarditis, Myocarditis, business.industry, Abatacept, Immune checkpoint inhibitors, Cancer, General Medicine, 030204 cardiovascular system & hematology, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, eye diseases, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, 03 medical and health sciences, 0302 clinical medicine, Immunology, medicine, 030212 general & internal medicine, Complication, business, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: Abatacept for Nivolumab-Induced Myocarditis Autoimmune myocarditis is a rare but often fatal complication of immune checkpoint inhibitor therapy for cancer. A case of glucocorticoid-refractory myoc...
Published: 2019
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76. EAACI position paper: Influence of dietary fatty acids on asthma, food allergy, and atopic dermatitis

Author: Berber Vlieg-Boerstra, Rosan Meyer, Cezmi A. Akdis, Antonella Muraro, Mary Feeney, Karine Adel-Patient, Sylwia Smolinska, Kate Maslin, Holger Garn, Ioana Agache, Isabella Pali-Schöll, Graham Roberts, Caroline Roduit, Karin Hoffmann-Sommergruber, Lars K. Poulson, Remo Frei, Bright I Nwaru, Harald Renz, Eva Untersmayr, George Du Toit, Matthew Greenhawt, Peter K. Smith, Carina Venter, Catherine Stanton, Stephan C. Bischoff, Liam O'Mahony, Clare Mills, Carlo Agostoni, Milena Sokolowska, Imke Reese, Nonhlanhla Lunjani, University of Colorado, University of Colorado [Boulder], Imperial College London, University of Gothenburg (GU), University Children’s Hospital Zurich, Medizinische Universität Wien = Medical University of Vienna, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris Saclay (COmUE), Sapientia Hungarian University of Transylvania, Ospedale Maggiore Policlinico, Università degli Studi di Milano = University of Milan (UNIMI), Christine Kühne Center, Partenaires INRAE, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), University of Hohenheim, King‘s College London, Guy's and St Thomas' Hospitals, Philipps Universität Marburg = Philipps University of Marburg, University of Colorado Anschutz [Aurora], University of Cape Town, MRC Lifecourse Epidemiology Unit, University of Southampton, School of Biological Sciences, Manchester Academic Health Sciences Centre, Manchester Institute of Biotechnology, University of Manchester, Università degli Studi di Padova = University of Padua (Unipd), Copenhagen University Hospitals, Dietary Counseling and Nutrition Therapy Centre, Institute of Laboratory Medicine, Helios-Hospital, The David Hide Asthma and Allergy Research Centre, St Mary's Hospital-University Hospital Southampton NHS Foundation Trust, NIHR Biomedical Research Centre, Griffith University [Brisbane], Department of Clinical Immunology, Wrocław Medical University, APC Microbiome Ireland, University College Cork (UCC), OLVG, Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Università degli Studi di Milano [Milano] (UNIMI), Philipps University of Marburg, Universita di Padova, Grifﬁth University, and Wroclaw Medical University
Subjects: 0301 basic medicine, Allergy, Lydia Becker Institute, [SDV]Life Sciences [q-bio], allergic, chemistry.chemical_compound, 0302 clinical medicine, Epidemiology, Immunology and Allergy, Rhinitis, 2. Zero hunger, dietary fatty acids, Fatty Acids, Age Factors, Atopic dermatitis, 3. Good health, Food Hypersensitivity, altered environmenta, Signal Transduction, Adult, medicine.medical_specialty, Immunology, Dermatitis, Atopic, Immunomodulation, 03 medical and health sciences, Immune system, Food allergy, ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation, Manchester Institute of Biotechnology, medicine, Animals, Humans, Microbiome, Nutrition, Asthma, Fatty acid metabolism, business.industry, Infant, Newborn, Infant, ResearchInstitutes_Networks_Beacons/manchester_institute_of_biotechnology, Lipid Metabolism, medicine.disease, Dietary Fats, Disease Models, Animal, 030104 developmental biology, 030228 respiratory system, chemistry, business
Abstract: International audience; The prevalence of allergic diseases such as allergic rhinitis, asthma, food allergy, and atopic dermatitis has increased dramatically during the last decades, which is associated with altered environmental exposures and lifestyle practices. The purpose of this review was to highlight the potential role for dietary fatty acids, in the prevention and management of these disorders. In addition to their nutritive value, fatty acids have important immunoregulatory effects. Fatty acid-associated biological mechanisms, human epidemiology, and intervention studies are summarized in this review. The influence of genetics and the microbiome on fatty acid metabolism is also discussed. Despite critical gaps in our current knowledge, it is increasingly apparent that dietary intake of fatty acids may influence the development of inflammatory and tolerogenic immune responses. However, the lack of standardized formats (ie, food versus supplement) and standardized doses, and frequently a lack of prestudy serum fatty acid level assessments in clinical studies significantly limit our ability to compare allergy outcomes across studies and to provide clear recommendations at this time. Future studies must address these limitations and individualized medical approaches should consider the inclusion of specific dietary factors for the prevention and management of asthma, food allergy, and atopic dermatitis.
Published: 2019
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77. Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study

Author: Javid Moslehi, Justin M. Balko, Joe-Elie Salem, Ali Manouchehri, Alexandra M Haugh, Bénédicte Lebrun-Vignes, Henry T. Quach, Andrew L. Mammen, Douglas B. Johnson, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Centre Régional de Pharmacovigilance (CRPV), 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), Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), National Institutes of Health [Bethesda] (NIH), Gestionnaire, Hal Sorbonne Université, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Cancer Research, MedDRA, [SDV]Life Sciences [q-bio], Guillain-Barre syndrome, Pharmacovigilance, 0302 clinical medicine, PD-1, Immunology and Allergy, Myasthenia gravis, Incidence (epidemiology), lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Molecular Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Encephalitis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Immunotherapy, Meningitis, Research Article, PD-L1, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Drug-Related Side Effects and Adverse Reactions, Immunology, lcsh:RC254-282, 03 medical and health sciences, Internal medicine, medicine, Neurotoxicity, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adverse effect, Retrospective Studies, Pharmacology, business.industry, Odds ratio, medicine.disease, Neuropathy, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, CTLA-4, Nervous System Diseases, business, 030215 immunology
Abstract: Background Immune checkpoint inhibitors (ICI) produce durable antitumor responses but provoke autoimmune toxicities, including uncommon but potentially devastating neurologic toxicities. The clinical features, including the spectrum, timing, and outcomes, of ICI-induced neurologic toxicities are not well characterized. Methods We performed disproportionality analysis using Vigibase, the World Health Organization pharmacovigilance database, comparing neurologic adverse event (AE) reporting in patients receiving ICIs vs. the full database. Neurologic AEs were classified by group queries using Medical Dictionary for Regulatory Activities, between database inception to September 28, 2018. Associations between ICIs and neurologic AEs were assessed using reporting odds ratios (ROR) and information component (IC). IC compares observed and expected values to find associations between drugs and AEs using disproportionate Bayesian reporting; IC025 (lower end of the IC 95% credibility interval) > 0 is considered statistically significant. Results Among the full database, 18,518,994 AEs were reported, including 48,653 with ICIs. ICIs were associated with higher incidence of myasthenia gravis (0.47% of ICI reports vs. 0.04% of the full database, ROR 16.5 [95% CI 14.5–18.9]; IC025 3.31), encephalitis (0.51% vs. 0.05%, ROR 10.4 [95% CI 9.2–11.8]; IC025 3.15), peripheral neuropathy (1.16% vs. 0.67%, IC025 0.68), and meningitis (0.15% vs. 0.06%, ROR 3.1 [95% CI 2.5–3.9]; IC025 1.01). Myasthenia gravis and encephalitis were associated with anti-PD-1 whereas other neurologic AEs were associated with anti-CTLA-4. Myasthenia gravis was characterized by high fatality rates (~ 20%), early onset (median 29 days), and frequent concurrent myocarditis and myositis; whereas other neurologic AEs had lower fatality rates (6–12%), later onset (median 61–80 days), and were non-overlapping. Conclusions ICIs produce a spectrum of distinct classes of neurologic AEs that can cause significant morbidity and mortality and tend to occur early and with class-specific associations. Electronic supplementary material The online version of this article (10.1186/s40425-019-0617-x) contains supplementary material, which is available to authorized users.
Published: 2019
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78. Orchestration of Tryptophan-Kynurenine Pathway, Acute Decompensation, and Acute-on-Chronic Liver Failure in Cirrhosis

Author: Claria, J., Moreau, R., Fenaille, F., Amoros, A., Junot, C., Gronbaek, H., Coenraad, M.J., Pruvost, A., Ghettas, A., Chu-Van, E., Lopez-Vicario, C., Oettl, K., Caraceni, P., Alessandria, C., Trebicka, J., Pavesi, M., Deulofeu, C., Albillos, A., Gustot, T., Welzel, T.M., Fernandez, J., Stauber, R.E., Saliba, F., Butin, N., Colsch, B., Moreno, C., Durand, F., Nevens, F., Banares, R., Benten, D., Gines, P., Gerbes, A., Jalan, R., Angeli, P., Bernardi, M., Arroyo, V., EASL Clif Consortium, Grifols Chair European Fdn Study C, Clària, Joan, Moreau, Richard, Fenaille, Françoi, Amorós, Alex, Junot, Christophe, Gronbaek, Henning, Coenraad, Minneke J, Pruvost, Alain, Ghettas, Aurélie, Chu-Van, Emeline, López-Vicario, Cristina, Oettl, Karl, Caraceni, Paolo, Alessandria, Carlo, Trebicka, Jonel, Pavesi, Marco, Deulofeu, Carme, Albillos, Agustin, Gustot, Thierry, Welzel, Tania M, Fernández, Javier, Stauber, Rudolf E, Saliba, Faouzi, Butin, Noémie, Colsch, Benoit, Moreno, Christophe, Durand, Françoi, Nevens, Frederik, Bañares, Rafael, Benten, Daniel, Ginès, Pere, Gerbes, Alexander, Jalan, Rajiv, Angeli, Paolo, Bernardi, Mauro, Arroyo, Vicente, Grifols Chair, Partenaires INRAE, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Université Paris Diderot - Paris 7 (UPD7), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Paris Saclay (COmUE), Aarhus University Hospital, Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Institut National de la Recherche Agronomique (INRA), Medical University Graz, Department of Medical and Surgical Sciences, Universita degli Studi di Padova, San Giovanni Battista Hosp, Div Gastroenterol & Hepatol, Turin, Italy, Rheinische Friedrich-Wilhelms-Universität Bonn, Hospital Universitario, Université libre de Bruxelles (ULB), Goethe-Universität Frankfurt am Main, Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Université Catholique de Louvain = Catholic University of Louvain (UCL), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Univ Hosp LMU Munich, Liver Ctr Munich, Dept Med 2, Munich, Germany, University College of London [London] (UCL), Universita di Padova, ICREA Academia Award, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universiteit Leiden-Universiteit Leiden, and Università degli Studi di Padova = University of Padua (Unipd)
Subjects: Liver Cirrhosis, Male, 0301 basic medicine, Cirrhosis, Kynurenine pathway, [SDV]Life Sciences [q-bio], medicine.medical_treatment, severity, Decompensated cirrhosis, Systemic inflammation, Gastroenterology, Tryptophan -- blood, chemistry.chemical_compound, 0302 clinical medicine, hepatic-encephalopathy, Prospective Studies, Renal Insufficiency, Indoleamine 2,3-dioxygenase, Hepatic encephalopathy, Kynurenine, Liver Cirrhosis -- blood -- complications -- mortality -- physiopathology, systemic inflammation, Europe -- epidemiology, Kynurenine -- blood, Hepatic Encephalopathy -- blood -- complications, Tryptophan, Bacterial Infections -- blood -- complications, Immunosuppression, Bacterial Infections, Sciences bio-médicales et agricoles, Middle Aged, Acute-On-Chronic Liver Failure -- blood -- etiology, metabolomics, 3. Good health, Europe, chromatography, Female, 030211 gastroenterology & hepatology, medicine.symptom, metabolomic, medicine.medical_specialty, indoleamine 2,3-dioxygenase, Decompensated cirrhosi, 03 medical and health sciences, Internal medicine, medicine, Humans, organ failure, Decompensation, plasma, Aged, Inflammation, Inflammation -- blood -- complications, Renal Insufficiency -- blood -- complications, Hepatology, business.industry, Acute-On-Chronic Liver Failure, blockade, medicine.disease, mortality, kynurenine, 030104 developmental biology, chemistry, Case-Control Studies, Hepatic Encephalopathy, business, metabolism
Abstract: Systemic inflammation (SI) is involved in the pathogenesis of acute decompensation (AD) and acute-on-chronic liver failure (ACLF) in cirrhosis. In other diseases, SI activates tryptophan (Trp) degradation through the kynurenine pathway (KP), giving rise to metabolites that contribute to multiorgan/system damage and immunosuppression. In the current study, we aimed to characterize the KP in patients with cirrhosis, in whom this pathway is poorly known. The serum levels of Trp, key KP metabolites (kynurenine and kynurenic and quinolinic acids), and cytokines (SI markers) were measured at enrollment in 40 healthy subjects, 39 patients with compensated cirrhosis, 342 with AD (no ACLF) and 180 with ACLF, and repeated in 258 patients during the 28-day follow-up. Urine KP metabolites were measured in 50 patients with ACLF. Serum KP activity was normal in compensated cirrhosis, increased in AD and further increased in ACLF, in parallel with SI; it was remarkably higher in ACLF with kidney failure than in ACLF without kidney failure in the absence of differences in urine KP activity and fractional excretion of KP metabolites. The short-term course of AD and ACLF (worsening, improvement, stable) correlated closely with follow-up changes in serum KP activity. Among patients with AD at enrollment, those with the highest baseline KP activity developed ACLF during follow-up. Among patients who had ACLF at enrollment, those with immune suppression and the highest KP activity, both at baseline, developed nosocomial infections during follow-up. Finally, higher baseline KP activity independently predicted mortality in patients with AD and ACLF. Conclusion: Features of KP activation appear in patients with AD, culminate in patients with ACLF, and may be involved in the pathogenesis of ACLF, clinical course, and mortality., info:eu-repo/semantics/published
Published: 2019
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79. Cardiac arrhythmia considerations of hormone cancer therapies

Author: Lee S. Nguyen, Joe-Elie Salem, Christian Funck-Brentano, Mary C Barber, Johanna Wassermann, Jean-Philippe Spano, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], CIC Paris Est, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université (SU), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], Gestionnaire, Hal Sorbonne Université, Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service de Pharmacologie médicale [CHU Pitié-Salpêtrière]
Subjects: 0301 basic medicine, Oncology, Male, Physiology, [SDV]Life Sciences [q-bio], Action Potentials, 030204 cardiovascular system & hematology, Anti-cancer drugs, Androgen deprivation therapy, Prostate cancer, 0302 clinical medicine, Breast cancer, Heart Rate, Risk Factors, Medicine, Aromatase, skin and connective tissue diseases, Testosterone, biology, Prognosis, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV] Life Sciences [q-bio], Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Antineoplastic Agents, Hormonal, Torsades de pointes, Breast Neoplasms, QT interval, Risk Assessment, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart Conduction System, Physiology (medical), Internal medicine, Animals, Humans, business.industry, Cancer, Prostatic Neoplasms, Arrhythmias, Cardiac, QT, medicine.disease, Atrial fibrillation, 030104 developmental biology, biology.protein, business
Abstract: International audience; Breast and prostate cancers are among the most prevalent cancers worldwide. Oestradiol and progesterone are major drivers for breast cancer proliferation, and androgens for prostate cancer. Endocrine therapies are drugs that interfere with hormone-activated pathways to slow cancer progression. Multiple new breakthrough drugs improving overall survival have recently been developed within this class. As the use of these latter drugs grows, incidence of cardiac arrhythmias has emerged as an unappreciated complication. These changes are not surprising given that sex hormones alter ventricular repolarization. Testosterone shortens action potential duration and QT interval duration, while oestradiol has an opposite effect. In patients with breast cancer, selective oestrogen receptor modulators are associated with more reports for long QT and torsade de pointes (TdP) than aromatase inhibitors, likely through an oestradiol-like effect on the heart. Cyclin-dependent kinase 4/6 inhibitors, a new class of anticancer drugs used in combination with endocrine therapies in hormone receptor positive breast cancer, are also variably associated with drug-induced long QT, particularly with ribociclib. In prostate cancer, androgen deprivation therapy is associated with long QT and TdP, and possibly atrial fibrillation for abiraterone. In this review, we have summarized the clinical and preclinical data focusing on cardiac arrhythmia considerations of hormone cancer therapies.
Published: 2019
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80. In vitro cytotoxic effects of secondary metabolites of DEHP and its alternative plasticizers DINCH and DINP on a L929 cell line

Author: Damien Richard, Fabien Nativel, Valérie Sautou, Olivier Roy, Pierre Pinta, Emmanuel Moreau, Jérémy Pinguet, Teuta Eljezi, Gaël Grimandi, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Pharmacologie Médicale [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), This study is a part of the ARMED® project and received financial support from the French National Agency for the Safety of Medicines and Health Products (ANSM) Grant/award number : AAPR-2012-009., Chezal, Jean-Michel, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-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), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de Chimie de Clermont-Ferrand - Clermont Auvergne (ICCF), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Service de Pharmacologie Médicale [Clermont-Ferrand]
Subjects: [CHIM.ANAL] Chemical Sciences/Analytical chemistry, Biocompatibility, Cyclohexanecarboxylic Acids, Metabolite synthesis, Cell Survival, Cytotoxicity, Phthalic Acids, 010501 environmental sciences, 01 natural sciences, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, In vivo, Plasticizers, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Diethylhexyl Phthalate, Cytotoxic T cell, Animals, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Dicarboxylic Acids, 030212 general & internal medicine, 0105 earth and related environmental sciences, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Chromatography, DINP, Chemistry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Public Health, Environmental and Occupational Health, Plasticizer, Metabolism, DINCH, In vitro, 3. Good health, Phthalic acid, Equipment and Supplies, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, DEHP-Alternative plasticizers, Metabolite synthesis, DINP, DINCH, Cytotoxicity, DEHP-Alternative plasticizers
Abstract: International audience; Background: Phthalic acid esters are widely used to improve the plasticity of PVC in medical devices (MD). The most famous plasticizer is DEHP, whose use in medical devices has been contested by the European authorities since 2008. Several alternative plasticizers are being considered to replace DEHP, such as DEHT, TOTM, DINP or DINCH, but they are also released from the PVC throughout their life cycle and are metabolized in the same way as DEHP. Objectives: Our study focuses on the in vitro cytotoxicity of two alternative plasticizers (DINCH and DINP) contained in certain medical devices. They are likely to migrate and be transformed in vivo into the primary and secondary metabolites by a metabolism similar to that of DEHP. This preliminary study is the first to assess the in vitro cytotoxicity of oxidized metabolites of DINCH and DINP based on the EN ISO 10-993-5 standards documents. Methods: We have studied the complete multi-step organic synthesis of secondary metabolites of DINP and DINCH and have performed cytotoxicity tests on L929 murine cells according to the ISO-EN ISO 10993-5 standard design for the biocompatibility of a MD. The tested concentrations of obtained metabolites (0.01, 0.05 and 0.1 mg/mL) covered the range likely to be found for DEHP (total metabolism) in biological fluids coming into direct contact 2 with the MD. The concentrations tested in our study were chosen based on a complete transformation of the plasticizers released after direct contact between a MD and the patient's blood. Results Only 7-oxo-MMeOCH is cytotoxic at the highest concentration (0.1 mg/mL) after 7 days of exposure, just like 5-oxo-MEHP for the same concentration. By contrast, 7-OH-MMeOP, 7-cx-MMeOP, 7-oxo-MMeOP, 7-OH-MMeOCH and 7-cx-MMeOCH were not found to be cytotoxic. Conclusion: The known concentrations of these secondary metabolites in urinary samples are in the μg/L range, i.e. about 100-1000 times lower than the concentrations tested in this study. Cytotoxicity is known to be dose-dependent but it is not always the case for endocrine perturbations and the secondary metabolites could induce endocrine perturbations at very low doses.
Published: 2019
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81. Accréditation du criblage toxicologique : recommandations du groupe SFBC — SFTA

Author: Maeva Wendremaire, Mireille Bartoli, Nathalie Allibe, Carine Garcia-Hejl, Emilie Roman, Jérôme Guitton, Catherine Ganière, Jérôme Grosjean, Franck Saint-Marcoux, Damien Richard, Sabine Cohen, Jean-Michel Gaulier, Emuri Abe, Antony Citterio-Quentin, Laboratoire de Pharmacologie et Toxicologie, Institut National de la Recherche Agronomique (INRA), CHU Grenoble, Laboratoire de biochimie, Service de Pharmacologie Médicale [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], CHU Limoges, Laboratoire de Pharmacologie-Toxicologie [CHU de Dijon], and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: 03 medical and health sciences, 0302 clinical medicine, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], 010401 analytical chemistry, 030216 legal & forensic medicine, Toxicology, 01 natural sciences, 0104 chemical sciences, 3. Good health
Abstract: Resume Le criblage toxicologique est une approche specifique de la toxicologie analytique qui fait appel a des outils analytiques tels que la CG-SM, la CL-UV (barrette de diodes) ou la CL-SM. Le criblage toxicologique permet la detection et l’identification simultanees d’un grand nombre de composes. Les resultats peuvent etre bases sur l’emploi d’une ou de plusieurs techniques. Dans le cadre du processus d’accreditation des examens de biologie medicale selon la norme NF EN ISO 15189, le groupe issu des societes savantes SFTA et SFBC recommande une demarche pour accrediter le criblage toxicologique. En effet, la complexite de l’accreditation de cette analyse provient en particulier du nombre eleve de composes susceptibles d’etre detectes. Les parametres de validation sont discutes dans le cadre specifique du criblage toxicologique en considerant deux approches distinctes : l’identification des composes ou l’identification et l’estimation d’une zone de concentration.
Published: 2019
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82. Endothelium structure and function in kidney health and disease

Author: Vincent Pernin, Claire Rigothier, Gilles Kaplanski, Jeremy Bellien, Pierre-André Jarrot, Lubka T. Roumenina, Marion Sallée, Stéphane Burtey, Dominique Guerrot, Moglie Le Quintrec, Véronique Frémeaux-Bacchi, Laetitia Dou, Noémie Jourde-Chiche, Fadi Fakhouri, Marie Frimat, 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 de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Immunotherapy in Transplantation And Autoimmunity (Team 3 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de pharmacologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Lille Inflammation Research International Center - U 995 (LIRIC), 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), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Lapeyronie [Montpellier] (CHU), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service d'immunologie biologique [Hôpital Européen Georges Pompidou [APHP], 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), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Service de Néphrologie [Rouen], INSERM., Assistance Publique-Hôpitaux de Paris (AP-HP)-Programme Hospitaliser de Recherche Clinique (PHRC) AOM08198., Association pour l'Information et la Recherche sur les maladies rénales Génétiques., The French Society of Nephrology., A grant from Appel d'Offre de Recherche Clinique (AORC) 2011-A01347., Assistance Publique-Hôpitaux de Marseille (AP-HM)-PHRC grant 2012-A00217-36., ANR-15-CE15-0001,INFLACOMP,Inflammation et lésions endothéliales induites par le Complément et l'hémolyse(2015), European Project, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Lille Inflammation Research International Center (LIRIC), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Médecine interne et immunologie clinique [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Service de Néphrologie, Dialyse et Transplantation (Hôpital Lapeyronie [Montpellier] CHU), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Bioingénierie tissulaire (BIOTIS), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immunologie [HEGP, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), 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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-École pratique des hautes études (EPHE), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Sorbonne Universités, Université Paris Descartes - Paris 5 (UPD5), The research was supported by grants from theAgence Nationale de la Recherche (ANR) JCJC–INFLACOMP2015–2018 (ANR-15-CE15-0001, to L.T.R.), INSERM (toL.T.R.), EU FP7 grant 2012–305608 (EURenOmics, to V.F.-B.), Assistance Publique-Hôpitaux de Paris (AP-HP)-Programme Hospitaliser de Recherche Clinique (PHRC)AOM08198 (to V.F.-B.), Association pour l'Information et laRecherche sur les maladies rénales Génétiques (AIRG) (toV.F.-B.), the French Society of Nephrology (to V.F.-B.), a grantfrom Appel d'Offre de Recherche Clinique (AORC) 2011-A01347 (to G.K.), and Assistance Publique-Hôpitaux deMarseille (AP-HM)-PHRC grant 2012-A00217-36 (to G.K.)., Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacologie [Rouen], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Le Bihan, Sylvie, Inflammation et lésions endothéliales induites par le Complément et l'hémolyse - - INFLACOMP2015 - ANR-15-CE15-0001 - AAPG2015 - VALID, and EU FP7 grant 2012–305608 - INCOMING
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, Endothelium, Angiogenesis, [SDV]Life Sciences [q-bio], TO-MESENCHYMAL TRANSITION, 030232 urology & nephrology, Kidney, urologic and male genital diseases, ANTIBODY-MEDIATED REJECTION, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, COMPLEMENT FACTOR-H, Podocyte, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Renal fibrosis, Medicine, Humans, DONOR-SPECIFIC ANTIBODIES, PROTEASE-ACTIVATED RECEPTOR-2, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, ANTIENDOTHELIAL CELL ANTIBODIES, Endothelial Cells, NEUTROPHIL EXTRACELLULAR TRAPS, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Nephrology, Renal physiology, Glomerular Filtration Barrier, cardiovascular system, HEMOLYTIC-UREMIC SYNDROME, Kidney Diseases, RENAL VASCULAR DYSFUNCTION, business, GROWTH-FACTOR RECEPTOR, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease
Abstract: International audience; The kidney harbours different types of endothelia, each with specific structural and functional characteristics. The glomerular endothelium, which is highly fenestrated and covered by a rich glycocalyx, participates in the sieving properties of the glomerular filtration barrier and in the maintenance of podocyte structure. The microvascular endothelium in peritubular capillaries, which is also fenestrated, transports reabsorbed components and participates in epithelial cell function. The endothelium of large and small vessels supports the renal vasculature. These renal endothelia are protected by regulators of thrombosis, inflammation and complement, but endothelial injury (for example, induced by toxins, antibodies, immune cells or inflammatory cytokines) or defects in factors that provide endothelial protection (for example, regulators of complement or angiogenesis) can lead to acute or chronic renal injury. Moreover, renal endothelial cells can transition towards a mesenchymal phenotype, favouring renal fibrosis and the development of chronic kidney disease. Thus, the renal endothelium is both a target and a driver of kidney and systemic cardiovascular complications. Emerging therapeutic strategies that target the renal endothelium may lead to improved outcomes for both rare and common renal diseases.
Published: 2019
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83. Co-expression network analysis identifies gonad- and embryo-associated protein modules in the sentinel species Gammarus fossarum

Author: Arnaud Chaumot, Marc-Antoine Guery, Christine Almunia, Natacha Koenig, Jean Armengaud, D Degli Esposti, Olivier Geffard, RiverLy (UR Riverly), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Institut National de la Recherche Agronomique (INRA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut Carnot 'Risque' initiative, ANR program PROTEOGAM : ANR-14-CE21-0006-02, ANR-14-CE21-0006,ProteoGam,Protéomique pour de nouveaux biomarqueurs en écotoxicologie chez les gammares: challenge de la biodiversité et immunoanalyse multiplexée comme outil de diagnostic(2014), Laboratoire Innovations technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay, Laboratoire Innovations technologiques pour la Détection et le Diagnostic (Li2D), Service de Pharmacologie et Immunoanalyse (SPI), and Partenaires INRAE
Subjects: Male, Proteomics, 0301 basic medicine, [SDV]Life Sciences [q-bio], Ecophysiology, RNA Splicing, Systems biology, ved/biology.organism_classification_rank.species, lcsh:Medicine, Computational biology, Genome, Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Gammarus, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], TOOL, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, SPERMATOGENESIS, Amphipoda, Protein Interaction Maps, lcsh:Science, Gonads, Model organism, Gene, Multidisciplinary, biology, ved/biology, Reproduction, lcsh:R, Gene Expression Regulation, Developmental, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, biology.organism_classification, CAGED GAMMARUS, Protein-protein interaction networks, 030104 developmental biology, CRUSTACEA, RNA editing, CELLS, Sentinel Species, Proteome, [SDE]Environmental Sciences, lcsh:Q, Female, 030217 neurology & neurosurgery
Abstract: Next generation sequencing and mass spectrometry technologies have recently expanded the availability of whole transcriptomes and proteomes beyond classical model organisms in molecular biology, even in absence of an annotated genome. However, the fragmented nature of transcriptomic and proteomic data reduces the ability to interpret the data, notably in non-model organisms. Network-based approaches may help extracting important biological information from -omics datasets. The reproductive cycle of the freshwater crustacean Gammarus fossarum.provides an excellent case study to test the relevance of a network analysis in non-model organisms. Here, we illustrated how the use of a co-expression network analysis (based on Weighted Gene Co-expression Network Analysis algorithm, WGCNA) allowed identifying protein modules whose expression profiles described germ cell maturation and embryonic development in the freshwater crustacean Gammarus fossarum. Proteome datasets included testes, ovaries or embryos samples at different maturation or developmental stages, respectively. We identified an embryonic module correlated with mid-developmental stages corresponding to the organogenesis and it was characterized by enrichment in proteins involved in RNA editing and splicing. An ovarian module was enriched in vitellogenin-like proteins and clottable proteins, confirming the diversity of proteins belonging to the large lipid transfer family involved in oocytes maturations in this freshwater amphipod. Moreover, our results found evidence of a fine-tuned regulation between energy production by glycolysis and actin-myosin-dependent events in G. fossarum spermatogenesis. This study illustrates the importance of applying systems biology approaches to emergent animal models to improve the understanding of the molecular mechanisms regulating important physiological events with ecological relevance.
Published: 2019
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84. Guest editor's personal foreword

Author: François Fenaille, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris Saclay (COmUE), Service de Pharmacologie et d'Immunoanalyse (SPI), and Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
Subjects: [SDV]Life Sciences [q-bio], 010401 analytical chemistry, MEDLINE, Library science, General Medicine, 010402 general chemistry, 01 natural sciences, Atomic and Molecular Physics, and Optics, 0104 chemical sciences, former students, scientific articles, Sociology, Spectroscopy, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019
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85. Optimization of the treatment with beta-lactam antibiotics in critically ill patients—guidelines from the French Society of Pharmacology and Therapeutics (Société Française de Pharmacologie et Thérapeutique—SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d’Anesthésie et Réanimation—SFAR)

Author: Guilhaumou, Romain, Benaboud, Sihem, BENNIS, YOUSSEF, Dahyot-Fizelier, Claire, Dailly, Eric, Gandia, Peggy, Goutelle, Sylvain, Lefeuvre, Sandrine, Mongardon, Nicolas, Roger, Claire, Scala-Bertola, Julien, Lemaitre, Florian, Garnier, Marc, CHU Marseille, Service de Pharmacologie Clinique [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Département de Pharmacologie Clinique [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Toulouse [Toulouse], Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Pharmacologie Clinique et Toxicologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Evaluation thérapeutique et pharmacologie périnatale et pédiatrique (EA_7323), Université Paris Descartes - Paris 5 (UPD5), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), 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), Microbiotes, Hôtes, Antibiotiques et Résistances bactériennes (MiHAR) (MiHAR), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Pharmacocinétique et de Toxicologie clinique [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Structure Interne de Génétique, Pôle de Biopathologie, Service d'anesthésie-réanimation SAMU94-SMUR94 [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité de réanimation médicale [CHU de Carémeau, Nîmes], Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Service d'anesthésie et réanimation [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP]-Sorbonne Université (SU), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-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, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Institut Fédératif de Biologie (IFB)
Subjects: Continuous infusion, Societies, Pharmaceutical, Critical Illness, Guidelines as Topic, Review, Therapeutic drug monitoring, beta-Lactamases, Dosage, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Drug Dosage Calculations, Pharmacokinetics, Serum Albumin, Societies, Medical, ComputingMilieux_MISCELLANEOUS, lcsh:Medical emergencies. Critical care. Intensive care. First aid, lcsh:RC86-88.9, Anti-Bacterial Agents, Beta-lactam antibiotics, Intensive Care Units, Treatment Outcome, Pharmacodynamics, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, France, Drug Monitoring, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Glomerular Filtration Rate
Abstract: Background Beta-lactam antibiotics (βLA) are the most commonly used antibiotics in the intensive care unit (ICU). ICU patients present many pathophysiological features that cause pharmacokinetic (PK) and pharmacodynamic (PD) specificities, leading to the risk of underdosage. The French Society of Pharmacology and Therapeutics (SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (SFAR) have joined forces to provide guidelines on the optimization of beta-lactam treatment in ICU patients. Methods A consensus committee of 18 experts from the two societies had the mission of producing these guidelines. The entire process was conducted independently of any industry funding. A list of questions formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes) was drawn-up by the experts. Then, two bibliographic experts analysed the literature published since January 2000 using predefined keywords according to PRISMA recommendations. The quality of the data identified from the literature was assessed using the GRADE® methodology. Due to the lack of powerful studies having used mortality as main judgement criteria, it was decided, before drafting the recommendations, to formulate only “optional” recommendations. Results After two rounds of rating and one amendment, a strong agreement was reached by the SFPT-SFAR guideline panel for 21 optional recommendations and a recapitulative algorithm for care covering four areas: (i) pharmacokinetic variability, (ii) PK-PD relationship, (iii) administration modalities, and (iv) therapeutic drug monitoring (TDM). The most important recommendations regarding βLA administration in ICU patients concerned (i) the consideration of the many sources of PK variability in this population; (ii) the definition of free plasma concentration between four and eight times the Minimal Inhibitory Concentration (MIC) of the causative bacteria for 100% of the dosing interval as PK-PD target to maximize bacteriological and clinical responses; (iii) the use of continuous or prolonged administration of βLA in the most severe patients, in case of high MIC bacteria and in case of lower respiratory tract infection to improve clinical cure; and (iv) the use of TDM to improve PK-PD target achievement. Conclusions The experts strongly suggest the use of personalized dosing, continuous or prolonged infusion and therapeutic drug monitoring when administering βLA in critically ill patients. Electronic supplementary material The online version of this article (10.1186/s13054-019-2378-9) contains supplementary material, which is available to authorized users.
Published: 2019
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86. Exploring the microvascular impact of red blood cell transfusion in intensive care unit patients

Author: Bertrand Guidet, Simon Bourcier, Geoffroy Hariri, Jeremy Bellien, Hafid Ait-Oufella, Dominique Charue, Naïke Bigé, Thomas Duflot, Jean-Luc Baudel, Eric Maury, Jean-Rémi Lavillegrand, Mohamad Mohty, Jérémie Lemarié, Zora Marjanovic, Jérémie Joffre, Olivier Blanc-Brude, Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Sorbonne Université (SU), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de pharmacologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), 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)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (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), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Service de pharmacologie [CHU Rouen]
Subjects: Male, medicine.medical_specialty, Endothelium, Bilirubin, Vasodilation, Microparticles, Critical Care and Intensive Care Medicine, Red blood cells, Gastroenterology, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, law, Internal medicine, medicine, Humans, Platelet, Prospective Studies, Aged, Aged, 80 and over, Simplified Acute Physiology Score, business.industry, Research, Transfusion, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, lcsh:RC86-88.9, Middle Aged, Intensive care unit, 3. Good health, Red blood cell, Intensive Care Units, medicine.anatomical_structure, chemistry, ROC Curve, SAPS II, Area Under Curve, Microvessels, Arachidonic acid, Female, business, Erythrocyte Transfusion, Vascular reactivity
Abstract: Background Red blood cell (RBC) transfusion is a common treatment for hospitalized patients. However, the effects of RBC transfusion on microvascular function remain controversial. Methods In a medical ICU in a tertiary teaching hospital, we prospectively included anemic patients requiring RBC transfusion. Skin microvascular reactivity was measured before and 30 min after RBC transfusion. Plasma was collected to analyze intravascular hemolysis and draw the lipidomic and cytokine profiles. Results In a cohort of 59 patients, the median age was 66 [55–81] years and SAPS II was 38 [24–48]. After RBC transfusion, endothelium-dependent microvascular reactivity improved in 35 (59%) patients, but worsened in 24 others (41%). Comparing clinical and biological markers revealed that baseline blood leucokyte counts distinguished improving from worsening patients (10.3 [5.7; 19.7] vs. 4.6 [2.1; 7.3] × 109/L; p = 0.001) and correlated with variations of microvascular reactivity (r = 0.36, p = 0.005). Blood platelet count was also higher in improving patients (200 [97; 280] vs 160 [40; 199] × 103/mL, p = 0.03) but did not correlate with variations of microvascular reactivity. We observed no intravascular hemolysis (HbCO, heme, bilirubin, LDH), but recorded a significant increase in RBC microparticle levels specific to improving patients after transfusion (292 [108; 531] vs. 53 [34; 99] MP/μL; p = 0.03). The improvement in microvascular dilation was positively correlated with RBC microparticle levels (R = 0.83, p
Published: 2019
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87. Metabolomics using Fourier transform mass spectrometry

Author: Christophe Junot, François Fenaille, Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, French Atomic Energy Commission, Ministry of Research, France European Commission, Philippe Schmitt-Kopplin, Basem Kanawati, ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Annotation, Phase Liquid-chromatography, Gas-chromatography, 01 natural sciences, Fourier transform ion cyclotron resonance, Plasma, 03 medical and health sciences, Biological condition, Metabolomics, Peak Alignment, Metabolite Identification, Metabolome, Biological media, [CHIM]Chemical Sciences, 030304 developmental biology, 0303 health sciences, Profiling Procedures, Molecular mass, Chemistry, Discriminating Signals, 010401 analytical chemistry, 0104 chemical sciences, Characterization (materials science), Metabolite profiling, Hplc-ms, Biological system, Retention Time
Abstract: Chapter 11; International audience; The metabolome is the set of small molecular mass compounds found in biological media, and metabolomics, which refers to as the analysis of metabolome in a given biological condition, deals with the large scale detection and quantification of metabolites in biological media. The metabolome is characterized by a large number of molecules exhibiting a high diversity of chemical structures and abundances, requiring complementary analytical platforms for extensive coverage. Among them, atmospheric pressure ionization Fourier transform mass spectrometry (FT/MS) instruments are now very popular because they provide accurate mass measurements with ppm and even sub-ppm errors, high and ultra-high resolving power, and also the possibility to perform MSn experiments for annotation and identification of metabolites.This chapter deals with the improvements provided by the different kinds of FT/MS instruments for metabolomics, together with their ability to cover the various analytical needs for metabolomics, from global metabolite profiling to structural characterization of compounds. The specificities of FT/MS in terms of data pre-processing and the input of accurate mass measurements for biological interpretation are also addressed.
Published: 2019
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88. Hematologic Complications of Immune Checkpoint Inhibitors

Author: Douglas B. Johnson, Arissa Young, Joe-Elie Salem, P. Brent Ferrell, Elizabeth J. Davis, Bénédicte Lebrun-Vignes, Javid Moslehi, Jennifer R. Green, Kristin K. Ancell, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, 0301 basic medicine, Oncology, Hemolytic anemia, Adult, Male, Cancer Research, medicine.medical_specialty, Side effect, Databases, Factual, Programmed Cell Death 1 Receptor, Pure red cell aplasia, Ipilimumab, Antibodies, Monoclonal, Humanized, B7-H1 Antigen, 03 medical and health sciences, Pharmacovigilance, 0302 clinical medicine, Antineoplastic Agents, Immunological, Risk Factors, Internal medicine, Neoplasms, medicine, Adverse Drug Reaction Reporting Systems, Humans, Aplastic anemia, Aged, Aged, 80 and over, Hemophagocytic lymphohistiocytosis, business.industry, Incidence, Immune‐Related Adverse Events, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, Thrombocytopenic purpura, Hematologic Diseases, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, business, medicine.drug
Abstract: Immune checkpoint inhibitors (ICIs) have improved outcomes for patients with cancer but related hematologic toxicities have been poorly described. Using VigiBase, the World Health Organization's pharmacovigilance database of individual case safety reports of adverse drug reactions, this study aimed to identify such cases of hematologic toxicities., Immune checkpoint inhibitors have improved outcomes for patients with numerous hematological and solid cancers. Hematologic toxicities have been described, but the spectrum, timing, and clinical presentation of these complications are not well understood. We used the World Health Organization's pharmacovigilance database of individual‐case‐safety‐reports (ICSRs) of adverse drug reactions, VigiBase, to identify cases of hematologic toxicities complicating immune checkpoint inhibitor therapy. We identified 168 ICSRs of immune thrombocytopenic purpura (ITP), hemolytic anemia (HA), hemophagocytic lymphohistiocytosis, aplastic anemia, and pure red cell aplasia in 164 ICSRs. ITP (n = 68) and HA (n = 57) were the most common of these toxicities and occurred concomitantly in four patients. These events occurred early on treatment (median 40 days) and were associated with fatal outcome in 12% of cases. Ipilimumab‐based therapy (monotherapy or combination with anti‐programmed death‐1 [PD‐1]) was associated with earlier onset (median 23 vs. 47.5 days, p = .006) than anti‐PD‐1/programmed death ligand‐1 monotherapy. Reporting of hematologic toxicities has increased over the past 2 years (98 cases between January 2017 and March 2018 vs. 70 cases before 2017), possibly because of increased use of checkpoint inhibitors and improved recognition of toxicities. Future studies should evaluate incidence of hematologic toxicities, elucidate risk factors, and determine the most effective treatment algorithms. Key Points. Immune‐mediated hematologic toxicities are a potential side effect of immune checkpoint inhibitors (ICIs).Providers should monitor complete blood counts during treatment with ICIs.Corticosteroids are the mainstay of treatment for immune‐mediated hematologic toxicities.Further research is needed to define patient‐specific risk factors and optimal management strategies for hematologic toxicities.
Published: 2019
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89. Drug‐induced aseptic meningitis: 329 cases from the French pharmacovigilance database analysis

Author: Bénédicte Lebrun-Vignes, Kevin Bihan, Nicolas Weiss, Christian Funck-Brentano, Hélène Théophile, Service de Pharmacologie médicale [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), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU), 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), Département Hospitalo-Universitaire de Pharmacologie de Bordeaux, CHU de Bordeaux Pellegrin [Bordeaux]-Université Victor Segalen - Bordeaux 2, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de neurologie 1 [CHU Pitié-Salpétrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Male, Databases, Factual, Antimetabolites, Database analysis, Intrathecal, 030226 pharmacology & pharmacy, Pharmacovigilance, 0302 clinical medicine, Anti-Infective Agents, Pharmacology (medical), 030212 general & internal medicine, Meningitis, Aseptic, Injections, Spinal, Vaccines, Anti-Inflammatory Agents, Non-Steroidal, Aseptic meningitis, Immunoglobulins, Intravenous, meningitis, Middle Aged, 3. Good health, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], France, Meningitis, pharmacoviglance, Adult, medicine.medical_specialty, Drug-induced aseptic meningitis, 03 medical and health sciences, Young Adult, Internal medicine, adverse effect, medicine, Adverse Drug Reaction Reporting Systems, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adverse effect, Glucocorticoids, Anesthetics, Pharmacology, business.industry, Original Articles, medicine.disease, drug-induced, aseptic meningitis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Adverse drug reaction
Abstract: International audience; AIMS: Drug-induced aseptic meningitis (DIAM) is an adverse drug reaction of exclusion; only few studies have addressed this iatrogenic disease. The aim was to characterize DIAM and to identify suspected drugs.METHODS: Data were collected from the analysis of the French Pharmacovigilance Database from inception (1 January 1985) to 8 March 2017. All cases were initially analysed according to the French imputability method by institutional pharmacologists (clinicians or pharmacists). Further analyses of well documented cases were then performed.RESULTS: In this study, 329 cases of aseptic meningitis were retrieved from the French Pharmacovigilance Database for a total of 429 suspected drugs. Analysis of 203 well documented cases, including 282 drugs, showed that the main reported classes were intravenous polyvalent immunoglobulin, nonsteroidal anti-inflammatory drugs (NSAIDs), vaccines, antimicrobials, intrathecal antimetabolites, corticosteroids and antalgics/anaesthetics (except NSAIDs). Lymphocytic (33.0%) and purulent (44.8%) meningitis represented the majority of cases of aseptic meningitis. In other cases, the cerebrospinal fluid was mixed (45-55% of neutrophils +45-55% of lymphocytes) or data about cerebrospinal fluid composition were lacking. Most DIAM cases (96%) had a favourable reported outcome with full recovery or minimal residual symptoms.CONCLUSION: The most frequently involved drugs in DIAM were intravenous polyvalent immunoglobulin, NSAIDs, vaccines, and antimicrobials and this without being able to differentiate them in terms of biological characteristics. Although further studies are needed to better understand the pathophysiological mechanisms of DIAM, a continuous enrichment of pharmacovigilance databases is essential to identify new signals and to help clinicians in the understanding of DIAM.
Published: 2019
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90. Les biomarqueurs de l’intoxication par l’ypérite

Author: Christophe Piérard, Nicolas Taudon, François Fenaille, Thierry DOUKI, Institut de Recherche Biomédicale des Armées (IRBA), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Département Interfaces pour l'énergie, la Santé et l'Environnement (DIESE), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Douki, Thierry, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)
Subjects: ADN, menace chimique, protéines, DNA, Sulfur mustard, glutathione, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], glutathion, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], metabolomics, chemical threat, proteins, métabolomique
Abstract: Sulfur mustard is a chemical warfare agent that damages the eyes, lungs and skin. In the latter, it induces severeburns that classify it as vesicant agents. Highly reactive, sulfur mustard has the ability to alkylate many biomolecules.The products derived from these reactions can be used, mainly using analytical chemistry methods, as biomarkersof exposure or effect. Sulfur mustard also greatly disrupts metabolism and protein induction. These responsescan be used to highlight longer-term effects., L’ypérite est un toxique de guerre endommageant les yeux, les poumons et la peau. Dans cette dernière, elle induitde graves brûlures qui la classent parmi les agents vésicants. Très réactive, elle possède des capacités d’alkylationde nombreuses biomolécules. Les produits qui en dérivent peuvent être utilisés, principalement en employantdes méthodes de chimie analytique, comme biomarqueurs d’exposition ou d’effet. L’ypérite perturbe égalementfortement le métabolisme et l’induction de protéines. Ces réponses sont utilisables pour mettre en évidencedes effets à plus long terme.
Published: 2019

91. Comparison of e‐cigarette use characteristics between exclusive e‐cigarette users and dual e‐cigarette and conventional cigarette users: an on‐line survey in France

Author: Remi Targhetta, Bertrand Nalpas, Pascal Perney, Ivan Berlin, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM), Santé mentale et santé publique (SMSP - U1178), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_treatment, 030508 substance abuse, Medicine (miscellaneous), Cigarette use, Nicotine, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Medicine, 030212 general & internal medicine, business.industry, Cross-sectional on-line survey, Odds ratio, Stepwise regression, nicotine intake from electronic cigarette, Confidence interval, 3. Good health, electronic cigarette only users, smoking cessation, Psychiatry and Mental health, Standard error, Dual users, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Smoking cessation, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, 0305 other medical science, business, Demography, medicine.drug
Abstract: International audience; Background and aims: Completely substituting e-cigarettes (EC) for combustible tobacco cigarettes reduces exposure to toxicants and carcinogens. However, a large proportion of EC users (dual users) continue to smoke conventional cigarettes. This study aimed to compare estimated nicotine intake and e-cigarette use characteristics between exclusive EC users and dual users.Design: Web-based anonymous cross-sectional survey.Setting: France.Participants: A total of 3189 adults, current users of electronic cigarettes (EC). Data collection between 4 October 2014 and 11 November 2014.Measurements: Primary outcome: estimated nicotine intake per day (mg) from participants' reports.Secondary outcomes: duration, frequency of EC use and nicotine content of e-liquids used/day. Dual use was defined as using at least one cigarette per day while also using EC.Findings: A total of 2836 respondents reported exclusive EC use and 353 reported being dual users. Backward stepwise logistic regression showed that dual users had higher estimated combined daily nicotine intake from e-liquids and cigarettes [estimate: 2.14, standard error (SE) = 0.26, adjusted odds ratio (aOR) = 8.48, 95% confidence interval (CI) = 5.11-14.09, P < 0.001], but lower daily nicotine intake from EC (estimate: -2.14, SE = 0.26, aOR = 0.12, CI = 0.07-0.196, P < 0.001) and reported fewer months of EC use (estimate: -0.31, SE = 0.14, aOR = 0.73, CI = 0.56-0.95, P = 0.022) compared with exclusive EC users.Conclusion: Dual e-cigarette users in France may have higher nicotine intake overall than exclusive e-cigarette users, but they may take in less nicotine from their e-cigarettes.
Published: 2019
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92. Multi-omics signature of brain amyloid deposition in asymptomatic individuals at-risk for Alzheimer's disease: The INSIGHT-preAD study

Author: Gaëlle Fontaine, Marie Lhomme, Arthur Tenenhaus, Stéphane Epelbaum, Laura Xicota, Inka Leroy, Marie-Claude Potier, François-Xavier Lejeune, Farid Ichou, Benoit Colsch, Bruno Dubois, Hugo Bertin, Marie-Odile Habert, Fanny Mochel, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), CentraleSupélec, Université Paris-Saclay, Centre d'Acquisition et de Traitement des Images [Paris], Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre des Maladies Cognitives et Comportementales [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), AvidFondation AlzheimerThis study was supported by INSERM in collaboration with Institut du Cerveau et de la Moelle Épinière (ICM), Institut Hospitalo-Universitaire-A ICM, and Pfizer, and was supported with funding from Pfizer and the Investissement d'Avenir (ANR-10-AIHU-06) that was used for the recruitment of clinical research assistants, neuropsychologists, and a study physician, ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Laboratoire d'Etude du Métabolisme des Médicaments (LEMM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Avid, Fondation Alzheimer, This study was supported by INSERM in collaboration with Institut du Cerveau et de la Moelle Épinière (ICM), Institut Hospitalo-Universitaire-A ICM, and Pfizer, and was supported with funding from Pfizer and the Investissement d'Avenir (ANR-10-AIHU-06) that was used for the recruitment of clinical research assistants, neuropsychologists, and a study physician, ANR-10-IAIHU-06,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2011), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), CEA Paris Saclay, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Sud - Paris 11 (UP11), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Potier, Marie-Claude, Unité Matériaux et Transformations - UMR 8207 (UMET), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Institut National de la Recherche Agronomique (INRA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), sans affiliation, Pfizer, Institut Hospitalo-Universitaire and Institut du Cerveau et de la Moelle Epiniere (IHU-A-ICM), Ministry of Research, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Gestionnaire, Hal Sorbonne Université, and Institut de Neurosciences Translationnelles de Paris - - IHU-A-ICM2010 - ANR-10-IAHU-0006 - IAHU - VALID
Subjects: 0301 basic medicine, Oncology, Male, Proteomics, Research paper, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 0302 clinical medicine, [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], 050207 economics, Aged, 80 and over, Univariate analysis, [STAT.AP]Statistics [stat]/Applications [stat.AP], Multi-omics, 050208 finance, 05 social sciences, Brain, General Medicine, Genomics, 3. Good health, Asymptomatic, 030220 oncology & carcinogenesis, Area Under Curve, Cohort, Female, medicine.symptom, [STAT.ME]Statistics [stat]/Methodology [stat.ME], medicine.medical_specialty, Amyloid, Protein Aggregation, Pathological, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Metabolomics, Alzheimer Disease, Internal medicine, Lipidomics, 0502 economics and business, medicine, Humans, Alzheimer, Amyloid PET, Biomarkers, Prediction, Aged, Amyloid beta-Peptides, Receiver operating characteristic, business.industry, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Omics, 030104 developmental biology, Case-Control Studies, business
Abstract: International audience; BACKGROUND: One of the biggest challenge in Alzheimer's disease (AD) is to identify pathways and markers of disease prediction easily accessible, for prevention and treatment. Here we analysed blood samples from the INveStIGation of AlzHeimer's predicTors (INSIGHT-preAD) cohort of elderly asymptomatic individuals with and without brain amyloid load.METHODS: We performed blood RNAseq, and plasma metabolomics and lipidomics using liquid chromatography-mass spectrometry on 48 individuals amyloid positive and 48 amyloid negative (SUVr cut-off of 0·7918). The three data sets were analysed separately using differential gene expression based on negative binomial distribution, non-parametric (Wilcoxon) and parametric (correlation-adjusted Student't) tests. Data integration was conducted using sparse partial least squares-discriminant and principal component analyses. Bootstrap-selected top-ten features from the three data sets were tested for their discriminant power using Receiver Operating Characteristic curve. Longitudinal metabolomic analysis was carried out on a subset of 22 subjects.FINDINGS: Univariate analyses identified three medium chain fatty acids, 4-nitrophenol and a set of 64 transcripts enriched for inflammation and fatty acid metabolism differentially quantified in amyloid positive and negative subjects. Importantly, the amounts of the three medium chain fatty acids were correlated over time in a subset of 22 subjects (p
Published: 2019
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93. Shotgun proteomics datasets acquired on Gammarus pulex animals sampled from the wild

Author: Gouveia, Duarte, Cogne, Yannick, Gaillard, Jean-Charles, Almunia, Christine, Pible, Olivier, François, ADELINE, Degli Esposti, Davide, Olivier, Geffard, Chaumot, Arnaud, Armengaud, J., Laboratoire Innovations technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), RiverLy (UR Riverly), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Institut National de Recherche en Sciences et Technologies pour l'Environnement et l'Agriculture (France), Commissariat a l'Energie Atomique et aux Energies Alternatives (France), ANR-14-CE21-0006,ProteoGam,Protéomique pour de nouveaux biomarqueurs en écotoxicologie chez les gammares: challenge de la biodiversité et immunoanalyse multiplexée comme outil de diagnostic(2014), LABORATOIRE INNOVATIONS TECHNOLOGIQUES POUR LA DETECTION ET LE DIAGNOSTIC LI2D SERVICE DE PHARMACOLOGIE ET IMMUNOANALYSE SPI CEA INRA BAGNOLS SUR CEZE FRA, IRSTEA LYON UR RIVERLY FRA, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Médicaments et Technologies pour la Santé (MTS), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay
Subjects: Proteomics, TOXICITE, [SDV]Life Sciences [q-bio], Cadmium contamination, GAMMARUS, toxicity, Sentinel animal, Amphipods, lcsh:Computer applications to medicine. Medical informatics, Ecotoxicology, proteins, CADMIUM, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], PROTEINE, [SDE]Environmental Sciences, lcsh:R858-859.7, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Intrapopulation variability, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, lcsh:Science (General), lcsh:Q1-390
Abstract: [Departement_IRSTEA]Eaux [TR1_IRSTEA]BELCA [ADD1_IRSTEA]Systèmes aquatiques soumis à des pressions multiples [Departement_IRSTEA]Eaux [TR1_IRSTEA]BELCA [ADD1_IRSTEA]Systèmes aquatiques soumis à des pressions multiples; International audience; This data article associated with the manuscript "Comparative proteomics in the wild: accounting for intrapopulation variability improves describing proteome response in a Gammarus pulex field population exposed to cadmium" refers to the shotgun proteomics analysis performed on 40 Gammarus pulex animals sampled from the wild. Proteins were extracted, digested with trypsin, and the resulting peptides were identified by tandem mass spectrometry. Here, we present the list of proteins from males and the list of proteins from females that are differentially detected between the Brameloup and the Pollon populations. Data are available via ProteomeXchange with identifiers PXD013656 and PXD013712, respectively.
Published: 2019
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94. Développement de matériaux poreux hybrides innovants pour l'analyse glycomique

Author: Maleval, M, Mayne-L'Hermite, M., Fenaille, F, Mugherli, L, Palacin, Serge, Laboratoire Edifices Nanométriques (LEDNA), Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M) (NIMBE UMR 3685), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Service de Pharmacologie et d'Immunoanalyse (SPI), and Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
Subjects: [CHIM.MATE] Chemical Sciences/Material chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry
Abstract: International audience; L'analyse glycomique consiste à établir le profil des oligosaccharides présents sur l'ensemble des glycoprotéines d'un fluide biologique d'intérêt (ex : plasma) . Cependant, la préparation des échantillons implique de nombreuses étapes souvent manuelles, très chronophages et peu compatibles avec l'analyse à haut débit des échantillons. Les matériaux préparés selon le procédé sol-gel, par leur grande adaptabilité en terme de porosité et de propriétés physico-chimiques, ont montré qu'ils pouvaient être utilisés pour une grande variété d'applications tels que la détection (capteurs) ou la capture de molécules d'intérêt , notamment dans le domaine biomédical. Dans cette optique, nous développons des matériaux à porosité bimodale pour faciliter et accélérer la préparation des échantillons dédiés à l'analyse glycomique. Les premiers résultats obtenus seront présentés, en particulier le procédé de synthèse, les modulations possibles des matériaux (microstructure et porosité) ainsi que la caractérisation de leurs propriétés texturales et microstructurales. Enfin, quelques résultats prometteurs obtenus à l'aide de ces matériaux sur des échantillons biologiquement pertinents seront également présentés.
Published: 2019

95. Comprehensive preterm breast milk metabotype associated with optimal infant early growth pattern

Author: Marie-Cécile Alexandre-Gouabau, Sophie Cholet, Agnès David-Sochard, Dominique Darmaun, Thomas Moyon, Yann Guitton, Clair-Yves Boquien, Anne-Lise Royer, François Fenaille, Hélène Billard, Jean-Christophe Rozé, Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut National de la Recherche Agronomique (INRA), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), European Milk Bank Association [Milan, Italie] (EMBA), Alexandre-Gouabau, Marie Cécile, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)
Subjects: 0301 basic medicine, Médecine humaine et pathologie, Physiology, lcsh:TX341-641, Breast milk, preterm infant, 03 medical and health sciences, chemistry.chemical_compound, lipidome, growth trajectory, breast milk metabolome, Metabolome, Food and Nutrition, Choline, Medicine, glycome, 2. Zero hunger, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Confounding, food and beverages, Lipidome, 3. Good health, free amino acid, 030104 developmental biology, chemistry, Alimentation et Nutrition, Cohort, Gestation, Population study, Human health and pathology, business, 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: Early nutrition impacts preterm infant early growth rate and brain development but can have long lasting effects as well. Although human milk is the gold standard for feeding new born full-term and preterm infants, little is known about the effects of its bioactive compounds on breastfed preterm infants&rsquo, growth outcomes. This study aims to determine whether breast milk metabolome, glycome, lipidome, and free-amino acids profiles analyzed by liquid chromatography-mass spectrometry had any impact on the early growth pattern of preterm infants. The study population consisted of the top tercile-Z score change in their weight between birth and hospital discharge (&ldquo, faster grow&rdquo, n = 11) and lowest tercile (&ldquo, slower grow&rdquo, n = 15) from a cohort of 138 premature infants (27&ndash, 34 weeks gestation). This holistic approach combined with stringent clustering or classification statistical methods aims to discriminate groups of milks phenotype and identify specific metabolites associated with early growth of preterm infants. Their predictive reliability as biomarkers of infant growth was assessed using multiple linear regression and taking into account confounding clinical factors. Breast-milk associated with fast growth contained more branched-chain and insulino-trophic amino acid, lacto-N-fucopentaose, choline, and hydroxybutyrate, pointing to the critical role of energy utilization, protein synthesis, oxidative status, and gut epithelial cell maturity in prematurity.
Published: 2019
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96. MetaboRank: network-based recommendation system to interpret and enrich metabolomics results

Author: Frainay, Clément, Aros, Sandrine, Chazalviel, Maxime, Garcia, Thomas, Vinson, Florence, Weiss, Nicolas, Colsch, Benoit, Sedel, Frédéric, Thabut, Dominique, Junot, Christophe, Jourdan, Fabien, Métabolisme et Xénobiotiques (ToxAlim-MeX), ToxAlim (ToxAlim), 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)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), MedDay Pharmaceuticals, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French Ministry of Research, National Research Agency as part of the French MetaboHUB, European Commission [654241], national metabolomics and fluxomics infrastructure [ANR-INBS-0010], European Project: 654241,H2020,H2020-EINFRA-2014-2,PhenoMeNal(2015), 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-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, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pharmacologie et d'Immunoanalyse (SPI), and Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
Subjects: Systems Biology, [SDV]Life Sciences [q-bio], Computational Biology, Humans, Metabolomics, Original Papers, Mass Spectrometry, Software
Abstract: Motivation Metabolomics has shown great potential to improve the understanding of complex diseases, potentially leading to therapeutic target identification. However, no single analytical method allows monitoring all metabolites in a sample, resulting in incomplete metabolic fingerprints. This incompleteness constitutes a stumbling block to interpretation, raising the need for methods that can enrich those fingerprints. We propose MetaboRank, a new solution inspired by social network recommendation systems for the identification of metabolites potentially related to a metabolic fingerprint. Results MetaboRank method had been used to enrich metabolomics data obtained on cerebrospinal fluid samples from patients suffering from hepatic encephalopathy (HE). MetaboRank successfully recommended metabolites not present in the original fingerprint. The quality of recommendations was evaluated by using literature automatic search, in order to check that recommended metabolites could be related to the disease. Complementary mass spectrometry experiments and raw data analysis were performed to confirm these suggestions. In particular, MetaboRank recommended the overlooked α-ketoglutaramate as a metabolite which should be added to the metabolic fingerprint of HE, thus suggesting that metabolic fingerprints enhancement can provide new insight on complex diseases. Availability and implementation Method is implemented in the MetExplore server and is available at www.metexplore.fr. A tutorial is available at https://metexplore.toulouse.inra.fr/com/tutorials/MetaboRank/2017-MetaboRank.pdf. Supplementary information Supplementary data are available at Bioinformatics online.
Published: 2019
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97. Detection and Quantification of Allergens in Foods and Minimum Eliciting Doses in Food-Allergic Individuals (ThRAll)

Author: Karine Adel-Patient, Anne-Catherine Huet, Rosa Pilolli, Nathalie Gillard, Chiara Nitride, Collette Larré, Olivier Tranquet, Hervé Bernard, Marc De Loose, Linda Monaci, Christof Van Pouke, E. N. Clare Mills, Adel-Patient, Karine, University of Manchester [Manchester], Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Research Institute for Agricultural, Fisheries and Food (ILVO), CER Groupe, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Institute of Sciences of Food Production (ISPA), Consiglio Nazionale delle Ricerche (CNR), Clare Mills, E. N., Adel-Patient, K., Bernard, H., De Loose, M., Gillard, N., Huet, A. -C., Larre, C., Nitride, C., Pilolli, R., Tranquet, O., Pouke, C. V., Monaci, L., Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR)
Subjects: food industry, ThRAll, Food industry, [SDV]Life Sciences [q-bio], Dose-Response Relationship, Immunologic, Food Contamination, 01 natural sciences, Analytical Chemistry, food allergens, 0404 agricultural biotechnology, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Environmental Chemistry, Animals, Humans, Nuts, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Food allergens, Chocolate, ThRAll project, mass spectrometry, 2. Zero hunger, Pharmacology, Food protein, business.industry, 010401 analytical chemistry, digestive, oral, and skin physiology, peptide markers, analytical method, 04 agricultural and veterinary sciences, Allergens, Plants, 040401 food science, 3. Good health, 0104 chemical sciences, Biotechnology, Milk, reference method, Data quality, Food processing, Fast Foods, allergens, food-allergic consumers, business, Agronomy and Crop Science, Food Hypersensitivity, food allergen, Food Science
Abstract: International audience; Risk-based approaches to managing allergens in foods are being developed by the food industry and regulatory authorities to support food-allergic consumers to avoid ingestion of their problem food, especially in relation to the traces of unintended allergens. The application of such approaches requires access to good quality data from clinical studies to support identification of levels of allergens in foods that are generally safe for most food-allergic consumers as well as analytical tools that are able to quantify allergenic food protein. The ThRAll project aims to support the application of risk-based approaches to food-allergen management in two ways. First, a harmonized quantitative MS-based prototype reference method will be developed for the detection of multiple food allergens in standardized incurred food matrices. This will be undertaken for cow’s milk, hen’s egg, peanut, soybean, hazelnut, and almond incurred into two highly processed food matrices, chocolate and broth powder. This activity is complemented by a second objective to support the development and curation of data on oral food challenges, which are used to define thresholds and minimum eliciting doses. This will be achieved through the development of common protocols for collection and curation of data that will be applied to allergenic foods for which there are currently data gaps.
Published: 2019
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98. Atherothrombotic risk stratification after acute myocardial infarction: the TIMI Risk Score for Secondary Prevention (TRS‐2P) in the light of the FAST‐MI registries

Author: Etienne Puymirat, Nadia Aissaoui, Gilles Lemesle, Marc P. Bonaca, Tabassome Simon, Victoria Tea, Francois Schiele, Gregory Ducrocq, Guillaume Cayla, Jean Ferrières, M. Fumery, Nicolas Danchin, Laurent Bonello, 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), Harvard Medical School [Boston] (HMS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Department of Epidemiology, Health Economics and Public Health, UMR 558 INSERM, Université de Toulouse, Centre Hospitalier Universitaire de Toulouse, Hôpital de Rangueil, CHU Toulouse [Toulouse], Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service Epidémiologie clinique et santé publique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Service de Pharmacologie médicale = service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Prémilleux, Annick, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, 0302 clinical medicine, prevention, HOSPITAL MORTALITY, score, 030212 general & internal medicine, Myocardial infarction, Secondary prevention, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Framingham Risk Score, ST elevation, Hazard ratio, General Medicine, Thrombolysis, FAST-MI, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, [SDV] Life Sciences [q-bio], Risk stratification, Cohort, Cardiology, Cardiology and Cardiovascular Medicine, hormones, hormone substitutes, and hormone antagonists, TIMI, endocrine system, medicine.medical_specialty, animal structures, HEART-DISEASE, AMERICAN-COLLEGE, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Intensive care, Internal medicine, acute myocardial infarction, medicine, MANAGEMENT, ASSOCIATION TASK-FORCE, business.industry, ACUTE CORONARY SYNDROMES, medicine.disease, TRENDS, mortality, Confidence interval, Residual risk, PROGNOSTICATION, VORAPAXAR, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background Guidelines recommend using risk stratification tools in acute myocardial infarction (AMI) to assist decision-making. The Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS-2P) has been recently developed to characterize long-term risk in patients with MI. Hypothesis We aimed to assess the TRS-2P in the French Registry of Acute ST Elevation or non-ST elevation MI registries. Methods We used data from three 1-month French registries, conducted 5 years apart, from 2005 to 2015, including 13 130 patients with AMI (52% ST-elevation myocardial infarction [STEMI]). Atherothrombotic risk stratification was performed using the TRS-2P score. Patients were divided in to three categories: G1 (low-risk, TRS-2P = 0/1); G2 (intermediate-risk, TRS-2P = 2); and G3 (high-risk, TRS-2P >= 3). Baseline characteristics and outcomes were analyzed according to TRS-2P categories. Results A total of 12 715 patients (in whom TRS-2P was available) were included. Prevalence of G1, G2, and G3 was 43%, 24%, and 33% respectively. Clinical characteristics and management significantly differed according to TRS-2P categories. TRS-2P successfully defined residual risk of death at 1 year (C-statistic 0.78): 1-year survival was 98% in G1, 94% in G2, and 78.5% in G3 (P < 0.001). Using Cox multivariate analysis, G3 was independently associated with higher risk of death at 1 year (hazard ratio [HR] 4.61; 95% confidence interval [CI]: 3.61-5.89), as G2 (HR 2.08; 95% CI: 1.62-2.65) compared with G1. The score appeared robust and correlated well with mortality in STEMI and NSTEMI populations, as well as in each cohort separately. Conclusions The TRS-2P appears to be a robust risk score, identifying patients at high risk after AMI irrespective of the type of MI and historical period.
Published: 2018
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99. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial

Author: Hang-Phuong Pham, Philippe Seksik, Beatrice Banneville, Olivier Chazouillères, Fabien Pitoiset, Julien Champey, Bruno Fautrel, David Saadoun, Laurent Beaugerie, Valérie Doppler, Patrice Cacoub, Karim El Soufi, Selim Aractingi, Christophe Corpechot, Roberta Lorenzon, David Klatzmann, Michelle Rosenzwajg, Francis Berenbaum, Claude C.A. Bernard, Eric Vicaut, Jérémie Mariau, Elodie Regnier, Joe-Elie Salem, Anne Daguenel-Nguyen, Jérémie Sellam, Arsène Mekinian, Claire Ribet, Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service de Gastroentérologie et nutrition [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Service de rhumatologie [CHU Saint-Antoine], Service d'hépatologie [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], Service de médecine interne [CHU Saint-Antoine], Immunologie - Immunopathologie - Immunothérapeutique (I3), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Service de Pharmacie [CHU Saint Antoine], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Gestionnaire, Hal Sorbonne Université, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Immunologie antivirale systémique et cérébrale, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Thérapie des maladies du muscle strié, Unité de Recherche Clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), ANR-16-RHUS-0001,iMAP,iMAP(2016), Bernard, Claude, Service de biothérapies [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Etude et de Recherche sur le Matériau Bois (LERMAB), Université de Lorraine (UL), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service d'hépatologie [Saint-Antoine], Service de Médecine Interne [CHU Saint-Antoine], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CIC Paris Est, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Adult, Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Immunology, Autoimmune hepatitis, medicine.disease_cause, T-Lymphocytes, Regulatory, General Biochemistry, Genetics and Molecular Biology, Autoimmunity, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Psoriasis, medicine, Immunology and Allergy, Humans, Immunologic Factors, Prospective Studies, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, Ankylosing spondylitis, business.industry, Middle Aged, medicine.disease, Ulcerative colitis, 3. Good health, Clinical trial, [SDV] Life Sciences [q-bio], 030104 developmental biology, Treatment Outcome, Rheumatoid arthritis, Interleukin-2, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, Granulomatosis with polyangiitis
Abstract: ObjectiveRegulatory T cells (Tregs) prevent autoimmunity and control inflammation. Consequently, any autoimmune or inflammatory disease reveals a Treg insufficiency. As low-dose interleukin-2 (ld-IL2) expands and activates Tregs, it has a broad therapeutic potential.AimWe aimed to assess this potential and select diseases for further clinical development by cross-investigating the effects of ld-IL2 in a single clinical trial treating patients with 1 of 11 autoimmune diseases.MethodsWe performed a prospective, open-label, phase I–IIa study in 46 patients with a mild to moderate form of either rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Behcet’s disease, granulomatosis with polyangiitis, Takayasu’s disease, Crohn’s disease, ulcerative colitis, autoimmune hepatitis and sclerosing cholangitis. They all received ld-IL2 (1 million IU/day) for 5 days, followed by fortnightly injections for 6 months. Patients were evaluated by deep immunomonitoring and clinical evaluation.Resultsld-IL2 was well tolerated whatever the disease and the concomitant treatments. Thorough supervised and unsupervised immunomonitoring demonstrated specific Treg expansion and activation in all patients, without effector T cell activation. Indication of potential clinical efficacy was observed.ConclusionThe dose of IL-2 and treatment scheme used selectively activate and expand Tregs and are safe across different diseases and concomitant treatments. This and preliminary indications of clinical efficacy should licence the launch of phase II efficacy trial of ld-IL2 in various autoimmune and inflammatory diseases.Trial registration numberNCT01988506.
Published: 2018
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100. Heat processing of peanut seed enhances the sensitization potential of the major peanut allergen Ara h 6

Author: Stéphane Hazebrouck, Hervé Bernard, Blanche Guillon, Karine Adel-Patient, Marie-Françoise Drumare, Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Paris Saclay (COmUE), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, Food processing, Hot Temperature, Arachis, Food Handling, [SDV]Life Sciences [q-bio], Mutant, in vitro digestion test, medicine.disease_cause, Immunoglobulin E, law.invention, Mice, 0302 clinical medicine, Allergen, law, Research Articles, Sensitization, 2. Zero hunger, Mice, Inbred BALB C, biology, Chemistry, Immunogenicity, food and beverages, medicine.anatomical_structure, Biochemistry, Seeds, Recombinant DNA, Female, lipids (amino acids, peptides, and proteins), Digestion, Research Article, 2S Albumins, Plant, Biotechnology, IgE induction, Allergenicity assessment, 03 medical and health sciences, Ara h 6, Botany, medicine, Animals, Potency, Peanut Hypersensitivity, Antigens, Plant, biochemical phenomena, metabolism, and nutrition, carbohydrates (lipids), Disease Models, Animal, 030104 developmental biology, 030228 respiratory system, biology.protein, Food Science
Abstract: International audience; SCOPE: Processing of food has been shown to impact IgE binding and functionality of food allergens. In the present study, we investigated the impact of heat processing on the sensitization capacity of Ara h 6, a major peanut allergen and one of the most potent elicitors of the allergic reaction. METHODS AND RESULTS: Peanut extracts obtained from raw or heat-processed peanut and some fractions thereof were biochemically and immunochemically characterized. These extracts/fractions, purified Ara h 6 or recombinant Ara h 6 including Ara h 6 mutants lacking disulfide bridges were used in in vitro digestion tests and mouse models of experimental sensitization. Peanut roasting led to the formation of complexes of high molecular weight, notably between Ara h 6 and Ara h 1, which supported the induction of IgE specific to native Ara h 6. On the contrary, a fraction containing free monomeric 2S albumins or purified native Ara h 6 displayed no intrinsic allergenicity. In addition to complex formation, heat denaturation and/or partial destabilization enhanced Ara h 6 immunogenicity and increased its sensitivity to digestion. CONCLUSION: These results suggest that sensitization potency and IgE binding capacity can be supported by different structures, modified and/or produced during food processing in interaction with other food constituents.
Published: 2016
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