Author: "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)" - Searchworks@Jio Institute Digital Library Search Results

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1,435 results on '"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)"'

1. Regression of Q waves and clinical outcomes following primary PCI in anterior STEMI

Author: Mathieu Schaaf, Inesse Boussaha, Claire Jossan, Thomas Bochaton, Sophie Pichot-Lamoureux, Denis Angoulvant, Nathan Mewton, Marc J. Claeys, Michel Ovize, Grégoire Rangé, Yuni de Framond, Olivier Dubreuil, David Garcia Dorado, Gilles Rioufol, CHU Tenon [APHP], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Department of Cardiology, Hospices Civils de Lyon (HCL), Johns Hopkins University School of Medicine [Baltimore], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and 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)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, Myocardial Infarction, Left ventricle remodeling, Stunned myocardium, 030204 cardiovascular system & hematology, Lower risk, Infarct size, QT interval, Ventricular Function, Left, Electrocardiography, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Internal medicine, medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, education, Creatine Kinase, Heart Failure, education.field_of_study, Ejection fraction, biology, Anterior ST-elevation myocardial infarction, business.industry, Percutaneous coronary intervention, Stroke Volume, Q wave regression, medicine.disease, 3. Good health, Heart failure, Conventional PCI, biology.protein, Cardiology, ST Elevation Myocardial Infarction, Creatine kinase, Human medicine, Cardiology and Cardiovascular Medicine, business
Abstract: Background: Pathological Q waves are correlated with infarct size, and Q-wave regression is associated with left ventricular ejection fraction improvement. There are limited data regarding the association of Q-wave regression and clinical outcomes. Our main objective was to assess the association of pathological Q wave evolution after re-perfusion with clinical outcomes after anterior STEMI.Methods: Standard 12-lead electrocardiograms (ECGs) were recorded in 780 anterior STEMI patients treated with primary percutaneous coronary intervention (PCI) from the CIRCUS trial. ECGs were recorded before and 90 min following PCI, as well as at hospitalization discharge and 12 months of follow-up. The number of classic ECG criteria Q waves was scored for each ECG. Patients were classified in the Q wave regression group if they had re-gression of at least one Q wave between the post-PCI, the discharge and/or one year ECGs. Patients were classified in the Q wave persistent group if they had the same number or greater between the post-PCI, the discharge and/ or 1 and one year ECGs. All-cause death and heart failure events were assessed for all patients at one year.Results: There were 323(43%) patients with persistent Q waves (PQ group), 378(49%) patients with Q wave re-gression (RQ group) and 60(8%) patients with non-Q wave MI (NQ group). Infarct size as measured by the peak creatine kinase was significantly greater in the PQ group compared to the RQ and NQ groups (4633 +/- 2784 IU/l vs. 3814 +/- 2595 IU/l vs. 1733 +/- 1583 IU/l respectively, p b 0.0001). At one year, there were 22 deaths (7%) in the PQ-group, 15 (4%) in the RQ-group and none in the NQ-group (p = 0.04). There was a 4-fold increase in the risk of death or heart failure in the PQ compared to the NQ group (HR 4.7 [1.1; 19.3]; p = 0.03), but there was no significant difference between NQ and RQ groups (HR 3.3 [0.8; 13.8]; p = 0.09).Conclusion: Ina population of anterior STEMI patients, persistent Q waves defined according to the classic ECG criteria after reperfusion was associated with a 4-fold increase in the risk of heart failure or death compared to non-Q-wave MI, while Q-wave regression was associated with significantly lower risk of events.(c) 2019 Elsevier Inc. All rights reserved.
Published: 2022

2. Funding kidney research as a public health priority

Author: Ziad A. Massy, Dimitrios S. Goumenos, Annette Bruchfeld, Ivan Rychlik, Carsten A. Wagner, Hans-Joachim Anders, Tom Oostrom, Carmine Zoccali, Giovambattista Capasso, Ron T. Gansevoort, María José Soler, Kate Stevens, Denis Fouque, Peter J. Blankestijn, Goce Spasovski, Danilo Fliser, Friedo W. Dekker, Kitty J Jager, Mario Cozzolino, Christoph Wanner, Raymond Vanholder, University of Zurich, Universita Mediterranea of Reggio Calabria [Reggio Calabria], Ghent University Hospital, European Kidney Health Alliance (EKHA), University hospital of Zurich [Zurich], Klinikum der Universität [München], University Medical Center [Utrecht], Karolinska University Hospital [Stockholm], University of the Study of Campania Luigi Vanvitelli, University of Milan, Leiden University Medical Center (LUMC), Saarland University [Saarbrücken], Université de la Sarre, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), 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), University Medical Center Groningen [Groningen] (UMCG), General University Hospital of Patras, University of Amsterdam [Amsterdam] (UvA), Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Dutch Kidney Foundation [Bussum, The Netherlands] (DKF), Charles University [Prague] (CU), Vall d’Hebron Research Institute (VHIR), Queen Elizabeth University Hospital (Glasgow), Ss. Cyril and Methodius University in Skopje, University of Würzburg, CarMeN, laboratoire, Università degli Studi di Milano = University of Milan (UNIMI), Université Claude Bernard Lyon 1 (UCBL), 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 Ss. Cyril and Methodius University in Skopje (UKIM)
Subjects: medicine.medical_specialty, kidney, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, 610 Medicine & health, 030204 cardiovascular system & hematology, 10052 Institute of Physiology, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, medicine, CKD, Humans, Transplantation, research, Health Priorities, business.industry, Public health, funding, Public relations, medicine.disease, Medical research, 3. Good health, [SDV] Life Sciences [q-bio], Europe, Seed money, Alliance, Framing (social sciences), scientific societies, Nephrology, 570 Life sciences, biology, Public Health, business, Working group, Social responsibility, Kidney disease
Abstract: Medical societies have a social responsibility to disseminate knowledge and inform health authorities on threats to public health posed by various diseases. Advocacy for health protection programmes and for medical research funding is now embedded into the missions of most scientific societies. To promote kidney research funding in Europe, the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA), rather than acting as an individual society advocating for the fight against kidney disease, has actively helped to create an alliance of national associations centred on kidney diseases, the European Kidney Health Alliance (EKHA), and joined the Biomedical Alliance (BMA). The ERA-EDTA is fully committed to supporting its working groups (WGs) and consortia of its members to allow them to produce valuable kidney research. The framing and formalization of projects, and the regulatory issues related to submission to the European Commission, are complex. To help WGs to gain expert advice from agencies with specific know-how, the ERA-EDTA has adopted a competitive approach. The best research projects proposed by WGs and consortia of other European investigators will receive seed funding to cover the costs of consultancy by expert agencies. Via its broader platforms, the EKHA and the BMA, the ERA-EDTA will strive towards broader recognition of kidney disease and related clusters of non-communicable diseases, by European and national agencies, as major threats to the qualities of life of their populations and their economies.
Published: 2022

3. Anti-inflammatory and anti-virus potential of poxytrins, especially protectin DX

Author: Michel Lagarde, Nathalie Bernoud-Hubac, Michel Guichardant, 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), Université Claude Bernard Lyon 1 (UCBL), 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: 0301 basic medicine, Docosahexaenoic Acids, medicine.drug_class, [SDV]Life Sciences [q-bio], Anti-Inflammatory Agents, Inflammation, Review, Virus Replication, Antiviral Agents, Biochemistry, Anti-inflammatory, 03 medical and health sciences, Lipoxygenase, medicine, Animals, Humans, chemistry.chemical_classification, Reactive oxygen species, 030102 biochemistry & molecular biology, biology, Chemistry, Glutathione peroxidase, Brain, General Medicine, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Prostaglandin-Endoperoxide Synthases, Docosahexaenoic acid, Fatty Acids, Unsaturated, biology.protein, Cyclooxygenase, medicine.symptom, Reactive Oxygen Species, Polyunsaturated fatty acid
Abstract: Poxytrins (Pufa Oxygenated Trienes), are dihydroxy derivatives from polyunsaturated fatty acids (PUFA) with adjacent hydroxyl groups to a conjugated triene having the specific E,Z,E geometry. They are made by the double action of one lipoxygenase or the combined actions of two lipoxygenases, followed by reduction of the resulting hydroperoxides by with glutathione peroxidase. Because of their E,Z,E conjugated triene, poxytrins may inhibit inflammation associated with cyclooxygenase (COX) activities, and reactive oxygen species (ROS) formation. In addition of inhibiting COX activities, at least one poxytrin, namely protectin DX (PDX) from docosahexaenoic acid (DHA), has also been reported as able to inhibit influenza virus replication by targeting its RNA metabolism., Highlights • Poxytrins are double lipoxygenase end-products from natural polyunsaturated fatty acids having at least three double bond. Their characteristic is to own a cis,trans, cis/E,Z,E conjugated triene. • Protectin DX/PDX is a poxytrin from double oxygenation of docosahexaenoic acid by 15/n-6-lipoxygenase. • As other poxytrins, PDX inhibits cyclooxygenase-dependent inflammation. Also, PDX inhibits the RNA influenza virus replication.
Published: 2020

4. Impact of Arterial Blood Pressure on Ultrasound Hemodynamic Assessment of Aortic Valve Stenosis Severity

Author: Hélène Thibault, Marion Rosset, Lisa Green, Gilles Rioufol, Gérard Finet, François Derimay, Ahmad Hayek, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), 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), Université Claude Bernard Lyon 1 (UCBL), 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: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Dimensionless index, Hemodynamics, 030204 cardiovascular system & hematology, Flow rate, Severity of Illness Index, Ventricular Function, Left, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Afterload, Mean transaortic gradient, Internal medicine, Aortic valve area, medicine, Humans, Arterial Pressure, Radiology, Nuclear Medicine and imaging, Prospective Studies, Ejection fraction, business.industry, Aortic stenosis, Ultrasound, afterload, Stroke Volume, Aortic Valve Stenosis, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Stenosis, medicine.anatomical_structure, Blood pressure, Echocardiography, Ventricle, Aortic Valve, Aortic valve stenosis, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; BACKGROUND: Aortic stenosis (AS) severity assessment is based on several indices. Aortic valve area (AVA) is subject to inaccuracies inherent to the measurement method, while velocities and gradients depend on hemodynamic status. There is controversy as to whether blood pressure directly affects common indices of AS severity. OBJECTIVES: The study objective was to assess the effect of systolic blood pressure (SBP) variation on AS indices, in a clinical setting. METHODS: A prospective, single-center study included 100 patients with at least moderately severe AS with preserved left ventricle ejection fraction. Patients underwent ultrasound examination during which AS severity indices were collected, with three hemodynamic conditions: (1) low SBP: \textless120 mm Hg; (2) intermediate SBP: between 120 and 150 mm Hg; (3) high SBP: ≥150 mm Hg. For each patient, SBP profiles were obtained by injection of isosorbide dinitrate or phenylephrine. RESULTS: At baseline state, 59% presented a mean gradient (G(mean)) ≥ 40 mm Hg, 44% a peak aortic jet velocity (V(peak)) ≥4 m/sec, 66% a dimensionless index (DI) ≤0.25, and 87% an indexed AVA (AVAi) ≤ 0.6 cm(2)/m(2). Compared with intermediate and low SBP, high SBP induced a significant decrease in G(mean) (39 ± 12 vs 43 ± 12 and 47 ± 12 mm Hg, respectively; P \textless .05) and in V(peak) (3.8 ± 0.6 vs 4.0 ± 0.6 and 4.2 ± 0.6 mm Hg; P \textless .05). Compared with the baseline measures, in 16% of patients with an initial G(mean)\textless 40 mm Hg, gradient rose above 40 mm Hg after optimization of the afterload (low SBP; P \textless .05). Conversely, DI and AVAi did not vary with changes in hemodynamic conditions. Flow rate, not stroke volume was found to impact G(mean) and V(peak) but not AVA and DI (P \textless .05). CONCLUSIONS: Hemodynamic conditions may affect the AS ultrasound assessment. High SBP, or afterload, leads to an underestimation of AS severity when based on gradients and velocities. Systolic blood pressure monitoring and control are crucial during AS ultrasound assessment.
Published: 2020

5. Type 1 Diabetes in People Hospitalized for COVID-19: New Insights From the CORONADO Study

Author: Sandrine Lablanche, Florence Galtier, Pierre Leroy, Vincent Dubée, Dominique Bonnefont-Rousselot, Patrick Saulnier, Matthieu Wargny, Manuel Etienne, Patrice Darmon, Anne-Laure Borel, Jean-Louis LAPLANCHE, Olivier Lesieur, Bertrand Cariou, Malak Taher, Lydia GUITTET, Vincent Minville, BRUNO MOURVILLIER, Jean-Pierre QUENOT, Bernard Bonnotte, Lucien Marchand, Team2 Carmen, Veronique Kerlan, Pascal Reynier, Nadia Sabbah, Matthieu PICHELIN, Jean-Charles Aurégan, Guillaume Martin-Blondel, Olivier Bourron, Blandine Rammaert, Pierre-Edouard Fournier, Coralie Amadou, Giulia Chinetti, Jean-Christophe Lagier, Didier Raoult, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), 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], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Sud Francilien, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service d'endocrinologie, diabétologie et nutrition [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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)-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), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Diabétologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CH Evry-Corbeil, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service de diabétologie [CHU Pitié-Salpétrière], Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, Hal Sorbonne Université
Subjects: Male, Pediatrics, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Pneumonia, Viral, Population, 030209 endocrinology & metabolism, law.invention, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, law, Diabetes mellitus, Internal Medicine, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, education, Pandemics, Case report form, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Glycated Hemoglobin, Advanced and Specialized Nursing, Inpatients, Type 1 diabetes, education.field_of_study, business.industry, e-Letters: Observations, COVID-19, Middle Aged, Prognosis, medicine.disease, Respiration, Artificial, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Diabetes Mellitus, Type 2, Hypertension, Etiology, Female, Observational study, Coronavirus Infections, business
Abstract: Since the start of the coronavirus disease 2019 (COVID-19) pandemic, patients with diabetes were rapidly recognized as a high-risk population for severe disease. Indeed, a high prevalence of diabetes among patients with COVID-19 who required hospitalization has been consistently reported, reaching 33.8% in 5,700 people hospitalized for COVID-19 in the New York City area (1). In addition, diabetes was associated with more than a doubled risk of intensive care unit (ICU) admission and more than a tripled risk of death (2). However, precise data regarding the type of diabetes are scarce. We report here the clinical characteristics and early prognosis of patients with type 1 diabetes (T1D) hospitalized for COVID-19 in the nationwide multicenter observational CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study (3). The aim of the CORONADO study was to describe the phenotypic characteristics and prognosis of patients with diabetes admitted with COVID-19 between 10 March and 10 April 2020 in 68 French hospitals. The protocol (ClinicalTrials.gov reg. no. NCT04324736) obtained all regulatory approvals as recently described (3). Inclusion criteria were 1 ) hospitalization for biologically and/or clinically/radiologically attested COVID-19 and 2 ) personal history of diabetes or newly diagnosed diabetes on admission. The composite primary end point combined tracheal intubation for mechanical ventilation and/or death on day 7 (D7). Secondary outcomes included death, tracheal intubation, and discharge on D7. Classification of diabetes was recorded in the electronic case report form as noted in the medical file by the physician in charge of the patient. In the present subanalysis, patients in whom diabetes was diagnosed on admission were excluded since the etiological diagnosis had not been formally established. All cases noted as T1D were carefully reviewed by local investigators and the steering committee …
Published: 2020

6. Mycoplasma hyopneumoniae J elicits an antioxidant response and decreases the expression of ciliary genes in infected swine epithelial cells

Author: Scheila G. Mucha, Sophie Rome, Marie-France Sagot, Laurent Guyon, Mariana Galvão Ferrarini, Carol Moraga, Florence Tardy, Alex Di Genova, Arnaldo Zaha, Centro de Biotecnologia [Porto Alegre] (CBiot), Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), Baobab, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), 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), Mycoplasmoses des Ruminants - UMR (MYCO), Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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)-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), CAPES782/13European Research Council (ERC)[247073]10CAPES CAPES-Cofecub doctoral fellowship CAPES post-doctoral fellowship (CAPES-Biologia Computacional) 611 23038.010043/2013-02CONICYT BECAS CHILE DOCTORADO 2016/FOLIO 72170320, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), and 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)
Subjects: 0301 basic medicine, Swine, [SDV]Life Sciences [q-bio], lcsh:Medicine, Article, Antioxidants, 03 medical and health sciences, 0302 clinical medicine, Mycoplasma hyopneumoniae, Bacterial Proteins, Gene expression, microRNA, Animals, Cilia, RNA, Messenger, Transcriptomics, lcsh:Science, Gene, Pathogen, Transcription factor, Cells, Cultured, Regulation of gene expression, Multidisciplinary, biology, Gene Expression Profiling, lcsh:R, Bacteriology, Epithelial Cells, Pneumonia of Swine, Mycoplasmal, biology.organism_classification, 3. Good health, Cell biology, Gene expression profiling, MicroRNAs, 030104 developmental biology, Gene Expression Regulation, miRNAs, lcsh:Q, Pathogens, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], 030217 neurology & neurosurgery, Biomarkers
Abstract: Mycoplasma hyopneumoniae is the most costly pathogen for swine production. Although several studies have focused on the host-bacterium association, little is known about the changes in gene expression of swine cells upon infection. To improve our understanding of this interaction, we infected swine epithelial NPTr cells with M. hyopneumoniae strain J to identify differentially expressed mRNAs and miRNAs. The levels of 1,268 genes and 170 miRNAs were significantly modified post-infection. Up-regulated mRNAs were enriched in genes related to redox homeostasis and antioxidant defense, known to be regulated by the transcription factor NRF2 in related species. Down-regulated mRNAs were enriched in genes associated with cytoskeleton and ciliary functions. Bioinformatic analyses suggested a correlation between changes in miRNA and mRNA levels, since we detected down-regulation of miRNAs predicted to target antioxidant genes and up-regulation of miRNAs targeting ciliary and cytoskeleton genes. Interestingly, most down-regulated miRNAs were detected in exosome-like vesicles suggesting that M. hyopneumoniae infection induced a modification of the composition of NPTr-released vesicles. Taken together, our data indicate that M. hyopneumoniae elicits an antioxidant response induced by NRF2 in infected cells. In addition, we propose that ciliostasis caused by this pathogen is partially explained by the down-regulation of ciliary genes.
Published: 2020

7. Phosphorylation of cyclophilin D at serine 191 regulates mitochondrial permeability transition pore opening and cell death after ischemia-reperfusion

Author: Stephen Hurst, Maya Dia, Fabrice Gonnot, Claire Crola Da Silva, Ludovic Gomez, Shey-Shing Sheu, Jefferson (Philadelphia University + Thomas Jefferson University), 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), United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA2R01HL0936711R01HL1372661R01HL122124T32AA007463French National Research Agency (ANR)16-CE17-0020-01, Université Claude Bernard Lyon 1 (UCBL), 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 CarMeN, laboratoire
Subjects: Male, 0301 basic medicine, Cancer Research, Programmed cell death, Oligomycin, [SDV]Life Sciences [q-bio], Immunology, Mutant, Myocardial Reperfusion Injury, 030204 cardiovascular system & hematology, Mitochondrial Membrane Transport Proteins, Article, Serine, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Ischemia, medicine, Animals, Myocytes, Cardiac, Phosphorylation, lcsh:QH573-671, Mice, Knockout, Cell Death, Mitochondrial Permeability Transition Pore, lcsh:Cytology, MPTP, Cell Biology, medicine.disease, Mitochondria, Cell biology, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Myocardial infarction, 030104 developmental biology, Mitochondrial permeability transition pore, chemistry, Reperfusion Injury, Mitochondrial Membranes, Reperfusion, Reperfusion injury, Cyclophilin D, Signal Transduction
Abstract: The mitochondrial permeability transition pore (mPTP) plays a critical role in the pathogenesis of cardiovascular diseases, including ischemia/reperfusion injury. Although the pore structure is still unresolved, the mechanism through which cyclophilin D (CypD) regulates mPTP opening is the subject of intensive studies. While post-translational modifications of CypD have been shown to modulate pore opening, specific phosphorylation sites of CypD have not yet been identified. We hypothesized here that phosphorylation of CypD on a serine residue controls mPTP opening and subsequent cell death at reperfusion. We combined in silico analysis with in vitro and genetic manipulations to determine potential CypD phosphorylation sites and their effect on mitochondrial function and cell death. Importantly, we developed an in vivo intramyocardial adenoviral strategy to assess the effect of the CypD phosphorylation event on infarct size. Our results show that although CypD can potentially be phosphorylated at multiple serine residues, only the phosphorylation status at S191 directly impacts the ability of CypD to regulate the mPTP. Protein-protein interaction strategies showed that the interaction between CypD and oligomycin sensitivity-conferring protein (OSCP) was reduced by 45% in the phosphoresistant S191A mutant, whereas it was increased by 48% in the phosphomimetic S191E mutant cells. As a result, the phosphoresistant CypD S191A mutant was protected against 18 h starvation whereas cell death was significantly increased in phosphomimetic S191E group, associated with mitochondrial respiration alteration and ROS production. As in vivo proof of concept, in S191A phosphoresistant rescued CypD-KO mice developed significantly smaller infarct as compared to WT whereas infarct size was drastically increased in S191E phosphomimetic rescued mice. We conclude that CypD phosphorylation at S191 residue leads to its binding to OSCP and thus sensitizes mPTP opening for the subsequent cell death.
Published: 2020

8. Use of Nanovesicles from Orange Juice to Reverse Diet-Induced Gut Modifications in Diet-Induced Obese Mice

Author: Berger, Emmanuelle, Colosetti, Pascal, Jalabert, Audrey, Meugnier, Emmanuelle, Wiklander, Oscar, Jouhet, Juliette, Errazuriz-Cerda, Elisabeth, Chanon, Stéphanie, Gupta, Dhanu, Rautureau, Gilles, Geloen, Alain, EL-Andaloussi, Samir, Panthu, Baptiste, Rieusset, Jennifer, Rome, Sophie, Martin-Laffon, Jacqueline, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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)-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), Department of Laboratory Medicine, Karolinska Institutet, LIPID, Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Université de Lyon, Centre de RMN à très hauts champs de Lyon (CRMN), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Olga Tribalat Institute (France) Benjamin Delessert Institute (France) INRAe (France) INFRASTRUCTURES DE RECHERCHE Resonance Magnetique Nucleaire, Tres Hauts Champs Fr3050 CNRS (France), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), and 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)
Subjects: obesity, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, lcsh:QH426-470, lcsh:Cytology, MTP, diet-induced gut modifications, lcsh:Genetics, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, ANGPTL4, dietary supplement, lipid metabolism, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, villi size, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Original Article, edible plant, lcsh:QH573-671, jejunum, extracellular vesicles, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, triglycerides, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: We have determined whether orange juice-derived nanovesicles (ONVs) could be used for the treatment of obesity-associated intestinal complications. ONVs were characterized by lipidomic, metabolomic, electron microscopy. In vitro, intestinal barriers (IBs = Caco-2+HT-29-MTX) were treated with ONVs and co-cultured with adipocytes to monitor IB fat release. In vivo, obesity was induced with a high-fat, high-sucrose diet (HFHSD mice) for 12 weeks. Then, half of HFHSD mice were gavaged with ONVs. One-month ONV treatment did not modify HFHSD-induced insulin resistance but reversed diet-induced gut modifications. In the jejunum, ONVs increased villi size, reduced triglyceride content, and modulated mRNA levels of genes involved in immune response (tumor necrosis factor [TNF]-α and interleukin [IL]-1β), barrier permeability (CLDN1, OCLN, ZO1), fat absorption, and chylomicron release. ONVs targeted microsomal triglyceride transfer protein (MTP) and angiopoietin-like protein-4 (ANGPTL4), two therapeutic targets to reduce plasma lipids and inflammation in gastrointestinal diseases. Interestingly, ONV treatment did not aggravate liver steatosis, as MTP mRNA was increased in the liver. Therefore, ONVs protected both intestine and the liver from fat overload associated with the HFHSD. As ONVs concentrated amino acids and bioactive lipids versus orange juice, which are deficient in obese patients, the use of ONVs as a dietary supplement could bring physiological relevant compounds in the jejunum to accelerate the restoration of intestinal functions during weight loss in obese patients., Graphical Abstract, This study demonstrated that orange juice-derived nanovesicles (ONVs) reversed diet-induced gut modifications in mice. ONVs increased villi size, reduced triglyceride content, and modulated genes involved in the immune response, barrier permeability, fat absorption, and chylomicron release. ONVs also protected both intestine and liver from fat overload by targeting MTP and ANGPTL4.
Published: 2020

9. Urinary Sodium-to-Potassium Ratio and Blood Pressure in CKD

Author: Natalia Alencar de Pinho, Jean Kaboré, Maurice Laville, Marie Metzger, Céline Lange, Christian Jacquelinet, Christian Combe, Denis Fouque, Luc Frimat, Carol Ayav, Bruce M. Robinson, Tilman Drueke, Ziad A. Massy, Bénédicte Stengel, Thierry Hannedouche, Bruno Moulin, Sébastien Mailliez, Gaétan Lebrun, Eric Magnant, Gabriel Choukroun, Benjamin Deroure, Adeline Lacraz, Guy Lambrey, Jean Philippe Bourdenx, Marie Essig, Thierry Lobbedez, Raymond Azar, Hacène Sekhri, Mustafa Smati, Mohamed Jamali, Alexandre Klein, Michel Delahousse, Séverine Martin, Isabelle Landru, Eric Thervet, Philippe Lang, Xavier Belenfant, Pablo Urena, Carlos Vela, Dominique Chauveau, Viktor Panescu, Christian Noel, François Glowacki, Maxime Hoffmann, Maryvonne Hourmant, Dominique Besnier, Angelo Testa, François Kuentz, Philippe Zaoui, Charles Chazot, Laurent Juillard, Stéphane Burtey, Adrien Keller, Nassim Kamar, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut de Recherche en Sciences de la Santé (IRSS), CNRST, 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), Agence de la biomédecine [Saint-Denis la Plaine], Service de Néphrologie Transplantation, Dialyse et Aphérèse [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Arbor Research Collaborative for Health, Hôpital Ambroise Paré [AP-HP], 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), Agence Nationale de la Recherche, ANR Agence Nationale de la Recherche, ANR, The CKD-REIN study is funded by the Agence Nationale de la Recherche through the 2010 «Cohortes-Investissements d’Avenir » program (ANR) and by the 2010 national Programme Hospitalier de Recherche Clinique . CKD-REIN is also supported through a public–private partnership with Amgen , Fresenius Medical Care , and GlaxoSmithKline (GSK) since 2012, Lilly France since 2013, Otsuka Pharmaceutical since 2015, Baxter and Merck Sharp & Dohme-Chibret (MSD France) from 2012 to 2017, Sanofi-Genzyme from 2012 to 2015, and Vifor Fresenius and AstraZeneca , since 2018. Inserm Transfert set up and has managed this partnership since 2011., Université Claude Bernard Lyon 1 (UCBL), 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), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Chronic Kidney Disease - Réseau Epidémiologie et Information en Néphrologie (CKD REIN), and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Urinary system, Population, 030232 urology & nephrology, 030204 cardiovascular system & hematology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gastroenterology, Excretion, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Interquartile range, Internal medicine, medicine, salt, 10. No inequality, education, sodium, education.field_of_study, business.industry, potassium, blood pressure, medicine.disease, 3. Good health, Blood pressure, Quartile, Nephrology, Albuminuria, medicine.symptom, business, chronic kidney disease, Kidney disease
Abstract: Introduction In the general population, urinary sodium-to-potassium (uNa/K) ratio associates more strongly with high blood pressure (BP) than either urinary sodium or potassium alone. Whether this is also the case among patients with chronic kidney disease (CKD) is unknown. Methods We studied the associations of spot urine sodium-to-creatinine (uNa/Cr), potassium-to-creatinine (uK/Cr), and uNa/K ratios with a single office BP reading in 1660 patients with moderate to severe CKD at inclusion in the CKD-REIN cohort. Results Patients' median age was 68 (interquartile range [IQR], 59–76) years; most were men (65%), had moderate CKD (57%), and albuminuria (72%). Mean systolic and diastolic BP was 142/78 mm Hg. Spot uNa/Cr and uNa/K ratios were positively associated with systolic, mean arterial, and pulse pressures. The mean adjusted difference in systolic BP between the highest and the lowest quartile (Q4 vs. Q1) was 4.24 (95% confidence interval [CI], 1.53–6.96) mm Hg for uNa/Cr and 4.79 (95% CI, 2.18–7.39) mm Hg for uNa/K. Quartiles of spot uK/Cr were not associated with any BP index. The higher the quartile of uNa/K, the higher the prevalence ratio of uncontrolled (Q4 vs. Q1, 1.43; 95% CI, 1.19–1.72) or apparently treatment-resistant hypertension (Q4 vs. Q1, 1.35; 95% CI, 1.14–1.60). Findings were consistent in a subset of 803 individuals with 2 BP readings. Conclusion In patients with CKD, higher urinary sodium excretion is associated with higher BP, but unlike in general population, lower potassium excretion is not. Urinary Na/K does not add significant value in assessing high BP risk, except perhaps for hypertension control assessment., Graphical abstract
Published: 2020

10. ERRα Expression in Bone Metastases Leads to an Exacerbated Antitumor Immune Response

Author: Soumaya El-Moghrabi, Martine Duterque-Coquillaud, Alexandra Lainé, Philippe Clézardin, Sandra Geraci, Cyril Boyault, Casina W.S. Kan, Emmanuelle Meugnier, Lamia Bouazza, Julien C. Marie, Yuji Yoshiko, Hector Hernandez-Vargas, Edith Bonnelye, Mathilde Proponnet-Guerault, Claire Benetollo, Mathilde Bouchet, Inflammasome NLRP3 – NLRP3 Inflammasome, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Régulations métaboliques, nutrition et diabètes (RMND), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), 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), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Institut de biologie de Lille - UMS 3702 (IBL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), ANR-10-LABX-0061,DEVWECAN,Development Cancer and Targeted Therapies(2010), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de 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), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Inserm UMR1069, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS), Médecine cellulaire et moléculaire (MCM), Université de Lille, Sciences et Technologies-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, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon], Université de Lyon-Université de Lyon-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), Bonnelye, Edith, Development Cancer and Targeted Therapies - - DEVWECAN2010 - ANR-10-LABX-0061 - LABX - VALID, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Cardiovasculaire, métabolisme, diabétologie et nutrition [CarMeN], Institut de biologie de Lille - UMS 3702 [IBL], Médecine cellulaire et moléculaire [MCM], Institut National de la Santé et de la Recherche Médicale [INSERM], Institut de Génomique Fonctionnelle de Lyon [IGFL], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) [IAB], Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS], and Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Subjects: 0301 basic medicine, Cancer Research, Chemokine, T-Lymphocytes, [SDV]Life Sciences [q-bio], Apoptosis, Mice, 0302 clinical medicine, Tumor Cells, Cultured, Tumor Microenvironment, Cytotoxic T cell, ComputingMilieux_MISCELLANEOUS, Mice, Inbred BALB C, biology, Prognosis, Primary tumor, 3. Good health, Gene Expression Regulation, Neoplastic, Receptors, Estrogen, Oncology, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Signal Transduction, [SDV.IMM] Life Sciences [q-bio]/Immunology, Mice, Nude, Bone Neoplasms, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 03 medical and health sciences, Transforming Growth Factor beta3, Breast cancer, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biomarkers, Tumor, medicine, Animals, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cell Proliferation, Chemokine CCL20, business.industry, medicine.disease, Xenograft Model Antitumor Assays, CCL20, 030104 developmental biology, Transforming growth factor, beta 3, biology.protein, Cancer research, Chemokine CCL17, business, Transforming growth factor
Abstract: Bone is the most common metastatic site for breast cancer. Although the estrogen-related receptor alpha (ERRα) has been implicated in breast cancer cell dissemination to the bone from the primary tumor, its role after tumor cell anchorage in the bone microenvironment remains elusive. Here, we reveal that ERRα inhibits the progression of bone metastases of breast cancer cells by increasing the immune activity of the bone microenvironment. Overexpression of ERRα in breast cancer bone metastases induced expression of chemokines CCL17 and CCL20 and repressed production of TGFβ3. Subsequently, CD8+ T lymphocytes recruited to bone metastases escaped TGFβ signaling control and were endowed with exacerbated cytotoxic features, resulting in significant reduction in metastases. The clinical relevance of our findings in mice was confirmed in over 240 patients with breast cancer. Thus, this study reveals that ERRα regulates immune properties in the bone microenvironment that contributes to decreasing metastatic growth. Significance: This study places ERRα at the interplay between the immune response and bone metastases of breast cancer, highlighting a potential target for intervention in advanced disease.
Published: 2020

11. Matrix Metalloproteinase-9 and Monocyte Chemoattractant Protein-1 Are Associated With Collateral Status in Acute Ischemic Stroke With Large Vessel Occlusion

Author: Camille Amaz, Nathan Mewton, Yves Berthezène, Claire Crola Da Silva, Marielle Buisson, Thomas Bochaton, Nathalie Dufay, Elodie Ong, Omer Eker, Alexandre Paccalet, Norbert Nighoghossian, Laurent Derex, Michel Ovize, Tae-Hee Cho, Laura Mechtouff, Stroke Department, Neurological Hospital, Hospices Civils de Lyon (HCL), 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), Virologie et pathogenèse virale (VPV), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales (MOTIVATE), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Neuroradiology Department, Neurological Hospital, Department of Cardiology, and Imagerie Tomographique et Radiothérapie
Subjects: Monocyte Chemoattractant Proteins, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, digital subtraction angiography, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, collateral circulation, Acute ischemic stroke, brain edema, Advanced and Specialized Nursing, medicine.diagnostic_test, business.industry, Matrix metalloproteinase 9, Digital subtraction angiography, Collateral circulation, Inflammatory biomarkers, Cardiology, matrix metalloproteinase 9, Neurology (clinical), monocyte chemoattractant proteins, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Large vessel occlusion, Monocyte chemoattractant protein
Abstract: Background and Purpose: In ischemic stroke, inflammatory status may condition the development of collateral circulation. Here we assessed the relationship between systemic inflammatory biomarkers and collateral status in large vessel occlusion before mechanical thrombectomy. Methods: HIBISCUS-STROKE is a cohort study including acute ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy following admission magnetic resonance imaging. MMP-9 (matrix metalloproteinase-9) and MCP-1 (monocyte chemoattractant protein-1) were measured on blood sampling collected at admission. Collateral status was assessed on pretreatment Digital subtraction angiography and categorized into poor (Higashida score, 0–2) and good (Higashida score, 3–4). A multiple logistic regression model was performed to detect independent markers of good collateral status. Results: One hundred and twenty-two patients were included, of them 71 patients (58.2%) had a good collateral status. In univariate analysis, low MMP-9 levels ( P =0.01), high MCP-1 levels ( P P =0.046), a high diastolic blood pressure ( P =0.049), the absence of tandem occlusion ( P =0.046), a high Alberta Stroke Program Early CT Score ( P P P =0.02) and high MCP-1 levels ( P Conclusions: Low MMP-9 and high MCP-1 levels were associated with good pretreatment collateral status in patients with acute ischemic stroke with large vessel occlusion. These results might suggest a relationship between collateral status and inflammation.
Published: 2020

12. Lung and chest wall mechanics in patients with acute respiratory distress syndrome, expiratory flow limitation, and airway closure

Author: Loredana Baboi, Emanuele Turbil, Bruno Louis, Louis-Marie Galerneau, Martin Cour, Nicolas Terzi, Mehdi Mezidi, Claude Guérin, Louis Kreitmann, Laurent Argaud, Hodane Yonis, STMicroelectronics [Crolles] (ST-CROLLES), Unité de soins intensifs médicaux [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), 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), Hôpital Edouard Herriot, Service Anesthésie Réanimation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), THALES Airborne Systems [Elancourt], and THALES
Subjects: ARDS, medicine.medical_specialty, Supine position, Physiology, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Humans, Prospective Studies, Expiration, Thoracic Wall, Lung, Positive end-expiratory pressure, Mechanical ventilation, Respiratory Distress Syndrome, expiratory flow limitation, business.industry, Exhalation, 030208 emergency & critical care medicine, acute respiratory distress syndrome, respiratory system, medicine.disease, medicine.anatomical_structure, 030228 respiratory system, airway closure, Respiratory Mechanics, Cardiology, business, Airway, positive end-expiratory pressure
Abstract: Tidal expiratory flow limitation (EFL), which may herald airway closure (AC), is a mechanism of loss of aeration in ARDS. In this prospective, short-term, two-center study, we measured static and dynamic chest wall (Est,cw and Edyn,cw) and lung (Est,L and Edyn,L) elastance with esophageal pressure, EFL, and AC at 5 cmH(2)O positive end-expiratory pressure (PEEP) in intubated, sedated, and paralyzed ARDS patients. For EFL determination, we used the atmospheric method and a new device allowing comparison of tidal flow during expiration to PEEP and to atmosphere. AC was validated when airway opening pressure (AOP) assessed from volume-pressure curve was found greater than PEEP by at least 1 cmH(2)O. EFL was defined whenever flow did not increase between exhalation to PEEP and to atmosphere over all or part of expiration. Elastance values were expressed as percentage of normal predicted values (%N). Among the 25 patients included, eight had EFL (32%) and 13 AOP (52%). Between patients with and without EFL Edyn,cw [median (1st to 3rd quartiles)] was 70 (16-127) and 102 (70-142) %N (P = 0.32) and Edyn,L338 (332-763) and 224 (160-275) %N (P \textless 0.001). The corresponding values for Est,cw and Est,L were 70 (56-88) and 85 (64-103) %N (P = 0.35) and 248 (206-348) and 170 (144-195) (P = 0.02), respectively. Dynamic E(L) had an area receiver operating characteristic curve of 0.88 [95% confidence intervals 0.83-0.92] for EFL and 0.74[0.68-0.79] for AOP. Higher Edyn,L was accurate to predict EFL in ARDS patients; AC can occur independently of EFL, and both should be assessed concurrently in ARDS patients.NEW & NOTEWORTHY Expiratory flow limitation (EFL) and airway closure (AC) were observed in 32% and 52%, respectively, of 25 patients with ARDS investigated during mechanical ventilation in supine position with a positive end-expiratory pressure of 5 cmH(2)O. The performance of dynamic lung elastance to detect expiratory flow limitation was good and better than that to detect airway closure. The vast majority of patients with EFL also had AC; however, AC can occur in the absence of EFL.
Published: 2020

13. Perceived Health and Quality of Life in Patients With CKD, Including Those With Kidney Failure: Findings From National Surveys in France

Author: Elodie Speyer, Denis Fouque, Stéphane Edet, Carole Ayav, Anne Durand, Ziad A. Massy, Karine Legrand, Bénédicte Stengel, Maurice Laville, Serge Briançon, Luc Frimat, Christian Combe, Stéphanie Gentile, Christian Jacquelinet, Willy Ngueyon Sime, Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), 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 de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), CHU Rouen, Normandie Université (NU), Centre d'Epidémiologie Clinique (CIC-EC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [Ambroise Paré], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, 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), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), and 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)
Subjects: Male, dialysis patients, symptom burden, patient well-being, medicine.medical_treatment, 030232 urology & nephrology, health status, Chronic kidney disease (CKD), survey data, Random Allocation, 0302 clinical medicine, Quality of life, kidney transplant patients, Outcome Assessment, Health Care, Medicine, Registries, 030212 general & internal medicine, education.field_of_study, Minimal clinically important difference, Middle Aged, 3. Good health, Renal Replacement Therapy, Nephrology, Female, health-related quality of life (HRQoL), France, Glomerular Filtration Rate, medicine.medical_specialty, Population, Renal function, patient-reported outcomes (PROs), Diagnostic Self Evaluation, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Humans, Renal Insufficiency, Chronic, education, Dialysis, business.industry, medicine.disease, Kidney Transplantation, Obesity, kidney failure, Cross-Sectional Studies, renal replacement therapy (RRT), end-stage renal disease (ESRD), Quality of Life, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Kidney disease
Abstract: International audience; RATIONALE & OBJECTIVE: Health-related quality of life (HRQoL) is a major outcome measure increasingly used in patients with chronic kidney disease (CKD). We evaluated the association between different stages of CKD and the physical and mental health domains of HRQoL.STUDY DESIGN: Cross-sectional study.SETTING & PARTICIPANTS: 2,693 outpatients with moderate (stage 3, estimated glomerular filtration rate [eGFR], 30-60mL/min/1.73m2) or advanced (stages 4-5, estimated glomerular filtration rate40% of those with advanced CKD or receiving dialysis, 12% with a functioning transplant, and 3% of the general population sample. HRQoL physical scores (adjusted for age, sex, education, obesity, and diabetes) were significantly lower in patients in all CKD subgroups than in the general population. For patients receiving dialysis, the magnitude of the difference in physical score versus the general population exceeded 4.5 points, the minimal clinically important difference for this score in this study; for both kidney transplant recipients and patients with advanced CKD, the magnitude of the difference was close to this threshold. For mental score, only dialysis patients had a score that differed from that of the general population by more than the minimal clinically important difference.LIMITATIONS: Cross-sectional study design for each subpopulation.CONCLUSIONS: This study highlights the degree to which perceived physical health is lower in the setting of CKD than in the general population, even in the absence of kidney failure, and calls for greater attention to CKD-related quality of life.
Published: 2020

14. Nomenclature for kidney function and disease: report of a Kidney Disease

Author: Caroline Vinck, Andrew S. Levey, Mark Lambie, Josephine P. Briggs, Andrew Davenport, Susan J. Allison, Stacy L. Christiansen, Shari E. Leventhal, Stephen B. Walsh, Joseph Laycock, Jonathan S. Bromberg, Paul M. Palevsky, Denis Fouque, Brenda R. Hemmelgarn, Jennifer St. Clair Russell, Lesley A. Inker, Pascale H. Lane, Michael Cheung, Rajnish Mehrotra, Detlef Bockenhauer, Adeera Levin, Matthias Kretzler, Mark A. Perazella, Ron T. Gansevoort, Kai-Uwe Eckardt, Lesley Rees, Daniel E. Weiner, John S. Gill, Harold I. Feldman, Julie R. Ingelfinger, Allison Tong, Michael Mittelman, Michel Jadoul, Pierre Ronco, Nijsje M. Dorman, Marlies Ostermann, Patricia Morrissey, Wolfgang C. Winkelmayer, Franz Schaefer, Eddie L. Greene, Ewout J. Hoorn, School of Metallurgy and Materials, University of Birmingham [Birmingham], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), 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), California Institute of Technology (CALTECH), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), and Internal Medicine
Subjects: 0301 basic medicine, medicine.medical_specialty, Glossary, kidney disease, precision medicine, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Renal function, Disease, Q1, 03 medical and health sciences, 0302 clinical medicine, kidney measures, medicine, patient-centeredness, Intensive care medicine, kidney function, Kidney, acute kidney diseases and disorders, business.industry, urogenital system, Acute kidney injury, Precision medicine, medicine.disease, R1, 3. Good health, kidney failure, 030104 developmental biology, medicine.anatomical_structure, acute kidney injury, Nephrology, Albuminuria, nomenclature, medicine.symptom, business, chronic kidney disease, Kidney disease
Abstract: The worldwide burden of kidney disease is rising, but public awareness remains limited, underscoring the need for more effective communication by stakeholders in the kidney health community. Despite this need for clarity, the nomenclature for describing kidney function and disease lacks uniformity. In June 2019, Kidney Disease: Improving Global Outcomes (KDIGO) convened a Consensus Conference with the goal of standardizing and refining the nomenclature used in the English language to describe kidney function and disease, and of developing a glossary that could be used in scientific publications. Guiding principles of the conference were that the revised nomenclature should be patient-centered, precise, and consistent with nomenclature used in the KDIGO guidelines. Conference attendees reached general consensus on the following recommendations: (i) to use "kidney" rather than "renal" or "nephro-" when referring to kidney disease and kidney function; (ii) to use "kidney failure" with appropriate descriptions of presence or absence of symptoms, signs, and treatment, rather than "end-stage kidney disease"; (iii) to use the KDIGO definition and classification of acute kidney diseases and disorders (AKD) and acute kidney injury (AKI), rather than alternative descriptions, to define and classify severity of AKD and AKI; (iv) to use the KDIGO definition and classification of chronic kidney disease (CKD) rather than alternative descriptions to define and classify severity of CKD; and (v) to use specific kidney measures, such as albuminuria or decreased glomerular filtration rate (GFR), rather than "abnormal" or "reduced" kidney function to describe alterations in kidney structure and function. A proposed 5-part glossary contains specific items for which there was general agreement. Conference attendees acknowledged limitations of the recommendations and glossary, but they considered standardization of scientific nomenclature to be essential for improving communication.
Published: 2020

15. Liver transplantation as a rescue therapy for severe neurologic forms of Wilson disease

Author: Aurélia Poujois, Rodolphe Sobesky, Wassilios G. Meissner, Anne-Sophie Brunet, Emmanuel Broussolle, Chloé Laurencin, Laurence Lion-François, Olivier Guillaud, Alain Lachaux, François Maillot, Jérémie Belin, Ephrem Salamé, Claire Vanlemmens, Bruno Heyd, Céline Bellesme, Dalila Habes, Christophe Bureau, Fabienne Ory-Magne, Pascal Chaine, Jean-Marc Trocello, Daniel Cherqui, Didier Samuel, Victor de Ledinghen, Jean-Charles Duclos-Vallée, France Woimant, National reference Centre for Wilson's Disease [Paris] (CRMR Wilson), Service de neurologie [Univ. Paris VII], 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)-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), Service d'Electroneuromyographie et Service de Neurologie C [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Lyon, Département d'hépatologie, Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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)-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), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe de Recherche en Economie Théorique et Appliquée (GREThA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Hôpital Claude Huriez [Lille], CHU Lille, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Badji Mokhtar de Annaba, CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, 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), Hôpital Paul Brousse, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Hôpital Purpan [Toulouse], and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
Subjects: Male, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Drug Resistance, Liver transplantation, Severity of Illness Index, Disability Evaluation, Young Adult, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Hepatolenticular Degeneration, Liver Function Tests, Modified Rankin Scale, Internal medicine, Severity of illness, Humans, Medicine, Survival rate, Retrospective Studies, medicine.diagnostic_test, business.industry, Parkinsonism, Retrospective cohort study, medicine.disease, Magnetic Resonance Imaging, Liver Transplantation, 3. Good health, Survival Rate, Female, 030211 gastroenterology & hepatology, Neurology (clinical), business, Liver function tests, 030217 neurology & neurosurgery
Abstract: ObjectiveTo evaluate the effect of liver transplantation (LT) in patients with Wilson disease (WD) with severe neurologic worsening resistant to active chelation.MethodsFrench patients with WD who underwent LT for pure neurologic indication were retrospectively studied. Before LT and at the last follow-up, neurologic impairment was evaluated with the Unified Wilson's Disease Rating Scale (UWDRS) score, disability with the modified Rankin Scale (mRS) score, and hepatic function with the Model for End-stage Liver Disease score, together with the presence of a Kayser-Fleischer ring (KFR), brain MRI scores, and copper balance. The survival rate and disability at the last follow-up were the coprimary outcomes; evolution of KFR and brain MRI were the secondary outcomes. Prognosis factors were further assessed.ResultsEighteen patients had LT. All were highly dependent before LT (median mRS score 5). Neurologic symptoms were severe (median UWDRS score 105), dominated by dystonia and parkinsonism. The cumulated survival rate was 88.8% at 1 year and 72.2% at 3 and 5 years. At the last follow-up, 14 patients were alive. Their mRS and UWDRS scores improved (p< 0.0001 andp= 0.0003). Eight patients had a major improvement (78% decrease of the UWDRS score), 4 a moderate one (41% decrease), and 2 a stable status. KFR and brain MRI scores improved (p= 0.0007). Severe sepsis (p= 0.011) and intensive care unit admission (p= 0.001) before LT were significantly associated with death.ConclusionsLT is a rescue therapeutic option that should be carefully discussed in selected patients with neurologic WD resistant to anticopper therapies (chelators or zinc salts) as it might allow patients to gain physical independency with a reasonable risk.Classification of evidenceThis study provides Class IV evidence that for patients with WD with severe neurologic worsening resistant to active pharmacologic therapy, LT might decrease neurologic impairment.
Published: 2020

16. Effect of bile acid supplementation on endogenous lipid synthesis in patients with short bowel syndrome: A pilot study

Author: Laurent Brondel, Jocelyne Drai, M. Lauverjat, Michel Beylot, Cécile Chambrier, Thomas Mouillot, P. Gelas, Patrick Hillon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, 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), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Hospices Civils de Lyon (HCL)
Subjects: Male, 0301 basic medicine, Pilot Projects, Critical Care and Intensive Care Medicine, Gastroenterology, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, Nutrition and Dietetics, Bile acid, Middle Aged, Short bowel syndrome, Ursodeoxycholic acid, ursodeoxycholic acid, 3. Good health, Cholesterol, gas-chromatography, Female, acid, medicine.drug, Adult, spectroscopy, medicine.medical_specialty, cholesterol-synthesis, medicine.drug_class, water, parenteral nutrition, 030209 endocrinology & metabolism, short bowel syndrome, Bile Acids and Salts, intestinal-failure, Young Adult, 03 medical and health sciences, total parenteral-nutrition, lipid, Internal medicine, medicine, Humans, Triglycerides, Aged, 030109 nutrition & dietetics, business.industry, Lipogenesis, hepatic lipogenesis, cholestatic liver-disease, Lipid metabolism, medicine.disease, Parenteral nutrition, intestinal failure-associated liver disease, chemistry, Dietary Supplements, Steatosis, business, metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ursodeoxycholic
Abstract: International audience; Background & aims: Short bowel syndrome patients (SBS) receiving parenteral nutrition (PN) often have dyslipidaemia and can develop intestinal failure-associated liver disease (IFALD). These patients demonstrate increased cholesterol synthesis and hepatic lipogenesis. These lipid disturbances may be due to a decreased concentration of the bile acid pool or malabsorption. The aim of this pilot study was to evaluate the effect of bile acid administration on lipid synthesis in patients with SBS. Methods: The 24 h fractional synthesis rate (FSR) of cholesterol and triglycerides was measured by the isotopic method (deuterated water) before and after 4 months of ursodeoxycholic acid (UDCA) treatment (20 mg/kg/day). Five short bowel patients (age: 53.4 +/- 19.2 years) who had normal liver function and lipid plasmatic profiles received 1920 +/- 300 ml of PN for 151 +/- 74 days (mean PN energy intake was 27.0 +/- 6.0 kcal/kg body weight, composed with 3.87 +/- 1.38 g/kg of carbohydrate, 0.72 +/- 0.25 g/kg of fat and 1.10 +/- 0.23 g/kg of amino acids). Plasma metabolites, liver enzymes, 7-cc-OH-cholesterol and steatosis levels were also evaluated before and after treatment. Student's t-tests were performed, and the results were expressed in means (+/- SD). Results: After treatment, decreases in the absolute values of cholesterol synthesis (0.31 +/- 0.12 mmol L-1 to 0.24 +/- 0.11 mmol L-1; p < 0.05), FSR of cholesterol (31.6 +/- 4.7% to 26.4 +/- 4.7%; p = 0.06) and FSR of triglycerides (12.8 +/- 5.8% to 9.2 +/- 5.5%; p < 0.01) were observed. Cholesterol and alanine aminotrans-ferase concentrations also decreased (ALT) (p < 0.05). The absolute values of triglyceride synthesis and triglyceride concentrations remained unchanged. Conclusions: In SBS patients, UDCA decreases the hepatic synthesis of triglycerides and cholesterol. These results suggest that UDCA could prevent the onset of the IFALD. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.
Published: 2020

17. Unlike for cellular mRNAs and other viral internal ribosome entry sites (IRESs), the eIF3 subunit e is not required for the translational activity of the HCV IRES

Author: Cendrine Faivre-Moskalenko, Pierre Jalinot, François-Loïc Cosset, Solène Denolly, Baptiste Panthu, Théophile Ohlmann, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physique et Centre Blaise Pascal, CNRS UMR5672, École normale supérieure - Lyon (ENS Lyon), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), 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), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: translation control, 0301 basic medicine, protein synthesis, in vitro reconstitution, Viral protein, Eukaryotic Initiation Factor-3, [SDV]Life Sciences [q-bio], eukaryotic translation initiation, host factor, Hepacivirus, Internal Ribosome Entry Sites, Biology, medicine.disease_cause, Biochemistry, Ribosome, Cell Line, Viral Proteins, 03 medical and health sciences, Eukaryotic translation, eukaryotic initiation factor 3 (eIF3), medicine, Protein biosynthesis, Animals, Humans, Gene silencing, Initiation factor, RNA, Messenger, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030102 biochemistry & molecular biology, internal ribosome entry site (IRES), this article, Translation (biology), Cell Biology, Hepatitis C, infection, 3. Good health, Cell biology, Internal ribosome entry site, 030104 developmental biology, ribosome, Protein Biosynthesis, RNA, Viral, RNA, Rabbits, viral infection, Ribosomes, hepatitis C virus (HCV), Protein Binding
Abstract: International audience; Viruses depend on the host cell translation machinery for their replication, and one common strategy is the presence of internal ribosome entry sites (IRESs) in the viral RNAs, using different sets of host translation initiation factors. The hepatitis C virus (HCV) IRES binds eukaryotic translation initiation factor 3 (eIF3), but the exact functional role of the eIF3 complex and of its subunits remains to be precisely defined. Toward this goal, here we focused on eIF3 subunit e. We used an in vitro assay combining a ribosome-depleted rabbit reticulocyte lysate and ribosomes prepared from HeLa or Huh-7.5 cells transfected with either control or eIF3e siRNAs. eIF3e silencing reduced translation mediated by the 5'UTR of various cellular genes and HCV-like IRESs. However, this effect was not observed with the bona fide HCV IRES. Silencing of eIF3e reduced the intracellular levels of the c, d, and l subunits of eIF3 and their association with the eIF3 core subunit a. A pulldown analysis of eIF3 subunits associated with the HCV IRES disclosed similar effects and that the a subunit is critical for binding to the HCV IRES. Carrying out HCV infections of control and eIF3e-silenced Huh-7.5 cells, we found that in agreement with the in vitro findings, eIF3e silencing does not reduce HCV replication and viral protein expression. We conclude that unlike for host cellular mRNAs, the entire eIF3 is not required for HCV RNA translation, favoring viral expression under conditions of low eIF3e levels.
Published: 2020

18. Uraemic toxin‐induced inflammation and oxidative stress in human endothelial cells: protective effect of polyphenol‐rich extract from açaí

Author: Patricia Leticia Trindade, Angela Castro Resende, Graziele Freitas de Bem, Christophe O. Soulage, Julio Beltrame Daleprane, Elaine Soares, Magna Cottini Fonseca Passos, Elisa B. Monteiro, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: Acai, Necrosis, Euterpe, Physiology, [SDV]Life Sciences [q-bio], uremic toxins, Inflammation, 030204 cardiovascular system & hematology, Pharmacology, Protective Agents, medicine.disease_cause, Antioxidants, endothelial dysfunction, Superoxide dismutase, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Human Umbilical Vein Endothelial Cells, medicine, Humans, oxidative stress, Secretion, Viability assay, Renal Insufficiency, Chronic, Endothelial dysfunction, Cells, Cultured, Nutrition and Dietetics, Cell Death, biology, Plant Extracts, Superoxide Dismutase, Chemistry, Polyphenols, General Medicine, medicine.disease, Endothelial stem cell, inflammation, biology.protein, Cytokines, medicine.symptom, Biomarkers, chronic kidney disease, 030217 neurology & neurosurgery, Oxidative stress
Abstract: NEW FINDING: What is the central question of this study? Polyphenols shows protective cardiometabolic actions in different disease models. A potential role of a polyphenols-rich extract from acai in preventing uremic toxin-induced endothelial dysfunction in endothelial cells has not been previously reported. What is the main finding and its importance? We showed that polyphenols from acai prevented cell death, restored the migratory capacity, protected from inflammation and contributed to antioxidant response restoration in endothelial cells exposed to uremic toxins. The protective role of acai from toxic effects exerted by uremic toxins presents a potential new therapeutic target in endothelial cells. ABSTRACT: Aims In chronic kidney disease (CKD), progressive loss of kidney function results in the accumulation of protein-bound uremic toxins such as p-cresyl-sulfate (p-CS) and indoxyl sulfate (IS). Among strategies to ameliorate uremic toxin harmful actions, phenolic compounds have been extensively studied. The main goal of this work was to evaluate the antioxidant and anti-inflammatory actions of phenolic-rich acai seed extract (ASE), in response to endothelial dysfunction induced by IS and p-CS, in human umbilical vein endothelial cells (HUVEC). Main methods Cells were treated with ASE (10 mug/mL) in the presence or absence of IS (61 mug/mL) and p-CS (40 mug/mL). Cell viability, cell death, cell migratory capacity and inflammatory biomarker expression were evaluated. Cellular antioxidant response was measured through the activity and expression of antioxidant enzymes and oxidative damage was evaluated. Key findings IS and p-CS lowered cell viability, triggered cell death and lowered the migratory capacity in endothelial cells (p \textless 0.05). ASE prevented cell death and restored the migratory capacity in cells exposed to IS. Both toxins up-regulated pro-inflammatory cytokine expression and ASE was able to beneficially counteract this effect. TNF-alpha secretion was greater in uremic toxins treated cells and ASE reversed this phenomenon in cells treated with both toxins concomitantly (p \textless 0.05). Regarding the antioxidant response, superoxide dismutase expression was strikingly lower in cells treated with both toxins, and ASE inhibited this harmful effect (p \textless 0.05). Significance From the results above, we conclude that ASE exerted protective effects on inflammation and oxidative stress caused by uremic toxins (particularly by IS) in human endothelial cells. This article is protected by copyright. All rights reserved.
Published: 2020

19. Treatment of hypoxia‐dependent cardiovascular diseases by myo‐inositol trispyrophosphate (ITPP)‐enhancement of oxygen delivery by red blood cells

Author: Michał Mączewski, Klaudia Brodaczewska, Bouchra El-Hafny-Rahbi, Claire Crola-Da Silva, Urszula Mackiewicz, Claudine Kieda, Aleksandra Paterek, Marta Oknińska, 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), Centre de biophysique moléculaire (CBM), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: 0301 basic medicine, Male, Erythrocytes, [SDV]Life Sciences [q-bio], Inositol Phosphates, Stimulation, cardiomyocytes, Pharmacology, Regenerative medicine, 03 medical and health sciences, Hemoglobins, Mice, 0302 clinical medicine, In vivo, oxygen delivery, medicine, Animals, Myocytes, Cardiac, Myocardial infarction, Rats, Wistar, business.industry, hypoxia, Cell Biology, Original Articles, Hypoxia (medical), medicine.disease, haemoglobin, In vitro, 3. Good health, Rats, Mice, Inbred C57BL, Oxygen, 030104 developmental biology, myocardial infarction, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Heart failure, Oxygen delivery, Erythrocyte Count, Molecular Medicine, Original Article, Female, medicine.symptom, business
Abstract: Heart failure is a consequence of progression hypoxia‐dependent tissue damages. Therapeutic approaches to restore and/or protect the healthy cardiac tissue have largely failed and remain a major challenge of regenerative medicine. The myo‐inositol trispyrophosphate (ITPP) is a modifier of haemoglobin which enters the red blood cells and modifies the haemoglobin properties, allowing for easier and better delivery of oxygen by the blood. Here, we show that this treatment approach in an in vivo model of myocardial infarction (MI) results in an efficient protection from heart failure, and we demonstrate the recovery effect on post‐MI left ventricular remodelling in the rat model. Cultured cardiomyocytes used to study the molecular mechanism of action of ITPP in vitro displayed the fast stimulation of HIF‐1 upon hypoxic conditions. HIF‐1 overexpression was prevented by ITPP when incorporated into red blood cells applied in a model of blood‐perfused cardiomyocytes coupling the dynamic shear stress effect to the enhanced O2 supply by modification of haemoglobin ability to release O2 in hypoxia. ITPP treatment appears a breakthrough strategy for the efficient and safe treatment of hypoxia‐ or ischaemia‐induced injury of cardiac tissue.
Published: 2020

20. Lactiplantibacillus plantarum WJL administration during pregnancy and lactation improves lipid profile, insulin sensitivity and gut microbiota diversity in dyslipidemic dams and protects male offspring against cardiovascular dysfunction in later life

Author: Whyara Karoline Almeida da Costa, François Leulier, Valdir A. Braga, Keyth Sulamitta de Lima Guimarães, Deoclécio Alves Chianca Júnior, José Luiz de Brito Alves, Emmanuelle Meugnier, Hubert Vidal, Sylvana Rendeiro de Noronha, Larissa Ramalho Brandão, Marciane Magnani, Kassem Makki, Josiane C. Cruz, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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)-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), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Inflammasome NLRP3 – NLRP3 Inflammasome, Centre International de Recherche en Infectiologie (CIRI), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Paraiba State Research Foundation (PRONEX) 007/2019 FAPESQ-PB-MCTI/CNPq, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre International de Recherche en Infectiologie - UMR (CIRI), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Offspring, [SDV]Life Sciences [q-bio], Physiology, 030204 cardiovascular system & hematology, Gut flora, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Lactation, medicine, Weaning, 2. Zero hunger, Pregnancy, medicine.diagnostic_test, biology, business.industry, General Medicine, medicine.disease, biology.organism_classification, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Lipid profile, business, Dyslipidemia, Food Science
Abstract: International audience; Background and aim: Maternal dyslipidemia is recognized as a risk factor for the development of arterial hypertension (AH) and cardiovascular dysfunction in offspring. Here we evaluated the effects of probiotic administration of a specific strain of Lactiplantibacillus plantarum(WJL) during pregnancy and lactation on gut microbiota and metabolic profile in dams fed with a high-fat and high-cholesterol (HFHC) diet and its long-term effects on the cardiovascular function in male rat offspring.Methods and results: Pregnant Wistar rats were allocated into three groups: dams fed a control diet (CTL = 5), dams fed a HFHC diet (DLP = 5) and dams fed a HFHC diet and receivingL. plantarum WJL during pregnancy and lactation (DLP-Lp(WJL)).L. plantarum WJL (1 x 10(9)CFU) or vehicle (NaCl, 0.9%) was administered daily by oral gavage for 6 weeks, covering the pregnancy and lactation periods. After weaning, male offspring received a standard diet up to 90 days of life. Biochemical measurements and gut microbiota were evaluated in dams. In male offspring, blood pressure (BP), heart rate (HR) and vascular reactivity were evaluated at 90 days of age. Dams fed with a HFHC diet during pregnancy and lactation had increased lipid profile and insulin resistance and showed dysbiotic gut microbiota. Administration of L. plantarum WJL to dams having maternal dyslipidemia improved gut microbiota composition, lipid profile and insulin resistance in them. Blood pressure was augmented and vascular reactivity was impaired with a higher contractile response and a lower response to endothelium-dependent vasorelaxation in DLP male offspring. In contrast, male offspring of DLP-Lp(WJL) dams had reduced blood pressure and recovered vascular function in later life.Conclusion: Administration ofL. plantarum WJL during pregnancy and lactation in dams improved gut microbiota diversity, reduced maternal dyslipidemia and prevented cardiovascular dysfunction in male rat offspring.
Published: 2020

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

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

22. Risk factors for vancomycin-resistant enterococcus acquisition during a large outbreak in patients aged 65 years and older

Author: Benjamin Mathis, Max Haine, Raphaële Girard, Marc Bonnefoy, Forschungszentrum Karlsruhe (FZK), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: Male, Aging, Multivariate analysis, [SDV]Life Sciences [q-bio], lcsh:Geriatrics, medicine.disease_cause, Logistic regression, Disease Outbreaks, Cohort Studies, older people, 0302 clinical medicine, Risk Factors, Vancomycin-resistant enterococcus, 030212 general & internal medicine, 10. No inequality, Aged, 80 and over, 0303 health sciences, education.field_of_study, Cross Infection, 3. Good health, Anti-Bacterial Agents, outbreak, Cohort, Female, France, Research Article, medicine.medical_specialty, Population, Context (language use), Vancomycin-Resistant Enterococci, 03 medical and health sciences, Vancomycin, Internal medicine, medicine, Humans, Vancomycin-resistant Enterococcus, Risk factor, education, Gram-Positive Bacterial Infections, Aged, Retrospective Studies, 030306 microbiology, business.industry, Outbreak, Vancomycin Resistance, biochemical phenomena, metabolism, and nutrition, lcsh:RC952-954.6, Geriatrics and Gerontology, business
Abstract: BackgroundIn the context of an aging population, identifying risk factors for Vancomycin-resistant enterococci (VRE), specific to older people, is important. However, if age is a known risk factor for VRE infection, a limited number of studies have focused on older patients. This study aimed to identify potential risk factors for VRE acquisition in a population aged 65 years and older, during a large VRE outbreak that occurred in a teaching hospital in Lyon, France, from December 2013 to July 2014.MethodsThe present retrospective, multi-center, descriptive, and analytical study used part of a previous cohort, and included only a sub-group of patients aged 65 years and older. The analysis of the factors included in the original study was completed with factors more specific to geriatric patients. Inclusion criteria were patients aged 65 years and older, in contact with a VRE index patient. Patients were screened by rectal swabs. Univariate and multivariate logistic regression analyses were performed.ResultsA total of 180 VRE contacts were included and 18 patients became carriers. Multivariate analysis showed that risk factors for VRE acquisition in older people included major contact type (RR: 5.31, 95%CI [1.33; 21.19]), number of antibiotics used (RR: 1.36, 95%CI [1.04; 1.76]), a score of McCabe = 2 (RR: 116.39, 95%CI [5.52; 2455.98]), ethylism (RR: 5.50, 95%CI [1.49; 20.25]), and dementia (RR: 7.50, 95%CI [1.89; 29.80]).ConclusionsThis study was able to demonstrate risk factors for VRE acquisition in older people. These risk factors should be taken into account when in the presence of older people in a VRE infected unit.
Published: 2019

23. Comparison of Early-Compartment Correction Equations for GFR Measurements

Author: Justine B. Bukabau, D. Monnet, Eric Yayo, Sandrine Lemoine, Ernest Kiswaya Sumaili, Pierre Delanaye, Etienne Cavalier, Elke Schaeffner, Emmanuelle Vidal-Petiot, Martin Flamant, Hans Pottel, Laurence Dubourg, Natalie Ebert, Université de Liège, Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU Henri Mondor, and Hôpital Universitaire Leuven
Subjects: Pathology, medicine.medical_specialty, Science & Technology, business.industry, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Urology & Nephrology, 030204 cardiovascular system & hematology, lcsh:Diseases of the genitourinary system. Urology, lcsh:RC870-923, GLOMERULAR-FILTRATION-RATE, 03 medical and health sciences, 0302 clinical medicine, Nephrology, IOHEXOL, Research Letter, Medicine, PLASMA-CLEARANCE, business, Compartment (pharmacokinetics), Life Sciences & Biomedicine
Abstract: ispartof: KIDNEY INTERNATIONAL REPORTS vol:5 issue:7 pages:1079-1081 ispartof: location:United States status: published
Published: 2020

24. Cyclosporine A: a valid candidate to treat COVID-19 patients with acute respiratory failure?

Author: Michel Ovize, Martin Cour, Laurent Argaud, 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), Department of Cardiology, Hospices Civils de Lyon (HCL), Hôpital Edouard Herriot, Service Anesthésie Réanimation, Hôpital Edouard Herriot [CHU - HCL], and Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)
Subjects: medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Respiratory Insufficiency/*drug therapy/epidemiology, Pneumonia, Viral, MEDLINE, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Pandemic, medicine, Humans, Acute respiratory failure, Intensive care medicine, Pandemics, Cyclosporine/*therapeutic use, 030304 developmental biology, 0303 health sciences, business.industry, Viral Epidemiology, Viral/*drug therapy/epidemiology, lcsh:Medical emergencies. Critical care. Intensive care. First aid, COVID-19, Pneumonia, lcsh:RC86-88.9, medicine.disease, Editorial, Treatment Outcome, Acute Disease, Cyclosporine, Coronavirus Infections/*drug therapy/epidemiology, Coronavirus Infections, Respiratory Insufficiency, business, 030217 neurology & neurosurgery
Published: 2020

25. Cyclosporine A prevents cardiac arrest-induced acute respiratory failure: a post-hoc analysis of the CYRUS trial

Author: Martin Cour, Michel Ovize, Laurent Argaud, Louis Kreitmann, Hôpital Edouard Herriot, Service Anesthésie Réanimation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 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), Department of Cardiology, and Hospices Civils de Lyon (HCL)
Subjects: 0303 health sciences, medicine.medical_specialty, Letter, business.industry, [SDV]Life Sciences [q-bio], Pain medicine, MEDLINE, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology, Emergency medicine, Post-hoc analysis, Cyclosporine, Humans, Medicine, Acute respiratory failure, Respiratory Insufficiency, business, Out-of-Hospital Cardiac Arrest, 030304 developmental biology
Published: 2020

26. Life/2020—the future of kidney disease

Author: Christoph Wanner, Denis Fouque, Peter Stenvinkel, Karolinska Institutet [Stockholm], 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), Hospices Civils de Lyon (HCL), University Hospital Wuerzburg, ROSSI, Sabine, Université Claude Bernard Lyon 1 (UCBL), 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 University Hospital Wuerzburg / Universitätsklinikum Würzburg
Subjects: Transplantation, medicine.medical_specialty, Introduction, business.industry, 030232 urology & nephrology, 030204 cardiovascular system & hematology, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Nephrology, Medicine, business, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Kidney disease
Abstract: International audience
Published: 2020

27. Lipopolysaccharide-Binding Protein, Soluble CD14, and the Long-Term Risk of Alzheimer’s Disease: A Nested Case-Control Pilot Study of Older Community Dwellers from the Three-City Cohort

Author: Cécilia Samieri, Jean-François Dartigues, Charline Buisson, Catherine Féart, Perrine André, Fabienne Laugerette, Catherine Helmer, Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), U 897 Department of Nutritional Epidemiology, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Bordeaux Segalen - Bordeaux 2, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), 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), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Fondation pour la Recherche Medicale, Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Région Bourgogne-Franche-Comté, Région Nouvelle-Aquitaine, Fondation de France, Ministry of Research-INSERM Program Cohortes et collections de données biologiques, Fondation Plan Alzheimer, Caisse Nationale pour la Solidarité et l'Autonomie (CNSA), and ITMO Santé Publique - Alliance nationale pour les sciences de la vie et de la sante (AVIESAN) [ISP05 2014]
Subjects: Male, 0301 basic medicine, endotoxins, Urban Population, [SDV]Life Sciences [q-bio], Lipopolysaccharide Receptors, Pilot Projects, Disease, soluble cluster, neuroinflammation, Pathogenesis, serum-levels, 0302 clinical medicine, oxidative stress, Aged, 80 and over, education.field_of_study, Membrane Glycoproteins, biology, Incidence, General Neuroscience, lipopolysaccharide, General Medicine, Alzheimer's disease, metabolic endotoxemia, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Cohort, Female, France, Independent Living, medicine.symptom, Lipopolysaccharide binding protein, lipopolysaccharide-binding protein, Population, Inflammation, 03 medical and health sciences, Alzheimer Disease, medicine, Humans, Dementia, education, Aged, lps, business.industry, interleukin-6, of differentiation-14, medicine.disease, 030104 developmental biology, inflammation, Case-Control Studies, Nested case-control study, Immunology, biology.protein, cells, beta, Neurosciences & Neurology, Geriatrics and Gerontology, Carrier Proteins, tumor-necrosis-factor, business, 030217 neurology & neurosurgery, Acute-Phase Proteins, dementia
Abstract: Background Identifying the mechanisms involved in the pathogenesis of Alzheimer's disease (AD) remains crucially important. Chronic age-related low-grade inflammation is considered to be one such mechanism, although its causes are unclear. Lipopolysaccharide (LPS)-type endotoxins, a major component of the outer membrane of Gram-negative bacteria, are known as potent pro-inflammatory molecules. Therefore, we hypothesized that greater exposure to circulating LPS, potentially mediated by the inflammatory pathway, would be a key step of the onset of AD. Objective The aim of this study was to investigate the link between plasma endotoxin-exposure, inflammation, and AD. Methods Applying a nested case-control design, we evaluated the associations among baseline plasma endotoxin-exposure (assessed by measuring LPS-binding protein (LBP) and soluble cluster of differentiation-14 (sCD14) levels), inflammation (assessed by measuring interleukin-6 (IL6) levels), and the odds of developing AD over 12 years. Selected from a population-based cohort, 212 incident cases of AD were matched with 424 controls without dementia with regard to age, gender, and education level. Results After adjusting for a large set of confounders, including the use of anti-inflammatory drugs, only higher LBP levels were significantly associated with a 30% higher odds of developing AD over 12 years (OR 1.30, 95% CIs [1.07-1.59]), regardless of IL6 levels. Conclusion This large case-control study provides preliminary results concerning plasma endotoxin-exposure among the elderly and suggests that higher LBP levels, an acute-phase reactant involved in the pro-inflammatory response to LPS, are associated with higher odds of developing AD.
Published: 2019

28. Predictive factors for category II pressure ulcers in older patients with hip fractures: a prospective study

Author: Matteo Chiarabelli, Cristiana Forni, Mattia Morri, Tania Sabattini, Elisa Ambrosi, Fabio D'Alessandro, Domenica Gazineo, Paolo Chiari, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and 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)
Subjects: medicine.medical_specialty, Time Factors, Nursing (miscellaneous), [SDV]Life Sciences [q-bio], Comorbidity, Dermatology, outcomes, Severity of Illness Index, surgery, scale, older people, pressure ulcers, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, prevention, Older patients, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, care, 030212 general & internal medicine, risk-factors, Prospective cohort study, Aged, risk, Aged, 80 and over, Pressure Ulcer, business.industry, Incidence, Incidence (epidemiology), factors, Length of Stay, Middle Aged, 3. Good health, Hospitalization, cardiovascular surgical-patients, hip fractures, prospective study, risk factors, Hip Joint, Fundamentals and skills, business, Older people
Abstract: Objective: To identify the incidence of category II or higher hospital-acquired pressure ulcers (HAPU) and significantly associated factors in older patients with hip fractures. PUs are a frequent complication in hip fracture patients, negatively impacting patients' quality of life, the health-care system and society. Method: A prospective cohort study was conducted. A consecutive sample of patients with pertrochanteric, femoral neck or subtrochanteric fractures requiring surgical treatment, were included. A stepwise, multiple regression was performed to identify factors associated with PU development. Results: A total of 761 patients aged ≥65 years were sampled. The incidence of category II or higher PUs was 12%. The study identified five factors that were significantly, independently associated with category II or higher PU development, including a higher preoperative Braden score (Hazard Ratio [HR]: 0.884; 95% confidence interval [CI]: 0.806–0.969), surgical procedure with osteosynthesis (HR 1.876; 95%CI: 1.183–2.975), a higher percentage of days with the presence of foam valve before surgery (HR: 1.010; 95%CI: 1.010–1.023) and a urinary catheter (HR: 1.013; 95%CI: 1.006–1.019) and diaper (HR: 1.007; 95% CI 1.001–1.013) in the postoperative period. Conclusion: Attention should be given by clinical staff to avoiding the use of foam valves, to limiting the use of diapers and to early removal of urinary catheters.
Published: 2019

29. Difficulty of the decision‐making process in emergency departments for end‐of‐life patients

Author: Pierre Le Coz, Marion Douplat, Véronique Potinet, Karim Tazarourte, Anne-Marie Schott, Julien Berthiller, Laurent Jacquin, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Espace éthique méditerranéen, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Edouard Herriot [CHU - HCL], Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), and 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)
Subjects: Male, medicine.medical_specialty, Nursing staff, Surrogate decision-maker, [SDV]Life Sciences [q-bio], Comorbidity, decision making, Hospitals, University, 03 medical and health sciences, death, medicine, Humans, Dementia, Prospective Studies, Decision-making, Aged, Aged, 80 and over, Terminal Care, emergency service, business.industry, 030503 health policy & services, Health Policy, Age Factors, Public Health, Environmental and Occupational Health, advance directives, Physical Functional Performance, medicine.disease, University hospital, humanities, 3. Good health, Withholding Treatment, Multicenter study, Emergency medicine, Female, France, Emergency Service, Hospital, 0305 other medical science, Nursing homes, business
Abstract: Background In emergency departments, for some patients, death is preceded by a decision of withholding or withdrawing life-sustaining treatments. This concerns mainly patients over 80, with many comorbidities. The decision-making process of these decisions in emergency departments has not been extensively studied, especially for noncommunicating patients. Aim The purpose of this study is to describe the decision-making process of withholding and withdrawing life-sustaining treatments in emergency departments for noncommunicating patients and the outcome of said patients. Design We conducted a prospective multicenter study in three emergency departments of university hospitals from September 2015 to January 2017. Results We included 109 patients in the study. Fifty-eight (53.2%) patients were coming from nursing homes and 52 (47.7%) patients had dementia. Decisions of withholding life-sustaining treatment concerned 93 patients (85.3%) and were more frequent when a surrogate decision maker was present 61 (65.6%) versus seven (43.8%) patients. The most relevant factors that lead to these decisions were previous functional limitation (71.6%) and age (69.7%). Decision was taken by two physicians for 80 patients (73.4%). The nursing staff and general practitioner were, respectively, involved in 31 (28.4%) and two (1.8%) patients. A majority of the patients had no advance directives (89.9%), and the relatives were implicated in the decision-making process for 96 patients (88.1%). Death in emergency departments occurred for 47 patients (43.1%), and after 21 days, 84 patients (77.1 %) died. Conclusion There is little anticipation in end-of-life decisions. Discussion with patients concerning their end-of-life wishes and the writing of advance directives, especially for patients with chronic diseases, must be encouraged early.
Published: 2019

30. Bicarbonate Supplement Restores Urinary Klotho Excretion in Chronic Kidney Disease: A Pilot Study

Author: Jocelyne Drai, Valerie Hage, Maurice Laville, Cédric Villain, Denis Fouque, Solenne Pelletier, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire de 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), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CRNH Rhône-Alpes, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), and 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)
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Urinary system, medicine.medical_treatment, 030232 urology & nephrology, Medicine (miscellaneous), Pilot Projects, urologic and male genital diseases, Gastroenterology, Excretion, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, Renal Insufficiency, Chronic, Klotho Proteins, Klotho, Dialysis, Aged, Glucuronidase, Acidosis, 030109 nutrition & dietetics, Nutrition and Dietetics, Sodium bicarbonate, business.industry, Metabolic acidosis, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, Sodium Bicarbonate, chemistry, Nephrology, Dietary Supplements, Female, medicine.symptom, business, Kidney disease
Abstract: OBJECTIVE: We tested the hypothesis that correcting acidosis may improve urinary Klotho excretion and serum alpha-Klotho. DESIGN: This is a prospective, interventional, nonrandomized, open-label trial study. In this study setting, metabolic acidosis is commonly observed during chronic kidney disease (CKD). We reported a positive relationship between serum bicarbonate (Sbicar) and serum alpha-Klotho in these patients. SUBJECTS: The study involved 20 patients with a known kidney disease referred for renal checkup. Inclusion criteria were age \textgreater/= 18 years, CKD stage 3-5 non dialysis, Sbicar \textless 22 mmol/L, and not receiving bicarbonate supplementation. INTERVENTION: Patients were then prescribed 1 g of oral sodium bicarbonate 3 times per day for 4 weeks. MAIN OUTCOME MEASURE: Patients were evaluated at two and 4 weeks by blood and urine measurements. RESULTS: Mean serum Klotho was 615 +/- 287 pg/mL, and mean serum Sbicar was 19.3 +/- 1.7 mmol/L at baseline. Sbicar increased from baseline at two (23.9 +/- 2.9 mmol/L, P \textless .001) and 4 weeks (23.4 +/- 1.9 mmol/L, P \textless .001). There was no change in serum Klotho at two (630 +/- 333 mmol/L) and 4 weeks (632 +/- 285 mmol/L). By contrast, urine Klotho/creatinine ratio, which was very low at baseline (34.6 +/- 31.6 pg/mmoL), increased by 320% at two weeks (P \textless .005) and by 280% at 4 weeks (P \textless .01). CONCLUSIONS: Correcting acidosis by oral administration of sodium bicarbonate rapidly increases the urine excretion of soluble alpha-Klotho in CKD patients. However, a 4-week bicarbonate treatment was not able to increase serum alpha-Klotho. A longer study may confirm this pilot observation and increase serum Klotho, which has been shown to exert a protective cardiovascular effect during CKD.
Published: 2019

31. Evolution of the human cold/menthol receptor, TRPM8

Author: Morad Roudbaraki, Samuel Blanquart, Martin Figeac, Natalia Prevarskaya, Philippe Delcourt, Christopher A. Emerling, Anne-Sophie Borowiec, Gabriel Bidaux, Andrea S. Meseguer, Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), 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), INSERM, Ministère de l'Education Nationale, Région Nord-Pas-de-Calais, Inria, Fondation pour la Recherche Médicale, Centre National de la Recherche Scientifique (CNRS), Dynamics, Logics and Inference for biological Systems and Sequences (Dyliss), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Rôle des canaux ioniques membranaires et du calcium intracellulaire dans la physiopathologie de la prostate, Université de Lille, Sciences et Technologies-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: 0106 biological sciences, 0301 basic medicine, Gene isoform, Bioinformatics, Evolution, [SDV]Life Sciences [q-bio], TRPM Cation Channels, Biology, 010603 evolutionary biology, 01 natural sciences, Cold and menthol receptor, Evolution, Molecular, Mice, Open Reading Frames, 03 medical and health sciences, Exon, Transient receptor potential channel, Alternative transcription, Splice variants, Cell Line, Tumor, Genetics, TRPM8, Animals, Humans, Protein Isoforms, RNA, Messenger, Molecular Biology, Gene, Phylogeny, Ecology, Evolution, Behavior and Systematics, Comparative genomics, Alternative splicing, Genetic Variation, Exons, Phylogenetics, Cold Temperature, Alternative Splicing, Menthol, HEK293 Cells, 030104 developmental biology, Evolutionary biology, Human genome, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Isoforms
Abstract: International audience; Genes showing versatile functions or subjected to fast expansion and contraction during the adaptation of species to specific ecological conditions, like sensory receptors for odors, pheromones and tastes, are characterized by a great plasticity through evolution. One of the most fascinating sensory receptors in the family of TRP channels, the cold and menthol receptor TRPM8, has received significant attention in the literature. Recent studies have reported the existence of TRPM8 channel isoforms encoded by alternative mRNAs transcribed from alternative promoters and processed by alternative splicing. Since the first draft of the human genome was accomplished in 2000, alternative transcription, alternative splicing and alternative translation have appeared as major sources of gene product diversity and are thought to participate in the generation of complexity in higher organisms. In this study, we investigate whether alternative transcription has been a driving force in the evolution of the human forms of the cold receptor TRPM8. We identified 33 TRPM8 alternative mRNAs (24 new sequences) and their associated protein isoforms in human tissues. Using comparative genomics, we described the evolution of the human TRPM8 sequences in eight ancestors since the origin of Amniota, and estimated in which ancestors the new TRPM8 variants originated. In order to validate the estimated origins of this receptor, we performed experimental validations of predicted exons in mouse tissues. Our results suggest a first diversification event of the cold receptor in the Boreoeutheria ancestor, and a subsequent divergence at the origin of Simiiformes.
Published: 2019

32. Bacillus cereusinfection in neonates and the absence of evidence for the role of banked human milk: Case reports and literature review

Author: Marc-Christian Domingo, Thérèse Perreault, Caroline Quach, Gilles Delage, Pierre Frange, Antoine Lewin, Jean-Charles Picaud, Virginie Rigourd, Cindy Lalancette, Marc Germain, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), and HemaQuebec
Subjects: Microbiology (medical), Epidemiology, [SDV]Life Sciences [q-bio], Bacillus cereus, Biology, Microbiology, 03 medical and health sciences, Molecular typing, 0302 clinical medicine, 030225 pediatrics, Humans, 030212 general & internal medicine, Holder pasteurization, Gram-Positive Bacterial Infections, Cross Infection, Milk, Human, Indirect contact, fungi, Infant, Newborn, Quebec, Bacillus cereus infection, biology.organism_classification, 3. Good health, Neonatal infection, Infectious Diseases, Milk Banks, Cereus, Infant, Extremely Low Birth Weight, Causal link
Abstract: Background:Banked human milk (BHM) has inherent infectious risks, even when pasteurized. Because of the ubiquity ofBacillus cereusin the environment and its ability to resist the Holder pasteurization process, there is a concern that BHM might lead to severeB. cereusinfections.Objective:We reviewed observed and published cases to determine the potential causal role of BHM as the source of these infections.Methods:Two infants in the province of Québec (Canada) developed aB. cereusneonatal infection, and both had received BHM. We conducted bacteriological studies to compare clinical isolates and those found in these cases.Results:After extended culture of BHM retention lots,B. cereuswas found to have been involved in batches related to the first case. However, molecular typing showed that the strain was different from the clinical isolate, therefore excluding BHM as the source of contamination. In the second case, aBrevibacillusspp was isolated, a species distinct from the clinical isolate.Conclusion:Based on these cases and others reported in the literature, a causal link betweenB. cereuscontaminated BHM and preterm neonatal infection has never been documented. Therefore, the risk that BHM can cause this infection remains theoretical. Given the widespread presence ofB. cereusin the hospital environment and its capacity to resist standard cleaning procedures, it seems likely that airborne or direct or indirect contact are the main sources of most, if not all, cases of severeB. cereusneonatal infections, even in babies exposed to BHM.
Published: 2019

33. Association between physical activity and sedentary behaviour on carotid atherosclerotic plaques: an epidemiological and histological study in 90 asymptomatic patients

Author: Antoine Millon, Mathilde Mura, Philippe Connes, Stéphanie Chanon, Nellie Della-Schiava, Vincent Pialoux, Patrick Lermusiaux, Aurélie Vieille-Marchiset, Pauline Mury, Virginie Nicaise, Diane Collet-Benzaquen, Erica N. Chirico, Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Laboratoire de l'intégration, du matériau au système (IMS), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Laboratoire sur les Vulnérabilités et l'Innovation dans le Sport (EA 7428) (L-VIS), Université de Lyon-Université de Lyon, Laboratoire Technipath, Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Hôpital Edouard Herriot [CHU - HCL], Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Cooper Medical School of Rowan University [Camden] (CMSRU), Institut Universitaire de France, and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, [SDV]Life Sciences [q-bio], medicine.medical_treatment, physical activity, Carotid endarterectomy, 030204 cardiovascular system & hematology, Metabolic equivalent, [SCCO]Cognitive science, 0302 clinical medicine, Risk Factors, Medicine, Orthopedics and Sports Medicine, 030212 general & internal medicine, Stroke, ComputingMilieux_MISCELLANEOUS, exercise physiology, Endarterectomy, Aged, 80 and over, Endarterectomy, Carotid, education.field_of_study, biology, cardiovascular, Fibrous cap, General Medicine, Plaque, Atherosclerotic, Carotid Arteries, medicine.anatomical_structure, Cardiovascular Diseases, Cardiology, Female, medicine.symptom, medicine.medical_specialty, Population, potential conflict of interest, Hemorrhage, Physical Therapy, Sports Therapy and Rehabilitation, Asymptomatic, lipids, 03 medical and health sciences, Internal medicine, absence of any commercial or financial relationships that could be construed as a, Humans, education, Exercise, Aged, business.industry, medicine.disease, Cross-Sectional Studies, Asymptomatic Diseases, Histopathology, Sedentary Behavior, business
Abstract: ObjectiveCarotid atherosclerotic plaques are a source of emboli for stroke. ‘Unstable’ carotid atherosclerotic plaques may have intraplaque haemorrhages, neovessels, prevalent macrophages, excessive calcium deposits, a large lipid core and a thin fibrous cap. Regular physical activity (PA) may lower the risk of plaques becoming unstable. We evaluated the association of both PA and sedentary behaviour (SB) with carotid plaque histopathology.Methods90 asymptomatic patients who were undergoing carotid endarterectomy for carotid artery narrowing identified on ultrasound reported their PA and SB by questionnaires. We calculated PA intensity in MET (metabolic equivalent of task)-min/week. For analysis, the population was divided into tertiles according to PA (T1PA: the less PA patients; T2PA: the intermediate PA patients; T3PA: the most physically active patients) (T1PAResultsIntraplaque haemorrhage was less frequent in the most physically active tertile (T3PA, 48%) versus T1PA (74%) and in the least sedentary tertile T1SB (50%) versus T3SB (71%). The intraplaque haemorrhage was less frequent in those who exercised more than 900 MET-min/week (59% vs 47% for >900 and ConclusionIn this cross-sectional study of asymptomatic patients who underwent endarterectomy (i) higher reported PA, (ii) intensity of PA and (iii) lower reported SB were associated with lower prevalence of intraplaque haemorrhage. This could be a mechanism whereby PA protects against cerebrovascular disease (stroke) and death.
Published: 2019

34. The Role for Protein Restriction in Addition to Renin-Angiotensin-Aldosterone System Inhibitors in the Management of CKD

Author: Laetitia Koppe, Denis Fouque, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), and 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)
Subjects: Male, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, synergy, Angiotensin-Converting Enzyme Inhibitors, keto-analogue, Pharmacology, urologic and male genital diseases, Severity of Illness Index, renin-angiotensin-aldosterone system (RAAS), chemistry.chemical_compound, 0302 clinical medicine, RAAS inhibition, 030212 general & internal medicine, Kidney, Aldosterone, Disease Management, angiotensin-converting enzyme inhibitor (ACEi), Prognosis, Combined Modality Therapy, 3. Good health, Low protein diet, Treatment Outcome, nutrition, medicine.anatomical_structure, Nephrology, Disease Progression, Female, angiotensin receptor blocker (ARB), Glomerular hyperfiltration, CKD progression, review, Renal function, chronic kidney disease (CKD), 03 medical and health sciences, dietary intervention, Renin–angiotensin system, Diet, Protein-Restricted, medicine, Humans, Renal Insufficiency, Chronic, Salt intake, business.industry, renal function, Glomerulosclerosis, medicine.disease, protein intake, chemistry, Kidney Failure, Chronic, proteinuria, business, Kidney disease
Abstract: In experimental studies a low-protein diet (LPD) and renin-angiotensin-aldosterone system (RAAS) inhibitors are both reported to slow the progression of chronic kidney disease (CKD) and reduce proteinuria. RAAS activity contributes to increased blood pressure, fluid retention, and positive sodium balance, but also to kidney damage by enhancing glomerular capillary filtration pressure and synthesis of profibrotic molecules such as transforming growth factor beta. It has been well established that an LPD decreases glomerular hyperfiltration and the generation of uremic toxins, as well as the burden of acid load, phosphorus, and sodium. In different animal CKD models, a significant reduction in proteinuria and glomerulosclerosis has been achieved when an RAAS inhibitor and LPD were combined. To date, high-quality intervention trials investigating this combined strategy are lacking. We summarize the experimental and clinical studies that have examined a potential additive action of these therapies on CKD progression. We outline potential mechanisms of action and additive efficacy of an LPD and RAAS inhibitors in CKD, with a particular emphasis on phosphate levels, uremic toxin production, acid load, and salt intake. Finally, although the evidence is inadequate to recommend combining RAAS inhibitors and an LPD to slow the progression of CKD, we provide a perspective to support a large-scale randomized clinical trial to study this combination.
Published: 2019

35. Postimplant biological aortic prosthesis degeneration: challenges in transcatheter valve implants

Author: Jean-François Obadia, Thierry Folliguet, Elham Bidar, Alessandro Parolari, Jolanda Kluin, Claudio Muneretto, Ehsan Natour, Rachid Zegdi, Piotr Suwalski, Nikolaos Bonaros, Nawwar Al-Attar, Malakh Shrestha, Roberto Lorusso, Martin Czerny, Prakash P Punjabi, Rafa Sadaba, Fabio Barili, Michele De Bonis, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Service de Chirurgie Cardiaque [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Cardiothoracic Surgery, ACS - Heart failure & arrhythmias, ACS - Atherosclerosis & ischemic syndromes, Bidar, Elham, Folliguet, Thierry, Kluin, Jolanda, Muneretto, Claudio, Parolari, Alessandro, Barili, Fabio, Suwalski, Piotr, Bonaros, Nikolao, Punjabi, Prakash, Sadaba, Rafa, De Bonis, Michele, Al-Attar, Nawwar, Obadia, Jean Francoi, Czerny, Martin, Shrestha, Malakh, Zegdi, Rachid, Natour, Ehsan, Lorusso, Roberto, MUMC+: MA Med Staf Artsass CTC (9), MUMC+: MA Med Staf Spec CTC (9), RS: Carim - V04 Surgical intervention, CTC, and RS: CARIM - R2.12 - Surgical intervention
Subjects: Aortic valve, Transcatheter aortic valve implant, Swine, [SDV]Life Sciences [q-bio], Degeneration (medical), 030204 cardiovascular system & hematology, FASTER DEGENERATION, 0302 clinical medicine, Aortic valve replacement, LONG-TERM OUTCOMES, Medicine, TRANSCATHETER AORTIC VALVE IMPLANT, Aged, 80 and over, HEART-VALVES, Structural valve degeneration, Transcatheter aortic valve degeneration, PATIENT MISMATCH, General Medicine, Middle Aged, 3. Good health, Prosthesis Failure, HANCOCK II BIOPROSTHESIS, medicine.anatomical_structure, Aortic Valve, Heart Valve Prosthesis, Cardiology and Cardiovascular Medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, PARAVALVULAR REGURGITATION, Transcatheter Aortic Valve Replacement, 03 medical and health sciences, medicine.artery, Animals, Humans, HIGH-RISK PATIENTS, HEMODYNAMIC DETERIORATION, Aged, Bioprosthesis, IN-VALVE, Aorta, business.industry, BOVINE PERICARDIUM, medicine.disease, Surgery, Tissue Degeneration, Stenosis, 030228 respiratory system, Implant, business
Abstract: International audience; Surgical aortic valve replacement (SAVR) is highly effective and can be achieved with relatively low risk in patients with severe aortic stenosis. Bioprostheses have been used most frequently during the past 60 years. However, the function of biological valves usually declines after 10-15 years from implant when structural valve degeneration occurs often mandating a reoperation once valve dysfunction becomes haemodynamically significant. Known for many years by surgeons and cardiologists taking care of patients with SAVR, the issue of postimplant structural valve degeneration has been recently highlighted also in patients with transcatheter aortic valve implant (TAVI). There is growing concern that TAVI valves exhibit structural valve degeneration due to inherent challenges of the deployment mode. The impact on postimplant degeneration of TAVI valves compared to SAVR has still to be understood and defined. Based on the ongoing process of expanding TAVI indications, several potential shortcomings and caveats, learned during the last 60 years of SAVR experience, should be taken into consideration to refine this technique.
Published: 2019

36. Red Blood cell IMPDH activity in adults and children with or without azathioprine: Relationship between thiopurine metabolites, ITPA and TPMT activities

Author: Anthony Conway, Audrey Beringer, Roselyne Boulieu, Antony Citterio-Quentin, Aishling Ryan, Amal El Mahmoudi, Alain Lachaux, Thibault Perret, Département de pédiatrie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut des Sciences Pharmaceutiques et Biologiques de Lyon - Département de Pharmacie Clinique, de Pharmacocinétique et d'Evaluation du Médicament, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and 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)
Subjects: Adult, Male, Erythrocytes, Adolescent, [SDV]Life Sciences [q-bio], Lymphocyte, Azathioprine, Pharmacology, Toxicology, 030226 pharmacology & pharmacy, Autoimmune Diseases, 03 medical and health sciences, IMP Dehydrogenase, 0302 clinical medicine, IMP dehydrogenase, medicine, Humans, Pyrophosphatases, Child, Aged, Retrospective Studies, Aged, 80 and over, chemistry.chemical_classification, biology, Thiopurine methyltransferase, business.industry, Age Factors, Methyltransferases, General Medicine, Metabolism, Middle Aged, Enzyme assay, 3. Good health, medicine.anatomical_structure, Enzyme, chemistry, Child, Preschool, biology.protein, Female, ITPA, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Inosine monophosphate dehydrogenase (IMPDH) is considered as the limiting enzyme of thiopurine metabolism for the formation of 6-thioguanine nucleotides (6-TGN). No data are available on the influence of RBC IMPDH activity on the metabolism of thiopurine drugs in individuals with IBD. The aims of this study were as follows: (a) to carry out a phenotypic study of RBC IMPDH activity in adults and children treated or not with azathioprine (AZA) for autoimmune diseases, and (b) to investigate the relationship between the activities of IMPDH, thiopurine metabolites, inosine triphosphatase (ITPA) and thiopurine methyltransferase (TPMT). IMPDH activity was determined in 97 adults and 67 children treated or not with AZA. 6-Thioguanine nucleotides (6-TGN), 6-methylmercaptopurine nucleotide (6-MeMPN) levels, and ITPA as well as TPMT activities were measured in RBCs by HPLC. Using the Gaussian mixture model, distribution of IMPDH activity was evaluated. Influence of age, sex and AZA treatment on IMPDH activity was also assessed. A bimodal distribution in IMPDH activity was found with 87% of patients exhibiting normal activity and 13% of patients with high activity. No influence of age, sex and AZA therapy was found. There is no relationship between TPMT, ITPA and IMPDH activities. A negative correlation between IMPDH activity and 6-MeMPN was shown in adults and children (rs = -0.335 P = 0.014 and rs = -0.383 P = 0.012, respectively). Our results suggest that AZA-treated patients exhibiting lower IMPDH activity could have higher Me-6MPN levels with higher risk of hepatotoxicity. We demonstrated that RBC matrix could be an interesting alternative to lymphocyte matrix to monitor thiopurine metabolites and enzyme activity.
Published: 2018

37. Hydroxyurea therapy modulates sickle cell anemia red blood cell physiology: Impact on RBC deformability, oxidative stress, nitrite levels and nitric oxide synthase signalling pathway

Author: Elie Nader, Marc Romana, Nicolas Guillot, Philippe Connes, Cyril Martin, Céline Renoux, Philippe Joly, Romain Fort, Marijke Grau, Bianca Collins, Alexandra Gauthier, Solène Poutrel, Giovanna Cannas, Katja Walpurgis, Wilhelm Bloch, Arnaud Hot, Mario Thevis, Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Médecine Interne, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Center for Preventive Doping Research, Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Pharmacogénétique et abords thérapeutiques des maladies héréditaires, Université des Antilles et de la Guyane (UAG)-Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: Adult, Male, Nitroprusside, 0301 basic medicine, Cancer Research, Erythrocytes, Physiology, Clinical Biochemistry, Anemia, Sickle Cell, Nitric Oxide, medicine.disease_cause, Biochemistry, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, Erythrocyte Deformability, medicine, Humans, Hydroxyurea, Phosphorylation, Nitrites, chemistry.chemical_classification, Reactive oxygen species, biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, hemic and immune systems, medicine.disease, Sickle cell anemia, 3. Good health, Nitric oxide synthase, Oxidative Stress, Red blood cell, 030104 developmental biology, medicine.anatomical_structure, chemistry, biology.protein, Female, Sodium nitroprusside, Hemoglobin, Nitric Oxide Synthase, Reactive Oxygen Species, Proto-Oncogene Proteins c-akt, Oxidative stress, Signal Transduction, circulatory and respiratory physiology, medicine.drug
Abstract: International audience; Hydroxyurea (HU) has been suggested to act as a nitric oxide (NO) donor in sickle cell anemia (SCA). However, little is known about the HU NO-related effects on red blood cell (RBC) physiology and NO signalling pathway. Thirty-four patients with SCA (22 under HU treatment (HU+) and 12 without (HU-)) and 17 healthy subjects (AA) were included. RBC nitrite content, deformability and reactive oxygen species (ROS) levels were measured. RBC NO-synthase (RBC-NOS) signalling pathway was assessed by the measurement of RBC-NOS serine 1177 and RBC-AKT serine 473 phosphorylation. We also investigated the in vitro effects of Sodium Nitroprusside (SNP), a NO donor, on the same parameters in SCA RBC. RBC nitrite content was higher in HU+ than in HU-and AA. RBC deformability was decreased in SCA patients compared to AA but the decrease was more pronounced in HU-. RBC ROS level was increased in SCA compared to AA but the level was higher in HU-than in HU+. RBC-NOS serine 1177 and RBC-AKT serine 473 phosphorylation were decreased in HU+ compared to HU-and AA. SCA RBC treated with SNP showed increased deformability, reduced ROS content and a decrease in AKT and RBC-NOS phosphorylation. Our study suggests that HU, through its effects on foetal hemoglobin and possibly on NO delivery, would modulate RBC NO signalling pathway, RBC rheology and oxidative stress.
Published: 2018

38. Sphingolipid-mediated inflammatory signaling leading to autophagy inhibition converts erythropoiesis to myelopoiesis in human hematopoietic stem/progenitor cells

Author: Franck Morceau, Marc Diederich, Christo Christov, Anthoula Gaigneaux, Jiyun Rhim, Mario Dicato, Marion Orsini, David Cheillan, Sébastien Chateauvieux, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Ceramide, Myeloid, Cellular differentiation, [SDV]Life Sciences [q-bio], ATG5, Sphingomyelin phosphodiesterase, Ceramides, Article, Autophagy-Related Protein 5, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Neoplasms, Macroautophagy, medicine, Autophagy, Autophagy-Related Protein-1 Homolog, Humans, Erythropoiesis, Phosphorylation, Molecular Biology, Inflammation, Myelopoiesis, Sphingolipids, Chemistry, Tumor Necrosis Factor-alpha, TOR Serine-Threonine Kinases, Gene Expression Regulation, Developmental, Anemia, Cell Differentiation, Cell Biology, Chronic inflammation, Hematopoietic Stem Cells, Sphingolipid, 3. Good health, Cell biology, Experimental models of disease, 030104 developmental biology, medicine.anatomical_structure, Sphingomyelin Phosphodiesterase, 030220 oncology & carcinogenesis, Haematological diseases, Signal Transduction
Abstract: Elevated levels of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFalpha) inhibit erythropoiesis and cause anemia in patients with cancer and chronic inflammatory diseases. TNFalpha is also a potent activator of the sphingomyelinase (SMase)/ceramide pathway leading to ceramide synthesis and regulating cell differentiation, proliferation, apoptosis, senescence, and autophagy. Here we evaluated the implication of the TNFalpha/SMase/ceramide pathway on inhibition of erythropoiesis in human CD34(+) hematopoietic stem/progenitor cells (CD34/HSPCs) from healthy donors. Exogenous synthetic C2- and C6-ceramide as well as bacterial SMase inhibited erythroid differentiation in erythropoietin-induced (Epo)CD34/HSPCs shown by the analysis of various erythroid markers. The neutral SMase inhibitor GW4869 as well as the genetic inhibition of nSMase with small interfering RNA (siRNA) against sphingomyelin phosphodiesterase 3 (SMPD3) prevented the inhibition by TNFalpha, but not the acid SMase inhibitor desipramine. Moreover, sphingosine-1-phosphate (S1P), a ceramide metabolite, restored erythroid differentiation, whereas TNFalpha inhibited sphingosine kinase-1, required for S1P synthesis. Analysis of cell morphology and colony formation demonstrated that erythropoiesis impairment was concomitant with a granulomonocytic differentiation in TNFalpha- and ceramide-treated EpoCD34/HSPCs. Inhibition of erythropoiesis and induction of granulomonocytic differentiation were correlated to modulation of hematopoietic transcription factors (TFs) GATA-1, GATA-2, and PU.1. Moreover, the expression of microRNAs (miR)-144/451, miR-146a, miR-155, and miR-223 was also modulated by TNFalpha and ceramide treatments, in line with cellular observations. Autophagy plays an essential role during erythropoiesis and our results demonstrate that the TNFalpha/neutral SMase/ceramide pathway inhibits autophagy in EpoCD34/HSPCs. TNFalpha- and ceramide-induced phosphorylation of mTOR(S2448) and ULK1(S758), inhibited Atg13(S355) phosphorylation, and blocked autophagosome formation as shown by transmission electron microscopy and GFP-LC3 punctae formation. Moreover, rapamycin prevented the inhibitory effect of TNFalpha and ceramides on erythropoiesis while inhibiting induction of myelopoiesis. In contrast, bafilomycin A1, but not siRNA against Atg5, induced myeloid differentiation, while both impaired erythropoiesis. We demonstrate here that the TNFalpha/neutral SMase/ceramide pathway inhibits erythropoiesis to induce myelopoiesis via modulation of a hematopoietic TF/miR network and inhibition of late steps of autophagy. Altogether, our results reveal an essential role of autophagy in erythroid vs. myeloid differentiation.
Published: 2018

39. Pollutants in Breast Milk

Author: Lapillonne, Alexandre, Bocquet, Alain, Briend, Andre, Chouraqui, Jean-Pierre, Darmaun, Dominique, Feillet, François, Frelut, Marie-Laure, Guimber, Dominique, Hankard, Regis, Peretti, Noël, Roze, Jean-Christophe, Simeoni, Umberto, Turck, Dominique, Dupont, Christophe, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut de Recherche pour le Développement (IRD), Université de Lausanne = University of Lausanne (UNIL), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre thérapeutique pédiatrique, Croix rouge française, Université de Lille, Université de Tours (UT), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Nantes (UN), Université de Lausanne (UNIL), Université de Tours, 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), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
Subjects: [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

40. Development and validation of a Score to Assess Risk of Medication Errors detected during medication reconciliation process at admission in Internal Medicine Unit: SCOREM study

Author: Audrey Castet-Nicolas, Anne Jalabert, Maxime Villiet, Camille Roubille, Laetitia Zerkowski, Valérie Macioce, Laura Lohan-Descamps, Pierre Fesler, Y. Audurier, Federico Manna, Cyril Breuker, Marie Faucanie, MORNET, Dominique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université de Montpellier (UM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-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), and Hôpital Lapeyronie [Montpellier] (CHU)
Subjects: Adult, medicine.medical_specialty, Medication history, [SDV]Life Sciences [q-bio], MEDLINE, Pharmacist, 030204 cardiovascular system & hematology, Pharmacists, 03 medical and health sciences, 0302 clinical medicine, Medication Reconciliation, Patient Admission, Internal medicine, medicine, Internal Medicine, Humans, Medication Errors, 030212 general & internal medicine, Medical prescription, ComputingMilieux_MISCELLANEOUS, Framingham Risk Score, business.industry, General Medicine, Emergency department, Stepwise regression, 3. Good health, Hospitalization, [SDV] Life Sciences [q-bio], Observational study, Female, business
Abstract: International audience; Background: Medication errors (ME) can be reduced through preventive strategies such as medication reconciliation. Such strategies are often limited by human resources and need targeting high risk patients.Aims: To develop a score to identify patients at risk of ME detected during medication reconciliation in a specific population from internal medicine unit.Methods: Prospective observational study conducted in an internal medicine unit of a French University Hospital from 2012 to 2016. Adult hospitalised patients were eligible for inclusion. Medication reconciliation was conducted by a pharmacist and consisted in comparing medication history with admission prescription to identify MEs. Risk factors of MEs were analysed using multivariate stepwise logistic regression model. A risk score was constructed using the split-sample approach. The split was done at random (using a fixed seed) to define a development data set (N = 1256) and a validation sample (N = 628). A regression coefficient-base scoring system was used adopting the beta-Sullivan approach (Sullivan's scoring).Results: Pharmacists detected 740 MEs in 368/1884 (19.5%) patients related to medication reconciliation. Female gender, number of treatments >7, admission from emergency department and during night or weekend were significantly associated with a higher risk of MEs. Risk score was constructed by attributing 1 or 2 points to these variables. Patients with a score ≥3 (OR [95% CI] 3.10 [1.15-8.37]) out of 5 (OR [95% CI] 8.11 [2.89-22.78]) were considered at high risk of MEs.Conclusions: Risk factors identified in our study may help prioritising patients admitted in internal medicine units who may benefit the most from medication reconciliation (ClinicalTrials.gov number NCT03422484).
Published: 2021

41. Imagerie de déformation/strain ventriculaire gauche : puis-je m’en passer au quotidien ?

Author: H. Thibault, 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), CCSD, Accord Elsevier, Université Claude Bernard Lyon 1 (UCBL), and 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)
Subjects: [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, business.industry, [SDV]Life Sciences [q-bio], Medicine, 030212 general & internal medicine, 030204 cardiovascular system & hematology, Cardiology and Cardiovascular Medicine, business
Published: 2020

42. Hypergravity as a gravitational therapy mitigates the effects of knee osteoarthritis on the musculoskeletal system in a murine model

Author: Stéphanie Chanon, Damien Cleret, Laurence Vico, Norbert Laroche, Benoit Dechaumet, Etienne Lefai, Marie-Thérèse Linossier, Arnaud Vanden-Bossche, Marie-Hélène Lafage-Proust, INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre National D'etudes Spatiales4800000899, ANR-10-EQPX-0026,DIGISCOPE,Infrastructure haute performance pour la visualisation interactive et collaborative(2010), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), 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), ROSSI, Sabine, and Equipements d'excellence - Infrastructure haute performance pour la visualisation interactive et collaborative - - DIGISCOPE2010 - ANR-10-EQPX-0026 - EQPX - VALID
Subjects: 0301 basic medicine, Male, Anabolism, Knees, Gene Expression, Myostatin, Hindlimb, Osteoarthritis, Knee Joints, Mice, 0302 clinical medicine, Skeletal Joints, Medicine and Health Sciences, Public and Occupational Health, Musculoskeletal System, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Multidisciplinary, biology, Muscles, Gastrocnemius Muscles, Osteoarthritis, Knee, Sports Science, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Connective Tissue, Cancellous Bone, Medicine, Legs, Anatomy, Research Article, medicine.medical_specialty, Science, Metaphysis, Hypergravity, 03 medical and health sciences, Rheumatology, Internal medicine, medicine, Genetics, Animals, Tibia, Sports and Exercise Medicine, Bone, Muscle, Skeletal, Exercise, Skeleton, 030203 arthritis & rheumatology, business.industry, Arthritis, Biology and Life Sciences, Soleus Muscles, Physical Activity, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Endocrinology, Biological Tissue, Physical Fitness, Body Limbs, biology.protein, Cortical bone, Diaphyses, business
Abstract: International audience; Insights into the effects of osteoarthritis (OA) and physical interventions on the musculoskeletal system are limited. Our goal was to analyze musculoskeletal changes in OA mice and test the efficacy of 8-week exposure to hypergravity, as a replacement of physical activity. 16-week-old male (C57BL/6J) mice allocated to sham control and OA groups not centrifuged (Ctrl 1g and OA 1g, respectively) or centrifuged at 2g acceleration (Ctrl 2g and OA 2g). OA 1g displayed decreased trabecular bone in the proximal tibia metaphysis and increased osteoclastic activity and local TNF alpha gene expression, all entirely prevented by 2g gravitational therapy. However, while cortical bone of tibia midshaft was preserved in OA 1g (vs. ctrl), it is thinner in OA 2g (vs. OA 1g). In the hind limb, OA at 1g increased fibers with lipid droplets by 48% in the tibialis anterior, a fact fully prevented by 2g. In Ctrl, 2g increased soleus, tibialis anterior and gastrocnemius masses. In the soleus of both Ctrl and OA, 2g induced larger fibers and a switch from type-II to type-I fiber. Catabolic (myostatin and its receptor activin RIIb and visfatine) and anabolic (FNDC5) genes dramatically increased in Ctrl 2g and OA 2g (p
Published: 2020

43. Spen modulates lipid droplet content in adult Drosophila glial cells and protects against paraquat toxicity

Author: Girard, Victor, Goubard, Valérie, Querenet, Matthieu, Seugnet, Laurent, Pays, Laurent, Nataf, Serge, Dufourd, Eloïse, Cluet, David, Mollereau, Bertrand, Davoust, Nathalie, Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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)-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), Banque de tissus et de cellules [CHU - HCL] (Hôpital Edouard Herriot), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), SFR Biosciences, Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), SFR Biosciences Projets Developpement Technologique Fondation Servier ENS Fond Recherche Fondation pour la Recherche Medicale French Ministry of Research and Education and Association France Parkinson, ANR-12-BSV1-0019,LipidinRetina,Dérégulation du métabolisme des lipides et conséquences sur la fonction et la survie des photorécépteurs: le rôle des gènes FATP chez la Drosophile et la souris(2012), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), ROSSI, Sabine, and BLANC - Dérégulation du métabolisme des lipides et conséquences sur la fonction et la survie des photorécépteurs: le rôle des gènes FATP chez la Drosophile et la souris - - LipidinRetina2012 - ANR-12-BSV1-0019 - BLANC - VALID
Subjects: Homeodomain Proteins, Male, Paraquat, Herbicides, Disease model, Parkinson's disease, [SDV]Life Sciences [q-bio], lcsh:R, lcsh:Medicine, Gene Expression Regulation, Developmental, RNA-Binding Proteins, Parkinson Disease, Lipid Droplets, Article, [SDV] Life Sciences [q-bio], Drosophila melanogaster, nervous system, Animals, Drosophila Proteins, lcsh:Q, lcsh:Science, Astrocyte, Neuroglia
Abstract: International audience; Glial cells are early sensors of neuronal injury and can store lipids in lipid droplets under oxidative stress conditions. Here, we investigated the functions of the RNA-binding protein, SPEN/SHARP, in the context of Parkinson's disease (PD). Using a data-mining approach, we found that SPEN/SHARP is one of many astrocyte-expressed genes that are significantly differentially expressed in the substantia nigra of PD patients compared with control subjects. Interestingly, the differentially expressed genes are enriched in lipid metabolism-associated genes. In a Drosophila model of PD, we observed that flies carrying a loss-of-function allele of the ortholog split-ends (spen) or with glial cell-specific, but not neuronal-specific, spen knockdown were more sensitive to paraquat intoxication, indicating a protective role for Spen in glial cells. We also found that Spen is a positive regulator of Notch signaling in adult Drosophila glial cells. Moreover, Spen was required to limit abnormal accumulation of lipid droplets in glial cells in a manner independent of its regulation of Notch signaling. Taken together, our results demonstrate that Spen regulates lipid metabolism and storage in glial cells and contributes to glial cell-mediated neuroprotection.
Published: 2020

44. Bis(monoacylglycero)phosphate, an important actor in the host endocytic machinery hijacked by SARS-CoV-2 and related viruses

Author: Françoise Hullin-Matsuda, Isabelle Delton, Céline Luquain-Costaz, Maxence Rabia, 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), and French Ministery of educationInstitut National de la Sante et de la Recherche Medicale (Inserm)European CommissionSFD (Societe Francophone du Diabete)AE 2016VML (Vaincre les Maladies Lysosomales)AO2018-6
Subjects: 0301 basic medicine, COVID-19, coronavirus disease-19, viruses, [SDV]Life Sciences [q-bio], CoV, coronavirus, MERS, Middle East Respiratory Syndrome, Endocytic cycle, CAD, cationic amphiphilic drug, MVE, multivesicular endosome, medicine.disease_cause, Biochemistry, Homeostasis, BMP, bis(monoacylglycero)phosphate [also known as lysobisphosphatidic acid (LBPA)], LE/Lys, late endosome/lysosome, Late endosome, ComputingMilieux_MISCELLANEOUS, Coronavirus, Chemistry, ILV, intraluminal vesicle, MCS, membrane contact sites, General Medicine, Endocytosis, 3. Good health, Cell biology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Monoglycerides, NPC, Niemann Pick type C, OSBP, oxysterol binding protein, extracellular vesicles, bis(monoacylglycero)phosphate, VSV, vesicular stomatitis virus, Endosome, CME, clathrin-mediated endocytosis, ACE2, angiotensin-converting enzyme 2, Article, 03 medical and health sciences, ESCRT, endosomal sorting complexes required for transport, oxysterol-binding protein (OSBP)-related proteins ORP, diC22:6-BMP, di-docosahexaenoyl BMP, medicine, Humans, SARS, severe acute respiratory syndrome, Niemann Pick type C disease NPC, OSBP, Unsaturated fatty acid, LSD, lysosomal storage disorder/disease, Host Microbial Interactions, 030102 biochemistry & molecular biology, SARS-CoV-2, cholesterol, ORP, OSBP-related protein, 030104 developmental biology, TMPRSS2, transmembrane serine protease 2, Lysophospholipids, NPC1
Abstract: Viruses, including the novel coronavirus SARS-CoV-2, redirect infected cell metabolism to their own purposes. After binding to its receptor angiotensin-converting enzyme 2 (ACE2) on the cell surface, the SARS-CoV-2 is taken up by receptor-mediated endocytosis ending in the acidic endolysosomal compartment. The virus hijacks the endosomal machinery leading to fusion of viral and endosomal membranes and release of the viral RNA into the cytosol. This mini-review specifically highlights the membrane lipid organization of the endosomal system focusing on the unconventional and late endosome/lysosome-specific phospholipid, bis(monoacylglycero)phosphate (BMP). BMP is enriched in alveolar macrophages of lung, one of the target tissue of SARS-CoV-2. This review details the BMP structure, its unsaturated fatty acid composition and fusogenic properties that are essential for the highly dynamic formation of the intraluminal vesicles inside the endosomes. Interestingly, BMP is necessary for infection and replication of enveloped RNA virus such as SARS-CoV-1 and Dengue virus. We also emphasize the role of BMP in lipid sorting and degradation, especially cholesterol transport in cooperation with Niemann Pick type C proteins (NPC 1 and 2) and with some oxysterol-binding protein (OSBP)-related proteins (ORPs) as well as in sphingolipid degradation. Interestingly, numerous virus infection required NPC1 as well as ORPs along the endocytic pathway. Furthermore, BMP content is increased during pathological endosomal lipid accumulation in various lysosomal storage disorders. This is particularly important knowing the high percentage of patients with metabolic disorders among the SARS-CoV-2 infected patients presenting severe forms of COVID-19., Highlights • Host cell cholesterol is required for efficient viral infection. • NPC and ORPs regulate cholesterol exit from endolysosomes and viral infection. • Endosomal phospholipid BMP interacts with sterol transport proteins NPC and ORPs. • BMP by controlling cholesterol trafficking could be involved in virus infection. • BMP could be a potential therapeutic target for COVID-19.
Published: 2020

45. An Integrated Analysis of miRNA and Gene Expression Changes in Response to an Obesogenic Diet to Explore the Impact of Transgenerational Supplementation with Omega 3 Fatty Acids

Author: Béatrice Morio, Nathalie Poupin, Alexandre Pinel, Karla Fabiola Corral-Jara, Sarah de Saint Vincent, Tao Ye, Frédéric Capel, Jean Paul Rigaudière, Laura Cantini, Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Métabolisme et Xénobiotiques (ToxAlim-MeX), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), 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), Avril Lesieur European Union (EU), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-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), LESUR, Hélène, and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Subjects: 0301 basic medicine, Male, obesity, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Gene Expression, Type 2 diabetes, Bioinformatics, Mice, 0302 clinical medicine, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, chemistry.chemical_classification, Metabolic Syndrome, Nutrition and Dietetics, microRNA, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Eicosapentaenoic acid, [SDV] Life Sciences [q-bio], lcsh:Nutrition. Foods and food supply, Polyunsaturated fatty acid, lcsh:TX341-641, Biology, Diet, High-Fat, liver, Article, 03 medical and health sciences, omega 3 fatty acids, Insulin resistance, Fatty Acids, Omega-3, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Insulin, medicine.disease, IRS2, Mice, Inbred C57BL, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Disease Models, Animal, MicroRNAs, 030104 developmental biology, chemistry, Dietary Supplements, Metabolic syndrome, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, transcriptome, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Food Science
Abstract: Insulin resistance decreases the ability of insulin to inhibit hepatic gluconeogenesis, a key step in the development of metabolic syndrome. Metabolic alterations, fat accumulation, and fibrosis in the liver are closely related and contribute to the progression of comorbidities, such as hypertension, type 2 diabetes, or cancer. Omega 3 (n-3) polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), were identified as potent positive regulators of insulin sensitivity in vitro and in animal models. In the current study, we explored the effects of a transgenerational supplementation with EPA in mice exposed to an obesogenic diet on the regulation of microRNAs (miRNAs) and gene expression in the liver using high-throughput techniques. We implemented a comprehensive molecular systems biology approach, combining statistical tools, such as MicroRNA Master Regulator Analysis pipeline and Boolean modeling to integrate these biochemical processes. We demonstrated that EPA mediated molecular adaptations, leading to the inhibition of miR-34a-5p, a negative regulator of Irs2 as a master regulatory event leading to the inhibition of gluconeogenesis by insulin during the fasting&ndash, feeding transition. Omics data integration provided greater biological insight and a better understanding of the relationships between biological variables. Such an approach may be useful for deriving innovative data-driven hypotheses and for the discovery of molecular&ndash, biochemical mechanistic links.
Published: 2020

46. Rapeseed Lecithin Increases Lymphatic Lipid Output and α-Linolenic Acid Bioavailability in Rats

Author: Chloé Robert, Charline Buisson, Laurence Fonseca, Elisabeth Errazuriz-Cerda, Carole Vaysse, Emmanuelle Meugnier, Leslie Couëdelo, Emmanuelle Loizon, Marie-Caroline Michalski, Carole Knibbe, 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), Equipe Nutrition, Santé et Biochimie des Lipides (ITERG), Artificial Evolution and Computational Biology (BEAGLE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2), Université de Lyon, 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), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and 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)-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)
Subjects: medicine.medical_specialty, food.ingredient, 030309 nutrition & dietetics, Medicine (miscellaneous), Biological Availability, Lecithin, Microsomal triglyceride transfer protein, 03 medical and health sciences, food, Internal medicine, Lecithins, lipid metabolism, medicine, Animals, emulsifier, Carnitine, 030304 developmental biology, 0303 health sciences, Nutrition and Dietetics, biology, Chemistry, Brassica napus, Lipid metabolism, Bioavailability, Rats, alpha-linolenic acid, Endocrinology, Postprandial, nutrition, lecithin, biology.protein, Lymph, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], medicine.drug, Chylomicron
Abstract: International audience; Background: Soybean lecithin, a plant-based emulsifier widely used in food, is capable of modulating postprandial lipid metabolism. With arising concerns of sustainability, alternative sources of vegetal lecithin are urgently needed, and their metabolic effects must be characterized.Objectives: We evaluated the impact of increasing doses of rapeseed lecithin (RL), rich in essential alpha-linolenic acid (ALA), on postprandial lipid metabolism and ALA bioavailability in lymph-cannulated rats.Methods: Male Wistar rats (8 weeks old) undergoing a mesenteric lymph duct cannulation were intragastrically administered 1 g of an oil mixture containing 4% ALA and 0, 1, 3, 10, or 30% RL (5 groups). Lymph fractions were collected for 6 h. Lymph lipids and chylomicrons (CMs) were characterized. The expression of genes implicated in intestinal lipid metabolism was determined in the duodenum at 6 h. Data was analyzed using either sigmoidal or linear mixed-effects models, or one-way ANOVA, where appropriate.Results: RL dose-dependently increased the lymphatic recovery (AUC) of total lipids (1100 mu g/mL.h per additional RL%; P = 0.010) and ALA (50 mu g/mL.h per additional RL%; P = 0.0076). RL induced a faster appearance of ALA in lymph, as evidenced by the exponential decrease of the rate of appearance of ALA with RL (R-2 = 0.26; P= 0.0064). Although the number of CMs was unaffected by RL, CM diameter was increased in the 30%-RL group, compared to the control group (0% RL), by 86% at 3-4 h (P = 0.065) and by 81% at 4-6 h (P = 0.0002) following administration. This increase was positively correlated with the duodenal mRNA expression of microsomal triglyceride transfer protein (Mttp; rho= 0.63; P= 0.0052). The expression of Mttp and secretion-associated, ras-related GTPase 1 gene homolog B (Sarl b, CM secretion), carnitine palmitoyltransferase IA (Cpt1a) and acyl-coenzyme A oxidase 1 (Acoxl, beta-oxidation), and fatty acid desaturase 2 (Fads2, bioconversion of ALA into long-chain n-3 PUFAs) were, respectively, 49%, 29%, 74%, 48%, and 55% higher in the 30%-RL group vs. the control group (P < 0.05).Conclusions: In rats, RL enhanced lymphatic lipid output, as well as the rate of appearance of ALA, which may promote its subsequent bioavailability and metabolic fate.
Published: 2020

47. Le trafic des triglycérides au travers de l’entérocyte : une vision mosaïque pour la modélisation mathématique

Author: Etienne, Julie, Penhoat, Armelle, Berry, Hugues, Michalski, Marie-Caroline, Knibbe, Carole, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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)-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), Institut National de la Santé et de la Recherche Médicale (INSERM), Artificial Evolution and Computational Biology (BEAGLE), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-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), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), 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)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), and Université de Lyon-Université Lumière - Lyon 2 (UL2)
Subjects: [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

48. Using a generic definition of cachexia in patients with kidney disease receiving haemodialysis: a longitudinal (pilot) study

Author: Helen Noble, Adrian Slee, Clare McKeaveney, John Mallett, Kamyar Kalantar-Zadeh, Andrew Davenport, Joanne Shields, Donal O'Donoghue, Ken Farrington, Samuel Porter, Denis Fouque, Alexander P. Maxwell, David S. Seres, Miles D. Witham, Joanne Reid, Gary Adamson, Robert Mullan, CarMeN, laboratoire, University College of London [London] (UCL), University of Ulster, University of Hertfordshire [Hatfield] (UH), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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)-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), University of California [Irvine] (UC Irvine), University of California (UC), Royal Victoria Hospital [Belfast, UK], Queen's University [Belfast] (QUB), Belfast City Hospital, Antrim Area Hospital - Northern Health and Social Care Trust [Antrim, Northern Ireland] (AAH-NHSCT), University of Manchester [Manchester], Bournemouth University [Poole] (BU), New York Presbyterian Hospital, Newcastle University [Newcastle], Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), University of California [Irvine] (UCI), and University of California
Subjects: Male, medicine.medical_specialty, Longitudinal study, Cachexia, phenotype, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, cachexia, 03 medical and health sciences, 0302 clinical medicine, Weight loss, Renal Dialysis, Internal medicine, medicine, Humans, definition, 030212 general & internal medicine, Longitudinal Studies, Dialysis, Aged, 2. Zero hunger, Aged, 80 and over, Transplantation, Hand Strength, business.industry, Repeated measures design, Longitudinal analysis, longitudinal analysis, Definition, Middle Aged, medicine.disease, 3. Good health, haemodialysis, [SDV] Life Sciences [q-bio], Haemodialysis, Phenotype, Nephrology, Female, Kidney Diseases, Hemodialysis, medicine.symptom, business, Body mass index, Kidney disease
Abstract: Background Research indicates that cachexia is common among persons with chronic illnesses and is associated with increased morbidity and mortality. However, there continues to be an absence of a uniformed disease-specific definition for cachexia in chronic kidney disease (CKD) patient populations. Objective The primary objective was to identify cachexia in patients receiving haemodialysis (HD) using a generic definition and then follow up on these patients for 12 months. Method This was a longitudinal study of adult chronic HD patients attending two hospital HD units in the UK. Multiple measures relevant to cachexia, including body mass index (BMI), muscle mass [mid-upper arm muscle circumference (MUAMC)], handgrip strength (HGS), fatigue [Functional Assessment of Chronic Illness Therapy (FACIT)], appetite [Functional Assessment of Anorexia/Cachexia Therapy (FAACT)] and biomarkers [C-reactive protein (CRP), serum albumin, haemoglobin and erythropoietin resistance index (ERI)] were recorded. Baseline analysis included group differences analysed using an independent t-test, dichotomized values using the χ2 test and prevalence were reported using the Statistical Package for the Social Sciences 24 (IBM, Armonk, NY, USA). Longitudinal analysis was conducted using repeated measures analysis. Results A total of 106 patients (30 females and 76 males) were recruited with a mean age of 67.6 years [standard deviation (SD) 13.18] and dialysis vintage of 4.92 years (SD 6.12). At baseline, 17 patients were identified as cachectic, having had reported weight loss (e.g. >5% for >6 months) or BMI Conclusion Globally, cachexia is a severe but frequently underrecognized problem. This is the first study to apply the defined characteristics of cachexia to a representative sample of patients receiving HD. Further, more extensive studies are required to establish a phenotype of cachexia in advanced CKD.
Published: 2020

49. Recommandations cliniques pratiques sur les soins péri- et postopératoires des fistules et greffes artérioveineuses pour hémodialyse chez l’adulte

Author: François Vrtovsnik, Catherine Lasseur, Philippe Chauveau, L Mercadal, Philippe Brunet, Laurent Juillard, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), 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), AURAD Aquitaine, 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), Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Claude Bernard Lyon 1 (UCBL), and 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)
Subjects: medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Peri, 030232 urology & nephrology, MEDLINE, Guideline, 030204 cardiovascular system & hematology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Clinical Practice, 03 medical and health sciences, 0302 clinical medicine, Nephrology, Medicine, business, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2020

50. Anti-PD1 and Anti-PDL1-Induced Hypophysitis: A Cohort Study of 17 Patients with Longitudinal Follow-Up

Author: Levy, Manon, Abeillon, Juliette, Dalle, Stéphane, Assaad, Souad, Borson-Chazot, Françoise, Disse, Emmanuel, Raverot, Gérald, Cugnet-Anceau, Christine, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and 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)
Subjects: nivolumab, programmed cell death 1 protein, lcsh:R, programmed cell death 1 ligand 1 protein, lcsh:Medicine, immunotherapy, pembrolizumab, adrenal insufficiency, Article, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, hypophysitis
Abstract: International audience; Hypophysitis, secondary to programmed cell death 1 protein (PD1) and programmed cell death 1 ligand 1 (PDL1) inhibitors, were thought to be rare, with only a few studies describing more than one case with long-term follow-up. The aim of the present study was to describe the clinical, laboratory, and morphological characteristics of PD1/PDL1 inhibitor-induced hypophysitis, and its long-term course. This cohort study was conducted at the University Hospital of Lyon, France, with longitudinal follow-up of patients. Seventeen cases of PD1/PDL1 inhibitor-induced hypophysitis were included. The median time to onset of hypophysitis was 28 weeks (range: 10-46). At diagnosis, 16 patients complained of fatigue, 12 of nausea or loss of appetite, while headache was rare. We found no imaging pituitary abnormality. All patients presented adrenocorticotropic hormone (ACTH) deficiency; other pituitary deficiencies were less common (n = 7). At last follow-up (median: 13 months), ACTH deficiency persisted in all but one patient and one patient recovered from gonadotropic deficiency. PD1/PDL1 inhibitor-induced hypophysitis is a clinical entity different from those associated to cytotoxic T-lymphocyte antigen-4 (CTLA4) inhibitors, with less obvious clinical and radiological signs, and probably a different mechanism. The paucity of symptoms demonstrates the need for systematic hormonal follow-up for patients receiving PD1/PDL1 inhibitors.
Published: 2020

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