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1. Bioactive Oxylipins Profile in Marine Microalgae

Author

Amandyne Linares-Maurizi, Guillaume Reversat, Rana Awad, Valérie Bultel-Poncé, Camille Oger, Jean-Marie Galano, Laurence Balas, Anaelle Durbec, Justine Bertrand-Michel, Thierry Durand, Rémi Pradelles, Claire Vigor, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Microphyt, MetaboHUB-MetaToul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), 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-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 Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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 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), This research was funded by ANRT CIFRE n° 2019/1281, and KARLI, Mélanie

Subjects
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, oxylipins, lipidomic, microalgae, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Drug Discovery, Pharmaceutical Science, oxidative stress, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, LC-MS/MS, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
Abstract

International audience; Microalgae are photosynthetic microscopic organisms that serve as the primary food source in aquatic environments. Microalgae can synthesize a wide variety of molecules, such as polyunsaturated fatty acids (PUFAs) of the omega-3 and omega-6 series. Oxidative degradation of PUFA due to radical and/or enzymatic conversion leads to the formation of oxylipins, which are compounds known for their bioactive properties. In the present study, we aim to profile oxylipins from five microalgae species grown in 10-L photo-bioreactors under optimal conditions. During their exponential phase, microalgae were harvested, extracted and analyzed by LC-MS/MS to determine the qualitative and quantitative profile of oxylipins for each species. The five different selected microalgae revealed a high diversity of metabolites, up to 33 non-enzymatic and 24 enzymatic oxylipins present in different concentrations. Taken together, these findings highlight an interesting role of marine microalgae as a source of bioactive lipids mediators, which we hypothesize have an important function in preventive health measures such as amelioration of inflammation. The rich mixture of oxylipins may display advantages to biological organisms, especially by providing for human health benefits including antioxidant, anti-inflammatory, neuroprotective or immunomodulator activities. Some oxylipins are also well known for their cardiovascular properties.

Published
2023
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2. Significance of developmental meningeal lymphatic dysfunction in experimental post-traumatic injury

Author

Anaïs Virenque, Hennariikka Koivisto, Salli Antila, Emma Zub, Erin Jane Rooney, Diana Miszczuk, Adrian Müller, Enija Stoka, Nicola Marchi, Kari Alitalo, Heikki Tanila, Francesco Mattia Noe, HiLIFE - Neuroscience Center (NC), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Wihuri Research Institute [Helsinki, Finland], Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), KARLI, Mélanie, Neuroscience Center, University of Helsinki, Helsinki Institute of Life Science HiLIFE, CAN-PRO - Translational Cancer Medicine Program, HUSLAB, and Kari Alitalo / Principal Investigator

Subjects
Traumatic Brain Injury, Meningeal Lymphatic Vessel, CCI, [SDV]Life Sciences [q-bio], Behavioral dysfunctions, 3112 Neurosciences, Chronic traumatic brain injury, mLV, 3124 Neurology and psychiatry, [SDV] Life Sciences [q-bio], Neuroinflammation, Controlled Cortical Injury, Cortical lesion development, TBI, General Earth and Planetary Sciences, Meningeal lymphatic vessels, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], General Environmental Science
Abstract

International audience; Understanding the pathological mechanisms unfolding after chronic traumatic brain injury (TBI) could reveal new therapeutic entry points. During the post-TBI sequel, the involvement of cerebrospinal fluid drainage through the meningeal lymphatic vessels was proposed. Here, we used K14-VEGFR3-Ig transgenic mice to analyze whether a developmental dysfunction of meningeal lymphatic vessels modifies post-TBI pathology. To this end, a moderate TBI was delivered by controlled cortical injury over the temporal lobe in male transgenic mice or their littermate controls. We performed MRI and a battery of behavioral tests over time to define the post-TBI trajectories. In vivo analyses were integrated by ex-vivo quantitative and morphometric examinations of the cortical lesion and glial cells. In post-TBI K14-VEGFR3-Ig mice, the recovery from motor deficits was protracted compared to littermates. This outcome is coherent with the observed slower hematoma clearance in transgenic mice during the first two weeks post-TBI. No other genotype-related behavioral differences were observed, and the volume of cortical lesions imaged by MRI in vivo, and confirmed by histology ex-vivo, were comparable in both groups. However, at the cellular level, post-TBI K14-VEGFR3-Ig mice exhibited an increased percentage of activated Iba1 microglia in the hippocampus and auditory cortex, areas that are proximal to the lesion. Although not impacting or modifying the structural brain damage and post-TBI behavior, a pre-existing dysfunction of meningeal lymphatic vessels is associated with morphological microglial activation over time, possibly representing a sub-clinical pathological imprint or a vulnerability factor. Our findings suggest that pre-existing mLV deficits could represent a possible risk factor for the overall outcome of TBI pathology.

Published
2022
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3. From CD16a Biology to Antibody-Dependent Cell-Mediated Cytotoxicity Improvement

Author

Coënon, Loïs, Villalba, Martin, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Sainte Catherine [Avignon], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and KARLI, Mélanie

Subjects
MESH: Killer Cells, Natural, MESH: Humans, MESH: Immunotherapy, [SDV]Life Sciences [q-bio], Receptors, IgG, Immunology, Antibody-Dependent Cell Cytotoxicity, Antibodies, Monoclonal, NK cells, MESH: Receptors, IgG, MESH: Antineoplastic Agents, Immunological, CD16a, MESH: Antibodies, Monoclonal, [SDV] Life Sciences [q-bio], Killer Cells, Natural, Antineoplastic Agents, Immunological, MESH: Biology, MESH: Antibody-Dependent Cell Cytotoxicity, Humans, Immunology and Allergy, monoclonal antibodies, Immunotherapy, cell therapy, ADCC, Biology
Abstract

International audience; Antibody-dependent cell-mediated cytotoxicity (ADCC) is a potent cytotoxic mechanism that is mainly mediated in humans by natural killer (NK) cells. ADCC mediates the clinical benefit of several widely used cytolytic monoclonal antibodies (mAbs), and increasing its efficacy would improve cancer immunotherapy. CD16a is a receptor for the Fc portion of IgGs and is responsible to trigger NK cell-mediated ADCC. The knowledge of the mechanism of action of CD16a gave rise to several strategies to improve ADCC, by working on either the mAbs or the NK cell. In this review, we give an overview of CD16a biology and describe the latest strategies employed to improve antibody-dependent NK cell cytotoxicity.

Published
2022
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4. Integrating general practitioners into crisis management would accelerate the transition from victim to effective professional: Qualitative analyses of a terrorist attack and catastrophic flooding

Author

Bernard Clary, Bélinda Baert, Gérard Bourrel, Michel Amouyal, Béatrice Lognos, Agnès Oude-Engberink, Elodie Million, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre d’Evaluation des programmes de Prévention Sante [Montpellier] (Plateforme CEPS), Université de Montpellier (UM), Dynamique des capacités humaines et des conduites de santé (EPSYLON), Université Paul-Valéry - Montpellier 3 (UPVM), and KARLI, Mélanie

Subjects
[SDV]Life Sciences [q-bio], general practice/family medicine, disasters, [SHS]Humanities and Social Sciences, Qualitative designs and methods, flooding, terrorist attacks, General Practitioners, general practice/ family medicine, MESH: Qualitative designs and methods, general, general practitioner, PTSD, Humans, MESH: Qualitative Research, Qualitative Research, MESH: Terrorism, MESH: Humans, MESH: Floods, Floods, MESH: General Practitioners, MESH: France, [SDV] Life Sciences [q-bio], Terrorism, [SHS] Humanities and Social Sciences, France, Family Practice, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

In 2018, Trèbes, 6,000 inhabitants with nine general practitioners (GPs) in southern France, experienced two tragedies; a terrorist attack in March, in which four people were killed, and a catastrophic flood in October, in which six people died and thousands more were affected.We aimed to obtain a substantive theory for improving crisis management by understanding the personal and professional effects of the two successive disasters on GPs in the same village.This qualitative study conducted complete interviews with eight GPs individually, with subsequent analyses involving the conceptualisation of categories based on grounded theory.The analysis revealed that GPs underwent a double status transition. First, doctors who experienced the same emotional shock as the population became victims; their usual professional relationship changed from empathy to sympathy. The helplessness they felt was amplified by the lack of demand from the state to participate in the first emergency measures; consequently, they lost their professional status. In a second phase, GPs regained their values and skills and acquired new ones, thus regaining their status as competent professionals. In this context, the participants proposed integrating a coordinated crisis management system and the systematic development of peer support.We obtained valuable information on the stages of trauma experienced by GPs, allowing a better understanding of the effects on personal/professional status. Thus, the inclusion of GPs in adaptive crisis management plans would limit the effects of traumatic dissociation while increasing their professional effectiveness.

Published
2022
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5. Glucose Starvation or Pyruvate Dehydrogenase Activation Induce a Broad, ERK5-Mediated, Metabolic Remodeling Leading to Fatty Acid Oxidation

Author

Abrar Ul Haq Khan, Hamideh Salehi, Catherine Alexia, Jose M. Valdivielso, Milica Bozic, Isabel C. Lopez-Mejia, Lluis Fajas, Sabine Gerbal-Chaloin, Martine Daujat-Chavanieu, Delphine Gitenay, Martin Villalba, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Bioingénierie et NanoSciences (LBN), Université de Montpellier (UM), Biomedical Research Institute of Lleida [Spain] (IRBLleida), Universitat de Lleida, Université de Lausanne = University of Lausanne (UNIL), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), This work was supported by INCA/DGOS PRT-K program 2021 (M.V., 2021-014). A.K.was the recipient of a fellowship from Higher Education Commission of Pakistan. This work wasalso supported by the 'Investissements d’avenir' Grant LabEx MAbImprove: ANR-10-LABX-53(M.V.). I.C.L.-M. is supported by a PRIMA grant from the Swiss National Science Foundation (SNSFPR00P3_193166)., and KARLI, Mélanie

Subjects
MESH: Oxidation-Reduction, [SDV]Life Sciences [q-bio], Fatty Acids, General Medicine, glycolysis, metabolic plasticity, MESH: Fatty Acids, MESH: Glucose, [SDV] Life Sciences [q-bio], metabolic flexibility, Glucose, ERK5, fatty acid oxidation, biochemistry, MESH: Mitogen-Activated Protein Kinase 7, MESH: Oxidoreductases, Oxidoreductases, Pyruvates, Oxidation-Reduction, Mitogen-Activated Protein Kinase 7, MESH: Pyruvates
Abstract

International audience; Cells have metabolic flexibility that allows them to adapt to changes in substrate availability. Two highly relevant metabolites are glucose and fatty acids (FA), and hence, glycolysis and fatty acid oxidation (FAO) are key metabolic pathways leading to energy production. Both pathways affect each other, and in the absence of one substrate, metabolic flexibility allows cells to maintain sufficient energy production. Here, we show that glucose starvation or sustained pyruvate dehydrogenase (PDH) activation by dichloroacetate (DCA) induce large genetic remodeling to propel FAO. The extracellular signal-regulated kinase 5 (ERK5) is a key effector of this multistep metabolic remodeling. First, there is an increase in the lipid transport by expression of low-density lipoprotein receptor-related proteins (LRP), e.g., CD36, LRP1 and others. Second, an increase in the expression of members of the acyl-CoA synthetase long-chain (ACSL) family activates FA. Finally, the expression of the enzymes that catalyze the initial step in each cycle of FAO, i.e., the acyl-CoA dehydrogenases (ACADs), is induced. All of these pathways lead to enhanced cellular FAO. In summary, we show here that different families of enzymes, which are essential to perform FAO, are regulated by the signaling pathway, i.e., MEK5/ERK5, which transduces changes from the environment to genetic adaptations.

Published
2022
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6. Post-market Clinical Follow-up (PMCF) GAP Analysis for Legacy Devices Class III between the Medical Device Directive (MDD 93/42/EEC) and the Medical Device Regulation (MDR 2017/745)

Author

Marina Makeenko, Thierry Chevallier, Biotechni SAS, Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie [CHU Nîmes] (BESPIM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), French alliance clinical trial [Paris] (F-CRIN), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Ana Roque, Ana Fred, Hugo Gamboa, and KARLI, Mélanie

Subjects
Clinical Investigation on Medical Device, [SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, High Risk Medical Device, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IB]Life Sciences [q-bio]/Bioengineering
Abstract

International audience; The passage from the MDD 93/42/CEE to the MDR 2017/745 remains a big challenge for the manufactures. The interpretation of the regulatory requirements stays unclear and can differ from one source to another, especially when it comes to the clinical evaluation. Will the data collected under the MDD 93/42/CEE be sufficient to prove the safety and security of the device? Under the directive each country was establishing its own requirements for the conduct of the studies. The MDR has standardized these rules, so that all the clinical data collections follow the same pathway. We will examine the PMCF of the class III devices already CE marked under the directive (legacy devices) to find out if the new requirements will be asked to be in compliance with the MDR. A Gap analysis between the MDD and MDR will help us in our research. A matrix in the form of a questionnaire will be established to help us verify compliance of the PMCF under the MDR.

Published
2022
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7. The Role of Massive Databases in the Post-market Clinical Follow-up of Medical Devices

Author

Marion Burland, Thierry Chevallier, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie [CHU Nîmes] (BESPIM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), French alliance clinical trial [Paris] (F-CRIN), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Institut Desbrest de santé publique (IDESP), and KARLI, Mélanie

Subjects
Post-Market Clinical Follow up, [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Massive Database, Medical Device, Real Life Study
Abstract

International audience; With the application of new European regulations on medical devices in May 2021, the requirements for clinical evaluation have been strongly reinforced. Post-marketing clinical follow-up is now a key activity for manufacturers to keep their medical devices on the market. The use of material-epidemiology studies and real-life databases has multiple strengths and advantages. However, the weaknesses and limitations identified do not yet allow manufacturers (especially small and medium-sized companies) to fully utilize these tools for post-market clinical follow-up. Yet certain technological and regulatory developments already implemented, and to be implemented over time, suggest that these tools could play a crucial role in the clinical monitoring of medical devices in the future. In order to better define the future use of real-life data in post-market clinical follow-up activities, a comprehensive update of technological and regulatory surveillance is still required.

Published
2022
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8. Intra-articular delivery of full-length antibodies through the use of an in situ forming depot

Author

Alexis Fayd'herbe De Maudave, Wilhem Leconet, Karine Toupet, Michael Constantinides, Guillaume Bossis, Marion de Toledo, Jérôme Vialaret, Christophe Hirtz, Adolfo Lopez-Noriega, Christian Jorgensen, Daniele Noël, Pascale Louis-Plence, Sylvestre Grizot, Martin Villalba, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), MedinCell SA, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut Sainte Catherine [Avignon], and KARLI, Mélanie

Subjects
0303 health sciences, Local delivery, Polymers, [SDV]Life Sciences [q-bio], Pharmaceutical Science, Biodegradable copolymers, 3. Good health, [SDV] Life Sciences [q-bio], Mice, 03 medical and health sciences, 0302 clinical medicine, Delayed-Action Preparations, 030220 oncology & carcinogenesis, Daratumumab, Animals, Full length monoclonal antibodies, Intra-articular, Rituximab, 030304 developmental biology
Abstract

International audience; Monoclonal antibodies (mAbs) are large size molecules that have demonstrated high therapeutic potential for the treatment of cancer or autoimmune diseases. Despite some excellent results, their intravenous administration results in high plasma concentration. This triggers off-target effects and sometimes poor targeted tissue distribution. To circumvent this issue, we investigated a local controlled-delivery approach using an in situ forming depot technology. Two clinically relevant mAbs, rituximab (RTX) and daratumumab (DARA), were formulated using an injectable technology based on biodegradable PEG-PLA copolymers. The stability and controlled release features of the formulations were investigated. HPLC and mass spectrometry revealed the preservation of the protein structure. In vitro binding of formulated antibodies to their target antigens and to their cellular FcγRIIIa natural killer cell receptor was fully maintained. Furthermore, encapsulated RTX was as efficient as classical intravenous RTX treatment to inhibit the in vivo tumor growth of malignant human B cells in immunodeficient NSG mice. Finally, the intra-articular administration of the formulated mAbs yielded a sustained local release associated with a lower plasma concentration compared to the intra-articular delivery of non-encapsulated mAbs. Our results demonstrate that the utilization of this polymeric technology is a reliable alternative for the local delivery of fully functional clinically relevant mAbs.

Published
2022
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9. Combined Medical Devices: Which Classification for These Borderline Products and Which Consequences for the Manufacturers - About a Use Case in Skin Healing Area

Author

Vaissière Anaïs, Chevallier Thierry, KARLI, Mélanie, Regentis-Pharma, Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie [CHU Nîmes] (BESPIM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), French alliance clinical trial [Paris] (F-CRIN), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Institut Desbrest de santé publique (IDESP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Cutaneous Healing, [SDV] Life Sciences [q-bio], Combined Medical Devices, Health Authorities, Combined Dressings, [SDV]Life Sciences [q-bio], Ancillary Substance, Peptide, European Regulation 2017/746, Classification, Medical Devices (MD)
Abstract

International audience; Skin healing is a rapidly expanding field, especially with the growing needs of an aging population and the increase in chronic pathologies (diabetes, venous ulcers, bedsores etc...). In order to offer ever more adapted solutions, manufacturers are competing in ingenuity to propose innovative medical devices that meet the expectations of patients, caregivers and the healthcare system. These developments raise many questions, particularly with regard to the classification of devices in the various risk classes and the naming of these wound healing devices. This article will focus on combined medical devices with the difficulties they pose for manufacturers and health authorities in terms of development, financial investment, risk-taking and the difficulty of classifying these so-called borderline products in the medical device universe.

Published
2022
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10. Importance of Patient Education for At-home Yoga Practice in Women With Hormonal Therapy-induced Pain During Adjuvant Breast Cancer Treatment: A Feasibility Study

Author

Kerstin Faravel, Marie-Eve Huteau, Marta Jarlier, Hélène de Forges, Laetitia Meignant, Pierre Senesse, Joanna Norton, William Jacot, Anne Stoebner, Institut du Cancer de Montpellier (ICM), 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), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and KARLI, Mélanie

Subjects
MESH: Yoga, Pain, MESH: Patient Education as Topic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, patient education, breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Patient Education as Topic, Humans, RC254-282, physiotherapy, MESH: Humans, hormonal therapy, Yoga, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Complementary and alternative medicine, Oncology, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Feasibility Studies, Female, MESH: Pain, MESH: Feasibility Studies, MESH: Female, MESH: Breast Neoplasms, Research Article
Abstract

Background Osteo-articular pain (OAP) is experienced by approximately 50% of women under hormonal therapy (HT) for breast cancer (BC), which increases the risk for therapy discontinuation. This study was aimed to assess benefits of yoga practice combined with patient education (PE) for at-home practice by evaluating feasibility among BC patients under HT and measuring OAP, flexibility and satisfaction. Methods Feasibility was evaluated by patient adherence as accomplishment of at least 4 out of 6 supervised yoga-PE sessions along with 70% or more at-home yoga sessions. Intervention (12 weeks) included two 6-weeks periods: P1 comprising one 90-minutes supervised yoga-PE session/week and 15-minutes daily at-home yoga and P2, daily autonomous at-home yoga sessions. Evaluations (at inclusion and by the end of each period) consisted in assessment of OAP on Visual Analog Scale (VAS), forward flexibility (cm) and patient satisfaction on Likert (0-10 points) scale. Results Between September 2018 and May 2019 we included 24 patients of median 53 years (range 36-72). Feasibility was validated by 83% successful adherence rate. Pain was significantly reduced from median VAS of 6 [range 4-10] to 4 [range 0-7] at the end of both P1 and P2 ( p Conclusion Combined physiotherapy-yoga-PE intervention is a feasible strategy to increase at-home yoga practice with potential benefit on pain, flexibility, and satisfaction, thus prompting further evaluations in larger randomized multicenter trials. ClinicalTrials.gov NCT04001751

Published
2021
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11. NK cells acquire CCR5 and CXCR4 by trogocytosis in people living with HIV-1

Author

Dang-Nghiem Vo, Nicolas Leventoux, Mauricio Campos-Mora, Sandrine Gimenez, Pierre Corbeau, Martin Villalba, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de génétique humaine (IGH), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Sainte Catherine [Avignon], This work was supported by the PRT-K program 2021-014 and from the 2021 AAP CompaniesOn Campus by the MUSE (Montpellier Université d’Excellence (MV). This work was alsosupported by the 'Investissements d’avenir' Grant LabEx MAbImprove: ANR-10-LABX-53 (M.V).This work has been supported by the 'Fondation ARC pour la recherche sur le cancer' (MC-M)., and KARLI, Mélanie

Subjects
CXCR4, [SDV] Life Sciences [q-bio], Pharmacology, Infectious Diseases, [SDV]Life Sciences [q-bio], NK cells, HIV-1, trogocytosis, CCR5, Drug Discovery, Immunology, Pharmacology (medical)
Abstract

NK cells play a major role in the antiviral immune response, including against HIV-1. HIV patients have impaired NK cell activity with decrease in CD56dim NK cells and increase in CD56−CD16+ subset and recently it has been proposed that a population of CD56+NKG2C+KIR+CD57+ cells represents antiviral memory NK cells. Antiretroviral therapy (ART) partly restores the functional activity of this lymphocyte lineage. NK cells when interacting with their targets can gain antigens from them by the process of trogocytosis. Here we show that NK cells can obtain CCR5 and CXCR4, but barely CD4, from T cell lines by trogocytosis in vitro. By UMAP (Uniform Manifold Approximation and Projection), we show that aviremic HIV patients have unique NK cell clusters that encompass for cells expressing CCR5, NKG2C and KIRs, but lack CD57 expression. Viremic patients have a larger proportion of CXCR4+ and CCR5+ NK cells than healthy donors (HD) and this is largely increased in CD107+ cells, suggesting a link between degranulation and trogocytosis. In agreement, UMAP identified a specific NK cell cluster in viremic HIV patients, which contains most of the CD107a+, CCR5+ and CXCR4+ cells. However, this cluster lacks NKG2C expression. Therefore, NK cells can gain CCR5 and CXCR4 by trogocytosis, which depends on degranulation.Author SummaryNK cells play a major role in the antiviral immune response, including against HIV-1. HIV-1 infection largely impacts NK cell lineage. However, identification of the NK cells fighting the virus and eliminating infected cells has remained elusive. By using FACs analysis and analyzing T cell markers, we identify specific NK cell subsets that have gained T cell antigen markers by trogocytosis. We show a strong association of degranulation and trogocytosis ex vivo suggesting that NK cells are eliminating or trying to eliminate HIV-1 infected cells.Moreover, we show that NK cells can obtain the HIV-1 coreceptors CCR5 and CXCR4, but barely CD4, from T cells. Therefore, by uncovering that NK cells gain CCR5 and CXCR4 by trogocytosis we show that NK cells are actively fighting against HIV-1 infection in viremic and aviremic patients. This should help to identify why certain patients better control the virus, to develop new anti-HIV-1, NK cell-based, immunotherapies and to understand if NK cells can be a new HIV-1 reservoir.

Published
2021
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12. Harnessing the Potential of NK Cell-Based Immunotherapies against Multiple Myeloma

Author

Chantal Reina-Ortiz, David Giraldos, Gemma Azaceta, Luis Palomera, Isabel Marzo, Javier Naval, Martín Villalba, Alberto Anel, KARLI, Mélanie, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Instituto de Investigación Sanitaria de Aragón [Zaragoza] (IIS Aragón), Hospital Clínico Universitario 'Lozano Blesa' [Zaragoza, Spain], Institut Sainte Catherine [Avignon], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and This research is part of the project PID2019-105128RB-I00 financed by MCIN/AEI/459 10.13039/501100011033/ and 'FEDER Una manera de hacer Europa' to AA and IM and has been460 also supported by Government of Aragon grant B31_20R to AA.

Subjects
allogeneic, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Receptors, Chimeric Antigen, QH301-705.5, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, NK cells, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, autologous, daratumumab, Killer Cells, Natural, [SDV.CAN] Life Sciences [q-bio]/Cancer, Tumor Microenvironment, Humans, Immunotherapy, Biology (General), [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Neoplasm Recurrence, Local, Multiple Myeloma, isatuximab
Abstract

International audience; Natural killer (NK) cell-based therapies have emerged as promising anticancer treatments due to their potency as cytolytic effectors and synergy with concurrent treatments. Multiple myeloma (MM) is an aggressive B-cell malignancy that, despite development of novel therapeutic agents, remains incurable with a high rate of relapse. In MM, the inhospitable tumor microenvironment prevents host NK cells from exerting their cytolytic function. The development of NK cell immunotherapy works to overcome this altered immune landscape and can be classified in two major groups based on the origin of the cell: autologous or allogeneic. In this review, we compare the treatments in each group, such as autologous chimeric antigen receptor (CAR) NKs and allogeneic off-the-shelf NK cell infusions, and their combinatorial effect with existing MM therapies including monoclonal antibodies and proteasome inhibitors. We also discuss their placement in clinical treatment regimens based on the immune profile of each patient. Through this examination, we would like to discover precisely when each NK cell-based treatment will produce the maximum benefit to the MM patient.

Published
2021
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13. Metformin Sensitizes Leukemic Cells to Cytotoxic Lymphocytes by Increasing Expression of Intercellular Adhesion Molecule-1 (ICAM-1)

Author

Martin Villalba, Francesco Bertolini, Joaquin Marco Brualla, Paolo Falvo, Catherine Alexia, Alexis Fayd'herbe de Maudave, Paul Massa, Stefania Orecchioni, Nerea Allende-Vega, Lois Coenon, Delphine Gitenay, Michael Constantinides, Isabel Marzo, Alberto Anel, Giulia Mitola, KARLI, Mélanie, Laboratoires d'excellence - Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used - - MAbImprove2010 - ANR-10-LABX-0053 - LABX - VALID, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Zaragoza - Universidad de Zaragoza [Zaragoza], European Institute of Oncology [Milan] (ESMO), Institut Sainte Catherine [Avignon], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), This work was supported by the PRT-K program 2018 and 2021(MV, 2018-021). This work was also supported by the 'Investissements d’avenir' Grant LabEx MAbImprove: ANR-10-LABX-53 (MV), the NK 001 project fnanced by the 'Fond Européen de Développement Régional ' (FEDER-FSE-IEJ 2014/2020) and by 'Région Occitanie Pyrénées-Méditerranée', by grant PID2019-105128RB-I00 from Ministerio de Ciencia e Innovación to AA and by Gobierno de Aragón (Group B31_20R) cofnanced by Feder 2014–2020 'Building Europe from Aragon' and Grants from AIRC and Italian Ministry of Health (FB)., and ANR-10-LABX-0053,MAbImprove,Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used(2010)

Subjects
Male, [SDV]Life Sciences [q-bio], Science, Intercellular Adhesion Molecule-1, Immunology, Article, Mice, Mice, Inbred NOD, Neoplasms, medicine, Tumor Cells, Cultured, Cytotoxic T cell, Animals, Humans, Cancer, ICAM-1, Multidisciplinary, Chemistry, allergology, Metformin, [SDV] Life Sciences [q-bio], Killer Cells, Natural, Cancer research, Medicine, medicine.drug
Abstract

Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

Published
2021
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14. Optimization of RNA extraction methods from human metabolic tissue samples of the COMET biobank

Author

Jonas Laget, Nathalie de Préville, Jérémy Leroy, Marie-Dominique Servais, Caroline Desmetz, David Nocca, F. Galtier, Flore Duranton, Sandra A. Rebuffat, Agathe Nouvel, Anne-Dominique Lajoix, Nicolas Builles, Biocommunication en Cardio-Métabolique (BC2M), Université de Montpellier (UM), RD-Néphrologie (R&D), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire Servier, CIC Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Département de chirurgie digestive et transplantation, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and KARLI, Mélanie

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, Science, Adipose tissue, Real-Time Polymerase Chain Reaction, Article, Specimen Handling, Transcriptome, Biomaterials, Endocrinology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, RNA, Messenger, Transcriptomics, Muscle, Skeletal, Biological Specimen Banks, Multidisciplinary, Chemistry, Gene Expression Profiling, RNA, Skeletal muscle, Housekeeping gene, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, medicine.anatomical_structure, Biochemistry, Adipose Tissue, Genetic Techniques, Liver, Cell culture, Medicine, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], RNA extraction, Homogenization (biology)
Abstract

Constitution of biobank of human tissues requires careful handling and storage of biological material, to guarantee the quality of samples. Tissue preparation is also critical for further applications such as transcriptomic profiling. In this study, our aim was to evaluate the impact of different disruption techniques (FastPrep-24 instrument, GentleMACS dissociator, and syringe/needle) and homogenizing buffers (RLT versus QIAzol) on RNA purity and quality of metabolic tissues (adipose tissues, liver and skeletal muscle) present in the COMET Biobank. For all homogenization methods used and tissue types, the A260/280 ratios reached values ≥ 1.8, which are in the range of what is found in human tissues and cell lines, while the A260/230 ratios were however ≤ 1.8, with the lowest value obtained with GentleMACS Dissociator. In addition, GentleMACS Dissociator combined with QIAzol reagent gave the highest RIN value and 28S/18S ratio for all tissues tested, except for muscle. Performing RT-qPCR, Ct values for different housekeeping genes can be influenced by extraction methods and RNA quality of samples. In conclusion, we have demonstrated that different disruption techniques and homogenizing buffers impact the purity and some quality markers of RNA, and can also impact quantification of mRNAs by RT-qPCR in human metabolic tissues.

Published
2021
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15. Paternal transmission of the Wolbachia CidB toxin underlies cytoplasmic incompatibility

Author

Béatrice Horard, Kevin Terretaz, Anne-Sophie Gosselin-Grenet, Hélène Sobry, Mathieu Sicard, Frédéric Landmann, Benjamin Loppin, 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 Biologie cellulaire de Montpellier (CRBM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Diversité, Génomes & Interactions Microorganismes - Insectes [Montpellier] (DGIMI), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Montpellier (UM), 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)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), MUSE program of the University of MontpellierAAP17REC-FRS04-GENEWOL, SchlumbergerFSER202002011118, ANR-16-CE02-0006,CIAWOL,Bases moléculaire et cellulaire de la diversité phénotypique de l'incompatibilté cytoplasmique chez les insectes(2016), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), KARLI, Mélanie, Bases moléculaire et cellulaire de la diversité phénotypique de l'incompatibilté cytoplasmique chez les insectes - - CIAWOL2016 - ANR-16-CE02-0006 - AAPG2016 - VALID, and Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID

Subjects
toxin-antidote, Male, Cytoplasm, cytoplasmic incompatibility, [SDV]Life Sciences [q-bio], General Biochemistry, Genetics and Molecular Biology, DNA replication stress, spermiogenesis, [SDV] Life Sciences [q-bio], Culex, Cytosol, fertilization, Animals, Drosophila, General Agricultural and Biological Sciences, CidA, Wolbachia, CidB
Abstract

International audience; Wolbachia are widespread endosymbiotic bacteria that manipulate the reproduction of arthropods through a diversity of cellular mechanisms. In cytoplasmic incompatibility (CI), a sterility syndrome originally discovered in the mosquito Culex pipiens, uninfected eggs fertilized by sperm from infected males are selectively killed during embryo development following the abortive segregation of paternal chromosomes in the zygote. Despite the recent discovery of Wolbachia CI factor (cif) genes, the mechanism by which they control the fate of paternal chromosomes at fertilization remains unknown. Here, we have analyzed the cytological distribution and cellular impact of CidA and CidB, a pair of Cif proteins from the Culex-infecting Wolbachia strain wPip. We show that expression of CidB in Drosophila S2R+ cells induces apoptosis unless CidA is co-expressed and associated with its partner. In transgenic Drosophila testes, both effectors colocalize in germ cells until the histone-to-protamine transition in which only CidB is retained in maturing spermatid nuclei. We further show that CidB is similarly targeted to maturing sperm of naturally infected Culex mosquitoes. At fertilization, CidB associates with paternal DNA regions exhibiting DNA replication stress, as a likely cause of incomplete replication of paternal chromosomes at the onset of the first mitosis. Importantly, we demonstrate that inactivation of the deubiquitylase activity of CidB does not abolish its cell toxicity or its ability to induce CI in Drosophila. Our study thus demonstrates that CI functions as a transgenerational toxin-antidote system and suggests that CidB acts by poisoning paternal DNA replication in incompatible crosses.

Published
2021
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16. When mentoring matters: a French mentoring program for women in science

Author

Julie Batut, Marina Kvaskoff, May C. Morris, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Unité de biologie moléculaire, cellulaire et du développement (MCD), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), 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, KARLI, Mélanie, Unité de biologie moléculaire, cellulaire et du développement - UMR5077 (MCD), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)

Subjects
0303 health sciences, Medical education, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), ComputingMilieux_THECOMPUTINGPROFESSION, 4. Education, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Biomedical Engineering, MEDLINE, Bioengineering, Applied Microbiology and Biotechnology, [SDV] Life Sciences [q-bio], ComputingMilieux_GENERAL, 03 medical and health sciences, 0302 clinical medicine, Molecular Medicine, Women in science, Sociology, ComputingMethodologies_GENERAL, 030217 neurology & neurosurgery, 030304 developmental biology, Biotechnology
Abstract

International audience; An innovative program addresses the need for support, encouragement and guidance on the part of women scientists in the early years of their career, during their PhD.

Published
2021
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17. Diagnostic criteria for cancer cachexia: reduced food intake and inflammation predict weight loss and survival in an international, multi-cohort analysis

Author

Florian Strasser, François Goldwasser, Vickie E. Baracos, Ioannis Gioulbasanis, Isabelle Bourdel-Marchasson, R. Thomas Jagoe, Maurizio Muscaritoli, Martin Chasen, Ola Wallengren, Bruno Gagnon, Barry Laird, Lene Thoresen, Federico Bozzetti, Pierre Senesse, Anne C. Voss, Chris Deans, Catherine Kubrak, Lisa Martin, Sean Kazemi, University of Alberta, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Université de Bordeaux (UB), University of Edinburgh, Université Laval [Québec] (ULaval), University of Toronto, Larissa University Hospital, Sahlgrenska University Hospital [Gothenburg], Abbott Nutrition R&D, Prévention et traitement de la perte protéique musculaire en situation de résistance à l'anabolisme (PRETRRAM (URP_4466)), Université Paris Cité (UPCité), Jewish General Hospital, Università degli Studi di Milano = University of Milan (UNIMI), Fribourg Cantonal Hospital, St. Olavs Hospital HF (St. Olav's University Hospital), Institut du Cancer de Montpellier (ICM), 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), and KARLI, Mélanie

Subjects
medicine.medical_specialty, reduced food intake, Canada, Cachexia, [SDV]Life Sciences [q-bio], Diseases of the musculoskeletal system, malnutrition, Gastroenterology, cachexia, Cancer, Inflammation, Malnutrition, Reduced food intake, Weight loss, Cohort Studies, Eating, Humans, Weight Loss, Neoplasms, Physiology (medical), Internal medicine, medicine, Clinical endpoint, cancer, Orthopedics and Sports Medicine, Performance status, Proportional hazards model, business.industry, Weight change, QM1-695, Original Articles, medicine.disease, [SDV] Life Sciences [q-bio], RC925-935, inflammation, Human anatomy, Original Article, medicine.symptom, weight loss, business, Cohort study
Abstract

International audience; Background: Cancer-associated weight loss (WL) associates with increased mortality. International consensus suggests that WL is driven by a variable combination of reduced food intake and/or altered metabolism, the latter often represented by the inflammatory biomarker C-reactive protein (CRP). We aggregated data from Canadian and European research studies to evaluate the associations of reduced food intake and CRP with cancer-associated WL (primary endpoint) and overall survival (OS, secondary endpoint).Methods: The data set included a total of 12,253 patients at risk for cancer-associated WL. Patient-reported WL history (% in 6 months) and food intake (normal, moderately, or severely reduced) were measured in all patients; CRP (mg/L) and OS were measured in N = 4960 and N = 9952 patients, respectively. All measures were from a baseline assessment. Clinical variables potentially associated with WL and overall survival (OS) including age, sex, cancer diagnosis, disease stage, and performance status were evaluated using multinomial logistic regression MLR and Cox proportional hazards models, respectively.Results: Patients had a mean weight change of -7.3% (±7.1), which was categorized as: ±2.4% (stable weight; 30.4%), 2.5-5.9% (19.7%), 6.0-10.0% (23.2%), 11.0-14.9% (12.0%), ≥15.0% (14.6%). Normal food intake, moderately, and severely reduced food intake occurred in 37.9%, 42.8%, and 19.4%, respectively. In MLR, severe WL (≥15%) (vs. stable weight) was more likely (P < 0.0001) if food intake was moderately [OR 6.28, 95% confidence interval (CI 5.28-7.47)] or severely reduced [OR 18.98 (95% CI 15.30-23.56)]. In subset analysis, adjusted for food intake, CRP was independently associated (P < 0.0001) with ≥15% WL [CRP 10-100 mg/L: OR 2.00, (95% CI 1.58-2.53)] and [CRP > 100 mg/L: OR 2.30 (95% CI 1.62-3.26)]. Diagnosis, stage, and performance status, but not age or sex, were significantly associated with WL. Median OS was 9.9 months (95% CI 9.5-10.3), with median follow-up of 39.7 months (95% CI 38.8-40.6). Moderately and severely reduced food intake and CRP independently predicted OS (P < 0.0001).Conclusions: Modelling WL as the dependent variable is an approach that can help to identify clinical features and biomarkers associated with WL. Here, we identify criterion values for food intake impairment and CRP that may improve the diagnosis and classification of cancer-associated cachexia.

Published
2021
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18. Les dangers de l'invasion plastique

Author

Fabre, Pascale, Lagarde, Fabienne, Bruzaud, Stephane, Duflos, Guillaume, Galgani, François, Gastaldi, Emmanuelle, George, Matthieu, Ghiglione, Jean-François, Huvet, Arnaud, Paul-Pont, Ika, ter Halle, Alexandra, Laboratoire Charles Coulomb (L2C), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des Molécules et Matériaux du Mans (IMMM), Le Mans Université (UM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Dupuy de Lôme (IRDL), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de sécurité des aliments de Maisons-Alfort (LSAl), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Laboratoire d'Océanographie Microbienne (LOMIC), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Interactions moléculaires et réactivité chimique et photochimique (IMRCP), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Fluides, Energie, Réacteurs, Matériaux et Transferts (FERMAT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), SMODD - Systèmes Moléculaires Organisés et Développement Durable (SMODD), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT), Challier Emeric, and KARLI, Mélanie

Subjects
[SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, [CHIM.POLY] Chemical Sciences/Polymers, [SDV.EE] Life Sciences [q-bio]/Ecology, environment, [CHIM.POLY]Chemical Sciences/Polymers, [SDU.OCEAN] Sciences of the Universe [physics]/Ocean, Atmosphere
Abstract

International audience

Published
2021

19. Diagnostic virologique (Encyclopédie Universalis)

Author

Simonin, Yannick, KARLI, Mélanie, Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]

Subjects
[SDV] Life Sciences [q-bio], [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Diagnostic clinique, [SDV]Life Sciences [q-bio], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Abstract

Diagnostic virologique; Identifier le micro-organisme responsable d’une maladie infectieuse, qu’elle soit virale ou associée à un autre pathogène, revêt une importante toute particulière. En effet, de ce diagnostic peut dépendre la prise en charge du patient, ce qui en est l’aspect le plus évident. L’identification des agents infectieux permet aussi le suivi de la propagation d’un virus ou d’une maladie virale au sein d’une population donnée. Cette surveillance peut aboutir à la mise en place de mesures de prévention et de contrôle adaptées à l’évolution de la situation sanitaire, comme cela est le cas par exemple depuis 2020 pour le suivi de la pandémie de Covid-19, causée par le virus SARS-CoV-2, et depuis plusieurs dizaines d’années pour les virus grippaux.

Published
2021

20. 2-Phenyl-1 H -pyrrole-3-carboxamide as a New Scaffold for Developing 5-HT 6 Receptor Inverse Agonists with Cognition-Enhancing Activity

Author

Xavier Bantreil, Anna Gwizdak, Gilles Subra, Joanna Golebiowska, Marcin Drop, Vittorio Canale, Jean Martinez, Gniewomir Latacz, Frédéric Lamaty, Paweł Zajdel, Andrzej J. Bojarski, Rafał Kurczab, Katarzyna Grychowska, Maciej Pawłowski, Piotr Popik, Séverine Chaumont-Dubel, Philippe Marin, Martyna Krawczyk, Maria Walczak, Agnieszka Nikiforuk, Paulina Koczurkiewicz-Adamczyk, Grzegorz Satała, KARLI, Mélanie, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Polska Akademia Nauk = Polish Academy of Sciences (PAN), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Cdk5 signaling, Metrics & More Article Recommendations Cognition, Physiology, medicine.drug_class, Cognitive Neuroscience, inverse agonism, Carboxamide, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cognition, [CHIM] Chemical Sciences, medicine, 5-HT 6 receptor, Inverse agonist, [CHIM]Chemical Sciences, Receptor, 2-phenyl-1H-pyrrole-3-carboxamide, constitutive activity, 5-HT receptor, 030304 developmental biology, 0303 health sciences, Quinoline, Cell Biology, General Medicine, attentional set shifting task, chemistry, 5-HT6 receptor, novel object recognition test, Serotonin, Signal transduction, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; Serotonin type 6 receptor (5-HT6R) has gained particular interest as a promising target for treating cognitive deficits, given the positive effects of its antagonists in a wide range of memory impairment paradigms. Herein, we report on degradation of the 1H-pyrrolo[3,2-c]quinoline scaffold to provide the 2-phenyl-1H-pyrrole-3-carboxamide, which is devoid of canonical indole-like skeleton and retains recognition of 5-HT6R. This modification has changed the compound's activity at 5-HT6R-operated signaling pathways from neutral antagonism to inverse agonism. The study identified compound 27 that behaves as an inverse agonist of the 5-HT6R at the Gs and Cdk5 signaling pathways. Compound 27 showed high selectivity and metabolic stability and was brain penetrant. Finally, 27 reversed scopolamine-induced memory decline in the novel object recognition test and exhibited procognitive properties in the attentional set-shifting task in rats. In light of these findings, 27 might be considered for further evaluation as a new cognition-enhancing agent, while 2-phenyl-1H-pyrrole-3-carboxamide might be used as a template for designing 5-HT6R inverse agonists.

Published
2021
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21. Threats and Opportunities for the Clinical Investigation of High-risk Medical Devices in the Context of the New European Regulations

Author

Lionel Pazart, Liesbet Geris, Sylvia Pelayo, Gabriel Gruionu, C. Lavet, H. A. Ferreira, Eirini Lekka, Thomas Lihoreau, Catherine Roussel, Yves Bayon, Isabel Rocha, Frédéric Barbot, T. Chevallier, Philippe Mabo, Nicos Maglaveras, Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), French alliance clinical trial [Paris] (F-CRIN), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Indiana University School of Medicine, Indiana University System, University of Craiova, CHU Pontchaillou [Rennes], Sofradim-Covidien, Centre d’Investigation Clinique 1429 [Garches] (CIC 1429), Hôpital Raymond Poincaré [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Medical Informatics [Aristotle University of Thessaloniki] (LOMI), Aristotle University of Thessaloniki, Université de Lisbonne, GIGA [Université Liège], Université de Liège, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and KARLI, Mélanie

Subjects
[SDV] Life Sciences [q-bio], EU MDR 2017/745, business.industry, [SDV]Life Sciences [q-bio], Clinical investigation, Medical Device Regulation, Context (language use), High-risk Medical Device, Clinical Investigation, Regulatory Science, Business, Public relations
Abstract

International audience; This position paper analyses the threats from the current situation of the clinical investigation to the expectations of the new European regulations focusing on high risk medical devices (HRMDs). We present also some opportunities to improve the feasibility and quality of clinical investigation. In summary, investigation protocols of medical devices, advised and authorized by the competent authorities, are few and heterogenous. There is a lack of quality in the existing studies, a lack of methodological knowledge and consequently high expectations for assistance from those involved in the design of clinical study protocols on HRMD. Guidance that is specific to the different type of devices is missing. Adaptive designs, pragmatic trial, usability methods, computer modeling and real world data are gaining more and more traction for assessing the safety and performance of high risk medical devices from a regulatory view-point.

Published
2021
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22. Comment on 'Meta-analysis reveals declines in terrestrial but increases in freshwater insect abundances'

Author

Jean-François Humbert, Dirk Maes, Pierre-André Cornillon, Laurence Gaume, Jean-Marc Bonmatin, Marion Desquilbet, Hans Van Dyck, Manuela Grippa, Régis Céréghino, David Goulson, Toulouse School of Economics (TSE-R), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Botanique et Modélisation de l'Architecture des Plantes et des Végétations (UMR AMAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Géosciences Environnement Toulouse (GET), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Laboratoire Ecologie Fonctionnelle et Environnement (LEFE), Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT), Institut d'écologie et des sciences de l'environnement de Paris (iEES Paris ), Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Mathématique de Rennes (IRMAR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Université Catholique de Louvain = Catholic University of Louvain (UCL), University of Sussex, ANR-16-IDEX-0006 (Investissements d’Avenir program), Agence Nationale de la Recherche, ANR-17-EURE-0010,CHESS,Toulouse Graduate School défis en économie et sciences sociales quantitatives(2017), ANR-16-IDEX-0006,MUSE,MUSE(2016), ANR-15-CE21-0006,IDAE,Institutionnalisations des agroécologies(2015), ANR-11-LABX-0020,LEBESGUE,Centre de Mathématiques Henri Lebesgue : fondements, interactions, applications et Formation(2011), Toulouse School of Economics (TSE), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Laboratoire Ecologie Fonctionnelle et Environnement (ECOLAB), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, KARLI, Mélanie, Toulouse Graduate School défis en économie et sciences sociales quantitatives - - CHESS2017 - ANR-17-EURE-0010 - EURE - VALID, MUSE - - MUSE2016 - ANR-16-IDEX-0006 - IDEX - VALID, and Institutionnalisations des agroécologies - - IDAE2015 - ANR-15-CE21-0006 - AAPG2015 - VALID

Subjects
0106 biological sciences, 0303 health sciences, Multidisciplinary, Insecta, Ecology, MEDLINE, Ecological data, Fresh Water, [SDV.BID]Life Sciences [q-bio]/Biodiversity, 010603 evolutionary biology, 01 natural sciences, 03 medical and health sciences, Geography, Fresh water, Meta-analysis, Animals, Humans, B- ECONOMIE ET FINANCE, Data selection, 030304 developmental biology, [SDV.BID] Life Sciences [q-bio]/Biodiversity
Abstract

Van Klink et al . (Reports, 24 April 2020, p. 417) argue for a more nuanced view of insect decline, and of human responsibility for this decline, than previously suggested. However, shortcomings in data selection and methodology raise questions about their conclusions on trends and drivers. We call for more rigorous methodology to be applied in meta-analyses of ecological data.

Published
2020
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23. Dissecting the NK cell population in hematological cancers confirms the presence of tumor cells and their impact on NK population function

Author

Martin Villalba, Catherine Alexia, Dang-Nghiem Vo, Michael Constantinides, Nerea Allende-Vega, Guillaume Cartron, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, KARLI, Mélanie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Trogocytosis, medicine.drug_class, Lymphocyte, Population, Cell, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, NK cells, Biology, Stem cell marker, Monoclonal antibody, Article, [SDV.CAN] Life Sciences [q-bio]/Cancer, AML, medicine, trogocytosis, education, Antibody-dependent cell-mediated cytotoxicity, education.field_of_study, Innate immune system, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, allergology, lcsh:R, UMAP, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, 3. Good health, medicine.anatomical_structure, Cancer research, Hodgkin lymphoma, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

The lymphocyte lineage natural killer (NK) cell is part of the innate immune system and protects against pathogens and tumor cells. NK cells are the main cell effectors of the monoclonal antibodies (mAbs) that mediates antibody-dependent cell cytotoxicity (ADCC). Hence, it is relevant to understand NK physiology and status to investigate the biological effect of mAbs in the clinic. NK cells are heterogeneous with multiple subsets that may have specific activity against different attacks. The presence of viral-sculpted NK cell populations has already been described, but the presence of cancer-sculpted NK cells remains unknown. Cancer induces a broad NK cell dysfunction, which has not been linked to a specific population. Here, we investigated the NK cell population by Uniform Manifold Approximation and Projection (UMAP) embed maps in Hodgkin lymphoma (HL) and acute myeloid leukemia (AML) patients at diagnosis and at least 30 days after treatment, which correlates with tumor cell clearance. We found that the NK lineage largely responded to the tumor by generating antitumor NK cells and renewing the population with a subset of immature NK cells. However, we failed to identify a specific &ldquo, memory-like&rdquo, subset with the NK cell markers used. Moreover, in patients in relapse, we found essentially the same NK populations as those found at diagnosis, suggesting that NK cells equally respond to the first or second tumor rise. Finally, we observed that previous cytomegalovirus (CMV) infection largely affects the tumor-associated changes in NK population, but the CMV-associated CD57+NKG2C+ NK cell population does not appear to play any role in tumor immunity.

Published
2020
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24. Formulation and Evaluation of SNEDDS Loaded with Original Lipophenol for the Oral Route to Prevent Dry AMD and Stragardt’s Disease

Author

Maxime Vincent, Laurianne Simon, Philippe Brabet, Philippe Legrand, Christophe Dorandeu, Josephine Lai Kee Him, Thierry Durand, Céline Crauste, Sylvie Begu, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Biologie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), ANR-18-CE18-0017,LipoPheRet,Les lipohenols de nouveaux anti-oxydants et stresseurs carbonylés pour combattre la dégénérescence maculaire(2018), KARLI, Mélanie, and APPEL À PROJETS GÉNÉRIQUE 2018 - Les lipohenols de nouveaux anti-oxydants et stresseurs carbonylés pour combattre la dégénérescence maculaire - - LipoPheRet2018 - ANR-18-CE18-0017 - AAPG2018 - VALID

Subjects
[SDV] Life Sciences [q-bio], antioxidant, dry age-related macular degeneration (AMD), genetic structures, [SDV]Life Sciences [q-bio], Pharmaceutical Science, self-nanoemulsifying drug delivery system (SNEDDS), Stargardt’s disease (STGD1), lipophenol, oral delivery
Abstract

Dry age-related macular degeneration (Dry AMD) and Stargardt’s disease (STGD1) are common eye diseases, characterized by oxidative and carbonyl stress (COS)-inducing photoreceptor degeneration and vision loss. Previous studies have demonstrated the protective effect of photoreceptors after the intravenous administration of a new lipophenol drug, phloroglucinol-isopropyl-DHA (IP-DHA). In this study, we developed an oral formulation of IP-DHA (BCS Class IV) relying on a self-nanoemulsifying drug delivery system (SNEDDS). SNEDDS, composed of Phosal® 53 MCT, Labrasol®, and Transcutol HP® at a ratio of 25/60/15 (w/w/w), led to a homogeneous nanoemulsion (NE) with a mean size of 53.5 ± 4.5 nm. The loading of IP-DHA in SNEDDS (SNEDDS-IP-DHA) was successful, with a percentage of IP-DHA of 99.7% in nanoemulsions. The in vivo study of the therapeutic potency of SNEDDS-IP-DHA after oral administration on mice demonstrated photoreceptor protection after the induction of retinal degeneration with acute light stress (73–80%) or chronic light stress (52–69%). Thus, SNEDDS formulation proved to increase the solubility of IP-DHA, improving its stability in intestinal media and allowing its passage through the intestinal barrier after oral force-fed administration, while maintaining its biological activity. Therefore, SNEDDS-IP-DHA is a promising future preventive treatment for dry AMD and STGD1.

Published
2022
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25. Histoire des épidémies

Author

Jean-Pierre Dedet, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Académie des sciences d'outre-mer, and KARLI, Mélanie

Subjects
[SDV] Life Sciences [q-bio], Histoire, épidémies, santé publique, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), [SHS] Humanities and Social Sciences, pandémies, [SHS]Humanities and Social Sciences
Abstract

International audience; Les épidémies sont aussi anciennes que l’Homme et toutes les populations en sont, ou en ont été, affectées à un moment ou à un autre de leur histoire. Certaines d’entre elles ont été responsables de nombres élevés, parfois considérables, de morts, et ont eu des conséquences sanitaires, sociales, culturelles, religieuses, politiques et économiques majeures. Phénomènes biologiques complexes, les épidémies résultent des interactions entre trois catégories de facteurs : les microbes responsables, les populations d’hôtes qu’ils colonisent, et l’environnement dans lequel cet ensemble évolue. La dynamique des épidémies a varié au cours des temps en fonction des évolutions de ces différents facteurs. Un rapide tour d’horizon sur les grandes épidémies du passé nous éclaire sur la compréhension des épidémies présentes. La connaissance des agents infectieux et de leur histoire naturelle apporte des enseignements utiles à l’organisation de la surveillance, au développement des outils diagnostiques et thérapeutiques, à la mise au point des moyens de lutte et à la conception des programmes de prévention des épidémies du futur.

Published
2020

26. Downregulation of Mitochondrial TSPO Inhibits Mitophagy and Reduces Enucleation During Human Terminal Erythropoiesis

Author

Naomi Taylor, Claude Hattab, Suella Martino, Mariano A. Ostuni, Sophie D. Lefevre, Martina Moras, Pedro Gonzalez-Menendez, Jérôme Larghero, Sandrina Kinet, Caroline Le Van Kim, KARLI, Mélanie, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Institut National de la Transfusion Sanguine [Paris] (INTS), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hematopoïèse et Immunothérapie, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CIC - Biotherapie - Saint Louis ((CIC-BT 301)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)

Subjects
Mitochondrion, MESH: Benzodiazepinones, MESH: Down-Regulation, lcsh:Chemistry, 0302 clinical medicine, MESH: RNA, Small Interfering, Mitophagy, Erythropoiesis, RNA, Small Interfering, lcsh:QH301-705.5, Spectroscopy, 0303 health sciences, Benzodiazepinones, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Kinetics, biology, VDAC, Chemistry, Cell Differentiation, General Medicine, Computer Science Applications, Cell biology, Mitochondria, Phenotype, MESH: Receptors, GABA, 030220 oncology & carcinogenesis, enucleation, MESH: Cell Differentiation, MESH: Cell Nucleus, Voltage-dependent anion channel, MESH: Mitochondria, MESH: Mitophagy, Down-Regulation, PINK1, MESH: Phenotype, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Downregulation and upregulation, Receptors, GABA, Erythroblast, Translocator protein, Humans, Physical and Theoretical Chemistry, Molecular Biology, 030304 developmental biology, Cell Nucleus, MESH: Humans, MESH: Erythropoiesis, Organic Chemistry, Kinetics, lcsh:Biology (General), lcsh:QD1-999, biology.protein, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, TSPO1
Abstract

International audience; Translocator protein (TSPO) and voltage dependent anion channels (VDAC) are two proteins forming a macromolecular complex in the outer mitochondrial membrane that is involved in pleiotropic functions. Specifically, these proteins were described to regulate the clearance of damaged mitochondria by selective mitophagy in non-erythroid immortalized cell lines. Although it is well established that erythroblast maturation in mammals depends on organelle clearance, less is known about mechanisms regulating this clearance throughout terminal erythropoiesis. Here, we studied the effect of TSPO1 downregulation and the action of Ro5-4864, a drug ligand known to bind to the TSPO/VDAC complex interface, in ex vivo human terminal erythropoiesis. We found that both treatments delay mitochondrial clearance, a process associated with reduced levels of the PINK1 protein, which is a key protein triggering canonical mitophagy. We also observed that TSPO1 downregulation blocks erythroblast maturation at the orthochromatic stage, decreases the enucleation rate, and increases cell death. Interestingly, TSPO1 downregulation does not modify reactive oxygen species (ROS) production nor intracellular adenosine triphosphate (ATP) levels. Ro5-4864 treatment recapitulates these phenotypes, strongly suggesting an active role of the TSPO/VDAC complex in selective mitophagy throughout human erythropoiesis. The present study links the function of the TSPO/VDAC complex to the PINK1/Parkin-dependent mitophagy induction during terminal erythropoiesis, leading to the proper completion of erythroid maturation.

Published
2020
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27. Global hyperactivation of enhancers stabilizes human and mouse naive pluripotency through inhibition of CDK8/19 Mediator kinases

Author

Pierre Savatier, Nuria Montserrat, Laia Richart-Ginés, Camille Stephan-Otto Attolini, Raquel Bernad, Susana Prieto, Marta I. Sierra, Joaquín Pastor, Magdalena Zernicka-Goetz, Sonia Sánchez Martínez, Daniel Fisher, Javier Munoz, Sandrina Nóbrega-Pereira, Noelia Alcazar, Ana Martinez-Val, Gonzalo Gómez-López, Mario F. Fraga, Marta N. Shahbazi, Elisabeth Simboeck, Carmen Blanco-Aparicio, Elena Garreta, Osvaldo Graña-Castro, Alain Camasses, Irène Aksoy, Sagrario Ortega, Cian J. Lynch, Maribel Muñoz-Martin, Isabel A. Calvo, Agustín F. Fernández, Manuel Serrano, Carolina Tarantino, Spanish National Cancer Research Center (CNIO), Barcelona Institute of Science and Technology (BIST), University of Cambridge [UK] (CAM), Institute for Research in Biomedicine ( iBiMED), Universidade de Aveiro, Institut Curie [Paris], Institut cellule souche et cerveau (U846 Inserm - UCBL1), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Instituto Universitario de Oncología del Principado de Asturias [Oviedo, Spain] (IUOPA), Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Division of Biology and Biological Engineering [Pasadena, USA] (BBE), California Institute of Technology (CALTECH), Institució Catalana de Recerca i Estudis Avançats (ICREA), Centre National de la Recherche Scientifique (CNRS), Leverhulme Trust, Wellcome Trust, Generalitat de Catalunya, European Research Council, Fondation pour la Recherche Médicale, European Commission, Agence Nationale de la Recherche (France), Université de Lyon, Ministerio de Economía y Competitividad (España), Centro Nacional de Investigaciones Oncológicas (España), Institut National du Cancer (France), Ligue Nationale contre le Cancer (France), Asociación Española Contra el Cáncer, Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, Agencia Estatal de Investigación (España), Principado de Asturias, Liberbank, Obra Social Cajastur, Banco Santander, Fundación Botín, Fundación 'la Caixa', Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and KARLI, Mélanie

Subjects
MESH: Signal Transduction, Cellular differentiation, [SDV]Life Sciences [q-bio], ADN, RNA polymerase II, Stem cells, Mice, 0302 clinical medicine, MESH: DNA Methylation, MESH: Animals, Phosphorylation, Promoter Regions, Genetic, Induced pluripotent stem cell, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, biology, Kinase, Chemistry, Cell Differentiation, Cyclin-Dependent Kinases, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], Enhancer Elements, Genetic, MESH: Cyclin-Dependent Kinases, 030220 oncology & carcinogenesis, MESH: Pluripotent Stem Cells, Female, RNA Polymerase II, Signal transduction, Cèl·lules mare, Metilació, Signal Transduction, Pluripotent Stem Cells, MESH: Cell Differentiation, Methylation, MESH: Cyclin-Dependent Kinase 8, 03 medical and health sciences, MESH: Promoter Regions, Genetic, Animals, Humans, Kinase activity, Enhancer, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH: Phosphorylation, Cell Biology, DNA, DNA Methylation, Cyclin-Dependent Kinase 8, MESH: RNA Polymerase II, biology.protein, Cyclin-dependent kinase 8, MESH: Enhancer Elements, Genetic, MESH: Female
Abstract

Pluripotent stem cells (PSCs) transition between cell states in vitro, reflecting developmental changes in the early embryo. PSCs can be stabilized in the naive state by blocking extracellular differentiation stimuli, particularly FGF–MEK signalling. Here, we report that multiple features of the naive state in human and mouse PSCs can be recapitulated without affecting FGF–MEK signalling or global DNA methylation. Mechanistically, chemical inhibition of CDK8 and CDK19 (hereafter CDK8/19) kinases removes their ability to repress the Mediator complex at enhancers. CDK8/19 inhibition therefore increases Mediator-driven recruitment of RNA polymerase II (RNA Pol II) to promoters and enhancers. This efficiently stabilizes the naive transcriptional program and confers resistance to enhancer perturbation by BRD4 inhibition. Moreover, naive pluripotency during embryonic development coincides with a reduction in CDK8/19. We conclude that global hyperactivation of enhancers drives naive pluripotency, and this can be achieved in vitro by inhibiting CDK8/19 kinase activity. These principles may apply to other contexts of cellular plasticity., M.N.S. was funded by a Leverhulme Trust early career fellowship. Work in the laboratory of M.Z.-G. was funded by the Wellcome Trust (098287/Z/12/Z) and the European Research Council (ERC) (669198). I.C. was funded by the Secretaria d’Universitats i Recerca de la Generalitat de Catalunya and European Social Fund. I.A. and P.S. were supported by the Fondation pour la Recherche Medicale (DEQ20170336757), Infrastructure Nationale en Biologie et Santé INGESTEM (ANR-11-INBS-0009), IHU-B CESAME (ANR-10-IBHU-003), LabEx REVIVE (ANR-10-LABX-73), LabEx DEVweCAN (ANR-10-LABX-0061) and LabEx CORTEX (ANR-11-LABX-0042) of University of Lyon within the programme ‘Investissements d’Avenir’ (ANR-11-IDEX-0007). Research by J.P., S.M. and C.B.-A. was supported in part by a grant from the Spanish Ministry of Economy and Competitiveness (SAF2013-44267-R) and by the CNIO. Work in the laboratory of D.F. was funded by the Institut National du Cancer (PLBIO10-068 and PLBIO15-005) and the Ligue National Contre le Cancer (EL2018.LNCC/DF). Work in the laboratory of N.M. was funded by the ERC, under the European Union Horizon 2020 research and innovation programme (StG-2014–640525_REGMAMKID), the Spanish Association Against Cancer (AECC/LABAE16006), Carlos III Health Institute (Red TerCel, CardioCel, RD16/0011/0027), Ministry of Economy and Competitiveness (MINECO) projects SAF2017–89782-R, SAF2015–72617-EXP and RYC-2014–16242, and the CERCA/Government of Catalonia (2017 SGR 1306). Work in the laboratory of S.O. was funded by SAF2013–44866-R from MINECO Spain. Work in the laboratory of M.F.F. was funded by Plan Nacional de I+D+I 2013–2016/FEDER (PI15/00892, to M.F.F. and A.F.F.); the ISCIII-Subdireccion General de Evaluación y Fomento de la Investigación and Plan Nacional de I+D+I 2008–2011/FEDER (CP11/00131, to A.F.F.); IUOPA (to M.I.S.); and the Asturias Regional Government (GRUPIN14–052, to M.F.F.). The IUOPA is supported by the Obra Social Liberbank-Cajastur, Spain. Work in the laboratory of M.S. was funded by the CNIO, the IRB and by grants from Spanish Ministry of Economy co-funded by the European Regional Development Fund (SAF2017-82613-R), ERC (ERC-2014-AdG/669622), Botin Foundation, Banco Santander (Santander Universities Global Division), laCaixa Foundation and Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement of Catalonia (Grup de Recerca consolidat 2017 SGR 282).

Published
2020
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28. Diagnostic Accuracy of the French Version of the Adult Attention Deficit / Hyperactivity Disorder Self-Report Screening Scale for DSM-5 (ASRS-5)

Author

Hélène Richard-Lepouriel, Régis Lopez, Rosetta Nicastro, Nader Perroud, Stéphanie Bioulac, Anne Sauvaget, Marie Gachet, Stéphanie Baggio, Sophie Bayard, Charlotte Kraemer, Sébastien Weibel, Martin Desseilles, Clémence Cabelguen, Université de Genève = University of Geneva (UNIGE), Dynamique des capacités humaines et des conduites de santé (EPSYLON), Université Montpellier 1 (UM1)-Université Paul-Valéry - Montpellier 3 (UPVM)-Université de Montpellier (UM), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Namur [Namur] (UNamur), Hôpital Lapeyronie [Montpellier] (CHU), CHU Strasbourg, Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Sommeil, Addiction et Neuropsychiatrie [Bordeaux] (SANPSY), Université de Bordeaux (UB)-CHU de Bordeaux Pellegrin [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), Motricité, interactions, performance EA 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), Université de Nantes (UN)-Université de Nantes (UN), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, Geneva University Hospital (HUG), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), KARLI, Mélanie, University of Geneva [Switzerland], Université de Montpellier (UM)-Université Paul-Valéry - Montpellier 3 (UPVM)-Université Montpellier 1 (UM1), Hôpital Universitaire de Genève, Sommeil, Attention et Neuropsychiatrie [Bordeaux] (SANPSY), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg-Université de Strasbourg (UNISTRA), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Le Mans Université (UM), Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Motricité, interactions, performance EA 4334 (MIP), Le Mans Université (UM)-Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), and Neuropsychiatrie : recherche épidémiologique et clinique

Subjects
050103 clinical psychology, Pediatrics, medicine.medical_specialty, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Diagnostic accuracy, Assessment, behavioral disciplines and activities, DSM-5, ddc:616.89, Healthy volunteers, mental disorders, Validation, medicine, Attention deficit hyperactivity disorder, 0501 psychology and cognitive sciences, Bipolar disorder, Self report, Borderline personality disorder, ddc:613, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, 05 social sciences, medicine.disease, 3. Good health, Clinical Psychology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Attention deficit, Screening, Psychology, 050104 developmental & child psychology
Abstract

International audience; Attention Deficit/Hyperactivity Disorder (ADHD) often persists into adulthood. However, few screening tools have been adaptedto assess adult ADHD using the DSM-5 criteria. This study assessed the diagnostic accuracy of a French version of the ADHDSelf-Report Screening for DSM-5 (ASRS-5). This multicentric cross-sectional study included 557 participants: 309 adult ADHDoutpatients without bipolar disorder (BD)/borderline personality disorder (BPD) (n = 236) or with BD/BPD (n = 36) and 285adults without ADHD who were either healthy volunteers (n = 248) or outpatients with BD or BPD (n = 37). Measures includedADHD diagnosis and the ASRS-5. The ASRS-5 was a good predictor of ADHD diagnosis (cut-off score ! 13/24: sensitivity =84.3%, specificity = 91.9%) in the sample of adult outpatients without comorbid disorders/healthy controls. Performances werelower with this cut-off score in some subgroups, notably low-severity ADHD symptomatology (sensitivity = 63.5%) and participantswith BD or BPD (sensitivity = 91.7%, specificity = 54.1%). The French ASRS-5 had acceptable screening properties,even if its performance varied according to clinical variables. Further evidence is needed for patients with comorbid disordershaving overlapping symptoms.

Published
2020
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29. The equilibrative nucleoside transporter ENT1 is critical for nucleotide homeostasis and optimal erythropoiesis

Author

Naomi Taylor, Yujin Zhang, Yang Xia, Marc Sitbon, Mahmoud Mikdar, Sylvia Sanquer, Cerina Chhuon, Pedro González-Menéndez, Narla Mohandas, Ida Chiara Guerrera, Anne-Claire Boschat, Slim Azouzi, Olivier Hermine, Thierry Peyrard, Sandrina Kinet, Yves Colin, Marion Serra, Xiaoli Cai, Caroline Le Van Kim, Abdoul Karim Dembele, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre National de Référence pour les Groupes Sanguins (CNRGS), CNRGS, Hematopoïèse et Immunothérapie, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), New York Blood Center, National Institutes of Health [Bethesda] (NIH), KARLI, Mélanie, Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], Iron, Immunology, ABCC4, Biochemistry, Equilibrative Nucleoside Transporter 1, 03 medical and health sciences, chemistry.chemical_compound, Cyclic nucleotide, Mice, Red Cells, Iron, and Erythropoiesis, 0302 clinical medicine, medicine, Animals, Homeostasis, Humans, Cyclic adenosine monophosphate, Erythropoiesis, Cells, Cultured, Mice, Knockout, Adenosine transport, biology, Nucleosides, Equilibrative nucleoside transporter, Cell Biology, Hematology, Hematopoietic Stem Cells, Adenosine, Adenosine Monophosphate, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, biology.protein, Nucleoside, medicine.drug
Abstract

This is a related article to: Nucleoside ENTry modulates erythropoiesis (cf ci-dessous); International audience; Abstract The tight regulation of intracellular nucleotides is critical for the self-renewal and lineage specification of hematopoietic stem cells (HSCs). Nucleosides are major metabolite precursors for nucleotide biosynthesis and their availability in HSCs is dependent on their transport through specific membrane transporters. However, the role of nucleoside transporters in the differentiation of HSCs to the erythroid lineage and in red cell biology remains to be fully defined. Here, we show that the absence of the equilibrative nucleoside transporter (ENT1) in human red blood cells with a rare Augustine-null blood type is associated with macrocytosis, anisopoikilocytosis, an abnormal nucleotide metabolome, and deregulated protein phosphorylation. A specific role for ENT1 in human erythropoiesis was demonstrated by a defective erythropoiesis of human CD34+ progenitors following short hairpin RNA-mediated knockdown of ENT1. Furthermore, genetic deletion of ENT1 in mice was associated with reduced erythroid progenitors in the bone marrow, anemia, and macrocytosis. Mechanistically, we found that ENT1-mediated adenosine transport is critical for cyclic adenosine monophosphate homeostasis and the regulation of erythroid transcription factors. Notably, genetic investigation of 2 ENT1null individuals demonstrated a compensation by a loss-of-function variant in the ABCC4 cyclic nucleotide exporter. Indeed, pharmacological inhibition of ABCC4 in Ent1−/− mice rescued erythropoiesis. Overall, our results highlight the importance of ENT1-mediated nucleotide metabolism in erythropoiesis.

Published
2020
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30. Candidate Biomarkers of Suicide Crisis Syndrome: What to Test Next? A Concept Paper

Author

Raffaella Calati, Lisa J. Cohen, Charles B. Nemeroff, Igor Galynker, Jorge Lopez-Castroman, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), KARLI, Mélanie, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Calati, R, Nemeroff, C, Lopez-Castroman, J, Cohen, L, and Galynker, I

Subjects
AcademicSubjects/MED00415, acuity, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, review, Poison control, Suicide prevention, 03 medical and health sciences, 0302 clinical medicine, Autonomic dysregulation, Medicine, Humans, Pharmacology (medical), [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], suicide, Endogenous opioid, Pharmacology, business.industry, AcademicSubjects/SCI01870, Mental Disorders, Human factors and ergonomics, biomarkers, Cognition, Syndrome, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, biomarker, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, Suicide crisis, Neurocognitive, 030217 neurology & neurosurgery, Clinical psychology
Abstract

BackgroundThere has been increasing interest in both suicide-specific diagnoses within the psychiatric nomenclature and related biomarkers. Because the Suicide Crisis Syndrome—an emotional crescendo of several interrelated symptoms—seems to be promising for the identification of individuals at risk of suicide, the aim of the present paper is to review the putative biological underpinnings of the Suicide Crisis Syndrome symptoms (entrapment, affective disturbance, loss of cognitive control, hyperarousal, social withdrawal).MethodsA PubMed literature search was performed to identify studies reporting a link between each of the 5 Suicide Crisis Syndrome symptoms and biomarkers previously reported to be associated with suicidal outcomes.ResultsDisturbances in the hypothalamic-pituitary-adrenal axis, with dysregulated corticotropin-releasing hormone and cortisol levels, may be linked to a sense of entrapment. Affective disturbance is likely mediated by alterations in dopaminergic circuits involved in reward and antireward systems as well as endogenous opioids. Loss of cognitive control is linked to altered neurocognitive function in the areas of executive function, attention, and decision-making. Hyperarousal is linked to autonomic dysregulation, which may be characterized by a reduction in both heart rate variability and electrodermal activity. Social withdrawal has been associated with oxytocin availability. There is also evidence that inflammatory processes may contribute to individual Suicide Crisis Syndrome symptoms.ConclusionThe Suicide Crisis Syndrome is a complex syndrome that is likely the consequence of distinct changes in interconnected neural, neuroendocrine, and autonomic systems. Available clinical and research data allow for development of empirically testable hypotheses and experimental paradigms to scrutinize the biological substrates of the Suicide Crisis Syndrome.

Published
2020
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31. Comparison of Stir Bar Sorptive Extraction and Solid Phase Microextraction of Volatile and Semi-Volatile Metabolite Profile of Staphylococcus Aureus

Author

Catherine Dunyach-Remy, Axelle Cadiere, Benoit Roig, Jean-Philippe Lavigne, Kevin Berrou, Détection, évaluation, gestion des risques CHROniques et éMErgents (CHROME) / Université de Nîmes (CHROME), Université de Nîmes (UNIMES), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and KARLI, Mélanie

Subjects
Staphylococcus aureus, Metabolite, stir bar sorptive extraction, Pharmaceutical Science, gas-chromatography–mass-spectrometry, bacterial metabolite analysis, medicine.disease_cause, Solid-phase microextraction, Hydrocarbons, Aromatic, 01 natural sciences, Article, Gas Chromatography-Mass Spectrometry, Analytical Chemistry, lcsh:QD241-441, 03 medical and health sciences, chemistry.chemical_compound, lcsh:Organic chemistry, Drug Discovery, medicine, Amines, Physical and Theoretical Chemistry, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Volatile Organic Compounds, 0303 health sciences, Chromatography, gas-chromatography-mass-spectrometry, 030306 microbiology, 010401 analytical chemistry, Organic Chemistry, Extraction (chemistry), Staphylococcal Infections, solid phase microextraction, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 0104 chemical sciences, chemistry, Chemistry (miscellaneous), Metabolome, Molecular Medicine, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Gas chromatography–mass spectrometry
Abstract

For the analysis of volatile bacterial compounds, solid phase microextraction (SPME) is currently the most widely used metabolite concentration technique. Recently, the potential of stir bar sorptive extraction (SBSE) for this use has been demonstrated. These two approaches were therefore used in combination with gas-chromatography coupled with mass-spectrometry (GC&ndash, MS) for the analysis of volatile and semi-volatile bacterial compounds produced by Staphylococcus aureus. In both cases, SPME and SBSE/headspace sorptive extraction (HSSE) enrichment was carried out in two coating phases. A whole analytical and statistical process was developed to differentiate the metabolites produced from the metabolites consumed. The results obtained with SBSE/HSSE and SPME were compared and showed the recovery of 90% of the compounds by SBSE/HSSE. In addition, we were able to detect the production of 12 volatile/semi-volatile compounds by S. aureus, six of which had never been reported before. The extraction by SBSE/HSSE showed higher concentration capacities and greater sensitivity than SPME concerning bacterial compounds, suggesting that this technique may therefore become the new preferred option for bacterial volatile and semi-volatile compound analysis.

Published
2020
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32. The Phosphatase PP1 Promotes Mitotic Slippage through Mad3 Dephosphorylation

Author

Simonetta Piatti, Antonella Ruggiero, Katsuhiko Shirahige, Yuki Katou, Martial Séveno, Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), University of Tokyo [Kashiwa Campus], Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), BioCampus (BCM), and KARLI, Mélanie

Subjects
0301 basic medicine, Saccharomyces cerevisiae Proteins, Mad2, BUB3, [SDV]Life Sciences [q-bio], Mitosis, Cell Cycle Proteins, Saccharomyces cerevisiae, Biology, General Biochemistry, Genetics and Molecular Biology, spindle assembly checkpoint, Chromosome segregation, 03 medical and health sciences, 0302 clinical medicine, mitotic slippage, Chromosome Segregation, protein phosphatase 1, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, mitotic checkpoint complex, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Anaphase, 0303 health sciences, Chemistry, Kinetochore, Nuclear Proteins, Mitotic checkpoint complex, Spindle apparatus, Cell biology, Spindle checkpoint, 030104 developmental biology, Mitotic exit, embryonic structures, M Phase Cell Cycle Checkpoints, Anaphase-promoting complex, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery
Abstract

Accurate chromosome segregation in mitosis requires the bipolar attachment of kinetochores to spindle microtubules. A conserved surveillance mechanism, the Spindle Assembly Checkpoint (SAC), responds to lack of kinetochore-microtubule connections and delays the onset of anaphase until all chromosomes are bipolarly attached. SAC signalling fires at kinetochores and involves the formation of a soluble Mitotic Checkpoint Complex (MCC) made by Mad2, Mad3/BubR1, Bub3 and Cdc20, which inhibits the ubiquitin ligase activity of the Anaphase Promoting Complex (APC). The mitotic delay imposed by SAC, however, is not everlasting. After a variable time during which kinetochores have failed to establish bipolar connections, cells escape from the SAC-induced mitotic arrest through a process called mitotic slippage. Mitotic slippage occurs in the presence of SAC signalling at kinetochores, but whether and how MCC stability and APC inhibition are actively controlled during slippage is not known. The PP1 phosphatase has emerged as a key factor in SAC silencing once all kinetochores are bipolarly attached. PP1 turns off SAC signalling through dephosphorylation of the SAC scaffold Knl1/Blinkin at kinetochores. Here we show that in budding yeast PP1 is also required for mitotic slippage. However, its involvement in this process is not linked to kinetochores but rather to MCC stability. We identify S268 of Mad3 as a critical target of PP1 in this process. Mad3 S268 dephosphorylation destabilises the MCC, but in spite of that, does not affect the initial SAC-induced mitotic arrest. Conversely, it accelerates mitotic slippage and overcomes the slippage defect of PP1 mutants. Thus, slippage is not the mere consequence of incomplete APC inactivation that brings about mitotic exit, as originally proposed, but involves the exertive antagonism between kinases and phosphatases.

Published
2020
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33. Discovery and quantification of lipoamino acids in bacteria

Author

Camille Petitfils, Jean-Marie Galano, Thierry Durand, Amandine Hueber, Pauline Le Faouder, Jean-François Martin, Jean-Claude Tabet, Justine Bertrand-Michel, Alexandre Guy, Geoffrey Langevin, Nicolas Cenac, MetaboHUB-MetaToul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), 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-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 Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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 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), Institut de Recherche en Santé Digestive (IRSD ), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), ToxAlim (ToxAlim), 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), Institut Parisien de Chimie Moléculaire (IPCM), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the French National Institutes of Health (Inserm) and Region Occitanie. NC is a recipient of the grant from ANR (ANR-18-CE14-0039-01) and NC & JBM are recipient of the grant from ANR (ANR-20-CE14-0011-01)., ANR-18-CE14-0039,LiBacPain,Les lipopeptides produits par le microbiote : de l'hypersensibilité à la thérapie dans le syndrome de l'intestin irritable(2018), ANR-20-CE14-0011,MILI,Signalisation des lipides du microbiote sur l'hôte(2020), KARLI, Mélanie, APPEL À PROJETS GÉNÉRIQUE 2018 - Les lipopeptides produits par le microbiote : de l'hypersensibilité à la thérapie dans le syndrome de l'intestin irritable - - LiBacPain2018 - ANR-18-CE14-0039 - AAPG2018 - VALID, Signalisation des lipides du microbiote sur l'hôte - - MILI2020 - ANR-20-CE14-0011 - AAPG2020 - VALID, MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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 des Sciences Appliquées - Toulouse (INSA Toulouse), 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, Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS-PSL), and Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS-PSL)

Subjects
Lipoaminoacids, Gram-positive bacteria, 010501 environmental sciences, medicine.disease_cause, 01 natural sciences, Biochemistry, Analytical Chemistry, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Escherichia coli, medicine, Humans, Environmental Chemistry, Trypsin, Sample preparation, Amino Acid Sequence, Asparagine, Spectroscopy, 030304 developmental biology, 0105 earth and related environmental sciences, chemistry.chemical_classification, Detection limit, 0303 health sciences, Chromatography, Mass spectrometry, biology, Microbiota, Lipidomic, Suspect screening, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Peptide Fragments, Amino acid, Triple quadrupole mass spectrometer, chemistry, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bacteria
Abstract

International audience; Improving knowledge about metabolites produced by the microbiota is a key point to understand its role in human health and disease. Among them, lipoamino acid (LpAA) containing asparagine and their derivatives are bacterial metabolites which could have an impact on the host. In this study, our aim was to extend the characterization of this family. We developed a semi-targeted workflow to identify and quantify new candidates. First, the sample preparation and analytical conditions using liquid chromatography (LC) coupled to high resolution mass spectrometry (HRMS) were optimized. Using a theoretical homemade database, HRMS raw data were manually queried. This strategy allowed us to find 25 new LpAA conjugated to Asn, Gln, Asp, Glu, His, Leu, Ileu, Pro, Lys, Phe, Trp and Val amino acids. These metabolites were then fully characterized by MS2, and compared to the pure synthesized standards to validate annotation. Finally, a quantitative method was developed by LC coupled to a triple quadrupole instrument, and linearity and limit of quantification were determined. 14 new LpAA were quantified in gram positive bacteria, Lactobacilus animalis, and 12 LpAA in Escherichia coli strain Nissle 1917.

Published
2022
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34. Heterogeneity of Cause, Care, and Prognosis in Severe Acute Kidney Injury in Hospitalized Patients: A Prospective Observational Study

Author

Ziyad Messikh, Laurent Muller, Jean-Yves Lefrant, Cedric Aglae, Olivier Moranne, S. Cariou, David-Paul De Brauwere, Pascal Reboul, Remi Trusson, Barbar Saber Davide, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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), Unité de réanimation médicale [CHU de Carémeau, Nîmes], Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), KARLI, Mélanie, and Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, Hospitalized patients, medicine.medical_treatment, 030232 urology & nephrology, 030204 cardiovascular system & hematology, lcsh:RC870-923, urologic and male genital diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, AKI, Internal medicine, medicine, Renal replacement therapy, care, Dialysis, Urine output, Creatinine, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Acute kidney injury, clinical epidemiology, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, Original Clinical Research, chemistry, Nephrology, dialysis, Observational study, prognosis, business, renal replacement therapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease
Abstract

KDIGO (Kidney Disease: Improving Global Outcomes) defines acute kidney injury (AKI) solely by serum creatinine (SCr) and urine output variation. Severe AKI is a syndrome covering various clinical situations.Objective:To describe severe AKI heterogeneity by department of hospitalization.Design:This is a prospective observational single-center study.Setting:Adult patients hospitalized in a French tertiary hospital from August 2016 to December 2017.Patients:All adults with severe AKI, defined by dialysis for AKI or an increase in SCr above 354 μmol/L.Measurements:Patient characteristics, clinical and laboratory presentation, AKI cause, medical indication for renal replacement therapy (RRT), planned palliative care, and vital status 30 days after severe AKI.Methods:A global description of patient characteristics, care, and prognosis and comparison by department of hospitalization: intensive care unit (ICU), nephrology, and others.Results:The study included 480 patients (73% men, median age: 72 years, range: 64-83), with medical histories including cardiovascular disease, diabetes, cancer, and chronic kidney disease. Principal causes were sepsis (104; 22%), hypovolemia (98; 20%), obstructive AKI (84; 18%), acute tubular necrosis (ATN; 74; 15%), and cardiorenal syndrome (51; 11%). Severe AKI was diagnosed in the ICU for 188 (39%) patients, the nephrology department for 130 (27%), and in other wards for 162 (34%). Patient characteristics differed by department for age, comorbidity, cause, and RRT use and indications. Palliative care was planned for 72 (15%) patients, most frequently in other wards.Limitations:We studied a subgroup of stage 3 KDIGO AKI patients in a single center without cardiac surgery.Conclusion:Patients hospitalized for severe AKI have frequent and various comorbidities, different clinical presentations, care, hospitalization in various departments, and different prognosis. The heterogeneity of this severe AKI implies the need for personalized care, which requires prognostic tools that include information besides SCr and diuresis., Le KDIGO définit l’insuffisance rénale aigüe (IRA) uniquement par une variation de la créatinine sérique (SCr) et de la diurèse. L’IRA grave est un syndrome couvrant diverses situations cliniques.Objectif:Décrire l’hétérogénéité de l’IRA grave selon l’unité d’hospitalisation.Type d’étude:Étude observationnelle prospective menée dans un seul centre.Sujets:Des adultes hospitalisés entre août 2016 et décembre 2017 dans un centre de soins tertiaires en France.Participants:Tous les adultes atteints d’IRA grave, définie par un traitement de dialyse ou un taux de SCr au-delà de 354 µmol/l.Mesures:Les caractéristiques du patient, le tableau clinique et de laboratoire, l’étiologie de l’IRA, l’indication médicale pour une thérapie de remplacement rénal (TRR), le plan de soins palliatifs et le statut vital 30 jours après l’épisode d’IRA grave.Méthodologie:Une description globale des caractéristiques des patients, des soins et du pronostic, ainsi qu’une comparaison selon l’unité d’hospitalisation: unité de soins intensifs (USI), néphrologie et autres.Résultats:L’étude portait sur 480 patients (73 % d’hommes) âgés de 64 à 83 ans (âge médian: 72 ans) avec des antécédents incluant maladies cardiovasculaires, diabète, cancer ou insuffisance rénale chronique. Les principales causes de l’IRA grave étaient une septicémie (104, 22 %), une hypovolémie (98, 20 %), une IRA obstructive (84, 18 %), une nécrose tubulaire aigüe (74, 15 %) ou un syndrome cardio-rénal (51, 11 %). Le diagnostic avait été posé à l’USI pour 188 patients (39 %), en néphrologie pour 130 patients (27 %) et dans d’autres unités pour 162 patients (34 %). Les caractéristiques des patients différaient entre les unités de soins en ce qui concerne l’âge, les comorbidités, l’étiologie et les indications de TRR. Un plan de soins palliatifs existait pour 72 patients (15 %), le plus souvent dans les autres unités.Limites:Nous avons étudié un sous-groupe de patients atteints d’IRA de stade 3 (classification KDIGO) dans un seul centre sans chirurgie cardiaque.Conclusion:Les patients hospitalisés pour une IRA grave présentent des comorbidités, des tableaux cliniques, des soins et des pronostics variés et sont admis dans différentes unités d’hospitalisation. Cette hétérogénéité de l’IRA grave met en relief le besoin de soins personnalisés qui nécessitent des outils pronostics basés sur des informations autres que la SCr et la diurèse.

Published
2019
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35. Association of circulating metabolites with healthy diet and risk of cardiovascular disease: analysis of two cohort studies

Author

Akbaraly, Tasnime, Wurtz, Peter, Singh-Manoux, Archana, Shipley, Martin J., Haapakoski, Rita, Lehto, Maili, Desrumaux, Catherine, Kähönen, Mika, Lehtimäki, Terho, Mikkilä, Vera, Hingorani, Aroon, Humphries, Steve E., Kangas, Antti J., Soininen, Pasi, Raitakari, Olli, Ala-Korpela, Mika, Kivimäki, Mika, Department of Epidemiology and Public Health, Imperial College London, Mécanismes moléculaires dans les démences neurodégénératives (MMDN), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), University of Oulu, University College of London [London] (UCL), 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), Tampere University Hospital, Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], University of Turku, University of Eastern Finland, University of Bristol [Bristol], Baker IDI Heart and Diabetes Institute 75 Commercial Rd, Melbourne, Victoria 3004, AustraliaBaker IDI Heart and Diabetes Institute 75 Commercial Rd, Melbourne, Victoria 3004, Australia, Baker Heart and Diabetes Institute (AUSTRALIA), Monash University [Melbourne], University of Helsinki, Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences, University of Tampere, KARLI, Mélanie, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Clinicum, and Department of Public Health

Subjects
Adult, Male, Magnetic Resonance Spectroscopy, lcsh:Medicine, Risk Assessment, Cohort Studies, Biological Factors, Humans, Metabolomics, CORONARY-HEART-DISEASE, NUCLEAR-MAGNETIC-RESONANCE, lcsh:Science, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, lcsh:R, Sisätaudit - Internal medicine, WOMEN, MEN, WHITEHALL II COHORT, Middle Aged, PARTICLE-SIZE, 3142 Public health care science, environmental and occupational health, Cardiovascular Diseases, 3121 General medicine, internal medicine and other clinical medicine, YOUNG FINNS, Metabolome, EATING INDEX, Female, lcsh:Q, FATTY-ACIDS, Diet, Healthy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Diet may modify metabolomic profiles towards higher or lower cardiovascular disease (CVD) risk. We aimed to identify metabolite profiles associated with high adherence to dietary recommendations - the Alternative Healthy Eating Index (AHEI) - and the extent to which metabolites associated with AHEI also predict incident CVD. Relations between AHEI score and 80 circulating lipids and metabolites, quantified by nuclear magnetic resonance metabolomics, were examined using linear regression models in the Whitehall II study (n = 4824, 55.9 ± 6.1 years, 28.0% women) and were replicated in the Cardiovascular Risk in Young Finns Study (n = 1716, 37.7 ± 5.0 years, 56.3% women). We used Cox models to study associations between metabolites and incident CVD over the 15.8-year follow-up in the Whitehall II study. After adjustment for confounders, higher AHEI score (indicating healthier diet) was associated with higher degree of unsaturation of fatty acids (FA) and higher ratios of polyunsaturated FA, omega-3 and docosahexaenoic acid relative to total FA in both Whitehall II and Young Finns studies. A concordance of associations of metabolites with higher AHEI score and lower CVD risk was observed in Whitehall II. Adherence to healthy diet seems to be associated with specific FA that reduce risk of CVD.

Published
2018
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36. A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study

Author

Guérin, C., Beuret, P., Constantin, J. M., Bellani, G., Garcia-Olivares, P., Roca, O., Meertens, J. H., Maia, P. Azevedo, Becher, T., Peterson, J., Larsson, A., Gurjar, M., Hajjej, Z., Kovari, F., Assiri, A. H., Mainas, E., Hasan, M. S., Morocho-Tutillo, D. R., Baboi, L., Chrétien, J. M., François, G., Ayzac, L., Chen, L., Brochard, L., Mercat, A., Hajjej, Zied, Sellami, Walid, Ferjani, M., Gurjar, Mohan, Assiri, Amer, Al Bshabshe, Ali, Almekhlafi, Ghaleb, Mandourah, Yasser, Hasan, Mohd Shahnaz, Rai, Vineya, Marzida, M., Corcoles Gonzalez, Virgilio, Sanchez Iniesta, Rafael, Garcia, Pablo, Garcia-Montesinos de la Peña, Manuel, Garcia Herrera, Adriana, Roca, Oriol, Garcia-de-Acilu, Marina, Masclans Enviz, Joan Ramon, Mancebo, Jordi, Heili, Sarah, Artigas Raventos, Antonio, Blanch Torra, Lluís, Roche-Campo, Ferran, Rialp, Gemma, Forteza, Catalina, Berrazueta, Ana, Martinez, Esther, Penuelas, Oscar, Jara-Rubio, Ruben, Mallat, Jihad, Thevenin, D., Zogheib, Elie, Mercat, Alain, Levrat, Albrice, Porot, Veronique, Bedock, B., Grech, Ludovic, Plantefeve, Gaetan, Badie, Julio, Besch, Guillaume, Pili-Floury, Sébastien, Guisset, Olivier, Robine, Adrien, Prat, Gwenael, Doise, Jean-Marc, Badet, Michel, Thouret, J. M., Just, Bernard, Perbet, Sébastien, Lautrette, Alexandre, Souweine, B., Chabanne, Russell, Danguy des Déserts, Marc, Rigaud, Jean-Philippe, Marchalot, Antoine, Rigaud, J. P., Bele, Nicolas, Beague, Sébastien, Hours, Sandrine, Marque, Sophie, Durand, Michel, Payen, J. F., Stoclin, Annabelle, Gaffinel, Alain, Winer, Arnaud, Chudeau, Nicolas, Tirot, Patrice, Thyrault, Martial, Paulet, Rémi, Thyrault, M., Aubrun, Frederic, Guerin, Claude, Floccard, Bernard, Rimmele, T., Argaud, Laurent, Hernu, Romain, Crozon Clauzel, Jullien, Wey, Pierre-François, Bourdin, Gael, Pommier, C., Cueuille, NadÃge, de Varax, null, Marchi, Elisa, Papazian, L., Jochmans, Sebastien, Monchi, M., Jaber, Samir, de Jong, Audrey, Moulaire, Valerie, Capron, Matthieu, Jarrige, L., Barberet, Guillaume, Lakhal, Karim, Rozec, B., Dellamonica, Jean, Robert, Alexandre, Bernardin, G., Danin, Pierre-Eric, Raucoules, M., Runge, Isabelle, Foucrier, Arnaud, Hamada, Sophie, Tesniere, Antoine, Fromentin, Mélanie, Samama, C. M., Mira, Jean-Paul, Diehl, Jean-Luc, Mekontso Dessap, Armand, Arbelot, Charlotte, Demoule, Alexandre, Roche, Anne, Similowski, T., Ricard, Jean-Damien, Gaudry, Stéphane, Dreyfuss, D., de Montmolin, Etienne, da Silva, Daniel, Verdiere, B., Ardisson, Fanny, Lemiale, Virginie, Azoulay, Elie, Bruel, Cédric, Tiercelet, Kelly, Fartoukh, Muriel, Voiriot, Guillaume, Hoffmann, Clement, Leclerc, T., Thille, Arnaud, Robert, Réné, Beuret, Pascal, Beduneau, Gaëtan, Beuzelin, Marion, Tamion, F., Morel, Jérôme, Tremblay, Aymeric, Molliex, S., Amal, Jean-Michel, Meaudre, Eric, Goutorbe, Philippe, Laffon, Marc, Gros, Antoine, Nica, Alexandru, Barjon, Genevieve, Dahyot-Fizelier, Claire, Imzi, Nadia, Gally, Josette, Real, null, Sauneuf, Bertrand, Souloy, Xavier, Girbes, Armand, Tuinman, Pieter Roel, Schultz, Marcus, Winters, Tineke, Mijzen, Lisa, Roekaerts, P. M. H. J., Vermeijden, Wytze, Beishuizen, Albertus, Trof, R., Corsten, Stijn, Kesecioglu, Jozef, Meertens, John, Dieperink, Wim, Pickers, Peter, Roovers, Noortje, Maia, Paulo, Duque, Melanie, Rua, Fernando, Pereira de Figueired, António Manuel, Ramos, Armindo, Fragoso, Elsa, Azevedo, Pilar, Gouveia, Joao, Costa E. Silva, Zélia, Silva, Goncalo, Chaves, Susana, Nobrega, J. J., Lopes, Luís, Valerio, Bernardino, Araujo, Ana Carolina, de Freitas, Paulo Telles, Bouw, Maria Jose, Melao, Maria, Granja, C., Marcal, Paulo, Fernandes, Antero, Joao, Gonçalves Pereira, Maia, Dionísio Faria, Spadaro, Savino, Volta, Carlo Alberto, Bellani, Giacomo, Citerio, G., Mauri, Tommaso, Alban, Laura, Pesenti, A., Mistraletti, Giovanni, Formenti, Paolo, Tommasino, C., Tardini, Francesca, Fumagalli, R., Colombo, Riccardo, Fossali, Tommaso, Catena, E., Todeschini, Manuel, Gnesin, Paolo, Cracchiolo, Andrea Neville, Palma, Daniela, Tetamo, R., Albiero, Daniela, Costantini, Elena, Raimondi, F., Coppadoro, Andrea, Vascotto, Ettore, Lusenti, F., Becher, Tobias, Schädler, Dirk, Weiler, N., Karagiannidis, Christian, Petersson, Johan, Konrad, D., Kawati, Rafael, Wessbergh, Joanna, Valtysson, J., Rockstroh, Matthias, Borgstrom, Sten, Larsson, Niklas, Thunberg, J., Camsooksai, Julie, Briggs, null, Kovari, Ferenc, Cuesta, J., Anwar, Sibs, O’Brien, B., Barberis, Luigi, Sturman, J., Mainas, Efstratios, Karatzas, S., Piza, Petr, Sottiaux, Thierry, Adam, J. F., Gawda, Ryszard, Gawor, Maen, Alqdah, M., Cohen, D., Brochard, Laurent, Baker, A., Ñamendys-Silva, Silvio Antonio, Garcia-Guillen, Francisco Javier, Morocho Tutillo, Diego Rolando, Jibaja Vega, Manuel, Zakalik, Graciela, Pagella, Gonzalo, Marengo, J., KARLI, Mélanie, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Université de Lyon, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Hospital General Universitario 'Gregorio Marañón' [Madrid], Vall d'Hebron University Hospital [Barcelona], CIBER de Epidemiología y Salud Pública (CIBERESP), University Medical Center Groningen [Groningen] (UMCG), Centro Hospitalar do Porto, Karolinska University Hospital [Stockholm], Karolinska Institutet [Stockholm], Uppsala University, University of Malaya [Kuala Lumpur, Malaisie], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], Université d'Angers - Faculté de médecine (UA UFR Médecine), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Other departments, Intensive Care Medicine, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Critical Care, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Université d'Angers (UA), Guã©rin, C, Beuret, P, Constantin, J, Bellani, G, Garcia-Olivares, P, Roca, O, Meertens, J, Maia, P, Becher, T, Peterson, J, Larsson, A, Gurjar, M, Hajjej, Z, Kovari, F, Assiri, A, Mainas, E, Hasan, M, Morocho-Tutillo, D, Baboi, L, Chrã©tien, J, Franã§ois, G, Ayzac, L, Chen, L, Brochard, L, Mercat, A, Sellami, W, Ferjani, M, Al Bshabshe, A, Almekhlafi, G, Mandourah, Y, Rai, V, Marzida, M, Corcoles Gonzalez, V, Sanchez Iniesta, R, Garcia, P, Garcia-Montesinos de la Peña, M, Garcia Herrera, A, Garcia-de-Acilu, M, Masclans Enviz, J, Mancebo, J, Heili, S, Artigas Raventos, A, Blanch Torra, L, Roche-Campo, F, Rialp, G, Forteza, C, Berrazueta, A, Martinez, E, Penuelas, O, Jara-Rubio, R, Mallat, J, Thevenin, D, Zogheib, E, Levrat, A, Porot, V, Bedock, B, Grech, L, Plantefeve, G, Badie, J, Besch, G, Pili-Floury, S, Guisset, O, Robine, A, Prat, G, Doise, J, Badet, M, Thouret, J, Just, B, Perbet, S, Lautrette, A, Souweine, B, Chabanne, R, Danguy des Déserts, M, Rigaud, J, Marchalot, A, Bele, N, Beague, S, Hours, S, Marque, S, Durand, M, Payen, J, Stoclin, A, Gaffinel, A, Winer, A, Chudeau, N, Tirot, P, Thyrault, M, Paulet, R, Aubrun, F, Guerin, C, Floccard, B, Rimmele, T, Argaud, L, Hernu, R, Crozon Clauzel, J, Wey, P, Bourdin, G, Pommier, C, Cueuille, N, de Varax, N, Marchi, E, Papazian, L, Jochmans, S, Monchi, M, Jaber, S, de Jong, A, Moulaire, V, Capron, M, Jarrige, L, Barberet, G, Lakhal, K, Rozec, B, Dellamonica, J, Robert, A, Bernardin, G, Danin, P, Raucoules, M, Runge, I, Foucrier, A, Hamada, S, Tesniere, A, Fromentin, M, Samama, C, Mira, J, Diehl, J, Mekontso Dessap, A, Arbelot, C, Demoule, A, Roche, A, Similowski, T, Ricard, J, Gaudry, S, Dreyfuss, D, de Montmolin, E, da Silva, D, Verdiere, B, Ardisson, F, Lemiale, V, Azoulay, E, Bruel, C, Tiercelet, K, Fartoukh, M, Voiriot, G, Hoffmann, C, Leclerc, T, Thille, A, Robert, R, Beduneau, G, Beuzelin, M, Tamion, F, Morel, J, Tremblay, A, Molliex, S, Amal, J, Meaudre, E, Goutorbe, P, Laffon, M, Gros, A, Nica, A, Barjon, G, Dahyot-Fizelier, C, Imzi, N, Gally, J, Real, N, Sauneuf, B, Souloy, X, Girbes, A, Tuinman, P, Schultz, M, Winters, T, Mijzen, L, Roekaerts, P, Vermeijden, W, Beishuizen, A, Trof, R, Corsten, S, Kesecioglu, J, Dieperink, W, Pickers, P, Roovers, N, Duque, M, Rua, F, Pereira de Figueired, A, Ramos, A, Fragoso, E, Azevedo, P, Gouveia, J, Costa E. Silva, Z, Silva, G, Chaves, S, Nobrega, J, Lopes, L, Valerio, B, Araujo, A, de Freitas, P, Bouw, M, Melao, M, Granja, C, Marcal, P, Fernandes, A, Joao, G, Maia, D, Spadaro, S, Volta, C, Citerio, G, Mauri, T, Alban, L, Pesenti, A, Mistraletti, G, Formenti, P, Tommasino, C, Tardini, F, Fumagalli, R, Colombo, R, Fossali, T, Catena, E, Todeschini, M, Gnesin, P, Cracchiolo, A, Palma, D, Tetamo, R, Albiero, D, Costantini, E, Raimondi, F, Coppadoro, A, Vascotto, E, Lusenti, F, Schã¤dler, D, Weiler, N, Karagiannidis, C, Petersson, J, Konrad, D, Kawati, R, Wessbergh, J, Valtysson, J, Rockstroh, M, Borgstrom, S, Larsson, N, Thunberg, J, Camsooksai, J, Briggs, N, Cuesta, J, Anwar, S, O’Brien, B, Barberis, L, Sturman, J, Karatzas, S, Piza, P, Sottiaux, T, Adam, J, Gawda, R, Gawor, M, Alqdah, M, Cohen, D, Baker, A, Ñamendys-Silva, S, Garcia-Guillen, F, Morocho Tutillo, D, Jibaja Vega, M, Zakalik, G, Pagella, G, and Marengo, J

Subjects
ARDS, RECEIVING MECHANICAL VENTILATION, Epidemiology, medicine.medical_treatment, cross-sectional studies, RESPIRATORY-DISTRESS-SYNDROME, vrouwelijk, buikligging, Critical Care and Intensive Care Medicine, respiratory distress syndrome, adult/therapy, law.invention, Positive-Pressure Respiration, Prone position, 0302 clinical medicine, Mechanical ventilation, prospectieve studies, Randomized controlled trial, law, middle aged, Medicine, FAILURE, adult/therapy, humans, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, RANDOMIZED CONTROLLED-TRIAL, respiratory distress syndrome, 3. Good health, cross-sectionele studies, ademnoodsyndroom, aged, female, SURVIVAL, middelbare leeftijd, medicine.medical_specialty, Pain medicine, positieve druk uitademing, NO, 03 medical and health sciences, male, mensen, Anesthesiology, ouderen, METAANALYSIS, business.industry, MORTALITY, 030208 emergency & critical care medicine, mannelijk, CARE, medicine.disease, prospective studies, EVOLUTION, body regions, 030228 respiratory system, Emergency medicine, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Introduction: While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low.Aim: This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints).Methods: The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles).Results: Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO2/FIO2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH(2)O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH(2)O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one).Conclusions: In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.

Published
2018
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37. Stricturing Crohn’s disease-like colitis in a patient treated with belatacept

Author

Guillaume Jeantet, Guillaume Pineton de Chambrun, Benjamin Rivière, Natalie Funakoshi, Jeanne Ramos, Moglie Le Quintrec, Sylvie Delmas, Jean Emmanuel Serre, Gaspard Dufour, Jean-Christophe Valats, Michael Bismuth, Roman Combes, Pierre Blanc, Anne Bozon, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), KARLI, Mélanie, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Crohn’s disease, Graft Rejection, Male, Case Report, Constriction, Pathologic, 030230 surgery, Gastroenterology, Inflammatory bowel disease, 0302 clinical medicine, Intestinal mucosa, CTLA-4 Antigen, Intestinal Mucosa, Kidney transplantation, Crohn's disease, Crohn\textquoterights disease, hemic and immune systems, Belatacept, General Medicine, Colonoscopy, Middle Aged, Colitis, 3. Good health, 030211 gastroenterology & hepatology, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Immunosuppressive Agents, medicine.drug, medicine.medical_specialty, medicine.drug_class, Colon, chemical and pharmacologic phenomena, Monoclonal antibody, HHV-6, Abatacept, 03 medical and health sciences, Internal medicine, medicine, Humans, Glucocorticoids, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Kidney Transplantation, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Withholding Treatment, Kidney Failure, Chronic, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) modifying agents have been involved in the development of intestinal inflammation, especially therapeutic monoclonal antibodies directed against CTLA-4. Here we report the appearance of a severe stricturing Crohn's disease-like colitis in a patient with a kidney allograft who was treated with belatacept, a recombinant CTLA-4-Ig fusion protein.

Published
2017
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38. Reply to Caccialanza et al

Author

P. Boisselier, Jean Bourhis, Pierre Senesse, Marie Vinches, S. Thezenas, N. Flori, Institut du Cancer de Montpellier (ICM), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), 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), and KARLI, Mélanie

Subjects
[SDV] Life Sciences [q-bio], Oncology, medicine.medical_specialty, Nutrition and Dietetics, Text mining, business.industry, [SDV]Life Sciences [q-bio], Internal medicine, medicine, MEDLINE, Medicine (miscellaneous), business, Chemoradiotherapy
Abstract

International audience; A double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX. Boisselier P, Kaminsky MC, Thézenas S, Gallocher O, Lavau-Denes S, Garcia-Ramirez M, Alfonsi M, Cupissol D, de Forges H, Janiszewski C, Geoffrois L, Sire C, Senesse P; Head and Neck Oncology and Radiotherapy Group (GORTEC). Am J Clin Nutr. 2020 Dec 10;112(6):1523-1531. doi: 10.1093/ajcn/nqaa227. PMID: 32936874 Clinical Trial. Immunonutrition in head and neck cancer patients undergoing chemoradiotherapy: an alternative approach for overcoming potential bias. Caccialanza R, Cereda E, Orlandi E, Filippi AR, Comoli P, Alberti A, Imarisio I, Pedrazzoli P, Bossi P. Am J Clin Nutr. 2021 Apr 6;113(4):1053-1054. doi: 10.1093/ajcn/nqaa421. PMID: 33822867 No abstract available.

Published
2021
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39. Renal graft intolerance syndrome in late graft failure patients: efficacy and safety of embolization as first-line treatment compared to surgical removal

Author

François Iborra, Saad Ed Dine Fadli, Nicolas Molinari, Georges Mourad, Ghalib Al Badaai, Thibaut Murez, Valérie Monnin, Vincent Pernin, Rodolphe Thuret, Valérie Garrigue, KARLI, Mélanie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Adult, Graft Rejection, Male, medicine.medical_specialty, Graft failure, Percutaneous, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, graft failure, medicine.medical_treatment, graft nephrectomy, 030232 urology & nephrology, Renal graft, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030230 surgery, Nephrectomy, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Surgical removal, medicine, Humans, Renal Insufficiency, Embolization, Aged, Retrospective Studies, Transplantation, business.industry, Retrospective cohort study, Middle Aged, renal transplantation, medicine.disease, Embolization, Therapeutic, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Surgery, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, graft embolization
Abstract

International audience; Although renal graft percutaneous embolization was introduced to avoid the risk associated with graft nephrectomy, there is no universal consensus about its indications and results. In order to evaluate the efficacy of graft embolization in the treatment of graft intolerance syndrome as well as its safety compared to surgical removal with respect to complications and other morbidity measures, We performed a retrospective observational study comparing two groups of patients treated for graft intolerance syndrome: Group 1: patients who had embolization as first-line treatment and Group 2: patients directly treated by surgical removal. 72 patients were included, (32 in Group 1 and 40 in Group 2); the postintervention follow-up continued for 12 months. Patients in Group 1 are older than those in Group 2. Otherwise, the two groups are similar concerning sex, manifestations of graft intolerance syndrome, diabetes and nutritional and functional status. The overall success rate of embolization in complete resolution of graft intolerance syndrome and ultimately avoidance of surgical removal was 84.37%. The surgical removal group had more serious complications, a longer hospital stay and needed more blood transfusions. We conclude that embolization of symptomatic renal grafts has considerable efficacy with less morbidity, and no serious complications compared to the standard surgical graft removal.

Published
2017
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40. Back-to-back comparison of penKID with NephroCheck® to predict acute kidney injury at admission in intensive care unit: a brief report

Author

Cyril Touchard, Etienne Gayat, Matthieu Legrand, Antoine Vieillard-Baron, Alexa Hollinger, Alexandre Mebazaa, Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Université Paris Diderot - Paris 7 (UPD7), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation medico-chirurgicale [CHU Raymond-Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], and KARLI, Mélanie

Subjects
medicine.medical_specialty, Letter, Point-of-Care Systems, Population, Renal function, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Interquartile range, law, Internal medicine, medicine, Humans, Protein Precursors, education, education.field_of_study, Creatinine, Tissue Inhibitor of Metalloproteinase-2, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Acute kidney injury, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, Enkephalins, lcsh:RC86-88.9, Acute Kidney Injury, medicine.disease, Intensive care unit, 3. Good health, Insulin-Like Growth Factor Binding Proteins, Intensive Care Units, chemistry, SAPS II, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease
Abstract

International audience; on behalf of the FROG ICU study investigators Acute kidney injury (AKI) is a frequent condition in critically ill patients that affects both short-and long-term outcome [1]. Its early detection remains a challenge, and diagnosis frequently occurs too late with cell damage already present. Implementation of novel biomarkers that reliably identify patients at risk or at an early stage of AKI could offer more efficient management strategies leading to better outcomes. In our investigation, we compared two promising AKI biomarkers: a marker of tubular injury commercialized as a lateral-flow test (NephroCheck®) [2], the product of urinary TIMP-2 (Tissue inhibitor of metalloprotease), and IGFBP 7 (Insulin-like growth factor binding protein; overall TIMP2xIGFBP7), and the filtration marker proenkephalin A 119-159 (penKid). penKid has been recently described as a valuable plasma biomarker of AKI in the acutely ill, including septic patients [3] and patients suffering from acute heart failure [4]. Proenkephalin represents a stable surrogate analyte of labile enkephalins, which are known as endogenous opioids, but also affects kidney function [5]. The aim of our study was to conduct a parallel assessment of the two biomarkers in an intensive care unit (ICU) population from the data of the FROG-ICU study. FROG-ICU has been designed to better understand long-term outcome after ICU discharge as well as risk factors for all-cause and cardiovascular morbidity and associated mortality (FROG-ICU study, ClinicalTrials.gov identifier NCT01367093). It was a large prospective multicenter cohort study with biological (plasma and urine) collection and one-year follow-up of ICU patients. FROG-ICU aims to allow risk stratification of ICU survivors in order to recognize the subset of patients who may benefit from early intervention to allow decreased cardiovascular morbidity and related mortality. The methodology of the FROG-ICU study was published in 2015. From the FROG study including 2087 critically ill patients we randomly selected 200 requiring mechanical ventilation or vasopressor support for more than 24 h with respect to the four categories of the renal Sequential Organ Failure Assessment (SOFA) score (i.e., creatinine level on admission of < 1.2 mg/dL (n = 80), 1.2 to 1.9 mg/dL (n = 40), 2 to 3.4 mg/dL (n = 40), and ≥ 3.5 mg/dL (n = 40)); 78% were male, with a median age of 65 years (interquartile range (IQR) 54–75). In the investigated cohort of a standard population of critically ill, the main cause of ICU admission was septic shock (26%), the median age was 65 years (IQR 54–75), the median SAPS II score was 51 (IQR 41–68), and the ICU mortality was 26%. Other causes of admission include out-of-hospital cardiac arrest (10%), acute respiratory failure (16%), acute neurological disorder (11%), and cardiogenic shock (8%). On ICU admission, the median (and IQR) value of estimated glomerular filtration rate for penKid and TIMP2xIGFBP7 was 47 mL/min (22–88), 85 pmol/L (48–40), and 0.6 UNIT (0.3–2), respectively. AKI was defined using the Kidney Disease Improvement Global Outcome (KDIGO) definition. Accordingly, we used both the variation in serum creatinine during the first 48 h after ICU admission and the maximal value during the 7 days following ICU admission. Admission serum creatinine was used as baseline serum creatinine when the estimated glomerular filtration rate (eGFR) was above 60 ml/min/1.73 m 2 at admission. Otherwise (n = 117, 59% of the study population), baseline serum

Published
2018
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41. GREEN APPROACHES FOR THE SYNTHESIS OF NUCLEOTIDES, THEIR CONJUGATES AND ANALOGUES

Author

Suzanne Peyrottes, Lucie Appy, Frédéric Lamaty, Anaïs Depaix, Béatrice Roy, Xavier Bantreil, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Peyrottes, Suzanne, and KARLI, Mélanie

Subjects
water chemistry, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, Biochemistry, Inorganic Chemistry, Mechanochemistry, [CHIM] Chemical Sciences, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [CHIM]Chemical Sciences, Nucleotide, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, 010405 organic chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Combinatorial chemistry, nucleotides, 0104 chemical sciences, chemistry, Organophosphorus chemistry, Water chemistry, mechanochemistry, Nucleoside, dinucleotides, Conjugate
Abstract

International audience; We have developed original one-pot and protecting group-free approaches, which are also userfriendly and reliable, to synthesize nucleotides and derivatives starting from nucleoside 5'-monophosphates. Both methods present convenient setup , i.e., non-dry solvents and reagents, substrates in their sodium or acid form, and commercially available and cheap phosphorus reagents as sodium and potassium salts.

Published
2019
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42. New Series of Acyclic Nucleoside Phosphonates as Potent Antimalarials

Author

Peyrottes, Suzanne, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and KARLI, Mélanie

Subjects
[CHIM] Chemical Sciences, [CHIM]Chemical Sciences, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

43. Drug discovery and optimization targeting CD73 to restore anticancer immune response

Author

Braka A., Rahila Rahimova, Suzanne Peyrottes, Lars Petter Jordheim, Caux, C., Laurent Chaloin, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), The Purine and Pyrimidine Society, and KARLI, Mélanie

Subjects
[CHIM] Chemical Sciences, [CHIM]Chemical Sciences, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

44. A ball-milling strategy for the synthesis of dinucleotides

Author

Appy, Lucie, Depaix, Anaïs, Bantreil, Xavier, Lamaty, Frédéric, Peyrottes, Suzanne, Roy, Béatrice, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and KARLI, Mélanie

Subjects
[CHIM.ORGA]Chemical Sciences/Organic chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

45. Performance of a new in-house medium Carba MTL-broth for the rapid detection of carbapenemase-producing Enterobacteriaceae

Author

Jean-Philippe Lavigne, Alix Pantel, Albert Sotto, Christophe de Champs, Catherine Dunyach-Remy, Abdelaziz Touati, Assia Mairi, Université Abderrahmane Mira [Béjaïa], Départment de microbiologie, FSNV Université A MIRA, Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire de Reims (CHU Reims), and KARLI, Mélanie

Subjects
0301 basic medicine, Microbiological Techniques, Carbapenemase-Producing Enterobacteriaceae, Time Factors, 030106 microbiology, Microbiology, Rapid detection, Sensitivity and Specificity, beta-Lactamases, Comparative evaluation, Developing countries, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Bacterial Proteins, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Mass Screening, 030212 general & internal medicine, Food science, Carbapenemase-producing Enterobacteriaceae, 2. Zero hunger, biology, Enterobacteriaceae Infections, General Medicine, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Enterobacteriaceae, 3. Good health, Culture Media, Infectious Diseases, Carbapenem-Resistant Enterobacteriaceae, chemistry, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Parasitology, Carba MTL-broth, Screening medium, Ertapenem, OXA-48-like
Abstract

Introduction: The spread of carbapenemase-producing Enterobacteriaceae (CPE) represents a major public health issue. Methods allowing rapid detection of carbapenemases in developing countries are therefore urgently needed. In the current study, we developed a new in-house medium for the rapid detection of CPE isolates, especially OXA-48 producers. Methodology: A panel of 144 clinical strains previously characterized was tested on in-house Carba MTL-broth medium using four different concentrations of ertapenem (0.5 to 2 mg/L), and compared to chromID® OXA-48 and chromID® CARBA (BioMérieux) media. Results: Comparative evaluation of the Carba MTL-broth with chromID® OXA-48 and chromID® CARBA showed that chromID® OXA-48 and Carba MTL-broth had the highest sensitivity for detection of OXA-48 producers (93.9% and 100%, respectively) comparatively to chromID® CARBA (21.2%). The chromID® OXA-48 had the highest specificity (100%), as compared to the Carba MTL-broth (65.5%) and chromID® CARBA (84.4%) for the detection of OXA-48 producers. Conclusions: The in-house Carba MTL-broth developed in this study is sensitive, inexpensive, an easy-to-use phenotypic method for the detection of OXA-48-producing enterobacteria. Given the burden of pan-drug resistance, its implementation in the microbiology laboratory of developing countries could be a useful tool for rapid detection of these bacteria.

Published
2019
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46. Determining the dose to be injected in the first clinical trials with monoclonal antibodies: Not so easy!

Author

Viala, Marie, Tosi, Diego, KARLI, Mélanie, Institut du Cancer de Montpellier (ICM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), and CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Monoclonal antibodies are a therapeutic tool frequently used in oncology, as they allow the specific targeting of molecules expressed by cancer cells and, in most cases, induce minimal toxic effects on healthy tissues. Because monoclonal antibodies frequently lack significant toxicity and are not associated to a direct relationship between dose and effect, the methods of clinical development traditionally used for chemotherapy agents are scarcely useful for this class of drugs. In addition, no consensus exists on the definition of parameters different from toxicity that could assist the process of dose selection of monoclonal antibody in early clinical trials., Les anticorps monoclonaux constituent une arme thérapeutique de plus en plus utilisée en oncologie car ils permettent de cibler très précisément les cellules cancéreuses tout en présentant l’avantage d’épargner les cellules saines des effets du traitement, avec, par conséquent, une réduction très importante de la toxicité. L’absence de toxicité significative et d’une relation directe entre dose et efficacité pour les anticorps rendent toutefois peu utiles les méthodes de sélection de la dose traditionnellement utilisées pour les médicaments de chimiothérapie. Il n’existe toutefois pas de consensus sur des paramètres alternatifs qui permettraient de sélectionner pendant les essais de phase précoce la meilleure dose de ces molécules pour le développement clinique ultérieur.

Published
2019
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47. French ccAFU guidelines – Update 2018–2020: Bladder cancer

Author

Géraldine Pignot, Serge Brunelle, Pierre Colin, Arnaud Mejean, Yann Neuzillet, Mathieu Roumiguié, Morgan Rouprêt, Evanguelos Xylinas, Nadine Houede, Alexandra Masson-Lecomte, Eva Compérat, Stéphane Larré, François Audenet, KARLI, Mélanie, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Association Française d'Urologie, Hôpital Foch [Suresnes], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Tenon [AP-HP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Urologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Privé La Louvière, AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
Bladder neoplams, medicine.medical_specialty, Survival, Urology, Bladder, 030232 urology & nephrology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cystectomy, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cytology, medicine, BCG, Urothelial carcinoma, Cancer, Gynecology, Bladder cancer, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Objective:To propose updated French guidelines for non-muscle invasive (NMIBC) and muscle-invasive (MIBC) bladder cancers.Methods:A Medline search was achieved between 2015 and 2018, as regards diagnosis, options of treatment and follow-up of bladder cancer, to evaluate different references with levels of evidence.Results:Diagnosis of NMIBC (Ta, T1, CIS) is based on a complete deep resection of the tumor. The use of fluorescence and a second-look indication are essential to improve initial diagnosis. Risks of both recurrence and progression can be estimated using the EORTC score. A stratification of patients into low, intermediate and high risk groups is pivotal for recommending adjuvant treatment: instillation of chemotherapy (immediate post-operative, standard schedule) or intravesical BCG (standard schedule and maintenance). Cystectomy is recommended in BCG-refractory patients. Extension evaluation of MIBC is based on contrast-enhanced pelvic-abdominal and thoracic CT-scan. Multiparametric MRI can be an alternative. Cystectomy associated with extended lymph nodes dissection is considered the gold standard for non-metastatic MIBC. It should be preceded by cisplatin-based neoadjuvant chemotherapy in eligible patients. An orthotopic bladder substitution should be proposed to both male and female patients with no contraindication and in cases of negative frozen urethral samples; otherwise transileal ureterostomy is recommended as urinary diversion. All patients should be included in an Early Recovery After Surgery (ERAS) protocol. For metastatic MIBC, first-line chemotherapy using platin is recommended (GC or MVAC), when performans status (PS < 1) and renal function (creatinine clearance > 60 mL/min) allow it (only in 50 % of cases). In second line treatment, immunotherapy with pembrolizumab demonstrated a significant improvement in overall survival.Conclusion:These updated French guidelines will contribute to increase the level of urological care for the diagnosis and treatment for NMIBC and MIBC., ObjectifProposer une mise à jour des recommandations dans la prise en charge des tumeurs de la vessie n’infiltrant pas le muscle vésical (TVNIM) et infiltrant le muscle vésical (TVIM).MéthodesUne revue systématique (Medline) de la littérature de 2015 à 2018 a été conduite par le ccAFU concernant les éléments du diagnostic, les options de traitement et la surveillance des TVNIM et TVIM, en évaluant les références avec leur niveau de preuve.RésultatsLe diagnostic de TVNIM (Ta, T1, CIS) se fait après une résection tumorale complète et profonde. L’utilisation de la fluorescence vésicale et l’indication d’un second look (4 à 6 semaines) contribuent à améliorer le diagnostic initial. Le risque de récidive et/ou progression tumorale est évalué en utilisant le score EORTC. La stratification des patients en faible, intermédiaire et haut risque permet de proposer le traitement adjuvant : instillations endovésicales de chimiothérapie (postopératoire immédiate, schéma d’attaque) ou de BCG (schéma d’attaque et d’entretien), voire l’indication d’une cystectomie pour les patients résistant au BCG. Le bilan d’extension d’une TVIM repose sur l’uro-scanner couplé au scanner thoracique. L’IRM pelvienne multiparamétrique peut être une alternative. La cystectomie associée à un curage ganglionnaire étendu est le traitement de référence des TVIM non métastatiques. Elle doit être précédée d’une chimiothérapie néoadjuvante à base de sels de platine chez les patients en bon état général avec une fonction rénale satisfaisante. Une entérocystoplastie est proposée chez l’homme et la femme en l’absence de contre-indications et lorsque la recoupe urétrale est négative à l’examen extemporané ; sinon l’urétérostomie cutanée transiléale est le mode de dérivation urinaire recommandé. L’inclusion de tous les patients dans un protocole de RAAC (récupération améliorée après chirurgie) est recommandée. Pour les TVIM métastatiques, une première ligne de chimiothérapie à base de sels de platine (GC ou MVAC) est recommandée, si l’état général (PS > 1) et la fonction rénale (clairance >60 mL/min) l’autorisent (50 % seulement des cas). En deuxième ligne de traitement, l’immunothérapie par pembrolizumab a démontré un bénéfice en survie globale.ConclusionCette actualisation des recommandations françaises doit contribuer à améliorer non seulement la prise en charge des patients, mais aussi le diagnostic et la décision thérapeutique des TVNIM et TVIM.

Published
2019
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48. Decision of Adjuvant Systemic Treatment in HR+ HER2- Early Invasive Breast Cancer: Which Biomarkers Could Help?

Author

Alexandre, Marie, Maran-Gonzalez, Aurélie, Viala, Marie, Firmin, Nelly, D’Hondt, Véronique, Gutowski, Marian, Bourgier, Céline, Jacot, William, Guiu, Séverine, Institut du Cancer de Montpellier (ICM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Département d'oncologie Médicale, CRLCC Val d'Aurelle - Paul Lamarque, 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), and KARLI, Mélanie

Subjects
adjuvant chemotherapy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, biomarkers, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; The decision to administer adjuvant chemotherapy in treatment of early invasive breast cancer (EBC) is often complex, particularly for hormone receptor-positive (HR+) diseases, and current guidelines often classify these patients in an intermediate-risk group. Several biomarkers are currently available in this indication, in order to obtain additional and more accurate prognostic information compared to classic clinicopathological characteristics and guide the indication of adjuvant chemotherapy, optimizing the efficacy/toxicity ratio. We conducted a systematic review to evaluate the clinical validity and clinical utility of five biomarkers (uPA/PAI-1, OncotypeDX®, MammaPrint®, PAM50, and EndoPredict®) in HR+/HER2- EBC, whatever the nodal status. A total of 89 studies met the inclusion criteria. Even though data currently available confirm the clinical validity of these biomarkers, there is a lack of data regarding clinical utility for most of them. Prospective studies in well-defined populations are needed to integrate these biomarkers in a decision strategy.

Published
2019
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49. Synthèse et Activité antipaludique de nouveaux analogues d’acyclonucléotides

Author

Cheviet, Thomas, Wein, S., Perigaud, Christian, Peyrottes, Suzanne, KARLI, Mélanie, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

50. Sequencing of the GBA coactivator, Saposin C, in Parkinson disease

Author

Roy N. Alcalay, Edward A. Fon, Jennifer A. Ruskey, Guy A. Rouleau, Christopher Liong, Nicolas Dupré, Etienne Leveille, Bouchra Ouled Amar Bencheikh, Ziv Gan-Or, Yves Dauvilliers, Dan Spiegelman, McGill University = Université McGill [Montréal, Canada], Columbia University Medical Center (CUMC), Columbia University [New York], Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Laval [Québec] (ULaval), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and KARLI, Mélanie

Subjects
0301 basic medicine, Aging, Parkinson's disease, Disease, Article, Saposins, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Coactivator, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Genetics, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, General Neuroscience, Parkinson Disease, Sequence Analysis, DNA, medicine.disease, 030104 developmental biology, Multiple comparisons problem, Glucosylceramidase, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Geriatrics and Gerontology, business, Glucocerebrosidase, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Developmental Biology
Abstract

Saposin C (SapC), encoded by PSAP, is required for the activity of glucocerebrosidase, encoded by GBA. While GBA mutations have been studied thoroughly in Parkinson disease (PD), genetic studies on SapC, are still lacking. Full sequencing of PSAP was performed in 1,123 PD patients and 1,153 controls, using targeted sequencing. Regression models adjusted for age and sex, and optimal sequence Kernel association test (SKAT-O) were performed. After correction for multiple comparisons, PSAP variants were not associated with PD. Two variants located within the SapC sequence were found in one PD patient each. SKAT-O analysis of SapC had nominal statistical significance (p=0.027), but not after correction for multiple comparisons. Combining data with a published dataset revealed that a total of four out of 2,290 PD patients (0.2%) had variants (p.G365C or p.T363M) within the binding and activation site with glucocerebrosidase, versus zero out of 2,838 controls (0%), but this was not statistically significant. Larger studies are necessary to examine the role of very rare SapC variants in PD.

Published
2018
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