Author: "Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )" - Searchworks@Jio Institute Digital Library Search Results

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3,762 results on '"Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )"'

1. Rapid protection induced by a single-shot Lassa vaccine in male cynomolgus monkeys

Author: Mathieu Mateo, Stéphanie Reynard, Natalia Pietrosemoli, Emeline Perthame, Alexandra Journeaux, Kodie Noy, Clara Germain, Xavier Carnec, Caroline Picard, Virginie Borges-Cardoso, Jimmy Hortion, Hélène Lopez-Maestre, Pierrick Regnard, Lyne Fellmann, Audrey Vallve, Stéphane Barron, Ophélie Jourjon, Orianne Lacroix, Aurélie Duthey, Manon Dirheimer, Maïlys Daniau, Catherine Legras-Lachuer, Caroline Carbonnelle, Hervé Raoul, Frédéric Tangy, Sylvain Baize, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Université de Strasbourg (UNISTRA), Simian Laboratory Europe (SILABE), Laboratoire P4 Jean Mérieux-Inserm [Lyon] (Unité de service 3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Européen de Recherche en Virologie et Immunologie [Lyon] (Tour Inserm CERVI), Délégation régionale Auvergne Rhône-Alpes [Bron, France], Institut National de la Santé et de la Recherche Médicale (INSERM), ViroScan3D SAS [Trévoux, France], Laboratoire d’innovation : vaccins – Innovation lab : vaccines, This study was funded by a grant from the Coalition for Epidemic Preparedness and Innovations (CEPI-CfP-001) to S. Baize and by a grant from the Agence Nationale de la Recherche (ANR-21-CE18-0004-01) to M. Mateo., and ANR-21-CE18-0004,EXPUNGER,Vaccins post exposition contre les virus emergents(2021)
Subjects: Multidisciplinary, [SDV]Life Sciences [q-bio], General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract: Lassa fever hits West African countries annually in the absence of licensed vaccine to limit the burden of this viral hemorrhagic fever. We previously developed MeV-NP, a single-shot vaccine protecting cynomolgus monkeys against divergent strains one month or more than a year before Lassa virus infection. Given the limited dissemination area during outbreaks and the risk of nosocomial transmission, a vaccine inducing rapid protection could be useful to protect exposed people during outbreaks in the absence of preventive vaccination. Here, we test whether the time to protection can be reduced after immunization by challenging measles virus pre-immune male cynomolgus monkeys sixteen or eight days after a single shot of MeV-NP. None of the immunized monkeys develop disease and they rapidly control viral replication. Animals immunized eight days before the challenge are the best controllers, producing a strong CD8 T-cell response against the viral glycoprotein. A group of animals was also vaccinated one hour after the challenge, but was not protected and succumbed to the disease as the control animals. This study demonstrates that MeV-NP can induce a rapid protective immune response against Lassa fever in the presence of MeV pre-existing immunity but can likely not be used as therapeutic vaccine.
Published: 2023

2. Cuticle architecture and mechanical properties: a functional relationship delineated through correlated multimodal imaging

Author: Nicolas Reynoud, Nathalie Geneix, Angelina D’Orlando, Johann Petit, Jeremie Mathurin, Ariane Deniset-Besseau, Didier Marion, Christophe Rothan, Marc Lahaye, Bénédicte Bakan, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), BioInformatique et BioStatistiques (BIBS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie du fruit et pathologie (BFP), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Chimie Physique (ICP), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), INRAE and Region Pays de la Loire (Fr)., and ANR-21-CE11-0035,COPLAnAR,COPLAnAR : cartography corrélative pour élucider les relations structure-propriétés de la cuticule des plantes(2021)
Subjects: hyperspectral, plant cuticle, Solanum lycopersicum, Physiology, nanomechanical, AFM PF-QNM, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, correlated multimodal imaging, Plant Science, Raman
Abstract: Cuticle are multifunctional hydrophobic biocomposites that protect aerial organs of plants. Along plant development, plant cuticle must accommodate different mechanical constraints combining extensibility and stiffness, the corresponding structure-function relationships are unknown. Recent data showed a fine architectural tuning of the cuticle architecture and the corresponding chemical clusters along fruit development which raise the question of their impact on the mechanical properties of the cuticle.We investigated the in-depth nanomechanical properties of tomato fruit cuticle from early development to ripening, in relation to chemical and structural heterogeneities by developing a correlative multimodal imaging approach.Unprecedented sharps heterogeneities were evidenced with the highlighting of an in-depth mechanical gradient and a ‘soft’ central furrow that were maintained throughout the plant development despite the overall increase in elastic modulus. In addition, we demonstrated that these local mechanical areas are correlated to chemical and structural gradients.This study shed light on a fine tuning of mechanical properties of cuticle through the modulation of their architecture, providing new insight for our understanding of structure-function relationships of plant cuticle and for the design of biosinpired material.
Published: 2023

3. Using a manifold-based approach to extract clinical codes associated with winter respiratory viruses at an emergency department

Author: Péalat, Clément, Bouleux, Guillaume, Cheutet, Vincent, Maignan, Maxime, Provoost, Luc, Pillet, Sylvie, Mory, Olivier, Décision et Information pour les Systèmes de Production (DISP), Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), CHU Grenoble, Physiopathologie et biothérapies des infections muqueuses (GIMAP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Time Series Clustering, Stiefel manifold, Healthcare management, Monitoring Emergency Departments, Delay coordinate embedding, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI]
Abstract: International audience; Every winter, respiratory viruses put most Emergency Departments (ED) around the world under intense pressure. To reduce the consequent stress for hospitals, anticipation of the massive increase of intakes for illness-based symptoms is essential. As the Covid-19 2020 pandemic clearly illustrates, patients are not systematically tested. The ED staff therefore has no real-time knowledge of the presence of the virus in the patients flow. To address this issue, we propose here to use the hospital's laboratory-confirmed database as an attractor for the manifold-based approach for clustering the clinical codes associated with respiratory viruses. We propose a new framework based on the embedding of time series onto the Stiefel manifold, coupled with a density-based clustering algorithm (HDBSCAN) enhanced by a reduction of dimension (UMAP) for the clustering on that manifold. In particular, we show, based on real data sets of two academic hospitals in France, the significant benefits of using geometrical approaches for time series clustering as compared to traditional methods.
Published: 2023

4. Structure, Morphology, and Surface Chemistry of Surgical Masks and Their Evolution up to 10 Washing Cycles

Author: Louise Wittmann, Joseph Garnier, Naomi Sakata, Elisabeth Auzias, Martin Dumoulin, Nathanaël Barlier, Théotime Bergese, Lara Leclerc, Florence Grattard, Paul O. Verhoeven, Jérémie Pourchez, Claude Botella, Jean-Marie Bluet, Béatrice Vacher, José Penuelas, Institut des Nanotechnologies de Lyon (INL), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et biothérapies des infections muqueuses (GIMAP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INL - Matériaux Fonctionnels et Nanostructures (INL - MFN), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Laboratoire de Tribologie et Dynamique des Systèmes (LTDS), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne (ENISE)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon
Subjects: [CHIM.POLY]Chemical Sciences/Polymers, Polymers and Plastics, pandemic, Process Chemistry and Technology, Organic Chemistry, washing, surgical masks, decontamination, Covid-19, polypropylene
Abstract: International audience; The Covid-19 crisis has led to a massive surge in the use of surgical masks worldwide, causing risks of shortages and high pollution. Various decontamination techniques are currently being studied to reduce these risks by allowing the reuse of masks. In this study, surgical masks were washed up to 10 times, each cycle under the same conditions. The consequences of the washing cycles on the structure, fiber morphology, and surface chemistry have been studied through several characterization techniques: scanning electron microscopy, wetting angle measurements, infrared spectroscopy, X-ray diffraction, and X-ray photoelectrons spectroscopy. The washing process did not induce large changes in the hydrophobicity of the surface, the contact angle remaining constant throughout the cycles. The composition observed in the IR spectrum also remained unchanged for washed masks up to 10 cycles. Some slight variations were observed during X-ray analysis: the crystallinity of the fibers as well as the size of the crystals increases with the number of wash cycles. The XPS analysis shows that after 10 cycles, the surface of the masks underwent a slight oxidation. In the SEM images, changes were observed in the arrangement of the fibers, which are more visible the more times the mask has been washed: they align themselves in bundles, form areas with holes in the mask layer, and are crushed in some areas.
Published: 2023

5. The conformation of glutenin polymers in wheat grain: some genetic and environmental factors associated with this important characteristic

Author: Gérard Branlard, Angelina d’Orlando, Ayesha Tahir, Marc Schmutz, Larbi Rhazi, Annie Faye, Thierry Aussenac, Génétique Diversité et Ecophysiologie des Céréales (GDEC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), BioInformatique et BioStatistiques (BIBS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), COMSATS University Islamabad (CUI), Institut Charles Sadron (ICS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Transformations et Agro-ressources (UT&A), and UniLaSalle
Subjects: Physiology, [SDV]Life Sciences [q-bio], Plant Science
Abstract: In a previous study we used asymmetric-flow field-flow fractionation to determine the polymer mass (Mw), gyration radius (Rw) and the polydispersity index of glutenin polymers (GPs) in wheat (Triticum aestivum). Here, using the same multi-location trials (4 years, 11 locations, and 192 cultivars), we report the factors that are associated with the conformation (Conf) of the polymers, which is the slope of Log(Rw) versus a function of Log(Mw). We found that Conf varied between 0.285 and 0.740, it had low broad-sense heritability (H2=16.8), and it was significantly influenced by the temperature occurring over the last month of grain filling. Higher temperatures were found to increase Rw and the compactness and sphericity of GPs. Alleles for both high- and low-molecular-weight glutenin subunits had a significant influence on the Conf value. Assuming a Gaussian distribution for Mw, the number of polymers present in wheat grains was computed for different kernel weights and protein concentrations, and it was found to exceed 1012 GPs per grain. Using atomic force microscopy and cryo-TEM, images of GPs were obtained for the first time. Under higher average temperature, GPs became larger and more spherical and consequently less prone to rapid hydrolysis. We propose some orientations that could be aimed at potentially reducing the impact of numerous GPs on people suffering from non-celiac gluten sensitivity.
Published: 2023

6. Validity and Performance of Blood Biomarkers for Alzheimer Disease to Predict Dementia Risk in a Large Clinic-Based Cohort

Author: Planche, Vincent, Bouteloup, Vincent, Pellegrin, Isabelle, Mangin, Jean-Francois, Dubois, Bruno, Ousset, Pierre-Jean, Pasquier, Florence, Blanc, Frédéric, Paquet, Claire, Hanon, Olivier, Bennys, Karim, Ceccaldi, Mathieu, Annweiler, Cédric, Krolak-Salmon, Pierre, Godefroy, Olivier, Wallon, David, Sauvee, Mathilde, Boutoleau-Bretonnière, Claire, Bourdel-Marchasson, Isabelle, Jalenques, Isabelle, Chene, Genevieve, Dufouil, Carole, Université de Bordeaux (UB), Centre Mémoire de Ressources et de Recherches [Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'immunologie et d'immunogénétique [CHU Bordeaux], Université Paris-Saclay, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), INSERM UMR 1287 Département d'hématologie, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe hospitalier Broca, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Nantes Université - UFR Lettres et Langages (Nantes Univ - UFR LL), Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), SFR UA 4201 Confluences (CONFLUENCES), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, CHU Rouen, Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), Centre Mémoire de Ressources et de Recherche [Grenoble] (CMRR), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de résonance magnétique des systèmes biologiques (CRMSB), Service d'Addictologie et Pathologie Duelles [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées, Service Instrumentation Conception Caractérisation (LAAS-I2C), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Neurology (clinical), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background and ObjectiveBlood biomarkers for Alzheimer disease (AD) have consistently proven to be associated with CSF or PET biomarkers and effectively discriminate AD from other neurodegenerative diseases. Our aim was to test their utility in clinical practice, from a multicentric unselected prospective cohort where patients presented with a large spectrum of cognitive deficits or complaints.MethodsThe MEMENTO cohort enrolled 2,323 outpatients with subjective cognitive complaint (SCC) or mild cognitive impairment (MCI) consulting in 26 French memory clinics. Participants had neuropsychological assessments, MRI, and blood sampling at baseline. CSF sampling and amyloid PET were optional. Baseline blood Aβ42/40 ratio, total tau, p181-tau, and neurofilament light chain (NfL) were measured using a Simoa HD-X analyzer. An expert committee validated incident dementia cases during a 5-year follow-up period.ResultsOverall, 2,277 individuals had at least 1 baseline blood biomarker available (n = 357 for CSF subsample, n = 649 for PET subsample), among whom 257 were diagnosed with clinical AD/mixed dementia during follow-up. All blood biomarkers but total tau were mildly correlated with their equivalence in the CSF (r = 0.33 to 0.46,p< 0.0001) and were associated with amyloid-PET status (p< 0.0001). Blood p181-tau was the best blood biomarker to identify amyloid-PET positivity (area under the curve = 0.74 [95% CI = 0.69; 0.79]). Higher blood and CSF p181-tau and NfL concentrations were associated with accelerated time to AD dementia onset with similar incidence rates, whereas blood Aβ42/40 was less efficient than CSF Aβ42/40. Blood p181-tau alone was the best blood predictor of 5-year AD/mixed dementia risk (c-index = 0.73 [95% CI = 0.69; 0.77]); its accuracy was higher in patients with clinical dementia rating (CDR) = 0 (c-index = 0.83 [95% CI = 0.69; 0.97]) than in patients with CDR = 0.5 (c-index = 0.70 [95% CI = 0.66; 0.74]). A “clinical” reference model (combining demographics and neuropsychological assessment) predicted AD/mixed dementia risk with a c-index = 0.88 [95% CI = 0.86–0.91] and performance increased to 0.90 [95% CI = 0.88; 0.92] when adding blood p181-tau + Aβ42/40. A “research” reference model (clinical model + apolipoprotein E genotype and AD signature on MRI) had a c-index = 0.91 [95% CI = 0.89–0.93] increasing to 0.92 [95% CI = 0.90; 0.93] when adding blood p181-tau + Aβ42/40. Chronic kidney disease and vascular comorbidities did not affect predictive performances.DiscussionIn a clinic-based cohort of patients with SCC or MCI, blood biomarkers may be good hallmarks of underlying pathology but add little to 5-year dementia risk prediction models including traditional predictors.
Published: 2022

7. Antiviral drugs in hospitalized patients with COVID-19 - the DisCoVeRy trial

Author: Bruno Mourvillier, François-Xavier Lescure, Dominique Costagliola, Alain Makinson, Valérie Pourcher, Odile Launay, Clément Dubost, Saad Nseir, Emmanuel Faure, Yazdan Yazdanpanah, Jean-Christophe Richard, Lila Bouadma, Kevin Bouiller, Juliette Saillard, Jean Reignier, Claire Andrejak, Alpha Diallo, Lionel Piroth, Jean-Philippe Lanoix, Violaine Tolsma, Christelle Delmas, Gilles Peytavin, André Cabié, Marion Noret, Karine Lacombe, Elisabeth Botelho-Nevers, Thérèse Staub, Johan Courjon, Florence Ader, Nathan Peiffer-Smadja, Jean-Christophe Navellou, Maya Hites, Jean Reuter, Noemie Mercier, Maude Bouscambert-Duchamp, François Danion, S. Gallien, Julien Poissy, Florent Wallet, Guillaume Martin-Blondel, Raphaël Clere-Jehl, Bruno Lina, Amandine Gagneux-Brunon, Antoine Kimmoun, Rostane Gaci, Olivier Epaulard, Axelle Dupont, François Raffi, Aline Dechanet, François Goehringer, Joy Mootien, Stéphane Jauréguiberry, Sylvie Leroy, Charles Burdet, Toni Alfaiate, Drifa Belhadi, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANRS - Maladies infectieuses émergentes (ANRS - MIE), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, Université de Médecine Carol Davila, Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS France Recherche Nord & sud Sida-hiv hépatites, Département d'Epidemiologie, Biostatistique et Recherche Clinique (DEBRC), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Service de Réanimation Médicale [CHRU Nancy], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), and Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Hospitalized patients, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Lopinavir, Hydroxychloroquine, Odds ratio, law.invention, Randomized controlled trial, law, Internal medicine, medicine, Ritonavir, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: BackgroundLopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a and hydroxychloroquine efficacy for COVID-19 have been evaluated, but detailed evaluation is lacking.ObjectiveTo determine the efficacy of lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a, hydroxychloroquine or remdesivir for improving the clinical, virological outcomes in COVID-19 inpatients.DesignOpen-label, randomized, adaptive, controlled trial.SettingMulti-center trial with patients from France.Participants583 COVID-19 inpatients requiring oxygen and/or ventilatory supportInterventionStandard of care (SoC, control), SoC plus lopinavir/ritonavir (400 mg lopinavir and 100 mg ritonavir every 12h for 14 days), SoC plus lopinavir/ritonavir plus IFN-ß-1a (44 μg of subcutaneous IFN-ß-1a on days 1, 3, and 6), SoC plus hydroxychloroquine (400 mg twice on day 1 then 400 mg once daily for 9 days) or SoC plus remdesivir (200 mg intravenously on day 1 then 100 mg once-daily for hospitalization duration or 10 days).MeasurementsThe primary outcome was the clinical status at day 15, measured by the WHO 7-point ordinal scale. Secondary outcomes included SARS-CoV-2 quantification in respiratory specimens and safety analyses.ResultsAdjusted Odds Ratio (aOR) for the WHO 7-point ordinal scale were not in favor of investigational treatments: lopinavir/ritonavirversuscontrol, aOR 0.83, 95%CI, 0.55 to 1.26, P=0.39; lopinavir/ritonavir-IFN-β-1aversuscontrol, aOR 0.69, 95%CI, 0.45 to 1.04, P=0.08; hydroxychloroquineversuscontrol, aOR 0.93, 95%CI, 0.62 to 1.41, P=0.75. No significant effect on SARS-CoV-2 RNA clearance in respiratory tract was evidenced. Lopinavir/ritonavir-containing treatments were significantly associated with more SAE.LimitationsNot a placebo-controlled, no anti-inflammatory agents tested.ConclusionNo improvement of the clinical status at day 15 nor SARS-CoV-2 RNA clearance in respiratory tract specimens by studied drugs. This comforts the recent Solidarity findings.RegistrationNCT04315948.FundingPHRC 2020, Dim OneHealth, REACTing
Published: 2023

8. Disability progression in multiple sclerosis patients using early first‐line treatments

Author: Mathilde, Lefort, Sandra, Vukusic, Romain, Casey, Gilles, Edan, Emmanuelle, Leray, Chantal, Nifle, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Département Méthodes quantitatives en santé publique (METIS), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Lyon], CHU Lyon, Fondation Eugène Devic EDMUS, This work was funded by the Eugène Devic EDMUS Foundation against Multiple Sclerosis and by the ARSEP Foundation (Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: beta-interferon, disability progression, Neurology, [SDV]Life Sciences [q-bio], glatiramer acetate, early treatment, Neurology (clinical), multiple sclerosis, observational studies, propensity score
Abstract: International audience; BACKGROUND: Therapeutic management of relapsing-remitting multiple sclerosis (RRMS) has evolved towards early treatment. The objective was to assess the impact of early treatment initiation on disability progression among RRMS first-line treated patients. METHODS: This study included all incident RRMS cases starting interferon or glatiramer acetate for the first time from 1996/01/01 to 2012/31/12 (N=5,279) from ten MS expert OFSEP centers (Observatoire Français de la Sclérose en Plaques). The delay from treatment start to attain an irreversible Expanded Disability Status Scale score of 3.0 were compared between "Early" group (N= 1,882; treated within 12 months following MS clinical onset) and "Later" group using propensity score weighted Kaplan-Meier methods, overall and stratified by age. RESULTS: Overall, the restricted mean time before reaching EDSS 3.0 (RMST) from treatment start was 11 years and two months for patients treated within the year following MS clinical onset and 10 years and seven months for patients treated later. Thus, early treated patients gained 7 months (95% CI: [4-11] months) in the time to reach EDSS 3.0 compared to patients treated later (treatment start delayed by 28 months). The difference in RMST was respectively six months (95% CI: [1-10] months) and 14 months (95% CI: [4-24] months) in the "≤40 years" age group and in the ">40 years" age group, in favour of early group. . CONCLUSIONS: Early treatment initiation resulted in a significant reduction of disability progression among patients with RRMS, and also among older patients.
Published: 2022

9. Analyse des risques pour la santé humaine et animale liés aux tiques du genre Hyalomma en France

Author: Bonnet, Sarah, Baize, Sylvain, Bertagnoli, Stéphane, Falchi, Alessandra, Figoni, Julie, Hoch, Thierry, Moutailler, Sara, Raffetin, Alice, René-Martellet, Magalie, Stachurski, Frederic, Vial, Laurence, Vourc’h, Gwenaël, Quillery, Elsa, Fite, Johanna, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Università di Corsica Pasquale Paoli [Université de Corse Pascal Paoli], Partenaires INRAE, Direction santé environnement travail - Santé Publique France, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Biologie moléculaire et immunologie parasitaires et fongiques (BIPAR), École nationale vétérinaire - Alfort (ENVA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Intercommunal Villeneuve-Saint-Georges (CHIV), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques (UMR EPIA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Anses, and Druesne, Christine
Subjects: human health, animal health, Fièvre hémorragique de Crimée-Congo, risk analysis, santé animale, [SDV]Life Sciences [q-bio], agents pathogènes, Hyalomma marginatum, virus, vector-borne disease, vecteur, [SDV] Life Sciences [q-bio], santé humaine, Hyalomma, FHCC, France, Crimean-Congo hemorrhagic fever (CCHF), Tique, tick-borne virus, vector, pathogen agents, maladie vectorielle, Tick, analyse de risque
Abstract: Citation suggérée : Anses. (2022). Analyse des risques pour la santé humaine et animale liés aux tiques du genreHyalomma en France. (Saisine 2020-SA-0039). Maisons-Alfort : Anses, 300 p.; Les populations de tiques du genre Hyalomma sont considérées en augmentation sur unepartie de leur aire de répartition, qui semble s'étendre en Europe depuis la fin du XXe siècle.La tique Hyalomma marginatum est présente en Corse depuis plusieurs décennies (Grech-Angelini et al. 2016). Hyalomma marginatum est considérée comme une espèce de tique invasive en France continentale, de récentes publications confirmant son installation sur le littoral méditerranéen (Vial et al. 2016; Stachurski et Vial 2018; Bahet al. 2022). D’autres espèces de Hyalomma sont également présentes en France, H. scupense en Corse (Grech-Angelini , 2016) et sur le continent (Vial et Stachurski, comm. pers.), et des données récentes montrent que H. lusitanicum serait également installée en France continentale (Stachurski, comm. pers.).Cette évolution est préoccupante, car ces tiques sont vectrices de nombreux agents pathogènes responsables de maladies pour l’être humain (notamment du virus de la fièvre hémorragique de Crimée-Congo – FHCC – ou de Rickettsies) et de maladies animales (notamment Babesia caballi responsable de la piroplasmose équine).Le virus de la FHCC (CCHFV) est responsable, chez l’être humain, de flambées de fièvre hémorragique sévère, dont le taux de létalité varie de 5 à près de 30 % (Spengler, Bergeron,et Spiropoulou 2019). Une séroprévalence du CCHFV de l’ordre de 10 % aurait récemment été mise en évidence chez les ruminants domestiques en Corse, sans qu’aucun cas humain n’ait encore été observé (Grech-Angelini et al. 2020). En 2016, deux cas autochtones de FHCC ont été confirmés à Madrid (Negredo et al. 2017), pour la première fois en Europe de l’Ouest.Une étude rétrospective, menée en 2020, a montré qu'un cas de FHCC était survenu dans la même province en 2013 (Negredo et al 2021). Depuis, des cas de FHCC, dont certains mortels, sont rapportés quasiment tous les ans en Espagne (2018, 2020, 2021, 2022). De plus, la circulation du virus est en recrudescence dans la région des Balkans et en Turquie.Aussi, l’Anses s’est autosaisie le 4 mars 2020 pour analyser les risques pour la santé humaineet animale liés aux tiques du genre Hyalomma en France.
Published: 2023

10. STLV-1 Commonly Targets Neurons in the Brain of Asymptomatic Non-Human Primates

Author: Brenda Rocamonde, Sandrine Alais, Rodolphe Pelissier, Valerie Moulin, Brigitte Rimbaud, Romain Lacoste, Noemie Aurine, Camille Baquerre, Bertrand Pain, Yuetsu Tanaka, Cyrille Mathieu, Hélène Dutartre, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oncogenèse rétrovirale – Retroviral Oncogenesis (OR), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Groupe hospitalier de La Rochelle, Station de primatologie (SP), Centre National de la Recherche Scientifique (CNRS), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Immunology [Okinawa, Japan] (Graduate School and Faculty of Medicine), and University of the Ryukyus [Okinawa]
Subjects: HTLV-1, inflammation, [SDV]Life Sciences [q-bio], Virology, neurotropism, Microbiology, microglial response
Abstract: International audience; The human T-cell leukemia virus (HTLV)-1 is responsible for an aggressive neurodegenerative disease (HAM/TSP) and multiple neurological alterations. The capacity of HTLV-1 to infect central nervous system (CNS) resident cells, together with the neuroimmune-driven response, has not been well-established. Here, we combined the use of human induced pluripotent stem cells (hiPSC) and of naturally STLV-1-infected nonhuman primates (NHP) as models with which to investigate HTLV-1 neurotropism. Hence, neuronal cells obtained after hiPSC differentiation in neural polycultures were the main cell population infected by HTLV-1. Further, we report the infection of neurons with STLV-1 in spinal cord regions as well as in brain cortical and cerebellar sections of postmortem NHP. Additionally, reactive microglial cells were found in infected areas, suggesting an immune antiviral response. These results emphasize the need to develop new efficient models by which to understand HTLV-1 neuroinfection and suggest an alternative mechanism that leads to HAM/TSP.
Published: 2023

11. Immunogenicity, safety and tolerability of a recombinant measles-vectored Lassa vaccine: A randomised, placebo-controlled, first-in-human trial

Author: Tschismarov, Roland, van Damme, Pierre, Germain, Clara, De Coster, Ilse, Mateo, Mathieu, Reynard, Stephanie, Journeaux, Alexandra, Tomberger, Yvonne, Withanage, Kanchanamala, Haslwanter, Denise, Terler, Katherine, Schrauf, Sabrina, Muellner, Matthias, Tauber, Erich, Ramsauer, Katrin, Baize, Sylvain, Themis Bioscience GmbH, University of Antwerp (UA), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)
Subjects: safety, phase 1, vaccine, [SDV]Life Sciences [q-bio], measles-vectored, Human medicine, General Medicine, live-attenuated, immunogenicity, Lassa virus, first in man, placebo-controlled clinical trial
Abstract: International audience; BackgroundLassa fever is a substantial health burden in west Africa. We evaluated the safety, tolerability, and immunogenicity of a recombinant, live-attenuated, measles-vectored Lassa fever vaccine candidate (MV-LASV).MethodsThis first-in-human phase 1 trial—consisting of an open-label dose-escalation stage and an observer-blinded, randomised, placebo-controlled treatment stage—was conducted at a single site at the University of Antwerp, Antwerp, Belgium, and involved healthy adults aged 18–55 years. Participants in the dose-escalation stage were sequentially assigned to a low-dose group (two intramuscular doses of MV-LASV at 2 × 104 times the median tissue culture infectious dose) or a high-dose group (two doses at 1 × 105 times the median tissue culture infectious dose). Participants in the double-blinded treatment stage were randomly assigned in a 2:2:1 ratio to receive low dose, high dose, or placebo. The primary endpoint was the rate of solicited and unsolicited adverse events up to study day 56 and was assessed in all participants who received at least one dose of investigational product. The trial is registered with ClinicalTrials.gov, NCT04055454, and the European Union Drug Regulating Authorities Clinical Trials Database, 2018-003647-40, and is complete.FindingsBetween Sept 26, 2019, and Jan 20, 2020, 60 participants were enrolled and assigned to receive placebo (n=12) or MV-LASV (n=48). All 60 participants received at least one study treatment. Most adverse events occurred during the treatment phase, and frequencies of total solicited or unsolicited adverse events were similar between treatment groups, with 96% of participants in the low-dose group, 100% of those in the high-dose group, and 92% of those in the placebo group having any solicited adverse event (p=0·6751) and 76% of those in the low-dose group, 70% of those in the high-dose group, and 100% of those in the placebo group having any unsolicited adverse event (p=0·1047). The only significant difference related to local solicited adverse events, with higher frequencies observed in groups receiving MV-LASV (24 [96%] of 25 participants in the low-dose group; all 23 [100%] participants in the high-dose group) than in the placebo group (6 [50%] of 12 participants; p=0·0001, Fisher-Freeman-Halton test). Adverse events were mostly of mild or moderate severity, and no serious adverse events were observed. MV-LASV also induced substantial concentrations of LASV-specific IgG (geometric mean titre 62·9 EU/ml in the low-dose group and 145·9 EU/ml in the high-dose group on day 42).InterpretationMV-LASV showed an acceptable safety and tolerability profile, and immunogenicity seemed to be unaffected by pre-existing immunity against the vector. MV-LASV is therefore a promising candidate for further development.FundingCoalition for Epidemic Preparedness Innovations.
Published: 2023

12. Scavenger Receptor Cysteine-Rich domains of Lysyl Oxidase-Like2 regulate endothelial ECM and angiogenesis through non-catalytic scaffolding mechanisms

Author: Marion Marchand, Jérémie Teillon, Stéphane Germain, Claudia Umana-Diaz, Florence Ruggiero, Corinne Ardidie-Robouant, Marilyne Malbouyres, Christophe Guilluy, A. Barret, Catherine Monnot, Laurent Muller, Romain Salza, Sylvie Ricard-Blum, Yoann Atlas, Cathy Pichol-Thievend, Philippe Girard, Pathologie et virologie moléculaire (PVM (UMR_7151)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathologie vasculaire et endocrinologie rénale - Chaire de médecine expérimentale (INSERM U36), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Assemblages Supramoléculaires Péricellulaires et Extracellulaires (ASPE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Inflammasome NLRP3 – NLRP3 Inflammasome, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Collège de France (CdF (institution)), Institut Mutualiste de Montsouris (IMM), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: Collagen Type IV, 0301 basic medicine, Angiogenesis, [SDV]Life Sciences [q-bio], Neovascularization, Physiologic, Lysyl oxidase, Cell Line, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, Human Umbilical Vein Endothelial Cells, medicine, Animals, Humans, Scavenger receptor, Molecular Biology, Zebrafish, Basement membrane, Binding Sites, LOXL2, biology, Chemistry, Dermis, Fibroblasts, Zebrafish Proteins, Extracellular Matrix, Fibronectins, Cell biology, Fibronectin, Surface coating, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Mutagenesis, Site-Directed, biology.protein, Amino Acid Oxidoreductases
Abstract: International audience; Lysyl oxidases are major actors of microenvironment and extracellular matrix (ECM) remodeling. These cross-linking enzymes are thus involved in many aspects of physiopathology, including tumor progression, fibrosis and cardiovascular diseases. We have already shown that Lysyl Oxidase-Like 2 (LOXL2) regulates collagen IV deposition by endothelial cells and angiogenesis. We here provide evidence that LOXL2 also affects deposition of other ECM components, including fibronectin, thus altering structural and mechanical properties of the matrix generated by endothelial cells. LOXL2 interacts intracellularly and directly with collagen IV and fibronectin before incorporation into ECM fibrillar structures upon exocytosis, as demonstrated by TIRF time-lapse microscopy. Furthermore, surface plasmon resonance experiments using recombinant scavenger receptor cysteine-rich (SRCR) domains truncated for the catalytic domain demonstrated their direct binding to collagen IV. We thus used directed mutagenesis to investigate the role of LOXL2 catalytic domain. Neither enzyme activity nor catalytic domain were necessary for collagen IV deposition and angiogenesis, whereas the SRCR domains were effective for these processes. Finally, surface coating with recombinant SRCR domains restored deposition of collagen IV by LOXL2-depleted cells. We thus propose that LOXL2 SRCR domains orchestrate scaffolding of the vascular basement membrane and angiogenesis through interactions with collagen IV and fibronectin, independently of the enzymatic crosslinking activity.
Published: 2023

13. Promoting HPV vaccination at school: a mixed methods study exploring knowledge, beliefs and attitudes of French school staff

Author: Bocquier, Aurélie, Branchereau, Marion, Gauchet, Aurélie, Bonnay, Stéphanie, Simon, Maïa, Ecollan, Marie, Chevreul, Karine, Mueller, Judith, Gagneux-Brunon, Amandine, Thilly, Nathalie, Study Group, Prevhpv, Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Centre Régional de Coordination des Dépistages des Cancers [Angers] (CRCDC Pays de la Loire), Laboratoire Inter-universitaire de Psychologie : Personnalité, Cognition, Changement Social (LIP-PC2S), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Grenoble Alpes (UGA), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et biothérapies des infections muqueuses (GIMAP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Département Méthodologie Promotion Investigation [CHRU Nancy] (MPI), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), The PrevHPV study is conducted with the support of IReSP and Inserm, and with financial support from ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé/ National Alliance for Life Sciences & Health) within the framework of the Cancer Plan., Département Méthodes quantitatives en santé publique (METIS), and Université de Rennes (UR)
Subjects: [STAT.AP]Statistics [stat]/Applications [stat.AP], Knowledge, Attitude, Vaccination, Middle school professionals, Human Papillomavirus, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Health Education, Mixed method study, School-based immunization programs
Abstract: International audience; BackgroundHPV vaccine coverage in France remained lower than in most other high-income countries. Within the diagnostic phase of the national PrevHPV program, we carried out a mixed methods study among school staff to assess their knowledge, beliefs and attitudes regarding HPV, HPV vaccine and vaccination in general, and regarding schools’ role in promoting HPV vaccination. MethodsMiddle school nurses, teachers and support staff from four French regions participated between January 2020 and May 2021. We combined: (i) quantitative data from self-administered online questionnaires ( n = 301), analysed using descriptive statistics; and (ii) qualitative data from three focus groups ( n = 14), thematically analysed.ResultsLess than half of respondents knew that HPV can cause genital warts or oral cancers and only 18% that no antiviral treatment exists. Almost 90% of the respondents knew the existence of the HPV vaccine but some misunderstood why it is recommended before the first sexual relationships and for boys; 56% doubted about its safety, especially because they think there is not enough information on this topic. Schools nurses had greater knowledge than other professionals and claimed that educating pupils about HPV was fully part of their job roles; however, they rarely address this topic due to a lack of knowledge/tools. Professionals (school nurses, teachers and support staff) who participated in the focus groups were unfavourable to offering vaccination at school because of parents’ negative reactions, lack of resources, and perceived uselessness. ConclusionsThese results highlight the need to improve school staff knowledge on HPV. Parents should be involved in intervention promoting HPV vaccination to prevent their potential negative reactions, as feared by school staff. Several barriers should also be addressed before organizing school vaccination programs in France.; IntroductionLa couverture vaccinale contre les papillomavirus humains (HPV) en France reste inférieure à celle de la plupart des autres pays développés. Dans le cadre de la phase diagnostique du projet PrevHPV, nous avons mené une étude mixte auprès de professionnels de l’Education Nationale afin d’explorer leurs connaissances, représentations et attitudes vis-à-vis des HPV, du vaccin contre les HPV et de la vaccination en général, ainsi qu’au sujet du rôle du milieu scolaire dans la promotion de la vaccination contre les HPV.MéthodesL’étude a été menée auprès d’infirmières scolaires, d’enseignants et de membres du personnel administratif et d’encadrement de collèges de quatre régions françaises entre janvier 2020 et mai 2021. Nous avons combiné : (i) des données quantitatives collectées via des questionnaires auto-administrés, en ligne (n = 301), analysées à l'aide de statistiques descriptives ; et (ii) des données qualitatives collectées lors de trois focus groups (n = 14), traitées par une analyse thématique de contenu.RésultatsMoins de la moitié des répondants au questionnaire en ligne savaient que les HPV peuvent provoquer des verrues génitales ou des cancers ORL et 18 % seulement qu'il n'existe pas de traitement antiviral contre les HPV. Près de 90 % des répondants connaissaient l'existence du vaccin contre les HPV, mais certains professionnels ne comprenaient pas pourquoi ce vaccin était recommandé avant les premiers rapports sexuels ou pour les garçons ; 56 % doutaient de son innocuité, notamment parce qu'ils pensaient qu'il n'y avait pas assez de recul sur ce vaccin. Les infirmières scolaires avaient de meilleures connaissances que les autres professionnels et reconnaissaient que l'éducation des élèves au sujet des HPV fait partie intégrante de leur mission ; cependant, elles abordaient rarement ce sujet, notamment en raison d'un manque de connaissances et/ou d'outils. Les professionnels (infirmières scolaires, enseignants et personnel administratif/d’encadrement) ayant participé aux focus groups n'étaient pas favorables à l'idée de proposer la vaccination contre les HPV en milieu scolaire, notamment en raison du manque de ressources, de la crainte d’être confrontés à des réactions négatives de la part des parents et car ils n’en percevaient pas l’utilité (la vaccination étant accessible dans d’autres lieux).ConclusionLes résultats de cette étude soulignent la nécessité d'améliorer les connaissances du personnel scolaire sur les HPV et sa vaccination. Les parents devraient être impliqués dans les interventions de promotion de la vaccination contre les HPV afin de prévenir d’éventuelles réactions négatives, comme le craignent les professionnels des collèges. Plusieurs obstacles doivent également être levés avant d'organiser la vaccination en milieu scolaire en France.
Published: 2023

14. Pathogenesis of recent Lassa virus isolates from lineages II and VII in cynomolgus monkeys

Author: Mateo, Mathieu, Hortion, Jimmy, Perthame, Emeline, Picard, Caroline, Reynard, Stéphanie, Journeaux, Alexandra, Germain, Clara, Carnec, Xavier, Baillet, Nicolas, Borges-Cardoso, Virginie, Pietrosemoli, Natalia, Vallve, Audrey, Barron, Stéphane, Jourjon, Ophélie, Lacroix, Orianne, Duthey, Aurélie, Dirheimer, Manon, Daniau, Maïlys, Legras-Lachuer, Catherine, Jouvion, Gregory, Carbonnelle, Caroline, Raoul, Hervé, Baize, Sylvain, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire P4 - Jean Mérieux, Centre Européen de Virologie/Immunologie-Institut National de la Santé et de la Recherche Médicale (INSERM), ViroScan3D SAS [Trévoux, France], Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), MATEO, MATHIEU, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université Paris Cité (UPCité), and Institut Pasteur [Paris]-Université Paris Cité (UPCité)
Subjects: Microbiology (medical), cynomolgus monkeys, Immunology, viral hemorrhagic fevers, MESH: Lassa Fever, Virus Replication, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Microbiology, Lassa Fever, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Animals, Humans, MESH: Animals, Lassa virus, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, pathogenesis, MESH: Virus Replication, MESH: Lassa virus, immune responses, Macaca fascicularis, Infectious Diseases, MESH: Macaca fascicularis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Parasitology
Abstract: We thank P. Regnard, P.H. Moreau, and L. Fellmann (SILABE, Strasbourg) for medical care given to the monkeys. We thank S. Mundweiller, S. Godard, E. Moissonnier, D. Thomas, S. Mely, B. Labrosse, D. Pannetier, and C. Leculier (P4 INSERM–Jean Merieux, US003, INSERM) for assistance in conducting the BSL-4 experiments. We thank M-A Dillies (HUB, Institut Pasteur) for helpful discussions. We thank G. Fourcaud and B. Lafoux (UBIVE, CIRI, Institut Pasteur) for technical help. We also thank L. Branco (Zalgen Labs) for providing recombinant proteins. We are grateful to the Coalition for Epidemic Preparedness and Innovations (R. Hatchett, G. Thiry, and M. Saville) and C. Gerke (Department of Innovation Development, Institut Pasteur) for invaluable support.; International audience; The area of Lassa virus (LASV) circulation is expanding, with the emergence of highly pathogenic new LASV lineages. Benin recently became an endemic country for LASV and has seen the emergence of a new LASV lineage (VII). The first two outbreaks in 2014 and 2016 showed a relatively high mortality rate compared to other outbreaks. We infected cynomolgus monkeys with two strains belonging to lineage II and lineage VII that were isolated from deceased patients during the 2016 outbreak in Benin. The lineage VII strain (L7) caused uniform mortality. Death was associated with uncontrolled viral replication, unbalanced inflammatory responses characterized by increased concentrations of pro- and anti-inflammatory mediators, and the absence of efficient immune responses, resembling the pathogenesis associated with the prototypic Josiah strain in monkeys. The lineage II strain (L2) showed apparently lower virulence than its counterpart, with a prolonged time to death and a lower mortality rate. Prolonged survival was associated with better control of viral replication, a moderate inflammatory response, and efficient T-cell responses. Transcriptomic analyses also highlighted important differences in the immune responses associated with the outcome. Both strains caused strong inflammation in several organs. Notably, meningitis and encephalitis were observed in the cerebral cortex and cerebellum in all monkeys, independently of the outcome. Due to their apparently high pathogenicity, emerging strains from lineage VII should be considered in preclinical vaccine testing. Lineage II would also be beneficial in pathogenesis studies to study the entire spectrum of Lassa fever severity.
Published: 2022

15. Cerebellar signals drive motor adjustments and visual perceptual changes during forward and backward adaptation of reactive saccades

Author: Alexis Cheviet, Jana Masselink, Eric Koun, Roméo Salemme, Markus Lappe, Caroline Froment-Tilikete, Denis Pélisson, Integrative Multisensory Perception, Action and Cognition (IMPACT), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Hospices Civils de Lyon (HCL), and Pelisson, Denis
Subjects: Cellular and Molecular Neuroscience, Trans-saccadic perception, [SCCO.NEUR]Cognitive science/Neuroscience, Cerebellum, Cognitive Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Saccades, Corollary discharge, Humans, Saccadic adaptation, Visuo-spatial representation, Adaptation, Physiological
Abstract: Saccadic adaptation ($SA$) is a cerebellar-dependent learning of motor commands ($MC$), which aims at preserving saccade accuracy. Since $SA$ alters visual localization during fixation and even more so across saccades, it could also involve changes of target and/or saccade visuospatial representations, the latter ($CDv$) resulting from a motor-to-visual transformation (forward dynamics model) of the corollary discharge of the $MC$. In the present study, we investigated if, in addition to its established role in adaptive adjustment of $MC$, the cerebellum could contribute to the adaptation-associated perceptual changes. Transfer of backward and forward adaptation to spatial perceptual performance (during ocular fixation and trans-saccadically) was assessed in eight cerebellar patients and eight healthy volunteers. In healthy participants, both types of $SA$ altered $MC$ as well as internal representations of the saccade target and of the saccadic eye displacement. In patients, adaptation-related adjustments of $MC$ and adaptation transfer to localization were strongly reduced relative to healthy participants, unraveling abnormal adaptation-related changes of target and $CDv$. Importantly, the estimated changes of $CDv$ were totally abolished following forward session but mainly preserved in backward session, suggesting that an internal model ensuring trans-saccadic localization could be located in the adaptation-related cerebellar networks or in downstream networks, respectively.
Published: 2022

16. Charge detection mass spectrometry on human-amplified fibrils from different synucleinopathies

Author: Aikaterini Tsirkou, Flora Kaczorowski, Mathieu Verdurand, Rana Raffoul, Jonathan Pansieri, Isabelle Quadrio, Fabien Chauveau, Rodolphe Antoine, Spectrométrie des biomolécules et agrégats (SPECTROBIO), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Radiopharmaceutical and Neurochemical Biomarkers (BIORAN), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nuffield Department of Clinical Neurosciences [Oxford], University of Oxford, and VIDAL, Armelle
Subjects: Amyloid, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, Synucleinopathies, Metals and Alloys, Brain, Parkinson Disease, General Chemistry, Mass Spectrometry, Catalysis, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Protein Aggregates, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, alpha-Synuclein, Materials Chemistry, Ceramics and Composites, Humans, [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]
Abstract: International audience; Amyloid fibrils are self-assembled mesoscopic protein aggregates, which can accumulate to form deposits or plaques in the brain. In vitro amplification of fibrils can be achieved with real-time quaking-induced conversion (RT-QuIC). However, this emerging technique would benefit from a complementary method to assess structural properties of the amplification products. This work demonstrates the feasibility of nanospray-charge-detection-mass-spectrometry (CDMS) performed on α-synuclein (αSyn) fibrils amplified from human brains with Parkinson's disease (PD) or Dementia with Lewy bodies (DLB) and its synergistic combination with RT-QuIC.
Published: 2022

17. EMDR for symptoms of depression, stress and burnout in health care workers exposed to COVID-19 (HARD): A study protocol for a trial within a cohort study

Author: Agnès Caille, Aude Allemang-Trivalle, Myriam Blanchin, Anne Rebion, Anne Sauvaget, Bénédicte Gohier, Philippe Birmes, Eric Bui, Eric Fakra, Marie-Odile Krebs, Cédric Lemogne, Nathalie Prieto, Isabelle Jalenques, Pierre Vidailhet, Bruno Aouizerate, Coraline Hingray, Wissam El-Hage, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), 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), MIP UR 4334 - T2 - Coordinations motrices (MIP T2), Motricité, interactions, performance UR 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Nantes Université - UFR des Sciences et Techniques des Activités Physiques et Sportives (Nantes Univ - UFR STAPS), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Le Mans Université (UM)-Nantes Université - UFR des Sciences et Techniques des Activités Physiques et Sportives (Nantes Univ - UFR STAPS), Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Nantes Université - UFR Lettres et Langages (Nantes Univ - UFR LL), Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Humanités, Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Massachusetts General Hospital [Boston], Université de Caen Normandie (UNICAEN), Normandie Université (NU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Psychiatric Disorders, Neuroscience Research and Clinical Research (PSYR2), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Jean Monnet - Saint-Étienne (UJM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Psychiatrie de l'Adulte A [CHU Clermont-Ferrand], CHU Clermont-Ferrand, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Fondation FondaMental [Créteil], 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, Centre hospitalier Charles Perrens [Bordeaux], Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Psychothérapique de Nancy [Laxou] (CPN), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), and Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: trial within a cohort study, stress, burnout, [SDV]Life Sciences [q-bio], depression, COVID-19, EMDR, health care workers, study protocol, TwiC
Abstract: Background: Stressful events during a pandemic are a major cause of serious health problems, such as burnout, depression and posttraumatic stress disorder (PTSD) among health care workers (HCWs). During three years, HCWs, on the frontline to fight the COVID-19 pandemic, have been at an increased risk of high levels of stress, anxiety, depression, burnout and PTSD. Regarding potential psychological interventions, Eye Movement Desensitization & Reprocessing (EMDR) is a structured, strongly recommended therapy based on its well-known efficacy in reducing PTSD symptoms and anxiety. Objectives: This study, designed as a trial within a cohort (TwiC), aims to 1) estimate the prevalence of depression, burnout and PTSD in a sample of HCWs after experiencing the COVID-19 emergency (cohort part) and 2) assess the efficacy and acceptability of 'EMDR + usual care' for HCWs from the cohort who report significant psychological symptoms (trial part). Methods: The study, designed as a TwiC, consists of a prospective cohort study (n = 3000) with an embedded, pragmatic, randomized open-label superiority trial with two groups (n = 900). Participants included in the trial part are HCWs recruited for the cohort with significant symptoms on at least one psychological dimension (depression, burnout, PTSD) at baseline, 3 months or 6 months, determined by using the Patient Health Questionnaire (PHQ-9), Professional Quality of Life (ProQOL) scale, and PTSD Checklist for the DSM-5 (PCL-5). The intervention consists of 12 separate EMDR sessions with a certified therapist. The control group receives usual care. The trial has three primary outcomes: changes in depression, burnout and PTSD scores from randomization to 6 months. All participants are followed up for 12 months. Conclusions: This study provides empirical evidence about the impact of the COVID-19 pandemic and the mental health burden it places on HCWs and assesses the effectiveness of EMDR as a psychological intervention. Trial registration NCT04570202
Published: 2023

18. Effects of discontinuous blue light stimulation on the electrophysiological properties of neurons lacking opsin expression in vitro: Implications for optogenetic experiments

Author: Anistasha Lightning, Marie Bourzeix, Corinne Beurrier, Nicola Kuczewski, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Neurobiology and Plasticity of Olfactory Perception (NEUROPOP), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: General Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, neurons, patch-clamp, heat production, optogenetics, optogenetics patch-clamp heat production neurons
Abstract: International audience
Published: 2023

19. The Activation of the RIG-I/MDA5 Signaling Pathway upon Influenza D Virus Infection Impairs the Pulmonary Proinflammatory Response Triggered by Mycoplasma bovis Superinfection

Author: Maria Gaudino, Adrien Lion, Eveline Sagné, Brandy Nagamine, Justine Oliva, Olivier Terrier, Elisabeth Errazuriz-Cerda, Anaëlle Scribe, Fatima-Zohra Sikht, Elisa Simon, Charlotte Foret-Lucas, Blandine Gausserès, Julie Lion, Ana Moreno, Emilie Dordet-Frisoni, Eric Baranowski, Romain Volmer, Mariette F. Ducatez, Gilles Meyer, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna 'Bruno Ubertini' (IZSLER), Innovations Thérapeutiques et Résistances (InTheRes), This study was funded by the by the Ecole Nationale Veterinaire de Toulouse (ENVT), project BQR-2020-ANIMEX, and the ICRAD-ERA NET cofund ANR-21-ICRD-0007, 'Deciphering the role of influenza D virus in bovine and human respiratory diseases in Europe.' Maria Gaudino was supported by a Ph.D. scholarship funded by the Departement Sante Animale (INRAE Toulouse) and the Region Occitanie. Maria Gaudino, Adrien Lion, Justine Oliva, Olivier Terrier, Fatima-Zohra Sikht, Romain Volmer, Gilles Meyer, and Mariette F. Ducatez are members of the French research network on influenza viruses (ResaFlu, GDR2073) financed by the CNRS., and ANR-21-ICRD-0007,PREVENTER,Deciphering the role of influenza D virus in bovine and human respiratory diseases in Europe(2021)
Subjects: coinfections, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, PCLS, cattle, Virology, Insect Science, respiratory viruses, Immunology, ex vivo, precision-cut lung slices, mycoplasma, influenza, Microbiology
Abstract: International audience; Concurrent infections with multiple pathogens are often described in cattle with respiratory illness. However, how the host-pathogen interactions influence the clinical outcome has been only partially explored in this species. Influenza D virus (IDV) was discovered in 2011. Since then, IDV has been detected worldwide in different hosts. A significant association between IDV and bacterial pathogens in sick cattle was shown in epidemiological studies, especially with Mycoplasma bovis. In an experimental challenge, IDV aggravated M. bovis-induced pneumonia. However, the mechanisms through which IDV drives an increased susceptibility to bacterial superinfections remain unknown. Here, we used the organotypic lung model precision-cut lung slices to study the interplay between IDV and M. bovis coinfection. Our results show that a primary IDV infection promotes M. bovis superinfection by increasing the bacterial replication and the ultrastructural damages in lung pneumocytes. In our model, IDV impaired the innate immune response triggered by M. bovis by decreasing the expression of several proinflammatory cytokines and chemokines that are important for immune cell recruitment and the bacterial clearance. Stimulations with agonists of cytosolic helicases and Toll-like receptors (TLRs) revealed that a primary activation of RIG-I/MDA5 desensitizes the TLR2 activation, similar to what was observed with IDV infection. The cross talk between these two pattern recognition receptors leads to a nonadditive response, which alters the TLR2-mediated cascade that controls the bacterial infection. These results highlight innate immune mechanisms that were not described for cattle so far and improve our understanding of the bovine host-microbe interactions and IDV pathogenesis.IMPORTANCE: Since the spread of the respiratory influenza D virus (IDV) infection to the cattle population, the question about the impact of this virus on bovine respiratory disease (BRD) remains still unanswered. Animals affected by BRD are often coinfected with multiple pathogens, especially viruses and bacteria. In particular, viruses are suspected to enhance secondary bacterial superinfections. Here, we use an ex vivo model of lung tissue to study the effects of IDV infection on bacterial superinfections. Our results show that IDV increases the susceptibility to the respiratory pathogen Mycoplasma bovis. In particular, IDV seems to activate immune pathways that inhibit the innate immune response against the bacteria. This may allow M. bovis to increase its proliferation and to delay its clearance from lung tissue. These results suggest that IDV could have a negative impact on the respiratory pathology of cattle.
Published: 2023

20. Hepatitis D virus interferes with hepatitis B virus RNA production via interferon-dependent and -independent mechanisms

Author: Julie Lucifora, Dulce Alfaiate, Caroline Pons, Maud Michelet, Ricardo Ramirez, Floriane Fusil, Fouzia Amirache, Axel Rossi, Anne-Flore Legrand, Emilie Charles, Serena Vegna, Rayan Farhat, Michel Rivoire, Guillaume Passot, Nicolas Gadot, Barbara Testoni, Charlotte Bach, Thomas F. Baumert, Anastasia Hyrina, Rudolf K. Beran, Fabien Zoulim, Andre Boonstra, Hildegard Büning, Eloi R. Verrier, François-Loïc Cosset, Simon P. Fletcher, Anna Salvetti, David Durantel, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Gilead Sciences, Inc. [Foster City, CA, USA], Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institute of Experimental Hematology [Hannover, Germany], Hannover Medical School [Hannover] (MHH), Application des ultrasons à la thérapie (LabTAU), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre pour l'innovation en cancérologie de Lyon (CICLY), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre Léon Bérard [Lyon], Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Croix-Rousse [CHU - HCL], Gastroenterology and Hepatology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), and Gastroenterology & Hepatology
Subjects: Hepatology, SDG 3 - Good Health and Well-being, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Sciences du Vivant [q-bio]/Médecine humaine et pathologie
Abstract: Background & Aims: Chronic coinfection with HBV and HDV leads to the most aggressive form of chronic viral hepatitis. Herein, we aimed to elucidate the molecular mechanisms underlying the widely reported observation that HDV interferes with HBV in most coinfected patients. Methods: Patient liver tissues, primary human hepatocytes, HepaRG cells and human liver chimeric mice were used to analyze the effect of HDV on HBV using virological and RNA-sequencing analyses, as well as RNA synthesis, stability and association assays. Results: Transcriptomic analyses in cell culture and mouse models of coinfection enabled us to define an HDV-induced signature, mainly composed of interferon (IFN)-stimulated genes (ISGs). We also provide evidence that ISGs are upregulated in chronically HDV/HBV-coinfected patients but not in cells that only express HDV antigen (HDAg). Inhibition of the hepatocyte IFN response partially rescued the levels of HBV parameters. We observed less HBV RNA synthesis upon HDV infection or HDV protein expression. Additionally, HDV infection or expression of HDAg alone specifically accelerated the decay of HBV RNA, and HDAg was associated with HBV RNAs. On the contrary, HDAg expression did not affect other viruses such as HCV or SARS-CoV-2. Conclusions: Our data indicate that HDV interferes with HBV through both IFN-dependent and IFN-independent mechanisms. Specifically, we uncover a new viral interference mechanism in which proteins of a satellite virus affect the RNA production of its helper virus. Exploiting these findings could pave the way to the development of new therapeutic strategies against HBV. Impact and implications: Although the molecular mechanisms remained unexplored, it has long been known that despite its dependency, HDV decreases HBV viremia in patients. Herein, using in vitro and in vivo models, we showed that HDV interferes with HBV through both IFN-dependent and IFN-independent mechanisms affecting HBV RNA metabolism, and we defined the HDV-induced modulation signature. The mechanisms we uncovered could pave the way for the development of new therapeutic strategies against HBV by mimicking and/or increasing the effect of HDAg on HBV RNA. Additionally, the HDV-induced modulation signature could potentially be correlated with responsiveness to IFN-α treatment, thereby helping to guide management of HBV/HDV-coinfected patients.
Published: 2023

21. Clinical features and outcomes of COVID-19 patients hospitalized for psychiatric disorders: a French multi-centered prospective observational study

Author: Claire Jansen, Pierre Thomas, Djamila Bennabi, Dominique Drapier, Thomas Schwitzer, Delphine Capdevielle, Noe Teboul, Pascal Delamillieure, Emmanuelle Corruble, Christophe Schmitt, Daniela Dobre, Olivier C. Martin, Pierre Abdel Ahad, Antoine Pelissolo, Clément Vansteene, Benjamin Rolland, Marion Leboyer, Raymund Schwan, Fabienne Ligier, Wanda Yekhlef, Antoine Yrondi, Raphaël Gaillard, William Lecoeur, Radoine Haoui, Mathilde Roser, Vincent Laprevote, Catherine Massoubre, Sonia Dollfus, Fabien Joubert, Philip Gorwood, 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, Centre Psychothérapique de Nancy [Laxou] (CPN), Faculté de Médecine [Nancy], Université de Lorraine (UL), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), GHU Paris Psychiatrie et Neurosciences, 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), Département de psychiatrie adulte, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital La Colombière, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Imagerie et Stratégies Thérapeutiques de la Schizophrénie (ISTS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier le Vinatier [Bron], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), 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), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Hôpital Sainte-Anne-Université Paris Cité (UPCité), Service Psychiatrie et psychologie médicale [CHU Toulouse], Pôle Psychiatrie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Gérard Marchant, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Psychiatrie et Neurosciences (U894), Centre Psychothérapique de Nancy (CPN), Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, HAL UR1, Admin, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Universitaire d’Addictologie de Lyon [CH Le Vinatier, Bron] (Pôle MOPHA - SUAL), 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), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Etablissement Public de Santé Alsace Nord, Partenaires INRAE, Hôpital Sainte-Anne-Université de Paris (UP), Etablissement public de santé de Ville-Evrard (EPS), Service Psychiatrie et psychologie médicale [CHU Purpan], CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Population, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Confusional state, Logistic regression, Lower risk, 03 medical and health sciences, 0302 clinical medicine, Organic mental disorders, Intensive care, medicine, Psychiatry, Prospective cohort study, education, Applied Psychology, Univariate analysis, education.field_of_study, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, Medical record, COVID-19, Odds ratio, medicine.disease, Mental health, Confidence interval, 030227 psychiatry, 3. Good health, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Original Article, Observational study, business, 030217 neurology & neurosurgery
Abstract: Background: At the beginning of COVID-19 pandemic, specific COVID/PSY wards were created in France to provide care for inpatients with COVID-19 and psychiatric disorders. In this multi-center prospective study, we set out to assess the clinical features and risk factors of somatic aggravation in patients hospitalized in COVID/PSY wards. Methods: Data were collected between 28 February and 30 May, 2020. We collected demographic data, psychiatric diagnoses, medical data and COVID-19-related clinical data. Somatic aggravation was estimated by the number of patients transferred to intensive care or medicine units, the number of deaths and the number of patients presenting a confusional state. A multivariate logistic model was used to assess the risk factors of confusional state and transfer to intensive care or medicine units. The risk of death was analysed by the univariate predictors of this outcome. Outcomes: 350 patients were included in the study. The number of inclusions peaked one week after that of the general population and declined more slowly. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit (OR 17.1; CI 4.9-59.3). Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age > 55 (OR 4.9; CI 2.1-11.4), an affective disorder (OR 4.1; CI 1.6-10.9), and severe respiratory symptoms (OR 4.6; CI 2.2-9.7) predicted a higher risk, while smoking (OR 0.3; CI 0.1-0.9) predicted a lower risk of a confusional state. Interpretation: COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and a high risk of confusion. COVID/PSY wards may play a role in reducing the mortality of COVID-19 in patients with psychiatric disorders. Funding Statement: There was no funding source for this study. Declaration of Interests: There are no conflicts of interest to be declared. Ethics Approval Statement: This observational study was conducted according to the principles of the Declaration of Helsinki. In accordance with French bioethics laws, it was classified as a non- interventional study, since it concerned anonymized clinical data that are routinely compiled in medical records. Compliance with French regulations on personal data collection was supervised by the personal data referent of the Centre Psychotherapique de Nancy. Patients, and their legal guardian when appropriate, were informed in writing, in agreement with national regulations for observational studies.
Published: 2023

22. Comparative study of GBP recruitment on two cytosol-dwelling pathogens, Francisella novicida and Shigella flexneri highlights differences in GBP repertoire and in GBP1 motif requirements

Author: Stanimira V Valeva, Manon Degabriel, Fanny Michal, Gabrielle Gay, John R Rohde, Felix Randow, Brice Lagrange, Thomas Henry, Inflammasome, Infections bactériennes et autoinflammation, Inflammasome, Bacterial Infections and Autoinflammation (I2BA), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Microbiology (medical), Infectious Diseases, General Immunology and Microbiology, [SDV]Life Sciences [q-bio], Immunology and Allergy, General Medicine
Abstract: Guanylate-Binding Proteins are interferon-inducible GTPases that play a key role in cell autonomous responses against intracellular pathogens. Despite sharing high sequence similarity, subtle differences among GBPs translate into functional divergences that are still largely not understood. A key GBP feature is the formation of supramolecular GBP complexes on the bacterial surface. Such complexes are observed when GBP1 binds lipopolysaccharide (LPS) from Shigella and Salmonella and further recruits GBP2-4. Here, we compared GBP recruitment on two cytosol-dwelling pathogens, Francisella novicida and S. flexneri. Francisella novicida was coated by GBP1 and GBP2 and to a lower extent by GBP4 in human macrophages. Contrary to S. flexneri, F. novicida was not targeted by GBP3, a feature independent of T6SS effectors. Multiple GBP1 features were required to promote targeting to F. novicida while GBP1 targeting to S. flexneri was much more permissive to GBP1 mutagenesis suggesting that GBP1 has multiple domains that cooperate to recognize F. novicida atypical LPS. Altogether our results indicate that the repertoire of GBPs recruited onto specific bacteria is dictated by GBP-specific features and by specific bacterial factors that remain to be identified.
Published: 2023

23. A MOPEVAC multivalent vaccine induces sterile protection against New World arenaviruses in non-human primates

Author: Stéphanie Reynard, Xavier Carnec, Caroline Picard, Virginie Borges-Cardoso, Alexandra Journeaux, Mathieu Mateo, Clara Germain, Jimmy Hortion, Laure Albrecht, Emeline Perthame, Natalia Pietrosemoli, Audrey Vallvé, Stéphane Barron, Aurélie Duthey, Orianne Lacroix, Ophélie Jourjon, Marie Moroso, Lyne Fellmann, Pierre-Henri Moreau, Maïlys Daniau, Catherine Legras-Lachuer, Manon Dirheimer, Caroline Carbonnelle, Hervé Raoul, Sylvain Baize, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire P4 - Jean Mérieux, Centre Européen de Virologie/Immunologie-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA), ViroScan3D SAS [Trévoux, France], Délégation régionale Auvergne Rhône-Alpes [Bron, France], and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Microbiology (medical), Antibodies Neutralizing, Arenaviruses New World, [SDV]Life Sciences [q-bio], Immunology, Vaccines Combined, Cell Biology, Applied Microbiology and Biotechnology, Microbiology, Macaca fascicularis, Genetics, Animals, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Glycoproteins
Abstract: International audience; Pathogenic New World arenaviruses (NWAs) cause haemorrhagic fevers and can have high mortality rates, as shown in outbreaks in South America. Neutralizing antibodies (Abs) are critical for protection from NWAs. Having shown that the MOPEVAC vaccine, based on a hyperattenuated arenavirus, induces neutralizing Abs against Lassa fever, we hypothesized that expression of NWA glycoproteins in this platform might protect against NWAs. Cynomolgus monkeys immunized with MOPEVACMAC, targeting Machupo virus, prevented the lethality of this virus and induced partially NWA cross-reactive neutralizing Abs. We then developed the pentavalent MOPEVACNEW vaccine, expressing glycoproteins from all pathogenic South American NWAs. Immunization of cynomolgus monkeys with MOPEVACNEW induced neutralizing Abs against five NWAs, strong innate followed by adaptive immune responses as detected by transcriptomics and provided sterile protection against Machupo virus and the genetically distant Guanarito virus. MOPEVACNEW may thus be efficient to protect against existing and potentially emerging NWAs.
Published: 2023

24. The smell of cooperativeness: Do human body odours advertise cooperative behaviours?

Author: Arnaud Tognetti, Valerie Durand, Dimitri Dubois, Melissa Barkat‐Defradas, Astrid Hopfensitz, Camille Ferdenzi, Karolinska Institutet [Stockholm], Institute for Advanced Study in Toulouse (IAST), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Centre d'Economie de l'Environnement - Montpellier (CEE-M), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-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), Groupe d'analyse et de théorie économique (GATE Lyon Saint-Étienne), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-15-CE33-0005,SINT,L'intelligence sociale: experiences et théories concernant les agents économiques(2015), emlyon business school (EM), 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), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, 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 Montpellier (UM), Groupe d'Analyse et de Théorie Economique Lyon - Saint-Etienne (GATE Lyon Saint-Étienne), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), PEPS CNRS HomoVox, ANR-11-LABX-0042,CORTEX,Construction, Fonction Cognitive et Réhabilitation du Cerveau(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), business school, emlyon, L'intelligence sociale: experiences et théories concernant les agents économiques - - SINT2015 - ANR-15-CE33-0005 - AAPG2015 - VALID, Construction, Fonction Cognitive et Réhabilitation du Cerveau - - CORTEX2011 - ANR-11-LABX-0042 - LABX - VALID, PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Centre d'Economie de l'Environnement - Montpellier - UMR 5211 (CEE-M), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Centre de recherche en neurosciences de Lyon (CRNL), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Body Odor, chemosensory cues, economic games, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, genetic structures, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, [SHS]Humanities and Social Sciences, Smell, Odorants, parasitic diseases, partner choice, Humans, [SHS.GESTION]Humanities and Social Sciences/Business administration, Female, body odours, Cooperative Behavior, Cues, [SHS.GESTION] Humanities and Social Sciences/Business administration, psychological phenomena and processes, General Psychology
Abstract: International audience; Several physical features influence the perception of how cooperative a potential partner is. While previous work focused on face and voice, it remains unknown whether body odours influence judgements of cooperativeness and if odour-based judgements are accurate. Here, we first collected axillary odours of cooperative and uncooperative male donors through a public good game and used them as olfactory stimuli in a series of tasks examining whether and how they influence cooperative decision-making in an incentivized economic game and ratings of cooperativeness. Our results show that having access to the donor's body odours provided a strategic advantage to women during economic decisions (but not to men): with age, women were more likely to cooperate with cooperative men and to avoid interacting with uncooperative men. Ratings of cooperativeness were nonetheless unrelated to the donors’ actual cooperativeness. Finally, while men with masculine and intense body odours were judged less cooperative, we found no evidence that donors’ actual cooperativeness was associated with less masculine or less intense body odour. Overall, our findings suggest that, as faces and voices, body odours influence perceived cooperativeness and might be used accurately and in a non-aware manner as olfactory cues of cooperativeness, at least by women.
Published: 2021

25. Human physiology adaptation to altered gravity environments

Author: Gilles Clément, Andrew P. Blaber, Olivier White, Jack J. W. A. van Loon, Nandu Goswami, Joyce M. Evans, Medical University Graz, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon Fraser University (SFU.ca), University of Kentucky (UK), Vrije Universiteit Amsterdam [Amsterdam] (VU), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Clement, Gilles, University of Kentucky, Centre de recherche en neurosciences de Lyon (CRNL), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Gravity (chemistry), [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Computer science, Aerospace Engineering, Hypergravity, Spaceflight, law.invention, Gravitation, [SCCO]Cognitive science, 03 medical and health sciences, 0302 clinical medicine, law, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Hypogravity, 030304 developmental biology, Cognitive science, 0303 health sciences, [SCCO] Cognitive science, Human physiology, Deconditioning, Artificial gravity, Sex, Microgravity, Adaptation, Centrifuge, 030217 neurology & neurosurgery
Abstract: International audience; Multiple transitions between gravity levels will occur during planetary exploration missions. In reaction to these gravitational transitions, physiological adaptation will be initiated. However, the physiological effects of longduration exposures to hypogravity and hypergravity are poorly understood. In this review we present an overview of how humans perceive gravity, review sex-based differences in adaptation to changes in gravity, and introduces rather limited evidence currently available related to the effects of partial gravity. The paper then argues that there is a need for more research to better understand the extent and dynamics of physiological adaptation mechanisms during gravity level transitions in spaceflight and proposes a need for artificial gravity (AG) as a multi-system countermeasure and explore the efficacy of AG as countermeasure between short and very long-arm centrifuges. Discussed here are the effects of acute short-arm AG application. The topical review also discusses the usage of chronic AG application via the innovative large-radius Hypergravity Human Habitat, H 3 , concept.
Published: 2021

26. Improvement of Insight with Non-Invasive Brain Stimulation in Patients with Schizophrenia: A Systematic Review

Author: Martin Blay, Ondine Adam, Rémy Bation, Filipe Galvao, Jérôme Brunelin, Marine Mondino, Centre Hospitalier le Vinatier [Bron], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Psychiatric Disorders, Neuroscience Research and Clinical Research (PSYR2), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), and MONDINO, Marine
Subjects: illness awareness, transcranial alternating current stimulation, transcranial random-noise stimulation, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, transcranial electrical stimulation, General Medicine, Review, electroconvulsive therapy, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, neuromodulation, transcranial magnetic stimulation, Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], transcranial direct current stimulation
Abstract: International audience; Patients with schizophrenia are often unaware of their condition and the consequences of their illness. This lack of insight results in impaired functioning, treatment non-adherence and poor prognosis. Here, we aimed to investigate the effects of non-invasive brain stimulation (NIBS) on two forms of insight, clinical and cognitive, in patients with schizophrenia. We conducted a systematic review of the literature registered in the PROSPERO database (CRD42020220323) according to PRISMA guidelines. The literature search was conducted in Medline and Web of Science databases based on studies published up until October 2020 that included pre-NIBS and post-NIBS measurements of clinical and/or cognitive insight in adults with schizophrenia. A total of 14 studies were finally included, and their methodological quality was assessed by using the QualSyst tool. Despite the lack of well-conducted large randomized-controlled studies using insight as the primary outcome, the available findings provide preliminary evidence that NIBS can improve clinical insight in patients with schizophrenia, with a majority of studies using transcranial direct current stimulation with a left frontotemporal montage. Further studies should investigate the effect of NIBS on insight as a primary outcome and how these effects on insight could translate into clinical and functional benefits in patients with schizophrenia.
Published: 2022

27. Glial Fibrillary Acidic Protein Autoimmunity

Author: Daniela Molinier-Tiganas, Jonathan Biberon, Quentin Bodard, Véronique Rogemond, Anne Ruiz, Bastien Bouldoires, Celine Derollez, Philippe Diraison, Daniela Andriuta, Alberto Vogrig, Amelie Leblanc, Thomas De Broucker, Aditya Ambati, Philippe Kerschen, Géraldine Picard, Thierry Tchoumi, Eve Chanson, Anne-Laure Kaminsky, Irina Grigorashvili-Coin, Clementine Fort, Fanny Duval, Roxana Genet, Jérôme Honnorat, Kumaran Deiva, Sergio Muñiz-Castrillo, Mathilde Goudot, Bastien Joubert, François Sellal, Gabriel Mirebeau, Anais Dutray, Marion Philbert, Guillaume Rieul, Véronique Bourg, Erwan Morvan, Jonathan Ciron, Adrien Bigot, Romain Marignier, Roxana Ameli, Lucie Hopes, Jean Louis Devoize, Nahema Issa, Mickael Bonnan, Elena-Camelia Rusu, Laurent Kremer, Florence Rulquin, Alice Gravier Dumonceau, Marie Benaiteau, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Institut NeuroMyoGène (INMG), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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), Centre de Référence Maladie Rare 'Syndromes neurologiques Paranéoplasiques', Hospices Civils de Lyon (HCL)-Hopital Neurologique, CHU Toulouse [Toulouse], Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Le Kremlin Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Excitabilité nerveuse et thérapeutique (ENT), Hôpital Henri Mondor-EA 4391, Service de Physiologie Explorations Fonctionnelles-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpitaux Civils de Colmar, Centre Psychothérapique de Nancy [Laxou] (CPN), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe hospitalier Pellegrin, CHU Bordeaux [Bordeaux], Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Saint Jean de Perpignan, Centre Hospitalier d'Angoulême (CH Angoulême), Université des Antilles - UFR des sciences médicales Hyacinthe Bastaraud (UA UFR SM), Université des Antilles (UA), CHU Clermont-Ferrand, Service de Neurologie [Brest], Hôpital d'Instruction des Armées 'Clermont-Tonnerre' (HIA), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de neurologie [Amiens], CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hôpital Pasteur [Nice] (CHU), CHU de Saint-Brieuc, CHU Pau, Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Université Grenoble Alpes (UGA), and ANR-18-RHUS-0012,BETPSY,Biomarkers in autoimmune EncephaliTis and Paraneoplastic neurological SYndromes(2018)
Subjects: Adult, Male, Pathology, medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Myelitis, Autoimmunity, Autoimmune Diseases, Cohort Studies, Autoimmune Diseases of the Nervous System, Cerebrospinal fluid, Glial Fibrillary Acidic Protein, medicine, Humans, Child, Autoantibodies, Retrospective Studies, biology, Glial fibrillary acidic protein, business.industry, Autoantibody, Meningoencephalitis, medicine.disease, Hyperintensity, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunohistochemistry, Neurology (clinical), Antibody, business
Abstract: Background and ObjectivesTo report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies.MethodsWe retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα since 2017 from 2 French referral centers.ResultsWe identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score ≤2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies.DiscussionGFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome.
Published: 2021

28. AN EARLY 3D‐MAP OF A TERRITORY? THE BRONZE AGE CARVED SLAB FROM SAINT‐BÉLEC, LEUHAN (BRITTANY, FRANCE)

Author: Laurent Aubry, Bernard Le Gall, Julie Pierson, Joël Rolet, Yvan Pailler, Pierre Stéphan, Clement Nicolas, Vincent Lacombe, Trajectoires - UMR 8215, Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Littoral, Environnement, Télédétection, Géomatique UMR 6554 (LETG), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université d'Angers (UA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire Géosciences Océan (LGO), Université de Brest (UBO)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Institut Français de Recherche pour l'Exploitation de la Mer - Brest (IFREMER Centre de Bretagne), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Bournemouth University [Poole] (BU), Centre National de la Recherche Scientifique (CNRS), Institut national de recherches archéologiques préventives - Centre de recherches archéologiques de Cesson-Sévigné (Inrap, Cesson-Sévigné), Institut national de recherches archéologiques préventives (Inrap), Université de Bretagne Occidentale - UFR Sciences et Techniques (UBO UFR ST), Université de Brest (UBO), Littoral, Environnement, Télédétection, Géomatique (LETG - Brest), Université de Brest (UBO)-Université de Rennes 2 (UR2)-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)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université (Nantes Univ)-Littoral, Environnement, Télédétection, Géomatique UMR 6554 (LETG), Université de Brest (UBO)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (Nantes Univ - IGARUN), Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (Nantes Univ - IGARUN), Nantes Université (Nantes Univ), Evaluating, understanding, supporting motor, perceptive and social Trajectories (TRAJECTOIRES), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Geo-Ocean (GEO-OCEAN), Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), DigiSCAN 3D, UMR 8215 Trajectoires (dir. O. Weller, CNRS)UMR 6554 LETG (dir. F. Gourmelon, CNRS)Collective Research Program ‘Éléments pour une nouvelle approche de l’âge du Bronze en Bretagne’ (dir. S. Blanchet,Inrap/DRAC Bretagne)Bournemouth University, and European Project: 841128,WATCH
Subjects: Bronze Age, 010506 paleontology, Archeology, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Planimetry, Geography, Planning and Development, Context (language use), 01 natural sciences, Prehistory, Arts and Humanities (miscellaneous), Brittany, Early world maps, Rock art, 0601 history and archaeology, Territorialisation, 0105 earth and related environmental sciences, Carving, 060102 archaeology, Spatial Analyses, SAINT, [SHS.GEO]Humanities and Social Sciences/Geography, 06 humanities and the arts, Archaeology, Geography, Slab, Spatial extent
Abstract: International audience; While early maps are known from all over the world, the key questions always involve: what exactly do they show? And what spatial extent do they cover? In this context, we recently used 3D-modelling to re-examine a carved stone slab datable to the Early Bronze Age (c.2150–1600 BC) that was found at Saint-Bélec in Brittany. We show that the surface of the slab had been shaped in three dimensions to represent the relief of the surrounding landscape in which it was found, while several engraved motifs on it evoke contemporary structures known archaeologically. We argue that the Saint-Bélec slab represents an area of c.545 km2 corresponding to the extent of a prehistoric political entity. The carving and subsequent burying of the slab can be linked to the postulated rise and fall of hierarchical societies and raises many wider questions about socio-economic structures in temperate Europe at that time.
Published: 2021

29. Detection of SARS‐CoV‐2 in two cats during the second wave of the COVID‐19 pandemic in France

Author: Nicolas Nesi, Meriadeg Ar Gouilh, Vincent Legros, Solène Denolly, Eric M. Leroy, Bertrand Boson, Alexandra Briend-Marchal, Serge G. Rosolen, Matthieu Fritz, 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]), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Clinique Vétérinaire Voltaire, Vebiotel - Laboratoire de Biologie Vétérinaire, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), French National Agency for Research : ANR-RA-COVID-19 (Geographical and temporal serological investigation of companion animal infection with SARS-CoV-2 during the second wave of COVID-19 in France, CoVet), IDEXLYON project of Université de Lyon as part of the 'Programme Investissements d’Avenir'. Grant Number: ANR-16-IDEX-0005, WHO throught the SARS-CoV-2 EvoZoone project, OIE through the European Union EBO-SURSY project, ANR-16-IDEX-0005,IDEXLYON,IDEXLYON(2016), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique et évolution des maladies infectieuses (GEMI), Gestionnaire, HAL Sorbonne Université 5, and IDEXLYON - - IDEXLYON2016 - ANR-16-IDEX-0005 - IDEX - VALID
Subjects: Coronavirus disease 2019 (COVID-19), Veterinary medicine, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), serology, mild‐respiratory clinical signs, Cat Diseases, SARS‐CoV‐2, Microsphere, Serology, 03 medical and health sciences, SF600-1100, Pandemic, Animals, Medicine, One Health, skin and connective tissue diseases, Pandemics, mild-respiratory clinical signs, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, CATS, General Veterinary, biology, medicine.diagnostic_test, SARS-CoV-2, 030306 microbiology, business.industry, cats, fungi, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, COVID-19, Original Articles, Virology, respiratory tract diseases, 3. Good health, body regions, NGS, Immunoassay, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Original Article, France, Antibody, business
Abstract: Although there are several reports in the literature of SARS‐CoV‐2 infection in cats, few SARS‐CoV‐2 sequences from infected cats have been published. In this study, SARS‐CoV‐2 infection was evaluated in two cats by clinical observation, molecular biology (qPCR and NGS), and serology (microsphere immunoassay and seroneutralization). Following the observation of symptomatic SARS‐CoV‐2 infection in two cats, infection status was confirmed by RT‐qPCR and, in one cat, serological analysis for antibodies against N‐protein and S‐protein, as well as neutralizing antibodies. Comparative analysis of five SARS‐CoV‐2 sequence fragments obtained from one of the cats showed that this infection was not with one of the three recently emerged variants of SARS‐CoV‐2. This study provides additional information on the clinical, molecular, and serological aspects of SARS‐CoV‐2 infection in cats., This study provides additional information on the clinical, molecular, and serological aspects of SARS‐CoV‐2 infection in cats.
Published: 2021

30. IL-33 drives polyfunctionality and antitumor activity of a unique ST2+ NK cell population

Author: Treilleux, Isabelle, MICHALLET, MARIE-CECILE, Valladeau-Guilemond, Jenny, Marçais, Antoine, Walzer, Thierry, Krebs, Philippe, Cerwenka, Adelheid, Hubert, Margaux, Caux, Christophe, Bendriss-Vermare, Nathalie, Département de Biopathologie, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Immunology and Microbial Science, The Scripps Research Institute [La Jolla, San Diego], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Schering-Plough Laboratories for Immunological Research, and Schering Plough Laboratories
Subjects: cancer immunosurveillance, cancer immunotherapy, IL-33, ST2/IL1RL1, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, NK cells, NK cells IL-33 ST2/IL1RL1 cancer immunosurveillance cancer immunotherapy, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
Abstract: ARTICLE EN REVISION FAVORABLE DANS SCIENCE IMMUNOLOGY; Natural Killer (NK) cell subsets differ to ensure complementary and crucial roles in tumor immunosurveillance. Their biology is critically regulated by cytokines. Here, we show that IL-33 synergizes with IL-12 to strongly activate a subset of CD56 dim NK cells acquiring ST2 expression. Transcriptomic and biological analysis of human ST2 + CD56 dim NK cells revealed a distinct intermediate differentiation state between canonical CD56 bright and CD56 dim NK cells, combining high proliferative properties, cytokines/chemokines production, and cytotoxicity. NK cells expressing ST2 protein or exhibiting a ST2-linked transcriptional signature were identified in human and mouse tumors. Accordingly, IL-12 unleashes human breast tumor ST2 + NK cell potential to produce IFN-γ in response to IL-33 and IL-33/IL-12 co-injection resulted in a NK-dependent IFN- secretion and anti-tumor effects in murine mammary tumors. An IL33 hi-NK hi score in solid tumors correlated with increased progressionfree patient survival. Our findings thus identify polyfunctional ST2 + NK cells which effector functions can be harnessed by IL-33 to boost anti-tumor immunity.
Published: 2022

31. Evidence of co-infections during Delta and Omicron SARS-CoV-2 variants co-circulation through prospective screening and sequencing

Author: Patricia, Combes, Maxime, Bisseux, Antonin, Bal, Pierre, Marin, Justine, Latour, Christine, Archimbaud, Amélie, Brebion, Hélène, Chabrolles, Christel, Regagnon, Jérémy, Lafolie, Gregory, Destras, Bruno, Simon, Jacques, Izopet, Laurence Josset, Cécile, Henquell, Audrey, Mirand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Thérapie ciblée combinatoire en Onco-Hématologie (EA3846), Université d'Auvergne - Clermont-Ferrand I (UdA), Service de Virologie Médicale et Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Université Clermont Auvergne, CNRS, LMGE, 63000 Clermont–Ferrand, France, Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Hôpital de la Croix-Rousse [CHU - HCL], Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire Microorganismes : Génome et Environnement (LMGE), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand] (3IHP ), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier de Vichy (CH Vichy), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Terrasol, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Microbiology (medical), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, Coinfection, Single nucleotide polymorphism screening, COVID-19, General Medicine, Recombination, SARS-CoV-2 co-infection, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Whole genome sequencing, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, Prospective Studies, Sequence Analysis, Delta and Omicron VOC
Abstract: International audience; Objectives: To describe Delta/Omicron SARS-CoV-2 variants co-infection detection and confirmation during the fifth wave of COVID-19 pandemics in France in 7 immunocompetent and epidemiologically unrelated patients.Methods: Since December 2021, the surveillance of Delta/Omicron SARS-CoV-2 variants of concern (VOC) circulation was performed through prospective screening of positive-samples using single nucleotide polymorphism (SNP) PCR assays targeting SARS-CoV-2 S-gene mutations K417N (Omicron specific) and L452R (Delta specific). Samples showing unexpected mutational profiles were further submitted to whole genome sequencing (WGS) using three different primer sets.Results: Between weeks 49-2021 and 02-2022, SARS-CoV-2 genome was detected in 3831 respiratory samples, of which 3237 (84.5%) were screened for VOC specific SNPs. Unexpected mutation profiles suggesting a dual Delta/Omicron population were observed in 7 nasopharyngeal samples (0.2%). These co-infections were confirmed by WGS. For 2 patients, the sequence analyses of longitudinal samples collected 7 to 11 days apart showed that Delta or Omicron can outcompete the other variant during dual infection. Additionally, for one of these samples, a recombination event between Delta and Omicron was detected.Conclusions: This work demonstrates that SARS-CoV-2 Delta/Omicron co-infections are not rare in high virus co-circulation periods. Moreover, co-infections can further lead to genetic recombination which may generate new chimeric variants with unpredictable epidemic or pathogenic properties that could represent a serious health threat.
Published: 2022

32. Adherence to opioid agonist therapy predicts uptake of direct-acting antivirals in people who use drugs: results from the French national healthcare database (the ANRS FANTASIO study)

Author: Benjamin Rolland, Caroline Lions, Vincent Di Beo, Patrizia Carrieri, Nicolas Authier, Tangui Barré, Jessica Delorme, Philippe Mathurin, François Bailly, Camelia Protopopescu, Fabienne Marcellin, Service Universitaire d’Addictologie de Lyon [CH Le Vinatier, Bron] (Pôle MOPHA - SUAL), Centre Hospitalier le Vinatier [Bron], Psychiatric Disorders, Neuroscience Research and Clinical Research (PSYR2), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hépatologie et d’addictologie [GH Nord, Lyon], HCL Groupement Hospitalier Nord [Lyon], Hôpital de la Croix-Rousse [CHU - HCL], and Hospices Civils de Lyon (HCL)
Subjects: Male, MESH: Antiviral Agents, [SDV]Life Sciences [q-bio], MESH: Delivery of Health Care, Medicine (miscellaneous), Hepacivirus, MESH: Analgesics, Opioid, Antiviral Agents, Humans, MESH: Hepacivirus, Drug use, DAA, MESH: Hepatitis C, MESH: Humans, Public Health, Environmental and Occupational Health, Hepatitis C, Chronic, Hepatitis C, MESH: Male, Buprenorphine, MESH: Hepatitis C, Chronic, Analgesics, Opioid, Psychiatry and Mental health, Female, Delivery of Health Care, MESH: Female, Methadone
Abstract: Background Opioid agonist therapy (OAT) is associated with reduced injection, reduced HCV transmission, and more opportunities to initiate hepatitis C virus (HCV) treatment in people who use drugs (PWUD). We aimed to study the extent to which adherence to OAT was predictive of increased uptake of direct-acting antivirals (DAA) in PWUD with chronic HCV infection. Methods Using the French national healthcare system database, we targeted PWUD (i.e. with a history of OAT) who had chronic HCV infection and were eligible for DAA during 2014–2016. Adherence to OAT was computed as a time-varying variable expressing the proportion of days covered by OAT receipt, over any six-month interval before DAA receipt. We used a Cox proportional hazards model to estimate the association between adherence to OAT and the rate of DAA uptake after adjustment for age, sex, alcohol use disorder, socioeconomic status, and liver disease severity. Results Among the 22,615 persons included in the ANRS FANTASIO study, 3438 (15.2%) initiated DAA during the study period. After multivariable adjustment, adherence to OAT was associated with a higher rate of DAA initiation. However, this association was not linear, and only individuals on OAT for 20% or more of the time in the previous six-month period had a higher rate of DAA initiation (adjusted hazard ratio [95% confidence interval]: 1.28 [1.18–1.38]). Other variables associated with DAA initiation were male sex, older age, cirrhosis or liver cancer, and higher socioeconomic status. Conclusions Adherence to OAT is a major predictor of DAA initiation in PWUD living with chronic HCV infection in France. Our results also suggest that even moderate adherence to OAT can facilitate DAA uptake. Adequate HCV training for OAT prescribers together with interventions to ensure adherence to OAT will help improve DAA initiation rates and reach HCV elimination goals.
Published: 2022

33. Lessons from the pandemic: Responding to emerging zoonotic viral diseases-a Keystone Symposia report

Author: Jennifer Cable, Anthony Fauci, William E. Dowling, Stephan Günther, Dennis A. Bente, Pragya Dhruv Yadav, Lawrence C. Madoff, Lin‐Fa Wang, Rahul K. Arora, Maria Van Kerkhove, May C. Chu, Thomas Jaenisch, Jonathan H. Epstein, Simon David William Frost, Daniel G. Bausch, Lisa E. Hensley, Éric Bergeron, Ioannis Sitaras, Michael D. Gunn, Thomas W. Geisbert, César Muñoz‐Fontela, Florian Krammer, Emmie de Wit, Pontus Nordenfelt, Erica Ollmann Saphire, Sarah C. Gilbert, Kizzmekia S. Corbett, Luis M. Branco, Sylvain Baize, Neeltje van Doremalen, Marco A. Krieger, Sue Ann Costa Clemens, Renske Hesselink, Dan Hartman, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Coalition for Epidemic Preparedness Innovations [Oslo] (CEPI), Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin [Hamburg, Germany] (BNITM), University of Texas Medical Branch at Galveston, California Institute of Technology (CALTECH), National Institute of Virology - National Influenza Center [Pune, India] (NIV), University of Massachusetts System (UMASS), Duke-NUS Medical School [Singapore], University of Calgary, University of Oxford, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Colorado Anschutz [Aurora], EcoHealth Alliance [New York], Microsoft Research [Redmond], Microsoft Corporation [Redmond, Wash.], Foundation for Innovative New Diagnostics (FIND), PREVAIL, Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Duke University [Durham], University of Manitoba [Winnipeg], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Lund University [Lund], La Jolla Institute for Immunology [La Jolla, CA, États-Unis], Harvard T.H. Chan School of Public Health, Zalgen Labs, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), Fiocruz Paraná - Instituto Carlos Chagas / Carlos Chagas Institute [Curitiba, Brésil] (ICC), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Università degli Studi di Siena = University of Siena (UNISI), Bill & Melinda Gates Foundation [Seattle], R.K.A. and M.V.K. presented work funded by the WHO Solidarity Response Fund and the German Federal Ministry of Health COVID-19 Research and Development. R.K.A. would also like to thank the following additional funders of SeroTracker's SARS-CoV-2 evidence synthesis efforts: the Public Health Agency of Canada through Canada's COVID-19 Immunity Task Force, the Robert Koch Institute, and the Canadian Medical Association Joule Innovation Fund. M.V.K. is employed by the WHO, and the authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions, policies, or views of WHO. E.d.W. and N.v.D. are supported by the Intramural Research Program of NIAID, NIH.
Subjects: Ebola virus, History and Philosophy of Science, General Neuroscience, [SDV]Life Sciences [q-bio], COVID-19, Nipah virus, vaccines, zoonotic diseases, infectious diseases, Lassa virus, General Biochemistry, Genetics and Molecular Biology
Abstract: International audience; The COVID-19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10-13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium "Lessons from the Pandemic: Responding to Emerging Zoonotic Viral Diseases" to discuss the successes and challenges of the COVID-19 pandemic and what lessons can be applied moving forward. Speakers focused on experiences not only from the COVID-19 pandemic but also from outbreaks of other pathogens, including the Ebola virus, Lassa virus, and Nipah virus. A general consensus was that investments made during the COVID-19 pandemic in infrastructure, collaborations, laboratory and manufacturing capacity, diagnostics, clinical trial networks, and regulatory enhancements-notably, in low-to-middle income countries-must be maintained and strengthened to enable quick, concerted responses to future threats, especially to zoonotic pathogens.
Published: 2022

34. The Needs, Use and Expectations of People Bereaved by Suicide Regarding Online Resources: An Online Survey

Author: Edouard Leaune, Héloïse Rouzé, Laurène Lestienne, Kushtrim Bislimi, Benoit Chalancon, Margot Morgiève, Pierre Grandgenèvre, Guillaume Vaiva, Nathalie Laplace, Emmanuel Poulet, Julie Haesebaert, Université de Lyon, Centre Hospitalier le Vinatier [Bron], Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherches insulaires et observatoire de l'environnement (CRIOBE), Université de Perpignan Via Domitia (UPVD)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Interactions, Corpus, Apprentissages, Représentations (ICAR), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Universitaire de Recherche et d'Exploration en psychiatrie [Lille] (CURE), Clinique de Psychiatrie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre National de Ressources et de Résilience [Lille] (CN2R), Centre pour l'innovation en cancérologie de Lyon (CICLY), Université de Lyon-Université de Lyon, Psychiatric Disorders, Neuroscience Research and Clinical Research (PSYR2), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Hospices Civils de Lyon (HCL)
Subjects: Male, Motivation, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, bereavement, online resource, Middle Aged, [SHS]Humanities and Social Sciences, Cross-Sectional Studies, Surveys and Questionnaires, suicide, survey, Humans, Female, Child
Abstract: International audience; Background: Online resources constitute a new and effective way to obtain support or information during bereavement processes. However, little is known about the needs, use and expectations of people bereaved by suicide regarding online resources. Method: The objective of our national cross-sectional online survey was to collect the use, needs and expectations of people bereaved by suicide regarding online resources. The data were collected from July to October 2021 through a 26-item online questionnaire hosted on the website LimeSurvey. Results: A total of 401 respondents fully completed the questionnaire. Their mean age was 45.7. The majority of participants were women bereaved by the suicide of their child or partner. Half of the participants were bereaved for less than 3 years and benefited from counselling during their bereavement process. Three-quarters of the participants used the Internet for their bereavement process, mainly to obtain information on suicide bereavement and suicide prevention and to access testimonies of other people bereaved by suicide. Three-quarters of the participants found that available online resources for people bereaved by suicide are insufficient and expected a dedicated web platform to be developed. Finding information on suicide bereavement and on suicide prevention, discussing with a mental health professional and accessing testimonies of other people bereaved by suicide were expected by a majority of the participants regarding the future platform. Receiving counselling and being bereaved by the death of a child were the most important factors in explaining patterns of use and expectations regarding online resources. Discussion: Our results offer precise insights into the needs, use and expectations of people bereaved by suicide regarding online resources. The development of web platforms offering access to reliable information on suicide bereavement and on suicide prevention to peers bereaved by suicide and help to seek counselling are urgently needed.
Published: 2022

35. Tomographic imaging: two examples of medical and archaeological applications

Author: Coli, Vanna Lisa, Binder, Didier, Blanc-Féraud, Laure, Leblond, Juliette, Cohen, Serge X., Gomart, Louise, Migliaccio, Claire, Culture et Environnements, Préhistoire, Antiquité, Moyen-Age (CEPAM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Analyse fonctionnelle pour la conception et l'analyse de systèmes (FACTAS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Morphologie et Images (MORPHEME), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut de Biologie Valrose (IBV), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut photonique d'analyse non-destructive européen des matériaux anciens (IPANEMA), Muséum national d'Histoire naturelle (MNHN)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Evaluating, understanding, supporting motor, perceptive and social Trajectories (TRAJECTOIRES), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Laboratoire d'Electronique, Antennes et Télécommunications (LEAT)
Subjects: [MATH]Mathematics [math], [SHS]Humanities and Social Sciences
Abstract: International audience
Published: 2022

36. Characterisation of a novel member of the Trim family as a novel pantropic viral inhibitor

Author: Song, Yuxin, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interaction hôte pathogène lors de l'infection lentivirale – Host-Pathogen Interaction during Lentiviral Infection (LP2L), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Ecole normale supérieure de lyon - ENS LYON, and Andrea Cimarelli
Subjects: Réponse innée, Trim, Innate response, SARS-CoV2, HIV, VIH, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Virus
Abstract: To identify novel cellular modulators of HIV-1 infection in IFN-stimulated myeloid cells, we have carried out a screen that combines functional and evolutionary analyses in THP-1-PMA cells that led us to the Tripartite Motif Protein 69 (Trim69), a poorly studied member of the Trim family of innate immunity regulators. Trim69 inhibits HIV-1, primate lentiviruses and the negative and positive-strand RNA viruses VSV and SARS-CoV2, overall indicating it is a broad- spectrum antiviral factor. Trim69 binds directly to microtubules and its antiviral activity is intimately linked to its ability to promote the accumulation of stable MTs, a specialized subset of microtubules. By analyzing the behavior of primary blood cells, we provide evidence that a program of MT stabilization is commonly observed in response to IFN-I in cells of the myeloid lineage and Trim69 is the key factor behind this program.Overall, our study identifies Trim69 as the first antiviral innate defense factor that regulates the properties of microtubules to limit viral spread, highlighting the possibility that the cytoskeleton may be a novel unappreciated fighting ground in the host-pathogen interactions that underlie viral infections.; Afin d’identifier de nouveaux modulateurs cellulaires de l'infection par le VIH-1 dans les cellules myéloïdes stimulées par l'IFN, nous avons réalisé un criblage qui combine des analyses fonctionnelles et évolutives dans les cellules THP-1-PMA. Ce crible nous ont conduit à la Tripartite Motif Protein 69 (Trim69), un membre peu étudié de la famille Trim des régulateurs de l'immunité innée. Trim69 inhibe le VIH-1, les lentivirus de primate et les virus à ARN à brin négatif et positif VSV et SARS-CoV2, indiquant globalement qu'il s'agit d'un facteur antiviral à large spectre. Trim69 se lie directement aux microtubules (MT) et son activité antivirale est intimement liée à sa capacité à favoriser l'accumulation de MT stables, un sous-ensemble spécialisé de microtubules. En analysant le comportement des cellules primaires du sang périphérique, nous apportons la preuve qu'un programme de stabilisation des MT est couramment observé en réponse à l'IFN-I dans les cellules de la lignée myéloïde et Trim69 est le facteur clé derrière ce programme.Dans l'ensemble, notre étude identifie Trim69 comme le premier facteur de défense innée antiviral qui régule les propriétés des microtubules afin de limiter la propagation virale, soulignant la possibilité que le cytosquelette soit un nouveau terrain de combat méconnu dans les interactions hôte-pathogène qui sous-tendent les infections virales.
Published: 2022

37. A Single Session of Bifrontal tDCS Can Improve Facial Emotion Recognition in Major Depressive Disorder: An Exploratory Pilot Study

Author: Laetitia Imbert, Rémi Moirand, Benoit Bediou, Olivier Koenig, Gabrielle Chesnoy, Eric Fakra, Jérôme Brunelin, Psychiatric Disorders, Neuroscience Research and Clinical Research (PSYR2), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], Université de Genève = University of Geneva (UNIGE), Laboratoire d'Etude des Mécanismes Cognitifs (EMC), Université Lumière - Lyon 2 (UL2), CHU Saint-Etienne, and Brunelin, Jérôme
Subjects: MDD, facial emotion recognition, [SDV.IB] Life Sciences [q-bio]/Bioengineering, tDCS, brain stimulation, depression, DLPFC, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [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, Medicine (miscellaneous), [SDV.IB]Life Sciences [q-bio]/Bioengineering, General Biochemistry, Genetics and Molecular Biology
Abstract: International audience; Emotional processing deficits are key features in major depressive disorder (MDD). Neuroimaging studies indicate that the dorsolateral prefrontal cortex (DLPFC) plays a pivotal role in both depressive symptoms and emotional processing. Recently, transcranial Direct Current Stimulations (tDCS) applied over the DLPFCs have held the promise to alleviate the symptoms in patients with MDD, but the effect on emotional processing in the patients is unclear. Here, we investigated the effect of a single session of tDCS over the DLPFCs on the emotional processing in patients with treatment-resistant MDD. In a randomized sham-controlled study, 35 patients received a single 30 min session of either active (2 mA, n = 18) or sham tDCS (n = 17). The anode was placed over the left and the cathode over the right DLPFC. Emotional processing accuracy was measured by a facial emotion recognition (FER) task. We observed an overall improvement in FER performance after the active tDCS, but not the sham tDCS. These exploratory results suggest that a single session of tDCS over the DLPFCs may improve FER in MDD, a crucial function of social cognition. Further studies are needed to investigate whether this acute improvement of FER in response to a single tDCS session could translate into clinical benefits or predict remission following repeated sessions of stimulation.
Published: 2022

38. Systematic MRI in persistent post-Covid-19 olfactory dysfunction should be reassessed

Author: Ioana Brudasca, Quentin Lisan, Romain Tournegros, Moustafa Bensafi, Camille Ferdenzi, Arnaud Fournel, Luna Denoix, Stéphane Tringali, Maxime Fieux, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Foch [Suresnes], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Biomécanique & Appareil Respiratoire (BAR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Ferdenzi, Camille
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, imaging, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Otorhinolaryngology, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, olfactory disorder, olfaction
Abstract: International audience; Background: Magnetic resonance imaging (MRI) is the gold standard in the etiological assessment of a persistent olfactory dysfunction (OD). While the utility of imaging in COVID-19-related OD has yet to be established, MRI is recommended in all patients with persistent OD. The high prevalence of the latter after SARS-CoV-2 infection means evaluating this strategy is an important public health matter.Methods:The main objective was to examine the impact of systematic MRI on the management of patients with OD. All adult patients consulting for persistent OD (>2 months) after primary SARS-COV-2 infection (PCR) between March 2020 and December 2021 were included (n = 67). The secondary objective was to evaluate the relationship between the severity of the OD as measured by psychophysical testing (ETOC) and the volume of the olfactory bulb (OB) measured by MRI.Results: All patients underwent MRI, and none led to a change in diagnosis or treatment. Among them, 82% (55/67) were considered normal by the radiologist on initial interpretation. There were no significant differences (visual analysis or OB volume) between groups (mild, moderate, and severe hyposmia).Conclusion: Systematic MRI may be unnecessary in patients whose persistent OD began soon (a few days) after confirmed SARS-CoV-2 infection.
Published: 2022

39. Peer presence elicits task-independent changes within and beyond the mentalizing network across children and adults

Author: Leslie Tricoche, Denis Pélisson, Léa Longo, Eric Koun, Alice Poisson, Jérôme Prado, Martine Meunier, Integrative Multisensory Perception, Action and Cognition (IMPACT), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité des pathologies du sommeil et équipe de recherche AESIO Santé unité de Saint-Etienne, Clinique médico chirurgicale mutualiste, and Pelisson, Denis
Subjects: [SCCO]Cognitive science, children, audience effect, literacy, [SCCO] Cognitive science, numeracy
Abstract: There is ample behavioral evidence that others’ mere presence can affect any behavior in human and non-human animals, generally facilitating the expression of mastered responses while impairing the acquisition of novel ones. Much less is known about i) how the brain orchestrates the modulation of such a wide array of behaviors by others’ presence and ii) when these neural underpinnings mature during development. To address these issues, fMRI data were collected in children and adults alternately observed and unobserved by a familiar peer. Subjects performed two tasks. One, numerosity comparison, depends on number-processing brain areas, the other, phonological comparison, on language-processing areas. Consistently with previous behavioral findings, peer observation facilitated both tasks, and children’s improvement was comparable to adults’. Regarding brain activation, we found virtually no evidence of observation-driven changes within the number- or language-related areas specific to each task. Rather, we observed the same task-independent changes for both numerosity and phonological comparisons. This unique neural signature encompassed a large brain network of domain-general areas involved in social cognition, especially mentalizing, attention, and reward. It was also largely shared by children and adults. The one exception was children’s right temporoparietal junction, which failed to show the observation- driven lesser deactivation seen in adults. These findings indicate that social facilitation of some human education-related skills is i) primarily orchestrated by domain-general brain networks, rather than by task-selective substrates, and ii) relatively mature early in the course of education, thus having a protracted impact on academic achievements that may have heretofore been underestimated.HighlightBasic math and reading skills were measured in children and adults.Participants were alternately observed and unobserved by a familiar peer.Behavior showed that children were as facilitated by peer observation as adults.fMRI data showed task-independent, observation-driven changes in mentalizing, attention, and reward brain regions.All adults’ neural changes were also found in children, except one located in right temporo- parietal junction.
Published: 2022

40. Factors associated with COVID-19 vaccine uptake among French population aged 65 years and older: results from a national online survey

Author: Yu-Jin Jung, Amandine Gagneux-Brunon, Marion Bonneton, Elisabeth Botelho-Nevers, Pierre Verger, Jeremy K. Ward, Odile Launay, CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et biothérapies des infections muqueuses (GIMAP), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7), and École des hautes études en sciences sociales (EHESS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Vaccines, COVID-19 Vaccines, Cross-Sectional Studies, Vaccination, COVID-19, Humans, Geriatrics and Gerontology, Aged, [SHS]Humanities and Social Sciences
Abstract: Background In France, the increase in COVID-19 vaccine uptake among older adults slowed down between May and June 2021. Using the data from a national survey, we aimed to assess COVID-19 vaccine uptake among French residents aged 65 years and older, particularly at risk of severe form of the infection, and identify factors associated with non-vaccination. Methods A cross-sectional online survey collected the immunization status/intention to get the COVID-19 vaccine, reasons for vaccination/non-vaccination and factors potentially associated with vaccine uptake between May 10 and 23, 2021 among a large sample of French residents. Characteristics of participants were compared according to immunization status. Factors potentially associated with non-vaccination were computed into a multivariate logistic regression. Results Among the 1941 survey participants, 1612 (83%) reported having received at least one dose of COVID-19 vaccine. Among the 329 unvaccinated, 197 (60%) declared having the intention to get vaccinated. Younger age (adjusted odds ratio (aOR) = 1.50; 95% confidence interval (CI), 1.05–2.14), thinking previously having COVID-19 (aOR = 4.01; 95% CI, 2.17–7.40), having suffered economic impact due to the pandemic (aOR = 2.63; 95% CI, 1.71–4.04), reporting an “unsafe” opinion about COVID-19 vaccine safety (aOR = 6.79; 95% CI, 4.50–10.26), reporting an “unsupportive” opinion about vaccination in general (aOR = 4.24; 95% CI, 2.77–6.49) were independent risk factors for non-vaccination. On the other hand, trust in COVID-19 vaccine information delivered by the doctor (aOR = 0.28; 95% CI, 0.16–0.48) and trust in the government’s actions (aOR = 0.50; 95% CI, 0.34–0.74) were independent protective factors for non-vaccination. Political affiliation also remained significantly associated with vaccine uptake. Conclusions Despite high overall COVID-19 vaccine uptake among the study participants, differences in vaccine uptake according to the level of concerns regarding COVID-19 vaccine safety, socioeconomic profile and trust in the government were observed. Our results reinforce the importance of “reaching out” vaccination strategy that specifically targets the most vulnerable fringe of older adult population.
Published: 2022

41. First clinical description of letermovir resistance mutation in cytomegalovirus UL51 gene and potential impact on the terminase complex structure

Author: Clotilde Muller, Valentin Tilloy, Emilie Frobert, Linda Feghoul, Isabelle Garrigue, Quentin Lepiller, Audrey Mirand, Egor Sidorov, Sébastien Hantz, Sophie Alain, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Hôpital Dupuytren [CHU Limoges], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Virologie Médicale et Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Université Clermont Auvergne, CNRS, LMGE, 63000 Clermont–Ferrand, France, Czech Statistical Office (CZSO), Jan Evangelista Purkyne University (UJEP), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], and CHU Limoges
Subjects: Pharmacology, Viral Proteins, Endodeoxyribonucleases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Drug Resistance, Viral, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Quinazolines, Cytomegalovirus, Humans, Acetates, Antiviral Agents
Abstract: Letermovir (LMV) is a human cytomegalovirus (HCMV) terminase inhibitor indicated as prophylaxis for HCMV-positive stem-cell recipients. Its mechanism of action involves at least the viral terminase proteins pUL56, pUL89 and pUL51. Despite its efficiency, resistance mutations were characterized in vitro and in vivo, largely focused on pUL56. To date, mutations in pUL51 in clinical resistance remain to be demonstrated.The pUL51 natural polymorphism was described by sequencing 54 LMV-naive strains and was compared to UL51 HCMV genes from 16 patients non-responding to LMV therapy (prophylaxis or curative). Recombinant viruses were built by «en-passant» mutagenesis to measure the impact of the new mutations on antiviral activity and viral growth. Structure prediction was performed by homology modeling. The pUL51 final-model was analyzed and aligned with the atomic coordinates of the monomeric HSV-1 terminase complex (PDB:6M5R).Among the 16 strains from treated-patients with LMV, 4 never described substitutions in pUL51 (D12E, 17del, A95V, V113L) were highlighted. These substitutions had no impact on viral fitness. Only UL51-A95V conferred 13.8-fold increased LMV resistance level by itself (IC50 = 29.246 ± 0.788).As an isolated mutation in pUL51 in a clinical isolate can lead to LMV resistance, genotyping for resistance should involve sequencing of the pUL51, pUL56 and pUL89 genes. With terminase modelling, we make the hypothesis that LMV could bind to domains were UL56-L257I and UL51-A95V mutations were localized.
Published: 2022

42. Bacterial Cross-Transmission between Inanimate Surfaces and Patients in Intensive Care Units under Real-World Conditions: A Repeated Cross-Sectional Study

Author: Elisabetta Kuczewski, Laetitia Henaff, Anne Regard, Laurent Argaud, Anne-Claire Lukaszewicz, Thomas Rimmelé, Pierre Cassier, Isabelle Fredenucci, Sophie Loeffert-Frémiot, Nagham Khanafer, Philippe Vanhems, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Santé publique, épidémiologie et écologie évolutive des maladies infectieuses (PHE3ID), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Agents Infectieux [Lyon] (IAI), Hôpital de la Croix-Rousse [CHU - HCL], HCL Groupement Hospitalier Nord [Lyon], Laboratoires Anios-Ecolab Company [Lezennes] (LAEC), CarMeN, laboratoire, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Acinetobacter baumannii, Cross Infection, hospital-acquired infection, Bacteria, environment, hospital, ICU, high-touch surfaces, bacteria, contamination, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Public Health, Environmental and Occupational Health, [SDV] Life Sciences [q-bio], Intensive Care Units, Cross-Sectional Studies, Humans
Abstract: Background/Objectives: Contaminated surfaces play an important role in the nosocomial infection of patients in intensive care units (ICUs). This study, conducted in two ICUs at Edouard Herriot Hospital (Lyon, France), aimed to describe rooms’ microbial ecology and explore the potential link between environmental contamination and patients’ colonization and/or infection. Methods: Environmental samples were realized once monthly from January 2020 to December 2021 on surfaces close to the patient (bedrails, bedside table, and dedicated stethoscope) and healthcare workers’ high-touch surfaces, which were distant from the patient (computer, worktop/nurse cart, washbasin, and hydro-alcoholic solution/soap dispenser). Environmental bacteria were compared to the cultures of the patients hospitalized in the sampled room over a period of ± 10 days from the environmental sampling. Results: Overall, 137 samples were collected: 90.7% of the samples close to patients, and 87.9% of the distant ones were positives. Overall, 223 bacteria were isolated, mainly: Enterococcus faecalis (15.7%), Pantoea agglomerans (8.1%), Enterobacter cloacae/asburiae (6.3%), Bacillus cereus and other Bacillus spp (6.3%), Enterococcusfaecium (5.8%), Stenotrophomonas maltophilia (5.4%), and Acinetobacter baumannii (4.9%). Throughout the study, 142 patients were included, of which, n = 67 (47.2%) were infected or colonized by at least one bacterium. In fourteen cases, the same bacterial species were found both in environment and patient samples, with the suspicion of a cross-contamination between the patient–environment (n = 10) and environment–patient (n = 4). Conclusions: In this work, we found a high level of bacterial contamination on ICU rooms’ surfaces and described several cases of potential cross-contamination between environment and patients in real-world conditions.
Published: 2022
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43. Plasma host protein signatures correlating with Mycobacterium tuberculosis activity prior to and during antituberculosis treatment

Author: Mame Diarra Bousso Ndiaye, Paulo Ranaivomanana, Lova Tsikiniaina Rasoloharimanana, Voahangy Rasolofo, Rila Ratovoson, Perlinot Herindrainy, Julio Rakotonirina, Matthieu Schoenhals, Jonathan Hoffmann, Niaina Rakotosamimanana, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Unité des Mycobactéries [Antananarivo, Madagascar] (IPM), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université d'Antananarivo, Direction scientifique [Antananarivo, Madagascar], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Chemokine CXCL10, Extracellular Matrix Proteins, Multidisciplinary, [SDV]Life Sciences [q-bio], Complement C1q, Antitubercular Agents, Humans, Mycobacterium tuberculosis, Prospective Studies, Blood Proteins, Tuberculosis, Lymph Node
Abstract: Background There is a need for rapid non-sputum-based tests to identify and treat patients infected with Mycobacterium tuberculosis (Mtb). In this study, performance of a human plasma protein signature for both TB triage and treatment monitoring has been evaluated. Methods A panel of seven host proteins CLEC3B, SELL, IGFBP3, IP10, CD14, ECM1 and C1Q were measured in the plasma of a prospective patient cohort undergoing anti-tubercular therapy to distinguish confirmed TB patients from control, to define culture slow and fast converters during an antituberculosis treatment and to monitor the treatment. To validate the protein signatures a Luminex xMAP® assay was used to quantify the proteins in unstimulated plasma isolated from the blood collected from HIV-negative pulmonary TB patients (ATB), at baseline and following 6-months of antituberculosis treatment, latently TB-infected individuals (LTBI) and healthy donors (HD). Protein signatures performances were evaluated using CombiROC algorithm and multivariate models. Findings: We measured the proteins in the plasma of 84 participants including 37 ATB, 24 LTBI and 23 HD. The seven plasma host proteins studied showed different levels between the TB clinical groups and when used separately or in combination, have variable performances for ATB triage and for treatment monitoring. Six of the plasma proteins (CLEC3B, SELL, IGFBP3, IP10, CD14 and C1Q) showed significant differences in normalised median fluorescence intensities when comparing ATB vs HD or LTBI while ECM1 revealed a significant association with early sputum culture conversion after 2 months following treatment (OR 0.004, p = 0.018). For both triage and treatment monitoring, a signature combining 4 host proteins markers (CLEC3B-ECM1-IP10-SELL) was identified, allowing to distinguish ATB from HD or LTBI (respectively, sensitivity = 94%, specificity = 92% and sensitivity = 89%, specificity = 91%) as well as the baseline distinction between slow vs fast sputum culture converters after two months of treatment (AUC = 0.87, sensitivity = 83%, specificity = 84%). Conclusion Our data demonstrate that using a combination of host plasma markers can generate a relevant biosignature for both TB triage and treatment monitoring meeting the WHO Target Product Profile for both purposes.
Published: 2022

44. Lived Experiences of Suicide Bereavement within Families: A Qualitative Study

Author: Clémence Creuzé, Laurène Lestienne, Maxime Vieux, Benoit Chalancon, Emmanuel Poulet, Edouard Leaune, Centre Hospitalier le Vinatier [Bron], Interactions, Corpus, Apprentissages, Représentations (ICAR), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Psychiatric Disorders, Neuroscience Research and Clinical Research (PSYR2), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Middle Aged, [SHS]Humanities and Social Sciences, suicide, bereavement, family, lived experiences, qualitative, Suicide, Humans, Female, Family, Grief, Child, Qualitative Research, Bereavement
Abstract: Backround: The lifetime prevalence of suicide exposure in the family is estimated at 3.8% in the general population. Familial bonds can constitute a crucial factor in determining individual bereavement outcomes via the interactional and communicational aspects of the bereavement process within the family. However, the literature on the lived experiences of suicide bereavement within the family remains scarce. Method: Our objectives were to qualitatively (a) assess the impact of suicide on different types of family members, (b) evaluate the interactions between the familial and individual bereavement processes, and (c) obtain precise insights into the familial interactions that occur following a suicide. We performed a qualitative study by conducting semidirected interviews with family members who had been bereaved by suicide. Computer-based and manual thematic analyses were used for data analysis. In order to mitigate biases related to the qualitative design of the data collection, two main measures were undertaken, namely triangulation and saturation. Results: Sixteen family members bereaved by suicide participated in our study, including a majority of women (n = 12). Mean age of participants was 56.4 and mean duration of suicide bereavement was 10.5 years. Most of the relatives deceased by suicide were middle-aged men who died by hanging or firearm. A total of six themes emerged from the analyses, namely (1) “familial trauma”, (2) “external adversity”, (3) “individual bereavement and familial interactions”, (4) “communicational and relational processes within the family”, (5) “perceived help and support within the family” and (6) “evolution over time”. Conclusion: We reported that suicide bereavement significantly impacts internal familial interactions via complex emotional and communication processes. Family conflicts, taboos or cohesion can occur in the aftermath of a suicide. We also found that familial coping strategies can shape individual reactions to the death on the part of each member of the family.
Published: 2022

45. Twice daily low frequency rTMS for treatment-resistant auditory hallucinations

Author: Jérôme Brunelin, Filipe Galvao, Marine Mondino, Psychiatric Disorders, Neuroscience Research and Clinical Research (PSYR2), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], and Brunelin, Jérôme
Subjects: Clinical Psychology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, rTMS, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Schizophrenia, Hallucination, Clozapine
Abstract: International audience; Background: Repetitive transcranial magnetic stimulation (rTMS) has emerged as a therapeutic solution in patients with treatment-resistant auditory verbal hallucinations. However, the optimal stimulation parameters remain unclear, especially for patients with clozapine-resistant symptoms. Method: In an open label retrospective study, we investigated whether parameters of stimulation that were useful in patients with major depressive disorder would help schizophrenia patients with treatment-resistant auditory verbal hallucinations. Fourteen participants, including 9 under clozapine, received 30 sessions of 1 Hz rTMS over 3 weeks (360 pulses per sessions delivered with 60 s 'on' and 30 s 'off' at 110% of the resting motor threshold, 2 sessions per day). Stimulations were applied over the left temporoparietal junction (T3-P3 according to 10/20 system). Results: After rTMS, a significant decrease of auditory verbal hallucinations was observed (À38.7% § 31.8, p = 0.003) on the Auditory Hallucination Rating Scale. The beneficial effects were also significant in the 9 patients who were also receiving clozapine (À34.9% § 28.4, p = 0.01). Conclusions: Low frequency rTMS, 30 sessions over 3 weeks, appears to be a suitable approach to decrease treatment-resistant auditory verbal hallucinations, including in patients with clozapine-resistant symptoms. Results from the current retrospective study in the clinical settings need to be confirmed by large-scale randomized sham-controlled trials.
Published: 2022

46. Attributable Mortality of Ventilator-associated Pneumonia Among Patients with COVID-19

Author: Vacheron, Charles-Hervé, Lepape, Alain, Savey, Anne, Machut, Anaïs, Timsit, Jean Francois, Comparot, Sylvie, Courno, Gaelle, Vanhems, Philippe, Landel, Verena, Lavigne, Thierry, Bailly, Sebastien, Bettega, Francois, Maucort-Boulch, Delphine, Friggeri, Arnaud, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Henry Gabrielle [CHU - HCL], Santé publique, épidémiologie et écologie évolutive des maladies infectieuses (PHE3ID), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Hôpital Edouard Herriot [CHU - HCL], Les Hôpitaux Universitaires de Strasbourg (HUS), Université de Strasbourg (UNISTRA), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Pôle de Santé Publique [Lyon], Service de Biostatistiques [Lyon], REA-REZO Study Group, ANR-19-P3IA-0003,MIAI,MIAI @ Grenoble Alpes(2019), SALAS, Danielle, MIAI @ Grenoble Alpes - - MIAI2019 - ANR-19-P3IA-0003 - P3IA - VALID, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV] Life Sciences [q-bio], COVID-19, population attributable fraction, attributable mortality, ventilator-associated pneumonia, [SDV]Life Sciences [q-bio]
Abstract: International audience; Rationale: Patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at higher risk of ventilator-associated pneumonia (VAP) and may have an increased attributable mortality (increased or decreased risk of death if VAP occurs in a patient) and attributable fraction (proportion of deaths that are attributable to an exposure) of VAP-related mortality compared with subjects without coronavirus disease (COVID-19). Objectives: Estimation of the attributable mortality of the VAP among patients with COVID-19. Methods: Using the REA-REZO surveillance network, three groups of adult medical ICU patients were computed: control group (patients admitted between 2016 and 2019; prepandemic patients), pandemic COVID-19 group (PandeCOV+), and pandemic non-COVID-19 group (PandeCOV-) admitted during 2020. The primary outcome was the estimation of attributable mortality and attributable fraction related to VAP in these patients. Using multistate modeling with causal inference, the outcomes related to VAP were also evaluated. Measurements and Main Results: A total of 64,816 patients were included in the control group, 7,442 in the PandeCOV- group, and 1,687 in the PandeCOV+ group. The incidence of VAP was 14.2 (95% confidence interval [CI], 13.9 to 14.6), 18.3 (95% CI, 17.3 to 19.4), and 31.9 (95% CI, 29.8 to 34.2) per 1,000 ventilation-days in each group, respectively. Attributable mortality at 90 days was 3.15% (95%, CI, 2.04% to 3.43%), 2.91% (95% CI, -0.21% to 5.02%), and 8.13% (95% CI, 3.54% to 12.24%), and attributable fraction of mortality at 90 days was 1.22% (95% CI, 0.83 to 1.63), 1.42% (95% CI, -0.11% to 2.61%), and 9.17% (95% CI, 3.54% to 12.24%) for the control, PandeCOV-, and PandeCOV+ groups, respectively. Except for the higher risk of developing VAP, the PandeCOV- group shared similar VAP characteristics with the control group. PandeCOV+ patients were at lower risk of death without VAP (hazard ratio, 0.62; 95% CI, 0.52 to 0.74) than the control group. Conclusions: VAP-attributable mortality was higher for patients with COVID-19, with more than 9% of the overall mortality related to VAP.
Published: 2022

47. PET metabolic imaging of time-dependent reorganization of olfactory cued fear memory networks in rats

Author: Anne-Marie Mouly, Philippe Litaudon, Nadine Ravel, Nicolas Costes, Caroline Bouillot, Luc Zimmer, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hospices Civils de Lyon (HCL), RAVEL, Nadine, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MOULY, Anne-Marie, and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Cognitive Neuroscience, [SDV]Life Sciences [q-bio], Hippocampus, Sensory system, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Piriform cortex, Odor, Animals, Fear conditioning, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Prefrontal cortex, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Memory Consolidation, Cued speech, 0303 health sciences, Recall, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Fear, Cued Fear conditioning, Recent memory, Odor fear conditioning, Rats, [SDV] Life Sciences [q-bio], [18F]FDG micro PET, Positron-Emission Tomography, Mental Recall, Memory consolidation, System-level consolidation, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Remote memory, Cues, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract: Memory consolidation involves reorganization at both the synaptic and system levels. The latter involves gradual reorganization of the brain regions that support memory and has been mostly highlighted using hippocampal-dependent tasks. The standard memory consolidation model posits that the hippocampus becomes gradually less important over time in favor of neocortical regions. In contrast, this reorganization of circuits in amygdala-dependent tasks has been less investigated. Moreover, this question has been addressed using primarily lesion or cellular imaging approaches thus precluding the comparison of recent and remote memory networks in the same animals. To overcome this limitation, we used microPET imaging to characterize, in the same animals, the networks activated during the recall of a recent versus remote memory in an olfactory cued fear conditioning paradigm. The data highlighted the drastic difference between the extents of the two networks. Indeed, although the recall of a recent odor fear memory activates a large network of structures spanning from the prefrontal cortex to the cerebellum, significant activations during remote memory retrieval are limited to the piriform cortex. These results strongly support the view that amygdala-dependent memories also undergo system-level reorganization, and that sensory cortical areas might participate in the long-term storage of emotional memories.
Published: 2022

48. Evaluation of commercial Anti-SARS-CoV-2 neutralizing antibody assays in seropositive subjects

Author: Kahina Saker, Bruno Pozzetto, Vanessa Escuret, Virginie Pitiot, Amélie Massardier-Pilonchéry, Bouchra Mokdad, Carole Langlois-Jacques, Muriel Rabilloud, Dulce Alfaiate, Nicolas Guibert, Jean-Baptiste Fassier, Antonin Bal, Sophie Trouillet-Assant, Mary-Anne Trabaud, Hospices Civils de Lyon (HCL), Commission Spécialisée Maladies infectieuses et maladies émergentes (CSMime), Haut Conseil de la Santé Publique (HCSP), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Gustave Eiffel, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut des Agents Infectieux [Lyon] (IAI), ASTREDHOR Sud-Ouest, Association nationale des structures d'expérimentation et de démonstration en ... et de démonstration en horticulture ornementale (ASTREDHOR), Hôpital de la Croix-Rousse [CHU - HCL], and Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath)
Subjects: Competitive anti-RBD immunoassays, History, Polymers and Plastics, SARS-CoV-2, Surrogate markers of protection, [SDV]Life Sciences [q-bio], COVID-19, Antibodies, Viral, Neutralizing antibodies, Antibodies, Neutralizing, Industrial and Manufacturing Engineering, Commercial tests, Infectious Diseases, Neutralization Tests, Virology, Humans, Business and International Management
Abstract: The virus neutralization test (VNT) is the reference for the assessment of the functional ability of neutralizing antibodies (NAb) to block SARS-CoV-2 entry into cells. New competitive immunoassays measuring antibodies preventing interaction between the spike protein and its cellular receptor are proposed as surrogate VNT (sVNT). We tested three commercial sVNT (a qualitative immunochromatographic test and two quantitative immunoassays named YHLO and TECO) together with a conventional anti-spike IgG assay (bioMérieux) in comparison with an in-house plaque reduction neutralization test (PRNT50) using the original 19A strain and different variants of concern (VOC), on a panel of 306 sera from naturally-infected or vaccinated patients. The qualitative test was rapidly discarded because of poor sensitivity and specificity. Areas under the curve of YHLO and TECO assays were, respectively, 85.83 and 84.07 (p-value >0.05) using a positivity threshold of 20 for PRNT50, and 95.63 and 90.35 (p-value =0.02) using a threshold of 80. However, the performances of YHLO and bioMérieux were very close for both thresholds, demonstrating the absence of added value of sVNT compared to a conventional assay for the evaluation of the presence of NAb in seropositive subjects. In addition, the PRNT50 assay showed a reduction of NAb titers towards different VOC in comparison to the 19A strain that could not be appreciated by the commercial tests. Despite the good correlation between the anti-spike antibody titer and the titer of NAb by PRNT50, our results highlight the difficulty to distinguish true NAb among the anti-RBD antibodies with commercial user-friendly immunoassays.
Published: 2022

49. Invasion muqueuse au cours de la colonisation nasale à Staphylococcus aureus

Author: Rigaill, Josselin, Physiopathologie et biothérapies des infections muqueuses (GIMAP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Philippe Berthelot, and Frédéric Laurent
Subjects: Décolonisation, Staphylococcus aureus, Microbiote, Microbiota, Colonisation nasale, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Internalisation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Corynebacterium, Antibiotiques, Intracellular, Decolonization, Antibiotics, Nasal colonization, Intracellulaire, Internalization
Abstract: The nasal vestibule is considered as the main site of colonization by Staphylococcus aureus in humans. However, this thesis work showed that S. aureus colonization of the posterior nasal cavity was similar in all aspects to vestibular colonization. This nasal carriage of S. aureus is associated with an increased risk of infection with the bacteria. Current decolonization strategies, principally based on the topical use of mupirocin, are associated with a high relapse rate of S. aureus nasal carriage. We were able to observe the presence of an intracellular reservoir of S. aureus on samples from healthy patients carrying the bacterium. The almost total lack of intracellular activity of mupricin that we measured on an in vitro model of nasal colonization could partly explain the decolonization failures observed with this molecule. An internalization pathway mediated by the S. aureus Eap protein through the ICAM-1 receptor could play an important role in an inflammatory context. Despite the promising preliminary results, this work did not confirm the involvement of these two molecules in the internalization of the bacterium. Finally, interactions between microorganisms are numerous and certain bacteria seem capable of preventing the implantation of S. aureus in the nasal mucosa. Based on 16S metagenomics data and the in vitro competition study, we were able to highlight, for the first time, the inhibitory capacity of some Corynebacterium propinquum strains on the growth and invasion capacity of numerous S. aureus strains.; Le vestibule nasal est considéré comme le principal site de colonisation par Staphylocccus aureus chez l’Homme. Ce travail de thèse a cependant montré que la colonisation par S. aureus de la cavité nasale postérieure était similaire en tout point à la colonisation vestibulaire. Le portage nasal de S. aureus est responsable d’une augmentation du risque d’infection par la bactérie. Les stratégies actuelles de décolonisation, basées avant tout sur l’utilisation topique de mupirocine, sont associées à un fort taux de rechute du portage de S. aureus. Nous avons pu observer la présence d’un réservoir intracellulaire de S. aureus sur des prélèvements de patients sains porteurs de la bactérie. La quasi absence d’activité intracellulaire de la mupirocine que nous avons mesurée sur un modèle in vitro de colonisation nasale, pourrait expliquer en partie les échecs de décolonisation observés avec cette molécule. Une voie d’internalisation médiée par la protéine Eap de S. aureus et le récepteur ICAM-1 pourrait jouer un rôle important dans l’entrée de la bactérie. Malgré des résultats préliminaires prometteurs, ce travail n’a pas confirmé l’implication de ces deux molécules dans l’internalisation de S. aureus. Enfin, les interactions entre microorganismes sont nombreuses, et certaines bactéries semblent capables d’empêcher l’implantation de S. aureus au niveau de la muqueuse nasale. Sur la base de données de métagénomique 16S et l’étude de compétition in vitro, nous avons pu mettre en évidence, pour la première fois, la capacité inhibitrice présentée par des souches de Corynebacterium propinquum sur la croissance et la capacité d’invasion d’une grande variété de souches de S. aureus.
Published: 2022

50. FRUIT BATS AS NATURAL RESERVOIR OF HIGHLY PATHOGENIC HENIPAVIRUSES: HIGH PERMISSIVENESS OF REPROGRAMMED PTEROPUS BAT CELLS

Author: Horvat, Branka, Aurine, Noémie, Gaudino, Maria, Fouret, Julien, Baquerre, Camille, Jean, Christian, Reynard, Olivier, Dumont, Claire, Rival-Gervier, Sylvie, Montillet, Guillaume, Kress, Clemences, Georges-Courbot, Marie-Claude, Legras-Lachuer, Catherine, Pain, Bertrand, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ViroScan3D SAS [Trévoux, France], Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire P4 - Jean Mérieux, and Centre Européen de Virologie/Immunologie-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; Bats are asymptomatic hosts for numerous viruses, including highly pathogenic zoonotic henipaviruses, Nipah (NiV) and Hendra. Understanding of how bats control viral infection requires better characterization of bat-derived viruses and development of relevant permissive cellular models. We analysed NiV isolate obtained from a Pteropus lylei bat in Cambodia in 2003 (CSUR381), where human outbreaks of NiV infection have not been detected so far. Full-genome sequencing and phylogenetic analyses confirmed that CSUR381 is part of the NiV-Malaysia genotype. Cell permissiveness was similar in both bat and human cell lines and replication of CSUR381 was alike to other two NiV isolates. In the hamster animal model CSUR381 induced lethal infection. These data suggest that the Cambodia batderived NiV isolate has high pathogenic potential, providing an insight for better risk assessment for future NiV outbreaks in Southeast Asia. Most of the available bat cells are immortalized lines, significantly impacting the overall cell response that may alter the virus-cell interactions. Therefore, by applying a somatic reprogramming protocol to Pteropus bat primary cells, using a novel combination of ESRRB, CDX2 and c-MYC transcription factors, we generated bat reprogrammed cells exhibiting neural stem cell-like characteristics. These cells present a unique interferon-stimulated transcriptomic signature but still produce and respond to IFN type I. In contrast to primary bat cells, these reprogrammed cells are highly susceptible to infection by Henipavirus, even more than Vero cells, commonly used for virus isolation. Future direct reprogramming of bat primary cells into various differentiated cell types should facilitate the isolation of new bat viruses and further studies of virus-bat interaction, towards better understating of the efficient bat anti-viral response.
Published: 2022

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