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1. Modifications of the endosomal compartment in fibroblasts from sporadic Alzheimer’s disease patients are associated with cognitive impairment

Author: Laura Xicota, Julien Lagarde, Fanny Eysert, Benjamin Grenier-Boley, Isabelle Rivals, Alexandra Botté, Sylvie Forlani, Sophie Landron, Clément Gautier, Cecilia Gabriel, Michel Bottlaender, Jean-Charles Lambert, Mounia Chami, Marie Sarazin, Marie-Claude Potier, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), GHU Paris Psychiatrie et Neurosciences, Université Paris Cité (UPCité), Université Paris-Saclay, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), 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), Université de Lille, CHU Lille, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Recherches SERVIER (IRS), Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Xicota, Laura
Subjects: [SDV] Life Sciences [q-bio], Cellular and Molecular Neuroscience, Psychiatry and Mental health, [SDV]Life Sciences [q-bio], Biological Psychiatry
Abstract: Morphological alterations of the endosomal compartment have been widely described in post-mortem brains from Alzheimer’s disease (AD) patients and subjects with Down syndrome (DS) who are at high risk for AD. Immunostaining with antibodies against endosomal markers such as Early Endosome Antigen 1 (EEA1) revealed increased size of EEA1-positive puncta. In DS, peripheral cells such as peripheral blood mononuclear cells (PBMCs) and fibroblasts, share similar phenotype even in the absence of AD. We previously found that PBMCs from AD patients have larger EEA1-positive puncta, correlating with brain amyloid load. Here we analysed the endosomal compartment of fibroblasts from a very well characterised cohort of AD patients (IMABio3) who underwent thorough clinical, imaging and biomarkers assessments. Twenty-one subjects were included (7 AD with mild cognitive impairment (AD-MCI), 7 AD with dementia (AD-D) and 7 controls) who had amyloid-PET at baseline (PiB) and neuropsychological tests at baseline and close to skin biopsy. Fibroblasts isolated from skin biopsies were immunostained with anti-EEA1 antibody and imaged using a spinning disk microscope. Endosomal compartment ultrastructure was also analysed by electron microscopy. All fibroblast lines were genotyped and their AD risk factors identified. Our results show a trend to an increased EEA1-positive puncta volume in fibroblasts from AD-D as compared to controls (p.adj = 0.12) and reveal enhanced endosome area in fibroblasts from AD-MCI and AD-AD versus controls. Larger puncta size correlated with PiB retention in different brain areas and with worse cognitive scores at the time of biopsy as well as faster decline from baseline to the time of biopsy. Finally, we identified three genetic risk factors for AD (ABCA1, COX7C and MYO15A) that were associated with larger EEA1 puncta volume. In conclusion, the endosomal compartment in fibroblasts could be used as cellular peripheral biomarker for both amyloid deposition and cognitive decline in AD patients.
Published: 2023

2. Soins de support nutritionnels dans le parcours des patients atteints de cancers œsogastriques

Author: de Moura, Alexandre, Turpin, Anthony, Neuzillet, Cindy, Institut Curie [Paris], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Lille, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Sarcopenia, Cancer Research, Oncology, Physical activity, [SDV]Life Sciences [q-bio], Malnutrition, Radiology, Nuclear Medicine and imaging, Esophagogastric neoplasm, Hematology, General Medicine, Prehabilitation, Nutrition
Abstract: International audience; Supportive care plays a central role in the management of patients with esophagogastric cancers, at all disease stages. Malnutrition has a high prevalence in this population, reaching up to 60 % of the patients. Sarcopenia and cachexia are also common. These complications have negative impact on functional abilities, quality of life and overall survival. They impair anti-tumor treatments effectiveness and increase their toxicity. Early detection and management are needed, before reaching advanced stages, which are refractory to therapeutic interventions. Specific nutritional support is recommended, relying on different nutritional support tools (dietetic counseling, oral supplements, artificial nutrition), depending on the clinical situation. When artificial nutrition is recommended, enteral nutrition (nasogastric tube, gastrostomy or jejunostomy) should be preferred. When enteral nutrition is impossible or insufficient, parenteral nutrition could be necessary. For patients with advanced esophagogastric cancers, digestive prostheses and decompressive radiation therapy may have a symptomatic benefit on dysphagia. Adapted physical activity is also recommended at all stages of cancer care and ongoing clinical trials will help to specify its modalities and to optimize its place in the therapeutic strategy. Finally, psychosocial support could be useful. A combined approach of these different interventions on the nutritional, physical and psychological aspects is beneficial for patients with esophagogastric cancers. This multimodal and multidisciplinary approach applies to both the early stages of the disease, with prehabilitation and/or rehabilitation to reduce perioperative morbidity and mortality and the advanced stages, with a benefit on survival and quality of life, in parallel with anti-tumor treatments.
Published: 2023

3. Eremoxylarins D–J, Antibacterial Eremophilane Sesquiterpenes Discovered from an Endolichenic Strain of Xylaria hypoxylon

Author: Alice Miral, Solenn Ferron, Isabelle Rouaud, Dinmukhammed Slyambayev, Latifa Bousarghin, Charline Camuzet, Sandrine Belouzard, Karin Séron, Pierre Le Pogam, Sylvain Tranchimand, Sophie Tomasi, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Biomolécules : Conception, Isolement, Synthèse (BioCIS), and Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY)
Subjects: Specialized metabolites, Pharmacology, Complementary and alternative medicine, Fungal compounds, Organic Chemistry, Drug Discovery, Pharmaceutical Science, Molecular Medicine, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Bioactive compounds, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Structural identification, Analytical Chemistry
Abstract: International audience; An endolichenic strain of the Ascomycetaceous Xylaria hypoxylon, cultivated alone or in coculture with another endolichenic fungus Dendrothyrium variisporum, produced seven new bioactive eremophilane sesquiterpenes eremoxylarins D−J (1−7). The isolated compounds disclosed a high similarity with the eremophilane core of the bioactive integric acid, and structures were elucidated by 1D and 2D NMR spectra and electronic circular dichroism (ECD) analyses. Eremoxylarins D, F, G, and I showed a selective activity against Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus with minimum inhibitory concentration (MIC) values between 0.39 and 12.5 μg/mL. Eremoxylarin I, the most antibacterial active sesquiterpene, was also active against HCoV-229E at a concentration nontoxic to the hepatoma Huh-7 cell line with an 50% inhibitory concentration (IC 50) of 18.1 μM and a 50% cytotoxic concentration (CC 50) of 46.6 μM.
Published: 2023

4. The structure of pathogenic huntingtin exon 1 defines the bases of its aggregation propensity

Author: Carlos A. Elena-Real, Amin Sagar, Annika Urbanek, Matija Popovic, Anna Morató, Alejandro Estaña, Aurélie Fournet, Christine Doucet, Xamuel L. Lund, Zhen-Dan Shi, Luca Costa, Aurélien Thureau, Frédéric Allemand, Rolf E. Swenson, Pierre-Emmanuel Milhiet, Ramon Crehuet, Alessandro Barducci, Juan Cortés, Davy Sinnaeve, Nathalie Sibille, Pau Bernadó, Centre de Biologie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Équipe Robotique et InteractionS (LAAS-RIS), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Institut Laue-Langevin (ILL), National Institutes of Health [Bethesda] (NIH), Beamline SWING, Synchrotron SOLEIL, Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Institute for Advanced Chemistry of Catalonia, Biologie Structurale Intégrative (ERL 9002 - BSI ), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), ANR-10-LABX-0012,EpiGenMed,From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow(2010), ANR-17-CE11-0022,GPCteR,Mécanismes moléculaires des régions C-terminales désordonnées et fonctionnelles des RCPG et impact sur les voies de la signalisation cellulaire dépendantes de l'arrestine(2017), ANR-19-P3IA-0004,ANITI,Artificial and Natural Intelligence Toulouse Institute(2019), European Project: 648030,H2020,ERC-2014-CoG,chemREPEAT(2015), and European Commission
Subjects: Huntington’s disease is a neurodegenerative disorder, poly-Q-related diseases, Pathogenic huntingtin, Structural Biology, [SDV]Life Sciences [q-bio], Proteins, Protein aggregation, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], HTT gene, Solution-state NMR, Molecular Biology
Abstract: Huntington's disease is a neurodegenerative disorder caused by a CAG expansion in the first exon of the HTT gene, resulting in an extended polyglutamine (poly-Q) tract in huntingtin (httex1). The structural changes occurring to the poly-Q when increasing its length remain poorly understood due to its intrinsic flexibility and the strong compositional bias. The systematic application of site-specific isotopic labeling has enabled residue-specific NMR investigations of the poly-Q tract of pathogenic httex1 variants with 46 and 66 consecutive glutamines. Integrative data analysis reveals that the poly-Q tract adopts long α-helical conformations propagated and stabilized by glutamine side chain to backbone hydrogen bonds. We show that α-helical stability is a stronger signature in defining aggregation kinetics and the structure of the resulting fibrils than the number of glutamines. Our observations provide a structural perspective of the pathogenicity of expanded httex1 and pave the way to a deeper understanding of poly-Q-related diseases., We thank G. Otting (Australian National University, Canberra, Australia) for providing the BL21 (DE3) Star::RF1-CBD3 strain. This work was supported by the European Research Council under the European Union’s H2020 Framework Programme (2014–2020)/ERC grant agreement no. 648030 and Labex EpiGenMed, an Investissements d’avenir program (grant no. ANR-10-LABX-12-01) awarded to P.B., grant no. ANR-17-CE11-0022-01 awarded to N.S. and grant no. ANR-19-PI3A-0004 awarded to J.C. The Centre for Structural Biology (CBS) is a member of France-BioImaging (FBI) and the French Infrastructure for Integrated Structural Biology, two national infrastructures supported by the French National Research Agency (grant nos. ANR-10-INBS-04-01 and ANR-10-INBS-05, respectively). A.U. is supported by a grant from the Fondation pour la Recherche Médicale (grant no. SPF20150934061). D.S. acknowledges a grant from the Métropole Européenne de Lille (PUSHUP). G. Levy (Université de Lille) is thanked for help with sample preparation and the 19F-NMR experiments. This work benefited from the high-performance computing resources of CSUC and the CALMIP supercomputing center under the allocations 2016-P16032 and 2021-P21043. The 600 MHz spectrometer for 19F-NMR measurements is funded by the Nord Region Council, CNRS, Institut Pasteur de Lille, the European Community (European Regional Development Fund, ERDF), the French Ministry of Research and the Université de Lille and by the CTRL CPER cofunded by the European Union with the ERDF, by the Hauts-de-France Regional Council (contract no. 17003781), Métropole Européenne de Lille (contract no. 2016_ESR_05) and the French State (contract no .2017-R3-CTRL-Phase1). We thank the SWING beamline at the SOLEIL synchrotron, Saint-Aubin, France (proposal 20181386), and P12 beamline at PETRAIII, Hamburg, Germany, for beamtime allocation to the project and assistance during data collection.
Published: 2023

5. Predictive value of the TRI-SCORE for in-hospital mortality after redo isolated tricuspid valve surgery

Author: Julien Dreyfus, Yohann Bohbot, Augustin Coisne, Yoan Lavie-Badie, Michele Flagiello, Baptiste Bazire, Florian Eggenspieler, Florence Viau, Elisabeth Riant, Yannick Mbaki, Damien Eyharts, Thomas Sénage, Thomas Modine, Martin Nicol, Fabien Doguet, Thierry Le Tourneau, Christophe Tribouilloy, Erwan Donal, Jacques Tomasi, Gilbert Habib, Christine Selton-Suty, Costin Radu, Pascal Lim, Richard Raffoul, Bernard Iung, Jean-Francois Obadia, Etienne Audureau, David Messika-Zeitoun, Centre cardiologique du Nord (CCN), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Lille, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre hospitalier universitaire de Nantes (CHU Nantes), Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Lariboisière-Fernand-Widal [APHP], CHU Rouen, Normandie Université (NU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Service de cardiologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Département de Cardiologie [Hôpital de la Timone - APHM], and Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: tricuspid valve insufficiency, Cardiology and Cardiovascular Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectivesThe TRI-SCORE reliably predicts in-hospital mortality after isolated tricuspid valve surgery (ITVS) on native valve but has not been tested in the setting of redo interventions. We aimed to evaluate the predictive value of the TRI-SCORE for in-hospital mortality in patients with redo ITVS and to compare its accuracy with conventional surgical risk scores.MethodsUsing a mandatory administrative database, we identified all consecutive adult patients who underwent a redo ITVS at 12 French tertiary centres between 2007 and 2017. Baseline characteristics and outcomes were collected from chart review and surgical scores were calculated.ResultsWe identified 70 patients who underwent a redo ITVS (54±15 years, 63% female). Prior intervention was a tricuspid valve repair in 51% and a replacement in 49%, and was combined with another surgery in 41%. A tricuspid valve replacement was performed in all patients for the redo surgery. Overall, in-hospital mortality and major postoperative complication rates were 10% and 34%, respectively. The TRI-SCORE was the only surgical risk score associated with in-hospital mortality (p=0.005). The area under the receiver operating characteristic curve for the TRI-SCORE was 0.83, much higher than for the logistic EuroSCORE (0.58) or EuroSCORE II (0.61). The TRI-SCORE was also associated with major postoperative complication rates and survival free of readmissions for heart failure.ConclusionRedo ITVS was rarely performed and was associated with an overall high in-hospital mortality and morbidity, but hiding important individual disparities. The TRI-SCORE accurately predicted in-hospital mortality after redo ITVS and may guide clinical decision-making process (www.tri-score.com).
Published: 2023

6. Cognitive Behavioral Therapy for Anxiety in Parkinson’s Disease Induces Functional Brain Changes

Author: Guillaume, Carey, Renaud, Lopes, Anja J H, Moonen, Anne E P, Mulders, Joost J A, de Jong, Gregory, Kuchcinski, Luc, Defebvre, Mark L, Kuijf, Kathy, Dujardin, Albert F G, Leentjens, 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), CHU Lille, Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Maastricht University [Maastricht], MJ Fox Foundation, Psychology 2, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, MUMC+: MA Niet Med Staf Psychologie (9), RS: MHeNs - R3 - Neuroscience, MUMC+: DA BV Research (9), Beeldvorming, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), and MUMC+: MA Med Staf Spec Psychiatrie (9)
Subjects: Cellular and Molecular Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, Neurology (clinical)
Abstract: BACKGROUND: Cognitive behavioral therapy (CBT) reduces anxiety symptoms in patients with Parkinson's disease (PD).OBJECTIVE: The objective of this study was to identify changes in functional connectivity in the brain after CBT for anxiety in patients with PD.METHODS: Thirty-five patients with PD and clinically significant anxiety were randomized over two groups: CBT plus clinical monitoring (10 CBT sessions) or clinical monitoring only (CMO). Changes in severity of anxiety symptoms were assessed with the Parkinson Anxiety Scale (PAS). Resting-state functional brain MRI was performed at baseline and after the intervention. Functional networks were extracted by an Independent Component Analysis (ICA). Functional connectivity (FC) changes between structures involved in the PD-related anxiety circuits, such as the fear circuit (involving limbic, frontal, and cingulate structures) and the cortico-striato-thalamo-cortical limbic circuit, and both within and between functional networks were compared between groups and regressed with anxiety symptoms changes.RESULTS: Compared to CMO, CBT reduced the FC between the right thalamus and the bilateral orbitofrontal cortices and increased the striato-frontal FC. CBT also increased the fronto-parietal FC within the central executive network (CEN) and between the CEN and the salience network. After CBT, improvement of PAS-score was associated with an increased striato-cingulate and parieto-temporal FC, and a decreased FC within the default-mode network and between the dorsal attentional network and the language network.CONCLUSION: CBT in PD-patients improves anxiety symptoms and is associated with functional changes reversing the imbalance between PD-related anxiety circuits and reinforcing cognitive control on emotional processing.
Published: 2023

7. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author: Mark K. Bakker, Jos P. Kanning, Gad Abraham, Amy E. Martinsen, Bendik S. Winsvold, John-Anker Zwart, Romain Bourcier, Tomonobu Sawada, Masaru Koido, Yoichiro Kamatani, Sandrine Morel, Philippe Amouyel, Stéphanie Debette, Philippe Bijlenga, Takiy Berrandou, Santhi K. Ganesh, Nabila Bouatia-Naji, Gregory Jones, Matthew Bown, Gabriel J.E. Rinkel, Jan H. Veldink, Ynte M. Ruigrok, Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian’an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex SF Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David CM Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth JF Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O’Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda WJH Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna MM Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin NA Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M. Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Lynn Cherkas, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Christian Kubisch, Michel D Ferrari, Andrea C Belin, Maija Wessman, Arn M J M van den Maagdenberg, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Dale R Nyholt, Masato Akiyama, Varinder S. Alg, Joseph P. Broderick, Ben M. Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M. Friedrich, Emília I. Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C. Hostettler, Henry Houlden, Juha E. Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y. Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A. Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W. M. Monique Verschuren, Robin G. Walters, David J. Werring, Cristen J. Willer, Daniel Woo, Bradford B. Worrall, Sirui Zhou, Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Systems Ecology, Sociology and Social Gerontology, Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J. E., Veldink, Jan H., Ruigrok, Ynte M., Girotto, G., All-In Stroke, Hunt, Group, Cadisp, Consortium for Blood Pressure, International, Headache Genetics Consortium, International, Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, International, Utrecht University [Utrecht], Baker Heart and Diabetes Institute (AUSTRALIA), University of Melbourne, University of Oslo (UiO), Norwegian University of Science and Technology (NTNU), Oslo University Hospital [Oslo], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), The University of Tokyo (UTokyo), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Université de Genève = University of Geneva (UNIGE), Excellence Laboratory LabEx DISTALZ, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), CHU Bordeaux [Bordeaux], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Otago [Dunedin, Nouvelle-Zélande], University of Leicester, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, HUNT All-In Stroke, CADISP group, International Consortium for Blood Pressure, International Headache Genetics Consortium, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group: Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian'an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex Sf Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David Cm Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth Jf Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O'Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda Wjh Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna Mm Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin Na Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tonu Esko, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Terho Lehtimäki, Antti-Pekka Sarin, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Paul M Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Jouke-Jan Hottenga, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Reedik Mägi, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Veikko Salomaa, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Lynn Cherkas, Linda M Pedersen, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Lili Milani, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Andres Metspalu, Christian Kubisch, David P Strachan, Michel D Ferrari, Andrea C Belin, Martin Dichgans, Maija Wessman, Arn M J M van den Maagdenberg, Dorret I Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Daniel I Chasman, Dale R Nyholt, Aarno Palotie, Masato Akiyama, Varinder S Alg, Sigrid Børte, Joseph P Broderick, Ben M Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M Friedrich, Emília I Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C Hostettler, Henry Houlden, Kristian Hveem, Juha E Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W M Monique Verschuren, Robin G Walters, David J Werring, Cristen J Willer, Daniel Woo, Bradford B Worrall, Sirui Zhou, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Admin, Oskar
Subjects: Advanced and Specialized Nursing, Incidence, risk assessment, Smoking/epidemiology, intracranial aneurysm, genetic heterogeneity, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Risk Factors, Intracranial Aneurysm/epidemiology, Humans, Subarachnoid Hemorrhage/epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, genetics, Neurology (clinical), aneurysmal subarachnoid hemorrhage, genetic, Cardiology and Cardiovascular Medicine
Abstract: Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20–1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01–1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59–0.67) to 0.65 (95% CI, 0.62–0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=−4.82×10 −3 per year [95% CI, −6.49×10 −3 to −3.14×10 −3 ]; P =1.82×10 −8 ), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86–0.98]; P =0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.
Published: 2023

8. Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab in Localized Deficient Mismatch Repair/Microsatellite Instability–High Gastric or Esophagogastric Junction Adenocarcinoma: The GERCOR NEONIPIGA Phase II Study

Author: Thierry André, David Tougeron, Guillaume Piessen, Christelle de la Fouchardière, Christophe Louvet, Antoine Adenis, Marine Jary, Christophe Tournigand, Thomas Aparicio, Jérôme Desrame, Astrid Lièvre, Marie-Line Garcia-Larnicol, Thomas Pudlarz, Romain Cohen, Salomé Memmi, Dewi Vernerey, Julie Henriques, Jérémie H. Lefevre, Magali Svrcek, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Institut Mutualiste de Montsouris (IMM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital privé Jean Mermoz [Lyon], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Cooperator Multidisciplinary Oncology Group (GERCOR), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and We thank Bristol Myers Squibb for supplying nivolumab and ipilimumab and for the partial financial support and the ARCAD (Aide et Recherche en Cancérologie Digestive) Foundation for partial financial support.
Subjects: nivolumab, Cancer Research, clinical trial, gastroesophageal junction, [SDV.CAN]Life Sciences [q-bio]/Cancer, stomach tumor, Adenocarcinoma, tumor recurrence, DNA Mismatch Repair, phase 2 clinical trial, mismatch repair, Oncology, Stomach Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Humans, pathology, Microsatellite Instability, genetics, Esophagogastric Junction, human, neoadjuvant therapy, Neoplasm Recurrence, Local, ipilimumab, antineoplastic agent, Aged
Abstract: PURPOSE In patients with resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma, surgery plus perioperative platinum-based chemotherapy is the standard of care. Perioperative chemotherapy remains debatable for gastric/GEJ adenocarcinoma with deficient mismatch repair (dMMR)/microsatellite instability–high (MSI-H). PATIENTS AND METHODS NEONIPIGA (ClinicalTrials.gov identifier: NCT04006262 ) phase II study evaluated neoadjuvant nivolumab 240 mg once every two weeks ×6 and ipilimumab 1 mg/kg once every six weeks ×2, followed by surgery and adjuvant nivolumab 480 mg once every four weeks (nine injections) in patients with locally advanced resectable dMMR/MSI-H, clinical (c) tumor (T)2-T4 node (N)x metastasis (M)0 gastric/GEJ adenocarcinoma. The primary end point was a pathological complete response (pCR) rate. RESULTS Between October 2019 and June 2021, 32 patients with dMMR/MSI-H gastric/GEJ adenocarcinoma were enrolled. The median age was 65.5 years (range, 40-80). Clinical stages were cT2-T3N0 (n = 9), cT2-T3N1 (n = 22), and cT3N1M1 (n = 1, wrongly included). With a median follow-up of 14.9 months (95% CI, 10.6 to 17.6), 32 patients received neoadjuvant immunotherapy (27 patients completed all cycles). Neoadjuvant therapy-related grade 3/4 adverse events occurred in six patients (19%). Twenty-nine patients underwent surgery; three did not have surgery and had complete endoscopic response with tumor-free biopsies and a normal computed tomography scan (two refused surgery and one had metastasis at inclusion). The rate of surgical morbidity (Clavien-Dindo classification) was 55% (one postoperative death occurred). All 29 patients had an R0 resection, and 17 (58.6%; 90% CI, 41.8 to 74.1) had pCR (pathological T0N0). Becker tumor regression grades 1a, 1b, 2, and 3 were observed in 17 patients, three (including two pathological T0N1), two, and seven patients, respectively. Of the 29 patients with surgery, 23 received adjuvant nivolumab. At database lock, no patient had relapse and one died without relapse. CONCLUSION Nivolumab and ipilimumab-based neoadjuvant therapy is feasible and associated with no unexpected toxicity and a high pCR rate in patients with dMMR/MSI-H resectable gastric/GEJ adenocarcinoma.
Published: 2023

9. Prognosis and chemosensitivity of non-colorectal alimentary tract cancers with microsatellite instability

Author: Claire Boyer, David Sefrioui, Romain Cohen, Romain Chautard, Marine Perrier, Hugo Lebrun, Gael Goujon, Vincent Hautefeuille, Marie Dior, Thomas Walter, Florence Mary, Silvain Manfredi, Francois-Xavier Caroli-Bosc, Baptiste Cervantes, Romain Coriat, Elise Deluche, Aziz Zaanan, Raphael Olivier, Olivier Bouché, Guillaume Piessen, Thierry Lecomte, Christophe Louvet, Pierre Michel, Thomas Aparicio, Thierry André, Julien Taieb, Violaine Randrian, David Tougeron, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Communications Cellulaires et Différenciation (CCD), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Université Paris Cité (UPCité), Centre de Bioinformatique (CBIO), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Hôpital Avicenne [AP-HP], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Hôpital Cochin [AP-HP], CHU Limoges, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Hepatology, [SDV]Life Sciences [q-bio], Gastroenterology, Humans, Microsatellite Instability, Middle Aged, Prognosis, Colorectal Neoplasms, Colorectal Neoplasms, Hereditary Nonpolyposis, DNA Mismatch Repair
Abstract: Data on outcomes of microsatellite instable and/or mismatch repair deficient (dMMR/MSI) digestive non-colorectal tumors are limited.To evaluate overall survival (OS) of patients with dMMR/MSI digestive non-colorectal tumor.All consecutive patients with a dMMR/MSI digestive non-colorectal tumor were included in this French retrospective multicenter study.One hundred and sixteen patients were included with a mean age of 63.6 years and 32.6% with a Lynch syndrome. Most tumors were oesophago-gastric (54.3%) or small bowel (32.8%) adenocarcinomas and at a localized stage at diagnosis (86.7%). In patients with localized tumors and R0 resection, median OS was 134.0 ± 64.2 months. Median disease-free survival (DFS) was 100.3 ± 65.7 months. Considering oesophago-gastric tumors, median DFS was improved when chemotherapy was added to surgery (not reached versus 22.8 ± 10.0 months, p = 0.03). In patients with advanced tumors treated by chemotherapy, median OS was 14.2 ± 1.9 months and median progression-free survival was 7.4 ± 1.6 months.dMMR/MSI digestive non-colorectal tumors are mostly diagnosed at a non-metastatic stage with a good prognosis. Advanced dMMR/MSI digestive non-colorectal tumors have a poor prognosis with standard chemotherapy.
Published: 2023

10. Tricyclic SpiroLactams Kill Mycobacteria In Vitro and In Vivo by Inhibiting Type II NADH Dehydrogenases

Author: Sushovan Dam, Salia Tangara, Claire Hamela, Theo Hattabi, Léo Faïon, Paul Carre, Rudy Antoine, Adrien Herledan, Florence Leroux, Catherine Piveteau, Maxime Eveque, Marion Flipo, Benoit Deprez, Laurent Kremer, Nicolas Willand, Baptiste Villemagne, Ruben C. Hartkoorn, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177 (M2SV), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut de Recherche en Infectiologie de Montpellier (IRIM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), the CPER grants were funded by European Union under the European Regional Development Fund (ERDF) and by the Hauts de Franceregional Council (contract n°20002842 and contract n°18006176), ANR-16-IDEX-0004,ULNE,ULNE(2016), ANR-19-CE18-0034,NL4TB,Nouvelle génération de composés Lead pour combattre la tuberculose(2019), and Willand, Nicolas
Subjects: [CHIM.ORGA]Chemical Sciences/Organic chemistry, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Antitubercular Agents, Mycobacterium tuberculosis, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, NAD, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Drug Discovery, Animals, Molecular Medicine, NADH, NADPH Oxidoreductases, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Zebrafish
Abstract: International audience; It is critical that novel classes of antituberculosis drugs are developed to combat the increasing burden of infections by multidrug-resistant strains. To identify such a novel class of antibiotics, a chemical library of unique 3-D bioinspired molecules was explored revealing a promising, mycobacterium specific Tricyclic SpiroLactam (TriSLa) hit. Chemical optimization of the TriSLa scaffold delivered potent analogues with nanomolar activity against replicating and nonreplicating Mycobacterium tuberculosis. Characterization of isolated TriSLa-resistant mutants, and biochemical studies, found TriSLas to act as allosteric inhibitors of type II NADH dehydrogenases (Ndh-2 of the electron transport chain), resulting in an increase in bacterial NADH/NAD+ ratios and decreased ATP levels. TriSLas are chemically distinct from other inhibitors of Ndh-2 but share a dependence for fatty acids for activity. Finally, in vivo proof-of-concept studies showed TriSLas to protect zebrafish larvae from Mycobacterium marinum infection, suggesting a vulnerability of Ndh-2 inhibition in mycobacterial infections.
Published: 2022

11. Can Dopamine Responsiveness Be Predicted in Parkinson’s Disease Without an Acute Administration Test?

Author: Betrouni, Nacim, Moreau, Caroline, Rolland, Anne-Sophie, Carrière, Nicolas, Viard, Romain, Lopes, Renaud, Kuchcinski, Gregory, Eusebio, Alexandre, Thobois, Stephane, Hainque, Elodie, Hubsch, Cecile, Rascol, Olivier, Brefel, Christine, Drapier, Sophie, Giordana, Caroline, Durif, Franck, Maltête, David, Guehl, Dominique, Hopes, Lucie, Rouaud, Tiphaine, Jarraya, Bechir, Benatru, Isabelle, Tranchant, Christine, Tir, Melissa, Chupin, Marie, Bardinet, Eric, Defebvre, Luc, Corvol, Jean-Christophe, Devos, David, 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 recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Lille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), 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), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), CHU Bordeaux [Bordeaux], Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), and Université de Picardie Jules Verne (UPJV)
Subjects: Antiparkinson Agents, Levodopa, Cellular and Molecular Neuroscience, Dopamine, [SCCO.NEUR]Cognitive science/Neuroscience, Humans, Parkinson Disease, Neurology (clinical), Magnetic Resonance Imaging
Abstract: Background: Dopamine responsiveness (dopa-sensitivity) is an important parameter in the management of patients with Parkinson’s disease (PD). For quantification of this parameter, patients undergo a challenge test with acute Levodopa administration after drug withdrawal, which may lead to patient discomfort and use of significant resources. Objective: Our objective was to develop a predictive model combining clinical scores and imaging. Methods: 350 patients, recruited by 13 specialist French centers and considered for deep brain stimulation, underwent an acute L-dopa challenge (dopa-sensitivity > 30%), full assessment, and MRI investigations, including T1w and R2* images. Data were randomly divided into a learning base from 10 centers and data from the remaining centers for testing. A machine selection approach was applied to choose the optimal variables and these were then used in regression modeling. Complexity of the modelling was incremental, while the first model considered only clinical variables, the subsequent included imaging features. The performances were evaluated by comparing the estimated values and actual values Results: Whatever the model, the variables age, sex, disease duration, and motor scores were selected as contributors. The first model used them and the coefficients of determination (R2) was 0.60 for the testing set and 0.69 in the learning set (p
Published: 2022

12. Immediate versus staged complete myocardial revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease: A post hoc analysis of the randomized FLOWER-MI trial

Author: Victoria Tea, Jean-François Morelle, Romain Gallet, Guillaume Cayla, Gilles Lemesle, Thibault Lhermusier, Jean-Guillaume Dillinger, Grégory Ducrocq, Denis Angouvant, Yves Cottin, Chekrallah Chamandi, Alicia le Bras, Philippe Gabriel Steg, Gilles Montalescot, Anaïs Charles Nelson, Tabassome Simon, Gilles Chatellier, Nicolas Danchin, Etienne Puymirat, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital privé Saint-Martin - Ramsay Santé, Service de Cardiologie [Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, IMRB - 'Biologie du système neuromusculaire' [Créteil] (U955 Inserm - UPEC), École nationale vétérinaire - Alfort (ENVA)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Alliance française pour les essais cliniques cardio-vasculaires - French Alliance for Cardiovascular Trials (FACT), Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Toulouse III Paul Sabatier - Faculté de médecine Purpan (UTPS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Service Cardiologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service de Chirurgie Thoracique et Vasculaire [Hôpital Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Physiopathologie et épidémiologie cérébro-cardiovasculaire [Dijon] (PEC2), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Cardiologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe Action, Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Unité de recherche Phytopharmacie et Médiateurs Chimiques (UPMC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), and Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Fractional flow reserve, Multivessel disease, MESH: Humans, MESH: Percutaneous Coronary Intervention / methods, Acute myocardial infarction, Coronary Artery Disease, General Medicine, MESH: Myocardial Revascularization / methods, MESH: Fractional Flow Reserve, Myocardial, Fractional Flow Reserve, Myocardial, MESH: Coronary Artery Disease / surgery, Percutaneous Coronary Intervention, Treatment Outcome, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Myocardial Revascularization, Humans, ST Elevation Myocardial Infarction, MESH: Coronary Artery Disease / diagnostic imaging, MESH: ST Elevation Myocardial Infarction / diagnostic imaging, Cardiology and Cardiovascular Medicine, MESH: ST Elevation Myocardial Infarction / therapy, MESH: Treatment Outcome
Abstract: International audience; Background: in patients with ST-segment elevation myocardial infarction and multivessel disease, percutaneous coronary intervention for non-culprit lesions is superior to treatment of the culprit lesion alone. The optimal timing for non-infarct-related artery revascularization - immediate versus staged - has not been investigated adequately. Aim: we aimed to assess clinical outcomes at 1 year in patients with ST-segment elevation myocardial infarction with multivessel disease using immediate versus staged non-infarct-related artery revascularization. Methods: outcomes were analysed in patients from the randomized FLOWER-MI trial, in whom, after successful primary percutaneous coronary intervention, non-culprit lesions were assessed using fractional flow reserve or angiography during the index procedure or during a staged procedure during the initial hospital stay, ≤5 days after the index procedure. The primary outcome was a composite of all-cause death, non-fatal myocardial infarction and unplanned hospitalization with urgent revascularization at 1 year. Results: among 1171 patients enrolled in this study, 1119 (96.2%) had complete revascularization performed during a staged procedure, and 44 (3.8%) at the time of primary percutaneous coronary intervention. During follow-up, a primary outcome event occurred in one of the patients (2.3%) with an immediate strategy and in 55 patients (4.9%) with a staged strategy (adjusted hazard ratio 1.44, 95% confidence interval 0.39-12.69; P=0.64). Conclusions: staged non-infarct-related artery complete revascularization was the strategy preferred by investigators in practice in patients with ST-segment elevation myocardial infarction with multivessel disease. This strategy was not superior to immediate revascularization, which, in the context of this trial, was used in a small proportion of patients. Further randomized studies are needed to confirm these observational findings.
Published: 2022

13. Harnessing the Vnn1 pantetheinase pathway boosts short chain fatty acids production and mucosal protection in colitis

Author: Virginie Millet, Thomas Gensollen, Michael Maltese, Melanie Serrero, Nathalie Lesavre, Christophe Bourges, Christophe Pitaval, Sophie Cadra, Lionel Chasson, Thien Phong Vu Man, Marion Masse, Juan Jose Martinez-Garcia, Fabrice Tranchida, Laetitia Shintu, Konrad Mostert, Erick Strauss, Patricia Lepage, Mathias Chamaillard, Achille Broggi, Laurent Peyrin-Biroulet, Jean-Charles Grimaud, Philippe Naquet, Franck Galland, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Harvard Medical School [Boston] (HMS), Brigham & Women’s Hospital [Boston] (BWH), Service de Gastro-entérologie [CHU Hôpital Nord - Marseille], Hôpital Nord [CHU - APHM]-Assistance publique Hôpitaux de Marseille (APHM), CIC - Hôpital Nord AP-HM Marseille, The Francis Crick Institute [London], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Stellenbosch University, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d’Hépato-gastro-entérologie et oncologie digestive [Hôpital Nord, AP-HM], and Hôpital Nord [CHU - APHM]
Subjects: [SDV]Life Sciences [q-bio], Gastroenterology
Abstract: ObjectiveIn the management of patients with IBD, there is a need to identify prognostic markers and druggable biological pathways to improve mucosal repair and probe the efficacy of tumour necrosis factor alpha biologics. Vnn1 is a pantetheinase that degrades pantetheine to pantothenate (vitamin B5, a precursor of coenzyme A (CoA) biosynthesis) and cysteamine. Vnn1 is overexpressed by inflamed colonocytes. We investigated its contribution to the tolerance of the intestinal mucosa to colitis-induced injury.DesignWe performed an RNA sequencing study on colon biopsy samples from patients with IBD stratified according to clinical severity and modalities of treatment. We generated the VIVA mouse transgenic model, which specifically overexpresses Vnn1 on intestinal epithelial cells and explored its susceptibility to colitis. We developed a pharmacological mimicry of Vnn1 overexpression by administration of Vnn1 derivatives.ResultsVNN1 overexpression on colonocytes correlates with IBD severity. VIVA mice are resistant to experimentally induced colitis. The pantetheinase activity of Vnn1 is cytoprotective in colon: it enhances CoA regeneration and metabolic adaptation of colonocytes; it favours microbiota-dependent production of short chain fatty acids and mostly butyrate, shown to regulate mucosal energetics and to be reduced in patients with IBD. This prohealing phenotype is recapitulated by treating control mice with the substrate (pantethine) or the products of pantetheinase activity prior to induction of colitis. In severe IBD, the protection conferred by the high induction of VNN1 might be compromised because its enzymatic activity may be limited by lack of available substrates. In addition, we identify the elevation of indoxyl sulfate in urine as a biomarker of Vnn1 overexpression, also detected in patients with IBD.ConclusionThe induction of Vnn1/VNN1 during colitis in mouse and human is a compensatory mechanism to reinforce the mucosal barrier. Therefore, enhancement of vitamin B5-driven metabolism should improve mucosal healing and might increase the efficacy of anti-inflammatory therapy.
Published: 2022

14. EACVI SIMULATOR-online study: evaluation of transoesophageal echocardiography knowledge and skills of young cardiologists

Author: Théo Pezel, Augustin Coisne, Błażej Michalski, Hatem Soliman, Nina Ajmone, Robin Nijveldt, Ivan Stankovic, Erwan Donal, Joost van der Maaten, Constantinos Papadopoulos, Thor Edvardsen, Denisa Muraru, Steffen E Petersen, Bernard Cosyns, Magnus Bäck, Philippe B Bertrand, Kristina H Haugaa, Niall Keenan, Université Paris Cité (UPCité), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Lódź, Universiteit Leiden, Radboud University [Nijmegen], University of Belgrade [Belgrade], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), University Medical Center Groningen [Groningen] (UMCG), Oslo University Hospital [Oslo], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), William Harvey Research Institute, Barts and the London Medical School, Universitair Ziekenhuis Brussel = University Hospital of Brussels (UZ Brussel), None, Clinical sciences, Cardio-vascular diseases, Cardiology, Pezel, T, Coisne, A, Michalski, B, Soliman, H, Ajmone, N, Nijveldt, R, Stankovic, I, Donal, E, van der Maaten, J, Papadopoulos, C, Edvardsen, T, Muraru, D, Petersen, S, and Cosyns, B
Subjects: EUROPEAN ASSOCIATION, education, knowledge, skills, IMPACT, [SDV]Life Sciences [q-bio], Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, General Medicine, PERFORMANCE, simulation, RECOMMENDATIONS, TRAINEES, transesophageal echocardiography (TOE), PAPER, Radiology, Nuclear Medicine and imaging, skill, Cardiology and Cardiovascular Medicine
Abstract: AimsTo assess the level of transesophageal echocardiography (TOE) knowledge and skills of young cardiologists.Methods and resultsA European Association of Cardiovascular Imaging (EACVI) online study using the first fully virtual simulation-based software was conducted in two periods (9–12 December 2021 and 10–13 April 2022). All young cardiologists eligible to participate (ConclusionOnline evaluation of young cardiologists around the world showed a relatively low level of TOE skills and knowledge. Prior participation to a TOE simulation-based training session, a higher number of TOE exams performed per week, and the EACVI certification for TOE were independently associated with a higher global score.
Published: 2022

15. Market concentration and the healthiness of packaged food and non-alcoholic beverage sales across the European single market

Author: Van Dam Iris, Vandevijvere Stefanie, Allais Olivier, Paris-Saclay Applied Economics (UMR PSAE), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service of Lifestyle and Chronic Diseases, Sciensano [Bruxelles], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and European Project
Subjects: Nutrition and Dietetics, Food industry, NOVA, Commerce, Public Health, Environmental and Occupational Health, Medicine (miscellaneous), Food supply, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Beverages, Europe, Market power, Food, Food environments, Humans, Market structure
Abstract: Objective:To assess the relationship between market concentration and diversity, as indicators of market structure, and the healthiness of food and beverage sales across Europe.Design:Market share (MS) data per country were used to calculate market concentration, assessed by the four-firm concentration ratio and market diversity, and by the number of companies with ≥1 % MS and the number of companies uniquely present in one European country. The healthiness of food sales was assessed by applying the NOVA classification (level of processing). Simple and multiple linear regressions were performed to assess the relationship between market concentration, diversity and the healthiness of food and beverage sales.Setting:The European single market.Participants:The twenty-seven European single market member states for which Euromonitor sales data were available at the most fine-grained Euromonitor packaged food and non-alcoholic beverage product subcategory level.Results:Increased market concentration with a country and a product category fixed effect significantly predicted increased sales of ultra-processed packaged food products. There was insufficient data variability in the level of processing of non-alcoholic beverage product categories to formulate conclusions for non-alcoholic beverages. Increased market diversity in turn significantly predicted reduced country-level sales of ultra-processed products.Conclusions:The results indicated a relationship between market structure and the healthiness of packed food products sold on the European market. However, more research with detailed nutritional data is warranted to document and quantify this interaction.
Published: 2022

16. Investigating drug resistance of Mycobacterium leprae in the Comoros: an observational deep-sequencing study

Author: Sofie Marijke Braet, Agathe Jouet, Alexandra Aubry, Magalie Van Dyck-Lippens, Esteban Lenoir, Younoussa Assoumani, Abdallah Baco, Aboubacar Mzembaba, Emmanuelle Cambau, Sidra Ezidio Gonçalves Vasconcellos, Leen Rigouts, Philip Noel Suffys, Epco Hasker, Philip Supply, Bouke Catherine de Jong, University of Antwerp (UA), Institute of Tropical Medicine [Antwerp] (ITM), Genoscreen [Lille], Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Mycobactéries et de la Résistance aux Antituberculeux [CHU Pitié-Salpêtrière] (CNR-MyRMA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Damien Foundation, 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), Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Supply, Philip, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ)
Subjects: Microbiology (medical), [SDV.GEN]Life Sciences [q-bio]/Genetics, Leprostatic Agents, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Microbiology, Comoros, Mycobacterium leprae, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Leprosy, Virology, Drug Resistance, Bacterial, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Drug Therapy, Combination, Human medicine, Rifampin, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Dapsone, Biology
Abstract: Despite strong leprosy control measures, including effective treatment, leprosy persists in the Comoros. As of May, 2022, no resistance to anti-leprosy drugs had been reported, but there are no nationally representative data. Post-exposure prophylaxis (PEP) with rifampicin is offered to contacts of patients with leprosy. We aimed to conduct a countrywide drug resistance survey and investigate whether PEP led to the emergence of drug resistance in patients with leprosy.In this observational, deep-sequencing analysis we assessed Mycobacterium leprae genomes from skin biopsies of patients in Anjouan and Mohéli, Comoros, collected as part of the ComLep (NCT03526718) and PEOPLE (NCT03662022) studies. Skin biopsies that had sufficient M leprae DNA (2000 bacilli in 2 μl of DNA extract) were assessed for the presence of seven drug resistance-associated genes (ie, rpoB, ctpC, ctpI, folP1, gyrA, gyrB, and nth) using Deeplex Myc-Lep (targeted next generation deep sequencing), with a limit of detection of 10% for minority M leprae bacterial populations bearing a polymorphism in these genes. All newly registered patients with leprosy for whom written informed consent was obtained were eligible for inclusion in the survey. Patients younger than 2 years or with a single lesion on the face did not have biopsies taken. The primary outcome of our study was the proportion of patients with leprosy (ie, new cases, patients with relapses or reinfections, patients who received single (double) dose rifampicin-PEP, or patients who lived in villages where PEP was distributed) who were infected with M leprae with a drug-resistant mutation for rifampicin, fluoroquinolone, or dapsone in the Comoros.Between July 1, 2017, and Dec 31, 2020, 1199 patients with leprosy were identified on the basis of clinical criteria, of whom 1030 provided a skin biopsy. Of these 1030 patients, 755 (73·3%) tested positive for the M leprae-specific repetitive element-quantitative PCR (qPCR) assay. Of these 755 patients, 260 (34·4%) were eligible to be analysed using Deeplex Myc-Lep. 251 (96·5%) were newly diagnosed with leprosy, whereas nine (3·4%) patients had previously received multidrug therapy. 45 (17·3%) patients resided in villages where PEP had been administered in 2015 or 2019, two (4·4%) of whom received PEP. All seven drug resistance-associated targets were successfully sequenced in 216 samples, 39 samples had incomplete results, and five had no results. No mutations were detected in any of the seven drug resistance-related genes for any patient with successfully sequenced results.This drug resistance survey provides evidence to show that M leprae is fully susceptible to rifampicin, fluoroquinolones, and dapsone in the Comoros. Our results also show, for the first time, the applicability of targeted sequencing directly on skin biopsies from patients with either paucibacillary or multibacillary leprosy. These data suggest that PEP had not selected rifampicin-resistant strains, although further support for this finding should be confirmed with a larger sample size.Effect:Hope, The Mission To End Leprosy, the Fonds Wetenschappelijk Onderzoek, the EU.
Published: 2022

17. Antibiotics with novel mode of action as new weapons to fight antimicrobial resistance

Author: Francesca Ruggieri, Nina Compagne, Kevin Antraygues, Maxime Eveque, Marion Flipo, Nicolas Willand, Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177 (M2SV), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille
Subjects: Pharmacology, Organic Chemistry, Drug Discovery, Antimicrobial resistance AMR, General Medicine, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; Antimicrobial resistance (AMR) is a major public health issue, causing 5 million deaths per year. Without any action plan, AMR will be in a near future the leading cause of death ahead of cancer. AMR comes from the ability of bacteria to rapidly develop and share resistance mechanisms towards current antibiotics, rendering them less effective. To circumvent this issue and avoid the phenomenon of cross-resistance, new antibiotics acting on novel targets or with new modes of action are required. Today, the pipeline of potential new treatments with these characteristics includes promising compounds such as gepotidacin, zoliflodacin, ibezapolstat, MGB-BP-3, CRS-3123, afabicin and TXA-709, which are currently in clinical trials, and lefamulin, which has been recently approved by FDA and EMA. In this review, we report the chemical synthesis, mode of action, structure-activity relationships, in vitro and in vivo activities as well as clinical data of these eight small molecules listed above.
Published: 2023

18. Allergic bronchopulmonary aspergillosis: A multidisciplinary review

Author: Amytis Roboubi, Camille Audousset, Émilie Fréalle, Anne-Laure Brun, François Laurent, Joana Vitte, Geoffrey Mortuaire, Guillaume Lefevre, Jacques Cadranel, Cécile Chenivesse, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie-Mycologie [CHRU LIlle], Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Foch [Suresnes], Espaces et Sociétés (ESO), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Le Mans Université (UM)-Université d'Angers (UA)-AGROCAMPUS OUEST-Université de Rennes 2 (UR2)-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), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Claude Huriez [Lille], CHU Lille, Université de Lille, Complexe de recherche interprofessionnel en aérothermochimie (CORIA), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Service de Pneumologie et Immuno-Allergologie [CHU LIlle], and Pole Cardio-vasculaire et pulmonaire [CHU Lille]
Subjects: Infectious Diseases, [SDV]Life Sciences [q-bio]
Abstract: Allergic bronchopulmonary aspergillosis (ABPA) is a rare disease characterized by a complex allergic inflam-matory reaction of airways against Aspergillus affecting patients with chronic respiratory diseases (asthma, cystic fibrosis). Exacerbation is often the way to diagnose ABPA and marks its evolution by its recurrent char-acter leading to cortico-requirement or long-term antifungal treatment. Early diagnosis allows treatment of ABPA at an initial stage, preventing recurrence of exacerbations and long-term complications, mainly repre-sented by bronchiectasis. This review of the literature aims to present the current state of the art in terms of diagnosis and treatment of ABPA from a multidisciplinary perspective. As there is no clinical, biological nor radiological specific sign, diagnostic criteria are regularly revised. They are mainly based on the elevation of total and specific IgE against Aspergillus fumigatus and the presence of suggestive CT abnormalities such as mucoid impaction and consolidations. ABPA management includes eviction of mold and pharmacological therapy. Exacerbations are treated in first line with a moderate dose of oral corticosteroids. Azole antifungal agents represent an alternative for the treatment of exacerbations and are the preferential strategy to reduce the future risk of exacerbations and for corticosteroids sparing. Asthma biologics may be of interest; how-ever, their place remains to be determined. Avoiding complications of ABPA while limiting the side effects of systemic drugs remains a major challenge of ABPA management. Several drugs, including new antifungals and asthma biologics, are currently being tested and may be useful in the future.(c) 2023 SFMM. Published by Elsevier Masson SAS. All rights reserved.
Published: 2023

19. Docosahexaenoic acid and etanercept could reduce functional and metabolic alterations during collagen-induced arthritis in rats without any synergistic effect

Author: Léger, Thibault, Brun, Aurélien, Lanchais, Kassandra, Rigaudière, Jean-Paul, Briat, Arnaud, Guitton, Yann, Marchand, Fabien, Tournadre, Anne, Capel, Frédéric, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Neuro-Dol (Neuro-Dol), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne (UCA), Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience
Published: 2023

20. Characteristics, management and outcomes of active cancer patients with cardiogenic shock

Author: Merdji, Hamid, Gantzer, Justine, Bonello, Laurent, Lamblin, Nicolas, Roubille, François, Levy, Bruno, Champion, Sebastien, Lim, Pascal, Schneider, Francis, Cariou, Alain, Khachab, Hadi, Bourenne, Jeremy, Seronde, Marie-France, Schurtz, Guillaume, Harbaoui, Brahim, Vanzetto, Gerald, Quentin, Charlotte, Curtiaud, Anais, Kurtz, Jean-Emmanuel, Combaret, Nicolas, Marchandot, Benjamin, Lattuca, Benoit, Biendel, Caroline, Leurent, Guillaume, Bataille, Vincent, Gerbaud, Edouard, Puymirat, Etienne, Bonnefoy, Eric, Aissaoui, Nadia, Delmas, Clément, Université de Strasbourg (UNISTRA), Institut de Cancérologie de Strasbourg Europe (ICANS), Assistance Publique - Hôpitaux de Marseille (APHM), Mediterranean Association for Research and Studies in Cardiology (MARS cardio), CHU Lille, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre 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), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: cardio-oncology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, cardiogenic shock, cancer, heart failure, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.CAN]Life Sciences [q-bio]/Cancer, prognosis
Abstract: International audience; Aims: Characteristics, management, and outcomes of patients with active cancer admitted for cardiogenic shock remain largely unknown. This study aimed to address this issue and identify the determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all etiologies.Methods and results: FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October 2016. "Active cancer" was defined as a malignancy diagnosed within the previous weeks with planned or ongoing anticancer therapy. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 51 (6.6%) had active cancer. Among them, the main cancer types were solid cancers (60.8%), and hematological malignancies (27.5%). Solid cancers were mainly urogenital (21.6%), gastrointestinal (15.7%), and lung cancer (9.8%). Medical history, clinical presentation, and baseline echocardiography were almost the same between groups. In-hospital management significantly differed: patients with cancers received more catecholamines or inotropes (norepinephrine 72 vs 52%, p=0.005 and norepinephrine-dobutamine combination 64.7 vs 44.5%, p=0.005), but had less mechanical circulatory support (5.9 vs 19.5%, p=0.016). They presented similar 30-day mortality rate (29 vs 26%) but a significantly higher mortality at one-year (70.6 vs 45.2%, p
Published: 2023

21. One Health compartment analysis of ESBL-producing Escherichia coli reveals multiple transmission events in a rural area of Madagascar

Author: Gay, Noellie, Rabenandrasana, Mamitina Alain Noah, Panandiniaina, Harielle Prisca, Rakotoninidrina, Marie Florence, Ramahatafandry, Ilo Tsimok’haja, Enouf, Vincent, Roger, François, Collard, Jean-Marc, Cardinale, Eric, Rieux, Adrien, Loire, Etienne, Epidemiology - Epidémiologie [Nouméa, Nouvelle-Calédonie], Institut Pasteur de Nouvelle-Calédonie, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Ministère chargé de l'Agriculture et de l'Élevage [Antananarivo, Madagascar], Pasteur International Bioresources network (PIBNet), Institut Pasteur [Paris] (IP), Peuplements végétaux et bioagresseurs en milieu tropical (UMR PVBMT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université de La Réunion (UR)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This project was funded by the Indian Ocean Health Agency (N.G., PhD fellowship), the INTERREG FEDER TROI 2018–2020 (E.C.) and the grant L’Oréal-UNESCO For Women in Science 2019 (N.G.). A.R. was financially supported by l’Agence Nationale pour la Recherche (JCJC MUSEOBACT contrat ANR-17-CE35-0009-01), the European Regional Development Fund (ERDF contract GURDT I2016-1731-0006632) and Région Réunion., and ANR-17-CE35-0009,MUSEOBACT,'Une nuit au musée': mieux reconstuire les emergences de bactéries pathogènes des cultures grâce à des échantillons historiques(2017)
Subjects: [SDV]Life Sciences [q-bio], [SDE]Environmental Sciences
Abstract: International audience; Background: ESBL-producing Escherichia coli (ESBL-Ec) is considered a key indicator for antimicrobial resistance (AMR) epidemiological surveillance in animal, human and environment compartments. There is likelihood of ESBL-Ec animal-human transmission but proof of cross-compartment transmission is still unclear.Objectives: To characterize ESBL-Ec genetic similarity in various compartments (humans, animals and environment) from a rural area of Madagascar.Methods: We collected ESBL-Ec isolates prospectively from humans, animals and the environment (water) between April and October 2018. These isolates were subject to WGS and analysed with cutting-edge phylogenomic methods to characterize population genetic structure and infer putative transmission events among compartments.Results: Of the 1454 samples collected, 512 tested positive for ESBL-Ec. We successfully sequenced 510 samples, and a phylogenomic tree based on 179 365 SNPs was produced. Phylogenetic distances between and amongst compartments were indistinguishable, and 104 clusters of recent transmission events between compartments were highlighted. Amongst a large diversity of ESBL-Ec genotypes, no lineage host specificity was observed, indicating the regular occurrence of ESBL-Ec transfer among compartments in rural Madagascar.Conclusions: Our findings stress the importance of using a phylogenomic approach on ESBL-Ec samples in various putative compartments to obtain a clear baseline of AMR transmissions in rural settings, where one wants to identify risk factors associated with transmission or to measure the effect of 'One Health' interventions in low- and middle-income countries.
Published: 2023

22. Intravenous versus subcutaneous tocilizumab in Takayasu arteritis: multicentre retrospective study

Author: Mekinian, Arsène, Biard, Lucie, Lorenzo, Dagna, Novikov, Pavel, Salvarani, Carlo, Espitia, Olivier, Sciascia, Savino, Michaud, Martin, Lambert, Marc, Hernández-Rodríguez, José, Schleinitz, Nicolas, Awisat, Abid, Puechal, Xavier, Aouba, Achille, Munoz Pons, Helene, Smitienko, Ilya, Gaultier, Jean Baptiste, Edwige, Le Mouel, Benhamou, Ygal, Perlat, Antoinette, Jego, Patrick, Goulenok, Tiphaine, Sacre, Karim, Lioger, Bertrand, Hassold, Nolan, Broner, Jonathan, Dufrost, Virginie, Sené, Thomas, Seguier, Julie, Maurier, Francois, Berthier, Sabine, Belot, Alexandre, Frikha, Faten, Denis, Guillaume, Audemard-Verger, Alexandra, Koné-Paut, Isabelle, Humbert, Sebastien, Woaye-Hune, Pascal, Tomelleri, Alessandro, Baldissera, Elena Marina, Kuwana, Masataka, Lo Gullo, Alberto, Mukuchyan, Vahan, Dellal, Azeddine, Gaches, Francis, Zeminsky, Pierre, Galli, Elena, Alvarado, Moya, Boiardi, Luigi, Muratore, Francesco, Vautier, Mathieu, Campochiaro, Corrado, Moiseev, Sergey, Vieira, Matheus, Cacoub, Patrice, Fain, Olivier, Saadoun, David, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Lille, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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), CHU Pitié-Salpêtrière [AP-HP], and The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Subjects: Inflammation, MESH: Antirheumatic Agents, MESH: Humans, MESH: Takayasu Arteritis, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Systemic vasculitis, MESH: Adult, MESH: Retrospective Studies, Autoimmune Diseases, MESH: Treatment Outcome
Abstract: Objectives: In this large multicentre study, we compared the effectiveness and safety of tocilizumab intravenous versus subcutaneous (SC) in 109 Takayasu arteritis (TAK) patients.Methods: We conducted a retrospective multicentre study in referral centres from France, Italy, Spain, Armenia, Israel, Japan, Tunisia and Russia regarding biological-targeted therapies in TAK, since January 2017 to September 2019.Results: A total of 109 TAK patients received at least 3 months tocilizumab therapy and were included in this study. Among them, 91 and 18 patients received intravenous and SC tocilizumab, respectively. A complete response (NIH
Published: 2023

23. Coregulation of extracellular vesicle production and fluconazole susceptibility in Cryptococcus neoformans

Author: Rizzo, Juliana, Trottier, Adèle, Moyrand, Frédérique, Coppée, Jean-Yves, Maufrais, Corinne, Zimbres, Ana Claudia G., Dang, Thi Tuong Vi, Alanio, Alexandre, Desnos-Ollivier, M., Mouyna, Isabelle, Péhau-Arnaude, Gérard, Commere, Pierre-Henri, Novault, Sophie, Ene, Iuliana, Nimrichter, Leonardo, Rodrigues, Marcio, Janbon, Guilhem, Biologie des ARN des Pathogènes fongiques - RNA Biology of Fungal Pathogens, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Universidade Federal do Rio de Janeiro (UFRJ), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Plate-forme de bioimagerie ultrastructurale - Ultrastructural BioImaging Core Facility, Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Hétérogénéité fongique - Fungal heterogeneity, 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), J.R. was supported by the Pasteur-Roux-Cantarini fellowship of Institut Pasteur and by FAPERJ - Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (E-26/204.456/2021). This work was supported by a CAPES COFECUB Grant no. 39712ZK to G.J., M.L.R., and L.N. The work was supported by an ANR grant (Projet ResistEV AAPG2021 CE35) to G.J., I.V.E., and A.A., T.T.V.D. was supported by the Pasteur - Paris University (PPU) International PhD Program. I.V.E. is supported by a CIFAR Azrieli Global Scholar Award., and ANR-21-CE35-0005,ResistEV,Etude des roles de vésicules extracellulaires sur la resistance aux antifongiques chez les champignons pathogènes(2021)
Subjects: fluconazole, Cryptococcus neoformans, antimicrobial resistance, extracellular vesicles, transcription factor, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
Abstract: International audience; Resistance to fluconazole (FLC), the most widely used antifungal drug, is typically achieved by altering the azole drug target and/or drug efflux pumps. Recent reports have suggested a link between vesicular trafficking and antifungal resistance. Here, we identified novel Cryptococcus neoformans regulators of extracellular vesicle (EV) biogenesis that impact FLC resistance. In particular, the transcription factor Hap2 does not affect the expression of the drug target or efflux pumps, yet it impacts the cellular sterol profile. Subinhibitory FLC concentrations also downregulate EV production. Moreover, in vitro spontaneous FLC-resistant colonies showed altered EV production, and the acquisition of FLC resistance was associated with decreased EV production in clinical isolates. Finally, the reversion of FLC resistance was associated with increased EV production. These data suggest a model in which fungal cells can regulate EV production in place of regulating the drug target gene expression as a first line of defense against antifungal assault in this fungal pathogen.IMPORTANCEExtracellular vesicles (EVs) are membrane-enveloped particles that are released by cells into the extracellular space. Fungal EVs can mediate community interactions and biofilm formation, but their functions remain poorly understood. Here, we report the identification of the first regulators of EV production in the major fungal pathogen Cryptococcus neoformans . Surprisingly, we uncover a novel role of EVs in modulating antifungal drug resistance. Disruption of EV production was associated with altered lipid composition and changes in fluconazole susceptibility. Spontaneous azole-resistant mutants were deficient in EV production, while loss of resistance restored initial EV production levels. These findings were recapitulated in C. neoformans clinical isolates, indicating that azole resistance and EV production are coregulated in diverse strains. Our study reveals a new mechanism of drug resistance in which cells adapt to azole stress by modulating EV production.
Published: 2023

24. Remdesivir for the treatment of hospitalised patients with COVID-19: final results from the DisCoVeRy randomised, controlled, open-label trial

Author: Florence Ader, Maude Bouscambert-Duchamp, Maya Hites, Nathan Peiffer-Smadja, Julien Poissy, Drifa Belhadi, Alpha Diallo, Christelle Delmas, Juliette Saillard, Aline Dechanet, Claire Fougerou, Minh-Patrick Lê, Gilles Peytavin, Noémie Mercier, Priyanka Velou, Sarah Tubiana, Xavier Lescure, Emmanuel Faure, Saad Nseir, Jean-Christophe Richard, Florent Wallet, François Goehringer, Benjamin Lefèvre, Antoine Kimmoun, François Raffi, Benjamin Gaborit, Jean Reignier, Jean-Philippe Lanoix, Claire Andrejak, Yoann Zerbib, Firouzé Bani-Sadr, Bruno Mourvilliers, François Danion, Yvon Ruch, Raphaël Clere-Jehl, Vincent Le Moing, Kada Klouche, Karine Lacombe, Guillaume Martin-Blondel, Fanny Vardon-Bounes, André Cabié, Jean-Marie Turmel, Lionel Piroth, Mathieu Blot, Élisabeth Botelho-Nevers, Amandine Gagneux-Brunon, Guillaume Thiery, François Bénézit, Rostane Gaci, Joy Mootien, Sébastien Gallien, Denis Garot, Kevin Bouiller, Loïc Epelboin, Stéphane Jauréguiberry, Alexandre Gaymard, Gil Verschelden, Sandra Braz, Joao Miguel Ferreira Ribeiro, Michael Joannidis, Thérèse Staub, Antoine Altdorfer, Richard Greil, Alexander Egle, Jérémie Guedj, Marion Noret, Roberto Roncon-Albuquerque, Jose-Artur Paiva, Bruno Lina, Dominique Costagliola, Yazdan Yazdanpanah, Charles Burdet, France Mentré, Hospices Civils de Lyon (HCL), Université libre de Bruxelles (ULB), 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, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), 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), Pôle de Recherche Clinique [Paris] (PRC), 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), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], 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), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), and Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie
Subjects: [SDV]Life Sciences [q-bio]
Abstract: BackgroundThe antiviral efficacy of remdesivir is still controversial. We aimed at evaluating its clinical effectiveness in hospitalised patients with COVID-19, with indication of oxygen and/or ventilator support. Following prior publication of preliminary results, here we present the final results after completion of data monitoring.MethodsIn this European multicentre, open-label, parallel-group, randomised, controlled trial (DisCoVeRy, NCT04315948; EudraCT2020-000936-23), participants were randomly allocated to receive usual standard of care (SoC) alone or in combination with remdesivir, lopinavir/ritonavir, lopinavir/ritonavir and IFN-β-1a, or hydroxychloroquine. Adult patients hospitalised with COVID-19 were eligible if they had clinical evidence of hypoxemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzyme, severe chronic kidney disease, any contra-indication to one of the studied treatments or their use in the 29 days before randomization, or use of ribavirin, as well as pregnancy or breast-feeding. Here, we report results for remdesivir + SoC versus SoC alone. Remdesivir was administered as 200 mg infusion on day 1, followed by once daily infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. Treatment assignation was performed via web-based block randomisation stratified on illness severity and administrative European region. The primary outcome was the clinical status at day 15 measured by the WHO 7-point ordinal scale, assessed in the intention-to-treat population.FindingsBetween March 22nd, 2020 and January 21st, 2021, 857 participants were randomised to one of the two arms in 5 European countries and 843 participants were included for the evaluation of remdesivir (control, n=423; remdesivir, n=420).At day 15, the distribution of the WHO ordinal scale was as follow in the remdesivir and control groups, respectively: Not hospitalized, no limitations on activities: 62/420 (14.8%) and 72/423 (17.0%); Not hospitalized, limitation on activities: 126/420 (30%) and 135/423 (31.9%); Hospitalized, not requiring supplemental oxygen: 56/420 (13.3%) and 31/423 (7.3%); Hospitalized, requiring supplemental oxygen: 75/420 (17.9%) and 65/423 (15.4%); Hospitalized, on non-invasive ventilation or high flow oxygen devices: 16/420 (3.8%) and 16/423 (3.8%); Hospitalized, on invasive mechanical ventilation or ECMO: 64/420 (15.2%) and 80/423 (18.9%); Death: 21/420 (5%) and 24/423 (5.7%). The difference between treatment groups was not statistically significant (OR for remdesivir, 1.02, 95% CI, 0.62 to 1.70, P=0.93). There was no significant difference in the occurrence of Serious Adverse Events between treatment groups (remdesivir, n=147/410, 35.9%, versus control, n=138/423, 32.6%, p=0.29).InterpretationRemdesivir use for the treatment of hospitalised patients with COVID-19 was not associated with clinical improvement at day 15.FundingEuropean Union Commission, French Ministry of Health, DIM One Health Île-de-France, REACTing, Fonds Erasme-COVID-ULB; Belgian Health Care Knowledge Centre (KCE), AGMT gGmbH, FEDER “European Regional Development Fund”, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Remdesivir was provided free of charge by Gilead.
Published: 2023

25. Effect of weight-adjusted intermediate-dose versus fixed-dose prophylactic anticoagulation with low-molecular-weight heparin on venous thromboembolism among noncritically and critically ill patients with COVID-19: the COVI-DOSE trial, a multicenter, randomised, open-label, phase 4 trial

Author: Zuily, Stéphane, Lefèvre, Benjamin, Sanchez, Olivier, Empis de Vendin, Ombeline, de Ciancio, Guillaume, Arlet, Jean-Benoît, Khider, Lina, Terriat, Béatrice, Greigert, Hélène, Robert, Céline, Louis, Guillaume, Trinh-Duc, Albert, Rispal, Patrick, Accassat, Sandrine, Thiery, Guillaume, Montani, David, Azarian, Réza, Meneveau, Nicolas, Soudet, Simon, Le Mao, Raphaël, Maurier, François, Le Moing, Vincent, Quéré, Isabelle, Yelnik, Cécile, Lefebvre, Nicolas, Martinot, Martin, Delrue, Maxime, Benhamou, Ygal, Parent, Florence, Roy, Pierre-Marie, Presles, Emilie, Goehringer, François, Mismetti, Patrick, Bertoletti, Laurent, Rossignol, Patrick, Couturaud, Francis, Wahl, Denis, Thilly, Nathalie, Laporte, Silvy, 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), F-Crin Innovte [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHR de Metz-Thionville, Centre Hospitalier Agen-Nérac, Hôpital Bicêtre, Université Paris-Saclay, Centre Hospitalier de Versailles André Mignot (CHV), Department of Cardiology, University Hospital Jean Minjoz, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), UNEOS, Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Lapeyronie [Montpellier] (CHU), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Lille, CHU Lille, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpitaux Civils de Colmar, Service d’Hématologie Biologique [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA), CHU d'Angers [Département Urgences], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université Jean Monnet - Saint-Étienne (UJM), 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), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Service de Chirurgie Vasculaire [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), 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 d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Centre Hospitalier Princesse Grace, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), French Ministry of Health, CAPNET, Grand-Est Region, Grand-Nancy Métropole., and COVI-DOSE investigators: Stéphane Zuily, Francis Couturaud, François Goehringer, Silvy Laporte, Patrick Mismetti, Emilie Presles, Patrick Rossignol, Nathalie Thilly, Denis Wahl, Thomas Lecompte, Emmanuel Oger, Marie-Antoinette Sevestre, Florence Parent, Ygal Benhamou, Pierre-Marie Roy, Tristan Gigante, Morgane Gilg, Pierre-Luc Maclot, Bénédicte Rossignol, Jonathan Udot, Hélène Bouteille, Andréa Buchmuller, Céline Peurière, El Mehdi Siaghy, Valérie Bouaziz, Charlotte Daguin, Benjamin Grosjean, Véronique Saunier, Laurence Verger, Madlyne Jacquot, Nadine Petitpain, Martin Charly, Laurent Tordella, Emilie Presles, Guillaume Baronnet, Elisabeth Baux, Athanase Benetos, Jean-Baptiste Blanvillain, Marie Conrad, Guilhem Courte, Aurélie Cravoisy-Popovic, Virginie Dufrost, Sébastien Gibot, Philippe Guerci, Laure Joly, Antoine Kimmoun, Matthieu Koszutski, Alexandrine Larue, Bruno Levy, Marie-Reine Losser, Mathieu Mattei, Lionel Nace, Emmanuel Novy, Pierre Perez, Jean-Pierre Pertek, Camille Rigaux, Alexis Sauvage, Evelyne Schvoerer, Carine Thivilier, Lev Volkov, Piotr Zieminski, Manil Benlounes, Charles Cheng, Jean-Baptiste de Fréminville, Grégoire Détriché, Emmanuel Flammarion, Guillaume Goudot, Amer Hamdan, Raphaël Hindré, Corina Manoli, Emmanuel Messas, Adrien Michon, Tristan Mirault, Jean Pastré, Marie-Aude Penet, Benjamin Planquette, Geoffroy Volle, Rémy Hamdan, Aline Laubriet-Jazayeri, Vincent Petit, Lionel Piroth, Jean Pierre Quenot, Mélissa Saccu, Damien Barraud, Zoé Cavalli, Rostane Gaci, Mathilde Andreu, Laurent Bertoletti, Andréa Buchmuller, Elodie De Magalhaes, Sophie Bulifon, Athénaïs Boucly, Nathan Ebstein, Marc Humbert, Xavier Jaïs, Mitja Jevnikar, Laurent Savale, Andrei Horia Seferian, Charlotte Colin, Timothée Ganem, Mehdi Roumila, Romain Chopard, Matthieu Besutti, Basile Mouhat, Claire Andrejak, Stéphane Dupas, Gaëlle Le Roy, Santhi Samy-Modeliar, Anne Coste, Alexandre Fauche, David Goetghebeur, Christophe Gut-Gobert, Clément Hoffmann, Baptiste Hourmant, Cécile L'hévéder, Emmanuelle Lemoigne, Olivier Nepveu, Raphaël Paret, Gaël Picart, Saïd Azerkan, Chadia Boudaa, Julien Campagne, Peter Eszto, Benoît Godbert, Jean-François Guichard, Marion Heschung, Antoine Legoff, Jacques Mariot, Pascale Martin, Magalie Mercy, Julie Perrin, Stéphane Raymond, Nathalie Vernier, Pierre Fesler, Pierrick Henneton, Cédric Mercuzot, Nathalie Pansu, Lucas Perez, Loïc Andre, Edgar Bakhache, Marie-Charlotte Chopin, Marie Gilbert, Marc Lambert, Mohammad Ryadh Pokeerbux, François Danion, Yves Hansmann, Estelle Rougier, Yvon Ruch, Dominique Stéphan, Axel Ursenbach, Isabelle Connerade, Simon Gravier, Damien Kayser, Jean-Marc Michel, Mahsa Mohseni, Waël Younes, Ruxandra Burlacu, Amanda Lopes, Stéphane Mouly, Kladoum Nassarmadji, Damien Sène, Virginie Siguret, Alain Stepanian, Cédric Annweiler, Antoine Brangier, Vincent Dubee, Samir Henni, Jeanne Hersant, Jocelyne Loison, Léa Kern, Jean-Baptiste Laine, Claire Neveux-Brecheteau, Lucia Perez, Ruben Benainous, Bénédicte Giroux-Leprieur, Marilucy Lopez-Sublet, Saïda Khaled-Jousselin, Yohann Bernard, Amélie Amiot, Jessica Breistroff, Emilie Detry, Kadidiatou Diallo, Agnès Didier, Nathalie Dumont, Julie Egensperger, Aurélie Emmerich, Nelly François, Fanny Gallo, Valérie George, Quentin Gérome, Aurélie Gutehrle, Laure Lehman, Séverine Petit, Vanessa Piard, Maximilien Saint-Gilles, Olivier Terenzi, Amélie Marquette, Hélène Mortelette, Mathilde Audry, Amélie Cransac, Marine Maillard, Anaïs Boyer, Floriana Gallo, Arielle Urbing, Imane Zahaf, Alexandra Byczko, Amina Chaalal, Georgette Berlier, Corinne Bernabe, Souad Bezzeghoud, Caroline Chaudier, Carole Chauvet, Marina Davier, Carine Labruyere, Estelle Perrin, Michaël Pierre, Claire-Annissa Chekirine, Florence Voivret, Ramdane Meftali, Ouaffa Sabri, Anaïs Beulaygue, Julie Gall, Laure Girard, Soumia Haddaoui, Scheherazade Rami, Auriane Couderc, Aude Le Breton, Marie-Line Perruche, Cindy Claudon, Ludivine Roussel, Aude Barnier, Tiphaine Blanchard, Bénédicte Le Gall, Mélanie Pelouin, Anne-Sophie Veillon, Quam Aquereburu, Charlène Delaygue, Zahoua Ait Idir, Jérémy Drugeon, Déborah Dubrulle, Rabah Tezkratt, Anne-Sophie Frantz, Julie Drouaine, Jacqueline Dubois, Magali Eyriey, Elina Haerrel, Mélinda Beaudenon, Mialy Guenet, Thibaud Lecerf, Stéphanie Marechal-Girault, Sami Rehaiem, Romain Simon, Florence Dangeul-Potier, Morgane Goulvent, Souha Fliss, Fadhila Messani, Béatrice Mizejewski, Brigitte Mugnier, Valérie Opderbeck, Brigitte Risse
Subjects: Anticoagulation, Heparin, [SDV]Life Sciences [q-bio], COVID-19, Venous thromboembolism
Abstract: International audience; Background: Venous thromboembolism is a major complication of coronavirus disease 2019 (COVID-19). We hypothesized that a weight-adjusted intermediate dose of anticoagulation may decrease the risk of venous thromboembolism COVID-19 patients.Methods: In this multicenter, randomised, open-label, phase 4, superiority trial with blinded adjudication of outcomes, we randomly assigned adult patients hospitalised in 20 French centers and presenting with acute respiratory SARS-CoV-2. Eligible patients were randomly assigned (1:1 ratio) to receive an intermediate weight-adjusted prophylactic dose or a fixed-dose of subcutaneous low-molecular-weight heparin during the hospital stay. The primary outcome corresponded to symptomatic deep-vein thrombosis (fatal) pulmonary embolism during hospitalization (COVI-DOSE ClinicalTrials.gov number: NCT04373707).Findings: Between May 2020, and April 2021, 1000 patients underwent randomisation in medical wards (noncritically ill) (80.1%) and intensive care units (critically ill) (19.9%); 502 patients were assigned to receive a weight-adjusted intermediate dose, and 498 received fixed-dose thromboprophylaxis. Symptomatic venous thromboembolism occurred in 6 of 502 patients (1.2%) in the weight-adjusted dose group and in 10 of 498 patients (2.1%) in the fixed-dose group (subdistribution hazard ratio, 0.59; 95% CI, 0.22-1.63; P = 0.31). There was a twofold increased risk of major or clinically relevant nonmajor bleeding: 5.9% in the weight-adjusted dose group and 3.1% in the fixed-dose group (P = 0.034).Interpretation: In the COVI-DOSE trial, the observed rate of thromboembolic events was lower than expected in patients hospitalized for COVID-19 infection, and the study was unable to show a significant difference in the risk of venous thromboembolism between the two low-molecular-weight-heparin regimens.
Published: 2023

26. Impact of corticosteroids use on midterm sequelae in survivors of COVID-19 admitted to hospital: A prospective cohort study

Author: Gault, Nathalie, Bachelet, Delphine, Laouénan, Cédric, Borie, Raphaël, Cracowski, Claire, Poissy, Julien, Faure, Karine, Lainé, Fabrice, Lefèvre, Benjamin, Isnard, Margaux, Patrier, Juliette, Launay, Odile, Costagliola, Dominique, Ghosn, Jade, Bouadma, Lila, Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique [Grenoble] (CIC Grenoble), CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), CIC - Vaccinologie - APHP (Cochin - Pasteur), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and REACTing (REsearch & ACtion emergING infectious diseases) consortium. Grant Number: PHRC20-0424 Ministère des Affaires Sociales et de la Santé
Subjects: [SDV]Life Sciences [q-bio], cohort study, sequelae, Covid-19, propensity score, corticosteroids
Abstract: International audience; An understanding of the midterm sequelae in COVID-19 and their association with corticosteroids use are needed. Between March and July 2020, we evaluated 1227 survivors of COVID-19, 3 months posthospitalization, of whom 213 had received corticosteroids within 7 days of admission. Main outcome was any midterm sequelae (oxygen therapy, shortness of breath, one major clinical sign, two minor clinical signs or three minor symptoms). Association between corticosteroids use and midterm sequelae was assessed using inverse propensity-score weighting models. Our sample included 753 (61%) male patients, and 512 (42%) were older than 65 years. We found a higher rate of sequelae among users than nonusers of corticosteroids (42% vs. 35%, odds ratio [OR] 1.40 [1.16-1.69]). Midterm sequelae were more frequent in users of low-dose corticosteroids than nonusers (64% vs. 51%, OR 1.60 [1.10-2.32]), whereas no association between higher doses (≥20 mg/day equivalent of dexamethasone) and sequelae was evidenced (OR 0.95 [0.56-1.61]). Higher risk of sequelae with corticosteroids use was observed among subjects with propensity score below the 90th percentile. Our study suggest that corticosteroids use during hospitalization for COVID-19 is associated with higher risk of midterm sequelae.
Published: 2023

27. LAM fatale ?

Author: Laguillaumie, Marie-Océane, Lewuillon, Clara, Touil, Yasmine, Lemonnier, Loïc, Idziorek, Thierry, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER], Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL], Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, and LabEx Ion Channels Science and Therapeutics [France]
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; La leucémie aiguë myéloïde (LAM) est une hémopathie maligne caractérisée par des aberrations génétiques de certains précurseurs hématopoïétiques de la lignée myéloïde qui entraînent un défaut de maturation et/ou de fonctionnement. Malgré une chimiothérapie intensive entraînant une rémission complète chez 50 à 80 % des patients, la rechute survient dans la majorité des cas. Bien que la signalisation calcique soit bien décrite dans les cancers solides, l’étude de cibles pertinentes dépendant du calcium a retenu peu d’attention dans la LAM jusqu’à aujourd’hui. L’objectif de cette revue est d’offrir une piste de réflexion sur l’identification de canaux calciques spécifiques et de voies de signalisation associées impliquées dans la LAM, et ainsi de promouvoir la recherche de nouvelles approches thérapeutiques efficaces ciblant spécifiquement ces voies.
Published: 2023

28. Novel Chronic Anaplasmosis in Splenectomized Patient, Amazon Rainforest

Author: Olivier Duron, Rachid Koual, Lise Musset, Marie Buysse, Yann Lambert, Benoît Jaulhac, Denis Blanchet, Kinan Drak Alsibai, Yassamine Lazrek, Loïc Epelboin, Pierre Deshuillers, Céline Michaud, Maylis Douine, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Laboratoire de Parasitologie [Cayenne, Guyane française], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Université de Strasbourg (UNISTRA), 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), The research was supported by funding from Investissements d’Avenir grants managed by the Agence Nationale de la Recherche (ANR, France, Laboratoire d’Excellence CEBA, ref. ANR-10-LABX-25-01)., and ANR-10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010)
Subjects: Microbiology (medical), Anaplasmosis, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Anaplasma, Rainforest, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Epidemiology, Animals, Humans, Rickettsia Infections, Brazil
Abstract: International audience; We report a case of unusual human anaplasmosis in the Amazon rainforest of French Guiana. Molecular typing demonstrated that the pathogen is a novel Anaplasma species, distinct to all known species, and more genetically related to recently described Anaplasma spp. causing infections in rainforest wild fauna of Brazil.
Published: 2022

29. Bleeding and thrombotic events in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study

Author: Mansour, Alexandre, Flecher, Erwan, Schmidt, Matthieu, Rozec, Bertrand, Gouin-Thibault, Isabelle, Esvan, Maxime, Fougerou, Claire, Levy, Bruno, Porto, Alizée, Ross, James, Para, Marylou, Manganiello, Sabrina, Lebreton, Guillaume, Vincentelli, André, Nesseler, Nicolas, Pierrot, Marc, Chocron, Sidney, Flicoteaux, Guillaume, Mauriat, Philippe, Ouattara, Alexandre, Roze, Hadrien, Huet, Olivier, Fischer, Marc-Olivier, Alessandri, Claire, Bellaïche, Raphel, Constant, Ophélie, de Roux, Quentin, Ly, André, Meffert, Arnaud, Merle, Jean-Claude, Mongardon, Nicolas, Picard, Lucile, Skripkina, Elena, Folliguet, Thierry, Fiore, Antonio, D’ostrevy, Nicolas, Morgan, Marie-Catherine, Guinot, Pierre-Grégoire, Nguyen, Maxime, Gaide-Chevronnay, Lucie, Terzi, Nicolas, Colin, Gwenhaël, Fabre, Olivier, Astaneh, Arash, Issard, Justin, Fadel, Elie, Fabre, Dominique, Girault, Antoine, Guihaire, Julien, Ion, Iolande, Menager, Jean Baptiste, Mitilian, Delphine, Mercier, Olaf, Stephan, François, Thes, Jacques, Jouan, Jerôme, Duburcq, Thibault, Loobuyck, Valentin, Moussa, Mouhammed, Mugnier, Agnes, Rousse, Natacha, Desebbe, Olivier, Fellahi, Jean-Luc, Henaine, Roland, Pozzi, Matteo, Richard, Jean-Christophe, Riad, Zakaria, Guervilly, Christophe, Hraiech, Sami, Papazian, Laurent, Castanier, Matthias, Chanavaz, Charles, Cadoz, Cyril, Gette, Sebastien, Louis, Guillaume, Portocarrero, Erick, Gaudard, Philippe, Brini, Kais, Bischoff, Nicolas, Kimmoun, Antoine, Mattei, Mathieu, Perez, Pierre, Bourdiol, Alexandre, Hourmant, Yannick, Mahé, Pierre-Joachim, Jaquet, Pierre, Lortat-Jacob, Brice, Mordant, Pierre, Nataf, Patrick, Patrier, Juliette, Provenchère, Sophie, Roué, Morgan, Sonneville, Romain, Tran-Dinh, Alexy, Wicky, Paul-Henri, Al Zreibi, Charles, Cholley, Bernard, Guyonvarch, Yannis, Hamada, Sophie, Harrois, Anatole, Matiello, Jordi, Kerforne, Thomas, Lacroix, Corentin, Brechot, Nicolas, Combes, Alain, Chommeloux, Juliette, Constantin, Jean Michel, D’alessandro, Cosimo, Demondion, Pierre, Demoule, Alexandre, Dres, Martin, Fadel, Guillaume, Fartoukh, Muriel, Hekimian, Guillaume, Juvin, Charles, Leprince, Pascal, Levy, David, Luyt, Charles Edouard, Pineton de Chambrun, Marc, Schoell, Thibaut, Fillâtre, Pierre, Massart, Nicolas, Nicolas, Roxane, Jonas, Maud, Vidal, Charles, Allou, Nicolas, Muccio, Salvatore, Di Perna, Dario, Ruggieri, Vito-Giovanni, Mourvillier, Bruno, Anselmi, Amedeo, Bounader, Karl, Launey, Yoann, Lebouvier, Thomas, Parasido, Alessandro, Reizine, Florian, Seguin, Philippe, Besnier, Emmanuel, Carpentier, Dorothée, Clavier, Thomas, Falcoz, Pierre-Emmanuel, Olland, Anne, Villard, Marion, Bounes, Fanny, Labaste, François, Minville, Vincent, Guillon, Antoine, Fedun, Yannick, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], 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), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital de la Timone [CHU - APHM] (TIMONE), University of California [Davis] (UC Davis), University of California (UC), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), 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), CHU Lille, Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and This work was supported by a grant from the university hospital of Rennes (Appel à projets CFTR2) and by a grant from the French society of thoracic and cardio-vascular surgery (Société française de chirurgie thoracique et cardio-vasculaire, Bourse Marc Laskar).
Subjects: Anticoagulation, [SDV]Life Sciences [q-bio], Bleeding, COVID-19, Thrombosis, ECMO, Critical Care and Intensive Care Medicine
Abstract: International audience; Purpose: To describe bleeding and thrombotic events and their risk factors in patients receiving extracorporeal membrane oxygenation (ECMO) for severe coronavirus disease 2019 (COVID-19) and to evaluate their impact on in-hospital mortality.Methods: The ECMOSARS registry included COVID-19 patients supported by ECMO in France. We analyzed all patients included up to March 31, 2022 without missing data regarding bleeding and thrombotic events. The association of bleeding and thrombotic events with in-hospital mortality and pre-ECMO variables was assessed using multivariable logistic regression models.Results: Among 620 patients supported by ECMO, 29% had only bleeding events, 16% only thrombotic events and 20% both bleeding and thrombosis. Cannulation site (18% of patients), ear nose and throat (12%), pulmonary bleeding (9%) and intracranial hemorrhage (8%) were the most frequent bleeding types. Device-related thrombosis and pulmonary embolism/thrombosis accounted for most of thrombotic events. In-hospital mortality was 55.7%. Bleeding events were associated with in-hospital mortality (adjusted odds ratio (adjOR) = 2.91[1.94-4.4]) but not thrombotic events (adjOR = 1.02[0.68-1.53]). Intracranial hemorrhage was strongly associated with in-hospital mortality (adjOR = 13.5[4.4-41.5]). Ventilation duration before ECMO ≥ 7 days and length of ECMO support were associated with bleeding. Thrombosis-associated factors were fibrinogen ≥ 6 g/L and length of ECMO support.Conclusions: In a nationwide cohort of COVID-19 patients supported by ECMO, bleeding incidence was high and associated with mortality. Intracranial hemorrhage incidence was higher than reported for non-COVID patients and carried the highest risk of death. Thrombotic events were less frequent and not associated with mortality. Length of ECMO support was associated with a higher risk of both bleeding and thrombosis, supporting the development of strategies to minimize ECMO duration.
Published: 2022

30. Heterogeneity of PD-MCI in Candidates to Subthalamic Deep Brain Stimulation: Associated Cortical and Subcortical Modifications

Author: Quentin, Devignes, Sami, Daoudi, Romain, Viard, Renaud, Lopes, Nacim, Betrouni, Gregory, Kuchcinski, Anne-Sophie, Rolland, Caroline, Moreau, Luc, Defebvre, Eric, Bardinet, Marie, Bonnet, Christine, Brefel-Courbon, Christine, Delmaire, Fouzia, El Mountassir, Frédérique, Fluchère, Anne, Fradet, Caroline, Giordana, Elodie, Hainque, Jean-François, Houvenaghel, Béchir, Jarraya, Hélène, Klinger, David, Maltête, Ana, Marques, Mylène, Meyer, Olivier, Rascol, Tiphaine, Rouaud, Melissa, Tir, Thomas, Wirth, Jean-Christophe, Corvol, David, Devos, Kathy, Dujardin, 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), CHU Lille, Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), 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)-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), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Building large instruments for neuroimaging: from population imaging to ultra-high magnetic fields (BAOBAB), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre Hospitalier Universitaire [Rennes], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Foch [Suresnes], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), 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), Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Amiens-Picardie, Les Hôpitaux Universitaires de Strasbourg (HUS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and ANR-10-IAIHU-06
Subjects: [SCCO.NEUR]Cognitive science/Neuroscience, Deep Brain Stimulation, shape analysis, Parkinson Disease, Magnetic Resonance Imaging, Cortical thickness, Cellular and Molecular Neuroscience, Cognition, radiomics, dual syndrome hypothesis, voxel-based morphometry, Humans, Cognitive Dysfunction, Neurology (clinical)
Abstract: International audience; Background: Parkinson’s disease mild cognitive impairment (PD-MCI) is frequent and heterogenous. There is no consensus about its influence on subthalamic deep brain stimulation (STN-DBS) outcomes. Objective: To determine the prevalence of PD-MCI and its subtypes in candidates to STN-DBS. Secondarily, we sought to identify MRI structural markers associated with cognitive impairment in these subgroups. Methods: Baseline data from the French multicentric PREDISTIM cohort were used. Candidates to STN-DBS were classified according to their cognitive performance in normal cognition (PD-NC) or PD-MCI. The latter included frontostriatal (PD-FS) and posterior cortical (PD-PC) subtypes. Between-group comparisons were performed on demographical and clinical variables as well as on T1-weighted MRI sequences at the cortical and subcortical levels. Results: 320 patients were included: 167 (52%) PD-NC and 153 (48%) PD-MCI patients. The latter group included 123 (80%) PD-FS and 30 (20%) PD-PC patients. There was no between-group difference regarding demographic and clinical variables. PD-PC patients had significantly lower global efficiency than PD-FS patients and significantly worse performance on visuospatial functions, episodic memory, and language. Compared to PD-NC, PD-MCI patients had cortical thinning and radiomic-based changes in the left caudate nucleus and hippocampus. There were no significant differences between the PD-MCI subtypes. Conclusion: Among the candidates to STN-DBS, a significant proportion has PD-MCI which is associated with cortical and subcortical alterations. Some PD-MCI patients have posterior cortical deficits, a subtype known to be at higher risk of dementia.
Published: 2022

31. Thiol Catalysis of Selenosulfide Bond Cleavage by a Triarylphosphine

Author: Olga Firstova, Oleg Melnyk, Vincent Diemer, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and Diemer, Vincent
Subjects: Phosphines, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Proteins, [CHIM.CATA] Chemical Sciences/Catalysis, Indicators and Reagents, Sulfhydryl Compounds, [CHIM.CATA]Chemical Sciences/Catalysis, Peptides, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Catalysis
Abstract: International audience; The arylthiol 4-mercaptophenylacetic acid (MPAA) is a powerful catalyst of selenosulfide bond reduction by the triarylphosphine 3,3′,3″-phosphanetriyltris(benzenesulfonic acid) trisodium salt (TPPTS). Both reagents are water-soluble at neutral pH and are particularly adapted for working with unprotected peptidic substrates. Contrary to trialkylphosphines such as tris(2-carboxyethyl)phosphine hydrochloride (TCEP), TPPTS has the advantage of not inducing deselenization reactions. We believe that the work reported here will be of value for those manipulating selenosulfide bonds in peptidic or protein molecules.
Published: 2022

32. A new species of Chryxus Champion, with taxonomic notes on other species of the genus (Hemiptera, Heteroptera, Reduviidae, Chryxinae)

Author: Hélcio R. Gil-Santana, John M. Leavengood Jr., Jean-Michel Bérenger, David dos Santos Martins, Jader Oliveira, Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), 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), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Universidade de São Paulo = University of São Paulo (USP), and Universidade Estadual Paulista Júlio de Mesquita Filho = São Paulo State University (UNESP)
Subjects: [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Insecta, Arthropoda, Reduvoidea, Panama, female and male genitalia, Chryxus, Assassin bugs, Biota, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Chryxinae, Hemiptera, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Animalia, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Animal Science and Zoology, Guyana, Reduviidae, Ecology, Evolution, Behavior and Systematics
Abstract: Chryxus garcetebarrettisp. nov. from Paraguay is described, taxonomical notes on C. bahianus Gil-Santana, Costa & Marques, 2007 and C. tomentosus Champion, 1899 are provided; the latter species is recorded from French Guiana for the first time; a redescription of the genus Chryxus Champion, 1899 and an updated key for the genera and species of Chryxinae are presented.
Published: 2022

33. La fibrose pulmonaire idiopathique

Author: Nathan Hennion, Jean-Luc Desseyn, Frédéric Gottrand, Lidwine Wémeau-Stervinou, Valérie Gouyer, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pneumologie et Immuno-Allergologie [CHU LIlle], Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Université de Lille, LillOA
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], General Medicine, General Biochemistry, Genetics and Molecular Biology
Abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease of unknown origin. It is characterized by aberrant scarring of the alveolar epithelium leading to an accumulation of extracellular matrix (ECM). Fibroblastic foci, consisting of fibroblasts and myofibroblasts, are responsible for the excessive production of ECM. The two therapeutic molecules available on the market to date only allow to slow down the evolution of the disease. In this review, we present the mechanisms involved in the progression of the disease, its treatments and the study models. La fibrose pulmonaire idiopathique. La fibrose pulmonaire idiopathique (FPI) est une maladie pulmonaire chronique, évolutive et mortelle dont l’origine est inconnue. Elle se caractérise par une cicatrisation aberrante de l’épithélium alvéolaire aboutissant à une accumulation de matrice extracellulaire (MEC). Les foyers fibroblastiques, constitués de fibroblastes et de myofibroblastes, sont responsables de la production excessive de MEC. Les deux seules molécules thérapeutiques disponibles sur le marché permettent seulement de ralentir l’évolution de la maladie. Dans cette revue, nous présentons les mécanismes impliqués dans la progression de la maladie, ses traitements et les modèles d’étude., La fibrose pulmonaire idiopathique (FPI) est une maladie pulmonaire chronique, évolutive et mortelle dont l’origine est inconnue. Elle se caractérise par une cicatrisation aberrante de l’épithélium alvéolaire aboutissant à une accumulation de matrice extracellulaire (MEC). Les foyers fibroblastiques, constitués de fibroblastes et de myofibroblastes, sont responsables de la production excessive de MEC. Les deux seules molécules thérapeutiques disponibles sur le marché ne permettent que de ralentir l’évolution de la maladie. Dans cette revue, nous présentons les mécanismes impliqués dans la progression de la maladie, ses traitements et les modèles d’étude.
Published: 2022

34. PPE Barcoding Identifies Biclonal Mycobacterium ulcerans Buruli Ulcer, Côte d’Ivoire

Author: B. G. O. Tchan, S. Ngazoa-Kakou, N. Aka, N. K. B. Apia, N. Hammoudi, M. Drancourt, J. Saad, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Institut Pasteur de Côte d'Ivoire, Réseau International des Instituts Pasteur (RIIP), Unité des mycobactéries tuberculeuses et atypiques, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
Subjects: Microbiology (medical), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, General Immunology and Microbiology, Ecology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Physiology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Cell Biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: We describe a new targeted sequencing approach that characterizes the PPE gene to disclose the simultaneous presence of different variants of a single pathogenic microorganism. This approach has direct implications on the understanding of pathogen diversity and natural history and potential therapeutic implications when dealing with obligate and opportunistic pathogens, such as Mycobacterium ulcerans presented here as a prototype.
Published: 2023

35. Activation of Nod2 signalling upon Norovirus infection enhances antiviral immunity and susceptibility to colitis

Author: Muharram, Ghaffar, Thépaut, Marion, Lobert, Pierre-Emmanuel, Grandjean, Teddy, Boulard, Olivier, Delacre, Myriam, Wakeford, Emmrich, Wheeler, Richard, Poulin, Lionel, Gomperts Boneca, Ivo, Lafont, Frank, Michallet, Marie-Cécile, Hober, Didier, Cadwell, Ken, Chamaillard, Mathias, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Pathogenèse virale du diabète de type 1 - ULR 3610 (Laboratoire de Virologie), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), New York University School of Medicine (NYU Grossman School of Medicine), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), and ANR-16-CE15-0021,PG-Brain,Modulation de l'activité du cerveau par le peptidoglycan bactérien(2016)
Subjects: Inflammation, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Macrophages, Norovirus, [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, Signalling, Colitis, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, NOD2
Abstract: International audience; Over 90% of epidemic nonbacterial gastroenteritis are caused by human Noroviruses (NoV) which are persisting in a substantial subset of people allowing their spread worldwide. It leads to a significant number of endemic cases and up to 70,000 children deaths in developing countries. NoVs are primarily transmitted through the fecal-oral route. To date studies have focused on the influence of the gut microbiota on viral clearance by enteric immunity. In this study, the use of the persistent mouse Norovirus S99 strain (MNoV_S99) allowed us to provide evidence that the norovirus-driven exacerbation of colitis severity relied on bacterial sensing by nucleotide-binding oligomerization domain 2 (Nod2). Similarly, another persistent MNoV_CR6 strain failed to exacerbate colitis severity in Nod2-deficient mice. In parallel, the viremia was heightened in these mice in comparison with control animals. Accordingly, a reduced level of phosphorylation of Signal Transducer and Activator of Transcription1 (STAT1) in Nod2-deficient macrophages infected by MNoV_S99 was measured. By contrast, STAT1 phosphorylation was increased in wild-type macrophages and associated with an induction of NOD2 expression. This in turn enhances myeloid cells response to muramyl dipeptide (MDP) resulting in downstream pro-inflammatory cytokine secretion and reduced noroviral production. Hence, our results uncover a previously unidentified virus-host-bacterial interplay that may represent a novel therapeutic target for treating noroviral origin gastroenteritis that may be linked with susceptibility to several common illnesses such as Crohn’s disease.
Published: 2023

36. Integrated Plan of Insecticide Resistance Surveillance in Mosquito Vectors in France

Author: James Devillers, Jean-Philippe David, Benoit Barrès, Haoues Alout, Bruno Lapied, Sébastien Chouin, Isabelle Dusfour, Catherine Billault, Farida Mekki, Isabelle Attig, Vincent Corbel, Centre de Traitement de l'Information Scientifique (CTIS), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon, Laboratoire d'Ecologie Alpine (LECA ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CAractérisation et Suivi des Phénomènes d'Evolution de Résistance aux pesticides (CASPER), Laboratoire de Lyon [ANSES], Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Lyon-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), Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SFR UA 4207 QUAlité et SAnté du Végétal (QUASAV), Université d'Angers (UA)-Ecole supérieure d'Agricultures d'Angers (ESA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université (Nantes Univ)-Institut Agro Rennes Angers, 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), Conseil départemental de la Charente-Maritime, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Direction de l'évaluation des produits réglementés (DEPR), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Vector Control Group (MIVEGEC-VCG), Evolution des Systèmes Vectoriels (ESV), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
Subjects: mosquito-borne diseases, mosquito surveillance, arboviruses, Insect Science, [SDV]Life Sciences [q-bio], insecticide resistance, France
Abstract: International audience; Mosquito-borne diseases such as malaria, dengue, or chikungunya have been re-emerging all over the world, including in Europe. Managing resistance to public health pesticides in mosquitoes is essential and requires global, integrated, and coordinated actions and strong engagement of decision-makers, scientists, and public health operators. In this context, the present work aims at proposing an integrated plan of resistance surveillance in France and in the French Overseas territories in order to provide graduated and appropriate responses according to the situation. Briefly, the plan relies on periodic monitoring of insecticide resistance at the population level in predefined sites using adequate biological, molecular, and/or biochemical approaches and a stratification of the level of resistance risk at the scale of territory to adjust surveillance and vector control actions. The plan relies on the latest methods and indicators used for resistance monitoring as recommended by the World Health Organization in order to prevent or slow down its extension in space and time. The plan has been developed for France but can be easily adapted to other countries in order to provide a coordinated response to the growing problem of mosquito resistance in Europe.
Published: 2023
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37. Conformation and Affinity Modulations by Multiple Phosphorylation Occurring in the BIN1 SH3 Domain Binding Site of the Tau Protein Proline-Rich Region

Author: Alessia Lasorsa, Krishnendu Bera, Idir Malki, Elian Dupré, François-Xavier Cantrelle, Hamida Merzougui, Davy Sinnaeve, Xavier Hanoulle, Jozef Hritz, Isabelle Landrieu, Biologie Structurale Intégrative (ERL 9002 - BSI ), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Masaryk University [Brno] (MUNI), ANR-15-CE16-0002,BINALZ,Interaction entre BIN1 et Tau: consequences physiologiques et pathophysiologiques pour la maladie d'Alzheimer(2015), and ANR-11-LABX-0009,DISTALZ,Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime(2011)
Subjects: phosphorylation, protein-protein interactions, intrinsically disordered proteins, Alzheimer's disease, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Biochemistry, tau protein, molecular dynamics, nuclear magnetic resonance spectroscopy
Abstract: International audience; An increase in phosphorylation of the Tau protein is associated with Alzheimer's disease (AD) progression through unclear molecular mechanisms. In general, phosphorylation modifies the interaction of intrinsically disordered proteins, such as Tau, with other proteins; however, elucidating the structural basis of this regulation mechanism remains challenging. The bridging integrator-1 gene is an AD genetic determinant whose gene product, BIN1, directly interacts with Tau. The proline-rich motif recognized within a Tau(210-240) peptide by the SH3 domain of BIN1 (BIN1 SH3) is defined as 216PTPP219, and this interaction is modulated by phosphorylation. Phosphorylation of T217 within the Tau(210-240) peptide led to a 6-fold reduction in the affinity, while single phosphorylation at either T212, T231, or S235 had no effect on the interaction. Nonetheless, combined phosphorylation of T231 and S235 led to a 3-fold reduction in the affinity, although these phosphorylations are not within the BIN1 SH3-bound region of the Tau peptide. Using nuclear magnetic resonance (NMR) spectroscopy, these phosphorylations were shown to affect the local secondary structure and dynamics of the Tau(210-240) peptide. Models of the (un)phosphorylated peptides were obtained from molecular dynamics (MD) simulation validated by experimental data and showed compaction of the phosphorylated peptide due to increased salt bridge formation. This dynamic folding might indirectly impact the BIN1 SH3 binding by a decreased accessibility of the binding site. Regulation of the binding might thus not only be due to local electrostatic or steric effects from phosphorylation but also to the modification of the conformational properties of Tau.
Published: 2023

38. Climate and land-use shape the spread of zoonotic yellow fever virus

Author: Sarah C. Hill, Simon Dellicour, Ingra M. Claro, Patricia C. Sequeira, Talita Adelino, Julien Thézé, Chieh-Hsi Wu, Filipe Romero Rebello Moreira, Marta Giovanetti, Sabrina L. Li, Jaqueline G. de Jesus, Felipe J. Colón-González, Heather R. Chamberlain, Oliver Pannell, Natalia Tejedor-Garavito, Fernanda de Bruycker-Nogueira, Allison A. Fabri, Maria Angélica Mares-Guia, Joilson Xavier, Alexander E. Zarebski, Arran Hamlet, Maria Anice Mureb Sallum, Antonio C. da Costa, Erika R. Manuli, Anna S. Levin, Luís Filipe Mucci, Rosa Maria Tubaki, Regiane Maria Tironi de Menezes, Juliana Telles de Deus, Roberta Spinola, Leila Saad, Esper G. Kallas, G.R. William Wint, Pedro S. Peixoto, Andreza Aruska de Souza Santos, Jane P. Messina, Oliver J. Brady, Andrew J. Tatem, Marc A. Suchard, Jairo A. Mendez-Rico, André Abreu, Renato Santana Aguiar, Oliver G. Pybus, Guy Baele, Philippe Lemey, Felipe Iani, Mariana S. Cunha, Ana M. Bispo de Filippis, Ester C. Sabino, Nuno R. Faria, Royal Veterinary College [London], University of London [London], Department of Zoology, University of Oxford, Spatial Epidemiology Lab (SpELL), Université libre de Bruxelles (ULB), Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Faculdade de Medicina da Universidade de São Paulo [São Paulo, Brésil], The Abdul Latif Jameel Institute for Disease and Emergency Analytics, Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Fundação Ezequiel Dias (FUNED), 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), School of Mathematics [Southampton], University of Southampton, Institute for Life Sciences, Laboratório de Biologia Molecular de Flavivírus [Rio de Janeiro], Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), School of Geography and the Environment [Oxford] (SoGE), School of Geography [Nottingham], University of Nottingham, UK (UON), Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population, Instituto de Ciências Biológicas [Goiânia, Brésil] (ICB), Imperial College London, Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Department of Zoology [Oxford]
Subjects: [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Zoonotic viruses that originate in wildlife harm global human health and economic prosperity1. Understanding virus transmission at the human-animal-environment interface is a key component of pandemic risk-reduction2,3. Zoonotic disease emergence is highest in biodiverse, tropical forests undergoing intensive land-use change4,5. Phylodynamic analyses of virus genomes can powerfully test epidemiological hypotheses, but are rarely applied to viruses of animals inhabiting these habitats. Brazil’s densely-populated Atlantic Forest and Cerrado region experienced in 2016–2021 an explosive human outbreak of sylvatic yellow fever, caused by repeated virus spillover from wild neotropical primates6. Here we use yellow fever virus (YFV) genome sequences and epidemiological data from neotropical primates, humans, and mosquito vectors to identify the environmental, demographic, and climatic factors determining zoonotic virus spread. Using portable sequencing approaches we generated 498 YFV genomes, resulting in a well-sampled dataset of zoonotic virus genomes sampled from wild mammals. YFV dispersal velocity was slower at higher elevation, in colder regions, and further away from main roads. Virus lineage dispersal was more frequent through wetter areas, areas with high neotropical primate density and through landscapes covered by mosaic vegetation. Higher temperatures were associated with higher virus effective population sizes, and peaks of transmission in warmer, wetter seasons were associated with higher virus evolutionary rates. Our study demonstrates how zoonotic disease transmission is linked to land-use and climate, underscoring the need for One-Health approaches to reducing the rate of zoonotic spillover.
Published: 2023

39. Emerging Infectious Diseases and New Pandemics: Dancing with a Ghost! Lessons in inter- and transdisciplinary research in French Guiana, South America

Author: Jean-François Guégan, Loïc Epelboin, Maylis Douine, Paul Le Turnier, Olivier Duron, Lise Musset, Christine Chevillon, Philippe Quénel, Mark Eric Benbow, Benoît de Thoisy, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), 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), Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Michigan State University [East Lansing], Michigan State University System, Laboratoire des Interactions Virus-Hôtes [Cayenne, Guyane Française], The authors are supported by an 'Investissement d'Avenir' grant from the Agence Nationale de la Recherche (CEBA ANR-10-LABX-2501). JFG, CC and MEB were supported by the joint NSF-NIH-NIFA Ecology and Evolution of Infectious Disease program [DEB 1911457], BdT by an European Regional Development Fund (RESERVOIRS) funding, and PLT benefited from a funding from ANRS-MIE. Funding sources had no involvement in the preparation and writing of the article, data interpretation and developed ideas, nor in the decision to submit the article for publication., Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), Internationale, and Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR)
Subjects: Microbiology (medical), Infectious Diseases, interdisciplinarity, biomedical research, transdisciplinarity, infectious disease, public health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, One Health, French Guiana
Abstract: This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.; In light of current international public health challenges, calls for inter- and transdisciplinary research are increasing, particularly in response to complex and intersecting issues. Although widely used under the One Health flag, it is still unclear how inter- and transdisciplinary science should be applied to infectious disease research, public health and the different stakeholders. Here, we present and discuss our common scientific and biomedical experience in French Guiana, South America, to conduct and enrich research in vector-borne and zoonotic infectious diseases with the aim to translate findings to public health and political stakeholders. We highlight the successful progressive dissolution of disciplinary boundaries that go beyond One Health positive-driven assumptions and argue that specific local conditions, as well as strong support from research and medical institutions, have facilitated an emulsion towards inter- and transdisciplinary science. This argument is intended to improve responses to public health concerns in French Guiana and other countries and regions of the world.
Published: 2023

40. Genes Involved in miRNA Biogenesis Are Not Downregulated in SARS-CoV-2 Infection

Author: Nathalie Garnier, Famara Sane, Layal Massara, Fabrice Soncin, Philippe Gosset, Didier Hober, Sabine Szunerits, Ilka Engelmann, Pathogenèse virale du diabète de type 1 - ULR 3610 (Laboratoire de Virologie), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), CHU Lille, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Integrated Micro Mechatronics Systems (LIMMS), The University of Tokyo (UTokyo)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, NanoBioInterfaces - IEMN (NBI - IEMN), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), This research was supported by I-SITE ULNE, the Centre Hospitalier Universitaire de Lilleand Université de Lille. N.G. wants to thank the Ecole Doctorale Biologie-Santé for a PhD fellowship., and ANR-16-IDEX-0004,ULNE,ULNE(2016)
Subjects: [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Ago2, SARS-CoV-2, Exportin-5, COVID-19, Drosha, DGCR8, Infectious Diseases, RNA interference, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, miRNA, Dicer
Abstract: International audience; miRNAs, small non-coding RNAs that regulate gene expression, are involved in various pathological processes, including viral infections. Virus infections may interfere with the miRNA pathway through the inhibition of genes involved in miRNA biogenesis. A reduction in the number and the levels of miRNAs expressed in nasopharyngeal swabs of patients with severe COVID-19 was lately observed by us, pointing towards the potential of miRNAs as possible diagnostic or prognostic biomarkers for predicting outcomes among patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The objective of the present study was to investigate whether SARS-CoV-2 infection influences the expression levels of messenger RNAs (mRNAs) of key genes involved in miRNA biogenesis. mRNA levels of AGO2, DICER1, DGCR8, DROSHA, and Exportin-5 (XPO5) were measured by quantitative reverse-transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal swab specimens from patients with COVID-19 and controls, as well as in cells infected with SARS-CoV-2 in vitro. Our data showed that the mRNA expression levels of AGO2, DICER1, DGCR8, DROSHA, and XPO5 were not significantly different in patients with severe COVID-19 when compared to patients with non-severe COVID-19 and controls. Similarly, the mRNA expression of these genes was not affected by SARS-CoV-2 infection in NHBE and Calu-3 cells. However, in Vero E6 cells, AGO2, DICER1, DGCR8, and XPO5 mRNA levels were slightly upregulated 24 h after infection with SARS-CoV-2. In conclusion, we did not find evidence for downregulation of mRNA levels of miRNA biogenesis genes during SARS-CoV-2 infection, neither ex vivo nor in vitro.
Published: 2023

41. Is 'moderate' aortic stenosis still the right name? A review of the literature

Author: Yohann Bohbot, Augustin Coisne, Alexandre Altes, Franck Levy, Chloé Di Lena, Samy Aghezzaf, Sylvestre Maréchaux, Dan Rusinaru, Christophe Tribouilloy, CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Lille, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Centre Cardio-Thoracique de Monaco (CCTM)
Subjects: General Medicine, Cardiology and Cardiovascular Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Current guidelines recommend aortic valve replacement for symptomatic or selected asymptomatic high-risk patients with severe aortic stenosis. Conversely, a watchful waiting attitude applies to patients with moderate aortic stenosis, regardless of their risk profile and symptoms, until the echocardiographic thresholds of severe aortic stenosis are reached. This strategy is based on data reporting high mortality in untreated severe symptomatic aortic stenosis, whereas moderate aortic stenosis has always been perceived as a non-threatening condition, with a benefit–risk balance against surgery. Meanwhile, numerous studies have reported a worrying event rate in these patients, surgical techniques and outcomes have improved significantly and the use of transcatheter aortic valve replacement has become more widespread and extended to lower-risk patients, leaving this strategy open to question, especially for patients with moderate aortic stenosis and left ventricular dysfunction. In this review, we summarize the current state of knowledge about moderate aortic stenosis progression and prognosis. We also discuss the particular case of moderate aortic stenosis associated with left ventricular dysfunction, and the ongoing trials that that might change our paradigm for the management of this “moderate” valvular heart disease.
Published: 2023

42. LSC17 score complements genetics and measurable residual disease in acute myeloid leukemia: an ALFA study

Author: Loic Vasseur, Laurène Fenwarth, Jérôme Lambert, Stéphane de Botton, Martin Figeac, Céline Villenet, Maël Heiblig, Pierre-yves Dumas, Christian Récher, Celine Berthon, Emilie Lemasle, Delphine Lebon, Juliette Lambert, Christine Terré, Karine Celli-Lebras, Hervé Dombret, Claude Preudhomme, Meyling H Cheok, Raphaël A. Itzykson, Nicolas Duployez, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, 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), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Claude Huriez [Lille], CHU Lille, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Thérapie génique et contrôle de l'expansion cellulaire (UMR E007), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Département de Génétique [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), and Service de pathologie [CHU Lille]
Subjects: [SDV]Life Sciences [q-bio], Hematology
Abstract: International audience; Whether the LSC17 gene expression can improve risk stratification in the context of NGS-based risk stratification and measurable residual disease (MRD) in AML patients treated intensively has not been explored. We analyzed LSC17 in 504 adult patients prospectively treated in the ALFA-0702 trial. Multiple (cyto)genetic alterations were associated with changes in LSC17, such as higher LSC17 in patients with RUNX1 or TP53 mutations, and lower scores in those with CEBPA and NPM1 mutations. LSC17-high patients had a lower rate of complete response (CR) or CR with incomplete platelet recovery (CRp) after one induction course in a multivariable analysis (OR=0.41, p=0.0007) accounting for European LeukemiaNet 2022 (ELN22) risk groups, age, and white blood cell (WBC) count. The LSC17-high status was associated with shorter overall survival (OS) (3-year OS: 70.0% versus 52.7% in LSC17-low patients, p
Published: 2023

43. Precision of neuronal localization in 2D cell cultures by using high-performance electropolymerized microelectrode arrays correlated with optical imaging

Author: Mahdi Ghazal, Corentin Scholaert, Corentin Dumortier, Camille Lefebvre, Nicolas Barois, Sebastien Janel, Mehmet Cagatay Tarhan, Morvane Colin, Luc Buée, Sophie Halliez, Sebastien Pecqueur, Yannick Coffinier, Fabien Alibart, Pierre Yger, Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), 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 d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Bio-Micro-Electro-Mechanical Systems - IEMN (BIOMEMS - IEMN), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Nanostructures, nanoComponents & Molecules - IEMN (NCM - IEMN), NanoBioInterfaces - IEMN (NBI - IEMN), Laboratoire Nanotechnologies et Nanosystèmes [Sherbrooke] (LN2), Université de Sherbrooke (UdeS)-École Centrale de Lyon (ECL), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Unité de neurosciences intégratives et computationnelles (UNIC), Centre National de la Recherche Scientifique (CNRS), 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), The authors thank the RENATECH network, and the engineers from IEMN for their support and the animal care staff of the EOPS facility (UMS-2014 US41 PLBS). This work is founded by ERC-CoG IONOS project #773 228, the LabEx DISTALZ, and the Joint Inserm-University Chairsprogram., Renatech Network, ANR-11-LABX-0009,DISTALZ,Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime(2011), and European Project: 773228,H2020,ERC-2017-COG,IONOS(2018)
Subjects: Neuronal localization, Spike Sorting, MEA, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, General Nursing
Abstract: Recently, the development of electronic devices to extracellularly record the simultaneous electrical activities of numerous neurons has been blooming, opening new possibilities to interface and decode neuronal activity. In this work, we tested how the use of EDOT electropolymerization to tune post-fabrication materials could optimize the cell/electrode interface of such devices. Our results showed an improved signal-to-noise ratio, better biocompatibility, and a higher number of neurons detected in comparison with gold electrodes. Then, using such enhanced recordings with 2D neuronal cultures combined with fluorescent optical imaging, we checked the extent to which the positions of the recorded neurons could be estimated solely via their extracellular signatures. Our results showed that assuming neurons behave as monopoles, positions could be estimated with a precision of approximately tens of micrometers.
Published: 2023

44. Nkx2-5 Loss of Function in the His-Purkinje System Hampers Its Maturation and Leads to Mechanical Dysfunction

Author: Caroline Choquet, Pierre Sicard, Juliette Vahdat, Thi Hong Minh Nguyen, Frank Kober, Isabelle Varlet, Monique Bernard, Sylvain Richard, Robert G. Kelly, Nathalie Lalevée, Lucile Miquerol, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Transcriptomique et génomique appliquée - Transcriptomics and Applied Genomics (TAG), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Hanoi University of Science and Technology (HUST), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: RSR’ complex, cell dropout, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], His-Purkinje system, fast conduction markers, Cx40, strain defects, cardiac dyssynchrony, Pharmacology (medical), General Pharmacology, Toxicology and Pharmaceutics, [SDV.BDD]Life Sciences [q-bio]/Development Biology
Abstract: International audience; The ventricular conduction or His-Purkinje system (VCS) mediates the rapid propagation and precise delivery of electrical activity essential for the synchronization of heartbeats. Mutations in the transcription factor Nkx2-5 have been implicated in a high prevalence of developing ventricular conduction defects or arrhythmias with age. Nkx2-5 heterozygous mutant mice reproduce human phenotypes associated with a hypoplastic His-Purkinje system resulting from defective patterning of the Purkinje fiber network during development. Here, we investigated the role of Nkx2-5 in the mature VCS and the consequences of its loss on cardiac function. Neonatal deletion of Nkx2-5 in the VCS using a Cx40-CreERT2 mouse line provoked apical hypoplasia and maturation defects of the Purkinje fiber network. Genetic tracing analysis demonstrated that neonatal Cx40-positive cells fail to maintain a conductive phenotype after Nkx2-5 deletion. Moreover, we observed a progressive loss of expression of fast-conduction markers in persistent Purkinje fibers. Consequently, Nkx2-5-deleted mice developed conduction defects with progressively reduced QRS amplitude and RSR’ complex associated with higher duration. Cardiac function recorded by MRI revealed a reduction in the ejection fraction in the absence of morphological changes. With age, these mice develop a ventricular diastolic dysfunction associated with dyssynchrony and wall-motion abnormalities without indication of fibrosis. These results highlight the requirement of postnatal expression of Nkx2-5 in the maturation and maintenance of a functional Purkinje fiber network to preserve contraction synchrony and cardiac function.
Published: 2023
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45. Comparison of effective regurgitant orifice area by the PISA method and tricuspid coaptation gap measurement to identify very severe tricuspid regurgitation and stratify mortality risk

Author: L. Tordjman, Y. Bohbot, J. Dreyfus, T. Le Tourneau, Y. Lavie-Badie, C. Selton-Suty, B. Elegamandji, G. L’official, A. Fraix, S. Aghezzaf, P.Y. Turgeon, D. Messika Zeitoun, M. Enriquez-Sarano, A. Coisne, E. Donal, C. Tribouilloy, CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Université de Picardie Jules Verne (UPJV), Centre cardiologique du Nord (CCN), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Mayo Clinic [Rochester], and CHU Lille
Subjects: very severe tricuspid regurgitation, coaptation gap, Cardiology and Cardiovascular Medicine, mortality, survival, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, effective regurgitant orifice area
Abstract: IntroductionVarious definitions of very severe (VS) tricuspid regurgitation (TR) have been proposed based on the effective regurgitant orifice area (EROA) or tricuspid coaptation gap (TCG). Because of the inherent limitations associated with the EROA, we hypothesized that the TCG would be more suitable for defining VSTR and predicting outcomes.Materials and methodsIn this French multicentre retrospective study, we included 606 patients with ≥moderate-to-severe isolated functional TR (without structural valve disease or an overt cardiac cause) according to the recommendations of the European Association of Cardiovascular Imaging. Patients were further stratified into VSTR according to the EROA (≥60 mm2) and then according to the TCG (≥10 mm). The primary endpoint was all-cause mortality and the secondary endpoint was cardiovascular mortality.ResultsThe relationship between the EROA and TCG was poor (R2 = 0.22), especially when the size of the defect was large. Four-year survival was comparable between patients with an EROA 2 vs. ≥60 mm2 (68 ± 3% vs. 64 ± 5%, p = 0.89). A TCG ≥10 mm was associated with lower four-year survival than a TCG p p = 0.019) and cardiovascular mortality (adjusted HR[95% CI] = 2.12[1.33–3.25], p = 0.001), whereas an EROA ≥60 mm2 was not associated with all-cause or cardiovascular mortality (adjusted HR[95% CI]: 1.16[0.81–1.64], p = 0.416, and adjusted HR[95% CI]: 1.07[0.68–1.68], p = 0.784, respectively)ConclusionThe correlation between the TCG and EROA is weak and decreases with increasing defect size. A TCG ≥10 mm is associated with increased all-cause and cardiovascular mortality and should be used to define VSTR in isolated significant functional TR.
Published: 2023

46. Enhanced cell viscosity: a new phenotype associated with lamin A/C alterations

Author: Cécile Jebane, Alice-Anaïs Varlet, Marc Karnat, Lucero M. Hernandez-Cedillo, Amélie Lecchi, Frédéric Bedu, Camille Desgrouas, Corinne Vigouroux, Marie-Christine Vantyghem, Annie Viallat, Jean-François Rupprecht, Emmanuèle Helfer, Catherine Badens, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Turing Centre for Living Systems [Marseille] (TCLS), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physique Théorique - UMR 7332 (CPT), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Amidex A-M-AAP-ID-17-66-170301-11.30
Subjects: [PHYS]Physics [physics], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft]
Abstract: Lamin A/C is a well-established key contributor to nuclear stiffness and its role in nucleus mechanical properties has been extensively studied. However, its impact on whole cell mechanics has been poorly addressed, even less so in terms of measurable physical parameters. In the present study, microfluidic experiments combined with theoretical analyses were performed to provide a quantitative estimation of the whole cell mechanical properties. This allowed the characterization of mechanical cell changes induced by lamin A/C alterations resulting from Atazanavir treatment or lipodystrophy-associated LMNA R482W pathogenic variant. Results unveil an increase in the long-time viscosity as a signature of cells affected by lamin A/C alterations. In addition, they show that the whole cell response to mechanical stress is driven not only by the nucleus but also by the nucleo-cytoskeleton links and the microtubule network. This enhanced cell viscosity assessed by our microfluidic device could represent a useful diagnosis marker for lamin-related diseases.
Published: 2023

47. Further insight into the involvement of PII1 in starch granule initiation in Arabidopsis leaf chloroplasts

Author: Vandromme, C. (Camille), Spriet, C. (Corentin), Putaux, J. (Jean‐Luc), Dauvillee, D. (David), Courseaux, A. (Adeline), D'hulst, C. (Christophe), Wattebled, F. (Fabrice), Université de Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Centre de Recherches sur les Macromolécules Végétales [CERMAV ], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur les Macromolécules Végétales (CERMAV), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: Physiology, starch granule number, starch, [SDV]Life Sciences [q-bio], starch initiation, Arabidopsis, Plant Science, PII1, SS4, starch granule size, starch synthase
Abstract: International audience; The control of starch granule initiation in plant leaves is a complex process that requires active enzymes like Starch Synthase 4 and 3 (SS4 or SS3) and several noncatalytic proteins such as Protein Involved in starch Initiation 1 (PII1). In Arabidopsis leaves, SS4 is the main enzyme that control starch granule initiation, but in its absence, SS3 partly fulfills this function. How these proteins collectively act to control the initiation of starch granules remains elusive. PII1 and SS4 physically interact, and PII1 is required for SS4 to be fully active. However, Arabidopsis mutants lacking SS4 or PII1 still accumulate starch granules. Combining pii1 KO mutation with either ss3 or ss4 KO mutations provide new insights of how the remaining starch granules are synthesized. The ss3 pii1 line still accumulates starch, while the phenotype of ss4 pii1 is stronger than that of ss4. Our results indicate first that SS4 initiates starch granule synthesis in the absence of PII1 albeit being limited to one large lenticular granule per plastid. Second, that if in the absence of SS4, SS3 is able to initiate starch granules with low efficiency, this ability is further reduced with the additional absence of PII1.
Published: 2023

48. Novel PD-L1-Targeted Phenyl-Pyrazolone Derivatives with Antioxidant Properties

Author: Romain Regnault, Frédérique Klupsch, Hassiba El-Bouazzati, Romain Magnez, Raphaël Le Biannic, Natascha Leleu-Chavain, Hania Ahouari, Hervé Vezin, Régis Millet, Jean-François Goossens, Xavier Thuru, Christian Bailly, Université de Lille, CNRS, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA], Institute for Translational Research in Inflammation - U 1286 [INFINITE (Ex-Liric)], Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277, Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement - UMR 8516 [LASIRE], Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER], Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 [MSAP], Lille Inflammation Research International Center - U 995 [LIRIC], Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 (MSAP), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement - UMR 8516 (LASIRE), Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)
Subjects: antioxidant, pyrazolone, Organic Chemistry, Pharmaceutical Science, aldehyde reactivity, cancer, immune checkpoint, PD-L1 binding, Analytical Chemistry, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Chemistry (miscellaneous), Drug Discovery, Molecular Medicine, Physical and Theoretical Chemistry
Abstract: International audience; Orally-active anticancer small molecules targeting the PD-1/PD-L1 immune checkpoint are actively searched. Phenyl-pyrazolone derivatives with a high affinity for PD-L1 have been designed and characterized. In addition, the phenyl-pyrazolone unit acts as a scavenger of oxygen free radicals, providing antioxidant effects. The mechanism is known for the drug edaravone (1) which is also an aldehyde-reactive molecule. The present study reports the synthesis and functional characterization of new molecules (2–5) with an improved anti-PD-L1 activity. The leading fluorinated molecule 5 emerges as a potent checkpoint inhibitor, avidly binding to PD-L1, inducing its dimerization, blocking PD-1/PD-L1 signaling mediated by phosphatase SHP-2 and reactivating the proliferation of CTLL-2 cells in the presence of PD-L1. In parallel, the compound maintains a significant antioxidant activity, characterized using electron paramagnetic resonance (EPR)-based free radical scavenging assays with the probes DPPH and DMPO. The aldehyde reactivity of the molecules was investigated using 4-hydroxynonenal (4-HNE), which is a major lipid peroxidation product. The formation of drug-HNE adducts, monitored by high resolution mass spectrometry (HRMS), was clearly identified and compared for each compound. The study leads to the selection of compound 5 and the dichlorophenyl-pyrazolone unit as a scaffold for the design of small molecule PD-L1 inhibitors endowed with antioxidant properties.
Published: 2023

49. Stillbirths and neonatal mortality in LMICs: A community-based mother-infant cohort study

Author: Rambliere, Lison, de Lauzanne, Agathe, Diouf, Jean-Baptiste, Zo, Andrianirina Zafitsara, Landau, Myriam, Herindrainy, Perlinot, Hivernaud, Delphine, Sarr, Fatoumata Diene, Sok, Touch, Vray, Muriel, Collard, Jean-Marc, Borand, Laurence, Delarocque-Astagneau, Elisabeth, Guillemot, Didier, Kermorvant-Duchemin, Elsa, Huynh, Bich-Tram, Study Group, Birdy, Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Roi Baudouin Guédiawaye [Dakar, Senegal], Centre Hospitalier de Soavinandriana (CENHOSOA), Unité d’Épidémiologie et de Recherche clinique [Antananarivo, Madagascar], Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Institut Pasteur de Dakar, Ministry of Health [Phnom Penh], Unité de Bactériologie Expérimentale [Antananarivo, Madagascar] (IPM), Johns Hopkins University School of Medicine [Baltimore], Hôpital Raymond Poincaré [Garches], and The present work was supported by internal resources from Paris-Sud University. The BIRDY 1 & 2 research projects were implemented with the financial support of the Monegasque Cooperation for development, the Total Foundation, and MSDAVENIR.
Subjects: [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics
Abstract: International audience; BackgroundThe exact timing, causes, and circumstances of stillbirth and neonatal mortality in low- and middle-income countries (LMICs) remain poorly described, especially for antenatal stillbirths and deaths occurring at home. We aimed to provide reliable estimates of the incidence of stillbirth and neonatal death in three LMICs (Madagascar, Cambodia and Senegal) and to identify their main causes and associated risk factors.MethodsThis study is based on data from an international, multicentric, prospective, longitudinal, community-based mother-infant cohort. We included pregnant mothers and prospectively followed up their children in the community. Stillbirths and deaths were systematically reported; information across healthcare settings was collected and verbal autopsies were performed to document the circumstances and timing of death.ResultsAmong the 4436 pregnancies and 4334 live births, the peripartum period and the first day of life were the key periods of mortality. The estimated incidence of stillbirth was 11 per 1000 total births in Cambodia, 15 per 1000 in Madagascar, and 12 per 1000 in Senegal. We estimated neonatal mortality at 18 per 1000 live births in Cambodia, 24 per 1000 in Madagascar, and 23 per 1000 in Senegal. Based on ultrasound biometric data, 16.1% of infants in Madagascar were born prematurely, where 42% of deliveries and 33% of deaths occurred outside healthcare facilities. Risk factors associated with neonatal death were mainly related to delivery or to events that newborns faced during the first week of life.ConclusionsThese findings underscore the immediate need to improve care for and monitoring of children at birth and during early life to decrease infant mortality. Surveillance of stillbirth and neonatal mortality and their causes should be improved to mitigate this burden in LMICs.
Published: 2023

50. Structure-activity relationships of actively FhuE transported rifabutin derivatives with potent activity against Acinetobacter baumannii

Author: M. Maingot, M. Bourotte, A.C. Vetter, B. Schellhorn, K. Antraygues, H. Scherer, M. Gitzinger, C. Kemmer, G.E. Dale, O. Defert, S. Lociuro, M. Brönstrup, N. Willand, V. Trebosc, Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177 (M2SV), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, and This research was financially co-funded by European Union underthe European Regional Development Fund (ERDF), by the Hauts DeFrance Regional Council (Contract n◦NP0020070) and by I-Site ULNE(ANR-16-IDEX-0004 ULNE).
Subjects: Pharmacology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, [SDV]Life Sciences [q-bio], Organic Chemistry, Drug Discovery, General Medicine, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience
Published: 2023

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