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1. Ultrastructural analysis of the dehydrated tardigrade Hypsibius exemplaris unveils an anhydrobiotic-specific architecture

Author: Yoshihisa Mori, Simon Galas, Chantal Cazevielle, Nelly Godefroy, Fumihisa Ono, Emilie Le Goff, Naurang L. Saini, Stephen Baghdiguian, Pierre Cuq, Myriam Richaud, Bodescot, Myriam, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Okayama University of Science, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), The present study was supported by the CNRS 'Défi Origines 2018' – Project GigaTardi (grant no. 265880 – Giga18)., Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Plateau MRI-COMET [Montpellier], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Institut des Neurosciences de Montpellier (INM), Università degli Studi di Roma 'La Sapienza' [Rome], École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), and Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]
Subjects: 0301 basic medicine, tardigrade, Cell, ultrastructural analysis, lcsh:Medicine, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Mitochondrion, Cellular imaging, Article, 03 medical and health sciences, Microscopy, Electron, Transmission, Organelle, medicine, Tardigrada, Electron microscopy, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Animals, Cellular organization, Desiccation, lcsh:Science, Cell Nucleus, Multidisciplinary, 030102 biochemistry & molecular biology, biology, Chemistry, Endoplasmic reticulum, lcsh:R, biology.organism_classification, Adaptation, Physiological, Cell biology, Mitochondria, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, 030104 developmental biology, medicine.anatomical_structure, tardigrade, ultrastructural analysis, morphological features, morphological features, Ultrastructure, [SDV.BA.ZI] Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, lcsh:Q, Tardigrade, Hypsibius
Abstract: Tardigrades can cope with adverse environmental conditions by turning into anhydrobiotes with a characteristic tun shape. Tun formation is an essential morphological adaptation for tardigrade entry into the anhydrobiotic state. The tun cell structure and ultrastructure have rarely been explored in tardigrades in general and never in Hypsibius exemplaris. We used transmission electron microscopy to compare cellular organization and ultrastructures between hydrated and anhydrobiotic H. exemplaris. Despite a globally similar cell organelle structure and a number of cells not significantly different between hydrated and desiccated tardigrades, reductions in the sizes of both cells and mitochondria were detected in dehydrated animals. Moreover, in anhydrobiotes, secretory active cells with a dense endoplasmic reticulum network were observed. Interestingly, these anhydrobiote-specific cells are in a close relationship with a specific extracellular structure surrounding each cell. It is possible that this rampart-like extracellular structure resulted from the accumulation of anhydrobiotic-specific material to protect the cells. Interestingly, after five hours of rehydration, the number of secretory cells decreased, and the specific extracellular structure began to disappear. Twenty-four hours after the beginning of rehydration, the cellular structure and ultrastructure were comparable to those observed in hydrated tardigrades.
Published: 2020

2. Whole and fractionated human platelet lysate biomaterials-based biotherapy induces strong neuroprotection in experimental models of amyotrophic lateral sclerosis

Author: Flore Gouel, Kelly Timmerman, Philippe Gosset, Cedric Raoul, Mary Dutheil, Aurélie Jonneaux, Guillaume Garçon, Caroline Moreau, Veronique Danel-Brunaud, James Duce, Thierry Burnouf, Jean-Christophe Devedjian, David Devos, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de 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), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Cambridge [UK] (CAM), Taipei Medical University, 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), Université de Lille, LillOA, CHU Lille, CNRS, Inserm, Université de Lille, Lille Neurosciences & Cognition (LilNCog) - U 1172, Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017, IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483, Institut des Neurosciences de Montpellier [INM], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], University of Cambridge [UK] [CAM], and Lille Neurosciences & Cognition - U 1172 [LilNCog]
Subjects: Motor Neurons, Neurotrophic growth factors, Superoxide Dismutase, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neurodegenerative diseases, Biophysics, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Bioengineering, Biocompatible Materials, Mice, Transgenic, Amyotrophic lateral sclerosis, Neuroprotection, Motoneuron, Biomaterials, Biological Therapy, [SDV.IB.BIO] Life Sciences [q-bio]/Bioengineering/Biomaterials, Disease Models, Animal, Mice, Mechanics of Materials, Ceramics and Composites, Platelet biomaterials, Animals, Humans, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials
Abstract: International audience; Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease of motor neurons leading to death within 3 years and without a curative treatment. Neurotrophic growth factors (NTFs) are pivotal for cell survival. A reason for the lack of patient efficacy with single recombinant NTF brain infusion is likely to be due to the synergistic neuroprotective action of multiple NTFs on a diverse set of signaling pathways. Fractionated (protein size
Published: 2021

3. Severity features of suicide attempters with epilepsy

Author: Jorge Lopez-Castroman, Isabelle Jaussent, Martin Pastre, Carolina Baeza-Velasco, Jean-Pierre Kahn, Marion Leboyer, Emmanuel Diaz, Philippe Courtet, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Psychopathologie et Processus de Santé (LPPS (URP_4057)), Université Paris Cité (UPCité), Université de Lorraine (UL), Fondation Santé des Etudiants de France, 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), CHU Henri Mondor, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Impulsivity, Epilepsy, [SDV]Life Sciences [q-bio], Suicide, Attempted, Attempted suicide, Personality Disorders, Suicidal Ideation, Psychiatry and Mental health, Seizures, Risk Factors, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Anticonvulsants, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biological Psychiatry, Self-injurious behavior
Abstract: International audience; Background: After the Food and Drug Administration alert about antiepileptic medication and suicide, incident epilepsy has been associated with first or recurrent suicide attempts independently of psychiatric comorbidities and antiepileptic treatment. Following this thread, the aim of this study was to analyze if epilepsy was associated with a higher severity of lifetime suicide attempts (SAs).Methods: Analyses were carried out on 1677 adults hospitalized between 1999 and 2012 after a SA in a specialized ward for affective episodes. Five severity features were studied: frequent SAs (>2), early onset of first SA (≤26 years), history of violent SA, high suicide intent and high lethality of the SA. Adjusted logistic regression models were used to estimate the association between the lifetime diagnosis of epilepsy and the severity features.Results: Among suicide attempters, ninety-three patients reported a lifetime diagnosis of epilepsy (5.5%). Epileptic patients diagnosed after the first SA were more likely to be frequent suicide attempters than non-epileptic ones. They showed also higher SA planification scores.Limitations: Diagnosis accuracy is limited by the use of self-reports for epilepsy. The lack of precise information about the disease course and treatment have not allowed for further statistical analysis. With regard to psychiatric comorbidities, personality disorders could not be taken into account.Conclusions: Suicide attempters with epilepsy present an increased severity in some aspects of their suicidal behavior regardless of demographic and clinical variables. Our results give support to the existence of a bidirectional association between epilepsy and suicidal behavior.
Published: 2022

4. Comparison of continuous with single-injection regional analgesia on patient experience after ambulatory orthopaedic surgery: a randomised multicentre trial

Author: Axel Maurice-Szamburski, Philippe Grillo, Philippe Cuvillon, Thierry Gazeau, Laurent Delaunay, Pascal Auquier, Sophie Bringuier, Xavier Capdevila, Clinique Juge - Clinique du sport [Marseille], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Initial MAnagement and prevention of acute orGan failures IN critically ill patiEnts (IMAGINE), Université de Montpellier (UM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Institut des Neurosciences de Montpellier (INM)
Subjects: Patient experience, Pain, Postoperative, MESH: Humans, Orthopaedic surgery, Rehabilitation, Ambulatory surgery, MESH: Patient Outcome Assessment, MESH: Quality of Life, MESH: Analgesics, Opioid, Catastrophising, MESH: Anesthetics, Local, MESH: Orthopedic Procedures, Continuous nerve block, Opioids, Analgesics, Opioid, Patient Outcome Assessment, MESH: Analgesia, Anesthesiology and Pain Medicine, Quality of Life, Humans, Orthopedic Procedures, Analgesia, Anesthetics, Local, MESH: Pain, Postoperative, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: The optimal approach to improving patient experience and analgesia after ambulatory orthopaedic surgery remains unclear.Methods: This multicentre, randomised clinical trial compared single-injection nerve block analgesia with home delivery of continuous nerve block analgesia by remote-controlled electronic pump. The primary outcome was patient-reported satisfaction (Evaluation du Vecu de l'Anesthesie Generale [EVAN-G]; 0-100) assessed on postoperative Day 2. Secondary outcomes focused on pain, opioid consumption, quality of rehabilitation, activity tracking using a wearable electronic device, and 90-day quality of life.Results: We randomly assigned 294 patients to continuous pump delivery or single injection. For subjects with normal level of pain catastrophising (Pain Catastrophizing Scale
Published: 2022

5. Association Between Vision and Brain Cortical Thickness in a Community-Dwelling Elderly Cohort

Author: Chloé Chamard, Jerome J Maller, Nicolas Menjot, Eloi Debourdeau, Virginie Nael, Karen Ritchie, Isabelle Carriere, Vincent Daien, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Monash University [Melbourne], General Electric Healthcare [Melbourne , VIC , Australia], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), University of Edinburgh, The University of Sydney, and Carrière, Isabelle
Subjects: vision, Cellular and Molecular Neuroscience, Ophthalmology, Eye and Brain, brain, visual function, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], cortical thickness, morphometry, Sensory Systems, MRI
Abstract: ChloÃ© Chamard,1,2 Jerome J Maller,3,4 Nicolas Menjot,5 Eloi Debourdeau,1 Virginie Nael,6 Karen Ritchie,2,7 Isabelle Carriere,2,&ast; Vincent Daien1,2,8,&ast; 1Department of Ophthalmology, Gui de Chauliac Hospital, Montpellier, F-34000, France; 2Institute for Neurosciences of Montpellier INM, University Montpellier, INSERM, Montpellier, F-34091, France; 3General Electric Healthcare, Melbourne, VIC, Australia; 4Monash Alfred Psychiatry Research Centre, Melbourne, VIC, Australia; 5Department of Neuroradiology, Gui de Chauliac Hospital, Montpellier, F-34000, France; 6Bordeaux Population Health Research Center, UMR 1219, University Bordeaux, INSERM, Bordeaux, F-33000, France; 7Department of Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK; 8The Save Sight Institute, Sydney Medical School, the University of Sydney, Sydney, NSW, Australia&ast;These authors contributed equally to this workCorrespondence: ChloÃ© Chamard, Department of Ophthalmology, Gui de Chauliac Hospital, 80 avenue Augustin Fliche, Montpellier, F-34000, France, Tel +33 6 33 55 65 06, Email chloe.chamard@gmail.comPurpose: Visual impairment is a major cause of disability and impairment of cognitive function in older people. Brain structural changes associated with visual function impairment are not well understood. The objective of this study was to assess the association between visual function and cortical thickness in older adults.Methods: Participants were selected from the French population-based ESPRIT cohort of 2259 community-dwelling adults â¥ 65 years old enrolled between 1999 and 2001. We considered visual function and brain MRI images at the 12-year follow-up in participants who were right-handed and free of dementia and/or stroke, randomly selected from the whole cohort. High-resolution structural T1-weighted brain scans acquired with a 3-Tesla scanner. Regional reconstruction and segmentation involved using the FreeSurfer image-analysis suite.Results: A total of 215 participants were included (mean [SD] age 81.8 [3.7] years; 53.0% women): 30 (14.0%) had central vision loss and 185 (86.0%) normal central vision. Vision loss was associated with thinner cortical thickness in the right insula (within the lateral sulcus of the brain) as compared with the control group (mean thickness 2.38 [0.04] vs 2.50 [0.03] mm, 4.8% thinning, pcorrected= 0.04) after adjustment for age, sex, lifetime depression and cardiovascular disease.Conclusion: The present study describes a significant thinning of the right insular cortex in older adults with vision loss. The insula subserves a wide variety of functions in humans ranging from sensory and affective processing to high-level cognitive processing. Reduced insula thickness associated with vision loss may increase cognitive burden in the ageing brain.Keywords: visual function, vision, cortical thickness, brain, morphometry, MRI
Published: 2022

6. Spontaneously occurring tumors in different wild-derived strains of hydra

Author: Boutry, Justine, Buysse, Marie, Tissot, Sophie, Cazevielle, Chantal, Hamede, Rodrigo, Dujon, Antoine, Ujvari, Beata, Giraudeau, Mathieu, Klimovich, Alexander, Thomas, Frédéric, Tökölyi, Jácint, Centre de Recherches Ecologiques et Evolutives sur le Cancer (MIVEGEC-CREEC), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), 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)-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), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Deakin University [Waurn Ponds], LIttoral ENvironnement et Sociétés (LIENSs), La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), Christian-Albrechts University of Kiel, University of Debrecen Egyetem [Debrecen], The Project is funded by Agence Nationale de la Recherche, Grant no. ANR-18-CE35-0009, Centre National de la Recherche Scientifique, International Associ-ated Laboratory Grant, Magyar Tudományos Akadémia, Grant no. Lendület LP2021/12, and ANR-18-CE35-0009,TRANSCAN,ECOLOGIE ET EVOLUTION DES CANCERS TRANSMISSIBLES(2018)
Subjects: [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, MESH: Humans, MESH: Chlamydiales, Multidisciplinary, MESH: Hydra, MESH: Fresh Water, MESH: Animals, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Female, MESH: Male
Abstract: Hydras are freshwater cnidarians widely used as a biological model to study different questions such as senescence or phenotypic plasticity but also tumoral development. The spontaneous tumors found in these organisms have been so far described in two female lab strains domesticated years ago (Hydra oligactis and Pelmatohydra robusta) and the extent to which these tumors can be representative of tumors within the diversity of wild hydras is completely unknown. In this study, we examined individuals isolated from recently sampled wild strains of different sex and geographical origin, which have developed outgrowths looking like tumors. These tumefactions have common features with the tumors previously described in lab strains: are composed of an accumulation of abnormal cells, resulting in a similar enlargement of the tissue layers. However, we also found diversity within these new types of tumors. Indeed, not only females, but also males seem prone to form these tumors. Finally, the microbiota associated to these tumors is different from the one involved in the previous lineages exhibiting tumors. We found that tumorous individuals hosted yet undescribed Chlamydiales vacuoles. This study brings new insights into the understanding of tumor susceptibility and diversity in brown hydras from different origins.
Published: 2023

7. High-Throughput Screening for Extracellular Inhibitors of the FLT3 Receptor Tyrosine Kinase Reveals Chemically Diverse and Druggable Negative Allosteric Modulators

Author: Romain Hany, Jean-Philippe Leyris, Guillaume Bret, Sylvie Mallié, Chamroeun Sar, Maxime Thouaye, Abdallah Hamze, Olivier Provot, Pierre Sokoloff, Jean Valmier, Pascal Villa, Didier Rognan, Plate-forme de chimie biologique intégrative de Strasbourg (PCBiS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), BIODOL Therapeutics [Clapiers], Laboratoire d'Innovation Thérapeutique (LIT), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), and ROGNAN, Didier
Subjects: Mice, HEK293 Cells, fms-Like Tyrosine Kinase 3, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Animals, Humans, Molecular Medicine, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, General Medicine, Ligands, Biochemistry, High-Throughput Screening Assays
Abstract: International audience; nhibiting receptor tyrosine kinases is commonly achieved by two main strategies targeting either the intracellular kinase domain by low molecular weight compounds or the extracellular ligand-binding domain by monoclonal antibodies. Identifying small molecules able to inhibit RTKs at the extracellular level would be highly desirable to gain exquisite selectivity but is believed to be challenging owing to the size of RTK endogenous ligands (cytokines, growth factors) and the topology of RTK extracellular domains. We here report the high-throughput screening of the French Chemical Library (48K compounds) for extracellular inhibitors of the Fms-like tyrosine kinase 3 (FLT3) receptor tyrosine kinase, by a homogeneous time-resolved fluorescence competition assay. A total of 679 small molecular weight ligands (1.4%) were confirmed to strongly inhibit (>75%) the binding of the fluorescent labeled FLT3 ligand (FL cytokine) to FLT3 overexpressed in HEK-293 cells, at two different concentrations (5 and 20 μM). Concentration-response curves, obtained for 111 lead-like molecules, confirmed the unexpected tolerance of the FLT3 extracellular domain for low molecular weight druggable inhibitors exhibiting submicromolar potencies, chemical diversity, and promising pharmacokinetic properties. Further investigation of one hit confirmed inhibitory properties in dorsal root ganglia neurons and in a mouse model of neuropathic pain.
Published: 2022

8. SpliceAI-visual: a free online tool to improve SpliceAI splicing variant interpretation

Author: Jean-Madeleine de Sainte Agathe, Mathilde Filser, Bertrand Isidor, Thomas Besnard, Paul Gueguen, Aurélien Perrin, Charles Van Goethem, Camille Verebi, Marion Masingue, John Rendu, Mireille Cossée, Anne Bergougnoux, Laurent Frobert, Julien Buratti, Élodie Lejeune, Éric Le Guern, Florence Pasquier, Fabienne Clot, Vasiliki Kalatzis, Anne-Françoise Roux, Benjamin Cogné, David Baux, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), Nantes Université (Nantes Univ), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, 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), 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, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and CHU Montpellier
Subjects: [SDV]Life Sciences [q-bio], Drug Discovery, Genetics, Molecular Medicine, Molecular Biology
Abstract: Abstract SpliceAI is an open-source deep learning splicing prediction algorithm that has demonstrated in the past few years its high ability to predict splicing defects caused by DNA variations. However, its outputs present several drawbacks: (1) although the numerical values are very convenient for batch filtering, their precise interpretation can be difficult, (2) the outputs are delta scores which can sometimes mask a severe consequence, and (3) complex delins are most often not handled. We present here SpliceAI-visual, a free online tool based on the SpliceAI algorithm, and show how it complements the traditional SpliceAI analysis. First, SpliceAI-visual manipulates raw scores and not delta scores, as the latter can be misleading in certain circumstances. Second, the outcome of SpliceAI-visual is user-friendly thanks to the graphical presentation. Third, SpliceAI-visual is currently one of the only SpliceAI-derived implementations able to annotate complex variants (e.g., complex delins). We report here the benefits of using SpliceAI-visual and demonstrate its relevance in the assessment/modulation of the PVS1 classification criteria. We also show how SpliceAI-visual can elucidate several complex splicing defects taken from the literature but also from unpublished cases. SpliceAI-visual is available as a Google Colab notebook and has also been fully integrated in a free online variant interpretation tool, MobiDetails (https://mobidetails.iurc.montp.inserm.fr/MD). Graphical abstract
Published: 2023

9. Meisosomes, folded membrane platforms, link the epidermis to the cuticle in C. elegans

Author: Dina Aggad, Nicolas Brouilly, Shizue Omi, Clara L. Essmann, Benoit Dehapiot, Cathy Savage-Dunn, Fabrice Richard, Chantal Cazevieille, Kristin A. Politi, David H. Hall, Remy Pujol, Nathalie Pujol, 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), Turing Centre for Living Systems [Marseille] (TCLS), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Department of Computer science [University College of London] (UCL-CS), University College of London [London] (UCL), College of Staten Island [CUNY] (CSI CUNY), City University of New York [New York] (CUNY), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Albert Einstein College of Medicine [New York], ANR-22-CE13-0037,SensoSkin,Comment la peau perçoit-elle les blessures?(2022), ANR-16-CONV-0001,CENTURI,CenTuri : Centre Turing des Systèmes vivants(2016), ANR-16-CE15-0001,ELEGINN,Analyse intégrée de l'immunité innée antifongique chez C. elegans(2016), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Aix Marseille Université (AMU), Neurobiologie de l'audition-plasticité synaptique, Institut National de la Santé et de la Recherche Médicale (INSERM), and ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011)
Subjects: Epidermis (zoology), Chemistry, [SDV]Life Sciences [q-bio], Mutant, Extracellular, Integrated stress response, Cytoskeleton, Moulting, Process (anatomy), Cuticle (hair), Cell biology
Abstract: Apical extracellular matrices (aECMs) form a physical barrier to the environment. InC. elegans, the epidermal aECM, the cuticle, is composed mainly of different types of collagen, associated in circumferential ridges separated by furrows. Here, we show that in mutants lacking furrows, the normal intimate connection between the epidermis and the cuticle is lost, specifically at the lateral epidermis, where, in contrast to the dorsal and ventral epidermis, there are no hemidesmosomes. At the ultrastructural level, there is a profound alteration of structures that we term “meisosomes”, in reference to eisosomes in yeast. We show that meisosomes are composed of stacked parallel folds of the epidermal plasma membrane, alternately filled with cuticle. We propose that just as hemidesmosomes connect the dorsal and ventral epidermis, above the muscles, to the cuticle, meisosomes connect the lateral epidermis to it. Moreover, furrow mutants present marked modifications of the biomechanical properties of their skin and exhibit a constitutive damage response in the epidermis. As meisosomes co-localise to macrodomains enriched in phosphatidylinositol (4,5) bisphosphate, they might act, like eisosomes, as signalling platforms, to relay tensile information from the aECM to the underlying epidermis, as part of an integrated stress response to damage.
Published: 2023

10. Complex regulation of Gephyrin splicing is a determinant of inhibitory postsynaptic diversity

Author: Raphaël Dos Reis, Etienne Kornobis, Alyssa Pereira, Frederic Tores, Judit Carrasco, Candice Gautier, Céline Jahannault-Talignani, Patrick Nitschké, Christian Muchardt, Andreas Schlosser, Hans Michael Maric, Fabrice Ango, Eric Allemand, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Régulation épigénétique - Epigenetic regulation, Max Planck Institute of Immunobiology and Epigenetics (MPI-IE), Max-Planck-Gesellschaft, University of Würzburg = Universität Würzburg, This study was supported by: - The Deutsche Forschungsgemeinschaft (DFG MA6957/1-1), M.M.H. - The ERANet NEURON/DECODE (18-NEUR-0004), F.A. - The REVIVE funding from ANR 'Laboratoire d’Excellence' (2011–2021), C.M and E.A. - The ANR KREM-AIF (ANR-21-CE17-0014-02), E.A., We thank Y. Lallemand and Y. Porozhan for their help in perfusing mouse for ribosomal fractionation, the iExplore and RIO-Imaging Platforms of Montpellier for their support, CSHL PacBio sequencing platform. We thank A.R. Krainer, M.L. Hastings, S. Dokudovskaya, O. Mauger, E. Batsché, O. Espeli, and P. Carroll for the critical reading of the manuscript. We thank L. Telley for his initial contribution to PACBIO analysis., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), ANR-21-CE17-0014,KREM-AIF,KREMEN2, un nouvel inhibiteur de l'auto-inflammation médié par NF-kB impliqué dans les maladies généiques humaines(2021), Ango, Fabrice, Laboratoires d'excellence - Stem Cells in Regenerative Biology and Medicine - - REVIVE2010 - ANR-10-LABX-0073 - LABX - VALID, and KREMEN2, un nouvel inhibiteur de l'auto-inflammation médié par NF-kB impliqué dans les maladies généiques humaines - - KREM-AIF2021 - ANR-21-CE17-0014 - AAPG2021 - VALID
Subjects: Proteomics, Multidisciplinary, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Membrane Proteins, General Physics and Astronomy, General Chemistry, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Receptors, GABA-A, General Biochemistry, Genetics and Molecular Biology, Receptors, GABA, Synapses, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Protein Isoforms, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Carrier Proteins
Abstract: Gephyrin (GPHN) regulates the clustering of postsynaptic components at inhibitory synapses and is involved in pathophysiology of neuropsychiatric disorders. Here, we uncover an extensive diversity of GPHN transcripts that are tightly controlled by splicing during mouse and human brain development. Proteomic analysis reveals at least a hundred isoforms of GPHN incorporated at inhibitory Glycine and gamma-aminobutyric acid A receptors containing synapses. They exhibit different localization and postsynaptic clustering properties, and altering the expression level of one isoform is sufficient to affect the number, size, and density of inhibitory synapses in cerebellar Purkinje cells. Furthermore, we discovered that splicing defects reported in neuropsychiatric disorders are carried by multiple alternative GPHN transcripts, demonstrating the need for a thorough analysis of the GPHN transcriptome in patients. Overall, we show that alternative splicing of GPHN is an important genetic variation to consider in neurological diseases and a determinant of the diversity of postsynaptic inhibitory synapses.
Published: 2022

11. Loss of glucocorticoid receptor phosphorylation contributes to cognitive and neurocentric damages of the amyloid-β pathway

Author: Yann Dromard, Margarita Arango-Lievano, Amelie Borie, Maheva Dedin, Pierre Fontanaud, Joan Torrent, Michael J. Garabedian, Stephen D. Ginsberg, Freddy Jeanneteau, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), New York University School of Medicine (NYU Grossman School of Medicine), Nathan Kline Institute, BioCampus (BCM), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Nathan S. Kline Institute for Psychiatric Research (NKI), New York State Office of Mental Health, Guerineau, Nathalie C., and freddy, jeanneteau
Subjects: Hydrocortisone, [SDV]Life Sciences [q-bio], Mice, Transgenic, Neuroimaging, Glucocorticoid receptor, Pathology and Forensic Medicine, Cellular and Molecular Neuroscience, Amyloid beta-Protein Precursor, Mice, Cognition, Receptors, Glucocorticoid, Alzheimer Disease, Memory, Animals, Humans, Receptor, trkB, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Phosphorylation, Amyloid beta-Peptides, Brain-Derived Neurotrophic Factor, Spine dynamics, [SDV] Life Sciences [q-bio], Disease Models, Animal, BDNF, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical)
Abstract: International audience; AbstractAberrant cortisol and activation of the glucocorticoid receptor (GR) play an essential role in age-related progression of Alzheimer's disease (AD). However, the GR pathways required for influencing the pathobiology of AD dementia remain unknown. To address this, we studied an early phase of AD-like progression in the well-established APP/PS1 mouse model combined with targeted mutations in the BDNF-dependent GR phosphorylation sites (serines 134/267) using molecular, behavioral and neuroimaging approaches. We found that disrupting GR phosphorylation (S134A/S267A) in mice exacerbated the deleterious effects of the APP/PS1 genotype on mortality, neuroplasticity and cognition, without affecting either amyloid-β deposition or vascular pathology. The dynamics, maturation and retention of task-induced new dendritic spines of cortical excitatory neurons required GR phosphorylation at the BDNF-dependent sites that amyloid-β compromised. Parallel studies in postmortem human prefrontal cortex revealed AD subjects had downregulated BDNF signaling and concomitant upregulated cortisol pathway activation, which correlated with cognitive decline. These results provide key evidence that the loss of neurotrophin-mediated GR phosphorylation pathway promotes the detrimental effects of the brain cortisol response that contributes to the onset and/or progression of AD dementia. These findings have important translational implications as they provide a novel approach to treating AD dementia by identifying drugs that increase GR phosphorylation selectively at the neurotrophic sites to improve memory and cognition.
Published: 2022

12. Brief Report: Frailty in Aging People Living With HIV: A Matched Controlled Study

Author: Matteo Vassallo, Louis Bernard, Jacques Reynes, Laure-Anne Gutierrez, Olivia Zaegel-Faucher, Laura Nailler, Claudine Berr, Pascale Leclercq, Claudine Barbuat, Marie Zins, Anna Ozguler, Lionel Lellouche, Alain Makinson, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Etudes montpelliéraines du monde anglophone (EMMA), Université Paul-Valéry - Montpellier 3 (UPVM), Aix Marseille Université (AMU), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de Cannes, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Raymond Poincaré [AP-HP], Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPC), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Grenoble Alpes (UGA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), and 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
Subjects: Male, Aging, HIV Infections, Comorbidity, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antiretroviral Therapy, Highly Active, Activities of Daily Living, Prevalence, Humans, Medicine, Pharmacology (medical), 030212 general & internal medicine, Depression (differential diagnoses), Aged, Frailty, Depression, business.industry, Confounding, Odds ratio, Middle Aged, medicine.disease, Confidence interval, CD4 Lymphocyte Count, 3. Good health, Cross-Sectional Studies, Infectious Diseases, Case-Control Studies, Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, Viral load, 030217 neurology & neurosurgery, Demography
Abstract: International audience; Background: We compared the prevalence of frailty among aging people living with HIV (PLHIV) with people without HIV from the ANS EP58 HAND 55–70 Study.Methods: Cross-sectional multicentric study which consecutively included 200 PLHIV and 1000 people without HIV from the French national CONSTANCES cohort, matched on age, sex, and education level. PLHIV were aged 55–70 years, with a HIV viral load < 50 copies/mL and a lymphocyte T-CD4 level > 200 cells/µL for the last 24 and 12 months, respectively. We measured frailty (>2 items) and prefrailty (one or 2 items) using a proxy of the 5-item Fried score. Multivariate logistic regression was performed to assess the association between HIV and frailty/prefrailty, adjusting for demographic, social, behavioral, and comorbidity confounders.Results: Outcome measures were available for 192 PLHIV and 822 people without HIV. The median age was 62 years, and 84.9% were men. Among PLHIV, the median CD4 cell count was 645.5 cells/µL. Prevalence of frailty/prefrailty was 5.73%/57.3% in PLHIV vs. 1.73%/52.2% in people without HIV, respectively. HIV was associated with prefrailty/frailty [odds ratio = 1.89; 95% confidence interval = 1.37 to 2.61), but after adjusting for social and behavioral factors and comorbidities, HIV was not significantly associated with prefrailty/frailty (odds ratio = 1.24; 95% confidence interval: = 0.84 to 1.81). In PLHIV only, frailty/prefrailty was associated with depressive symptomatology, kidney disease, and time since HIV infection.Conclusions: Prevalence of frailty is increased in aging PLHIV with well-controlled HIV disease, but other factors than HIV are predominant, particularly depression and comorbidities.
Published: 2021

13. Dissemination of circulating tumor cells at night: role of sleep or circadian rhythm?

Author: Yves, Dauvilliers, Frédéric, Thomas, Catherine, Alix-Panabières, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Recherches Ecologiques et Evolutives sur le Cancer (MIVEGEC-CREEC), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), 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)-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), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), and F.T. is supported by the MAVA foundation. C.A‑P. is supported by funding from the European Union Horizon 2020Research and Innovation program under the Marie Skłodowska‑Curie grant agreement No. 765492, by The National Institute of Cancer (INCa, http:// www.e‑cancer. fr), SIRIC Montpellier Cancer Grant NCa_Inserm_DGOS_12553, and the ERA‑NET TRANSCAN 2 JTC 2016 PROLIPSY, la Fondation ARC pour la Recherche sur le cancer and les Fonds de dotation AFER pour la recherche médicale.
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, MESH: Sleep, Circulating tumor cells, Circadian cycle, MESH: Neoplastic Cells, Circulating, Neoplastic Cells, Circulating, Circadian Rhythm, Metastasis, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Humans, MESH: Circadian Rhythm, Sleep
Abstract: International audience; The analysis of blood for circulating tumor cells (CTCs) called liquid biopsy has opened new avenues for cancer diagnostic and management, as well as the comprehension of the metastatic cascade [1]. As metastasis is responsible for about 90% of cancer deaths [2], it is of utmost importance to decrease the survival of CTCs, mostly to target specifically the metastasis-competent CTCs while they are reaching distant organs [3]. How CTCs are disseminating through the bloodstream? In advanced cancers, CTCs can travel as clusters or microemboli in the blood. CTCs traveling in a group seem to be released from hypoxic tumor regions [4] and clearly present a specific hypomethylation pattern related to stem cell features, underlying their higher aggressiveness [5]. Consequently, CTC clusters predict a poorer prognosis compared to single CTCs. Interestingly, CTC microemboli can also include other cell types, such as immune cells and/or cancer-associated fibroblasts from the tumor microenvironment, which have a higher capacity to survive and to metastasize. When CTCs are traveling the most? This specific question has already arised in 2020 when Cortés-Hernández et al. hypothesized that, because of evolutionary ecology reasons, malignant cells, including CTCs, should behave differently between day and night [6]. The recent work of Diamantopoulou et al. showed that the levels of CTCs increased at night in humans with breast cancer and mouse models of breast cancer and that CTCs in the rest-phase are more likely to metastasize [7]. This non-continuous generation of CTCs within the rest phase, if confirmed, will undoubtedly have major medical implications. However, key questions remain at this stage: Is it sleep and/or the circadian rhythm involved in the formation of CTCs and the metastatic spread of cancer, and by which specific mechanisms? The biology of most, if not all, living things is regulated by biological rhythms, in particular sleep and the circadian rhythm [8]. Due to the extreme diversity of cells typically generated in tumors, natural selection acting on cells, and/or groups of cells, may
Published: 2022

14. Molecular and clinical description of patients with GABA A receptor gene variants ( GABRA1 , GABRB2 , GABRB3 , GABRG2 ): a cohort study, review of literature, and genotype‐phenotype correlations

Author: Maillard, Pierre‐yves, Baer, Sarah, Schaefer, Élise, Desnous, Béatrice, Villeneuve, Nathalie, Lépine, Anne, Fabre, Alexandre, Lacoste, Caroline, El Chehadeh, Salima, Piton, Amélie, Porter, Louise Frances, Perriard, Caroline, Abi Wardé, Marie‐thérèse, Spitz, Marie‐aude, Laugel, Vincent, Lesca, Gaëtan, Putoux, Audrey, Ville, Dorothée, Mignot, Cyril, Héron, Delphine, Nabbout, Rima, Barcia, Giulia, Rio, Marlène, Roubertie, Agathe, Meyer, Pierre, Paquis-Flucklinger, Véronique, Patat, Olivier, Lefranc, Jérémie, Gerard, Marion, de Bellescize, Julietta, Villard, Laurent, de Saint Martin, Anne, Milh, Mathieu, Les Hôpitaux Universitaires de Strasbourg (HUS), 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), Hôpital de la Timone [CHU - APHM] (TIMONE), 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), Institut de génétique médicale d’Alsace, Hospices Civils de Lyon (HCL), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), 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), Département de génétique médicale [Hôpital de la Timone - APHM], 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), and MORNET, Dominique
Subjects: [SDV] Life Sciences [q-bio], Channelopathy, Developmental and Epileptic Encephalopathy, [SDV]Life Sciences [q-bio], Genetic generalized Epilepsy, GABA A receptor
Abstract: International audience; Objective: GABAA receptor subunit variants have recently been associated with neurodevelopmental disorders and/or epilepsy. The phenotype linked with each gene is becoming better known. Because of their common molecular structure and physiological role, it seemed interesting to describe a putative phenotype associated with GABAA -receptor-related disorders as a whole and seek possible genotype/phenotype correlations.Methods: We collected clinical, electrophysiological, therapeutic, and molecular data from patients affected with GABAA receptor subunit variants (GABRA1, GABRB2, GABRB3, GABRG2) through a national French collaboration using the EPIGENE network and compared them to the one already described in the literature.Results: We gathered the reported patients in 3 epileptic phenotypes: 15 patients with fever-related epilepsy (40%), 11 with early developmental epileptic encephalopathy (30%), 10 with generalized epilepsy spectrum (27%), and 1 patient without seizures (3%). We did not find a specific phenotype for any gene, but we showed that the location of variants on the transmembrane (TM) segment was associated with a more severe phenotype, irrespective of the GABAA receptor subunit gene, whereas N-terminal variants seemed to be related to milder phenotypes.Significance: GABAA receptor subunit variants are associated with highly variable phenotypes despite their molecular and physiological proximity. None of the genes described here was associated with a specific phenotype. On the other hand, it appears that the location of the variant on the protein may be a marker of severity. Variant location may have important weight in the development of targeted therapeutics.
Published: 2022

15. New Keratoconus Risk Factors: A Cross-Sectional Case—Control Study

Author: Eloi Debourdeau, Gabriel Planells, Chloe Chamard, David Touboul, Max Villain, Pascal Demoly, Fanny Babeau, Pierre Fournie, Vincent Daien, Service d'Ophtalmologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Bordeaux [Bordeaux], Médecine de précision par intégration de données et inférence causale (PREMEDICAL), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and The University of Sydney
Subjects: Ophthalmology, Article Subject, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Purpose. To evaluate risk factors associated with keratoconus in a monocentric cross-sectional case-control study. Methods. This observational study occurred from June 2019 to February 2021 in a university hospital (France). The case group consisted of 195 patients with keratoconus in at least one eye who were followed up by a corneal specialist. The control group consisted of 195 patients without any evidence of keratoconus on slit-lamp examination and corneal topography, who were matched 1 : 1 to controls by age and sex. Data were collected by a self-completed paper questionnaire before the consultation, and a multivariate logistic regression was performed. Results. Multivariate analysis revealed significant associations of keratoconus with family history (odds ratio [OR] = 22.2, p < 0.001 ), rubbing eyes (OR = 10.9, p < 0.001 ), allergy (any kind) (OR = 3.80, p < 0.001 ), smoking exposure (OR = 2.08, p = 0.017 ), and dry eyes (OR = 1.77, p = 0.045 f). The worst eye was associated with the more rubbed eye ( p < 0.001 ) and the more pressed eye during the night according to sleeping position ( p < 0.041 ). Conclusion. This study confirmed the association between keratoconus and eye rubbing, family history, and allergy. It highlighted the role of pressure on the eyes during sleep. Other less known risk factors such as dry eyes and smoking exposure should be explored in future studies.
Published: 2022

16. The autism-associated Meis2 gene is necessary for cardiac baroreflex regulation in mice

Author: J Roussel, R Larcher, P Sicard, P Bideaux, S Richard, F Marmigère, J Thireau, MORNET, Dominique, 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), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Montpellier Ressources Imagerie, Biocampus, CNRS, INSERM, Universite Montpellier, Montpellier, France, BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Mice, Multidisciplinary, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Sensory Receptor Cells, Autism Spectrum Disorder, Heart Rate, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Animals, Autistic Disorder, Baroreflex, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: Recent understanding of Autism Spectrum Disorder (ASD) showed that peripheral primary mechanosensitive neurons involved in touch sensation and central neurons affected in ASD share transcriptional regulators. Mutant mice for ASD-associated transcription factors exhibit impaired primary tactile perception, and restoring those genes specifically in primary sensory neurons rescue some of the anxiety-like behavior and social interaction defects.Interestingly, peripheral mechanosensitive sensory neurons also project to internal organs including the cardio-vascular system, and an imbalance of the cardio-vascular sympatho-vagal regulation is evidenced in ASD and intellectual disability. ASD patients have decreased vagal tone, suggesting dysfunction of sensory neurons involved in cardio-vascular sensing.In light of our previous finding that the ASD-associated Meis2 gene is necessary for normal touch neurons development and function, we investigated here if its inactivation in mouse peripheral sensory neurons also affects cardio-vascular sympatho-vagal regulation and baroreflex. Combining echocardiography, pharmacological challenge, blood pressure monitoring and heart rate variability analysis, we found that Meis2 mutant mice exhibited a blunted vagal response independently of any apparent cardiac malformation. These results suggest that defects in primary sensory neurons with mechanosensitive identity could participate in the imbalanced cardio-vascular sympatho-vagal tone found in ASD patients, reinforcing current hypotheses on the role of primary sensory neurons in the etiology of ASD.
Published: 2022

17. Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates

Author: Claire M. Bringuier, Jean-Christophe Perez, Emilie Aloy, Gaëtan Poulen, Nicolas Lonjon, Christophe Goze-Bac, Maida Cardoso, Yannick Nicolas Gerber, Hassan Boukhaddaoui, Florence E. Perrin, Emaëlle V.F. Artus, Nadine Mestre-Francés, Mécanismes moléculaires dans les démences neurodégénératives (MMDN), 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)-Université de Montpellier (UM), Laboratoire Charles Coulomb (L2C), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Perrin, Florence, Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Regional Imaging Platform, Montpellier Ressources Imagerie (MRI), BioCampus, Montpellier, France, Institut Universitaire de France (IUF), and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)
Subjects: Male, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV]Life Sciences [q-bio], primates, Medicine (miscellaneous), microglia, Gene Expression, Transcriptome, Mice, 0302 clinical medicine, Oral administration, Receptor, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Spinal cord injury, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Microglia, rodent, medicine.anatomical_structure, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Cheirogaleidae, Spinal cord pathology, Research Paper, proliferation, Neurogenesis, Central nervous system, Mice, Transgenic, Anisoles, Lesion, 03 medical and health sciences, Downregulation and upregulation, medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroinflammation, Spinal Cord Injuries, 030304 developmental biology, Cell Proliferation, Inflammation, business.industry, Recovery of Function, Functional recovery, medicine.disease, spinal cord injury, Mice, Inbred C57BL, Disease Models, Animal, Pyrimidines, Neuroinflammatory Diseases, Cancer research, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: No curative treatment is available for any deficits induced by spinal cord injury (SCI). Following injury, microglia undergo highly diverse activation processes, including proliferation, and play a critical role on functional recovery.In a translational objective, we investigated whether a transient pharmacological reduction of microglia proliferation after injury is beneficial for functional recovery after SCI in mice and nonhuman primates. The colony stimulating factor-1 receptor (CSF1R) regulates proliferation, differentiation, and survival of microglia, we thus used an oral administration of GW2580, a CSF1R inhibitor.First, transient post-injury GW2580 administration in mice improves motor function recovery, promotes tissues preservation and/or reorganization (identified by coherent anti-stokes Raman scattering microscopy), and modulates glial reactivity.Second, post-injury GW2580-treatment in nonhuman primates reduces microglia proliferation, improves functional motor function recovery, and promotes tissue protection. Notably, three months after lesion microglia reactivity returned to baseline value.Finally, to initiate the investigation on molecular mechanisms induced by a transient post-SCI GW2580-treatment, we used microglia-specific transcriptomic analysis in mice. Notably, we detected a downregulation in the expression of inflammatory-associated genes and we identified genes that were up-regulated by SCI and further downregulated by the treatment.Thus, a transient oral GW2580 treatment post-injury may provide a promising therapeutic strategy for SCI patients and may also be extended to other central nervous system disorders displaying microglia activation.
Published: 2021

18. LIX1-mediated changes in mitochondrial metabolism control the fate of digestive mesenchyme-derived cells

Author: Amandine Guérin, Claire Angebault, Sandrina Kinet, Chantal Cazevieille, Manuel Rojo, Jérémy Fauconnier, Alain Lacampagne, Arnaud Mourier, Naomi Taylor, Pascal de Santa Barbara, Sandrine Faure, 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), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), and Rojo, Manuel
Subjects: Linoleic acid, mtROS, [SDV]Life Sciences [q-bio], Organic Chemistry, Clinical Biochemistry, Sarcoma, YAP1/TAZ, Biochemistry, Cristae, Mitochondria, Mesoderm, Mitochondrial Proteins, Cell fate, Smooth muscle, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cysteine, Reactive Oxygen Species, Phospholipids, Transcription Factors
Abstract: International audience; YAP1 and TAZ are transcriptional co-activator proteins that play fundamental roles in many biological processes, from cell proliferation and cell lineage fate determination to tumorigenesis. We previously demonstrated that Limb Expression 1 (LIX1) regulates YAP1 and TAZ activity and controls digestive mesenchymal progenitor proliferation. However, LIX1 mode of action remains elusive. Here, we found that endogenous LIX1 is localized in mitochondria and is anchored to the outer mitochondrial membrane through S-palmitoylation of cysteine 84, a residue conserved in all LIX1 orthologs. LIX1 downregulation altered the mitochondrial ultrastructure, resulting in a significantly decreased respiration and attenuated production of mitochondrial reactive oxygen species (mtROS). Mechanistically, LIX1 knock-down impaired the stability of the mitochondrial proteins PHB2 and OPA1 that are found in complexes with mitochondrial-specific phospholipids and are required for cristae organization. Supplementation with unsaturated fatty acids counteracted the effects of LIX1 knock-down on mitochondrial morphology and ultrastructure and restored YAP1/TAZ signaling. Collectively, our data demonstrate that LIX1 is a key regulator of cristae organization, modulating mtROS level and subsequently regulating the signaling cascades that control fate commitment of digestive mesenchyme-derived cells.
Published: 2022

19. Disturbances in sleep, circadian rhythms and daytime functioning in relation to coronavirus infection and Long-COVID - a multinational ICOSS study

Author: Merikanto, I., Dauvilliers, Y., Chung, F., Holzinger, B., De Gennaro, L., Wing, Y. K., Korman, M., Partinen, M., Benedict, C., Bjelajac, A., Bjorvatn, B., Yin Chan, N., Hrubos-Strom, H., Inoue, Y., Kirov, R., Landtblom, A. -M., Leger, D., Matsui, K., Morin, C. M., Mota-Rolim, S., Nadorff, M. R., Penzel, T., Plazzi, G., Reis, C., Yordanova, J., Kortesoja, L., Merikanto, De Santis, A., Bolstad, C., Nadorff, de Macedo, T. F., Cunha, A. S., Mota-Rolim, Nierwetberg, F., Agami, D., Schwartsberg, E., Korman, Koumanova, S., Lyamova, L., Yordanova, Kristoffersson, A., Berntsson, S., Liu, Y., Ferreira, D., Avdagic, S. C., Delale, E. A., Macan, J., Ross, B., Vidovic, D., Lyamova, V. K., Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Finnish Institute for Health and Welfare [Helsinki, Finland] (FIHW), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University Health Network, University of Toronto, Medizinische Universität Wien = Medical University of Vienna, Fondazione Santa Lucia [IRCCS], Clinical and Behavioral Neurology [IRCCS Santa Lucia], The Chinese University of Hong Kong [Hong Kong], Ariel University, Terveystalo Oy, Helsinki Sleep Clinic [Helsinki], and Herrada, Anthony
Subjects: Cognitive Neuroscience, 03 medical and health sciences, Behavioral Neuroscience, Post-Acute COVID-19 Syndrome, 0302 clinical medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], chronotype, COVID-19, dreams, fatigue, pandemic, rapid eye movement behaviour disorder, Fatigue, 030304 developmental biology, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Pandemic, SARS-CoV-2, Chronotype, Circadian Rhythm, Sleep, General Medicine, 3. Good health, Dreams, Rapid eye movement behaviour disorder, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; This protocol paper describes the second survey produced by the International Covid Sleep Study (ICOSS) group with the aim to examine the associations between SARS-CoV-2 infection and sleep, sleepiness, and circadian problems as potential predisposing factors for more severe COVID-19 disease profile and for development of Long-COVID in the general population. The survey consists of 47 questions on sleep, daytime sleepiness, circadian rhythm, health, mental wellbeing, life habits, and socioeconomic situation before and during the pandemic, and conditional questions to those reporting having had coronavirus infection, being vaccinated, or suffering from particular sleep symptoms or sleep disorders. Surveys will be administered online between May and November 2021 in Austria, Brazil, Bulgaria, Canada, China, Croatia, Finland, France, Germany, Israel, Italy, Japan, Norway, Portugal, Sweden and USA. Data collected by the survey will give valuable information on the open questions regarding COVID-19 disease risk factors, symptomatology and evolution of Long-COVID, and on other long-term consequences related to the pandemic.
Published: 2022

20. The interplay between cognition, depression, anxiety, and sleep in primary Sjogren’s syndrome patients

Author: Goulabchand, Radjiv, Castille, Elodie, Navucet, Sophie, Etchecopar‐etchart, Damien, Matos, Aurélie, Maria, Alexandre, Gutierrez, Laure, Le Quellec, Alain, Menjot de Champfleur, Nicolas, Gabelle, Audrey, Guilpain, Philippe, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Institut d’Imagerie Fonctionnelle Humaine [CHU Montpellier] (I2FH), Laboratoire Charles Coulomb (L2C), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: MESH: Fatigue, Sleep Wake Disorders, MESH: Humans, Multidisciplinary, MESH: Anxiety, MESH: Depression, MESH: Sleep, Depression, Autoimmune diseases, MESH: Quality of Life, MESH: Cognition, Anxiety, MESH: Sleep Wake Disorders, MESH: Sjogren's Syndrome, Cognition, Sjogren's Syndrome, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Quality of Life, Humans, Dementia, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Sleep, Fatigue
Abstract: Primary Sjögren’s syndrome (pSS) is an autoimmune disease with frequent neurological involvement. Memory complaints are common, but their precise patterns remain unclear. We wanted to characterize patterns of neurocognitive profiles in pSS patients with cognitive complaints. Only pSS patients with memory complaints were included, prospectively. Cognitive profiles were compiled through a comprehensive cognitive evaluation by neuropsychologists. Evaluations of anxiety, depression, fatigue, sleep disorders and quality of life were performed for testing their interactions with cognitive profiles. All 32 pSS patients showed at least borderline cognitive impairment, and 17 (53%) exhibited a pathological cognitive profile: a hippocampal profile (37%), a dysexecutive profile (22%), and an instrumental profile (16%) (possible overlap). Regarding the secondary objectives: 37% of patients were depressed, and 48% exhibited a mild-to-severe anxiety trait. Sleep disorders were frequent (excessive daytime sleepiness (55%), high risk for sleep apnea (45%), and insomnia (77%)). Cognitive impairments could not be explained alone by anxiety, depression or sleep disorders. Fatigue level was strongly associated with sleep disorders. Our study highlights that cognitive complaints in pSS patients are supported by measurable cognitive impairments, apart from frequently associated disorders such as depression, anxiety or sleep troubles. Sleep disorders should be screened.
Published: 2022

21. Speech Biomarkers in Rapid Eye Movement Sleep Behavior Disorder and Parkinson Disease

Author: Jacques Montplaisir, Paul C. Timm, Erik K. St. Louis, Evi Holzknecht, Petr Dusek, Klaus Seppi, Evžen Růžička, Luke N. Teigen, Tereza Tykalová, Sara Marelli, Ronald B. Postuma, Andrea Galbiati, Karel Sonka, Michal Novotný, Amélie Pelletier, Mahboubeh Habibi, Yves Dauvilliers, Annette Janzen, Wolfgang H. Oertel, Jan Rusz, Luigi Ferini-Strambi, Jan Hlavnička, Birgit Högl, Ambra Stefani, Jean Gagnon, Elisa Evangelista, Anna Laura Rassu, Rusz, Jan, Hlavnička, Jan, Novotný, Michal, Tykalová, Tereza, Pelletier, Amelie, Montplaisir, Jacque, Gagnon, Jean-Francoi, Dušek, Petr, Galbiati, Andrea, Marelli, Sara, Timm, Paul C, Teigen, Luke N, Janzen, Annette, Habibi, Mahboubeh, Stefani, Ambra, Holzknecht, Evi, Seppi, Klau, Evangelista, Elisa, Rassu, Anna Laura, Dauvilliers, Yve, Högl, Birgit, Oertel, Wolfgang, St Louis, Erik K, Ferini-Strambi, Luigi, Růžička, Evžen, Postuma, Ronald B, Šonka, Karel, Czech Technical University in Prague (CTU), First Faculty of Medicine Charles University [Prague], Hôpital du Sacré-Coeur de Montréal, McGill University Health Center [Montreal] (MUHC), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Mayo Clinic [Rochester], Philipps Universität Marburg = Philipps University of Marburg, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Retiveau, Nolwenn
Subjects: 0301 basic medicine, Male, Disease, REM Sleep Behavior Disorder, Audiology, Behavior disorder, Dysarthria, MESH: Aged, 80 and over, 0302 clinical medicine, Research Articles, MESH: Aged, Aged, 80 and over, MESH: Middle Aged, MESH: Speech, Parkinsonism, Parkinson Disease, Middle Aged, Europe, Neurology, Disease Progression, Biomarker (medicine), MESH: Disease Progression, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, medicine.symptom, Research Article, medicine.medical_specialty, Rapid eye movement sleep, Prodromal Symptoms, REM sleep behavior disorder, 03 medical and health sciences, medicine, Humans, Speech, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Prodromal Symptoms, Aged, MESH: Humans, business.industry, Disease progression, medicine.disease, MESH: Male, 030104 developmental biology, MESH: REM Sleep Behavior Disorder, MESH: Biomarkers, MESH: Europe, Neurology (clinical), business, MESH: Female, MESH: Parkinson Disease, 030217 neurology & neurosurgery, Biomarkers
Abstract: International audience; Objective: This multilanguage study used simple speech recording and high-end pattern analysis to provide sensitive and reliable noninvasive biomarkers of prodromal versus manifest α-synucleinopathy in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and early-stage Parkinson disease (PD).Methods: We performed a multicenter study across the Czech, English, German, French, and Italian languages at 7 centers in Europe and North America. A total of 448 participants (337 males), including 150 with iRBD (mean duration of iRBD across language groups 0.5-3.4 years), 149 with PD (mean duration of disease across language groups 1.7-2.5 years), and 149 healthy controls were recorded; 350 of the participants completed the 12-month follow-up. We developed a fully automated acoustic quantitative assessment approach for the 7 distinctive patterns of hypokinetic dysarthria.Results: No differences in language that impacted clinical parkinsonian phenotypes were found. Compared with the controls, we found significant abnormalities of an overall acoustic speech severity measure via composite dysarthria index for both iRBD (p = 0.002) and PD (p < 0.001). However, only PD (p < 0.001) was perceptually distinct in a blinded subjective analysis. We found significant group differences between PD and controls for monopitch (p < 0.001), prolonged pauses (p < 0.001), and imprecise consonants (p = 0.03); only monopitch was able to differentiate iRBD patients from controls (p = 0.004). At the 12-month follow-up, a slight progression of overall acoustic speech impairment was noted for the iRBD (p = 0.04) and PD (p = 0.03) groups.Interpretation: Automated speech analysis might provide a useful additional biomarker of parkinsonism for the assessment of disease progression and therapeutic interventions. ANN NEUROL 2021;90:62-75.
Published: 2021

22. Glioma stem cells invasive phenotype at optimal stiffness is driven by MGAT5 dependent mechanosensing

Author: David Cornu, Julien Cambedouzou, Luc Bauchet, Jean-Philippe Hugnot, Ali Saleh, Hugues Duffau, Christine Fabre, James W. Dennis, Norbert Bakalara, Marta Martin-Fernandez, Cunjie Zhang, Thomas Iskratsch, Emilie Marhuenda, Retiveau, Nolwenn, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Queen Mary University of London (QMUL), Institut Européen des membranes (IEM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Mount Sinai Hospital [Toronto, Canada] (MSH), University of Toronto, Laboratoire Charles Coulomb (L2C), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and SATT AxLRMENRT fellowship (CBS2 Doctoral School)INSERM/INCA project PC201216 (Gliomatrack)
Subjects: 0301 basic medicine, Cancer Research, Glycosylation, Mechanotransduction, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Stiffness, Extracellular matrix, 0302 clinical medicine, Cell Movement, MESH: Cell Movement, Migration, RC254-282, biology, Brain Neoplasms, Chemistry, Mgat5, MESH: Glioblastoma, EMT, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cell biology, Phenotype, Oncology, MESH: N-Acetylglucosaminyltransferases, MESH: Brain Neoplasms, Neoplastic Stem Cells, Galectin, Stem cell, endocrine system, animal structures, Integrin, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), [SDV.BC]Life Sciences [q-bio]/Cellular Biology, N-Acetylglucosaminyltransferases, MESH: Phenotype, Focal adhesion, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neurosphere, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Epithelial–mesenchymal transition, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 3D-nanofibre scaffold, MESH: Humans, Research, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Neoplastic Stem Cells, Biomaterial, 030104 developmental biology, biology.protein, Glioblastoma, 030217 neurology & neurosurgery
Abstract: Background Glioblastomas stem-like cells (GSCs) by invading the brain parenchyma, remains after resection and radiotherapy and the tumoral microenvironment become stiffer. GSC invasion is reported as stiffness sensitive and associated with altered N-glycosylation pattern. Glycocalyx thickness modulates integrins mechanosensing, but details remain elusive and glycosylation enzymes involved are unknown. Here, we studied the association between matrix stiffness modulation, GSC migration and MGAT5 induced N-glycosylation in fibrillar 3D context. Method To mimic the extracellular matrix fibrillar microenvironments, we designed 3D-ex-polyacrylonitrile nanofibers scaffolds (NFS) with adjustable stiffnesses by loading multiwall carbon nanotubes (MWCNT). GSCs neurosphere were plated on NFSs, allowing GSCs migration and MGAT5 was deleted using CRISPR-Cas9. Results We found that migration of GSCs was maximum at 166 kPa. Migration rate was correlated with cell shape, expression and maturation of focal adhesion (FA), Epithelial to Mesenchymal Transition (EMT) proteins and (β1,6) branched N-glycan binding, galectin-3. Mutation of MGAT5 in GSC inhibited N-glycans (β1–6) branching, suppressed the stiffness dependence of migration on 166 kPa NFS as well as the associated FA and EMT protein expression. Conclusion MGAT5 catalysing multibranched N-glycans is a critical regulators of stiffness induced invasion and GSCs mechanotransduction, underpinning MGAT5 as a serious target to treat cancer.
Published: 2021

23. Prefrontal activity during experimental ostracism and daily psychache in suicide attempters

Author: Philippe Courtet, Emilie Olié, Nicolas Menjot de Champfleur, Joel Swendsen, Mathilde M. Husky, Jeremy Deverdun, Adrian Alacreu Crespo, Emmanuelle Le Bars, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Hôpital Lapeyronie [Montpellier] (CHU), Laboratoire de psychologie:Santé et qualité de vie, Université Bordeaux Segalen - Bordeaux 2, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d’Imagerie Fonctionnelle Humaine [CHU Montpellier] (I2FH), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), Université de Bordeaux (UB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Swendsen, Joel, and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)
Subjects: Social exclusion, Brain activity and meditation, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Suicide, Attempted, Gyrus Cinguli, Suicidal Ideation, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Major depressive episode, Ecological momentary assessment, Anterior cingulate cortex, Social stress, Depressive Disorder, Major, Suicide attempt, fMRI, Psychological pain, Social cue, 16. Peace & justice, 030227 psychiatry, Suicide, Psychiatry and Mental health, Clinical Psychology, medicine.anatomical_structure, Social Isolation, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Psychology, Insula, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Background Suicidal behaviors can result from a complex interaction between social stressors and individual vulnerability. Evidence suggests a specific neural processing of social cues in suicide attempters without knowledge of how it relates to real-world experiences. Objective To investigate the association between brain activity during experimental social exclusion (measured by functional MRI) and psychological pain in daily life (assessed by Ecological Momentary Assessment) in patients with a lifetime history of suicide attempt. Methods Thirty-three euthymic females with a history of a major depressive episode were recruited: 13 suicide attempters and 20 affective controls (no history of suicide attempt). Functional MRI scans were acquired while participants played the Cyberball game, a validated social exclusion paradigm. After fMRI, participants completed EMA for a one-week period. Five times per day, they were asked to rate their psychological pain, hopelessness and the negativity of daily events. EMA indices (psychological pain, hopelessness and their interaction with negative events) were correlated with cerebral activations using a ROI approach (orbitofrontal, dorsal and ventrolateral prefrontal cortices, anterior cingulate cortex and insula) in each group. Results We found a negative correlation between daily ratings of psychological pain and orbitofrontal activation for exclusion versus inclusion during the Cyberball game in suicide attempters but not in affective controls. We did not find correlations between cerebral activation and daily hopelessness ratings. Limitations Small sample size Conclusion Scanner-based orbitofrontal activity during social exclusion relates to psychological pain in daily life which participates in suicide risk among vulnerable individuals.
Published: 2021

24. Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy—analysis of registry data

Author: Caroline Ovaert, Sylvie Tuffery-Giraud, Sarah Leonard-Louis, Anthony Béhin, Sophie Guillaumont, Maximilien Sochala, Emmanuelle Campana-Salort, Frédérique Audic, Michèle Mayer, Damien Bonnet, Raul Juntas Morales, Mireille Cossée, Isabelle Desguerre, Christophe Meune, Pascal Laforêt, Rabah Ben Yaou, Brigitte Chabrol, Djillali Annane, David Orlikowski, François Godart, Malika Saadi, Helge Amthor, Tanya Stojkovic, Ulrike Walther-Louvier, Frédéric Lofaso, Pascal Amedro, Raphaël Porcher, Céline Tard, Claire Delcourte, Vincent Tiffreau, Karim Wahbi, Christine Barnerias, Guillaume Bassez, Bertrand Fontaine, Arnaud Isapof, Gregoire De La Villeon, Guy Vaksmann, François Rivier, Denis Duboc, Henri Marc Bécane, Philippe Ravaud, Hélène Prigent, Emmanuelle Jaillette, Abdallah Fayssoil, Bruno Eymard, Université de Lille, Univ. Artois, Univ. Littoral Côte d’Opale, Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 [URePSSS], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Département de génétique médicale [Hôpital de la Timone - APHM], 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), Clinique de pneumologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 (URePSSS), Université d'Artois (UA)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille, Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pitié-Salpêtrière [AP-HP], Hôpital Cochin [AP-HP], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Filière Neuromusculaire (FILNEMUS), Infection et inflammation (2I), Université de Montpellier (UM), Centre Hospitalier de Versailles André Mignot (CHV), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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, Centre d’Investigation Clinique 1429 [Garches] (CIC 1429), Hôpital Raymond Poincaré [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie Pédiatrique [Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Raymond Poincaré [AP-HP], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), and 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)
Subjects: Duchenne muscular dystrophy, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Cardiomyopathy, Angiotensin-Converting Enzyme Inhibitors, Heart failure, Angiotensin-converting enzyme inhibitors, 030204 cardiovascular system & hematology, Lower risk, Ventricular Function, Left, Angiotensin Receptor Antagonists, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Registries, cardiovascular diseases, 030212 general & internal medicine, Medical prescription, Child, ComputingMilieux_MISCELLANEOUS, Heart Failure, biology, business.industry, Proportional hazards model, Hazard ratio, Angiotensin-converting enzyme, medicine.disease, Confidence interval, 3. Good health, Muscular Dystrophy, Duchenne, Treatment Outcome, Child, Preschool, biology.protein, Cardiology and Cardiovascular Medicine, business, cardiomyopathy
Abstract: Aims To estimate the effect of prophylactic angiotensin-converting enzyme inhibitors (ACEi) on survival in Duchenne muscular dystrophy (DMD). Methods and results We analysed the data from the French multicentre DMD Heart Registry (ClinicalTrials.gov: NCT03443115). We estimated the association between the prophylactic prescription of ACEi and event-free survival in 668 patients aged 8 to 13 years, with normal left ventricular function, using (i) a Cox model with intervention as a time-dependent covariate, (ii) a propensity-based analysis comparing ACEi treatment vs. no treatment, and (iii) a set of sensitivity analyses. The study outcomes were overall survival and hospitalizations for heart failure (HF) or acute respiratory failure. Among the 668 patients included in the DMD Heart Registry, 576 (mean age 6.1 ± 2.8 years) were eligible for this study, of whom 390 were treated with ACEi prophylactically. Death occurred in 53 patients (13.5%) who were and 60 patients (32.3%) who were not treated prophylactically with ACEi, respectively. In a Cox model with intervention as a time-dependent variable, the hazard ratio (HR) associated with ACEi treatment was 0.49 [95% confidence interval (CI) 0.34–0.72] and 0.47 (95% CI 0.31–0.17) for overall mortality after adjustment for baseline variables. In the propensity-based analysis, 278 patients were included in the treatment group and 834 in the control group, with 18.5% and 30.4% 12-year estimated probability of death, respectively. ACEi were associated with a lower risk of death (HR 0.39; 95% CI 0.17–0.92) and hospitalization for HF (HR 0.16; 95% CI 0.04–0.62). All other sensitivity analyses yielded similar results. Conclusion Prophylactic ACEi treatment in DMD was associated with a significantly higher overall survival and lower rates of hospitalization for HF.
Published: 2021

25. Posterior Quadratus Lumborum Block in Total Hip Arthroplasty: A Randomized Controlled Trial

Author: Xavier Capdevila, Sophie Bringuier, Helen Nguyen, Olivier Choquet, Sophia Margareta Brixel, Yassir Aarab, Philippe Biboulet, Fabien Swisser, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hôpital Lapeyronie [Montpellier] (CHU), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Retiveau, Nolwenn
Subjects: medicine.medical_treatment, Analgesic, MESH: Analgesia, Patient-Controlled, MESH: Analgesics, Opioid, MESH: Anesthetics, Local, MESH: Length of Stay, law.invention, Sufentanil, 03 medical and health sciences, 0302 clinical medicine, MESH: Saline Solution, Randomized controlled trial, 030202 anesthesiology, Interquartile range, law, medicine, MESH: Arthroplasty, Replacement, Hip, MESH: Double-Blind Method, MESH: Pain, Postoperative, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, MESH: Humans, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Ropivacaine, business.industry, Quadratus lumborum muscle, MESH: Nerve Block, Arthroplasty, MESH: Prospective Studies, MESH: Ropivacaine, MESH: Male, MESH: Morphine, Anesthesiology and Pain Medicine, Anesthesia, Morphine, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, medicine.drug
Abstract: BackgroundPain management is important for ensuring early mobilization after hip arthroplasty; however, the optimal components remain controversial. Recently, the quadratus lumborum block has been proposed as an analgesic option. The current study tested the hypothesis that the posterior quadratus lumborum block combined with multimodal analgesia decreases morphine consumption after hip arthroplasty.MethodsThis study was a prospective, randomized, double-blind, placebo-controlled trial. Before general anesthesia, 100 participating patients scheduled for elective total hip arthroplasty were randomly allocated to receive a 30-ml injection posterior to the quadratus lumborum muscle with either 0.33% ropivacaine (n = 50) or normal saline (n = 50). For all patients, multimodal analgesia included systematic administration of acetaminophen, ketoprofen, and a morphine intravenous patient-controlled analgesia. The primary outcome was total intravenous morphine consumption in the first 24 h. Secondary outcomes recorded intraoperative sufentanil consumption; morphine consumption in the postanesthesia care unit; pain scores at extubation and at 2, 6, 12, and 24 h; motor blockade; time to first standing and ambulation; hospital length of stay; and adverse events.ResultsThere was no significant difference in the 24-h total morphine consumption (ropivacaine group, median [interquartile range], 13 [7 to 21] versus saline group, 16 [9 to 21] mg; median difference, −1.5; 95% CI, −5 to 2; P = 0.337). Pain scores were not different between the groups (β = −0.4; 95% CI, −0.9 to 0.2; P = 0.199). There was no statistical difference between the two groups in intraoperative sufentanil consumption, morphine consumption in the postanesthesia care unit, motor blockade, times to first standing (median difference, 0.83 h; 95% CI, −1.7 to 3.4; P = 0.690) and ambulation (median difference, −1.85 h; 95% CI, −4.5 to 0.8; P = 0.173), hospital length of stay, and adverse events.ConclusionsAfter elective hip arthroplasty, neither morphine consumption nor pain scores were reduced by the addition of a posterior quadratus lumborum block to a multimodal analgesia regimen.Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is New
Published: 2021

26. Exacerbated age-related hearing loss in mice lacking the p43 mitochondrial T3 receptor

Author: Affortit, Corentin, Casas, François, Ladrech, Sabine, Ceccato, Jean-Charles, Bourien, Jérôme, Coyat, Carolanne, Puel, Jean-Luc, Lenoir, Marc, Wang, Jing, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Dynamique Musculaire et Métabolisme (DMEM), Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neurobiologie de l'audition-plasticité synaptique, Institut National de la Santé et de la Recherche Médicale (INSERM), China Agriculture University [Beijing], Fondation de l'Avenir Et2-675, Fondation Gueules Cassees 77-2017, ANR-10-LABX-0012,EpiGenMed,From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow(2010), Institut des Neurosciences de Montpellier (INM), Raynaud, Christelle, and Laboratoires d'excellence - From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow - - EpiGenMed2010 - ANR-10-LABX-0012 - LABX - VALID
Subjects: Male, Aging, Receptors, Thyroid Hormone, Age-related hearing loss, Thyroid hormones, [SDV]Life Sciences [q-bio], Presbycusis, T3 receptor, [SDV] Life Sciences [q-bio], p43 mitochondrial, Mice, lcsh:Biology (General), otorhinolaryngologic diseases, p43 mitochondrial T3 receptor, Animals, Mitochondrial dysfunction, lcsh:QH301-705.5, Research Article
Abstract: Background Age-related hearing loss (ARHL), also known as presbycusis, is the most common sensory impairment seen in elderly people. However, the cochlear aging process does not affect people uniformly, suggesting that both genetic and environmental (e.g., noise, ototoxic drugs) factors and their interaction may influence the onset and severity of ARHL. Considering the potential links between thyroid hormone, mitochondrial activity, and hearing, here, we probed the role of p43, a N-terminally truncated and ligand-binding form of the nuclear receptor TRα1, in hearing function and in the maintenance of hearing during aging in p43−/− mice through complementary approaches, including in vivo electrophysiological recording, ultrastructural assessments, biochemistry, and molecular biology. Results We found that the p43−/− mice exhibit no obvious hearing loss in juvenile stages, but that these mice developed a premature, and more severe, ARHL resulting from the loss of cochlear sensory outer and inner hair cells and degeneration of spiral ganglion neurons. Exacerbated ARHL in p43−/− mice was associated with the early occurrence of a drastic fall of SIRT1 expression, together with an imbalance between pro-apoptotic Bax, p53 expression, and anti-apoptotic Bcl2 expression, as well as an increase in mitochondrial dysfunction, oxidative stress, and inflammatory process. Finally, p43−/− mice were also more vulnerable to noise-induced hearing loss. Conclusions These results demonstrate for the first time a requirement for p43 in the maintenance of hearing during aging and highlight the need to probe the potential link between human THRA gene polymorphisms and/or mutations and accelerated age-related deafness or some adult-onset syndromic deafness. Supplementary Information The online version contains supplementary material available at 10.1186/s12915-021-00953-1.
Published: 2021

27. A ROD–CONE DYSTROPHY IS SYSTEMATICALLY ASSOCIATED TO THE RTN4IP1 RECESSIVE OPTIC ATROPHY

Author: Patrizia Amati-Bonneau, Xavier Zanlonghi, Claire-Marie Dhaenens, Gaël Manes, Béatrice Bocquet, Agathe Roubertie, Isabelle Meunier, Guy Lenaers, Majida Charif, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Mohamed 1 Oujda MAROC, UF Génopathies - Laboratoire de Biochimie et Biologie Moléculaire [Lille] (LBBM), Université de Lille, Sciences et Technologies-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Biochimie et Génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Clinique Jules-Vernes [Nantes], MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), and LENAERS, Guy
Subjects: Male, Visual acuity, genetic structures, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Visual Acuity, inherited optic neuropathy, RTN4IP1, Original Study, Fluorescein Angiography, Child, rod–cone dystrophy, medicine.diagnostic_test, General Medicine, Middle Aged, Pedigree, [SDV] Life Sciences [q-bio], Phenotype, Mitochondrial respiratory chain, Female, medicine.symptom, Tomography, Optical Coherence, Adult, medicine.medical_specialty, Adolescent, Fundus Oculi, Retinal ganglion, Mitochondrial Proteins, Young Adult, Atrophy, Ophthalmology, Electroretinography, medicine, Rod-cone dystrophy, Humans, Retrospective Studies, Cerebellar ataxia, business.industry, recessive disease, Dystrophy, DNA, medicine.disease, eye diseases, Mutation, sense organs, Visual Fields, Carrier Proteins, business, Cone-Rod Dystrophies
Abstract: Although RTN4IP1 has been firmly associated to recessive optic atrophies, we identified by systematic examination of the 55° fundus autofluorescence frames and the peripheral spectral-domain optical coherence tomographic images, a progressive rod–cone dystrophy in all individuals with biallelic RTN4IP1 mutations., Purpose: RTN4IP1 biallelic mutations cause a recessive optic atrophy, sometimes associated to more severe neurological syndromes, but so far, no retinal phenotype has been reported in RTN4IP1 patients, justifying their reappraisal. Methods: Seven patients from four families carrying biallelic RTN4IP1 variants were retrospectively reviewed, with emphasis on their age of onset, visual acuity, multimodal imaging including color and autofluorescence frames, spectral-domain optical coherence tomography with RNFL and macular analyses. Results: Seven patients from four RTN4IP1 families developed in their first decade of life a bilateral recessive optic atrophy with severe central visual loss, and primary nystagmus developed in 5 of 7 patients. Six patients were legally blind. In a second stage, the seven individuals developed a rod–cone dystrophy, sparing the macular zone and the far periphery. This retinal damage was identified by 55° field fundus autofluorescence frames and also by spectral-domain optical coherence tomography scans of the temporal part of the macular zone in five of the seven patients. Full-field electroretinography measurements disclosed reduced b-wave amplitude of the rod responses in all patients but two. Family 4 with the p.R103H and c.601A > T (p.K201*) truncating mutation had further combined neurological signs with cerebellar ataxia, seizures, and intellectual disability. Conclusion: RTN4IP1 recessive optic atrophy is systematically associated to a rod–cone dystrophy, which suggests that both the retinal ganglion cells and the rods are affected as a result of a deficit in the mitochondrial respiratory chain. Thus, systematic widefield autofluorescence frames and temporal macular scans are recommended for the evaluation of patients with optic neuropathies.
Published: 2020

28. Exploring the middle ear function in patients with a cluster of symptoms including tinnitus, hyperacusis, ear fullness and/or pain

Author: Philippe Fournier, Dany Paleressompoulle, Marie-José Esteve Fraysse, Fabien Paolino, Arnaud Devèze, Frédéric Venail, Arnaud Noreña, Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Méditerranéen de Recherche et de Traitement des Acouphènes (IMERTA), Hôpital Privé Clairval [Marseille], Department of Otology and Skull Base Surgery, Ramsay Health Care, Clairval Hospital, 317 Bd du Redon, 13009 Marseille, France, Clairval Hospital, Laboratory of Applied Biomechanisms, Faculty of Medicine, Aix-Marseille University, Service hospitalo-universitaire de médecine et santé au travail, Faculté des Sciences Médicales et Paramédicales, AP-HM La Timone, Aix Marseille Univ 27, boulevard Jean Moulin, Marseille Cedex 5 13385, France, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Aix Marseille Université (AMU)
Subjects: [SDV]Life Sciences [q-bio], Sensory Systems
Abstract: Middle ear muscle (MEM) abnormalities have been proposed to be involved in the development of ear-related symptoms such as tinnitus, hyperacusis, ear fullness, dizziness and/or otalgia. This cluster of symptoms have been called the Tonic Tensor Tympani Syndrome (TTTS) because of the supposed involvement of the tensor tympani muscle (TTM). However, the putative link between MEM dysfunction and the symptoms has not been proven yet and the detailed mechanisms (the causal chain) of TTTS are still elusive. It has been speculated that sudden loud sound (acoustic shock) may impair the functioning of the MEM, specifically the TTM, after an excessive contraction. This would result in inflammatory processes, activation of the trigeminal nerve and a change of the MEMs state into a hypersensitive one, that may be associated to the cluster of symptoms listed above. The goal of this study is to provide further insights into the mechanisms of TTTS. The middle ear function of 11 patients who reported TTTS symptoms has been investigated using either admittancemetry and/or measurement of air pressure in the sealed external auditory canal. While the former method measured the middle ear stiffness the latter provides an estimate of the tympanic membrane displacement. Most patients displayed results consistent with phasic contractions of the TTM (n = 9) and/or Eustachian Tube (ET) dysfunction (n = 6). The MEM contraction or ET dysfunction could be evoked by acoustic stimulation (n = 3), somatic maneuvers (n = 3), or pressure changes in the ear canal (n = 3). Spontaneous TTM contraction (n = 1) or ET opening (n = 1) could also be observed. Finally, voluntary contraction of MEM was also reported (n = 5). On the other hand, tonic contraction of the TTM could not be observed in any patient. The implications of these results for the mechanisms of TTTS are discussed.
Published: 2022

29. Movement disorders in valine métabolism diseases caused by HIBCH and ECHS1 deficiencies

Author: Marie‐Céline François‐Heude, Elise Lebigot, Emmanuel Roze, Marie Thérèse Abi Warde, Claude Cances, Lena Damaj, Caroline Espil, Joel Fluss, Pascale de Lonlay, Ilse Kern, Guy Lenaers, Arnold Munnich, Pierre Meyer, Marie‐Aude Spitz, Stéphanie Torre, Diane Doummar, Guy Touati, Nicolas Leboucq, Agathe Roubertie, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Bicêtre, 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), CHU Strasbourg, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], CHU Bordeaux [Bordeaux], Hôpitaux Universitaires de Genève (HUG), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), Hôpital Cochin [AP-HP], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), 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 Trousseau [APHP], Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and MORNET, Dominique
Subjects: Movement Disorders, ECHS1, [SDV]Life Sciences [q-bio], Valine, [SDV] Life Sciences [q-bio], Dystonia, Neurology, Chorea, Dystonic Disorders, Humans, Abnormalities, Multiple, Coenzyme A, Neurology (clinical), Thiolester Hydrolases, HIBCH, Leigh Disease, inherited metabolic disease, Amino Acid Metabolism, Inborn Errors, Enoyl-CoA Hydratase
Abstract: International audience; Background and purpose: HIBCH and ECHS1 genes encode two enzymes implicated in the critical steps of valine catabolism, 3-hydroxyisobutyryl-coenzyme A (CoA) hydrolase (HIBCH) and short-chainenoyl-CoA hydratase (ECHS1), respectively. HIBCH deficiency (HIBCHD) and ECHS1 deficiency (ECHS1D) generate rare metabolic dysfunctions, often revealed by neurological symptoms. The aim of this study was to describe movement disorders spectrum in patients with pathogenic variants in ECHS1 and HIBC.Methods: We reviewed a series of 18 patients (HIBCHD: 5; ECHS1D: 13) as well as 105 patients from the literature. We analysed the detailed phenotype of HIBCHD (38 patients) and ECHS1D (85 patients), focusing on MDs.Results: The two diseases have a very similar neurological phenotype, with an early onset before 10 years of age for three clinical presentations: neonatal onset, Leigh-like syndrome (progressive onset or acute neurological decompensation), and isolated paroxysmal dyskinesia. Permanent or paroxysmal MDs were recorded in 61% of HIBCHD patients and 72% of ECHS1D patients. Patients had a variable combination of either isolated or combined MD, and dystonia was the main MD. These continuous MDs included dystonia, chorea, parkinsonism, athetosis, myoclonus, tremors, and abnormal eye movements. Patients with paroxysmal dyskinesia (HIBCHD: 4; ECHS1D: 9) usually had pure paroxysmal dystonia with normal clinical examination and no major impairment in psychomotor development. No correlation could be identified between clinical pattern (especially MD) and genetic pathogenic variants.Conclusions: Movement disorders, including abnormal ocular movements, are a hallmark of HIBCHD and ECHS1D. MDs are not uniform; dystonia is the most frequent, and various types of MD are combined in single patient.
Published: 2022

30. Epilepsy and Associated Factors Among Adults Hospitalized for Attempted Suicide

Author: Brizard, Basma Akrout, Courtet, Philippe, Jaussent, Isabelle, Lopez-Castroman, Jorge, Leboyer, Marion, Kahn, Jean Pierre, Baeza-Velasco, Carolina, Laboratoire de Psychopathologie et Processus de Santé (LPPS (URP_4057)), Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), 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), CHU Henri Mondor, Université de Lorraine (UL), and Fondation Santé des Etudiants de France
Subjects: Adult, Psychiatric Status Rating Scales, Psychiatry and Mental health, Cross-Sectional Studies, Epilepsy, Risk Factors, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Craniocerebral Trauma, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Suicide, Attempted, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Suicidal behaviors are known to be increased in people with epilepsy compared to the general population. However, few studies have explored the frequency of epilepsy in a large sample of suicide attempters, and scarce data exist about differences and similarities between epileptic attempters (EA) and nonepileptic attempters (NEA). The aim of this study was to explore the frequency of epilepsy as well as psychopathological and somatic factors among suicide attempters.Methods: In this multicenter cross-sectional study, 1,229 adults hospitalized for attempted suicide were included during the period between July 2001 and December 2015. They were assessed with the Mini-International Neuropsychiatric Interview for DSM-IV Axis I mental disorders. Data concerning sociodemographic and somatic diseases, including epilepsy, were collected.Results: Sixty-five patients (5.3%) had epilepsy. EA had significantly fewer mean ± SD years of education compared with NEA (11.2 ± 3.2 vs 12.1 ± 2.9; P = .011) as well as increased rates of head trauma (29.2% for EA vs 16.2% for NEA; P = .007), antiepileptic use (35.4% for EA vs 23.8% for NEA; P = .036), and lifetime substance abuse and/or dependance (49.2% for EA vs 36.1% for NEA; P = .034). Multivariate analyses showed that years of education, head trauma, and panic disorder with agoraphobia predicted belonging to the EA group.Conclusions: These results suggest that epilepsy is overrepresented among suicide attempters. Few psychopathological differences as well as differences in somatic comorbidities except head trauma were observed between EA and NEA in this sample. These results contribute to draw a clinical profile of people with epilepsy in the population of suicide attempters.
Published: 2022

31. Prionoids in amyotrophic lateral sclerosis

Author: Philippe Gosset, William Camu, Cedric Raoul, Alexandre Mezghrani, Raoul, Cédric, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Kazan Federal University (KFU)
Subjects: prion-like, amyotrophic lateral sclerosis, therapy, General Engineering, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, physiopathology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, protein aggregation
Abstract: Amyotrophic lateral sclerosis (ALS) is the third most frequent neurodegenerative disease after Alzheimer’s and Parkinson’s disease. ALS is characterized by the selective and progressive loss of motoneurons in the spinal cord, brainstem and cerebral cortex. Clinical manifestations typically occur in midlife and start with focal muscle weakness, followed by the rapid and progressive wasting of muscles and subsequent paralysis. As with other neurodegenerative diseases, the condition typically begins at an initial point and then spreads along neuroanatomical tracts. This feature of disease progression suggests the spreading of prion-like proteins called prionoids in the affected tissues, which is similar to the spread of prion observed in Creutzfeldt-Jakob disease. Intensive research over the last decade has proposed the ALS-causing gene products Cu/Zn superoxide dismutase 1, TAR DNA-binding protein of 43 kDa, and fused in sarcoma as very plausible prionoids contributing to the spread of the pathology. In this review, we will discuss the molecular and cellular mechanisms leading to the propagation of these prionoids in ALS.
Published: 2022

32. Peace, not war in Ukraine or anywhere else, please

Author: Jean-Yves Lefrant, Romain Pirracchio, Dan Benhamou, Marc-Olivier Fischer, Rosanna Njeim, Bernard Allaouchiche, Sophie Bastide, Matthieu Biais, Lionel Bouvet, Olivier Brissaud, Sorin J. Brull, Xavier Capdevila, Nicola Clausen, Philippe Cuvillon, Christophe Dadure, Jean-Stéphane David, Bin Du, Sharon Einav, Victoria Eley, Patrice Forget, Tomoko Fujii, Anne Godier, Dean P. Gopalan, Sophie Hamada, Ahmed Hasanin, Olivier Joannes-boyau, Sébastien Kerever, Éric Kipnis, Kerstin Kolodzie, Ruth Landau, Arthur Le Gall, Morgan Le Guen, Matthieu Legrand, Emmanuel Lorne, Frédéric J. Mercier, Nicolas Mongardon, Sheila Myatra, Armelle Nicolas-Robin, Mark John Peters, Hervé Quintard, Jordi Rello, Philippe Richebé, Jason Alexander Roberts, Antoine Rocquilly, Filippo Sanfilippo, Antoine Schneider, Mircea T. Sofonea, Francis Veyckemans, Paul Zetlaoui, Ahed Zeidan, Laurent Zieleskiewicz, Marzena Zielinska, Britta Von Ungern-Sternberg, Osama Abou Arab, Alice Blet, Fanny Bounes, Matthieu Boisson, Anaïs Caillard, Aude Carillion, Thomas Clavier, Denis Frasca, Arthur James, Stéphanie Sigaut, Sacha Rozencwajg, Pierre Albaladejo, Hervé Bouaziz, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Initial MAnagement and prevention of acute orGan failures IN critically ill patiEnts (IMAGINE), Université de Montpellier (UM), Société française d'anesthésie et de réanimation (SFAR), SFAR, University of California [San Francisco] (UC San Francisco), University of California (UC), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Département d'anesthésiologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hospices Civils de Lyon (HCL), CHU Bordeaux [Bordeaux], Mayo Clinic [Jacksonville], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Odense University Hospital (OUH), Unité de réanimation médicale [CHU de Carémeau, Nîmes], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Peking Union Medical College Hospital [Beijing] (PUMCH), The Hebrew University of Jerusalem (HUJ), University of Queensland [Brisbane], University of Aberdeen, The Jikei University School of Medicine, 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), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN), Cairo University - Faculty of Medicine, Service de Réanimation Médicale [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Département d’Anesthésie-Réanimation-SMUR [Hôpital Lariboisière], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, 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, CHU Lille, Columbia University Medical Center (CUMC), Columbia University [New York], CHU Pontchaillou [Rennes], Hôpital Foch [Suresnes], Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Clinique du Millénaire - Oc Santé [Montpellier], Oc Santé [Montpellier], AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Homi Bhabha National Institute (HBNI), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK] (GOSHC), Centre Hospitalier Universitaire de Nice (CHU Nice), Universitat Internacional de Catalunya [Barcelona] (UIC), Hôpital Maisonneuve-Rosemont, Service des Urgences [CHU Nantes], Hôtel-Dieu de Nantes, Università degli studi di Catania = University of Catania (Unict), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), 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), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia] (KFSHRC), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Wrocław Medical University, The University of Western Australia (UWA), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service SAMU-SMUR [CHU Toulouse], Pôle Médecine d'urgences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacologie des anti-infectieux et antibiorésistance (PHAR2), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des urgences [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Service de réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), 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), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Hôpital Beaujon [AP-HP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Service de Réanimation Médicale [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Warfare, Anesthesiology and Pain Medicine, MESH: Humans, MESH: Warfare, MESH: Ukraine, ARTICLE CLINIQUE, Humans, General Medicine, Critical Care and Intensive Care Medicine, Ukraine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; War is back in Europe. With all its horrific pictures and live videos.In its report issued on the 24th of March 2022, the World Health Organization (WHO) [1] states that the Ukrainian conflict has involved 18 million persons so far, with 3.4 million refugees in bordering countries and 6.4 million persons internally displaced (Fig. 1). In this report, 1,035 deaths and 1,650 civilian injuries were reported in Ukraine without any reported data from Russia.
Published: 2022

33. A Non-Invasive Neonatal Signature Predicts Later Development of Atopic Diseases

Author: Sereme Youssouf, Michel Moise, Mezouar Soraya, Guindo Oumar Cheick, Kaba Lanceï, Grine Ghiles, Mura Thibault, Mège Jean-Louis, Tran Tu Anh, Corbeau Pierre, Filleron Anne, Vitte Joana, 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), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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 des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie [CHU Nîmes] (BESPIM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM), Institut de génétique humaine (IGH), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut Desbrest de santé publique (IDESP), COMBE, Isabelle, GenoScience Pharma [Marseille] (GSP), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Methanogenic Archaea, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Allergy, Atopy, Fecal mediator and cytokine, Preterm birth, biology_other, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [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, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract: International audience; Background: Preterm birth is a major cause of morbidity and mortality in infants and children. Non-invasive methods for screening the neonatal immune status are lacking. Archaea, a prokaryotic life domain, comprise methanogenic species that are part of the neonatal human microbiota and contribute to early immune imprinting. However, they have not yet been characterized in preterm neonates. Objective: To characterize the gut immunological and methanogenic Archaeal (MA) signature in preterm neonates, using the presence or absence of atopic conditions at the age of one year as a clinical endpoint. Methods: Meconium and stool were collected from preterm neonates and used to develop a standardized stool preparation method for the assessment of mediators and cytokines and characterize the qPCR kinetics of gut MA. Analysis addressed the relationship between immunological biomarkers, Archaea abundance, and atopic disease at age one. Results: Immunoglobulin E, tryptase, calprotectin, EDN, cytokines, and MA were detectable in the meconium and later samples. Atopic conditions at age of one year were positively associated with neonatal EDN, IL-1β, IL-10, IL-6, and MA abundance. The latter was negatively associated with neonatal EDN, IL-1β, and IL-6. Conclusions: We report a non-invasive method for establishing a gut immunological and Archaeal signature in preterm neonates, predictive of atopic diseases at the age of one year.
Published: 2022

34. Premature termination codons in SOD1 causing Amyotrophic Lateral Sclerosis are predicted to escape the nonsense-mediated mRNA decay

Author: Anne Polge, Claire Guissart, Jovana Kantar, Kevin Mouzat, Paul Vilquin, Cédric Raoul, Baptiste Louveau, Serge Lumbroso, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biochimie [CHRU Nîmes], Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Biopathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Raoul, Cédric, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: endocrine system diseases, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Nonsense-mediated decay, SOD1, Mutation, Missense, lcsh:Medicine, Biology, RNA decay, Article, 03 medical and health sciences, 0302 clinical medicine, Superoxide Dismutase-1, medicine, Genetics, Missense mutation, Humans, RNA, Messenger, Motor neuron disease, Amyotrophic lateral sclerosis, lcsh:Science, Gene, 030304 developmental biology, 0303 health sciences, Messenger RNA, Multidisciplinary, Molecular medicine, Amyotrophic Lateral Sclerosis, Medical genetics, lcsh:R, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, humanities, 3. Good health, Nonsense Mediated mRNA Decay, Codon, Nonsense, Codon, Terminator, lcsh:Q, Haploinsufficiency, 030217 neurology & neurosurgery
Abstract: Amyotrophic lateral sclerosis (ALS) is the most common and severe adult-onset motoneuron disease and has currently no effective therapy. Approximately 20% of familial ALS cases are caused by dominantly-inherited mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), which represents one of the most frequent genetic cause of ALS. Despite the overwhelming majority of ALS-causing missense mutations in SOD1, a minority of premature termination codons (PTCs) have been identified. mRNA harboring PTCs are known to be rapidly degraded by nonsense-mediated mRNA decay (NMD), which limits the production of truncated proteins. The rules of NMD surveillance varying with PTC location in mRNA, we analyzed the localization of PTCs in SOD1 mRNA to evaluate whether or not those PTCs can be triggered to degradation by the NMD pathway. Our study shows that all pathogenic PTCs described in SOD1 so far can theoretically escape the NMD, resulting in the production of truncated protein. This finding supports the hypothesis that haploinsufficiency is not an underlying mechanism of SOD1 mutant-associated ALS and suggests that PTCs found in the regions that trigger NMD are not pathogenic. Such a consideration is particularly important since the availability of SOD1 antisense strategies, in view of variant treatment assignment.
Published: 2020

35. Pituitary metastasis of malignant melanoma misdiagnosed as pituitary adenoma: A case report and systematic review of the literature

Author: Sam Ng, Valentin Favier, Julien Boetto, Louis Crampette, Valérie Rigau, Gaëtan Poulen, Isabelle Raingeard, Service de Neurochirurgie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CCSD, Accord Elsevier, and Institut des Neurosciences de Montpellier (INM)
Subjects: MESH: Fatal Outcome, Pituitary gland, Dissémination leptoméningée, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, medicine.medical_treatment, Endoscopic surgery, Metastasis, MESH: Magnetic Resonance Imaging, Fatal Outcome, 0302 clinical medicine, Positron Emission Tomography Computed Tomography, Leptomeningeal carcinomatosis, Melanoma, Métastase, MESH: Middle Aged, Brain Neoplasms, Transsphénoidal, Middle Aged, Magnetic Resonance Imaging, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, MESH: Diagnostic Errors, Pituitary metastasis, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Radiology, Adenoma, medicine.medical_specialty, MESH: Melanoma, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 03 medical and health sciences, Pituitary adenoma, Cerebrospinal fluid fistula, medicine, Humans, Pituitary Neoplasms, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Hypophyse, Diagnostic Errors, MESH: Pituitary Neoplasms, Mélanome, Transsphenoidal surgery, MESH: Adenoma, MESH: Humans, business.industry, Chirurgie endoscopique, Transsphenoidal, medicine.disease, Pituitary, Surgery, Neurology (clinical), MESH: Positron Emission Tomography Computed Tomography, business, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; We report a case of malignant melanoma revealed by a metastasis to the pituitary gland. The tumor was misdiagnosed as a pituitary adenoma and aggressive transsphenoidal surgery was complicated by a cerebrospinal fluid fistula. Nine weeks later, the patient presented multiple leptomeningeal and brain metastases spreading from the sellar region. Regarding these observations, we conducted a systematic review of the literature in order to investigate clinicoradiological features that should lead clinicians to suspect pituitary metastasis and how it should impact the surgical management.
Published: 2020

36. HFUS Imaging of the Cochlea: A Feasibility Study for Anatomical Identification by Registration with MicroCT

Author: Frédéric Venail, Nabil Zemiti, Philippe Poignet, Mohamed Akkari, Lucas Lavenir, Gérard Subsol, Conception et commande de robots pour la manipulation (DEXTER), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Image & Interaction (ICAR), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Zemiti, Nabil, Robotique médicale et mécanismes parallèles (DEXTER), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Institut des Neurosciences de Montpellier (INM)
Subjects: Computer-assisted surgery, Computer science, medicine.medical_treatment, 0206 medical engineering, Biomedical Engineering, 02 engineering and technology, Microcomputed tomography, [SPI.AUTO]Engineering Sciences [physics]/Automatic, otorhinolaryngologic diseases, medicine, Electrode array, Inner ear, Cochlea, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing, business.industry, Ultrasound, 020601 biomedical engineering, High-frequency ultrasound, Basilar membrane, [SPI.AUTO] Engineering Sciences [physics]/Automatic, Modiolus (cochlea), medicine.anatomical_structure, sense organs, business, US/CT registration, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Biomedical engineering
Abstract: International audience; Cochlear implantation consists in electrically stimulating the auditory nerve by inserting an electrode array inside the cochlea, a bony structure of the inner ear. In the absence of any visual feedback, the insertion results in many cases of damages of the internal structures. This paper presents a feasibility study on intraoperative imaging and identification of cochlear structures with high-frequency ultrasound (HFUS). 6 ex-vivo guinea pig cochleae were subjected to both US and microcomputed tomography (µCT) we respectively referred as intraoperative and preoperative modalities. For each sample, registration based on simulating US from the scanner was performed to allow a precise matching between the visible structures. According to two otologists, the procedure led to a Target Registration Error (TRE) of 0.32 mm ± 0.05. Thanks to referring to a better preoperative anatomical representation, we were able to intraoperatively identify the modiolus, both scalae vestibuli and tympani and deduce the location of the basilar membrane, all of which is of great interest for cochlear implantation. Our main objective is to extend this procedure to the human case and thus provide a new tool for inner ear surgery.
Published: 2020

37. Analytical evaluation of the novel VITROS BRAHMS procalcitonin immunoassay

Author: Anne Marie Dupuy, Jean-Paul Cristol, Valentin Montagnon, Stéphanie Badiou, Anne Sophie Bargnoux, Nils Kuster, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), MORNET, Dominique, and Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM)
Subjects: 030213 general clinical medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clinical Biochemistry, 030204 cardiovascular system & hematology, Procalcitonin, 03 medical and health sciences, 0302 clinical medicine, Limit of Detection, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Mathematics, Immunoassay, Detection limit, Chromatography, medicine.diagnostic_test, General Medicine, 3. Good health, [SDV] Life Sciences [q-bio], Method comparison, Regression Analysis, Hemolysis index, hormones, hormone substitutes, and hormone antagonists
Abstract: To determine the analytical performance of Novel VITROS BRAHMS Procalcitonin Immunoassay on VITROS 3600 and correlation with BRAHMS PCT sensitive KRYPTOR reference method. Analytical performances including imprecision studies, linearity, limit of detection (LoD) and determination of hemolysis index were performed for VITROS BRAHMS PCT assay. Imprecision was assessed on plasma pool and internal control with 2 levels. The method comparison was performed using 162 plasma obtained from clinical departments. The total imprecision was acceptable and all CV were
Published: 2020

38. Clinical phenotype and loss of the slow skeletal muscle troponin T in three new patients with recessive TNNT1 nemaline myopathy

Author: A. Madelaine, Julie Brocard, Mireille Cossée, Isabelle Marty, Anne-Cécile Coville, Michel Koenig, Christine Ioos, C. Thèze, John Rendu, Klaus Dieterich, Aurore Siegfried, Julien Fauré, Claude Cances, Henri Pegeot, Eloïse Baudou, Pascale Marcorelle, Norma B. Romero, Emmanuelle Lacène, Emmanuelle Uro Coste, Murielle Dobrzynski, Raul Juntas Morales, Justine Géraud, Neurologie générale et maladies inflammatoires du système nerveux [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHRU Brest, Pôle de Biologie Pathologie (CHU - BREST - Biologie pathologie), Hôpital Raymond Poincaré [AP-HP], Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Institut des Neurosciences de Montpellier (INM)
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, diagnosis, [SDV]Life Sciences [q-bio], Biopsy, Nonsense mutation, neuromuscular diseases, Slow skeletal muscle troponin T, Myopathies, Nemaline, 03 medical and health sciences, Exon, 0302 clinical medicine, Nemaline myopathy, Troponin T, Genetics, medicine, Humans, Genetic Predisposition to Disease, Diagnostics, Genetics (clinical), Genetic Association Studies, Sequence Deletion, business.industry, Homozygote, Skeletal muscle, Muscle weakness, Computational Biology, High-Throughput Nucleotide Sequencing, Infant, Sequence Analysis, DNA, medicine.disease, musculoskeletal system, Immunohistochemistry, Hypotonia, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Phenotype, Child, Preschool, Mutation, Female, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: BackgroundCongenital nemaline myopathies are rare pathologies characterised by muscle weakness and rod-shaped inclusions in the muscle fibres.MethodsUsing next-generation sequencing, we identified three patients with pathogenic variants in the Troponin T type 1 (TNNT1) gene, coding for the troponin T (TNT) skeletal muscle isoform.ResultsThe clinical phenotype was similar in all patients, associating hypotonia, orthopaedic deformities and progressive chronic respiratory failure, leading to early death. The anatomopathological phenotype was characterised by a disproportion in the muscle fibre size, endomysial fibrosis and nemaline rods. Molecular analyses of TNNT1 revealed a homozygous deletion of exons 8 and 9 in patient 1; a heterozygous nonsense mutation in exon 9 and retention of part of intron 4 in muscle transcripts in patient 2; and a homozygous, very early nonsense mutation in patient 3.Western blot analyses confirmed the absence of the TNT protein resulting from these mutations.DiscussionThe clinical and anatomopathological presentations of our patients reinforce the homogeneous character of the phenotype associated with recessive TNNT1 mutations. Previous studies revealed an impact of recessive variants on the tropomyosin-binding affinity of TNT. We report in our patients a complete loss of TNT protein due to open reading frame disruption or to post-translational degradation of TNT.
Published: 2020

39. Preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy

Author: Nicolas Pinquier, Philippe Brabet, Joseph Vercauteren, Céline Crauste, Nicolas Taveau, David Cia, Thierry Durand, Vasiliki Kalatzis, Espérance Moine, Laurent Guillou, Aurélie Cubizolle, Crauste, Céline, APPEL À PROJETS GÉNÉRIQUE 2018 - Les lipohenols de nouveaux anti-oxydants et stresseurs carbonylés pour combattre la dégénérescence maculaire - - LipoPheRet2018 - ANR-18-CE18-0017 - AAPG2018 - VALID, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), SATT AxLR, ANR-18-CE18-0017,LipoPheRet,Les lipohenols de nouveaux anti-oxydants et stresseurs carbonylés pour combattre la dégénérescence maculaire(2018), and Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM)
Subjects: 0301 basic medicine, Retinal degeneration, Light, genetic structures, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Pharmacology, medicine.disease_cause, Biochemistry, 0302 clinical medicine, 1234567890(), Mice, Knockout, Retinal Degeneration, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Medicine, Molecular Medicine, Disease Susceptibility, Tomography, Optical Coherence, Visual phototransduction, Retinopathy, cis-trans-Isomerases, Docosahexaenoic Acids, QD415-436, Phloroglucinol, Biologics, Retina, Article, Retinoids, 03 medical and health sciences, Phenols, Retinal Diseases, In vivo, Electroretinography, medicine, Animals, Molecular Biology, business.industry, Macular degeneration, medicine.disease, eye diseases, Mice, Inbred C57BL, Disease Models, Animal, Kinetics, 030104 developmental biology, RPE65, 030221 ophthalmology & optometry, sense organs, business, Oxidative stress
Abstract: Environmental light has deleterious effects on the outer retina in human retinopathies, such as ABCA4-related Stargardt’s disease and dry age-related macular degeneration. These effects involve carbonyl and oxidative stress, which contribute to retinal cell death and vision loss. Here, we used an albino Abca4−/− mouse model, the outer retina of which shows susceptibility to acute photodamage, to test the protective efficacy of a new polyunsaturated fatty acid lipophenol derivative. Anatomical and functional analyses demonstrated that a single intravenous injection of isopropyl-phloroglucinol-DHA, termed IP-DHA, dose-dependently decreased light-induced photoreceptor degeneration and preserved visual sensitivity. This protective effect persisted for 3 months. IP-DHA did not affect the kinetics of the visual cycle in vivo or the activity of the RPE65 isomerase in vitro. Moreover, IP-DHA administered by oral gavage showed significant protection of photoreceptors against acute light damage. In conclusion, short-term tests in Abca4-deficient mice, following single-dose administration and light exposure, identify IP-DHA as a therapeutic agent for the prevention of retinal degeneration., Experimental & Molecular Medicine: Vision loss: Shedding light on how to prevent retinal damage Treating retinal damage in both aging and young patients might now be easier, thanks to treatment with a lipophenol, an omega-3 fatty acid linked to an antioxidant. The retina is the part of the eye that senses light, aided by light-sensitive pigments. However, these light-sensitive pigments can be converted by light to toxic byproducts, and in some individuals, these toxic byproducts can accumulate, damaging the retina and leading to vision loss. Philippe Brabet at the Montpellier Institute of Neuroscience in France and co-workers found that lipophenol treatment protected retinal cells from damage in a mouse model of retinal disease, and that a single dose has been effective in preserving vision. These results may help in finding new treatments for retinal diseases such as Stargardt disease and age-related macular degeneration.
Published: 2020

40. Electrophysiological features of chronic inflammatory demyelinating polyradiculoneuropathy associated with IgG4 antibodies targeting neurofascin 155 or contactin 1 glycoproteins

Author: Kouton, Ludivine, Boucraut, José, Devaux, Jérome, Rajabally, Yusuf, Adams, David, Antoine, Jean Christophe, Bourdain, Frédéric, Brodovitch, Alexandre, Camdessanché, Jean-Philippe, Cauquil, Cécile, Ciron, Jonathan, Dubard, Thierry, Echaniz-Laguna, Andoni, Grapperon, Aude-Marie, Juntas-Morales, Raul, Kremer, Laurent, Kuntzer, Thierry, Labeyrie, Céline, Lanfranco, Luca, Léger, Jean-Marc, Maisonobe, Thierry, Mavroudakis, Nicolas, Mecharles-Darrigol, Sylvie, Merle, Philippe, Noury, Jean-Baptiste, Rouaud, Violaine, Tard, Céline, Théaudin, Marie, Vallat, Jean-Michel, Viala, Karine, Attarian, Shahram, Delmont, Emilien, Ludivine, Kouton, José, Boucraut, Jérome, Devaux, Yusuf, Rajabally, David, Adams, Christophe, Antoine, Frédéric, Bourdain, Alexandre, Brodovitch, Jean-Philippe, Camdessanché, Cécile, Cauquil, Jonathan, Ciron, Thierry, Dubard, Andoni, Echaniz-Laguna, Aude-Marie, Grapperon, Raul, Juntas-Morales, Laurent, Kremer, Thierry, Kuntzer, Céline, Labeyrie, Luca, Lanfranco, Jean-Marc, Léger, Thierry, Maisonobe, Nicolas, Mavroudakis, Sylvie, Mecharles-Darrigol, Philippe, Merle, Jean- Baptiste, Noury, Violaine, Rouaud, Céline, Tard, Marie, Théaudin, Jean-Michel, Vallat, Karine, Viala, Shahram, Attarian, Emilien, Delmont, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University Hospitals Birmingham [Birmingham, Royaume-Uni], Hôpital Foch [Suresnes], Adhésion et Inflammation (LAI), Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie, CHU Saint-Etienne, Institut des Neurosciences de Montpellier (INM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Male, Pathology, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neural Conduction, Nerve conduction velocity, 0302 clinical medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Node of Ranvier, biology, 05 social sciences, Middle Aged, Sensory Systems, 3. Good health, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Neurology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Antibody, Contactin 1, medicine.medical_specialty, 050105 experimental psychology, 03 medical and health sciences, Physiology (medical), medicine, Humans, 0501 psychology and cognitive sciences, Nerve Growth Factors, Aged, Autoantibodies, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Polyradiculoneuropathy, medicine.disease, Median nerve, Median Nerve, Electrophysiology, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, chemistry, Immunoglobulin G, biology.protein, Neurology (clinical), Glycoprotein, business, Cell Adhesion Molecules, 030217 neurology & neurosurgery
Abstract: Objective Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) with antibodies against neurofascin 155 (Nfasc155) or contactin-1 (CNTN1) have distinctive clinical features. Knowledge on their electrophysiological characteristics is still scarce. In this study, we are investigating whether these patients have specific electrophysiological characteristics. Methods The electrophysiological data from 13 patients with anti-Nfasc155 IgG4 antibodies, 9 with anti-CNTN1 IgG4 antibodies were compared with those of 40 consecutive CIDP patients without antibodies. Results All the patients with antibodies against Nfasc155 or CNTN1 fulfilled the EFNS/PNS electrodiagnostic criteria for definite CIDP. There was no electrophysiological difference between patients with anti-CNTN1 and anti-Nfasc155 antibodies. Nerve conduction abnormalities were heterogeneously distributed along nerves trunks and roots. They were more pronounced than in CIDP without antibodies. Motor conduction velocity on median nerve 7.4 ms were predictive of positive antibodies against the node of Ranvier with a sensitivity of 59% and a specificity of 93%. Conclusions Marked conduction abnormalities may suggest the presence of positive antibodies against the node of Ranvier. Significance Anti-Nfasc155 and anti-CNTN1 antibodies target the the paranodal axo-glial domain but are associated with nerve conduction abnormalities mimicking a “demyelinating” neuropathy.
Published: 2020

41. Mechanism of action of s1p receptor modulators in multiple sclerosis: The double requirement

Author: William Camu, Régis Bordet, Eric Thouvenot, David-Axel Laplaud, Jérôme De Seze, Jean-Christophe Ouallet, Département de Pharmacologie Médicale [Lille] (Pôle Recherche), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (BMNST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Nîmes], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Le Bihan, Sylvie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Faculté de Médecine Henri Warembourg - Université de Lille, Institut des Neurosciences de Montpellier (INM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Multiple Sclerosis, Sphingosine-1-phosphate, [SDV]Life Sciences [q-bio], Sphingosine-1-phosphate receptor, Neuroprotection, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Neuroinflammation, Sphingosine, Animals, Humans, Medicine, 030212 general & internal medicine, Neurodegeneration, Receptor, Sphingosine-1-Phosphate Receptors, Fingolimod Hydrochloride, business.industry, Multiple sclerosis, Brain, Fingolimod, medicine.disease, [SDV] Life Sciences [q-bio], Neurology, chemistry, Immune System, Neurology (clinical), Lysophospholipids, business, Neuroscience, Immunosuppressive Agents, 030217 neurology & neurosurgery, Signal Transduction, medicine.drug
Abstract: International audience; The ideal treatment for multiple sclerosis (MS) would target both the neuroinflammatory component of the disease (peripheral and central) and its neurodegenerative component, via modulation of a ubiquitous and pleiotropic common target. Sphingosine-1-phosphate (S1P), a product of sphingosine metabolism, regulates many biological functions (including cell proliferation and survival, cell migration, the immune response and cardiovascular function) via five subtypes of receptor. These receptors are expressed in all types of brain cells where they modulate a number of processes involved in neuronal plasticity, including myelination, neurogenesis and neuroprotection. This profile has aroused interest in modulation of S1P function as a therapeutic target in many brain diseases, particularly those in which the immune system plays a role in the development of brain lesions. Fingolimod, a S1P receptor modulator, exerts its beneficial effects in MS through its anti-inflammatory and anti-neurodegenerative effects. This review discusses recent evidence indicating that fingolimod may target both the inflammatory and neurodegenerative components of the disease process in MS.
Published: 2020

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

Author: Marion Burland, Thierry Chevallier, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie [CHU Nîmes] (BESPIM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), French alliance clinical trial [Paris] (F-CRIN), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Institut Desbrest de santé publique (IDESP), and KARLI, Mélanie
Subjects: Post-Market Clinical Follow up, [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Massive Database, Medical Device, Real Life Study
Abstract: International audience; With the application of new European regulations on medical devices in May 2021, the requirements for clinical evaluation have been strongly reinforced. Post-marketing clinical follow-up is now a key activity for manufacturers to keep their medical devices on the market. The use of material-epidemiology studies and real-life databases has multiple strengths and advantages. However, the weaknesses and limitations identified do not yet allow manufacturers (especially small and medium-sized companies) to fully utilize these tools for post-market clinical follow-up. Yet certain technological and regulatory developments already implemented, and to be implemented over time, suggest that these tools could play a crucial role in the clinical monitoring of medical devices in the future. In order to better define the future use of real-life data in post-market clinical follow-up activities, a comprehensive update of technological and regulatory surveillance is still required.
Published: 2022

43. Complaints of daytime sleepiness, insomnia, hypnotic use, and risk of dementia: a prospective cohort study in the elderly

Author: Clémence Cavaillès, Claudine Berr, Catherine Helmer, Audrey Gabelle, Isabelle Jaussent, Yves Dauvilliers, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale, Université de Bordeaux, Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation, Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Mutuelle Générale de l'Education Nationale, Agence Française de Sécurité Sanitaire des Produits de Santé, Conseil Régional Aquitaine, Conseil régional de Bourgogne-Franche-Comté, Conseil Régional Languedoc-Roussillon, Fondation de France, ANR-07-LVIE-0004,ESPRIT-VIE,Interaction entre la vulnérabilité génétique, la dysrégulation biologique et le stress dans la dépression du sujet âgé(2007), ANR-06-PNRA-0005,COGINUT,COGINUT : Cognition, anti-oxydants, acides gras: approche interdisciplinaire du rôle de la nutrition dans le vieillissement du cerveau(2006), Admin, Oskar, Longévité et vieillissement - Interaction entre la vulnérabilité génétique, la dysrégulation biologique et le stress dans la dépression du sujet âgé - - ESPRIT-VIE2007 - ANR-07-LVIE-0004 - LVIE - VALID, and Programme National de Recherches en Alimentation et Nutrition Humaine (PNRA) - COGINUT : Cognition, anti-oxydants, acides gras: approche interdisciplinaire du rôle de la nutrition dans le vieillissement du cerveau - - COGINUT2006 - ANR-06-PNRA-0005 - PNRA - VALID
Subjects: Sleepiness, Epidemiology, Cognitive Neuroscience, Neurosciences. Biological psychiatry. Neuropsychiatry, Disorders of Excessive Somnolence, Insomnia complaints, Hypnotic use, Elderly, Risk Factors, Sleep Initiation and Maintenance Disorders, mental disorders, Humans, Hypnotics and Sedatives, Prospective Studies, RC346-429, Aged, Research, Neurology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Alzheimer, Cohort studies, Dementia, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology. Diseases of the nervous system, Neurology (clinical), RC321-571
Abstract: Background Sleep disturbances are common in elderly and occur frequently in dementia. The impact of excessive daytime sleepiness (EDS), insomnia complaints, sleep quality, and hypnotics on the risk of all-cause dementia, Alzheimer disease (AD), and dementia with vascular component (DVC) remains unclear, as does the association between sleep profile and plasma β-amyloid levels. Methods Analyses were carried out on 6851 participants aged 65 years and over randomly recruited from three French cities and free of dementia at baseline. A structured interview and self-questionnaire assessed sleep complaints (EDS, insomnia complaints, sleep quality) and medications at baseline. Incident cases of dementia were diagnosed systematically over a 12-year period. Multivariate Cox models were used to estimate the risk of dementia associated with the sleep complaints considered individually and globally. Plasma β-amyloid levels were measured by an xMAP-based assay technology in 984 subjects. Results After adjustment for socio-demographic characteristics, lifestyle, APOE-ε4, cardiovascular factors, and depressive status, EDS had a higher risk of all-cause dementia (HR = 1.21; 95%CI = [1.01–1.46]) and DVC (HR = 1.58; 95%CI = [1.07–2.32]) but not AD. Persistent use of hypnotics increased the risk for all-cause dementia, specifically AD (HR = 1.28; 95%CI = [1.04–1.58]), but not DVC. No association was found for insomnia complaints and sleep quality taken as individual factors or combined with EDS on the risk of dementia. No association was found between β-amyloid, sleep complaints, and incident dementia. Conclusions The results suggest a deleterious role of EDS and hypnotics on dementia. Further studies are required to elucidate the mechanisms involved in these associations and whether its management can prevent the risk of dementia.
Published: 2022

44. Exposure to ambient air pollution and cognitive decline: results of the prospective Three-City cohort study

Author: Jeanne Duchesne, Laure-Anne Gutierrez, Isabelle Carrière, Thibault Mura, Jie Chen, Danielle Vienneau, Kees de Hoogh, Catherine Helmer, Bénédicte Jacquemin, Claudine Berr, Marion Mortamais, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institute for Risk Assessment Sciences [Utrecht, The Netherlands] (IRAS), Utrecht University [Utrecht], Swiss Tropical and Public Health Institute [Basel], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de 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), Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, Institut National de la Santé et de la Recherche Médicale, Université de Bordeaux, Fondation pour la Recherche Médicale, Mutuelle Générale de l'Education Nationale, Agence Nationale de la Recherche, and Chard-Hutchinson, Xavier
Subjects: Air Pollutants, Cohort, Environmental Exposure, Environmental sciences, Cohort Studies, Black carbon, Cognition, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Air Pollution, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, GE1-350, Cognitive Dysfunction, Female, Particulate Matter, Prospective Studies, Nitrogen dioxide, Aged, General Environmental Science
Abstract: International audience; BACKGROUND: Growing epidemiological evidence suggests an adverse relationship between exposure to air pollutants and cognitive decline. However, there is still some heterogeneity in the findings, with inconsistent results depending on the pollutant and the cognitive domain considered. We wanted to determine whether air pollution was associated with global and domain-specific cognitive decline. METHODS: This analysis used data from the French Three-City prospective cohort (participants aged 65 and older at recruitment and followed for up to 12 years). A battery of cognitive tests was administered at baseline and every 2 years, to assess global cognition (Mini Mental State Examination, MMSE), visual memory (Benton Visual Retention Test), semantic fluency (Isaacs Set Test) and executive functions (Trail Making Tests A and B). Exposure to fine particulate matter (PM(2.5)), nitrogen dioxide (NO(2)) and black carbon (BC) at the participants' residential address during the 5 years before the baseline visit was estimated with land use regression models. Linear mixed models and latent process mixed models were used to assess the association of each pollutant with global and domain-specific cognitive decline. RESULTS: The participants' (n = 6380) median age was 73.4 years (IQR: 8.0), and 61.5% were women. At baseline, the median MMSE score was 28 (IQR: 3). Global cognition decline, assessed with the MMSE, was slightly accelerated among participants with higher PM(2.5) exposure: one IQR increment in PM(2.5) (1.5 µg/m(3)) was associated with accelerated decline (β: -0.0060 [-0.0112; -0.0007] standard unit per year). Other associations were inconsistent in direction, and of small magnitude. CONCLUSION: In this large population-based cohort, higher PM(2.5) exposure was associated with accelerated global cognition decline. We did not detect any significant association for the specific cognitive domains or the other pollutants. Evidence concerning PM(2.5) effects on cognition is growing, but more research is needed on other ambient air pollutants.
Published: 2022
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45. Outdoor air pollution exposure and cognitive performance: findings from the enrolment phase of the CONSTANCES cohort

Author: Mohammad Javad Zare Sakhvidi, Jun Yang, Emeline Lequy, Jie Chen, Kees de Hoogh, Noémie Letellier, Marion Mortamais, Anna Ozguler, Danielle Vienneau, Marie Zins, Marcel Goldberg, Claudine Berr, Bénédicte Jacquemin, 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 ), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Utrecht University [Utrecht], Swiss Tropical and Public Health Institute [Basel], Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), The Caisse Nationale d’Assurance Maladie, and partly funded by Merck Sharp and Dohme and L’Oréal, the French National Research Agency, and Fondation de France., and Chard-Hutchinson, Xavier
Subjects: Adult, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Health (social science), Adolescent, Health Policy, Public Health, Environmental and Occupational Health, Medicine (miscellaneous), [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Environmental Exposure, Middle Aged, Young Adult, Cognition, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Air Pollution, Humans, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Particulate Matter, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Aged
Abstract: Background Air pollution exposure is one of the modifiable risk factors of cognitive decline. We aimed to test the association between exposure to several outdoor air pollutants and domain-specific cognitive performance. Methods In this cross-sectional study, we used data from the enrolment phase of the French CONSTANCES cohort. From the 220 000 people (aged 18-69 years) randomly recruited in the French CONSTANCES cohort, participants aged 45 years old or older (104 733 people) underwent a comprehensive cognitive assessment (verbal episodic memory, language skills, and executive functions). After exclusion of those who were not suitable for our analysis, 61 462 participants with available data were included in the analyses. We used annual mean concentrations at residential addresses, derived from land-use regression models, to assign exposure to particulate matter with aerodynamic diameters less than 2·5 μm (PM2·5), nitrogen dioxide (NO2), and black carbon. We used multiple linear regression models with different covariate adjustments to test the associations between each pollutant and cognitive outcomes. We did several sensitivity analyses, including multilevel modelling, meta-analysis by centre of recruitment, and exclusion of specific population groups. Findings We found significantly poorer cognitive function, especially on semantic fluency and domains of executive functions, with an increase in exposure to black carbon and NO2. Exposure to PM2·5 was mainly significant for the semantic fluency test. We found that decrease in cognitive performance with an increase of one interquartile range of exposure ranged from 1% to nearly 5%. The largest effect size (percentage decrease) for both PM2.5 and NO2 was found for the semantic fluency test (PM2.5 4·6%, 95% CI 2·1-6·9 and NO2 3·8%, 1·9-5·7), whereas for black carbon, the largest effect size was found for the digit symbol substitution test of the domains of executive functions (4·5%, 2·7-6·3). Monotonic and linear exposure-response associations were found between air pollution exposure and cognitive performance, starting from a low level of exposures. Interpretation Significantly poorer cognitive performance was associated with exposure to outdoor air pollution even at low levels of exposure. This highlights the importance of further efforts to reduce exposure to air pollution. Funding The Caisse Nationale d'Assurance Maladie, and partly funded by Merck Sharp & Dohme and L'Oréal, the French National Research Agency, and Fondation de France. Translation For the French translation of the abstract see Supplementary Materials section.
Published: 2022

46. Analysis of Splicing Regulation by Third-Generation Sequencing

Author: Allemand, Eric, Ango, Fabrice, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Ango, Fabrice
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: International audience
Published: 2022

47. Air quality improvement and incident dementia: Effects of observed and hypothetical reductions in air pollutant using parametric g‐computation

Author: Noémie Letellier, Laure‐Anne Gutierrez, Jeanne Duchesne, Chen Chen, Sindana Ilango, Catherine Helmer, Claudine Berr, Marion Mortamais, Tarik Benmarhnia, Berr, Claudine, Herbert Wertheim School of Public Health and Human Longevity Science, Scripps Institution of Oceanography (SIO - UC San Diego), University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Washington School of Public Health, 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), Hôpital Gui de Chauliac, and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: particulate matter, [SDE] Environmental Sciences, Air Pollutants, Epidemiology, Health Policy, air pollution, g-formula, Environmental Exposure, Quality Improvement, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, [SDE]Environmental Sciences, Humans, Neurology (clinical), Geriatrics and Gerontology, causal inference, dementia
Abstract: International audience; Introduction: No evidence exists about the impact of air pollution reduction on incidence of dementia. The aim of this study was to quantify how air quality improvement leads to dementia-incidence benefits.Methods: In the French Three-City cohort (12 years of follow-up), we used parametric g-computation to quantify the expected number of prevented dementia cases under different hypothetical interventions with particulate matter measuring
Published: 2022

48. A disease-associated mutation in thyroid hormone receptor α1 causes hearing loss and sensory hair cell patterning defects in mice

Author: Affortit, Corentin, Blanc, Fabian, Nasr, Jamal, Ceccato, Jean-Charles, Markossian, Suzy, Guyot, Romain, Puel, Jean-Luc, Flamant, Frédéric, Wang, Jing, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by the Labex EpiGenMed, an 'Investissements d'avenir' program (ANR-10-LABX-12-01), the Fondation de l'Avenir (Et2-675), the Fondation Gueules Cassees (77-2017), the Fondation Recherche Medicale (REP202110014234), and European Union's Horizon 2020 research and innovation program (825753, ERGO)., ANR-10-LABX-0012,EpiGenMed,From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow(2010), and European Project: 825753,ERGO
Subjects: Mice, Thyroid Hormones, [SDV]Life Sciences [q-bio], Mutation, Animals, Cell Biology, Deafness, Hearing Loss, Molecular Biology, Biochemistry, Thyroid Hormone Receptors alpha
Abstract: Resistance to thyroid hormone due to mutations in THRA , which encodes the thyroid hormone receptor α (TRα1), shows variable clinical presentation. Mutations affecting TRβ1 and TRβ2 cause deafness in mice and have been associated with deafness in humans. To test whether TRα1 also affects hearing function, we used mice heterozygous for a frameshift mutation in Thra that is similar to human THRA mutations ( Thra S1/ + mice) and reduces tissue sensitivity to thyroid hormone. Compared to wild-type littermates, Thra S1/+ mice showed moderate high-frequency sensorineural hearing loss as juveniles and increased age-related hearing loss. Ultrastructural examination revealed aberrant orientation of ~20% of sensory outer hair cells (OHCs), as well as increased numbers of mitochondria with fragmented morphology and autophagic vacuoles in both OHCs and auditory nerve fibers. Molecular dissection of the OHC lateral wall components revealed that the potassium ion channel Kcnq4 was aberrantly targeted to the cytoplasm of mutant OHCs. In addition, mutant cochleae showed increased oxidative stress, autophagy, and mitophagy associated with greater age-related cochlear cell damage, demonstrating that TRα1 is required for proper development of OHCs and for maintenance of OHC function. These findings suggest that patients with THRA mutations may present underdiagnosed, mild hearing loss and may be more susceptible to age-related hearing loss.
Published: 2022
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49. Identification of the First Single GSDME Exon 8 Structural Variants Associated with Autosomal Dominant Hearing Loss

Author: Luke Mansard, Christel Vaché, Julie Bianchi, Corinne Baudoin, Isabelle Perthus, Bertrand Isidor, Catherine Blanchet, David Baux, Michel Koenig, Vasiliki Kalatzis, Anne-Françoise Roux, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Clermont-Ferrand, Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Montpellier (UM), and MORNET, Dominique
Subjects: [SDV] Life Sciences [q-bio], Medicine (General), R5-920, DFNA5, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Case Report, GSDME, single-exon CNV, hearing loss
Abstract: GSDME, also known as DFNA5, is a gene implicated in autosomal dominant nonsyndromic hearing loss (ADNSHL), affecting, at first, the high frequencies with a subsequent progression over all frequencies. To date, all the GSDME pathogenic variants associated with deafness lead to skipping of exon 8. In two families with apparent ADNSHL, massively parallel sequencing (MPS) integrating a coverage-based method for detection of copy number variations (CNVs) was applied, and it identified the first two causal GSDME structural variants affecting exon 8. The deleterious impact of the c.991-60_1095del variant, which includes the acceptor splice site sequence of exon 8, was confirmed by the study of the proband’s transcripts. The second mutational event is a complex rearrangement that deletes almost all of the exon 8 sequence. This study increases the mutational spectrum of the GSDME gene and highlights the crucial importance of MPS data for the detection of GSDME exon 8 deletions, even though the identification of a causal single-exon CNV by MPS analysis is still challenging.
Published: 2022

50. Plasma Amyloid Beta Predicts Conversion to Dementia in Subjects with Mild Cognitive Impairment: The BALTAZAR Study

Author: Hanon, Olivier, Vidal, Jean-Sébastien, Lehmann, Sylvain, Bombois, Stéphanie, Allinquant, Bernadette, Baret-Rose, Christiane, Tréluyer, Jean-Marc, Abdoul, Hendy, Gelé, Patrick, Delmaire, Christine, Blanc, Frédéric, Mangin, Jean-François, Buée, Luc, Touchon, Jacques, Hugon, Jacques, Vellas, Bruno, Galbrun, Evelyne, Benetos, Athanase, Berrut, Gilles, Paillaud, Elena, Wallon, David, Castelnovo, Giovanni, Volpe-Gillot, Lisette, Paccalin, Marc, Robert, Philippe, Godefroy, Olivier, Camus, Vincent, Belmin, Joël, Vandel, Pierre, Novella, Jean-Luc, Duron, Emmanuelle, Rigaud, Anne-Sophie, Schraen-Maschke, Susanna, Gabelle, Audrey, Groupe hospitalier Broca, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maladie d'Alzheimer : marqueurs génétiques et vasculaires, neuropsychologies (EA 4468), Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Evaluation thérapeutique et pharmacologie périnatale et pédiatrique (EA_7323), Université Paris Descartes - Paris 5 (UPD5), CIC - Mère Enfant Necker Cochin Paris Centre (CIC 1419), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Unité de recherche clinique / Centre d'investigation clinique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA), Service Instrumentation Conception Caractérisation (LAAS-I2C), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, Université Paris-Saclay, 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, NeuroTMULille International Laboratory [Lille] (UNIV LILLE / TMU), Université de Lille, Excellence Laboratory LabEx DISTALZ, Centres Mémoire de Ressources et de Recherche Montpellier (CMRR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut du Vieillissement, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, CHU Toulouse [Toulouse], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Emile Roux [AP-HP], Service de Gériatrie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Motricité, interactions, performance EA 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), Université de Nantes (UN)-Université de Nantes (UN), 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), Cancer Research and Personalized Medicine - CARPEM [Paris], 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)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Léopold-Bellan, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de 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), Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Charles Foix [AP-HP], Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Reims (CHU Reims), 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, Hôpital Paul Brousse, Université Paris Cité (UPCité), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), 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), Centre Mémoire de Ressources et de Recherches (CMRR), Université de Montpellier (UM), Université de Toulouse (UT)-Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Motricité, interactions, performance UR 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Nantes Université - UFR des Sciences et Techniques des Activités Physiques et Sportives (Nantes Univ - UFR STAPS), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), 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 Mémoire de Ressources et de Recherche [Nice] (CMRR Nice), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA)
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; INTRODUCTION: Blood-based biomarkers are the next challenge for Alzheimer's disease (AD) diagnosis and prognosis. METHODS: Mild cognitive impairment (MCI) participants (N = 485) of the BALTAZAR study, a large-scale longitudinal multicenter cohort, were followed-up for 3 years. A total of 165 of them converted to dementia (95% AD). Associations of conversion and plasma amyloid beta (Aβ)1-42 , Aβ1-40 , Aβ1-42 /Aβ1-40 ratio were analyzed with logistic and Cox models. RESULTS: Converters to dementia had lower level of plasma Aβ1-42 (37.1 pg/mL [12.5] vs. 39.2 [11.1] , P value = .03) and lower Aβ1-42 /Aβ1-40 ratio than non-converters (0.148 [0.125] vs. 0.154 [0.076], P value = .02). MCI participants in the highest quartile of Aβ1-42 /Aβ1-40 ratio (>0.169) had a significant lower risk of conversion (hazard ratio adjusted for age, sex, education, apolipoprotein E \epsilon4, hippocampus atrophy = 0.52 (95% confidence interval [0.31-0.86], P value = .01). DISCUSSION: In this large cohort of MCI subjects we identified a threshold for plasma Aβ1-42 /Aβ1-40 ratio that may detect patients with a low risk of conversion to dementia within 3 years.
Published: 2022

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