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14,348 results on '"[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology"'

1. Exploration of fMRI brain responses to oral sucrose after Roux-en-Y gastric bypass in obese yucatan minipigs in relationship with microbiota and metabolomics profiles

Author

Damien Bergeat, Nicolas Coquery, Yentl Gautier, Sarah Clotaire, Émilie Vincent, Véronique Romé, Sylvie Guérin, Isabelle Le Huërou-Luron, Sophie Blat, Ronan Thibault, David Val-Laillet, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], Service d'endocrinologie diabétologie et nutrition [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, This study was funded by the Hed-O-Shift INRA Priority Action of the AlimH Division (Nutrition, Chemical Food Safety and Consumer Behaviour) and coordinated by David Val-Laillet. Damien Bergeat also received funding from the European Society for Clinical Nutrition and Metabolism to perform part of this project., and Bernard, Emilie

Subjects
Bariatric surgery, Gastric bypass, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Nutrition and Dietetics, Microbiota, Brain, Obesity, Critical Care and Intensive Care Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Functional MRI
Abstract

International audience; Background & aimsIn most cases, Roux-en-Y gastric bypass (RYGBP) is an efficient intervention to lose weight, change eating behavior and improve metabolic outcomes in obese patients. We hypothesized that weight loss induced by RYGBP in obese Yucatan minipigs would induce specific modifications of the gut–brain axis and neurocognitive responses to oral sucrose stimulation in relationship with food intake control.MethodsAn integrative study was performed after SHAM (n = 8) or RYGBP (n = 8) surgery to disentangle the physiological, metabolic and neurocognitive mechanisms of RYGBP. BOLD fMRI responses to sucrose stimulations at different concentrations, brain mRNA expression, cecal microbiota, and plasma metabolomics were explored 4 months after surgery and integrated with WGCNA analysis.ResultsWe showed that weight loss induced by RYGBP or SHAM modulated differently the frontostriatal responses to oral sucrose stimulation, suggesting a different hedonic treatment and inhibitory control related to palatable food after RYGBP. The expression of brain genes involved in the serotoninergic and cannabinoid systems were impacted by RYGBP. Cecal microbiota was deeply modified and many metabolite features were differentially increased in RYGBP. Data integration with WGCNA identified interactions between key drivers of OTUs and metabolites features linked to RYGBP.ConclusionThis longitudinal study in the obese minipig model illustrates with a systemic and integrative analysis the mid-term consequences of RYGBP on brain mRNA expression, cecal microbiota and plasma metabolites. We confirmed the impact of RYGBP on functional brain responses related to food reward, hedonic evaluation and inhibitory control, which are key factors for the success of anti-obesity therapy and weight loss maintenance.

Published
2023

2. Associations of white blood cell and platelet counts with specific depressive symptom dimensions in patients with bipolar disorder: Analysis of data from the FACE-BD cohort

Author

Aiste, Lengvenyte, Robertas, Strumila, Raoul, Belzeaux, Bruno, Aouizerate, Caroline, Dubertret, Emmanuel, Haffen, Pierre-Michel, Llorca, Paul, Roux, Mircea, Polosan, Raymund, Schwan, Michel, Walter, Thierry, D'Amato, Dominique, Januel, Marion, Leboyer, Frank, Bellivier, Bruno, Etain, Alvydas, Navickas, Emilie, Olié, Philippe, Courtet, 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), Vilnius University [Vilnius], Fondation FondaMental [Créteil], Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier Charles Perrens [Bordeaux], 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), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Centre Hospitalier de Versailles André Mignot (CHV), 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, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Psychothérapique de Nancy [Laxou] (CPN), Hopital de Bohars - CHRU Brest (CHU - BREST ), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche Clinique de l'Hôpital de Ville-Evrard [Neuilly-sur-​Marne] (URCVE), Etablissement public de santé de Ville-Evrard (EPS), 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 [Créteil], Hôpital Lariboisière-Fernand-Widal [APHP], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), ANR-10-COHO-0010,Psy-COH,FondaMental-Cohortes(2010), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Centre Psychothérapique de Nancy (CPN), CHU Henri Mondor, Guerineau, Nathalie C., Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID, and Cohortes - FondaMental-Cohortes - - Psy-COH2010 - ANR-10-COHO-0010 - COHO - VALID

Subjects
Inflammation, Blood cells, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Bipolar disorder, Depression, Endocrine and Autonomic Systems, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Immunology, [SDV] Life Sciences [q-bio], Behavioral Neuroscience, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Heterogeneity, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Evidences suggest that inflammation is increased in a subgroup of patients with depression. Moreover, increased peripheral inflammatory markers (cells and proteins) are associated with some, but not all depressive symptoms. On the other hand, similar studies on bipolar disorders mainly focused on blood cytokines. Here, we analysed data from a large (N = 3440), well-characterized cohort of individuals with bipolar disorder using Kendall partial rank correlation, multivariate linear regression, and network analyses to determine whether peripheral blood cell counts are associated with depression severity, its symptoms, and dimensions. Based on the self-reported 16-Item Quick Inventory of Depressive Symptomatology questionnaire scores, we preselected symptom dimensions based on literature and data-driven principal component analysis. We found that the counts of all blood cell types were only marginally associated with depression severity. Conversely, white blood cell count was significantly associated with the sickness dimension and its four components (anhedonia, slowing down, fatigue, and appetite loss). Platelet count was associated with the insomnia/restlessness dimension and its components (initial, middle, late insomnia and restlessness). Principal component analyses corroborated these results. Platelet count was also associated with suicidal ideation. In analyses stratified by sex, the white blood cell count-sickness dimension association remained significant only in men, and the platelet count-insomnia/restlessness dimension association only in women. Without implying causation, these results suggest that peripheral blood cell counts might be associated with different depressive symptoms in individuals with bipolar disorder, and that white blood cells might be implicated in sickness symptoms and platelets in insomnia/agitation and suicidal ideation.

Published
2023

3. Molecular and clinical diversity in primary central nervous system lymphoma

Author

Hernández-Verdin, I., Kirasic, E., Wienand, K., Mokhtari, K., Eimer, S., Loiseau, H., Rousseau, A., Paillassa, J., Ahle, G., Lerintiu, F., Uro-Coste, E., Oberic, L., Figarella-Branger, D., Chinot, O., Gauchotte, G., Taillandier, L., Marolleau, J.-P., Polivka, M., Adam, C., Ursu, R., Schmitt, A., Barillot, N., Nichelli, L., Lozano-Sánchez, F., Ibañez-Juliá, M.-J., Peyre, M., Mathon, B., Abada, Y., Charlotte, F., Davi, F., Stewart, C., de Reyniès, A., Choquet, S., Soussain, C., Houillier, C., Chapuy, B., Hoang-Xuan, K., Alentorn, A., 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), University Medical Center Göttingen (UMG), Freie Universität Berlin, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Bordeaux [Bordeaux], Imagerie moléculaire et thérapies innovantes en oncologie (IMOTION), Université de Bordeaux (UB), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Hôpitaux Civils de Colmar, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris Diderot - Paris 7 (UPD7), Hopital Saint-Louis [AP-HP] (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Sorbonne Université (SU), Centre Hospitalier Saint Jean de Perpignan, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut Curie - Saint Cloud (ICSC), DESSAIVRE, Louise, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Anatomie Pathologique [CHRU Nancy], and École pratique des hautes études (EPHE)

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Oncology, tumor heterogeneity, Hematology, multi-omics, microenvironment, PCNSL, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity.To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data.Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue.The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions.

Published
2023

4. Post-vaccination SARS-CoV-2 antibody kinetics and protection duration against Omicron in elderly population

Author

Chloé Dimeglio, Pauline Trémeaux, Fabrice Herin, Isabelle Da-Silva, Marion Porcheron, Guillaume Martin-Blondel, Caroline Gernigon, Sabine Chapuy-Regaud, Hélène Villars, Jacques Izopet, Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Maladies Professionnelles et Environnementales [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Pôle Gériatrie [CHU Toulouse], and Benson-Rumiz, Alicia

Subjects
MESH: Aged, Microbiology (medical), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: COVID-19* / prevention & control, MESH: Kinetics, SARS-CoV-2, Vaccination, COVID-19, MESH: Vaccination, Antibodies, Viral, Kinetics, Infectious Diseases, MESH: SARS-CoV-2, Humans, MESH: Antibodies, Viral, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Aged
Abstract

International audience; Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 is particularly severe in older individuals because of an impaired immune response.1 The vaccines presently available are less efficacious in older individuals, because of the senescence of their immune systems.2 A recent letter in Journal of Infection showed the need of a third vaccine dose due to a waning antibody response against new SARS-CoV-2 variants in healthy and immunocompromised individuals.3 In this study, we analysed the protection against Omicron provided by the immune responses of nursing home residents (NHRs) and a population of healthcare workers (HCWs).

Published
2022

5. Est-ce que vraiment, les médecins sont (comme) des anges ?

Author

Gross, Olivia, Ruelle, Yannick, Laboratoire éducations et promotion de la santé (LEPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Département universitaire de médecine générale, Université Sorbonne Paris Nord (DUMG USPN), Centres municipaux de santé universitaires de Pantin (CMSU Pantin), and Ruelle, Yannick

Subjects
[SHS.PHIL] Humanities and Social Sciences/Philosophy, Issues, ethics and legal aspects, [SHS.SOCIO]Humanities and Social Sciences/Sociology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Health (social science), [SHS.SOCIO] Humanities and Social Sciences/Sociology, Health Policy, [SHS.PHIL]Humanities and Social Sciences/Philosophy, [SDV.ETH] Life Sciences [q-bio]/Ethics, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.ETH]Life Sciences [q-bio]/Ethics
Abstract

International audience; Une polémique sur une page Facebook® fréquentée majoritairement par des médecins a suscité cet article. Cette dernière a éclaté à propos d’une femme qui demandait à être examinée par une femme médecin, dans un contexte d’examen gynécologique faisant suite à un viol. La teneur des positions qui ont été exprimées donne l’occasion de discuter du rôle des soignants dans un contexte de traumatisme, présent comme passé. Deux approches ont été mobilisées pour guider l’analyse : le pragmatisme et le modèle de l’université de Buffalo axé sur la non-réactivation des traumatismes. Selon l’acception pragmatiste, le premier devoir des soignants est de faire en sorte que l’expérience de soins soit la plus positive possible. Quant au modèle de Buffalo, il précise qu’il s’agit plus particulièrement de favoriser la sécurité émotionnelle des patients et que cet objectif devrait orienter tous les services de soins rendus. Il invite à réaliser que les personnes ayant subi des traumatismes sont devenues réactives à des situations auxquelles des individus non concernés ne seraient pas sensibles, parmi lesquelles en particulier, le manque de contrôle sur leur situation. Enfin, si le modèle de Buffalo est particulièrement pertinent dans le cadre de services de santé accueillant un public susceptible d’avoir connu des traumatismes, les mêmes principes pourraient être convoqués au-delà. En effet, ils valent de manière générale car ils correspondent à ce que l’on a raison d’estimer : le développement de l’empowerment des personnes, au sein d’institutions justes et bientraitantes.

Published
2022

6. Development of versatile allele-specific siRNAs able to silence all the dominant dynamin 2 mutations

Author

Swati Dudhal, Lylia Mekzine, Bernard Prudhon, Karishma Soocheta, Bruno Cadot, Kamel Mamchaoui, Delphine Trochet, Marc Bitoun, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Bitoun, Marc

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, allele-specific silencing, MT: RNA/DNA Editing, migration, gene therapy, dominant centronuclear myopathy, adhesion, dynamin 2, RNA interference, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Drug Discovery, endocytosis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Molecular Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Dominant centronuclear myopathy (CNM) is a rare form of congenital myopathy associated with a wide clinical spectrum, from severe neonatal to milder adult forms. There is no available treatment for this disease due to heterozygous mutations in the DNM2 gene encoding Dynamin 2 (DNM2). Dominant DNM2 mutations also cause rare forms of Charcot-Marie-Tooth disease and hereditary spastic paraplegia, and deleterious DNM2 overexpression was noticed in several diseases. The proof of concept for therapy by allele-specific RNA interference devoted to silence the mutated mRNA without affecting the normal allele was previously achieved in a mouse model and patient-derived cells, both expressing the most frequent DNM2 mutation in CNM. In order to have versatile small interfering RNAs (siRNAs) usable regardless of the mutation, we have developed allele-specific siRNAs against two non-pathogenic single-nucleotide polymorphisms (SNPs) frequently heterozygous in the population. In addition, allele-specific siRNAs against the p.S619L DNM2 mutation, a mutation frequently associated with severe neonatal cases, were developed. The beneficial effects of these new siRNAs are reported for a panel of defects occurring in patient-derived cell lines. The development of these new molecules allows targeting the large majority of the patients harboring DNM2 mutations or overexpression by only a few siRNAs.

Published
2022

7. Clinical characteristics associated with discrepancies between self- and clinician-rated suicidal ideation in patients with bipolar disorder (FACE-BD cohort)

Author

Bénédicte Nobile, Raoul Belzeaux, Bruno Aouizerate, Caroline Dubertret, Emmanuel Haffen, Pierre-Michel Llorca, Paul Roux, Mircea Polosan, Raymund Schwan, Michel Walter, Romain Rey, Dominique Januel, Marion Leboyer, Frank Bellivier, Bruno Etain, Philippe Courtet, Emilie Olié, 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), Fondation FondaMental [Créteil], Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Centre hospitalier Charles Perrens [Bordeaux], Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Centre Hospitalier de Versailles André Mignot (CHV), 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, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Université de Lorraine (UL), Centre Psychothérapique de Nancy [Laxou] (CPN), Hopital de Bohars - CHRU Brest (CHU - BREST ), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], Unité de Recherche Clinique de l'Hôpital de Ville-Evrard [Neuilly-sur-​Marne] (URCVE), Etablissement public de santé de Ville-Evrard (EPS), 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), 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), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Hôpital Lariboisière-Fernand-Widal [APHP], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Centre Psychothérapique de Nancy (CPN), and Guerineau, Nathalie C.

Subjects
Psychiatry and Mental health, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Biological Psychiatry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Suicidal ideation (SI) is a major suicide risk factor; therefore, it is crucial to identify individuals with SI. Discrepancies between the clinicians and patients' estimation of SI may lead to under-evaluating the suicide risk. Yet, studies on discrepancies between self- and clinician-rated SI are lacking, although identifying the patients' sociodemographic and clinical characteristics associated with such discrepancies might help to reduce the under-evaluation risk. Therefore, the aim of this study was to identify features associated with SI rating discrepancies in patients with bipolar disorder (BD) because of the high prevalence of suicide in this population. Among the patients recruited by the French network of FondaMental expert centers for BD, patients with SI (i.e. ≥2 for item 12 of the Quick Inventory of Depressive Symptomatology-Self Report and/or ≥3 for item 10 of the clinician-rated Montgomery and Åsberg Depression Rating Scale) were selected and divided in concordant (i.e. SI in both self- and clinician-rated questionnaires; n = 130; 25.6%), and discordant (i.e. SI in only one questionnaire; n = 377; 74.4%). Depression severity was the feature most associated with SI evaluation discrepancy, especially in patients with SI identified only with the self-rated questionnaire. Clinician may under-evaluate SI presence in patients with low depression level.

Published
2023

8. How to improve intubation in the intensive care unit. Update on knowledge and devices

Author

Audrey De Jong, Sheila Nainan Myatra, Oriol Roca, Samir Jaber, 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Saint Eloi (CHRU Montpellier), Homi Bhabha National Institute (HBNI), Instituto de Salud Carlos III [Madrid] (ISC), and Hospital Universitari Parc Taulí [Sabadell, Spain] (HUPT)

Subjects
Complications, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Critical Illness, Critical Care and Intensive Care Medicine, Respiration, Artificial, Videolaryngoscopy, Airway, Intensive Care Units, Intubation, Intratracheal, Humans, Intubation, Videolaryngoscope, Hypoxia, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Tracheal intubation in the critically ill is associated with serious complications, mainly cardiovascular collapse and severe hypoxemia. In this narrative review, we present an update of interventions aiming to decrease these complications. MACOCHA is a simple score that helps to identify patients at risk of difficult intubation in the intensive care unit (ICU). Preoxygenation combining the use of inspiratory support and positive end-expiratory pressure should remain the standard method for preoxygenation of hypoxemic patients. Apneic oxygenation using high-flow nasal oxygen may be supplemented, to prevent further hypoxemia during tracheal intubation. Face mask ventilation after rapid sequence induction may also be used to prevent hypoxemia, in selected patients without high-risk of aspiration. Hemodynamic optimization and management are essential before, during and after the intubation procedure. All these elements can be integrated in a bundle. An airway management algorithm should be adopted in each ICU and adapted to the needs, situation and expertise of each operator. Videolaryngoscopes should be used by experienced operators

Published
2022

9. MicroRNAs in kidney injury and disease

Author

Nassim Mahtal, Olivia Lenoir, Claire Tinel, Dany Anglicheau, Pierre-Louis Tharaux, Tharaux, Pierre-Louis, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris Cité (UPCité)

Subjects
[SDV] Life Sciences [q-bio], MicroRNAs, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Nephrology, [SDV]Life Sciences [q-bio], Humans, Acute Kidney Injury, Renal Insufficiency, Chronic, Kidney, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by degrading or repressing the translation of their target messenger RNAs. As miRNAs are critical regulators of cellular homeostasis, their dysregulation is a crucial component of cell and organ injury. A substantial body of evidence indicates that miRNAs are involved in the pathophysiology of acute kidney injury (AKI), chronic kidney disease and allograft damage. Different subsets of miRNAs are dysregulated during AKI, chronic kidney disease and allograft rejection, which could reflect differences in the physiopathology of these conditions. miRNAs that have been investigated in AKI include miR-21, which has an anti-apoptotic role, and miR-214 and miR-668, which regulate mitochondrial dynamics. Various miRNAs are downregulated in diabetic kidney disease, including the miR-30 family and miR-146a, which protect against inflammation and fibrosis. Other miRNAs such as miR-193 and miR-92a induce podocyte dedifferentiation in glomerulonephritis. In transplantation, miRNAs have been implicated in allograft rejection and injury. Further work is needed to identify and validate miRNAs as biomarkers of graft function and of kidney disease development and progression. Use of combinations of miRNAs together with other molecular markers could potentially improve diagnostic or predictive power and facilitate clinical translation. In addition, targeting specific miRNAs at different stages of disease could be a promising therapeutic strategy.

Published
2022

10. Treatment times, functional outcome, and hemorrhage rates after switching to tenecteplase for stroke thrombolysis: Insights from the TETRIS registry

Author

Gaspard Gerschenfeld, Jean-Sébastien Liegey, François-Xavier Laborne, Marion Yger, Victoire Lyon, Thomas Checkouri, Bertille Tricard-Dessagne, Gaultier Marnat, Frédéric Clarençon, Nicolas Chausson, Guillaume Turc, Igor Sibon, Sonia Alamowitch, Stéphane Olindo, Service d'Urgences Cérébro-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Infrastructure de recherche clinique en psychiatrie adulte [ICM Paris] (iCRIN psychiatrie), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département Médico-Universitaire Neurosciences [Sorbonne Université] (DMU Neurosciences), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Tenon [AP-HP], CHU Bordeaux [Bordeaux], Centre Hospitalier Sud Francilien, 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), GHU Paris Psychiatrie et Neurosciences, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, and Gerschenfeld, Gaspard

Subjects
thrombolysis, Ischemic stroke, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, tenecteplase, process times, Original Research Articles, Neurology (clinical), acute stroke therapy, Cardiology and Cardiovascular Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Introduction: The encouraging efficacy and safety data on intravenous thrombolysis with tenecteplase in ischemic stroke and its practical advantages motivated our centers to switch from alteplase to tenecteplase. We report its impact on treatment times and clinical outcomes. Methods: We retrospectively analyzed clinical and procedural data of patients treated with alteplase or tenecteplase in a comprehensive (CSC) and a primary stroke center (PSC), which transitioned respectively in 2019 and 2018. Tenecteplase enabled in-imaging thrombolysis in the CSC. The main outcomes were the imaging-to-thrombolysis and thrombolysis-to-puncture times. We assessed the association of tenecteplase with 3-month functional independence and parenchymal hemorrhage (PH) with multivariable logistic models. Results: We included 795 patients, 387 (48.7%) received alteplase and 408 (51.3%) tenecteplase. Both groups (tenecteplase vs alteplase) were similar in terms of age (75 vs 76 years), baseline NIHSS score (7 vs 7.5) and proportion of patients treated with mechanical thrombectomy (24.1% vs 27.5%). Tenecteplase patients had shorter imaging-to-thrombolysis times (27 vs 36 min, p a 1.68, 95% CI 1.15–2.48, p a 0.68, 95% CI 0.41–1.12, p = 0.13). Conclusion: Switch from alteplase to tenecteplase reduced process times and may improve functional outcome, with similar safety profile.

Published
2022

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