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

1. Determining PD-L1 Status in Patients With Triple-Negative Breast Cancer: Lessons Learned From IMpassion130

Author: Jary, Marine, Liu, Wen-Wei, Yan, Dongyao, Bai, Isaac, Muranyi, Andrea, Colle, Elise, Brocheriou, Isabelle, Turpin, Anthony, Radosevic-Robin, Nina, Bourgoin, Pierre, Penault-Llorca, Frédérique, Cohen, Romain, Vernerey, Dewi, André, Thierry, Borg, Christophe, Shanmugam, Kandavel, Svrcek, Magali, Liu, Wen‐wei, Cooperator Multidisciplinary Oncology Group (GERCOR), CHU Clermont-Ferrand, Ventana Medical Systems, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'oncologie médicale (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), CHU Saint-Antoine [AP-HP], Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Breast Cancer Translational Research Laboratory, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Translational Cancer Research Unit [Antwerp], Philipps Universität Marburg = Philipps University of Marburg, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Division of Pathology and Laboratory Medicine, Università degli Studi di Milano = University of Milan (UNIMI)-European Institute of Oncology [Milan] (ESMO), University of the Sunshine Coast (USC), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Pathology, Aberdeen University Medical School, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), VU Medical Center, Cell Biology and Biotherapy Unit, INT-Fondazione Pascale, Department of Oncology and Metabolism [Sheffield, UK], The University of Sheffield [Sheffield, U.K.], Institute for Surgical Pathology, University hospital of Zurich [Zurich], Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Oncologie Médicale [CHU Saint -Antoine], 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Oncologie Médicale [CHU Saint-Antoine], HAL-SU, Gestionnaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), 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), and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Subjects: Cancer Research, Biopsy, Best practice, BluePrint 80-gene signature, Predictive, DNA Mismatch Repair, pMMR, B7-H1 Antigen, Cohort Studies, Breast cancer, MESH: Tumor Microenvironment, Tumor Microenvironment, MESH: B7-H1 Antigen, Prospective Studies, MESH: Lymphocytes, Tumor-Infiltrating, MESH: Cohort Studies, Oligometastatic colorectal cancer, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, high/low risk, immune profile, General Medicine, Immunohistochemistry, External quality assessment, 3. Good health, MESH: DNA Mismatch Repair, Oncology, Cytological techniques, Colonic Neoplasms, Molecular Medicine, HER2-low, Colorectal Neoplasms, PD-L1, Histology, Serum proteins, T lymphocytes, [SDV.CAN]Life Sciences [q-bio]/Cancer, Prognostic, Non-small cell lung carcinoma, Lymphocytes, Tumor-Infiltrating, Molecular diagnostics, Genetics, Humans, early breast cancer, MESH: Colonic Neoplasms, MESH: Humans, Liquid biopsy, gene expression profiles, MammaPrint 70-gene signature, Plasma proteins, Biomarker, MESH: Prospective Studies, digestive system diseases, Next-generation sequencing, Trastuzumab-deruxtecan, MESH: Tissue Fixation, hallmarks of cancer, MESH: Colorectal Neoplasms, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; In the era of immune checkpoint inhibitors, understanding the metastatic microenvironment of proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer (CRC) is of paramount importance to both prognostication and the development of more effective novel therapies. In this study, primary and paired metastasis tissue samples were collected from patients with resectable metastatic CRC treated with adjuvant FOLFOX or peri-operative chemotherapy in the MIROX phase III prospective study. In total, 74 cancer tissues were stained for CD3, CD8, Forkhead box protein 3 (FOXP3), programmed cell death protein-1 (PD-1, invasive front, stromal, intra-epithelial compartments), and programmed death-ligand 1 (PD-L1, tumor, immune cells). The immune profiling of primary CRC had a limited value to predict the immune context of paired metastases for all markers but CD3+. The expression of CD8 and PD-L1 was higher in metastases after neoadjuvant FOLFOX. In metastases, both CD3 T cells at the invasive front and PD-L1 expressions on immune cells were predictive of better disease-free survival. These results show that the effect of FOLFOX on modifying the immune microenvironment in resected CRC metastases and measurement of PD-L1 expression and tumor-infiltrating CD8 T cells in pMMR/MSS metastatic tissue samples could improve treatment strategies of metastatic CRC patients.
Published: 2022

2. MicroRNA regulatory networks associated with abnormal muscle repair in survivors of critical illness

Author: Christopher J, Walsh, Carlos, Escudero King, Muskan, Gupta, Pamela J, Plant, Margaret J, Herridge, Sunita, Mathur, Pingzhao, Hu, Judy, Correa, Sameen, Ahmed, Anne, Bigot, Claudia C, Dos Santos, Jane, Batt, Keenan Research Centre for Biomedical Science [Toronto, ON, Canada], Li Ka Shing Knowledge Institute [Toronto, ON, Canada]-St. Michael’s Hopsital [Toronto, ON, Canada], University of Toronto, University of Manitoba [Winnipeg], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Submitted on behalf of the MusclE and Nerve Dysfunction (MEND)-ICU Group and Canadian Critical Care Translational Biology Group (CCCTBG), and Gestionnaire, HAL Sorbonne Université 5
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, ICU-acquired weakness, Critical Illness, Muscles, Muscle weakness, Microarray, Gene network analysis, Myoblasts, Mice, MicroRNAs, Muscle regeneration, Physiology (medical), Animals, Humans, Muscle atrophy, Orthopedics and Sports Medicine, Survivors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Intensive care unit (ICU)-acquired weakness is characterized by muscle atrophy and impaired contractility that may persist after ICU discharge. Dysregulated muscle repair and regeneration gene co-expression networks are present in critical illness survivors with persistent muscle wasting and weakness. We aimed to identify microRNAs (miRs) regulating the gene networks and determine their role in the self-renewal of muscle in ICU survivors.Methods: Muscle whole-transcriptome expression was assessed with microarrays in banked quadriceps biopsies obtained at 7 days and 6 months post-ICU discharge from critically ill patients (n = 15) in the RECOVER programme and healthy individuals (n = 8). We conducted an integrated miR-messenger RNA analysis to identify miR/gene pairs associated with muscle recovery post-critical illness and evaluated their impact on myoblast proliferation and differentiation in human AB1167 and murine C2C12 cell lines in vitro. Select target genes were validated with quantitative PCR.Results: Twenty-two miRs were predicted to regulate the Day 7 post-ICU muscle transcriptome vs. controls. Thirty per cent of all differentially expressed genes shared a 3'UTR regulatory sequence for miR-424-3p/5p, which was 10-fold down-regulated in patients (P < 0.001) and correlated with quadriceps size (R = 0.86, P < 0.001), strength (R = 0.75, P = 0.007), and physical function (Functional Independence Measures motor subscore, R = 0.92, P < 0.001) suggesting its potential role as a master regulator of early recovery of muscle mass and strength following ICU discharge. Network analysis demonstrated enrichment for cellular respiration and muscle fate commitment/development related genes. At 6 months post-ICU discharge, a 14-miR expression signature, including miRs-490-3p and -744-5p, identified patients with muscle mass recovery vs. those with sustained atrophy. Constitutive overexpression of the novel miR-490-3p significantly inhibited AB1167 and C2C12 myoblast proliferation (cell count AB1167 miR-490-3p mimic or scrambled-miR transfected myoblasts 7926 ± 4060 vs. 14 159 ± 3515 respectively, P = 0.006; proportion Ki67-positive nuclei AB1167 miR-490-3p mimic or scrambled-miR transfected myoblasts 0.38 ± 0.07 vs. 0.54 ± 0.06 respectively, P < 0.001; proliferating cell nuclear antigen expression AB1167 miR-490-3p mimic or scrambled-miR transfected myoblasts 11.48 ± 1.97 vs. 16.75 ± 1.19 respectively, P = 0.040). Constitutive overexpression of miR-744-5p, a known regulator of myogenesis, significantly inhibited AB1167 and C2C12 myoblast differentiation (fusion index AB1167 miR-744-5p mimic or scrambled-miR transfected myoblasts 8.31 ± 7.00% vs. 40.29 ± 9.37% respectively, P < 0.001; myosin heavy chain expression miR-744-5p mimic or scrambled-miR transfected myoblasts 0.92 ± 0.39 vs. 13.53 ± 5.5 respectively, P = 0.01).Conclusions: Combined functional transcriptomics identified 36 miRs including miRs-424-3p/5p, -490-3p, and -744-5p as potential regulators of gene networks associated with recovery of muscle mass and strength following critical illness. MiR-490-3p is identified as a novel regulator of myogenesis.
Published: 2022

3. Association Between FIASMAs and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID‐19: An Observational Multicenter Study

Author: Hoertel, Nicolas, Sánchez-Rico, Marina, Gulbins, Erich, Kornhuber, Johannes, Carpinteiro, Alexander, Lenze, Eric J., Reiersen, Angela M., Abellán, Miriam, de la Muela, Pedro, Vernet, Raphaël, Blanco, Carlos, Cougoule, Céline, Neuraz, Antoine, Gorwood, Philip, Alvarado, Jesús M., Meneton, Pierre, Limosin, Frédéric, Ancel, Pierre-Yves, Bauchet, Alain, Beeker, Nathanaël, Benoit, Vincent, Bernaux, Mélodie, Bellamine, Ali, Bey, Romain, Bourmaud, Aurélie, Breant, Stéphane, Burgun, Anita, Carrat, Fabrice, Caucheteux, Charlotte, Champ, Julien, Cormont, Sylvie, Daniel, Christel, Dubiel, Julien, Ducloas, Catherine, Esteve, Loic, Frank, Marie, Garcelon, Nicolas, Gramfort, Alexandre, Griffon, Nicolas, Grisel, Olivier, Guilbaud, Martin, Hassen-Khodja, Claire, Hemery, François, Hilka, Martin, Sophie Jannot, Anne, Lambert, Jerome, Layese, Richard, Leblanc, Judith, Lebouter, Léo, Lemaitre, Guillaume, Leprovost, Damien, Lerner, Ivan, Levi Sallah, Kankoe, Maire, Aurélien, Mamzer, Marie-France, Martel, Patricia, Mensch, Arthur, Moreau, Thomas, Orlova, Nina, Paris, Nicolas, Rance, Bastien, Ravera, Hélène, Rozes, Antoine, Salamanca, Elisa, Sandrin, Arnaud, Serre, Patricia, Tannier, Xavier, Treluyer, Jean-Marc, van Gysel, Damien, Varoquaux, Gaël, Vie, Jill Jen, Wack, Maxime, Wajsburt, Perceval, Wassermann, Demian, Zapletal, Eric, 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 Corentin Celton [Issy-les-Moulineaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), University of Duisburg-Essen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Hôpital Européen Georges Pompidou [APHP] (HEGP), National Institute on Drug Abuse [Bethesda] (NIDA), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), CHU Necker - Enfants Malades [AP-HP], Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, AP-HP / Université de Paris / INSERM COVID-19 research collaboration, AP-HP COVID CDR Initiative, 'Entrepôt de Données de Santé' AP-HP Consortium: Pierre-Yves Ancel, Alain Bauchet, Nathanaël Beeker, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal, Martinez Rico, Clara, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), National Institute on Drug Abuse [Bethesda], Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, 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 de Paris (UP), Collaborators : AP-HP / Université de Paris / INSERM COVID-19 research collaboration, AP-HP COVID CDR Initiative, 'Entrepôt de Données de Santé' AP-HP Consortium: Pierre-Yves Ancel, Alain Bauchet, Nathanaël Beeker, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien Van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), École Pratique des Hautes Études (EPHE), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), 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)-École Pratique des Hautes Études (EPHE), Imagine - Institut des maladies génétiques (IMAGINE - U1163), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Medizin, law.invention, Cohort Studies, COVID-19 Testing, medications, Randomized controlled trial, law, Clinical endpoint, Intubation, Pharmacology (medical), Enzyme Inhibitors, acid sphingomyelinase, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, treatment, Inverse probability weighting, Hazard ratio, Middle Aged, 3. Good health, Hospitalization, [SDV] Life Sciences [q-bio], Sphingomyelin Phosphodiesterase, Female, FIASMA, Adult, medicine.medical_specialty, Adolescent, intubation, Young Adult, Internal medicine, Intubation, Intratracheal, medicine, Humans, ceramide, Aged, Retrospective Studies, Pharmacology, SARS-CoV-2, Proportional hazards model, business.industry, COVID-19, mortality, Confidence interval, COVID-19 Drug Treatment, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Collaborators : AP-HP / Université de Paris / INSERM COVID-19 research collaboration, AP-HP COVID CDR Initiative, “Entrepôt de Données de Santé” AP-HP Consortium: Pierre-Yves Ancel, Alain Bauchet, Nathanaël Beeker, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien Van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal; International audience; Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide system may be central to SARS-CoV-2 infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe COVID-19 in an observational multicenter study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking a FIASMA medication at the time of their hospital admission. The primary endpoint was a composite of intubation and/or death. We compared this endpoint between patients taking vs. not taking a FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD=12.5), the primary endpoint occurred in 104 patients (37.5%) receiving a FIASMA medication, and 1,060 patients (41.4%) who did not. Despite being significantly and substantially associated with older age and greater medical severity, FIASMA medication use was significantly associated with reduced likelihood of intubation or death in both crude (HR=0.71; 95%CI=0.58-0.87; p
Published: 2021

4. Characterisation of early ultrastructural changes in the cerebral white matter of CADASIL small vessel disease using high‐pressure freezing/freeze‐substitution

Author: Nicolas Dupré, Rikesh M. Rajani, Guillaume van Niel, Valérie Domenga-Denier, Xavier Heiligenstein, Anne Joutel, Martinez Rico, Clara, 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 Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), and University of Vermont [Burlington]
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, small vessel disease, Histology, Freeze Substitution, inner tongue, Uranyl acetate, CADASIL, Corpus callosum, myelin splitting, Corpus Callosum, Pathology and Forensic Medicine, White matter, Mice, 03 medical and health sciences, chemistry.chemical_compound, Myelin, 0302 clinical medicine, Physiology (medical), medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Myelin Sheath, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Chemistry, CD68, high pressure freezing/freeze-substitution, medicine.disease, White Matter, Hyperintensity, 030104 developmental biology, medicine.anatomical_structure, Neurology, Freeze substitution, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; Aims: The objective of this study was to elucidate the early white matter changes in CADASIL small vessel disease.Methods: We used high-pressure freezing and freeze substitution (HPF/FS) in combination with high-resolution electron microscopy (EM), immunohistochemistry and confocal microscopy of brain specimens from control and CADASIL (TgNotch3R169C ) mice aged 4-15 months to study white matter lesions in the corpus callosum.Results: We first optimised the HPF/FS protocol in which samples were chemically prefixed, frozen in a sample carrier filled with 20% polyvinylpyrrolidone and freeze-substituted in a cocktail of tannic acid, osmium tetroxide and uranyl acetate dissolved in acetone. EM analysis showed that CADASIL mice exhibit significant splitting of myelin layers and enlargement of the inner tongue of small calibre axons from the age of 6 months, then vesiculation of the inner tongue and myelin sheath thinning at 15 months of age. Immunohistochemistry revealed an increased number of oligodendrocyte precursor cells, although only in older mice, but no reduction in the number of mature oligodendrocytes at any age. The number of Iba1 positive microglial cells was increased in older but not in younger CADASIL mice, but the number of activated microglial cells (Iba1 and CD68 positive) was unchanged at any age.Conclusion: We conclude that early WM lesions in CADASIL affect first and foremost the myelin sheath and the inner tongue, suggestive of a primary myelin injury. We propose that those defects are consistent with a hypoxic/ischaemic mechanism.
Published: 2021

5. Autosomal Recessive Cerebellar Ataxias With Elevated Alpha‐Fetoprotein: Uncommon Diseases, Common Biomarker

Author: Mathilde Renaud, Christine Tranchant, Michel Koenig, Mathieu Anheim, Service de Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, 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), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Herrada, Anthony
Subjects: MESH: Multifunctional Enzymes, Cerebellar Ataxia, MESH: DNA Helicases, MESH: Ataxia Telangiectasia, Ataxia Telangiectasia, alpha-fetoprotein, 03 medical and health sciences, 0302 clinical medicine, Cogan Syndrome, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Cogan Syndrome, 030304 developmental biology, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Humans, MESH: RNA Helicases, oculomotor apraxia, DNA Helicases, Nuclear Proteins, Multifunctional Enzymes, MESH: Phosphotransferases (Alcohol Group Acceptor), digestive system diseases, MESH: Cerebellar Ataxia, 3. Good health, DNA-Binding Proteins, Phosphotransferases (Alcohol Group Acceptor), DNA Repair Enzymes, MESH: DNA Repair Enzymes, recessive ataxia, Neurology, DNA/RNA repair, MESH: Biomarkers, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], alpha-Fetoproteins, MESH: alpha-Fetoproteins, Neurology (clinical), MESH: Nuclear Proteins, Biomarkers, RNA Helicases, MESH: DNA-Binding Proteins, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; alpha-Fetoprotein (AFP) is a biomarker of several autosomal recessive cerebellar ataxias (ARCAs), especially ataxia telangiectasia (AT) and ataxia with oculomotor apraxia (AOA) type 2 (AOA2). More recently, slightly elevated AFP has been reported in AOA1 and AOA4. Interestingly, AOA1, AOA2, AOA4, and AT are overlapping ARCAs characterized by oculomotor apraxia, with oculocephalic dissociation, choreo-dystonia, and/or axonal sensorimotor neuropathy, in addition to cerebellar ataxia with cerebellar atrophy. The genetic backgrounds in these disorders play central roles in nuclear maintenance through DNA repair [ATM (AT), APTX (AOA1), or PNKP (AOA4)] or RNA termination [SETX (AOA2)]. Partially discriminating thresholds of AFP have been proposed as a way to distinguish between ARCAs with elevated AFP. In these entities, elevated AFP may be an epiphenomenon as a result of liver transcriptional dysregulation. AFP is a simple and reliable biomarker for the diagnosis of ARCA in performance and interpretation of next-generation sequencing. Here, we evaluated clinical, laboratory, imaging, and molecular data of the group of ARCAs that share elevated AFP serum levels that have been described in the past two decades. © 2020 International Parkinson and Movement Disorder Society.
Published: 2020

6. Effectiveness of drugs acting on adrenergic receptors in the treatment for tobacco or alcohol use disorders: systematic review and meta‐analysis

Author: Isabelle Ingrand, Claire Lafay-Chebassier, Marcello Solinas, Nematollah Jaafari, Nicolas Doux, Paul Vanderkam, Soghra Ebrahimighavam, Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Henri Laborit (CHL), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie clinique et Vigilances [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Allameh Tabataba’i University (ATU), Centre de Recherches sur la Cognition et l'Apprentissage (CeRCA), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Université de Poitiers, Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche clinique intersectorielle en psychiatrie du Centre Hospitalier Henri Laborit, and SOLINAS, Marcello
Subjects: Adult, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, media_common.quotation_subject, adrenergic blockers, 030508 substance abuse, Medicine (miscellaneous), Alcohol use disorder, alcohol use disorder, Placebo, beta-adrenergic receptors, alpha-adrenergic receptors, law.invention, tobacco use disorder, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Tobacco, Humans, Medicine, 030212 general & internal medicine, media_common, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Adrenergic agonists, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Abstinence, medicine.disease, Receptors, Adrenergic, 3. Good health, Clonidine, Alcoholism, Psychiatry and Mental health, Systematic review, Pharmaceutical Preparations, Meta-analysis, Smoking cessation, Smoking Cessation, 0305 other medical science, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; Aim : To assess the efficacy of drugs directly acting on alpha- and beta-adrenergic receptors in the treatment of patients suffering from tobacco or alcohol use disorder.Methods : Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies were identified through PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials and clinicaltrial.gov. We selected only randomized controlled trials with adult patients with tobacco or alcohol use disorders according to DSM-5 criteria. Interventions included any molecule having a direct pharmacological action on alpha- or beta-adrenergic receptors (agonist or antagonist). Comparators were placebo or other validated pharmacotherapies. The duration of the intervention was a minimum of 1 month, with 3 months of follow-up. Measurements included smoking cessation for tobacco; for alcohol, we selected abstinence, alcohol consumption (drinks per day or week) and heavy drinking days (HDD). Ten studies with tobacco and six with alcohol use disorder were included in the qualitative synthesis and fifteen studies in the quantitative analysis.Results: We found that clonidine, an alpha-2 agonist, significantly increased smoking abstinence [relative risk = 1.39 with a 95% confidence interval (CI) = 1.04, 1.84]. Beta-blockers had no significant effect on smoking abstinence. The alpha-1 antagonists prazosin and doxazosin decreased alcohol consumption [SMD = −0.32 (−0.56, −0.07)] but had no effect on abstinence or HDD.Conclusions : The noradrenaline system may represent a promising mechanism to target in tobacco and alcohol use disorders.
Published: 2020

7. Hematological findings and complications of <scp>COVID</scp> ‐19

Author: Theodoros N. Sergentanis, Evangelos Terpos, Efstathios Kastritis, Grigoris T. Gerotziafas, Ioannis Ntanasis-Stathopoulos, Marianna Politou, Ismail Elalamy, Meletios A. Dimopoulos, Theodora Psaltopoulou, National and Kapodistrian University of Athens (NKUA), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie biologique [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Gestionnaire, Hal Sorbonne Université, Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, medicine.drug_class, Critical Illness, [SDV]Life Sciences [q-bio], Low molecular weight heparin, Thrombophilia, Gastroenterology, Procalcitonin, 03 medical and health sciences, 0302 clinical medicine, Lymphopenia, Internal medicine, Humans, Medicine, Critical Reviews, Blood coagulation test, Disseminated intravascular coagulation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hematology, biology, SARS-CoV-2, business.industry, C-reactive protein, COVID-19, Critical Review, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, 030220 oncology & carcinogenesis, Hemostasis, biology.protein, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: International audience; COVID-19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL-6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID-19 patients. Elevated D-Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life-threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID-19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.
Published: 2020

8. Clinical characteristics of familial hypocalciuric hypercalcaemia type 1: A multicentre study of 77 adult patients

Author: Jean-Philippe Haymann, Anne Lienhardt, Antoine Tabarin, Agnès Linglart, Philippe Caron, Yves Reznik, Thierry Brue, Dominique Martin-Coignard, Ivan Tack, Alexandre Buffet, Rosa Vargas-Poussou, Delphine Vezzosi, Marguerite Hureaux, Caroline Silve, Corinne Magdelaine, Jean-Marc Kuhn, C. Mouly, Solange Grunenwald, Antoine Bennet, CHU Toulouse [Toulouse], 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), CHU Limoges, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Rouen, Normandie Université (NU), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Service d'endocrinologie, diabète, maladies métaboliques [Hôpital de la Conception - APHM], Aix Marseille Université (AMU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Bordeaux [Bordeaux], Centre Hospitalier Le Mans (CH Le Mans), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Gall, Valérie
Subjects: Adult, medicine.medical_specialty, Hypercalcaemia, Endocrinology, Diabetes and Metabolism, Osteoporosis, familial hypocalciuric hypercalcaemia, 030209 endocrinology & metabolism, Gastroenterology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, parathyroid adenoma, Internal medicine, medicine, Humans, Renal colic, primary hyperparathyroidism, calcium‐sensing receptor, Retrospective Studies, Parathyroid adenoma, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Middle Aged, Hyperparathyroidism, Primary, medicine.disease, Urinary calcium, 3. Good health, 030220 oncology & carcinogenesis, Hypercalcemia, Calcium, Kidney stones, medicine.symptom, Differential diagnosis, business, Receptors, Calcium-Sensing, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Primary hyperparathyroidism
Abstract: International audience; ObjectiveFamilial hypocalciuric hypercalcaemia type 1 (FHH1), related to heterozygous loss‐of‐function mutations of the calcium‐sensing receptor gene, is the main differential diagnosis for primary hyperparathyroidism. The aim of our study was to describe clinical characteristics of adult patients living in France with a genetically confirmed FHH1.Design and patientsThis observational, retrospective, multicentre study included 77 adults, followed up in 32 clinical departments in France, with a genetic FHH1 diagnosis between 2001 and 2012.ResultsHypercalcaemia was diagnosed at a median age of 53 years [IQR: 38‐61]. The diagnosis was made after clinical manifestations, routine analysis or familial screening in 56, 34 and 10% of cases, respectively, (n = 58; data not available for 19 patients). Chondrocalcinosis was present in 11/51 patients (22%), bone fractures in 8/56 (14%) and renal colic in 6/55 (11%). The median serum calcium was 2.74 mmol/L [IQR: 2.63‐2.86 mmol/L], the median plasma parathyroid hormone level was 4.9 pmol/L [3.1‐7.1], and the median 24‐hour urinary calcium excretion was 2.8 mmol/24 hours [IQR: 1.9‐4.0]. Osteoporosis (dual X‐ray absorptiometry) or kidney stones (renal ultrasonography) were found in 6/38 patients (16%) and 9/32 patients (28%), respectively. Fourteen patients (18%) underwent parathyroid surgery; parathyroid adenoma was found in three patients (21%) and parathyroid hyperplasia in nine patients (64%). No correlation between genotype and phenotype was established.ConclusionThis large cohort study demonstrates that FHH1 clinical characteristics can be atypical in 33 patients (43%). Clinicians should be aware of this rare differential diagnosis in order to adopt an appropriate treatment strategy.
Published: 2020

9. Efficacy of THN102 (a combination of modafinil and flecainide) on vigilance and cognition during 40‐hour total sleep deprivation in healthy subjects: Glial connexins as a therapeutic target

Author: Sauvet, Fabien, Erblang, Mégane, Gomez-Merino, Danielle, Rabat, Arnaud, Guillard, Mathias, Dubourdieu, Dominique, Lefloch, Hervé, Drogou, Catherine, van Beers, Pascal, Bougard, Clément, Bourrrilhon, Cyprien, Arnal, Pierrick, Rein, Werner, Mouthon, Franck, Brunner-Ferber, Francoise, Leger, Damien, Dauvilliers, Yves, Chennaoui, Mounir, Charvériat, Mathieu, Gomez‐merino, Danielle, Brunner‐ferber, Francoise, Nowak, Cécile, Sommeil-Vigilance-Fatigue et Santé Publique (VIFASOM (URP_7330)), Institut de Recherche Biomédicale des Armées (IRBA)-Université Paris Cité (UPCité), Institut de Recherche Biomédicale des Armées (IRBA), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Theranexus [Lyon], Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Recherche Biomédicale des Armées (IRBA)-Université de Paris (UP), and Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 030226 pharmacology & pharmacy, Connexins, Cognition, 0302 clinical medicine, Pharmacology (medical), 030212 general & internal medicine, media_common, Cross-Over Studies, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Wakefulness-Promoting Agents, Healthy Volunteers, flecainide, 3. Good health, Drug Combinations, Memory, Short-Term, Treatment Outcome, Anesthesia, modafinil, medicine.symptom, Arousal, Neuroglia, Somnolence, medicine.drug, Vigilance (psychology), Adult, safety, media_common.quotation_subject, psychomotor vigilance task, Placebo, working memory, Young Adult, 03 medical and health sciences, mental disorders, Tower of London test, Cardiac conduction, Reaction Time, medicine, Humans, Wakefulness, Pharmacology, business.industry, Modafinil, Psychomotor vigilance task, Original Articles, sleep deprivation, sustained attention, Sleep deprivation, executive function, business, Psychomotor Performance, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Aims THN102 is a novel combination of modafinil and low‐dose flecainide, targeting glial connexin activity to modulate modafinil effects. We investigated THN102 efficacy compared to modafinil and to placebo on vigilance and cognitive function during 40‐hour total sleep deprivation (TSD). Methods Twenty healthy men participated in a double‐blind, randomized, incomplete‐block 3‐period cross‐over trial with 5 treatments (n = 12 per group): placebo (PBO), modafinil 100 mg (MOD100), THN102 100/1, 100/3, 100/9 (modafinil 100 mg and flecainide 1, 3 or 9 mg). Each period included a baseline day and a TSD day with treatments administered 3 times (01:00, 09:00 and 19:00). Reaction time in psychomotor vigilance test, subjective somnolence and vital signs were assessed before and during treatment. Working memory (2‐Back) and executive processes (Go/noGo for vigilance and inhibition, Wisconsin card sorting task for mental flexibility, and Tower of London test for planning) were evaluated at 16:30. Results At 5 hours postdose−1 (after 23 hours TSD, primary endpoint), THN102 100/1 resulted in statistically higher psychomotor vigilance test speed vs MOD100 (3.97 ± 0.09 vs 3.74 ± 0.14, P < .05). No increase in effect was observed with higher flecainide doses in combinations. Most THN102 doses vs MOD100 also improved the number of correct responses in 2‐Back and Go errors in Go/noGo (P < .05 for all doses), and perseverative responses in Wisconsin card sorting task (for 100/1 and 100/9). No impact on cardiac conduction was noted with THN102, and safety was similar to MOD100. Conclusions THN102 seems more efficient than modafinil on vigilance, working memory and executive functions, opening new perspectives in management of hypersomnolence disorders.
Published: 2019

10. Whole‐genome sequencing revealsListeria monocytogenesdiversity and allows identification of long‐term persistent strains in Brazil

Author: Marc Lecuit, Srinand Sreevatsan, Douglas R. Call, Alexandra Moura, Joshua J. Woodward, Adelle P. McFarland, Johannetsy J. Avillan, Nicole Herman, Luís Augusto Nero, Anderson Carlos Camargo, Universidade Federal de Vicosa (UFV), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Paul G. Allen School for Global Animal Health [WSU, USA], Washington State University (WSU), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, University of Washington [Seattle], Michigan State University [East Lansing], Michigan State University System, Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), The present material is based upon work supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)., The authors express their gratitude to Deyse Vallim and Ernesto Hofer from the Laboratory of Bacterial Zoonoses (FioCruz, Brazil) for provision of bacterial strains from CLIST collection., Universidade Federal de Viçosa = Federal University of Viçosa (UFV), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and DIAKITE, andrée
Subjects: Meat, Virulence, Biology, medicine.disease_cause, Microbiology, Genome, Article, resistance, 03 medical and health sciences, Listeria monocytogenes, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, Listeriosis, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Gene, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Whole genome sequencing, Genetics, whole genome sequencing, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, Genetic diversity, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 030306 microbiology, molecular typing, Genetic Variation, persistence, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Stop codon, virulence, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Food Microbiology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Multilocus sequence typing, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Brazil, Genome, Bacterial, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Multilocus Sequence Typing
Abstract: International audience; Advances in whole-genome sequencing (WGS) technologies have documented genetic diversity and epidemiology of the major foodborne pathogen Listeria monocytogenes (Lm) in Europe and North America, but data concerning South America are scarce. Here, we examined the population structure and genetic diversity of this major foodborne pathogen collected in Brazil. Based on core genome multilocus sequence typing (cgMLST), isolates from lineages I (n = 22; 63%) and II (n = 13; 37%) were distributed into 10 different sublineages (SLs) and represented 31 new cgMLST types (CTs). The most prevalent SLs were SL9 (n = 9; 26%), SL3 (n = 6; 17%) and SL2 and SL218 (n = 5; 14%). Isolates belonging to CTs L2-SL9-ST9-CT4420 and L1-SL315-ST520-CT4429 were collected 3 and 9 years apart, respectively, revealing long-term persistence of Lm in Brazil. Genetic elements associated with stress survival were present in 60% of isolates (57% SSI-1 and 3% SSI-2). Pathogenic islands were present in 100% (LIPI-1), 43% (LIPI-3) and 6% (LIPI-4) of the isolates. Mutations leading to premature stop codons were detected in the prfA and inlA virulence genes. This study is an important contribution to understanding the genomic diversity and epidemiology of Lm in South America. In addition, the results highlight the importance of using WGS to reveal Lm long-term persistence.
Published: 2019

11. Distinct oncogenes drive different genome and epigenome alterations in human mammary epithelial cells

Author: Beatrice Orsetti, Ambre Bender, Claude Sardet, Anne Saumet, Stanislas du Manoir, Elouan Cleroux, Amanda Abi-Khalil, Emeline Schmitt, Jacques Colinge, Charles Theillet, Michael Weber, William Jacot, Claire Fonti, Michael Dumas, Theillet, Charles, Blanc - Altérations épigénétiques et génétiques associées aux étapes précoces de la transformation maligne : étude d'un système modèle sur cellules primaires hMEC - - ESCATMO2009 - ANR-09-BLAN-0261 - Blanc - VALID, Identification of novel functions and regulators of DNA methylation in mammals - TRANSMETH - - EC:FP7:ERC2014-06-01 - 2019-05-31 - 615371 - VALID, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), Agence Nationale pour la Recherche ANR projet blanc ESCATMO. Anne Saumet was supported by ESCATMO, MESR doctoral fellowship to Claire Fonti. SIRIC Montpellier Cancer Grant INCa_Inserm_DGOS_12553. European Research Council ERC Consolidator grant n°615371 to Michael Weber., ANR-09-BLAN-0261,ESCATMO,Altérations épigénétiques et génétiques associées aux étapes précoces de la transformation maligne : étude d'un système modèle sur cellules primaires hMEC(2009), and European Project: 615371,EC:FP7:ERC,ERC-2013-CoG,TRANSMETH(2014)
Subjects: Cancer Research, Gene Dosage, Mice, SCID, Genome, Epigenesis, Genetic, Mice, 0302 clinical medicine, oncogene, Gene expression, Oncogene Proteins, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Cell biology, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, Oncology, 030220 oncology & carcinogenesis, DNA methylation, Heterografts, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Cell type, Mice, Nude, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Wnt1 Protein, Biology, Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Cyclin E, Animals, Humans, Epigenetics, Mammary Glands, Human, genome, Gene, 030304 developmental biology, Oncogene, Genome, Human, modifications, Epithelial Cells, cell type, Oncogenes, Epigenome, DNA Methylation, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Claire Fonti and Anne Saumet contributed equally to this work.; International audience; Molecular subtypes of breast cancer are defined on the basis of gene expression and genomic/epigenetic pattern differences. Different subtypes are thought to originate from distinct cell lineages, but the early activation of an oncogene could also play a role. It is difficult to discriminate the respective inputs of oncogene activation or cell type of origin. In this work, we wished to determine whether activation of distinct oncogenic pathways in human mammary epithelial cells (HMEC) could lead to different patterns of genetic and epigenetic changes. To this aim, we transduced shp53 immortalized HMECs in parallel with the CCNE1, WNT1 and RASv12 oncogenes which activate distinct oncogenic pathways and characterized them at sequential stages of transformation for changes in their genetic and epigenetic profiles. We show that initial activation of CCNE1, WNT1 and RASv12, in shp53 HMECs results in different and reproducible changes in mRNA and micro-RNA expression, copy number alterations (CNA) and DNA methylation profiles. Noticeably, HMECs transformed by RAS bore very specific profiles of CNAs and DNA methylation, clearly distinct from those shown by CCNE1 and WNT1 transformed HMECs. Genes impacted by CNAs and CpG methylation in the RAS and the CCNE1/WNT1 clusters showed clear differences, illustrating the activation of distinct pathways. Our data show that early activation of distinct oncogenic pathways leads to active adaptive events resulting in specific sets of CNAs and DNA methylation changes. We, thus, propose that activation of different oncogenes could have a role in reshaping the genetic landscape of breast cancer subtypes.
Published: 2019

12. An augmented food strategy leads to complete energy compensation during a 15‐day military training expedition in the cold

Author: Pauline Oustric, David Thivel, Graham Finlayson, Philippe Colin, Chloé Lavoué, Julien Siracusa, Didier Chapelot, Cyprien Bourrilhon, Keyne Charlot, Thivel, David, Institut de Recherche Biomédicale des Armées (IRBA), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), University of Leeds, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), 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), Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), 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), Laboratoire de Biologie de l'Exercice pour la Performance et la Santé (LBEPS), and Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)
Subjects: Adult, Male, energy deficiency, Food intake, Physiology, Physical Exertion, Reward value, Energy balance, 030204 cardiovascular system & hematology, Thirst, Fat mass, Eating, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Animal science, rations, Physiology (medical), [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], arctic, energy compensation, QP1-981, Humans, Medicine, military training, ComputingMilieux_MISCELLANEOUS, Carbohydrate intake, Morning, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Original Articles, Cold Temperature, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Military Personnel, Original Article, medicine.symptom, Energy Intake, Energy Metabolism, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, food preferences, Field conditions
Abstract: Soldiers on military expeditions usually fail to compensate for the increase in energy expenditure, with potential deleterious consequences. We therefore analyzed the characteristics of energy compensation in 12 male soldiers, during a 15‐day expedition in the cold, while alleviating some of the contextual limitations of food intake (~20‐MJ daily bags of easy‐to‐use, highly palatable and familiar foods with multiple and long breaks allowed during the day). Body and fat mass losses were low and moderate, respectively (−1.13 ± 1.42% and −19.5 ± 15.6%, respectively, p, We analyzed the characteristics of energy compensation in 12 male soldiers, during a 15‐day expedition in the cold, while alleviating some of the contextual limitations of food intake (~20‐MJ daily bags of easy‐to‐use, highly palatable and familiar foods with multiple and long breaks allowed during the day). This study indicates that complete energy compensation can be reached in challenging field conditions when food intake is facilitated, offering some guidelines to limit energy deficit during operational missions.
Published: 2021

13. Bernard–Soulier syndrome: first human case due to a homozygous deletion of GP9 gene

Author: Florentine Garaix, Dorsaf Ghalloussi, Michel Tsimaratos, Caroline Rousset‐Rouvière, Noémie Saut, Marie-Christine Alessi, Hervé Chambost, Paul Saultier, Véronique Baccini, Cornel Popovici, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire d'hématologie biologique [Hôpital de la Timone - Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de pédiatrie, d'hématologie et d'oncologie [Hôpital de La Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), and Prémilleux, Annick
Subjects: Male, Platelet aggregation, [SDV]Life Sciences [q-bio], Platelet disorder, thrombocytopenia, platelet membrane, Biology, platelet genetic diseases, Bernard–Soulier syndrome, 03 medical and health sciences, 0302 clinical medicine, Bone Marrow, medicine, Humans, platelet disorders, Gene, Sequence Deletion, 030304 developmental biology, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Infant, Newborn, Bernard-Soulier Syndrome, Hematology, medicine.disease, Pedigree, 3. Good health, [SDV] Life Sciences [q-bio], Platelet Glycoprotein GPIb-IX Complex, platelet aggregation, Immunology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: International audience; Bernard–Soulier Syndrome (BSS) is a rare (1:1 million) hereditary bleeding disorder caused by defects in the platelet glycoprotein (GP)‐Ib/IX/V complex, a receptor for von Willebrand factor (VWF) and thrombin (Lanza, 2006; Berndt & Andrews, 2011). Patients typically present with epistaxis, petechial or gingival bleeding with onset already in infancy. They present with macrothrombocytopenia and their platelets do not agglutinate in response to ristocetin, while maintaining a normal aggregation in response to a variety of aggregating agents. GPIb/IX/V complex consists of two GPIbα and four GPIbβ subunits stabilized by disulphide bonds (Luo et al., 2007). This heterodimer is non‐covalently associated with two GPIX and one GPV subunits. The N‐terminal residues of GPIbα form seven leucine‐rich repeats (LRRs) and include the binding sites for VWF and thrombin. BSS is due to biallelic loss‐of‐function pathogenic variants (deletions, insertions and nonsense mutations) in GPIBA, GPIBB or GP9 genes encoding GPIb/IX/V complex (Savoia et al., 2014). However, so far, no mutation in GP5 causing BSS has been reported yet. Most of the mutations prevent the formation of the complex or trafficking it through the endoplasmic reticulum and Golgi apparatus and alter receptor expression (Salles et al., 2008; Savoia et al., 2011; Nurden et al., 2012).
Published: 2020

14. A clinical and histopathological study of malformations observed in fetuses infected by the Zika virus

Author: Marc Thiry, Christian Alfano, Férechté Encha-Razavi, Marine Driessen, Tania Attié-Bitach, Michel Vekemans, Marianne Leruez-Ville, Laurent Nguyen, Yves Ville, Thérèse Couderc, Marc Lecuit, Aurélie Beaufrère, Nicolas Thelen, Maryse Bonnière, Bettina Bessières, Laboratoire Histologie Embryologie Cytogénétique [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), Service de Gynécologie Obstétrique [CHU Necker], GIGA-Neurosciences [Université Liège], GIGA [Université Liège], Université de Liège-Université de Liège, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This project was funded in part by the European Union's Horizon 2020 Research and Innovation Program under ZIKAlliance Grant Agreement N° 734548 (to L.N. and M.L.) and by the LabEx IBEID, Institut Pasteur, and INSERM., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 734548,ZIKAlliance(2016), DIAKITE, andrée, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, A global alliance for Zika virus control and prevention - ZIKAlliance - 2016-10-01 - 2019-09-30 - 734548 - VALID, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP]
Subjects: 0301 basic medicine, Microcephaly, Pathology, [SDV]Life Sciences [q-bio], MESH: Brain/virology, Zika virus, MESH: Pregnancy, 0302 clinical medicine, Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, microcephaly, Research Articles, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Zika Virus Infection, General Neuroscience, MESH: Aborted Fetus/physiopathology, Brain, meningoencephalitis, Meningoencephalitis, 3. Good health, Micrencephaly, [SDV] Life Sciences [q-bio], fetus, MESH: Brain/pathology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Aborted Fetus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, ER stress, Meningitis, Brazil, Hydrocephalus, medicine.medical_specialty, MESH: Hydrocephalus/pathology, MESH: Microcephaly, Pathology and Forensic Medicine, ZIKV infection, 03 medical and health sciences, MESH: Zika Virus Infection/pathology, medicine, Humans, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Fetus, MESH: Humans, business.industry, MESH: Fetus, Zika Virus, MESH: Zika Virus/pathogenicity, medicine.disease, biology.organism_classification, 030104 developmental biology, Neurology (clinical), MESH: Brazil, business, MESH: Female, micrencephaly, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; Background: The recent outbreak of Zika virus (ZIKV) infection and the associated increased prevalence of microcephaly in Brazil underline the impact of viral infections on embryo-fetal development. The aim of the present study is to provide a detailed clinical and histopathological study of the fetal disruption caused by the ZIKV, with a special focus on the associated neuropathological findings. Methods: A detailed feto-placental examination, as well as neuropathological and neurobiological studies were performed on three fetuses collected after pregnancy termination between 22 and 25 weeks of gestation (WG), because brain malforma-tions associated with a maternal and fetal ZIKV infection was diagnosed. Results: In all three cases, the maternal infection occurred during the first trimester of pregnancy. A small head was observed on the ultrasound examination of the second trimester of pregnancy and led to the diagnosis of ZIKV fetopathy and pregnancy termination. The fetal histopathological examination was unremarkable on the viscera but showed on the testis an interstitial lymphocytic infiltrate. The placenta contained a Hofbauer cells hyperplasia with signs of inflammation. Neu-ropathological findings included a meningoencephalitis and an ex vacuo hydrocepha-lus. Immunohistochemical studies showed the presence of T lymphocytic and histiocytic meningitis associated with an abundant cerebral astroglial and macrophagic reaction. In situ hybridization demonstrated, abundant ZIKV particles within the cerebral parenchyma mainly in the ventricular/subventricular zone and in the cortical plate. In addition massive cells death and endoplasmic reticulum damage were present. Conclusion: The present study reports on the clinical and histopathological findings observed in three fetuses infected by the ZIKV. It emphasizes the severity of brain damages and the minimal visceral and placental changes observed upon ZIKV infection. This confirms the selective neurotropism of ZIKV. Finally, it allows us to describe the cascade of multifactorial developmental defects leading to microcephaly.
Published: 2018

15. Aspergillus fumigatus in cystic fibrosis: An update on immune interactions and molecular diagnostics in allergic bronchopulmonary aspergillosis

Author: Joana Vitte, Jean-Christophe Dubus, Thomas Romain, Martine Reynaud-Gaubert, Stéphane Ranque, Ania Carsin, Jean-Louis Mege, COMBE, Isabelle, Assistance Publique - Hôpitaux de Marseille (APHM), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), and INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, Cystic Fibrosis, Immunology, Cystic fibrosis, Aspergillus fumigatus, 03 medical and health sciences, 0302 clinical medicine, Immune system, Fibrosis, medicine, Humans, Immunology and Allergy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, business.industry, Aspergillosis, Allergic Bronchopulmonary, biology.organism_classification, medicine.disease, Molecular diagnostics, 3. Good health, 030104 developmental biology, 030228 respiratory system, Respiratory failure, Host-Pathogen Interactions, biology.protein, Antibody, Allergic bronchopulmonary aspergillosis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; A wide spectrum of pathological conditions may result from the interaction of Aspergillus fumigatus and the immune system of its human host. Allergic bronchopulmonary aspergillosis is one of the most severe A.fumigatus-related diseases due to possible evolution toward pleuropulmonary fibrosis and respiratory failure. Allergic bronchopulmonary aspergillosis occurs almost exclusively in cystic fibrosis or asthmatic patients. An estimated 8%-10% of patients with cystic fibrosis experience this condition. The diagnosis of allergic bronchopulmonary aspergillosis relies on criteria first established in 1977. Progress in the understanding of host-pathogen interactions in A.fumigatus and patients with cystic fibrosis and the ongoing validation of novel laboratory tools concur to update and improve the diagnosis of allergic bronchopulmonary aspergillosis.
Published: 2017

16. Prospective assessment of the predictive value of the BRCA1 gene status in sarcoma patients treated with trabectedin: an updated analysis of the EORTC 62091 trial

Author: F. Collin, Philippe Pourquier, Antoine Italiano, Saskia Litière, Nathan Touati, Alessandro Gronchi, Laboratory of Solid Tumors Genetics, Nice University Hospital, European Organization for Research and Treatment of Cancer (EORTC), EORTC, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Signalisation et Mecanismes Moleculaires de l'Apoptose, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Val d'Aurelle - Paul Lamarque, Institut Bergonié [Bordeaux], Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], and Herrada, Anthony
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], education, [SDV.CAN]Life Sciences [q-bio]/Cancer, law.invention, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Randomized controlled trial, law, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Trabectedin, Brca1 gene, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Clinical Cancer Research, medicine.disease, Predictive value, 3. Good health, Clinical trial, Editorial, 030104 developmental biology, 030220 oncology & carcinogenesis, Predictive value of tests, Sarcoma, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; We describe the predictive value of BRCA1 gene status on trabectedin efficacy and found no correlation despite the mechanisms of action of this drug that rely on DNA repair systems.
Published: 2018

17. Anatomical, functional and quality-of-life results for mastoid and epitympanic obliteration with bioactive glass s53p4: a prospective clinical study

Author: Daniele Bernardeschi, Evelyne Ferrary, Olivier Sterkers, Yann Nguyen, Nadya Pyatigorskaya, Daniele De Seta, Giulia Corallo, Francesca Yoshie Russo, HAL-UPMC, Gestionnaire, Réhabilitation Chirurgicale mini-Invasive et Robotisée de l'Audition, Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oto-Rhino-Laryngologie [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), Unité d’Otologie, implants auditifs et chirurgie de la base du crâne [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Università degli Studi di Siena = University of Siena (UNISI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Male, middle-ear, revision, Tympanic Membrane, Mastoidectomy, medicine.medical_treatment, Dentistry, Otoscopy, surgery, 0302 clinical medicine, Quality of life, Surveys and Questionnaires, Prospective Studies, 030223 otorhinolaryngology, Prospective cohort study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, bone-graft, cavities, Cholesteatoma, Middle Aged, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Adult, Reoperation, medicine.medical_specialty, Adolescent, canal wall, 03 medical and health sciences, Patient experience, otorhinolaryngologic diseases, medicine, Humans, cholesteatoma, Aged, chronic otitis-media, granules, Bioactive glass S53P4, business.industry, Tympanoplasty, medicine.disease, Surgery, Otorhinolaryngology, Bone Substitutes, Quality of Life, Prospective clinical study, Glass, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objective To analyse the anatomical, functional and quality-of-life results when using bioactive glass in mastoid and epitympanic obliteration. Design Prospective clinical study. Setting Tertiary referral centre. Participants Forty-one cases (39 patients) operated between May 2013 and January 2015. Main outcome measures Anatomical results were evaluated by otomicroscopy 1 year after surgery and using imaging to detect residual disease. Functional results were studied by postoperative hearing gain. Quality of life was assessed with the Glasgow Benefit Inventory questionnaire and the success of surgery by a surgery-specific questionnaire. Results At 1 year, all patients presented a well-healed external auditory canal, with an intact tympanic membrane. In cases with cholesteatoma (n = 23), no recurrent retraction pockets or residual disease were observed on imaging studies. The overall air–bone gap closure was 7.7 ± 1.84 dB (mean ± se of the mean, P < 0.001, paired t-test). No significant differences were found on hearing results when comparing primary versus revision surgery, canal-wall-up versus canal-wall-down obliterations, type of tympanoplasty and presence of cholesteatoma (multifactor anova). The Glasgow Benefit Inventory improved with an average score of 28 and the success of surgery questionnaire showed a significant improvement in ear discharge and a moderate improvement in hearing and equilibrium. Conclusions The use of bioactive glass for mastoid and epitympanic obliteration in canal-wall-down or canal-wall-up tympanoplasties is an effective procedure in both primary and revision surgery. The anatomical and functional results appear to be well correlated with patient experience and to the improvement in quality of life.
Published: 2016

18. A Kv7.2 mutation associated with early onset epileptic encephalopathy with suppression-burst enhances Kv7/M channel activity

Author: Florence Molinari, Laurent Aniksztejn, Mathieu Milh, Jérôme Devaux, Laurent Villard, Affef Abidi, Hélène Becq, Caroline Lacoste, Agathe Roubertie, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Hôpital Lapeyronie [Montpellier] (CHU), Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U901), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie et neurologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Villard, Laurent, and Institut des Neurosciences de Montpellier (INM)
Subjects: Male, 0301 basic medicine, Indoles, Patch-Clamp Techniques, Pyridines, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.GEN] Life Sciences [q-bio]/Genetics, Phenylenediamines, medicine.disease_cause, Hippocampus, Linopirdine, Membrane Potentials, 0302 clinical medicine, KCNQ2 Potassium Channel, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], M-current, ComputingMilieux_MISCELLANEOUS, Neurons, KCNQ2, Membrane potential, Mutation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Axon initial segment, Potassium channel, Cell biology, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Neurology, Anticonvulsants, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Spasms, Infantile, medicine.drug, Ankyrins, CHO Cells, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Cricetulus, Potassium Channel Blockers, medicine, Animals, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Patch clamp, [SDV.GEN]Life Sciences [q-bio]/Genetics, Potassium channel blocker, Early onset epileptic encephalopathy, Electric Stimulation, 030104 developmental biology, Gain of function, Carbamates, Neurology (clinical), Neuroscience, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; Mutations in the KCNQ2 gene encoding the voltage-gated potassium channel subunit Kv7.2 cause early onset epileptic encephalopathy (EOEE). Most mutations have been shown to induce a loss of function or to affect the subcellular distribution of Kv7 channels in neurons. Herein, we investigated functional consequences and subcellular distribution of the p.V175L mutation of Kv7.2 (Kv7.2 V175L) found in a patient presenting EOEE. We observed that the mutation produced a 25–40 mV hyperpolarizing shift of the conductance–voltage relationship of both the homomeric Kv7.2 V175L and hetero-meric Kv7.2 V175L /Kv7.3 channels compared to wild-type channels and a 10 mV hyper-polarizing shift of Kv7.2 V175L /Kv7.2/Kv7.3 channels in a 1:1:2 ratio mimicking the patient situation. Mutant channels also displayed faster activation kinetics and an increased current density that was prevented by 1 lM linopirdine. The p.V175L mutation did not affect the protein expression of Kv7 channels and its localization at the axon initial segment. We conclude that p.V175L is a gain of function mutation. This confirms previous observations showing that mutations having opposite consequences on M channels can produce EOEE. These findings alert us that drugs aiming to increase Kv7 channel activity might have adverse effects in EOEE in the case of gain-of-function variants.
Published: 2016

19. MIFlowCyt‐EV: a framework for standardized reporting of extracellular vesicle flow cytometry experiments

Author: Welsh, Joshua A, Van Der Pol, Edwin, Arkesteijn, Ger J A, Bremer, Michel, Brisson, Alain, Coumans, Frank, Dignat-George, Françoise, Duggan, Erika, Ghiran, Ionita, Giebel, Bernd, Görgens, André, Hendrix, An, Lacroix, Romaric, Lannigan, Joanne, Libregts, Sten F W M, Lozano-Andrés, Estefanía, Morales-Kastresana, Aizea, Robert, Stephane, De Rond, Leonie, Tertel, Tobias, Tigges, John, De Wever, Olivier, Yan, Xiaomei, Nieuwland, Rienk, Wauben, Marca H M, Nolan, John P, Jones, Jennifer C, LS Celbiologie-Algemeen, Celbiologie, dB&C I&I, ProdInra, Migration, National Cancer Institute, Vrije Universiteit Amsterdam [Amsterdam] (VU), Utrecht University [Utrecht], University of Duisberg Essen, Partenaires INRAE, Université Bordeaux, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), The Scintillon Institute, Harvard Medical School [Boston] (HMS), Evox Therapeutics Limited, University of Duisburg-Essen, Karolinska Institutet [Stockholm], Ghent University Hospital, Aix Marseille Université (AMU), University of Virginia, University of Cambridge [UK] (CAM), Beth Israel Deaconess Medical Center, Xiamen University, 1ZIA-BC011502, NIH UG3 TR002881, VENI 13681 VENI 15924, NIH UG3 TR002881 U01-126497 U01-OD -019750 R01 CA218500 R01 HL1266497, LS Celbiologie-Algemeen, Celbiologie, dB&C I&I, VU University Amsterdam, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, CCA - Imaging and biomarkers, ACS - Microcirculation, Graduate School, and Laboratory Specialized Diagnostics & Research
Subjects: 0301 basic medicine, Histology, Standardization, Computer science, SOCIETY, Medizin, Médecine humaine et pathologie, cytométrie de flux, standardisation, Sample (statistics), Extracellular vesicles, Field (computer science), 03 medical and health sciences, Consistency (database systems), 0302 clinical medicine, framework, Medicine and Health Sciences, lcsh:QH573-671, standardization, reporting, Measure (data warehouse), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, lcsh:Cytology, MICROPARTICLES, flow cytometry, vésicule extracellulaire, Cell Biology, Extracellular vesicle, Data science, 030104 developmental biology, 030220 oncology & carcinogenesis, CELLS, Key (cryptography), Human health and pathology, Position Paper, SENSITIVITY, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Extracellular vesicles (EVs) are small, heterogeneous and difficult to measure. Flow cytometry (FC) is a key technology for the measurement of individual particles, but its application to the analysis of EVs and other submicron particles has presented many challenges and has produced a number of controversial results, in part due to limitations of instrument detection, lack of robust methods and ambiguities in how data should be interpreted. These complications are exacerbated by the field's lack of a robust reporting framework, and many EV-FC manuscripts include incomplete descriptions of methods and results, contain artefacts stemming from an insufficient instrument sensitivity and inappropriate experimental design and lack appropriate calibration and standardization. To address these issues, a working group (WG) of EV-FC researchers from ISEV, ISAC and ISTH, worked together as an EV-FC WG and developed a consensus framework for the minimum information that should be provided regarding EV-FC. This framework incorporates the existing Minimum Information for Studies of EVs (MISEV) guidelines and Minimum Information about a FC experiment (MIFlowCyt) standard in an EV-FC-specific reporting framework (MIFlowCyt-EV) that supports reporting of critical information related to sample staining, EV detection and measurement and experimental design in manuscripts that report EV-FC data. MIFlowCyt-EV provides a structure for sharing EV-FC results, but it does not prescribe specific protocols, as there will continue to be rapid evolution of instruments and methods for the foreseeable future. MIFlowCyt-EV accommodates this evolution, while providing information needed to evaluate and compare different approaches. Because MIFlowCyt-EV will ensure consistency in the manner of reporting of EV-FC studies, over time we expect that adoption of MIFlowCyt-EV as a standard for reporting EV- FC studies will improve the ability to quantitatively compare results from different laboratories and to support the development of new instruments and assays for improved measurement of EVs.
Published: 2020

20. Non‐proteinuric renal al amyloidosis in waldenström's macroglobulinemia

Author: Dominique Guerrot, Arnaud François, Isabelle Etienne, Anaïs Lesourd, Service des maladies infectieuses et tropicales [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Equipe de Recherche sur les Rationalités Philosophiques et les Savoirs (ERRAPHIS), Université Toulouse - Jean Jaurès (UT2J), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA), Service de néphrologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de Néphrologie [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université de Toulouse (UT)-Université de Toulouse (UT), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], VILLIER, Venceslas, Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), and Département de Pathologie [CHU Rouen]
Subjects: 0303 health sciences, Pathology, medicine.medical_specialty, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Kidney pathology, Macroglobulinemia, General Medicine, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Renal AL amyloidosis, Nephrology, medicine, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030304 developmental biology, Biopsy methods
Abstract: International audience
Published: 2019

21. Interleukin-10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection byStreptococcus pneumoniae

Author: Hernán F. Peñaloza, Pamela A. Nieto, Natalia Muñoz-Durango, María José Parga, Javiera Torres, Francisco J. Salazar-Echegarai, Manuel Álvarez-Lobos, Susan M. Bueno, Claudia A. Riedel, Alexis M. Kalergis, Departamento de Microbiologıa y Genetica Molecular [Santiago, Chile] (Facultad de Ciencias Biologicas), Pontificia Universidad Católica de Chile (UC), Departamento de Anatomia Patologica [Santiago, Chile] (Facultad de Medicina), Departamento de Gastroenterologıa [Santiago, Chile] (Facultad de Medicina), Departamento de Ciencias Biologicas [Santiago, Chile] (Facultad de Ciencias Biologicas y Facultad de Medicina), Universidad Andrés Bello [Santiago] (UNAB), 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), Departamento de Inmunologıa Clınica y Reumatologıa [Santiago, Chile] (Escuela de Medicina), This study was supported by the following grants: FONDO NACIONAL DE CIENCIA Y TECNOLOGIA DE CHILE (FONDECYT numbers 1140010, 1110604, 1100971, 1131012, 1150862 and 1110397), Millennium Institute on Immunology and Immunotherapy P09/016-F and Grant ‘Nouvelles Equipes-nouvelles thématiques’ from the La Région Pays De La Loire. HFP, PAN, NMD and MJP are supported by the Comision Nacional de Investigacion Cientıﬁca y Tecnologica (CONICYT). AMK is a Chaire De La Région Pays De La Loire, Chercheur Etranger D’excel-lence, France., and Le Bihan, Sylvie
Subjects: medicine.medical_treatment, Interleukin-1beta, Immunology, Inflammation, Biology, medicine.disease_cause, Pathogenesis, Sepsis, Interferon-gamma, Mice, 03 medical and health sciences, 0302 clinical medicine, neutrophils, Streptococcus pneumoniae, medicine, Animals, Immunology and Allergy, Lung, 030304 developmental biology, Mice, Knockout, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Tumor Necrosis Factor-alpha, bacterial infection, Brain, Original Articles, Pneumonia, Pneumococcal, medicine.disease, Bacterial Load, cytokines, Interleukin-10, respiratory tract diseases, 3. Good health, Mice, Inbred C57BL, Interleukin 10, Otitis, Cytokine, Neutrophil Infiltration, Pneumococcal pneumonia, systemic bacterial infection, medicine.symptom, lung inﬂammation, Spleen, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: International audience; Streptococcus pneumoniae is a major aetiological agent of pneumonia worldwide, as well as otitis media, sinusitis, meningitis and sepsis. Recent reports have suggested that inﬂammation of lungs due to S. pneumoniae infection promotes bacterial dissemination and severe disease. However, the contribution of anti-inﬂammatory molecules to the pathogenesis of S. pneumoniae remains unknown. To elucidate whether the production of the anti-inﬂammatory cytokine interleukin-10 (IL-10) is beneﬁcial or detrimental for the host during pneumococcal pneumonia, we performed S. pneumoniae infections in mice lacking IL-10 (IL-10[-/-] mice). The IL-10/[-/-] mice showed increased mortality, higher expression of proinﬂammatory cytokines, and an exacerbated recruitment of neutrophils into the lungs after S. pneumoniae infection. However, IL-10[-/-] mice showed signiﬁcantly lower bacterial loads in lungs, spleen, brain and blood, when compared with mice that produced this cytokine. Our results support the notion that production of IL-10 during S. pneumoniae infection modulates the expression of pro-inﬂammatory cytokines and the inﬁltration of neutrophils into the lungs. This feature of IL-10 is important to avoid excessive inﬂammation of tissues and to improve host survival, even though bacterial dissemination is less efﬁcient in the absence of this cytokine.
Published: 2015

22. Physical Activity and Amyloid-β Brain Levels in Elderly Adults with Intact Cognition and Mild Cognitive Impairment

Author: Claire Vinel, Philipe De Souto Barreto, Marc Bonnefoy, Francois Cotton, PERRET Bertrand, Olivier Rouaud, Pierre Payoux, Christophe Cognard, Daviet, Jean-Christophe, Géosciences Paris Sud ( GEOPS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CRLCC Eugène Marquis ( CRLCC ), Epidémiologie et anlyses en santé publique: risques, maladies chroniques et handicaps, Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Géosciences Paris Sud (GEOPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: Male, Oncology, Gerontology, Apolipoprotein E, medicine.medical_specialty, Multivariate analysis, Amyloid, Physical activity, Standardized uptake value, Motor Activity, Cognition, Alzheimer Disease, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, Humans, Medicine, Dementia, Cognitive Dysfunction, Aged, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Amyloid beta-Peptides, medicine.diagnostic_test, business.industry, Brain, medicine.disease, Cross-Sectional Studies, Positron emission tomography, Positron-Emission Tomography, Female, Geriatrics and Gerontology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectives To examine the associations between amyloid-β brain deposition and physical activity (PA) in elderly adults without dementia and to investigate whether the association has a dose-response relationship. Design Cross-sectional study. Setting French community-dwelling people. Participants Elderly adults with normal or mildly impaired cognition (mean age 74.7 ± 4.2; 60.4% female) with available information on current self-reported PA and amyloid-β brain deposition measured using positron emission tomography (PET) using the PET-ligand florbetapir F 18 (n = 268). Measurements A standardized uptake value ratio (SUVR) was obtained for each subject. Participants were divided according to amyloid plaque cortical retention defined according to a SUVR cutoff of 1.10 (SUVR+ vs SUVR−). Results Bivariate and multivariate analyses showed that PA was not significantly associated with SUVR. SUVR+ and SUVR− participants did not differ in terms of volume (continuous PA variables) and levels (categorical PA variables) of PA. PA was not correlated with SUVR in apolipoprotein E e4 carriers or noncarriers. PA was not associated with cognitive function. Conclusion Although PA protects against dementia, there is no solid evidence that this protection involves a reduction in amyloid-β brain deposition. Further studies are needed to determine whether PA (ideally measured at several time-points using objective measures) is involved in the pathophysiology of Alzheimer's disease.
Published: 2015

23. Physical Activity Level Among Stroke Patients Hospitalized in a Rehabilitation Unit

Author: Stéphane Mandigout, Jean-Yves Salle, Jean-Christophe Daviet, Benoit Borel, Justine Lacroix, B. Kammoun, Daviet, Jean-Christophe, Handicap, Activité, Vieillissement, Autonomie, Environnement (HAVAE), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service de Médecine Physique et de Réadaptation [CHU Limoges], CHU Limoges, and Université de Limoges (UNILIM)
Subjects: Male, 030506 rehabilitation, medicine.medical_specialty, Time Factors, Stroke patient, Barthel index, medicine.medical_treatment, Physical Therapy, Sports Therapy and Rehabilitation, 03 medical and health sciences, 0302 clinical medicine, Accelerometry, medicine, Humans, Exercise, Stroke, Aged, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Rehabilitation, business.industry, Stroke Rehabilitation, Rehabilitation unit, Middle Aged, medicine.disease, Physical activity level, Hospitalization, Neurology, Physical therapy, Female, Neurology (clinical), Energy Metabolism, 0305 other medical science, business, Hospital Units, Simple correlation, Body mass index, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Background The current literature contains little information about the level of physical activity of hospitalized patients who have had a stroke. Improving knowledge in the area could help optimize rehabilitation. Objectives To determine the level of physical activity of hospitalized patients who have had a stroke to discover if they achieved the recommended 30 minutes of physical activity per day (equivalent to 142 kcal) during sessions of 10 consecutive minutes. Setting Physical and Rehabilitation Medicine Unit of the Jean Rebeyrol Hospital, Limoges, France. Participants All patients (N = 88) who had sustained a stroke within the previous 6 months were included over a period of 7 months. Main Outcome Measures The duration of physical activity and related energy expenditure were estimated using a SenseWear armband (BodyMedia [Jawbone]). Subjects wore the sensor on the nonparetic arm for 2 consecutive days from 9 am to 4:30 pm, corresponding to the period spent daily on rehabilitation. The Fisher simple correlation test and Mann-Whitney nonparametric test were performed. Results A total of 88 patients aged 66 ± 17 years with a mean poststroke period of 43 ± 34 days and a mean Barthel Index of 61 ± 25/100 were enrolled in the study. Between 9 am and 4:30 pm, patients took part in an average of 23 ± 30 minutes of physical activity (equivalent to 91 ± 122 kcal). Correlations were found between physical activity time in the hospital and physical activity before the stroke occurred ( r = 0.345, P r = 0.284, P = .0002), body mass index ( r = −0.440, P r = −0.183, P = .0194). Conclusion It was found that 62% of patients did not achieve the recommended amount of physical activity. Sessions dedicated to physical activity could motivate patients who have had a stroke and help them meet recommendations before leaving the rehabilitation unit.
Published: 2015

24. Variants associated with Gaucher disease in multiple system atrophy

Author: Shigeru Koyano, Masatoyo Nishizawa, Masashi Aoki, Ryuji Kaji, Paola Sandroni, Yasuo Nakahara, Eliezer Masliah, Yuishin Izumi, Sid Gilman, Akio Kikuchi, Masaaki Matsushima, Susumu Kusunoki, Hiroyuki Ishiura, Yaeko Ichikawa, Miho Murata, Mizuki Ito, Tatsuhiko Yuasa, Takeo Kato, Takamichi Hattori, Ullrich Wüllner, Mitsunori Yamada, Atsushi Iwata, Kenju Hara, Caroline M. Tanner, Alexis Brice, Laurie J. Ozelius, Yoshiyuki Kuroiwa, Kazuaki Kanai, Walter A. Kukull, Garth A. Nicholson, Alexandra Durr, Kinya Ishikawa, Tomoyoshi Kondo, Jun Mitsui, Hidenao Sasaki, Hidehiro Mizusawa, Akiyoshi Kakita, Kenji Nakashima, Phillip A. Low, Masahiro Horiuchi, Thomas Klockgether, Shoji Tsuji, Jun Goto, Satoshi Kuwabara, Ichiro Yabe, John Q. Trojanowski, Shigeo Murayama, Hidetoshi Date, Alessandro Filla, Mathew B. Stern, Hiroshi Takashima, Tsutomu Yasuda, Tatiana Foroud, Yuji Takahashi, Hitoshi Takahashi, Gen Sobue, Yasushi Osaki, Osamu Onodera, Nobutaka Hattori, Tatsushi Toda, Virginia M.-Y. Lee, Kazuko Hasegawa, Kimihito Arai, Takashi Matsukawa, Hirohisa Watanabe, Yoshio Momose, Mitsutoshi Yamamoto, Kenichi Yasui, Wataru Satake, Budrul Ahsan, Hijiri Ito, Department of neurology, The University of Tokyo (UTokyo), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Department of neurology and geriatrics, Kagoshima University, Department of pathology, Niigata University, department of clinical research, Department of Neurology and Neurological Science, Tokyo Medical and Dental University-Graduate School of Medicine, Division of neurology, Chiba University, Department of clinical neurology and stroke medicine, Yokohama National University, Sagamihara National Hospital, Kamagaya Hospital, Department of clinical neuroscience, University of Tokushima, Tokushima University-Tokushima University, Departments of neurology, hematology, metabolism, endocrinology and diabetology, YAMAGATA UNIVERSITY, Yamagata University-Yamagata University, Department of geriatrics, cardiology and neurology, Kochi Medical school, St. Marianna University, Kawasaki, Department of neuropathology and the Brain bank for aging research, Tokyo Metropolitan Institute of Gerontology, National center hospital of neurology and psychiatry, Division of neurology/molecular brain science, Kobe University, Department of Neurological Sciences, Università degli studi di Napoli Federico II, Rheinische Friedrich-Wilhelms-Universität Bonn, Concord Hospital, Michigan State University [East Lansing], Michigan State University System-Michigan State University System, Parkinson's disease research education and clinical center, Department of epidemiology, University of Washington [Seattle], Parkinson's disease and movement disorders center, University of Pennsylvania [Philadelphia], Institute of aging, Udall Parkinson's research center, Department of neurosciences, University of California [San Diego] (UC San Diego), University of California-University of California, Departments of genetics and genomic sciences and neurology, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University System-Indiana University System, Administateur, HAL Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sagamihara National Hospital [Kanagawa, Japan], University of Naples Federico II = Università degli studi di Napoli Federico II, University of Pennsylvania, University of California (UC)-University of California (UC), Mitsui, Jun, Matsukawa, Takashi, Sasaki, Hidenao, Yabe, Ichiro, Matsushima, Masaaki, Dürr, Alexandra, Brice, Alexi, Takashima, Hiroshi, Kikuchi, Akio, Aoki, Masashi, Ishiura, Hiroyuki, Yasuda, Tsutomu, Date, Hidetoshi, Ahsan, Budrul, Iwata, Atsushi, Goto, Jun, Ichikawa, Yaeko, Nakahara, Yasuo, Momose, Yoshio, Takahashi, Yuji, Hara, Kenju, Kakita, Akiyoshi, Yamada, Mitsunori, Takahashi, Hitoshi, Onodera, Osamu, Nishizawa, Masatoyo, Watanabe, Hirohisa, Ito, Mizuki, Sobue, Gen, Ishikawa, Kinya, Mizusawa, Hidehiro, Kanai, Kazuaki, Hattori, Takamichi, Kuwabara, Satoshi, Arai, Kimihito, Koyano, Shigeru, Kuroiwa, Yoshiyuki, Hasegawa, Kazuko, Yuasa, Tatsuhiko, Yasui, Kenichi, Nakashima, Kenji, Ito, Hijiri, Izumi, Yuishin, Kaji, Ryuji, Kato, Takeo, Kusunoki, Susumu, Osaki, Yasushi, Horiuchi, Masahiro, Kondo, Tomoyoshi, Murayama, Shigeo, Hattori, Nobutaka, Yamamoto, Mitsutoshi, Murata, Miho, Satake, Wataru, Toda, Tatsushi, Filla, Alessandro, Klockgether, Thoma, Wüllner, Ullrich, Nicholson, Garth, Gilman, Sid, Tanner, Caroline M, Kukull, Walter A, Stern, Mathew B, Lee, Virginia M. Y, Trojanowski, John Q, Masliah, Eliezer, Low, Phillip A, Sandroni, Paola, Ozelius, Laurie J, Foroud, Tatiana, and Tsuji, Shoji
Subjects: medicine.medical_specialty, Disease, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Logistic regression, Bioinformatics, Gastroenterology, Atrophy, Internal medicine, mental disorders, medicine, ddc:610, Research Articles, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Dementia with Lewy bodies, [SCCO.NEUR]Cognitive science/Neuroscience, General Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Odds ratio, medicine.disease, Control subjects, Confidence interval, nervous system diseases, 3. Good health, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Neurology (clinical), business, Glucocerebrosidase, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objective : Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case–control series.Methods : We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants.Results : In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel–Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14–5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15–5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 × 10−3).Interpretation : The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.
Published: 2015

25. Improving postpartum glucose screening after gestational diabetes mellitus: a cohort study to evaluate the multicentre IMPACT initiative

Author: Lionel Carbillon, C. Khiter, D. Leboeuf, L. Vittaz, F. Faghfouri, Hélène Bihan, Paul Valensi, A. Lepagnol, Gérard Reach, H. Dauphin, Emmanuel Cosson, ProdInra, Migration, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Nord (Paris 13), Université Paris Descartes - Paris 5 (UPD5), Ballanger Hospital, Partenaires INRAE, De La Fontaine Hospital, Hôpital Privé de la Seine Saint Denis, De La Fontaine Hospital, Department of Obstetrics and Gynecology, and Novo Nordisk, France
Subjects: epices score, Endocrinology, Diabetes and Metabolism, Suburban Health, deprivation, Cohort Studies, 0302 clinical medicine, Endocrinology, prevention, Pregnancy, Risk Factors, australian woman, follow-up, Insulin, 030212 general & internal medicine, risk, 2. Zero hunger, Glucose tolerance test, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, Obstetrics, Postpartum Period, 3. Good health, Gestational diabetes, outcome, Female, France, history, guideline, Cohort study, Adult, medicine.medical_specialty, Adolescent, complication, 030209 endocrinology & metabolism, Prediabetic State, Young Adult, 03 medical and health sciences, Patient Education as Topic, Diabetes mellitus, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Retrospective Studies, Gynecology, business.industry, Retrospective cohort study, Odds ratio, Glucose Tolerance Test, medicine.disease, Diabetes, Gestational, Early Diagnosis, Diabetes Mellitus, Type 2, Patient Compliance, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Postpartum period, Follow-Up Studies
Abstract: Aims To evaluate a mobilization campaign, the IMPACT initiative, which included multidisciplinary meetings, provision of information and a systematic prescription of an oral glucose tolerance test to improve the rate of glucose screening in women with gestational diabetes mellitus in the four largest maternity units in our area, starting in March 2011. Methods We retrospectively compared the level of self-reported screening during the first 6 months postpartum of women who gave birth after having been diagnosed with gestational diabetes before (January 2009 to December 2010) and after the IMPACT campaign (April 2011 to February 2012). Results We included 961 women (589 in the period before and 372 in the period after the campaign was initiated) with a mean ± sd age of 33.2 ± 5.3 years and BMI of 27.8 ± 5.3 kg/m². Multivariate analysis, stratified using a propensity score in order to limit bias caused by imbalance between both periods, showed that the postpartum screening rate was higher after the campaign began (48.9 vs 33.3%, odds ratio 1.7, 95% CI 1.1–2.5; P = 0.019) and higher in women who received insulin treatment during pregnancy (odds ratio 2.3, 95% CI 1.5–3.6; P
Published: 2014

26. Control of asthma by omalizumab: the role of CD4+Foxp3+regulatory T cells

Author: Philippe Saint-Pierre, B. Michaud, Jocelyne Just, Flore Amat, Anne Perrine Foray, Pauline Tallon, Lucienne Chatenoud, Nathalie C. Lambert, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'allergologie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Diabète de Type 1 : mécanismes et traitements immunologiques, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Centre de l'Asthme et des Allergies [CHU Trousseau], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Mathématiques de Toulouse UMR5219 (IMT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), AMAT, Flore, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Mathématiques de Toulouse UMR5219 ( IMT ), Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-PRES Université de Toulouse-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), and Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: 0301 basic medicine, CD4 antigen, medicine.drug_class, Immunology, Omalizumab, Disease, Immunoglobulin E, Monoclonal antibody, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Immune system, immune system diseases, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Immunology and Allergy, Medicine, ComputingMilieux_MISCELLANEOUS, Asthma, [STAT.AP]Statistics [stat]/Applications [stat.AP], [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, business.industry, FOXP3, medicine.disease, respiratory tract diseases, 3. Good health, 030104 developmental biology, 030228 respiratory system, chemistry, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; Allergic asthma is an inflammatory disease of the airways, resulting from an inappropriate immune response to inhaled allergens, which involves multiple inflammatory cells and mediators that contribute to airway hyper-responsiveness. Omalizumab is a monoclonal antibody, specifically directed to the C-Epsilon3 domain of immunoglobulin E (IgE), indicated as an additional therapy in severe allergic asthma [1]. Impaired function of regulatory T cells (Treg) is incriminated in the aberrant asthma inflammatory response [2].
Published: 2016

27. Quantitative and qualitative changes in anti‐Neu5Gc antibody response following rabbit anti‐thymocyte IgG induction in kidney allograft recipients

Author: Janka Slatinska, Shani Leviatan Ben-Arye, Petra Hruba, Hai Yu, Ondrej Viklicky, Xi Chen, Vered Padler-Karavani, Gwénaëlle Evanno, Dominique Blanchard, Jean Marie Bach, Odile Duvaux, Juliette Rousse, Apolline Salama, Jean-Paul Soulillou, Xenothera [Nantes, France], Department of Cell Research and Immunology, Tel Aviv University (TAU), Transplant laboratory [Prague, Czech Republic], Institute for Clinical and Experimental Medicine (IKEM), Department of Nephrology [Prague, Czech Republic] (Transplant Center), Department of Chemistry [Univ California Davis] (Chemistry - UC Davis), University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunoregulation And Immunointervention in Transplantation and Autoimmunity (Team 4 - U1064 Inserm - CRTI), 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)-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), Ministry of Health., Czech Republic‐conceptual development of research organization (Institute for Clinical and Experimental Medicine‐IKEM, IN 0002300)., A grant from The Israeli Ministry of Science, Technology and Space No. 62466 and the 7th Framework Program FP7‐Health‐2013‐INNOVATION‐1‐603049 of the European Commission., European Project: 603049,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,TRANSLINK(2013), Le Bihan, Sylvie, Defining the role of xeno-directed and autoimmune events in patients receiving animal-derived bioprosthetic heart valves - TRANSLINK - - EC:FP7:HEALTH2013-09-01 - 2017-08-31 - 603049 - VALID, Tel Aviv University [Tel Aviv], Department of Chemistry [Davis, CA, USA], University of California-University of California, Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), and Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Recherche Agronomique (INRA)
Subjects: Adult, Male, medicine.medical_treatment, Clinical Biochemistry, mechanism, 030204 cardiovascular system & hematology, gal, Biochemistry, Antibodies, Epitope, 03 medical and health sciences, 0302 clinical medicine, Antigen, Transplantation Immunology, Immunity, medicine, Humans, Immunologic Factors, Transplantation, Homologous, Prospective Studies, 030212 general & internal medicine, Aged, Immunity, Cellular, Thymocytes, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, n-glycolyneuraminic acid, Immunosuppression, human xeno-antoantibodies, General Medicine, Middle Aged, Kidney Transplantation, neu5gc, 3. Good health, Transplantation, Thymocyte, Cross-Sectional Studies, Polyclonal antibodies, Case-Control Studies, Immunoglobulin G, Immunology, biology.protein, Female, Neuraminic Acids, Antibody, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Antibodies of non-human mammals are glycosylated with carbohydrate antigens, such as galactose-α-1-3-galactose (α-Gal) and N-glycolylneuraminic acid (Neu5Gc). These non-human carbohydrate antigens are highly immunogenic in humans due to loss-of-function mutations of the key genes involved in their synthesis. Such immunogenic carbohydrates are expressed on therapeutic polyclonal rabbit anti-human T-cell IgGs (anti-thymocyte globulin; ATG), the most popular induction treatment in allograft recipients. To decipher the quantitative and qualitative response against these antigens in immunosuppressed patients, particularly against Neu5Gc, which may induce endothelial inflammation in both the graft and the host. We report a prospective study of the antibody response against α-Gal and Neu5Gc-containing glycans following rabbit ATG induction compared to controls. We show a drop in the overall levels of anti-Neu5Gc antibodies at 6 and 12 months post-graft compared to the pre-existing levels due to the major early immunosuppression. However, in contrast, in a cross-sectional study there was a highly significant increase in anti-Neu5Gc IgGs levels at 6 months post-graft in the ATG-treated compared to non-treated patients(P = 0.007), with a clear hierarchy favouring anti-Neu5Gc over anti-Gal response. A sialoglycan microarray analysis revealed that the increased anti-Neu5Gc IgG response was still highly diverse against multiple different Neu5Gc-containing glycans. Furthermore, some of the ATG-treated patients developed a shift in their anti-Neu5Gc IgG repertoire compared with the baseline, recognizing different patterns of Neu5Gc-glycans. In contrast to Gal, Neu5Gc epitopes remain antigenic in severely immunosuppressed patients, who also develop an anti-Neu5Gc repertoire shift. The clinical implications of these observations are discussed.
Published: 2019

28. Delayed hysteroscopic resection of retained tissues and uterine conservation after conservative treatment for placentaaccreta

Author: Philippe Soyer, Etienne Gayat, Delphine Hequet, Emmanuel Barranger, Olivier Morel, Cécile Malartic, UL, IADI, Service de gynécologie et obstétrique [Hopital Lariboisière - Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service d'Obstétrique et de Gynécologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de radiologie Ostéo-Articulaire [AP-HP, Hôpital Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, medicine.medical_specialty, Placenta accreta, Uterus, Hysteroscopy, Placenta Accreta, Pelvic Pain, Hysteroscopic resection, 03 medical and health sciences, 0302 clinical medicine, Abnormal placenta, Pregnancy, Placenta, medicine, Humans, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, business.industry, Pelvic pain, Fertility Preservation, Obstetrics and Gynecology, General Medicine, medicine.disease, 3. Good health, Surgery, Conservative treatment, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, medicine.symptom, business, Organ Sparing Treatments, Placenta, Retained, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Conservative management of both the uterus and the abnormal placenta, which is left inside the uterus at the time of delivery, is one option of placenta accreta management. Complete elimination of the residual placenta is the main challenge of this procedure. Aim To report the role, efficacy and safety of hysteroscopic resection in women presenting with severe pelvic pain and chronic intra-uterine retention after conservative treatment of placenta accreta. Material and methods Four consecutive women who were treated with hysteroscopic resection of retained tissues after conservative treatment of placenta accreta or percreta at the time of delivery. Clinical files and surgical procedures were reviewed. All procedures were performed because of chronic pelvic pain and the absence of a complete spontaneous placental elimination. Results All procedures were successful and uneventful. The uterus was conserved with a complete disappearance of the symptoms in the four women, and two of them became pregnant. Conclusion Hysteroscopic resection seems effective and safe for shortening the duration of placental elimination after conservative treatment in women with severe pelvic pain due to uterine retention. This approach allows conserving the uterus and future fertility.
Published: 2013

29. Normal values for fundus perimetry with the MAIA microperimeter and short-term repeatability evaluation

Author: Philippe Koehrer, A.M. Bron, G. Assad, F. Baudin, C Creuzot, C. Meillon, ProdInra, Migration, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre des Sciences du Goût et de l'Alimentation (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté [COMUE] (UBFC), and European Association for Vision and Eye Research (EVER). BEL.
Subjects: 0303 health sciences, medicine.medical_specialty, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, General Medicine, Normal values, Repeatability, Fundus (eye), Term (time), 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 030221 ophthalmology & optometry, Medicine, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030304 developmental biology
Abstract: National audience; Purpose To assess retinal sensitivity by means of microperimetry and to evaluate the intersession fluctuation using the MAIA microperimeter in healthy volunteers. Methods Prospective, monocentre study. Fifty‐six healthy volunteers (age range, 20–80 years), underwent an automatic, full‐threshold microperimetry of the central field (custom grid, area of 10° in diameter, 37 stimulated points), with the MAIA microperimeter (CenterVue, Padova, Italy). A subgroup of 24 subjects was retested after 1 h (test 2) and 1 week (test 3) to determine the repeatability of the technique. A subgroup of 22 subjects was also tested on the OPKO microperimeter (Optos, Dunfermline, Scotland) (area of 10° in diameter, 28 stimulated points). Results Median age was 30 years [25.3–47.8]. The overall mean sensitivity for test 1 was 29.4 ± 1.4 dB, 29.8 ± 1.0 dB for test 2 and 29.9 ± 1.1 dB for test 3, respectively. Linear regression analysis showed a significant 0.5 dB sensitivity loss for each decade of life (r² = 0.27). In a subset of 24 subjects, the repeatability of the test performed at 3 separate visits showed a statistically significant difference between test 1 and 3 (p < 0.004). Test 2 and 3 showed consistent values over time (p = 0.160). Furthermore, the MAIA showed higher threshold values than the OPKO for all test locations. Linear regression of the perimetric results showed significant correlation between the 2 machines (r = 0.44; p < 0.001). Conclusions This study found an age‐related macular sensitivity loss. These findings are in agreement with previous data obtained with the MP1 and the OPKO microperimeters. The increase in sensitivity between test 1 and test 2 and 3 should be taken into account in clinical practice. Automatic fundus perimetry with the MAIA microperimeter allows for accurate, repeatable examination, if a training session is performed.
Published: 2016

30. The montrachet study

Author: C Creuzot, Christine Binquet, A.M. Bron, ProdInra, Migration, Centre des Sciences du Goût et de l'Alimentation (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bourgogne Franche-Comté [COMUE] (UBFC), and European Association for Vision and Eye Research (EVER). BEL.
Subjects: 03 medical and health sciences, Ophthalmology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 0302 clinical medicine, genetic structures, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 030221 ophthalmology & optometry, General Medicine, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, eye diseases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, 3. Good health
Abstract: National audience; Summary The Montrachet Study (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases) is a population‐based derived from the 3C Study performed in Dijon. In 2009–2011, 1153 participants from the 3 Cities Study, aged 75 years or more, had an initial eye examination. Apart from the old age of this population, the main interest is that information on cardiovascular and neurologic diseases and a large comprehensive database (blood samples, genetic testing, cognitive tests, MRI) were available. Our first results showed us that despite the high prevalence of self‐reported eye diseases in this elderly population, visual impairment was low and increased with age. These results can improve our knowledge on the characteristics of ocular data in the elderly as well as the relations between eye and age‐related vascular and neurologic diseases.
Published: 2016

31. Vitamin D and mental health: optimizing in the midst of the complexity

Author: Didier Wion, V. Landel, Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN (NICN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BrainTech Laboratory [CHU Grenoble Alpes - Inserm U1205] (Brain Tech Lab ), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), BrainTech Laboratory [CHU Grenoble Alpes - Inserm U1205], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), and wion, didier
Subjects: medicine.medical_specialty, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Vitamins, Vitamin D Deficiency, medicine.disease, Mental health, vitamin D deficiency, 030227 psychiatry, 03 medical and health sciences, Psychiatry and Mental health, Mental Health, 0302 clinical medicine, medicine, Vitamin D and neurology, Humans, Vitamin D, Psychiatry, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience
Published: 2017

32. Measurement of aortic arch pulse wave velocity in cardiovascular MR: Comparison of transit time estimators and description of a new approach

Author: Nadjia Kachenoura, A. Decesare, Muriel Lefort, Alain Herment, Elie Mousseaux, Alban Redheuil, Anas Dogui, Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie [CHU HEGP], 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), and Gestionnaire, Hal Sorbonne Université
Subjects: Adult, Aortic arch, medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], Aorta, Thoracic, 030204 cardiovascular system & hematology, Cardiovascular System, Body Mass Index, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine.artery, Ascending aorta, medicine, Humans, Radiology, Nuclear Medicine and imaging, Pulse wave velocity, Aorta, Mathematics, Reproducibility, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Reproducibility of Results, Estimator, Sigmoid function, Middle Aged, Magnetic Resonance Imaging, Surgery, [SDV] Life Sciences [q-bio], Femoral Artery, Carotid Arteries, Pulsatile Flow, cardiovascular system, Aortic stiffness, Nuclear medicine, business, Blood Flow Velocity, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Purpose: To investigate the efficiency of a new method (TT-Upslope) for transit time (Δt) estimation from cardiovascular MR (CMR) velocity curves. Materials and Methods: Fifty healthy volunteers (40 ± 15 years) underwent applanation tonometry to estimate carotid–femoral pulse wave velocity (cf-PWV) and carotid pressure measurements, and CMR to estimate aortic arch-PWV and ascending aorta distensibility (AAD). The Δt was calculated with TT-Upslope by minimizing the area delimited by two sigmoid curves fitted to the systolic upslope of the ascending (AAC) and descending (DAC) aorta velocity curves, and compared with previously described methods: TT-Point using the half maximum of AAC and DAC, TT-Foot using AAC and DAC feet, and TT-Wave by minimizing the area between AAC and DAC curves using cross correlation. Results: All the Δt methods provided a high reproducibility of arch-PWV. However, TT-Upslope and TT-Wave resulted in better correlations with aging (r = 0.83/r = 0.83 versus r = 0.47/r = 0.72), cf-PWV (r = 0.69/r = 0.70 versus r = 0.34/r = 0.59), and AAD (r = 0.81/r = 0.71 versus r = 0.61/r = 0.60). Furthermore, TT-Upslope resulted in stronger relationship between arch-PWV and AAD according to a theoretical model and provided better characterization of older subjects compared with TT-Wave. Conclusion: Arch-PWV estimated with CMR using the TT-Upslope method was found to be reproducible and accurate, providing strong correlations with age and aortic stiffness indices. J. Magn. Reson. Imaging 2011;33:1321–1329. © 2011 Wiley-Liss, Inc.
Published: 2011

33. TFPI-2 silencing increases tumour progression and promotes metalloproteinase 1 and 3 induction through tumour-stromal cell interactions

Author: Stéphanie Petiot, Antoine Touzé, Yves Courty, Guillaume Gaud, Stéphanie Lerondel, Yves Gruel, Benjamin Brillet, Sophie Iochmann, P. Reverdiau, Florian Seigneuret, Audrey Guillon-Munos, Nathalie Heuzé-Vourc'h, ProdInra, Migration, U618, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Francois Rabelais [Tours], Transgenèse et archivage d'animaux modèles (TAAM), Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours)
Subjects: Male, Lung Neoplasms, Integrin alpha1, micro interfering RNA (miRNA), Metastasis, Mice, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Tumor Microenvironment, GLIOMA-CELLS, Neoplasm Metastasis, Mice, Inbred BALB C, 0303 health sciences, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, matrix metalloproteinases, Articles, cell invasion, Extracellular Matrix, 3. Good health, Cell biology, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, MESSENGER-RNA SYNTHESIS, Molecular Medicine, RNA Interference, Signal Transduction, tissue factor pathway inhibitor-2, Collagen Type IV, GROWTH-FACTOR, Stromal cell, Transplantation, Heterologous, Down-Regulation, Mice, Nude, Biology, 03 medical and health sciences, LUNG-CANCER, Cell Line, Tumor, medicine, Animals, Humans, Neoplasm Invasiveness, Cell adhesion, education, non-small cell lung cancer, Cell Proliferation, Glycoproteins, 030304 developmental biology, MELANOMA-CELLS, Tumor microenvironment, Cell growth, tumour growth, Cancer, cell adhesion, IN-VITRO, Cell Biology, medicine.disease, Tissue-factor-pathway inhibitor 2, TISSUE, Cancer cell, integrins, Laminin, Stromal Cells, FACTOR PATHWAY INHIBITOR-2, SUPPRESSOR GENE, Neoplasm Transplantation, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Tissue factor pathway inhibitor-2 (TFPI-2) is a potent inhibitor of plasmin which activates matrix metalloproteinases (MMPs) involved in degradation of the extracellular matrix. Its secretion in the tumour microenvironment makes TFPI-2 a potential inhibitor of tumour invasion and metastasis. As demonstrated in aggressive cancers, TFPI-2 is frequently down-regulated in cancer cells, but the mechanisms involved in the inhibition of tumour progression remained unclear. We showed in this study that stable TFPI-2 down-regulation in the National Cancer Institute (NCI)-H460 non-small cell lung cancer cell line using specific micro interfering micro-interfering RNA promoted tumour progression in a nude mice orthotopic model that resulted in an increase in cell invasion. Moreover, TFPI-2 down-regulation enhanced cell adhesion to collagen IV and laminin via an increase in alpha(1) integrin on cell surface, and increased MMP expression (mainly MMP-1 and -3) contributing to cancer cell invasion through basement membrane components. This study also reveals for the first time that pulmonary fibroblasts incubated with conditioned media from TFPI-2 silencing cancer cells exhibited increased expression of MMPs, particularly MMP-1, -3 and -7, that are likely involved in lung cancer cell invasion through the surrounding stromal tissue, thus enhancing formation of metastases.
Published: 2011

34. Gentamicin, norfloxacin and lysozyme concentration in human tears: in vivo and in vitro study

Author: C. Garcher, A. Lallemand, C. Bonnin, A.M. Bron, ProdInra, Migration, and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: Adult, Male, Adolescent, Egg lysozyme, chemical and pharmacologic phenomena, In Vitro Techniques, gentamicin, Pharmacology, Microbiology, Cornea, chemistry.chemical_compound, In vivo, medicine, Humans, In vitro study, heterocyclic compounds, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, lysozyme, Norfloxacin, ocular surface, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Chemistry, hemic and immune systems, General Medicine, biochemical phenomena, metabolism, and nutrition, infection, In vitro, Ophthalmology, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Tears, Muramidase, Gentamicin, Gentamicins, Ophthalmic Solutions, Lysozyme, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Hen's egg lysozyme (HEL) activity was measured in vitro with gentamicin and norfloxacin by a turbidimetric technique. Gentamicin at the concentration of 10(-3) M inhibited HEL activity by 39%, while 10(-3) M norfloxacin did not affect HEL activity. However, an in vivo study in healthy persons did not show any significant statistical difference in tear lysozyme activity when 0.3% gentamicin or 0.3% norfloxacin were topically applied.
Published: 2009

35. Total Protein Level in Cerebrospinal Fluid is Stable in Elderly Adults

Author: Denis Guilloteau, Christian R. Andres, Emilie Beaufils, Patrick Vourc'h, Karl Mondon, Laurent Mereghetti, Diane Dufour-Rainfray, Chantal Gendrot, Emilie Vierron, Caroline Hommet, ProdInra, Migration, Laboratoire de Médecine Nucléaire, Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Francois Rabelais [Tours], 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 de Tours), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Service de Bactériologie–Virologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Aging, Pediatrics, medicine.medical_specialty, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, MEDLINE, Cerebrospinal Fluid Proteins, Middle Aged, 030204 cardiovascular system & hematology, Spinal Puncture, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, medicine, Humans, Elderly adults, Geriatrics and Gerontology, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Aged, Cerebrospinal Fluid, Total protein
Abstract: International audience
Published: 2013

36. Selective CD28 antagonist prevents Aldara-induced skin inflammation in non-human primates

Author: Elisabeth Cassagnau, Gilles Blancho, Jeremy Hervouet, Stéphanie Le Bas-Bernardet, Melanie Chevalier, Lyssia Belarif, David Minault, Caroline Mary, Bernard Vanhove, Nicolas Poirier, Veronique Daguin, 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), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Effimune SAS [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), The Progreffe and Centaure foundations (France) and the IHU-Cesti project, supported by Nantes Metropole and the Pays de la Loire Region., European Project, Le Bihan, Sylvie, and TRIAD (EU-FP7-Health program EC-GA N°281493) - INCOMING
Subjects: CD28, Administration, Topical, T-Lymphocytes, non-human primate, Inflammation, Dermatology, 030230 surgery, Lymphocyte Activation, Biochemistry, B7-H1 Antigen, 03 medical and health sciences, 0302 clinical medicine, CD28 Antigens, skin inflammation, Psoriasis, medicine, Animals, CTLA-4 Antigen, Aminoquinolines, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Skin, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Imiquimod, Non human primate, Aldara, business.industry, Antagonist, psoriasis, medicine.disease, Immunology, B7-1 Antigen, Lymphocyte activation, B7-2 Antigen, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Papio, 030215 immunology
Abstract: International audience
Published: 2016

37. Motion perception in early glaucoma

Author: Catherine Creuzot-Garcher, Anna Francoz, Thierry Pozzo, Am Bron, Alessandro Carlini, Department of Ophthalmology, Shinshu University School of Medicine, Laboratoire d'Etude de l'Apprentissage et du Développement [Dijon] (LEAD), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), ProdInra, Archive Ouverte, Laboratoire d'Etude de l'Apprentissage et du Développement [Dijon] ( LEAD ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), and Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: visual field, medicine.medical_specialty, 641 perception, genetic structures, Open angle glaucoma, 758 visual fields, Glaucoma, perception, Stimulus (physiology), Standard deviation, champ visuel, 03 medical and health sciences, 0302 clinical medicine, Optics, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Ophthalmology, medicine, Motion perception, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 030304 developmental biology, ganglion, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 531 ganglion cells, business.industry, General Medicine, Early glaucoma, cell, medicine.disease, Peripheral, Visual field, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, [ SDV.MHEP.OS ] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 030221 ophthalmology & optometry, cellule, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Purpose: The aim of our study was to underline the changes in the movement perception for early glaucoma. Our working hypothesis consisted in inquiring if the impairment of the magnocellular pathway may modify the movement perception capabilities in the visual field, more particularly in its peripheral area.Methods: We included 14 healthy subjects and 14 patients with early primary open angle glaucoma. A moving target was presented on a semicircular screen (1.8 m diameter); participants were asked to localize the Ending Point (EP) of each movement. Each stimulus consisted in a white dot (0,72° of diameter) moving horizontally with the imposed velocity profile. Two different laws of motion were displayed: a “biological” motion corresponding to the recording of an arm pointing movement, consisting in a bell-shaped velocity profile, and a “non-biological” motion corresponding to a constant velocity profile. The study field was divided into 4 quadrants and 2 eccentricities: EP may be displayed in the “peri-central” (10° from the foveal axis) or peripheral (20° from the foveal axis) visual field. Two trajectories length were presented (10° and 20°). Each stimulus with same characteristics was displayed two times. Thus the experiment was constituted by 192 trials, presented in a random order. For every participant we calculated the PCE (Position Constant Error) which was defined as the average difference between the estimation of the EP indicated by the participant versus the true location of the same target. The PVE (Position Variable Error) was defined as the standard deviation of the responses of each participant.Results: All the participants overestimated the EP (13.23 ± 8.87 mm for healthy subjects and 17.06 ± 13.07 mm for glaucoma patients, p = 0.2518). The PVE was 28.14 ± 6.86 mm for healthy subjects and 40.95 ± 9.83 mm for glaucoma patients (p = 0.0004). There was a significant difference in the PVE for both groups when stimulus moved accordingly to the “non-biological” velocity profile (p = 0.0001). Glaucoma patients had substantial PVE increase when the target image had a “non-biological” speed profile (p = 0.0388).Conclusions: This study desrcibed disorders in movement perception and localization in patients with early glaucoma.Particularly, the unexpected lack of difference between normal subjects and patients in localizing a moving stimulus strongly suggested that the visual deficiency could be partly compensated by endogenous informations.
Published: 2013

38. Traumatic brain injury among female offenders in a prison population: results of the FleuryTBI study

Author: Jean-Jacques Weiss, Pascale Pradat-Diehl, Mathilde Chevignard, Laurence Watier, Anne Lécu, M. Fix, Eric Durand, Laboratoire d'Imagerie Biomédicale (LIB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de médecine physique et de réadaptation (MPR), Fondation Sainte Marie, Pharmacoépidémiologie et maladies infectieuses (PhEMI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Veille Sanitaire (INVS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Consultation et de soins ambulatoires des maisons d'arrêt de Fleury-Mérogis (UCSA), Centre Ressources francilien du traumatisme crânien [Paris], Service de Rééducation des pathologies neurologiques acquises de l'enfant [Hôpitaux de Saint Maurice], Hôpitaux de Saint Maurice (HNSM), Service de Médecine Physique et de Réadaptation [CHU Pitié-Salpêtrière] (MPR), 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), HAL-UPMC, Gestionnaire, Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine physique et de réadaptation [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Paris, 030506 rehabilitation, medicine.medical_specialty, Adolescent, inmates, Traumatic brain injury, media_common.quotation_subject, neuropsychology, Prison, Perceived health, Young Adult, 03 medical and health sciences, Behavioral Neuroscience, Epilepsy, 0302 clinical medicine, Brain Injuries, Traumatic, female prisoners, Health care, medicine, Humans, Psychiatry, Original Research, media_common, Prison population, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Prisoners, traumatic brain injury, Head injury, Neuropsychology, Criminals, 16. Peace & justice, medicine.disease, nervous system diseases, 3. Good health, nervous system, Female, 0305 other medical science, Psychology, business, head injury, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Aim The study was designed to estimate the prevalence of traumatic brain injury (TBI) in a French prison population of female offenders, study the variables known to be associated with TBI, and compare our results with those obtained among male offenders as described in a previous paper. Participants All female offenders (adults and juveniles) consecutively admitted to Fleury-Merogis prison over a 3-month period were included in the study. Method During the admission procedure, female offenders were interviewed by healthcare staff using a self-reported questionnaire. Results In all, 100 female offenders were included. The rate of self-reported TBI was high, with a prevalence of 21%. The first cause of TBI was violence related (35%) and a majority of female offenders with a history of TBI reported having sustained more than one TBI. When compared with those who did not report a TBI, epilepsy and use of alcohol were higher among female offenders with a history of TBI. Perceived health was significantly worse for women who reported a TBI. Conclusions This study findings provide additional evidence that TBI among offender populations is serious and that specific actions need to be developed and implemented in correctional settings such as screening for TBI upon arrival.
Published: 2016

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