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39 results on '"Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)"'

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

Author

Gérard Branlard, Angelina d’Orlando, Ayesha Tahir, Marc Schmutz, Larbi Rhazi, Annie Faye, Thierry Aussenac, Génétique Diversité et Ecophysiologie des Céréales (GDEC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), BioInformatique et BioStatistiques (BIBS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), COMSATS University Islamabad (CUI), Institut Charles Sadron (ICS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Transformations et Agro-ressources (UT&A), and UniLaSalle

Subjects
Physiology, [SDV]Life Sciences [q-bio], Plant Science
Abstract

In a previous study we used asymmetric-flow field-flow fractionation to determine the polymer mass (Mw), gyration radius (Rw) and the polydispersity index of glutenin polymers (GPs) in wheat (Triticum aestivum). Here, using the same multi-location trials (4 years, 11 locations, and 192 cultivars), we report the factors that are associated with the conformation (Conf) of the polymers, which is the slope of Log(Rw) versus a function of Log(Mw). We found that Conf varied between 0.285 and 0.740, it had low broad-sense heritability (H2=16.8), and it was significantly influenced by the temperature occurring over the last month of grain filling. Higher temperatures were found to increase Rw and the compactness and sphericity of GPs. Alleles for both high- and low-molecular-weight glutenin subunits had a significant influence on the Conf value. Assuming a Gaussian distribution for Mw, the number of polymers present in wheat grains was computed for different kernel weights and protein concentrations, and it was found to exceed 1012 GPs per grain. Using atomic force microscopy and cryo-TEM, images of GPs were obtained for the first time. Under higher average temperature, GPs became larger and more spherical and consequently less prone to rapid hydrolysis. We propose some orientations that could be aimed at potentially reducing the impact of numerous GPs on people suffering from non-celiac gluten sensitivity.

Published
2023

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

Author

Stanimira V Valeva, Manon Degabriel, Fanny Michal, Gabrielle Gay, John R Rohde, Felix Randow, Brice Lagrange, Thomas Henry, Inflammasome, Infections bactériennes et autoinflammation, Inflammasome, Bacterial Infections and Autoinflammation (I2BA), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Microbiology (medical), Infectious Diseases, General Immunology and Microbiology, [SDV]Life Sciences [q-bio], Immunology and Allergy, General Medicine
Abstract

Guanylate-Binding Proteins are interferon-inducible GTPases that play a key role in cell autonomous responses against intracellular pathogens. Despite sharing high sequence similarity, subtle differences among GBPs translate into functional divergences that are still largely not understood. A key GBP feature is the formation of supramolecular GBP complexes on the bacterial surface. Such complexes are observed when GBP1 binds lipopolysaccharide (LPS) from Shigella and Salmonella and further recruits GBP2-4. Here, we compared GBP recruitment on two cytosol-dwelling pathogens, Francisella novicida and S. flexneri. Francisella novicida was coated by GBP1 and GBP2 and to a lower extent by GBP4 in human macrophages. Contrary to S. flexneri, F. novicida was not targeted by GBP3, a feature independent of T6SS effectors. Multiple GBP1 features were required to promote targeting to F. novicida while GBP1 targeting to S. flexneri was much more permissive to GBP1 mutagenesis suggesting that GBP1 has multiple domains that cooperate to recognize F. novicida atypical LPS. Altogether our results indicate that the repertoire of GBPs recruited onto specific bacteria is dictated by GBP-specific features and by specific bacterial factors that remain to be identified.

Published
2023

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

Author

Alexis Cheviet, Jana Masselink, Eric Koun, Roméo Salemme, Markus Lappe, Caroline Froment-Tilikete, Denis Pélisson, Integrative Multisensory Perception, Action and Cognition (IMPACT), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Hospices Civils de Lyon (HCL), and Pelisson, Denis

Subjects
Cellular and Molecular Neuroscience, Trans-saccadic perception, [SCCO.NEUR]Cognitive science/Neuroscience, Cerebellum, Cognitive Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Saccades, Corollary discharge, Humans, Saccadic adaptation, Visuo-spatial representation, Adaptation, Physiological
Abstract

Saccadic adaptation ($SA$) is a cerebellar-dependent learning of motor commands ($MC$), which aims at preserving saccade accuracy. Since $SA$ alters visual localization during fixation and even more so across saccades, it could also involve changes of target and/or saccade visuospatial representations, the latter ($CDv$) resulting from a motor-to-visual transformation (forward dynamics model) of the corollary discharge of the $MC$. In the present study, we investigated if, in addition to its established role in adaptive adjustment of $MC$, the cerebellum could contribute to the adaptation-associated perceptual changes. Transfer of backward and forward adaptation to spatial perceptual performance (during ocular fixation and trans-saccadically) was assessed in eight cerebellar patients and eight healthy volunteers. In healthy participants, both types of $SA$ altered $MC$ as well as internal representations of the saccade target and of the saccadic eye displacement. In patients, adaptation-related adjustments of $MC$ and adaptation transfer to localization were strongly reduced relative to healthy participants, unraveling abnormal adaptation-related changes of target and $CDv$. Importantly, the estimated changes of $CDv$ were totally abolished following forward session but mainly preserved in backward session, suggesting that an internal model ensuring trans-saccadic localization could be located in the adaptation-related cerebellar networks or in downstream networks, respectively.

Published
2022

4. Pulmonary aspergillosis in critically ill patients with Coronavirus Disease 2019 (COVID-19)

Author

F. Wallet, Laurent Argaud, Florence Persat, Jean Turc, Jean Menotti, Jean-Christophe Richard, Charline Miossec, Martine Wallon, Damien Dupont, S. Paulus, Florence Ader, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université de Lyon-Université de Lyon, Hôpital Edouard Herriot [CHU - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Hôpital Louis Pradel [CHU - HCL], Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CarMeN, laboratoire, Centre de recherche en neurosciences de Lyon (CRNL), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Critical Illness, [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Aspergillosis, intensive care unit, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, pulmonary aspergillosis, Pandemic, Humans, Medicine, 030212 general & internal medicine, Aged, Aged, 80 and over, Invasive Pulmonary Aspergillosis, 0303 health sciences, Aspergillus, biology, SARS-CoV-2, 030306 microbiology, Critically ill, business.industry, Brief Report, COVID-19, General Medicine, Middle Aged, acute respiratory distress syndrome, medicine.disease, biology.organism_classification, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, Pulmonary aspergillosis, Infectious Diseases, AcademicSubjects/SCI00960, Female, AcademicSubjects/MED00010, business, COVID-19 associated pulmonary aspergillosis (CAPA)
Abstract

Occurrence of putative invasive pulmonary aspergillosis was screened in 153 consecutive adult intensive care unit (ICU) patients with respiratory samples addressed for mycological diagnosis during a 6-week period at the emergence of coronavirus disease 2019 (COVID-19) pandemic. Positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) was observed for 106 patients (69.3%). Nineteen of them (17.9%) with positive Aspergillus results were considered as having putative invasive pulmonary aspergillosis. These observations underline the risk of pulmonary aspergillosis in COVID-19 patients, even in patients not previously known to be immunosuppressed, advocating active search for Aspergillus infection and prompt antifungal treatment. Standardized surveillance protocols and updated definitions for ICU putative invasive pulmonary aspergillosis are needed. Lay Abstract Adult ICU patients with respiratory samples addressed for mycological diagnosis were screened during the emergence of COVID-19 pandemic. Positive SARS-CoV-2 PCR was observed for 106 patients, nineteen of them (17.9%) having aspergillosis. This underlines the risk of aspergillosis in COVID-19 patients.

Published
2020

5. Care through cohort studies: sociological survey of the PROOF cohort study on vascular and cognitive aging

Author

Thomas Bujon, Vololona Rabeharisoa, Frédéric Roche, Rodolphe Charles, Jean-Claude Barthélémy, Angélique Savall, Système Nerveux Autonome - Epidémiologie, Physiologie, Ingénierie, Santé (SNA-EPIS), Université Jean Monnet [Saint-Étienne] (UJM)-Centre Hospitalier Universitaire de Saint-Etienne, Université Jean Monnet [Saint-Étienne] (UJM), Triangle : action, discours, pensée politique et économique (TRIANGLE), Centre National de la Recherche Scientifique (CNRS)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Centre de Sociologie de l'Innovation i3 (CSI i3), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Système Nerveux Autonome - Epidémiologie, Physiologie, Ingénierie, Santé (SNA - EPIS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Université Jean Monnet - Saint-Étienne (UJM), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut interdisciplinaire de l’innovation (I3), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-MINES ParisTech - École nationale supérieure des mines de Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)

Subjects
Cognitive aging, Gerontology, Aging, research ethics, Participant observation, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Humans, 030212 general & internal medicine, Research ethics, [SHS.SOCIO]Humanities and Social Sciences/Sociology, 030505 public health, human experimentation, Public Health, Environmental and Occupational Health, Medical safety, General Medicine, care : cohort studies, Research Personnel, Cognitive Aging, Cohort, Research studies, 0305 other medical science, Qualitative research, Cohort study
Abstract

Background The success of health research depends on the involvement of participants. Few studies have examined the participation of subjects in cohorts. Drawing on a sociological survey on a French cohort around aging, this study proposes to question the nature of interactions between researchers and subjects that would help to understand the motivations of subjects to participate and remain in health research studies. Methods Qualitative study combining participant observation within the research laboratory that conducted the cohort and semi-structured interviews with subjects included in the cohort and with members of the research team. Results This study highlights the existence of two-way care: from the laboratory to the subjects and from the cohort to researchers. Health research seems to correspond to a complex association between subjects concerned with aging and the expected benefits of exceptional monitoring. Research is incorporated into subjects’ daily lives, allowing a shift in the purpose of research from overmedicalization to medical safety that subjects experienced as a form of care. Conclusions In cohort studies, care is understood as a form of attention to the person through high-quality medical follow-up. Aging is turned into a matter of concern that subjects, in collaboration with researchers, strive to control.

Published
2020

6. Efficacy of colistin alone and in various combinations for the treatment of experimental osteomyelitis due to carbapenemase-producing Klebsiella pneumoniae

Author

L. Gatin, Azzam Saleh-Mghir, Omar Aimer, Aurélien Dinh, Idir Ghout, Aurélie Jayol, Pierre Tattevin, Frédéric Laurent, Patrice Nordmann, William Mouton, Marie-Clémence Verdier, Anne-Claude Crémieux, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Raymond Poincaré [AP-HP], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Reference des Staphylocoques, Université de Lyon, CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Ambroise Paré [AP-HP], French National Agency, AAP-2013–055, Agence Nationale de Sécurité du Médicament, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Microbiology (medical), Klebsiella pneumoniae, medicine.drug_class, [SDV]Life Sciences [q-bio], Antibiotics, Microbial Sensitivity Tests, Tigecycline, Pharmacology, Fosfomycin, Meropenem, 03 medical and health sciences, Drug Resistance, Multiple, Bacterial, Drug Resistance, Bacterial, polycyclic compounds, medicine, Animals, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Antiinfective agent, Dose-Response Relationship, Drug, biology, Colistin, 030306 microbiology, business.industry, Drug Synergism, Osteomyelitis, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, biology.organism_classification, Anti-Bacterial Agents, Klebsiella Infections, 3. Good health, Disease Models, Animal, Carbapenem-Resistant Enterobacteriaceae, Infectious Diseases, bacteria, Drug Therapy, Combination, lipids (amino acids, peptides, and proteins), Gentamicin, Rabbits, business, medicine.drug
Abstract

ObjectivesIn a new experimental model of carbapenemase-producing Klebsiella pneumoniae osteomyelitis we evaluated the efficacy of colistin alone and in various combinations and examined the emergence of colistin-resistant strains and cross-resistance to host defence peptides (HDPs).MethodsKPC-99YC is a clinical strain with intermediate susceptibility to meropenem (MIC = 4 mg/L) and full susceptibility to gentamicin, colistin and tigecycline (MICs = 1 mg/L) and fosfomycin (MIC = 32 mg/L). Time–kill curves were performed at 4× MIC. Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 cfu. Treatment started 14 days later for 7 days in seven groups: (i) control; (ii) colistin; (iii) colistin + gentamicin; (iv) colistin + tigecycline; (v) colistin + meropenem; (vi) colistin + meropenem + gentamicin; and (vii) colistin + fosfomycin.ResultsIn vitro, colistin was rapidly bactericidal, but regrowth occurred after 9 h. Combinations of colistin with meropenem or fosfomycin were synergistic, whereas combination with tigecycline was antagonistic. In vivo, colistin alone was not effective. Combinations of colistin with meropenem or fosfomycin were bactericidal (P ConclusionsIn this model, combinations of colistin plus meropenem, with or without gentamicin, or colistin plus fosfomycin were the only effective therapies. The combination of colistin and tigecycline should be administered with caution, as it may be antagonistic in vitro and in vivo.

Published
2019

7. No evident association of nasal carriage of Staphylococcus aureus or its small-colony variants with cotrimoxazole use or ANCA-associated vasculitis relapses

Author

Jason Tasse, Narimane Nekkab, Frédéric Laurent, Loïc Guillevin, Boun Kim Tan, Yoann Crabol, Christine Vinter, Xavier Puéchal, Centre hospitalier Saint Joseph - Saint Luc [Lyon], Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Réseau International des Instituts Pasteur (RIIP), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), 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), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Adult, Male, Staphylococcus aureus, medicine.medical_specialty, Microscopic Polyangiitis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Churg-Strauss Syndrome, medicine.disease_cause, Gastroenterology, Rheumatology, Recurrence, Internal medicine, Trimethoprim, Sulfamethoxazole Drug Combination, Eosinophilic, Secondary Prevention, medicine, Humans, Pharmacology (medical), Prospective Studies, Nose, business.industry, Granulomatosis with Polyangiitis, Antibiotic Prophylaxis, Middle Aged, Staphylococcal Infections, medicine.disease, Phenotype, Treatment Outcome, medicine.anatomical_structure, Carriage, Nasal Swab, Female, France, Nasal Cavity, Vasculitis, business, Microscopic polyangiitis, Granulomatosis with polyangiitis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

ObjectiveTo identify the role of Staphylococcus aureus (SA) or its intracellular small-colony variant phenotype (SCV) with co-trimoxazole (CTX) or ANCA-associated vasculitis (AAV) activity.MethodsAll consecutive AAV patients with granulomatosis with polyangiitis (GPA), eosinophilic GPA or microscopic polyangiitis, followed at the French National Vasculitis Referral Center (09/2012–05/2013), and hospitalized non-AAV controls, exclusively for SA/SCV carriage comparisons, were enrolled. All had bilateral anterior nasal swab cultures. Nasal SA or SCV carriage was determined and associations with relapse(s), BVAS, ANCA-positivity, anti-staphylococcal and immunosuppressant use, were analysed ⩾4 years post-inclusion.ResultsNasal SA carriage rates did not differ among AAVs (P = 0.53): GPA (24/80; 30%), EGPA (7/28; 25%) and microscopic polyangiitis (3/11; 27.3%); and the rate was less frequent in controls than in GPA patients not taking CTX (P = 0.04). AAV patients taking CTX prophylaxis had less nasal SA carriage (8.7% vs 36.2%; P = 0.02). Nasal SA carriage or CTX use did not modify relapse rates, BVAS or ANCA-positivity at inclusion or during follow-up. Nasal SCV carriage, found in 15/207 (7.2%) patients, was similar for GPA (10/24; 41.7%), microscopic polyangiitis (2/7; 28.6%) and eosinophilic GPA (2/3; 66.7%), but higher (P = 0.02) than controls (1/14; 7.1%). SCV carriage by AAV groups did not modify relapse rates or ANCA positivity at inclusion or during follow-up; a trend towards higher BVAS was observed only for anti-PR3 ANCA patients.ConclusionNasal SA or SCV carriage was comparable among AAVs but more frequent than in controls. Nasal SA or SCV carriage and CTX use did not modify AAV relapse rates.

Published
2019

8. Trends in the Control Strategies for Occupational Exposure to Carcinogenic, Mutagenic, and Reprotoxic Chemicals in France (2003–2010)

Author

Morgane Plantier, Barbara Charbotel, Nathalie Havet, Alexis Penot, Béatrice Fervers, Magali Morelle, Laboratoire de Sciences Actuarielle et Financière (SAF), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Groupe d'analyse et de théorie économique (GATE Lyon Saint-Étienne), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Département Cancer and Environnement, Centre Léon Bérard, Université de Lyon, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université de Lyon-Université de Lyon-Université Gustave Eiffel, École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Groupe d'analyse et de théorie économique (GATE), Université Lumière - Lyon 2 (UL2)-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE), Université de Lyon-Université de Lyon-Institut National de Recherche sur les Transports et leur Sécurité (INRETS), Groupe d'Analyse et de Théorie Economique Lyon - Saint-Etienne (GATE Lyon Saint-Étienne), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Control (management), 010501 environmental sciences, 01 natural sciences, Hazardous Substances, 03 medical and health sciences, 0302 clinical medicine, Environmental health, Humans, Medicine, CARCINOGENS, Occupations, Personal Protective Equipment, Personal protective equipment, Occupational Health, 0105 earth and related environmental sciences, [SHS.STAT]Humanities and Social Sciences/Methods and statistics, business.industry, OCCUPATIONAL EXPOSURE, Public Health, Environmental and Occupational Health, Regression analysis, Middle Aged, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, 030210 environmental & occupational health, Ventilation, Employment contract, Cross-Sectional Studies, Logistic Models, PROTECTION MEASURES, 8. Economic growth, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Occupational exposure, business, Mutagens
Abstract

International audience; Background: European directives stipulate that French employers take all available measures to reduce the use of carcinogenic, mutagenic, and reprotoxic chemicals (CMRs). Our study explores the trends for the various control measures that are available to employees exposed to CMRs, at two time points (2003 and 2010).Method: Our study assessed data from the 2003 and the 2010 French national cross-sectional survey of occupational hazards (SUMER). The availability of collective protections (source-based controls and general ventilation) and personal protective equipment (PPE) was explored. Trends in the availability of protective measures were studied using multilevel logistic regressions.Results: Exposure situations without any protective measures decreased considerably between 2003 and 2010 (29.9% vs. 17.9%, respectively). The increase in the proportion of exposure situations involving source-based controls (e.g., an isolation chamber, local exhaust ventilation, etc.) was, however, much less. Multiple regression analysis showed that the protection strategies depended on the job characteristics (e.g., work schedules, the employment contract, and the occupation) as well as the size of the company. There were noticeable changes between 2003 and 2010. For example, differences in protections available between full-time and part-time workers disappeared in the 7-year period, while those between executives/managers and other employees increased, as did the gaps between large and small companies. Conclusion: Although the overall increase in exposure situations involving protective measures masks a number of differences in exposure between employee categories, it is a step in the right direction. Source-based controls appeared to be implemented more for exposures with the longest durations, and PPE was very often combined with collective protections, which is what is currently recommended.

Published
2019

9. Evaluation of the ability of linezolid and tedizolid to eradicate intraosteoblastic and biofilm-embedded Staphylococcus aureus in the bone and joint infection setting

Author

Jérôme Josse, Sébastien Lustig, Tristan Ferry, Virginie Tafani, Lélia Abad, Christian Chidiac, Frédéric Laurent, Florent Valour, Alan Diot, Jason Tasse, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cadic, Ifsttar, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Microbiology (medical), Staphylococcus aureus, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, 030106 microbiology, Tetrazoles, Virulence, Microbial Sensitivity Tests, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, medicine.disease_cause, Microbiology, BIOMECANIQUE, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Osteoarthritis, medicine, Humans, Granulocyte Precursor Cells, Pharmacology (medical), 030212 general & internal medicine, Viability assay, Oxazolidinones, Pharmacology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Linezolid, Biofilm, OS, Models, Theoretical, Staphylococcal Infections, biochemical phenomena, metabolism, and nutrition, Anti-Bacterial Agents, 3. Good health, Infectious Diseases, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, chemistry, Biofilms, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Toxicity, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, JOINT INFECTION, Tedizolid, BONE, Intracellular
Abstract

Objectives: Prolonged use of linezolid for bone and joint infection (BJI) is limited by its long-term toxicity. The better safety profile of tedizolid, a recently developed oxazolidinone, could offer an alternative. However, its efficacy against biofilm-embedded and intracellular Staphylococcus aureus, the two main bacterial reservoirs associated with BJI chronicity, is unknown.Methods: Using three S. aureus strains (6850 and two clinical BJI isolates), linezolid and tedizolid were compared regarding their ability: (i) to target the S. aureus intracellular reservoir in an in vitro model of osteoblast infection, using three concentrations increasing from the bone concentration reached with standard therapeutic doses (Cbone = 2.5 × MIC; Cplasm = 10 × MIC; Cmax = 40 × MIC); (ii) to eradicate mature biofilm [minimal biofilm eradication concentration (MBEC)]; and (iii) to prevent biofilm formation [biofilm MIC (bMIC) and confocal microscopy].Results: Linezolid and tedizolid weakly reduced the intracellular inoculum of S. aureus in a strain-dependent manner despite the similar MICs for the tested strains, but improved cell viability even in the absence of an intracellular bactericidal effect. Conversely, linezolid and tedizolid were ineffective in eradicating mature biofilm formed in vitro, with MBEC >2000 and >675?mg/L, respectively. bMICs of tedizolid were 4-fold lower than those of linezolid for all strains.Conclusions: Linezolid and tedizolid alone are not optimal candidates to target bacterial phenotypes associated with chronic forms of BJI. Despite weak intracellular activity, they both reduce infection-related cytotoxicity, suggesting a role in modulating intracellular expression of staphylococcal virulence factors. Although inactive against biofilm-embedded S. aureus, both-but particularly tedizolid-are able to prevent biofilm formation.

Published
2018

10. Inequalities in the control of the occupational exposure in France to carcinogenic, mutagenic and reprotoxic chemicals

Author

Alexis Penot, Barbara Charbotel, Morgane Plantier, Magali Morelle, Nathalie Havet, Béatrice Fervers, Laboratoire de Sciences Actuarielle et Financière (SAF), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Groupe d'Analyse et de Théorie Economique Lyon - Saint-Etienne (GATE Lyon Saint-Étienne), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement UMRT9002 (UMRESTTE), Université de Lyon-Université de Lyon-Institut National de Recherche sur les Transports et leur Sécurité (INRETS)-Institut de Veille Sanitaire (INVS), Centre Léon Bérard [Lyon], Groupe d'analyse et de théorie économique (GATE Lyon Saint-Étienne), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, medicine.medical_specialty, Inequality, Cross-sectional study, media_common.quotation_subject, Control (management), Hazardous Substances, Occupational safety and health, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Occupational Exposure, Environmental health, Prevalence, medicine, Humans, 030212 general & internal medicine, Occupational Health, ComputingMilieux_MISCELLANEOUS, media_common, 030503 health policy & services, Collective protection, Public health, Public Health, Environmental and Occupational Health, Health Status Disparities, Middle Aged, [SDE.ES]Environmental Sciences/Environmental and Society, Intervention (law), Cross-Sectional Studies, Work (electrical), [SHS.ENVIR]Humanities and Social Sciences/Environmental studies, [SDE]Environmental Sciences, 8. Economic growth, Carcinogens, Female, France, Business, 0305 other medical science, Mutagens
Abstract

Background Our study examined the social disparities that exist in the implementation of protection measures for occupational exposure to carcinogenic, mutagenic and reprotoxic agents in France, and its aim was to identify which types of employees/jobs require priority action. Methods We analyzed data from the 2010 French national cross-sectional survey of occupational hazards. The availability of the various collective and individual protections was explored. The associations of job and company characteristics with protective measures were studied by multilevel regressions. Results Effective collective protection measures were implemented in 25% of the exposure situations. Managers and intellectual professionals, who accumulated lower CMR exposure prevalences, durations, and intensities than blue-collar workers, benefited the most from effective collective protections. The availability of effective collective protection measures was not influenced by the size of the company. The presence of a Committee for health, safety, and work conditions, as well as intervention of occupational health and safety officers in the past 12 months were associated with a lower exposure intensity, but not with the implementation of more protection measures. Longer exposure durations were associated with more effective collective protection. Conclusion Substantial discrepancies were observed in exposure levels and protection measures as a function of the characteristics of employees' jobs and the companies that they work for. The main priority in regard to prevention should be a focus on unskilled workers, since their collective protection still appears to be insufficient, while their exposure lengths and intensities were the most substantial.

Published
2018

11. Cortico-Amygdala-Striatal Activation by Modafinil/Flecainide Combination

Author

Jian-Sheng Lin, Christian Giaume, Dominique Vodovar, Claire Leroy, Mathieu Charvériat, Nicolas Tournier, Yves Dauvilliers, Franck Mouthon, Géraldine Pottier, Adeline Duchêne, Catriona Wimberley, Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Theranexus [Lyon], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Integrated Physiology of the Brain Arousal Systems (WAKING), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), 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), VODOVAR, Dominique, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Centre de recherche en neurosciences de Lyon (CRNL), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, MESH: Flecainide, Cataplexy, [SDV]Life Sciences [q-bio], narcolepsy, Modafinil, MESH: Rats, Sprague-Dawley, Striatum, Pharmacology, Regular Research Articles, MESH: Corpus Striatum, Rats, Sprague-Dawley, MESH: Modafinil, 0302 clinical medicine, MESH: Fluorodeoxyglucose F18, MESH: Amygdala, MESH: Animals, Pharmacology (medical), Cerebral Cortex, Voltage-Gated Sodium Channel Blockers, Flecainide, medicine.diagnostic_test, Wakefulness-Promoting Agents, Amygdala, MESH: Positron-Emission Tomography, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.TOX] Life Sciences [q-bio]/Toxicology, Drug Combinations, Psychiatry and Mental health, medicine.anatomical_structure, Positron emission tomography, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, medicine.drug, FDG PET imaging, MESH: Rats, 03 medical and health sciences, Fluorodeoxyglucose F18, medicine, Brain positron emission tomography, Animals, MESH: Drug Combinations, business.industry, MESH: Wakefulness-Promoting Agents, medicine.disease, MESH: Voltage-Gated Sodium Channel Blockers, Corpus Striatum, MESH: Male, MESH: Cerebral Cortex, neuroglia, Rats, 030104 developmental biology, Positron-Emission Tomography, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, astroglial connexin, business, 030217 neurology & neurosurgery, Narcolepsy
Abstract

International audience; Background: Modafinil, a nonamphetaminic wake-promoting compound, is prescribed as first line therapy in narcolepsy, an invalidating disorder characterized by excessive daytime sleepiness and cataplexy. Although its mode of action remains incompletely known, recent studies indicated that modafinil modulates astroglial connexin-based gap junctional communication as administration of a low dose of flecainide, an astroglial connexin inhibitor, enhanced the wake-promoting and procognitive activity of modafinil in rodents and healthy volunteers. The aim of this study is to investigate changes in glucose cerebral metabolism in rodents, induced by the combination of modafinil+flecainide low dose (called THN102).Methods: The impact of THN102 on brain glucose metabolism was noninvasively investigated using 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography imaging in Sprague-Dawley male rats. Animals were injected with vehicle, flecainide, modafinil, or THN102 and further injected with 18F-2-fluoro-2-deoxy-D-glucose followed by 60-minute Positron Emission Tomography acquisition. 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography images were coregistered to a rat brain template and normalized from the total brain Positron Emission Tomography signal. Voxel-to-voxel analysis was performed using SPM8 software. Comparison of brain glucose metabolism between groups was then performed.Results: THN102 significantly increased regional brain glucose metabolism as it resulted in large clusters of 18F-2-fluoro-2-deoxy-D-glucose uptake localized in the cortex, striatum, and amygdala compared with control or drugs administered alone. These regions, highly involved in the regulation of sleep-wake cycle, emotions, and cognitive functions were hence quantitatively modulated by THN102.Conclusion: Data presented here provide the first evidence of a regional brain activation induced by THN102, currently being tested in a phase II clinical trial in narcoleptic patients.

Published
2018

12. Progress and Prospects in Gender Visibility at SMBE Annual Meetings

Author

Avelyne S. Villain, Clémentine Vignal, Andrea J. Betancourt, Maud I. Tenaillon, Jos Käfer, Marie S. A. Fernandez, Gabriel A. B. Marais, Sexe et évolution, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Artificial Evolution and Computational Biology (BEAGLE), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Ecologie et Neuro-Ethologie Sensorielles (ENES), Université Jean Monnet [Saint-Étienne] (UJM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) (GQE-Le Moulon), Centre National de la Recherche Scientifique (CNRS)-AgroParisTech-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Recherche Agronomique (INRA), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Inria Grenoble - Rhône-Alpes, Université de Lyon-Université Lumière - Lyon 2 (UL2), Sensory Neuro-Ethology (ENES), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS), Marais, Gabriel A. B., Tenaillon, Maud I., Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, and Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS)

Subjects
0301 basic medicine, Letter, Science, gender ratio, leaky pipeline, conference statistics, questions, oral communications, talk duration, Biology, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, 03 medical and health sciences, 5. Gender equality, Genetics, Humans, 10. No inequality, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Ecology, Evolution, Behavior and Systematics, Medical education, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Visibility (geometry), Attendance, [SDV.BDD.MOR]Life Sciences [q-bio]/Development Biology/Morphogenesis, [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, 030104 developmental biology, Workforce, Female, Women in science, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Women, Working
Abstract

International audience; Reduced visibility of women in science is thought to be one of the causes of their underrepresentation among scientists, in particular at senior positions. Visibility is achieved through publications, and through conference attendance and presentations. Here, we investigated gender differences in visibility at the annual meetings of the Society of Molecular Biology and Evolution. The analysis of meeting programs showed a regular increase in female speakers for the last 16 years. Data on abstract submission suggest that there are no gender-related preferences in the acceptance of contributed presentations at the most recent meetings. However, data collected on-site in 2015 and 2016 show that women asked only ∼25% of the questions, that is, much less than expected given the female attendance. Understanding the reasons for this pattern is necessary for the development of policies that aim to reduce imbalance in visibility.

Published
2018

13. Distinct Thresholds of Infliximab Trough Level Are Associated with Different Therapeutic Outcomes in Patients with Inflammatory Bowel Disease

Author

Bernard Flourié, Gilles Boschetti, Xavier Roblin, Stéphane Nancey, Laurent Peyrin-Biroulet, Emilie Deltedesco, Stéphane Paul, Nicolas Williet, J.M. Phelip, Gérard Duru, Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Université de Lyon, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire d'Immunologie, Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CHU Saint Etienne

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Severity of Illness Index, Inflammatory bowel disease, Gastroenterology, Tertiary Care Centers, Feces, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Gastrointestinal Agents, Maintenance therapy, Internal medicine, Severity of illness, medicine, Humans, Immunology and Allergy, Prospective Studies, Young adult, Prospective cohort study, business.industry, Remission Induction, Middle Aged, Inflammatory Bowel Diseases, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Infliximab, 3. Good health, C-Reactive Protein, Logistic Models, ROC Curve, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Trough level, Female, 030211 gastroenterology & hepatology, France, Drug Monitoring, Calprotectin, business, Leukocyte L1 Antigen Complex, Biomarkers, medicine.drug
Abstract

International audience; BACKGROUND: Several studies have reported a strong correlation between infliximab (IFX) trough levels (trough levels of infliximab [TLI]) and clinical remission (CR). We aimed to determine threshold values of TLI associated with the occurrence of CR, with or without normal inflammatory biomarkers, including serum C-reactive protein (CRP) and fecal calprotectin (fCal). METHODS: We included prospectively all consecutive patients with inflammatory bowel disease under IFX therapy (5 mg/kg every 8 wk) for at least 6 months. Disease activity (using the Crohn's Disease Activity Index or Mayo score) was recorded, and TLI, CRP, and fCal were measured before IFX infusion. RESULTS: Two hundred thirteen patients (131 Crohn's disease) were included. The median TLIs were higher in patients who achieved CR compared with those in patients who did not (2.6 versus 1.2 μg/mL, P \textless 0.01). The median TLI were higher in patients achieving CR with CRP normalization or CR with fCal \textless250 μg/g in comparison with patients with persistent elevated CRP or fCal (3.5 versus 1.6 μg/mL, P \textless 0.01 and 4.9 versus 1.8 μg/mL, P \textless 0.001, respectively). Finally, the median TLIs were higher in patients achieving CR with normal CRP and fCal \textless50 μg/g in comparison with patients without strictly normal biomarkers (5.9 versus 2.1 μg/mL, P \textless 0.001). The more the expected level of response to IFX was stringent, the more the median TLI and optimal thresholds were high. CONCLUSIONS: Threshold values of TLI differ according to therapeutic outcomes expected in patients with inflammatory bowel disease under maintenance therapy with IFX.

Published
2017

14. Familial Mediterranean fever mutations are hypermorphic mutations that specifically decrease the activation threshold of the Pyrin inflammasome

Author

Véronique Hentgen, Flora Magnotti, Agnès Duquesne, Thomas Henry, Bénédicte F. Py, Marine Desjonquères, Mathilde Penel-Page, Yvan Jamilloux, Mathieu Gerfaud-Valentin, Pascal Sève, Alexandre Belot, Luca Cantarini, Vanessa Remy-Piccolo, Amandine Martin, Rolando Cimaz, Thierry Walzer, Lucie Lefeuvre, Audrey Laurent, Emilie Bourdonnay, Omran Allatif, Sarah Benezech, Inflammasome, Infections bactériennes et autoinflammation, Inflammasome, Bacterial Infections and Autoinflammation (I2BA), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Interne [Hôpital Croix Rousse, CHU Lyon], CHU Lyon-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), AOU Meyer, Interdepartmental Research Center of Systemic Autoimmune and Autoinflammatory Diseases, Policlinico Le Scotte, Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, BioInformatique et BioStatistiques (BIBS), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Centre de Référence des Maladies AutoInflammatoires (CeRéMAI), Centre Hospitalier de Versailles André Mignot (CHV), L'Hôpital Nord-Ouest [Villefranche sur Saône], Inflammasome NLRP3 – NLRP3 Inflammasome, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Salmonella typhimurium, rho GTP-Binding Proteins, 0301 basic medicine, Inflammasomes, Autoinflammation, Familial mediterranean fever, IL-18, IL-1β, Inflammasome, MEFV, NLRC4, NLRP3, Pyrin, Adenosine Triphosphate, Adolescent, Adult, Antigens, Bacterial, Bacterial Proteins, Bacterial Toxins, CARD Signaling Adaptor Proteins, Calcium-Binding Proteins, Case-Control Studies, Cell Death, Child, Child, Preschool, Familial Mediterranean Fever, Female, Healthy Volunteers, Humans, Interleukin-18, Interleukin-1beta, Ionophores, Middle Aged, Monocytes, Mutation, NLR Family, Pyrin Domain-Containing 3 Protein, Nigericin, Rheumatology, Pharmacology (medical), Familial Mediterranean fever, Pyrin domain, Exon, 0302 clinical medicine, ComputingMilieux_MISCELLANEOUS, Bacterial, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Interleukin 18, medicine.drug, Clostridium difficile toxin B, NLR Family, 03 medical and health sciences, medicine, Antigens, Preschool, 030203 arthritis & rheumatology, business.industry, medicine.disease, Pyrin Domain-Containing 3 Protein, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030104 developmental biology, Immunology, business
Abstract

Objectives FMF is the most frequent autoinflammatory disease and is associated in most patients with bi-allelic MEFV mutations. MEFV encodes Pyrin, an inflammasome sensor activated following RhoGTPase inhibition. The functional consequences of MEFV mutations on the ability of Pyrin variants to act as inflammasome sensors are largely unknown. The aim of this study was to assess whether MEFV mutations affect the ability of Pyrin to detect RhoGTPase inhibition and other inflammasome stimuli. Methods IL-1β and IL-18 released by monocytes from healthy donors (HDs) and FMF patients were measured upon specific engagement of the Pyrin, NLRP3 and NLRC4 inflammasomes. Cell death kinetics following Pyrin activation was monitored in real time. Results Monocytes from FMF patients secreted significantly more IL-1β and IL-18 and died significantly faster than HD monocytes in response to low concentrations of Clostridium difficile toxin B (TcdB), a Pyrin-activating stimulus. Monocytes from patients bearing two MEFV exon 10 pathogenic variants displayed an increased Pyrin inflammasome response compared with monocytes from patients with a single exon 10 pathogenic variant indicating a gene-dosage effect. Using a short priming step, the response of monocytes from FMF patients to NLRP3- and NLRC4-activating stimuli was normal indicating that MEFV mutations trigger a specific hypersensitivity of monocytes to low doses of a Pyrin-engaging stimulus. Conclusion Contrary to the NLRP3 mutations described in cryopyrin-associated periodic syndrome, FMF-associated MEFV mutations do not lead to a constitutive activation of Pyrin. Rather, FMF-associated mutations are hypermorphic mutations that specifically decrease the activation threshold of the Pyrin inflammasome without affecting other canonical inflammasomes.

Published
2017

15. Insular and Ventrolateral Orbitofrontal Cortices Differentially Contribute to Goal-Directed Behavior in Rodents

Author

Shauna L. Parkes, Pascal Ravassard, Etienne Coutureau, Juan-Carlos Cerpa, Mathieu Wolff, Guillaume Ferreira, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, European Project: 267196,EC:FP7:PEOPLE,FP7-PEOPLE-2010-COFUND,AGREENSKILLS(2012), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Value (ethics), instrumental conditioning, Cognitive Neuroscience, Action Potentials, Prefrontal Cortex, In Vitro Techniques, Choice Behavior, Brain mapping, Action selection, Extinction, Psychological, [SCCO]Cognitive science, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Transduction, Genetic, medicine, Animals, Rats, Long-Evans, Prefrontal cortex, ComputingMilieux_MISCELLANEOUS, Brain Mapping, outcome devaluation, [SCCO.NEUR]Cognitive science/Neuroscience, Chemogenetics, Extinction (psychology), Heterotrimeric GTP-Binding Proteins, Rats, Luminescent Proteins, 030104 developmental biology, medicine.anatomical_structure, Action (philosophy), Cerebral cortex, [SCCO.PSYC]Cognitive science/Psychology, DREADD, Conditioning, Operant, action, reversal, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Psychology, Goals, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; The medial prefrontal cortex (mPFC) has long been considered a critical site in action control. However, recent evidence indicates that the contribution of cortical areas to goal-directed behavior likely extends beyond mPFC. Here, we examine the function of both insular (IC) and ventrolateral orbitofrontal (vlOFC) cortices in action-dependent learning. We used chemogenetics to study the consequences of IC or vlOFC inhibition on acquisition and performance of instrumental actions using the outcome devaluation task. Rats first learned to associate actions with desirable outcomes. Then, one of these outcomes was devalued and we assessed the rats' choice between the 2 actions. Typically, rats will bias their selection towards the action that delivers the still valued outcome. We show that chemogenetic-induced inhibition of IC during choice abolishes goal-directed control whereas inhibition during instrumental acquisition is without effect. IC is therefore necessary for action selection based on current outcome value. By contrast, vlOFC inhibition during acquisition or the choice test impaired goal-directed behavior but only following a shift in the instrumental contingencies. Our results provide clear evidence that vlOFC plays a critical role in action-dependent learning, which challenges the popular idea that this region of OFC is exclusively involved in stimulus-dependent behaviors.

Published
2017

16. Factors associated with carriage of carbapenem-non-susceptible Enterobacteriaceae in North-Eastern France and outcomes of infected patients

Author

Thomas Guillard, Anne Limelette, Aurore Thierry, Lucien Brasme, Véronique Vernet-Garnier, Anaëlle Muggeo, Coralie Barbe, Odile Bajolet, Christophe de Champs, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA), CHU Reims (CHU Reims), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Laboratoire de Bactériologie–Virologie-Hygiène Hospitalière, Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Carbapenem, Multivariate analysis, Klebsiella pneumoniae, [SDV]Life Sciences [q-bio], Antibiotics, 0302 clinical medicine, Risk Factors, Pharmacology (medical), 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Cross Infection, biology, Mortality rate, Enterobacteriaceae Infections, Middle Aged, Hospitals, Anti-Bacterial Agents, 3. Good health, Infectious Diseases, Carrier State, Female, France, medicine.drug, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, 030106 microbiology, Microbial Sensitivity Tests, Microbiology, 03 medical and health sciences, Internal medicine, Enterobacter cloacae, medicine, Humans, Aged, Pharmacology, business.industry, biology.organism_classification, Klebsiella Infections, Carbapenem-Resistant Enterobacteriaceae, Carriage, Carbapenems, Case-Control Studies, Concomitant, business
Abstract

Background Carbapenems are frequently used as a last resort to treat infections caused by multidrug-resistant Gram-negative organisms, thus carbapenem-non-susceptible Enterobacteriaceae (CNSE) is an emerging health threat. Objectives To assess risk factors and outcomes of CNSE carriage. Patients and methods We conducted a matched case-control study in six hospitals in North-Eastern France. The controls were patients harbouring carbapenem-susceptible Enterobacteriaceae. Fifty-five cases and 110 controls were included. Results Most of the CNSE isolates were Enterobacter cloacae and Klebsiella pneumoniae . Carbapenemase production was observed in 40% of isolates and they produced OXA-48 only. CNSE carriage was significantly associated with recent antibiotic use ( P = 0.014), particularly carbapenems ( P = 0.03) and fluoroquinolones ( P = 0.016). A multivariate analysis using conditional logistic regression showed that the presence of concomitant infection(s) (OR: 9.83; 95% CI 3.04-21.39, P = 0.0031), nosocomial infections (OR: 7.84; 95% CI 2.00-12.54, P = 0.0063) and a high age (OR: 1.07; 95% CI 1.01-1.06, P = 0.038) were independently associated with CNSE carriage. Moreover, patients infected with CNSE had worse outcomes: fewer resolved infections at 1 month ( P = 0.02), and they had a higher mortality rate ( P = 0.0004) and longer hospital stays ( P = 0.02). Conclusions We identified three independent risk factors for CNSE carriage as well as worse outcomes in infected patients in North-Eastern France. This highlights the importance of early detection of CNSE and the need for antimicrobial therapy re-evaluation after bacteriological analysis has been performed.

Published
2017

17. Costs of Crohnʼs Disease According to Severity States in France

Author

Bernard Flourié, Guillaume Cadiot, Edouard Louis, Benjamin Pariente, Fady Daniel, Philippe Marteau, Jacques Moreau, Stéphane Nancey, Mathurin Fumery, Eric Lerebours, Bernard Duclos, Gilles Boschetti, Yoram Bouhnik, Arnaud Bourreille, Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Registre EPIMAD, Normandie Université (NU)-Normandie Université (NU)-CHU Amiens-Picardie-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Departement de Gastroentérologie, Hôpital de Hautepierre [Strasbourg], Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), CIC Plurithématique de Nantes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ministère des Affaires sociales et de la Santé-Direction générale de l'offre de soins (DGOS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hépato-gastroentérologie (CHU Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Université de Liège, Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Total cost, [SDV]Life Sciences [q-bio], clinical course, costs, Severity of Illness Index, Young Adult, 03 medical and health sciences, Indirect costs, 0302 clinical medicine, Cost of Illness, Crohn Disease, Gastrointestinal Agents, Severity of illness, medicine, health economics, Humans, Immunology and Allergy, Prospective Studies, Child, Prospective cohort study, health care economics and organizations, Aged, Crohn's disease, Gastrointestinal agent, Models, Statistical, business.industry, severity states, Gastroenterology, Health Care Costs, Middle Aged, medicine.disease, Infliximab, Hospitalization, Child, Preschool, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Observational study, France, business, medicine.drug
Abstract

International audience; Background: To describe the medico-economic characteristics of Crohn's disease (CD), we implemented a multicenter study in France. Methods: From 2004 to 2006, disease severity states, direct (hospital and extra hospital) and indirect costs were prospectively collected over 1 year in patients with CD naive from anti-tumor necrosis factor alpha (infliximab) at inclusion. Economic valorization was performed from the French Social Insurance perspective, and a statistical modeling over 10 years was performed. Results: In 341 patients, the mean total costs of management were epsilon 6024 per year (epsilon 4675 for direct costs). As compared to patients in remission, costs were 4 to 6 times higher in patients in an active period and 19 times higher for patients requiring surgery (SURG). The most important expense items were medical and surgical hospitalizations (56% of total costs), including cost of infliximab (36% of hospitalization costs, i.e., 20% of total costs), indirect costs (22%), and drugs (11%). The statistical modeling over 10 years showed that most of the clinical course was spent in drug-responsive state (54%) with 26% of costs or in remission (32%) with 11% of costs; time spent in a SURG state was small (3.2%) but generated 48% of total costs. Conclusions: Before the introduction of self-injectable anti-tumor necrosis factor alpha, the most important expenses were supported by hospitalizations, explaining why the most costly states were for patients requiring SURG or dependent on inhospital administrated drugs. Projected data show that most time is spent in a stabilized state with appropriate treatments or in remission, and that costs associated with SURG are high.

Published
2016

18. Salvage Debridement, Antibiotics and Implant Retention ('DAIR') With Local Injection of a Selected Cocktail of Bacteriophages: Is It an Option for an Elderly Patient With Relapsing Staphylococcus aureus Prosthetic-Joint Infection?

Author

Cyril Courtin, Tristan Ferry, Jérôme JOSSE, Yannick HERRY, Mikhail Dziadzko, Frederic Laurent, Stanislas GUNST, Florent Valour, Cédric Dananché, Jean-luc Besse, Florence ADER, Camille Kolenda, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de référence des infections ostéo-articulaires complexes Rhône Alpes Auvergne, Hospices Civils de Lyon (HCL), Service Pharmacie, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France, parent, Pherecydes Pharma, Service de Chirurgie Orthopédique [Centre Albert Trillat], Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.drug_class, medicine.medical_treatment, 030106 microbiology, Antibiotics, medicine.disease_cause, Clinical success, suppressive therapy, 03 medical and health sciences, bacteriophage, medicine, Elderly patient, DAIR, Debridement, business.industry, prosthetic-joint infection, Prosthetic joint infection, S. aureus, 3. Good health, Surgery, 030104 developmental biology, Infectious Diseases, Oncology, Staphylococcus aureus, Implant, Local injection, business
Abstract

[PubMed Central:\hrefhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240628PMC6240628] [DOI:\hrefhttps://dx.doi.org/10.1093/ofid/ofy26910.1093/ofid/ofy269] [PubMed:\hrefhttps://www.ncbi.nlm.nih.gov/pubmed/3029248130292481]; International audience; Local injection of a bacteriophages mix during debridement, antibiotics and implant retention ("DAIR") was performed to treat a relapsing Staphylococcus aureus chronic prosthetic joint infection (PJI). This salvage treatment was safe and associated with a clinical success. Scientific evaluation of the potential clinical benefit of bacteriophages as antibiofilm treatment in PJI is now feasible and required.

Published
2018

19. Shedding of Ebola Virus Surface Glycoprotein Is a Mechanism of Self-regulation of Cellular Cytotoxicity and Has a Direct Effect on Virus Infectivity

Author

Philip Lawrence, Beatriz Escudero-Perez, Olga Dolnik, Valentina A. Volchkova, Hans-Dieter Klenk, Viktor E. Volchkov, Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity (BMPV), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Philipps Universität Marburg, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Philipps Universität Marburg = Philipps University of Marburg

Subjects
viruses, Biology, Virus Replication, medicine.disease_cause, Virus, Cell Line, Cercopithecus aethiops, shedding, Viral Proteins, Viral entry, Chlorocebus aethiops, medicine, Animals, Immunology and Allergy, Vero Cells, shed GP, Infectivity, Budding, Membrane Glycoproteins, Ebola virus, Virulence, infectivity, Virion, glycoprotein GP, Hemorrhagic Fever, Ebola, Virus Internalization, Ebolavirus, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virology, 3. Good health, Infectious Diseases, Amino Acid Substitution, Viral replication, Cell culture, Ebola, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Vero cell, cytotoxicity, Hemorrhagic Fever, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International audience; The surface glycoprotein (GP) is responsible for Ebola virus (EBOV) attachment and membrane fusion during virus entry. Surface expression of highly glycosylated GP causes marked cytotoxicity via masking of a wide range of cellular surface molecules, including integrins. Considerable amounts of surface GP are shed from virus-infected cells in a soluble truncated form by tumor necrosis factor α-converting enzyme. In this study, the role of GP shedding was investigated using a reverse genetics approach by comparing recombinant viruses possessing amino acid substitutions at the GP shedding site. Virus with an L635V substitution showed a substantial decrease in shedding, whereas a D637V substitution resulted in a striking increase in the release of shed GP. Variations in shedding efficacy correlated with observed differences in the amounts of shed GP in the medium, GP present in virus-infected cells, and GP present on virions. An increase in shedding appeared to be associated with a reduction in viral cytotoxicity, and, vice versa, the virus that shed less was more cytotoxic. An increase in shedding also resulted in a reduction in viral infectivity, whereas a decrease in shedding efficacy enhanced viral growth characteristics in vitro. Differences in shedding efficacy and, as a result, differences in the amount of mature GP available for incorporation into budding virions did not equate to differences in overall release of viral particles. Likewise, data suggest that the resulting differences in the amount of mature GP on the cell surface led to variations in the GP content of released particles and, as a consequence, in infectivity. In conclusion, fine-tuning of the levels of EBOV GP expressed at the surface of virus-infected cells via GP shedding plays an important role in EBOV replication by orchestrating the balance between optimal virion GP content and cytotoxicity caused by GP.

Published
2015

20. Thalamic Responses to Nociceptive-Specific Input in Humans: Functional Dichotomies and Thalamo-Cortical Connectivity

Author

Hélène Bastuji, Luis Garcia-Larrea, Caroline Perchet, Michel Magnin, Maud Frot, Stéphanie Mazza, Central Integration of Pain [Lyon], Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), NeuroPain - CRNL, Laboratoire d'Etude des Mécanismes Cognitifs (EMC), Université Lumière - Lyon 2 (UL2), INSERM E342, and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Nociception, 0301 basic medicine, Drug Resistant Epilepsy, MESH: Nociception, intracerebral EEG, Ventral posterolateral nucleus, 0302 clinical medicine, Cortex (anatomy), Neural Pathways, Evoked Potentials, Cerebral Cortex, MESH: Middle Aged, MESH: Drug Resistant Epilepsy, Middle Aged, Electrodes, Implanted, MESH: Evoked Potentials, cortex, nociceptive stimulus, medicine.anatomical_structure, MESH: Young Adult, Thalamic Nuclei, MESH: Lasers, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Nociceptive Stimulus, MESH: Electrocorticography, Psychology, Adult, Cognitive Neuroscience, Thalamus, Sensory system, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, MESH: Thalamic Nuclei, thalamus, Physical Stimulation, medicine, Humans, human, MESH: Physical Stimulation, Latency (engineering), MESH: Humans, MESH: Neural Pathways, Lasers, MESH: Adult, MESH: Cerebral Cortex, MESH: Male, 030104 developmental biology, MESH: Electrodes, Implanted, Electrocorticography, MESH: Female, Neuroscience, Nucleus, 030217 neurology & neurosurgery
Abstract

International audience; While nociceptive cortical activation is now well characterized in humans, understanding of the nociceptive thalamus remains largely fragmentary. We used laser stimuli and intracerebral electrodes in 17 human subjects to record nociceptive-specific field responses in 4 human thalamic nuclei and a number of cortical areas. Three nuclei known to receive spinothalamic (STT) projections in primates (ventro-postero-lateral [VPL], anterior pulvinar [PuA], and central lateral [CL]) exhibited responses with similar latency, indicating their parallel activation by nociceptive afferents. Phase coherence analysis, however, revealed major differences in their functional connectivity: while VPL and PuA drove a limited set of cortical targets, CL activities were synchronized with a large network including temporal, parietal, and frontal areas. Our data suggest that STT afferents reach simultaneously a set of lateral and medial thalamic regions unconstrained by traditional nuclear borders. The broad pattern of associated cortical networks suggests that a single nociceptive volley is able to trigger the sensory, cognitive, and emotional activities that underlie the complex pain experience. The medial pulvinar, an associative nucleus devoid of STT input, exhibited delayed responses suggesting its dependence on descending cortico-thalamic projections. Its widespread cortical connectivity suggests a role in synchronizing parietal, temporal, and frontal activities, hence contributing to the access of noxious input to conscious awareness.

Published
2015

21. Teaching Norms: Direct Evidence of Parental Transmission

Author

Brouwer, Thijs, Galeotti, Fabio, Villeval, Marie, Department of economics, Tilburg University, Tilburg University [Netherlands], Groupe d'Analyse et de Théorie Economique Lyon - Saint-Etienne (GATE Lyon Saint-Étienne), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), ANR-11-LABX-0042,CORTEX,Construction, Fonction Cognitive et Réhabilitation du Cerveau(2011), and ANR-16-IDEX-0005,IDEXLYON,IDEXLYON(2016)

Subjects
Economics and Econometrics, Parenting, JEL: C - Mathematical and Quantitative Methods/C.C9 - Design of Experiments/C.C9.C93 - Field Experiments, JEL: D - Microeconomics/D.D6 - Welfare Economics/D.D6.D63 - Equity, Justice, Inequality, and Other Normative Criteria and Measurement, Social Norms, Transmission, Field Experiment, Norm Enforcement, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, JEL: D - Microeconomics/D.D1 - Household Behavior and Family Economics
Abstract

We examine the educative role played by parents in social norm transmission. Using a field experiment, we study whether parents enforce and comply more with norms when their children are present compared to when they are not. We compare similar parents when or after they drop off or pick up their children at school. We find that parents accompanying children, in contrast to parents alone, are more likely to punish norm violators and to provide help to strangers when there is no violation. They also tend to substitute more direct punishment with withholding help as a means of indirect punishment.

Published
2022

22. Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

Author

Saison, J., Ferry, Tristan, Demaret, J., Maucort-Boulch, Delphine, Venet, F., Perpoint, T., Ader, Florence, Icard, V., Chidiac, Christian, Monneret, G., Study, Lyon HIV Cohort, Laboratoire d'Immunologie, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Laboratoire de Virologie [HCL-Hôpital de la Croix Rousse], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Biostatistiques [Lyon], and Hospices Civils de Lyon (HCL)

Subjects
Adult, Male, HAART, Regulatory T cell, T-Lymphocytes, T cell, Immunology, Antiretroviral Therapy, chemical and pharmacologic phenomena, HIV Infections, Biology, Lymphocyte Activation, T-Lymphocytes, Regulatory, regulatory T cells, immune activation, Immunophenotyping, Immune system, Antiretroviral Therapy, Highly Active, medicine, Humans, Immunology and Allergy, Highly Active, Viremia, Aged, Immunity, Cellular, immunological response, Immunity, HLA-DR Antigens, Odds ratio, Middle Aged, Viral Load, Regulatory, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, CD4 Lymphocyte Count, 3. Good health, Cross-Sectional Studies, Treatment Outcome, medicine.anatomical_structure, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cohort, very low-level viraemia, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cellular, CD8, Research Article, Immune activation
Abstract

International audience; The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (T(regs)) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4(+) T cell count (\textgreater or \textless 500/mm(3)). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4(+) lymphocytes, including T(reg) subsets, and CD8(+) T cells was performed. Percentages of activated CD4(+) T cells, T(regs), effector T(regs) and terminal effector T(regs) were found to be significantly elevated in iIR. Neither the percentage of activated CD8(+) T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4(+) T cell count and percentage of T(regs) were the only two parameters associated independently with iIR [odds ratio (OR) = 2\textperiodcentered339, P = 0\textperiodcentered001, and OR = 0\textperiodcentered803, P = 0\textperiodcentered041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4(+) and CD8(+) T cells, T(reg) percentages and very low-level viraemia. Causative interactions between T(regs) and CD4(+) T cells should now be explored prospectively in a large patients cohort.

Published
2014

23. Genetic association between helpless trait and depression-related phenotypes: evidence from crossbreeding studies with H/Rouen and NH/Rouen mice

Author

Luc Zimmer, J.-M. Vaugeois, Benoit Martin, Malika El Yacoubi, Joëlle Adrien, Michel Hamon, Daniela Popa, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuropsychopharmacologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, medicine.medical_specialty, Anhedonia, mouse model, Mice, Inbred Strains, Learned helplessness, Motor Activity, Neuropsychological Tests, Selective breeding, tail suspension test, 03 medical and health sciences, 0302 clinical medicine, Species Specificity, depressive disorder, Genetic drift, Dietary Sucrose, Fluoxetine, Internal medicine, medicine, Animals, Genetic Predisposition to Disease, Pharmacology (medical), sleep, Psychiatry, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Genetic association, Pharmacology, 0303 health sciences, Tail suspension test, Disease Models, Animal, Psychiatry and Mental health, Phenotype, Endocrinology, Antidepressive Agents, Second-Generation, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Psychology, Crossbreeding, 030217 neurology & neurosurgery, Personality, Behavioural despair test, medicine.drug
Abstract

Genetic factors are believed to be involved in the aetiology of unipolar depressive disorders. We have previously described a model built up by selective breeding of mice with different responses in the tail suspension test, a screening test for potential antidepressants. In this model, helpless H/Rouen mice are essentially immobile in this test, as well as in the Porsolt forced-swim test, whereas non-helpless NH/Rouen mice show the opposite behaviour, i.e. very low immobility. However, it is unclear whether or not the other phenotypic differences (forced swim test, locomotor activity, sucrose test, sleep patterns, effect of fluoxetine) observed between H/Rouen and the NH/Rouen mice may be attributed to a genetic drift phenomenon during the selection step, rather than being related to the trait of selection. In this study we used reciprocal crossbreeding between H/Rouen and NH/Rouen mice and obtained a segregating F2 population in order to determine whether phenotypic differences between the two lines co-segregate with the trait of selection. In the segregating F2 population, we found significant and strong genetic correlations between helplessness in the tail suspension test and some phenotypical features associated with depressive disorders such as 'alterations of sleep patterns', behavioural response to fluoxetine, immobility duration in the forced swim test, and anhedonia. Our results converge with clinical observations in depressed humans. These results strengthen the validity of the H/Rouen mouse as a model of depression, notably for preclinical studies with antidepressants. In addition, this model should open the way to identifying genes related to depression-like behaviours.

Published
2011

24. French utopian socialists as the first pioneers in development

Author

Ludovic Frobert, Triangle : action, discours, pensée politique et économique (TRIANGLE), Centre National de la Recherche Scientifique (CNRS)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Economics and Econometrics, 060106 history of social sciences, media_common.quotation_subject, JEL: B - History of Economic Thought, Methodology, and Heterodox Approaches/B.B1 - History of Economic Thought through 1925/B.B1.B14 - Socialist • Marxist, Poison control, Utopian socialism, Development, Politics, Saint-Simonianism, Utopia, 0502 economics and business, Economics, 0601 history and archaeology, 050207 economics, Order (virtue), JEL: B - History of Economic Thought, Methodology, and Heterodox Approaches/B.B5 - Current Heterodox Approaches/B.B5.B51 - Socialist • Marxian • Sraffian, media_common, Fourierism, 05 social sciences, Perspective (graphical), 06 humanities and the arts, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, 16. Peace & justice, Epistemology, Law, [SHS.HIST]Humanities and Social Sciences/History, Realism
Abstract

It is the purpose of this paper to present a reassessment of the works of the first nineteenth century French Utopian Socialists. It is well known that their contributions have been highly criticised, from both the economic and social point of view and the political or ethical one. Recent commentators, mostly historians and philosophers, have, however, underlined the realistic ambition and the reformist spirit of those approaches. This paper aims to develop this perspective. Indeed, it is my intention to defend the idea that the realism of utopia can be even better characterised by economists: the analyses of Leroux, Enfantin, Chevalier, Buchez or Considérant can be interpreted in terms of development. We study more specifically the initial flowering between 1830 and 1835 of the writings of the Saint-Simonians (Enfantin, Chevalier, Pereire), the works of the dissidents (Buchez, Leroux) and those of the main supporters of Fourier (Considerant, Transon, Lechevalier). We will conduct our survey proceeding from the notion of 'vision' proposed recently by Robert Heilbroner. We then examine whether these socialist pioneers really worked in order to elaborate a 'vision' in terms of 'development'. Copyright The Author 2010. Published by Oxford University Press on behalf of the Cambridge Political Economy Society. All rights reserved., Oxford University Press.

Published
2010

25. Translation of intronless RNAs is strongly stimulated by the Epstein–Barr virus mRNA export factor EB2

Author

Théophile Ohlmann, Evelyne Manet, Emiliano P. Ricci, Henri Gruffat, Cahora Medina-Palazon, Didier Decimo, Fabrice Mure, Contrôle traductionnel des ARNm eucaryotes et viraux – Translational control of Eukaryotic and Viral RNAs, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virologie humaine, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon, Manet, Evelyne, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Herpesvirus 4, Human, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, RNA Transport, Cell Line, Viral Proteins, 03 medical and health sciences, Genes, Reporter, Polysome, Genetics, Protein biosynthesis, Humans, RNA, Messenger, Nuclear export signal, Gene, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Messenger RNA, 030302 biochemistry & molecular biology, Intron, RNA, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Translation (biology), Phosphoproteins, Introns, 3. Good health, Polyribosomes, Protein Biosynthesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Trans-Activators
Abstract

International audience; The Epstein-Barr virus protein (EB2) allows the nuclear export of a particular subset of early and late viral RNAs derived from intronless genes. EB2 is conserved among most herpesvirus members and its presence is essential for the production of infectious particles. Here we show that, besides its role as a nuclear export factor, EB2 strongly stimulates translation of unspliced mRNAs without affecting overall cellular translation. Interestingly, this effect can be reversed by the addition of an intron within the gene. The spliced mRNA is then efficiently exported and translated even in the absence of EB2. Moreover, we show that EB2 associates with translating ribosomes and increases the proportion of its target RNA in the polyribosomal fraction. Finally, testing of EB2 homolog proteins derived from EBV-related herpesviruses, shows that, even if they play similar roles within the replication cycle of their respective virus, their mechanisms of action are different.

Published
2009

26. Neural representations of absolute and relative magnitudes in symbolic and nonsymbolic formats

Author

Parnika Bhatia, Léa Longo, Hanna Chesnokova, Jérôme Prado, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Prado, Jérôme

Subjects
Adult, intraparietal, [SCCO.NEUR]Cognitive science/Neuroscience, Cognitive Neuroscience, fMRI, [SCCO.NEUR] Cognitive science/Neuroscience, Magnetic Resonance Imaging, math cognition, Cellular and Molecular Neuroscience, Parietal Lobe, numbers, fractions, [SCCO.PSYC]Cognitive science/Psychology, [SCCO.PSYC] Cognitive science/Psychology, Humans, Mathematics
Abstract

Humans differ from other animal species in their unique ability to use symbols to represent numerical information. This ability is thought to emerge from the “neural recycling” of mechanisms supporting nonsymbolic magnitudes in the intraparietal sulcus (IPS), a hypothesis that has been applied to both absolute magnitudes (e.g., whole numbers) and relative magnitudes (e.g., fractions). Yet, evidence for the neuronal recycling hypothesis is inconsistent for absolute magnitudes and scarce for relative magnitudes. Here, we investigated to what extent the neural representations of absolute and relative magnitudes in symbolic and nonsymbolic formats overlap in the IPS. In a functional magnetic resonance imaging (fMRI) adaptation design, 48 adult participants were sequentially presented with lines, whole numbers, line ratios, and fractions that varied (vs. not varied) in magnitudes. Univariate analyses showed that the extent to which IPS mechanisms associated with whole numbers relied on mechanisms associated with lines depended upon participants’ arithmetic fluency. Multivariate analyses revealed that the right IPS encoded differences in format (nonsymbolic vs. symbolic) across both absolute and relative magnitudes. Therefore, IPS activity associated with magnitude processing may depend on the presentation format (nonsymbolic vs. symbolic) more than it depends on the type of magnitude (absolute vs. relative), at least for most adult participants.

Published
2022

27. Gut Inflammation in Mice Leads to Reduction in αvβ8 Integrin Expression on CD103+CD11b-Dendritic Cells

Author

Helena Paidassi, Dania Chanab, Mathilde Boucard-Jourdin, Mucosal Immunity, Vaccination, and Biometrics -- Immunité des muqueuses, vaccinations et biothérapies, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Integrins, chemical and pharmacologic phenomena, Context (language use), T-Lymphocytes, Regulatory, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigens, CD, In vivo, Animals, Medicine, Mesenteric lymph nodes, Colitis, ComputingMilieux_MISCELLANEOUS, biology, business.industry, Gastroenterology, hemic and immune systems, Dendritic Cells, General Medicine, medicine.disease, In vitro, Disease Models, Animal, medicine.anatomical_structure, Integrin alpha M, Immunology, Cancer research, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, business, 030215 immunology, Transforming growth factor
Abstract

We have read with great interest the study by Boschetti and colleagues.1 The authors demonstrate that in the context of dextran sodium sulphate [DSS]–induced acute experimental colitis, neoconversion of naive T cells into induced regulatory T cells [iTregs] in mesenteric lymph nodes [MLNs] is impaired. In addition, they observe that MLN dendritic cells [DCs] from colitic mice have a reduced ability to promote induction of Tregs in vitro as compared with DCs from control mice.1 The generation of iTreg is dependent on transforming growth factor [TGF]–β, which must be activated by αvβ8 integrin on DCs for the in vivo generation of intestinal iTregs and maintenance of immune homeostasis.2–4 MLN CD103-expressing DCs play a critical role in this process, and DSS-induced colitis is associated with a decreased proportion of CD103+ DCs [Figure 1A], as shown by Boschetti et al. 1 They thus propose that during …

Published
2016

28. Seventeen Cases of Daptomycin-Induced Eosinophilic Pneumonia in a Cohort of Patients Treated for Bone and Joint Infections: Proposal for a New Algorithm

Author

Truong-Thanh Pham, Romain Garreau, Fabien Craighero, Vincent Cottin, Benoît Ben Said, Sylvain Goutelle, Tristan Ferry, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Geneva University Hospitals and Geneva University, Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL], Hôpital Louis Pradel [CHU - HCL], Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon, Institut des Sciences Pharmaceutiques et Biologiques (ISPB), Université de Lyon-Université de Lyon, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Daptomycin, Oncology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Daptomycin-induced eosinophilic pneumonia, [SDV.IMM]Life Sciences [q-bio]/Immunology, BJI, Bone and joint infections
Abstract

Background Daptomycin is increasingly used in the treatment of bone and joint infections (BJIs) and may be responsible for daptomycin-induced eosinophilic pneumonia (DIEP), a potentially severe adverse drug reaction. The aim of this study was to describe DIEP in patients treated at a referral center for the management of BJI, and to revisit current definitions of this disease. Methods Patients treated from 1 January 2012 to 31 March 2021 were included in a prospective cohort (NCT02817711), in which all potential serious adverse events are prospectively recorded. Patients diagnosed with DIEP were retrospectively analyzed using different definitions. Results In a total of 4664 patients included in the cohort during the study period, 1021 patients (21.9%) received daptomycin, of whom 17 (1.7%) were diagnosed with DIEP. Most patients were male (n = 11 [64.7%]), and periprosthetic joint infection was the commonest BJI (n = 12 [70.6%]). Only 1 patient had bronchoalveolar lavage (BAL) eosinophil count ≥25%, while most patients had peripheral blood eosinophilia (n = 15 [88.2%]). Chest computed tomography (CT) was compatible with eosinophilic pneumonia in 13 of 14 cases (92.9%). All patients recovered upon discontinuation of daptomycin. Using the different definitions available, only a minority of cases fulfilled existing criteria for DIEP. We propose a new algorithm that includes specific CT scan signs, and systemic instead of BAL eosinophilia. Conclusions DIEP is a rare event that requires prompt discontinuation of the causative antibiotic. Current criteria to diagnose definite DIEP are too restrictive and not easily applicable in clinical practice. A new algorithm is proposed here (Lyon algorithm) to facilitate the early identification of DIEP.

Published
2022

29. Meningoencephalitis Due to Toscana Virus in a French Traveler Returning From Central Italy

Author

Philippe Bossi, Hervé Zeller, François Bricaire, Pierre Hausfater, Bruno Riou, Isabelle Schuffenecker, Loïc Epelboin, Service des maladies infectieuses et tropicales [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), Service des Urgences [CHU Pitié-Salpêtrière], 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)-Sorbonne Université (SU), Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)

Subjects
Male, MESH: Sandfly fever Naples virus, Antibodies, Viral, 0302 clinical medicine, Meningoencephalitis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Phlebotomus Fever, Travel medicine, 030212 general & internal medicine, Phlebotomus, MESH: Travel, MESH: Aged, MESH: Immunoglobulin G, Travel, 0303 health sciences, biology, MESH: Meningitis, Viral, General Medicine, Meningitis, Viral, MESH: Immunoglobulin M, 3. Good health, Italy, France, Meningitis, Encephalitis, medicine.medical_specialty, MESH: Phlebotomus Fever, 03 medical and health sciences, stomatognathic system, parasitic diseases, medicine, Humans, MESH: Meningoencephalitis, Aged, MESH: Humans, 030306 microbiology, Toscana virus, business.industry, MESH: Italy, Sandfly fever Naples virus, biology.organism_classification, medicine.disease, Virology, MESH: Male, MESH: France, Immunoglobulin M, Immunoglobulin G, Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Antibodies, Viral
Abstract

International audience; Toscana virus (TOSV) is an arthropod-borne virus transmitted by sand flies of Phlebotomus species that has been recognized as an agent associated with acute meningitis and encephalitis around the Mediterranean. We report the first imported case of meningoencephalitis due to TOSV in a traveler returning from Central Italy to France.

Published
2008

30. P443 Risk of incident Cancer in Patients with Inflammatory Bowel Disease with Prior Breast Cancer: a Multicentre Cohort Study

Author

G Le Cosquer, C Gilletta, A Amiot, P Rivière, M Nachury, C Rouillon, Y Bouhnik, V Abitbol, S Nancey, M Fumery, G Savoye, A Biron, L Picon, L Peyrin-Biroulet, M Vidon, C Reenaers, M Simon, B Caron, M Serrero, R Altwegg, A Benezech, F Goutorbe, J F Rahier, L Beaugerie, A L Pelletier, L Caillo, D Laharie, F Poullenot, CHI Créteil, CHU Bordeaux [Bordeaux], Hôpital Claude Huriez [Lille], CHU Lille, CHU Clichy, Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Universitaire de Nancy (CHU Nancy), Centre Hospitalier Universitaire de Liège (CHU-Liège), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille, CHU Montpellier, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Gastroenterology, General Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background Breast cancer is the most common malignancy observed in patients with inflammatory bowel diseases (IBD) unrelated to the disease or its treatment (Poullenot F et al. JCC 2022). The main aim of our study was to assess the risk of incident cancer according to the IBD treatment given in patients with prior breast cancer. Methods Consecutive IBD patients with prior breast cancer diagnosis were included in a multicenter retrospective cohort from 25 tertiary centres. Inclusion date corresponded to the diagnosis of index cancer. Follow up was calculated from the first administration of immunomodulator after cancer diagnosis (or cancer diagnosis date in absence of treatment) to the occurrence of incident cancer, corresponding to recurrence of breast cancer or de novo cancer, or to the last follow-up visit. Patients were categorized according to the use or not of immunomodulator after cancer diagnosis: thiopurines, methotrexate, anti-TNF, vedolizumab, ustekinumab. Crude incidence rates were compared between patients receiving at least one immunomodulator and those without immunomodulator before and after matching on age, lymph node, and metastasis extension and tumor’s grade, using a propensity-score analysis with a 1:1 ratio. Results Among the 151 identified patients, 80 patients with full available data were analyzed: 76 (95%) women; mean age at index cancer diagnosis: 51.5 years [standard deviation (SD): 11.5 years]; 44 (55%) with Crohn’s disease, 35 (44 %) ulcerative colitis and 1 (1 %) indeterminate colitis; median IBD duration at inclusion was 13 years [interquartile range (IQR) 6-21]. After a median follow up of 84 months [IQR 49-154], 16 (20%) incident cancers were observed: 12 (15%) recurrences and 4 (5%) cancer de novo. Three (4%) patients died from cancer related cause during the follow up. 39 (49%) patients received no immunomodulator and, 11 (14%) were treated with thiopurines, 6 (7.5%) with methotrexate, 18 (22.5%) with anti-TNF, 5 (6%) with vedolizumab and one (1%) with ustekinumab. Those treatments were initiated with a median interval of 24 months [IQR 7-48] after cancer diagnosis. Crude incidence rate per 1000 person-years were 47.97 for patients not exposed to any immunomodulator and 12.61 for the others (p=0.0248). After matching, adjusted crude incidence rates per 1000 person-years were 50 and 27.27, respectively (p=0.3798). Rates of survival without incident cancer were not different between the two groups after matching on age, lymph node, metastasis extension, and tumor’s grade (p=0.17) (Figure 1). Conclusion In the present multicenter retrospective cohort, incident cancer risk among patient with IBD and prior breast cancer was not increased in patients subsequently exposed to immunomodulators.

Published
2023

31. Inhibitory control dysfunction in parkinsonian impulse control disorders

Author

Gianni Pezzoli, Garance M. Meyer, Roberto Cilia, Charlotte Spay, Gabriel Gaugain, Philippe Boulinguez, Alina Beliakova, Bénédicte Ballanger, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centro Parkinson/Parkinson Institute, ASST ‘‘Gaetano Pini/CTO,’, and Fondazione IRCCS Istituto Neurologico 'Carlo Besta'

Subjects
Male, Impulse control disorder, Precuneus, impulsivity, Neuropsychological Tests, Electroencephalography, Impulsivity, Choice Behavior, 050105 experimental psychology, Executive Function, 03 medical and health sciences, precuneus, 0302 clinical medicine, Parkinsonian Disorders, Dopamine, Parietal Lobe, medicine, Humans, 0501 psychology and cognitive sciences, Parkinson, Aged, Brain Mapping, Supplementary motor area, medicine.diagnostic_test, business.industry, 05 social sciences, Middle Aged, medicine.disease, Executive functions, Anticipation, Disruptive, Impulse Control, and Conduct Disorders, inhibitory control, Inhibition, Psychological, medicine.anatomical_structure, Impulsive Behavior, Female, beta, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Nerve Net, medicine.symptom, Beta Rhythm, business, Neuroscience, Psychomotor Performance, 030217 neurology & neurosurgery, medicine.drug
Abstract

Impulse control disorders (ICDs) in Parkinson’s disease have been associated with dysfunctions in the control of value- or reward-based responding (choice impulsivity) and abnormalities in mesocorticolimbic circuits. The hypothesis that dysfunctions in the control of response inhibition (action impulsivity) also play a role in Parkinson’s disease ICDs has recently been raised, but the underlying neural mechanisms have not been probed directly. We used high-resolution EEG recordings from 41 patients with Parkinson’s disease with and without ICDs to track the spectral and dynamical signatures of different mechanisms involved in inhibitory control in a simple visuomotor task involving no selection between competing responses and no reward to avoid potential confounds with reward-based decision. Behaviourally, patients with Parkinson’s disease with ICDs proved to be more impulsive than those without ICDs. This was associated with decreased beta activity in the precuneus and in a region of the medial frontal cortex centred on the supplementary motor area. The underlying dynamical patterns pinpointed dysfunction of proactive inhibitory control, an executive mechanism intended to gate motor responses in anticipation of stimulation in uncertain contexts. The alteration of the cortical drive of proactive response inhibition in Parkinson’s disease ICDs pinpoints the neglected role the precuneus might play in higher order executive functions in coordination with the supplementary motor area, specifically for switching between executive settings. Clinical perspectives are discussed in the light of the non-dopaminergic basis of this function.

Published
2020

32. MixMir: microRNA motif discovery from gene expression data using mixed linear models

Author

Kevin Chen, Liyang Diao, Scott Norton, Antoine Marçais, BioMaPS Institute for Quantitative Biology, Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Cellular and Molecular Biology, University of Connecticut (UCONN), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Ribonuclease III, Untranslated region, Messenger, DEAD-box RNA Helicases, Mice, 0302 clinical medicine, Gene expression, 3' Untranslated Regions, Oligonucleotide Array Sequence Analysis, Mice, Knockout, Genetics, 0303 health sciences, education.field_of_study, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Methods Online, Sequence Analysis, Algorithms, Sequence analysis, Knockout, Population, Genomics, Computational biology, Biology, 03 medical and health sciences, microRNA, Animals, RNA, Messenger, Nucleotide Motifs, education, Gene, Embryonic Stem Cells, 030304 developmental biology, Messenger RNA, Sequence Analysis, RNA, Three prime untranslated region, Gene Expression Profiling, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Gene expression profiling, MicroRNAs, Adrenal Cortex, Linear Models, biology.protein, RNA, 030217 neurology & neurosurgery, Dicer
Abstract

International audience; microRNAs (miRNAs) are a class of ~22nt non-coding RNAs that potentially regulate over 60% of human protein-coding genes. miRNA activity is highly specific, differing between cell types, developmental stages and environmental conditions, so the identification of active miRNAs in a given sample is of great interest. Here we present a novel computational approach for analyzing both mRNA sequence and gene expression data, called MixMir. Our method corrects for 3' UTR background sequence similarity between transcripts, which is known to correlate with mRNA transcript abundance. We demonstrate that after accounting for kmer sequence similarities in 3' UTRs, a statistical linear model based on motif presence/absence can effectively discover active miRNAs in a sample. MixMir utilizes fast software implementations for solving mixed linear models, which are widely used in genome-wide association studies (GWASs). Essentially we use 3' UTR sequence similarity in place of population cryptic relatedness in the GWAS problem. Compared to similar methods such as miReduce, Sylamer and cWords, we found that MixMir performed better at discovering true miRNA motifs in three mouse Dicer-knockout experiments from different tissues, two of which were collected by our group. We confirmed these results on protein and mRNA expression data obtained from miRNA transfection experiments in human cell lines. MixMir can be freely downloaded from https://github.com/ldiao/MixMir.

Published
2014

33. K3-EDTA differentially inhibits the growth of Candida strains according to their azole resistance status

Author

Emilie Josse, Jean Menotti, Martine Wallon, Maxime Pichon, Damien Dupont, Pauline Tirard-Collet, Florence Persat, Hospices Civils de Lyon (HCL), Institut des Agents Infectieux [Lyon] (IAI), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), and PICHON, Maxime

Subjects
Azoles, Antifungal Agents, Microbiological culture, food.ingredient, Serial dilution, Ethylene diamine, Azole resistance, Microbial Sensitivity Tests, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, food, Drug Resistance, Fungal, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Sodium citrate, Humans, Agar, antimicrobial resistance, Candida albicans, Incubation, Edetic Acid, Candida, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Chemistry, Candidiasis, EDTA, General Medicine, biology.organism_classification, Infectious Diseases, fungal infections, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Abstract

The diagnosis of the life-threatening invasive Candida infections is mainly established using culture of specimens that might be collected on different devices including ethylene diamine tetraacetic acid (EDTA)-coated tubes. Despite the knowledge that EDTA inhibits bacterial cultures, and its use to treat oral fungal infections, its impact on Candida cultures has not been completely assessed. This study aimed at assessing it on azole-resistant and azole-susceptible strains. Clinical and American Type Culture Collection (ATCC) strains for Candida albicans (CA), C. glabrata (CGS), C. krusei (CK), azole-susceptible and azole-resistant strains of C. glabrata (CGS and CGR), C. lipolytica (CL), and C. inconspicua (CI) were characterized using MALDI-TOF MS and susceptibility testing and then incubated (1) with serial dilutions of tripotassic EDTA (0%–500% of the concentration in a sample tube) for 2 hours before plating onto ChromID Can2 agar; (2) for 0, 2, 4, 6, 7, or 8 hours at EDTA concentrations at 20% and 33% before seeding; and (3) with sodium citrate or lithium heparinate instead of EDTA for 2 hours before plating. After 48 hours at 35°C, colony-forming units were automatically quantified. An inhibitory effect of EDTA was observed, at different concentrations, for CA (20%), CGS (100%), and CGR (500%) (P < .05), but none was observed for CL, CI, and CK. The effect increased with incubation duration, at a faster rate for azole-susceptible strains. K3-EDTA inhibits Candida growth and EDTA-coated tubes should not be used for mycological culture-based analyses. The correlation between EDTA inhibition and Candida azole-resistance offers perspectives for the development of selective agar and new antifungal strategies.

Published
2019

34. P465 Is golimumab serum level predictive of clinical remission after intensification for loss of response in patients with ulcerative colitis?

Author

Fumery, Mathurin, Nancey, S., Filippi, J., Altwegg, R., Hebuterne, X., Boschetti, G., Veyrard, P., Yzet, Clara, Paul, S., Roblin, X., CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de Gastroentérologie, Hôpital de l'Archet 2, Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)

Subjects
[SDV]Life Sciences [q-bio], Gastroenterology, General Medicine, ComputingMilieux_MISCELLANEOUS
Abstract

Background Loss of response to golimumab occurs in nearly 40% of patients with ulcerative colitis (UC). Unlike others anti-TNF, no study has reported a correlation between serum golimumab level and response to drug intensification. The objective of this study was therefore to determine a threshold of serum golimumab before intensification predictive of clinical remission after optimization. Methods We included consecutive patients with UC and loss of response to golimumab (Mayo score between 6 and 12 and an endoscopic Mayo sub-score> 1) in a prospective multicentric cohort. Patients with loss of response at 50 mg / 4 weeks (W) and 100 mg / 4W underwent therapeutic intensification at 100 mg / 4W and 100 mg / 2W, respectively. Patients were followed prospectively with a first evaluation between weeks 2 and 4 (visit 2) and between weeks 4 and 8 (visit 3) after intensification. Clinical remission was defined by partial Mayo score ≤ 1. Serum level and anti-golimumab antibodies were evaluated at each visit (Lisa Tracker, Theradiag France). Results A total of 47 patients (female, 50%; median age, 39 years (IQR, 27–52) treated with golimumab for a median of 20.4 weeks (IQR, 10.7–38.3) were included. The median partial Mayo score was 6 (IQR, 5–7) and the endoscopic Mayo score was 3 (IQR, 2–3). The median golimumab serum level before intensification was 2.23 µg / mL (IQR, 1.02–3.96) and only three patients (6.2%) had anti-drug antibodies. After a total of 50 drug intensification, 23 (48.9%) patients had clinical response (100 mg / 4W: 14/25 (58.3%); 100 mg / 2W: 9/25 (36%)), 10 (21%) clinical remission and 18 (39%) endoscopic response. The median golimumab levels before intensification were respectively 2.17 µg / mL (IQR, 0.97–3.25) and 2.47 (IQR, 1.10–4.05) in responders and non-responders (p = 0.66), and 1.11 µg / mL (IQR, 0.59–2.29) and 2.47 µg / mL (IQR, 1.21–3.83) in patients with and without clinical remission after intensification (p = 0.054). In multivariate analysis, intensification to golimumab 100 mg / 2W (vs 100 mg / 4W) (OR, 0.11 [95%CI, 0.01 - 0.87], p=0.037) and change of golimumab level between V1 and V2 (OR, 1.48 [95%CI, 1.02 - 2.14], p=0.037) were significantly associated with clinical remission after intensification. Only one serious adverse event (infection) was reported during the 24-week follow-up. Conclusion In this prospective multicentric study, half of patients recaptured response following golimumab intensification in UC. Change of golimumab level was predictive of clinical remission after intensification.

Published
2022

35. Relationship Between Odor Intensity Estimates and COVID-19 Prevalence Prediction in a Swedish Population

Author

Zachary F. Mainen, Gernot Ernst, Eva Mishor, Franklin Mariño-Sánchez, Shiri Karagach, Monique A. M. Smeets, Thomas Hummel, Danielle Honigstein, Aharon Ravia, Johan N. Lundström, Moustafa Bensafi, Sagit Shushan, Camille Ferdenzi, Artin Arshamian, Caterina Dinnella, Behzad Iravani, Kobi Snitz, Kazushige Touhara, Noam Sobel, Sara Spinelli, Ofer Perl, Masako Okamoto, Yehudah Roth, Reut Weissgross, Erminio Monteleone, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Leerstoel Smeets, and Social-cognitive and interpersonal determinants of behaviour

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Physiology, Anosmia, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, coronavirus, Population prevalence, population prevalence, Disease, Olfactory dysfunction, AcademicSubjects/SCI01180, olfactory dysfunction, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Swedish population, Physiology (medical), Medicine, 030212 general & internal medicine, education, education.field_of_study, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, COVID-19, Sensory Systems, 3. Good health, Large sample, Coronavirus, Odor, Original Article, Coronavirus, anosmia, olfactory dysfunction, COVID-19, population prevalence, business, anosmia, 030217 neurology & neurosurgery, Demography
Abstract

In response to the coronavirus disease 2019 (COVID-19) pandemic, countries have implemented various strategies to reduce and slow the spread of the disease in the general population. For countries that have implemented restrictions on its population in a stepwise manner, monitoring of COVID-19 prevalence is of importance to guide the decision on when to impose new, or when to abolish old, restrictions. We are here determining whether measures of odor intensity in a large sample can serve as one such measure. Online measures of how intense common household odors are perceived and symptoms of COVID-19 were collected from 2440 Swedes. Average odor intensity ratings were then compared to predicted COVID-19 population prevalence over time in the Swedish population and were found to closely track each other (r = −0.83). Moreover, we found that there was a large difference in rated intensity between individuals with and without COVID-19 symptoms and the number of symptoms was related to odor intensity ratings. Finally, we found that individuals progressing from reporting no symptoms to subsequently reporting COVID-19 symptoms demonstrated a large drop in olfactory performance. These data suggest that measures of odor intensity, if obtained in a large and representative sample, can be used as an indicator of COVID-19 disease in the general population. Importantly, this simple measure could easily be implemented in countries without widespread access to COVID-19 testing or implemented as a fast early response before widespread testing can be facilitated.

Published
2020
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36. Physical activity to reduce mortality risk

Author

S. Celle, Pascal Edouard, Delphine Maudoux, Gremeaux, Martin Garet, Frédéric Roche, J. C. Barthelemy, David Hupin, Pichot, Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])

Subjects
Time Factors, business.industry, [SDV]Life Sciences [q-bio], Physical activity, 030204 cardiovascular system & hematology, Exercise Therapy, 03 medical and health sciences, 0302 clinical medicine, Autonomic Nervous System Diseases, Meta-Analysis as Topic, Cardiovascular Diseases, Risk Factors, Cause of Death, Environmental health, Humans, Medicine, Healthy Lifestyle, Self Report, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, Exercise, Aged
Published
2017

37. Are Host Genetics the Predominant Determinant of Persistent NasalStaphylococcus aureusCarriage in Humans?

Author

Cécile Angebault, François Rousset, Loïc Epelboin, Claire Dupont, Assiya El Miniai, Olivier Clermont, Sophie Jarraud, Alex van Belkum, Brandusa Elena Lixandru Lixandru, Raymond Ruimy, Mélanie Bertine, Gilles Peroz, Mehri Tavakol, Gerard Lina, Magaly Renard, Mathilde Lescat, Félix Djossou, Laurence Armand Lefevre, Régis Marc Bettinger, Antoine Andremont, Michèle Bes, François Vandenesch, Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Service de médecine interne et maladies tropicales, CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, laboratoire de biomécanique et bioinginérie, Laboratoire de mécanique des solides (LMS), École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris-Centre National de la Recherche Scientifique (CNRS), Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Université de Guyane (UG), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Staphylocoques, Hospices Civils de Lyon (HCL), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogenie des Staphylocoques, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), R&D Microbiologie, bioMerieux SA, BIOMERIEUX, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Emergence de la résistance bactérienne in vivo (EA3964), Université Paris Diderot - Paris 7 (UPD7), Developmental Biology, Medical Microbiology & Infectious Diseases, École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)

Subjects
Male, Rural Population, [SDV]Life Sciences [q-bio], Prevalence, MESH: Staphylococcus aureus/isolation & purification, medicine.disease_cause, Gene Frequency, Risk Factors, Polymorphism (computer science), Genotype, Immunology and Allergy, Aged, 80 and over, Genetics, 0303 health sciences, education.field_of_study, Epidemiological Factors, Middle Aged, Staphylococcal Infections, Bacterial Typing Techniques, 3. Good health, C-Reactive Protein, Infectious Diseases, Staphylococcus aureus, Carrier State, Female, Nasal Cavity, MESH: Nasal Cavity/microbiology, Adult, Adolescent, Population, Single-nucleotide polymorphism, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Microbiology, Young Adult, 03 medical and health sciences, medicine, Humans, education, Aged, MESH: Staphylococcal Infections/genetics, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Polymorphism, Genetic, 030306 microbiology, Indians, South American, DNA Fingerprinting, MESH: Carrier State/microbiology, Carriage, Interleukin-4, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background. Staphylococcus aureus nasal carriage is influenced by multifactorial interactions which are difficult to study in open populations. Therefore, we concomitantly assessed the epidemiological, microbiological, and human-genetic carriage-related factors in a nearly closed population. Methods. In 2006 and 2008, we collected nasal S. aureus strains, human DNA, and epidemiological data from 154 adult Wayampi Amerindians living in an isolated village in the Amazonian forest. The genetics of the strains (multilocus sequence type, spa type, and toxin-content type), epidemiological risk factors, antibiotic exposure, and allelic polymorphism of human genes putatively involved in carriage of the persistent carriers were compared with those of other volunteers. Results. Overall carriage prevalence was 41.7% in 2006 and 57.8% in 2008, but the overall prevalence of persistent carriage was only 26%. The rare and phylogenetically distant multilocus sequence type ST1223 was present in 18.5% of the carriers in 2006 and 34.8% in 2008. No epidemiological factors or antibiotic exposure were significantly associated with persistent carriage, but single nucleotide polymorphism distribution in C-reactive proteins C2042T and C1184T and interleukin-4 C524T genes was significantly associated (P=.02, by global test). Conclusion. Host genetic factors appeared to be the predominant determinant for S. aureus persistent nasal carriage in humans.

Published
2010

38. Parietal Damage Dissociates Saccade Planning from Presaccadic Perceptual Facilitation

Author

Jacques Luauté, Annabelle Blangero, Heiner Deubel, N. Laverdure, Yves Rossetti, Romeo Salemme, Werner X. Schneider, Aarlenne Z. Khan, Dominique Boisson, Laure Pisella, Gilles Rode, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Hôpital Henry Gabrielle [CHU - HCL], and Hospices Civils de Lyon (HCL)

Subjects
Adult, Male, genetic structures, Cognitive Neuroscience, media_common.quotation_subject, Posterior parietal cortex, Functional Laterality, 050105 experimental psychology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Discrimination, Psychological, 0302 clinical medicine, Saccadic suppression of image displacement, Parietal Lobe, Perception, Saccades, Humans, Attention, 0501 psychology and cognitive sciences, ComputingMilieux_MISCELLANEOUS, media_common, Visual search, 05 social sciences, Eye movement, Gaze, Saccadic masking, Cerebrovascular Disorders, Data Interpretation, Statistical, Saccade, Visual Perception, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Visual Fields, Psychology, Psychomotor Performance, 030217 neurology & neurosurgery, Cognitive psychology
Abstract

Neuro-CognitivePsychology, Bielefeld University, Bielefeld 33501, GermanyA well-known theory in the field of attention today is the premotortheory of attention which suggests that the mechanisms involved ineye movements are the same as those for spatial attention shifts.We tested a parietal damaged patient with unilateral optic ataxiaand 4 controls on a dual saccade/attentional task and showa dissociation between saccadic eye movements and presaccadicperceptual enhancement at the saccade goal. Remarkably, thoughthe patient was able to make the appropriate saccades to the left,impaired visual field (undistinguishable from saccades to his right,intact visual field), he was unable to discriminate the letter at thesaccade goal (whereas his performance was like controls for letterdiscrimination in his right visual field). This suggests that saccadeplanning and presaccadic perceptual facilitation are separable—planning a saccade to a location does not necessitate that theprocessing of this location is enhanced. Based on these results, wesuggest that the parietal cortex is necessary for the couplingbetween saccade planning and presaccadic perceptual facilitation.Keywords: attention, optic ataxia, parietal cortex, saccadesIntroductionEye movements and attention are very closely related.Normally, when we want to pay attention to an object, wemove our eyes so as to foveate on it (i.e., we shift our gaze) andthis is known as overt attention. However, it is also possible toshift attention without moving the eyes. This process is knownas covert attention. Both overt and covert attention have thesame objective: to enhance a location in space for furtherprocessing, either by bringing the object into higher-precisionprocessing pathways associated with central vision (Anstis1998), or by enhancing the efficiency of the processing inperipheral vision selectively at this specific location (Bushnellet al. 1981).According to the premotor theory of attention (Rizzolatti1983; Rizzolatti et al. 1987, 1994), a command to shift attentionis the same as a command to shift gaze. In both cases, attentionis shifted (covertly or overtly). This theory suggests thatpreparing a saccade to a peripheral target location involves thesame process as orienting selective attention to this peripherallocation, except that this process is then followed by the motorexecution. Inversely, any saccade will be associated witha spatially specific enhancement of processing at the locationof the saccade goal, i.e. saccades to a spatial location cannotoccur without a previous shift of attention to the location(Hoffman and Subramaniam 1995; Kowler et al. 1995; Goldberget al. 2006). In a behavioral study, Deubel and Schneider (1996)tested subjects’ ability to discriminate letter symbols atlocations around or at the saccade target location, beforesaccadic execution. They found that letter discrimination wasbest when it was in the same position as the saccade goal. Theability to discriminate a letter at any location other than thegoal of the saccade decreased to chance level. By showing thatwhen a saccade is executed toward a peripheral target, it ispreceded by a phenomenon of ‘‘presaccadic facilitation’’ ofletter discrimination specifically at this precise peripherallocation, this paradigm confirmed the spatial and temporalrelationship between saccades and attention: attention isoriented before saccadic execution toward the specific locationof the saccade goal, and may thus share common mechanismswith saccadic preparation (Schneider and Deubel 2002).Central to this theory is the finding that the same areas in thebrain that are involved in gaze or eye movements are alsoinvolved in attention shifts (Ignashchenkova et al. 2004; Mooreand Fallah 2004; Goldberg et al. 2006). One of the key areasshown to be involved in both attention and saccadic eyemovements is the lateral intraparietal area (LIP) in the monkeyposterior parietal cortex (Goldberg et al. 2006). We thereforetested involvement of the parietal cortex in the couplingbetween presaccadic attentional shifts and eye movements byobserving the performance of a patient with unilateral opticataxia due to damage to the right posterior parietal cortex. Ifsaccade planning and attentional shifts involve the samemechanisms, we should find a similar pattern of performancein target discrimination and saccade execution to the damagedvisual field. On the other hand, a dissociation between saccadicperformance and target discrimination performance couldsuggest that separate neural substrates govern attention andsaccade planning, but those processes could be coupled andoccur simultaneously. A second possibility could be that theparietal cortex mediates the coupling between a network ofareas involved in saccade planning and presaccadic facilitation,such as frontal and temporal areas. In normal behavior, it isimpossible to distinguish between a coupling and a commonsubstrate, however the impaired region/pathways in thispatient may provide valuable insight into these mechanisms.We tested the patient and 4 control subjects on a simplifiedversion of the task used by Deubel and Schneider (1996). In ourtask the saccade was always directed to the same location (at10 visual degrees of eccentricity) leftward or rightward.Subjects were then required to discriminate letters presentedbriefly during the saccade latency either at the saccade goal orat nonsaccade goal locations 3 closer or further away in thesame visual field. This task allowed us to test the presence ofpresaccadic facilitation, 1) at the location of the saccade goaland 2) at surrounding locations, testing for potential spatialdistortions in attentional shifts. Spatial distortions have been

Published
2008

39. Complete Human and Rat Ex Vivo Spermatogenesis from Fresh or Frozen Testicular Tissue

Author

Laurent David, Ingrid Plotton, Antonine Blondet, Philippe Durand, Nicolas Morel-Journel, Marie-Hélène Perrard, Nicolas Sereni, H. Lejeune, Caroline Schluth-Bolard, Sandrine Giscard d′Estaing, Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Conseil Général de l’Alimentation, de l’Agriculture et des Espaces Ruraux (CGAAER), Ingénierie des Matériaux Polymères (IMP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Communications Cellulaires et Différenciation (CCD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), inconnu, Inconnu, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA (UMR_8109)), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude sur le Polymorphisme des Micro-Organismes, UMR CNRS-IRD 9926 (CEPM), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon

Subjects
Male, hollow cylinder, 0301 basic medicine, Cryopreservation, Rats, Sprague-Dawley, bioreactor, Bioreactors, 0302 clinical medicine, Testis, In Situ Hybridization, Fluorescence, ComputingMilieux_MISCELLANEOUS, [SDV.BDD.GAM]Life Sciences [q-bio]/Development Biology/Gametogenesis, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Hydrogels, [CHIM.MATE]Chemical Sciences/Material chemistry, General Medicine, Seminiferous Tubules, Spermatids, Seminiferous tubule, medicine.anatomical_structure, Adult, medicine.medical_specialty, fertility preservation, Offspring, In Vitro Techniques, Biology, human spermatogenesis, 03 medical and health sciences, Species Specificity, Internal medicine, medicine, Animals, Humans, RNA, Messenger, Spermatogenesis, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Cell Biology, Protamine, Culture Media, Rats, [CHIM.POLY]Chemical Sciences/Polymers, 030104 developmental biology, Endocrinology, Reproductive Medicine, biology.protein, chitosan, Ex vivo, Fluorescence in situ hybridization, Hormone
Abstract

International audience; Until now, complete ex vivo spermatogenesis has been reported only in the mouse. In this species, the duration of spermatogenesis is 35 days, whereas it is 54 days in the rat and 74 days in humans. We performed long-term (until 60 days) cultures of fresh or frozen rat or human seminiferous tubule segments in a bioreactor made of a hollow cylinder of chitosan hydrogel. Testicular tissues were obtained from 8- or 20-day-old male rats or from adult human subjects who had undergone hormone treatments leading to a nearly complete regression of their spermatogenesis before bilateral orchiectomy for gender reassignment. The progression of spermatogenesis was assessed by cytological analyses of the cultures; it was related to a dramatic increase in the levels of the mRNAs specifically expressed by round spermatids, Transition protein 1, Transition protein 2, and Protamine 3 in rat cultures. From 2% to 3.8% of cells were found to be haploid cells by fluorescence in situ hybridization analysis of human cultures. In this bioreactor, long-term cultures of seminiferous tubule segments from prepubertal rats or from adult men allowed completion of the spermatogenic process leading to morphologically mature spermatozoa. Further studies will need to address the way of optimizing the yield of every step of spermatogenesis by adjusting the composition of the culture medium, the geometry, and the material properties of the chitosan hydrogel bioreactors. Another essential requirement is to assess the quality of the gametes produced ex vivo by showing their ability to produce normal offspring (rat) or their biochemical normality (human).

Published
2016

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