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QT Interval, Antipsychotics and Correlates Among Patients with Schizophrenia: Cross-Sectional Data from the Multicentric Real-World FACE-SZ
No full textInternational audienc
Mind wandering during implicit learning is associated with increased periodic EEG activity and improved extraction of hidden probabilistic patterns
No full textInternational audienceMind wandering, occupying 30-50% of our waking time, remains an enigmatic phenomenon in cognitive neuroscience. A large number of studies showed a negative association between mind wandering and attention-demanding (model-based) tasks in both natural settings and laboratory conditions. Mind wandering, however, does not seem to be detrimental for all cognitive domains, and was observed to benefit creativity and problem-solving. We examined if mind wandering may facilitate model-free processes, such as probabilistic learning, which relies on the automatic acquisition of statistical regularities with minimal attentional demands. We administered a well-established implicit probabilistic learning task combined with thought probes in healthy adults (N = 37, 30 females). To explore the neural correlates of mind wandering and probabilistic learning, participants were fitted with high-density electroencephalography. Our findings indicate that probabilistic learning was not only immune to periods of mind wandering but was positively associated with it. Spontaneous, as opposed to deliberate mind wandering, was particularly beneficial for extracting the probabilistic patterns hidden in the visual stream. Cortical oscillatory activity in the low-frequency (slow and delta) range, indicative of covert sleep-like states, was associated with both mind wandering and improved probabilistic learning, particularly in the early stages of the task. Given the importance of probabilistic implicit learning in predictive processing, our findings provide novel insights into the potential cognitive benefits of task-unrelated thoughts in addition to shedding light on its neural mechanisms. Statement of significance Mind wandering poses an unresolved puzzle for cognitive neuroscience: it is associated with poor performance in various cognitive domains, yet humans spend 30-50% of their waking time mind wandering. We proposed that mind wandering may be beneficial for less attention-demanding cognitive processes requiring automatic, habitual learning. We assessed an implicit probabilistic learning task measuring the ability to extract (without awareness) hidden regularities from the information stream. Participants showed superior performance in probabilistic learning during periods of mind wandering, especially when such task-unrelated thoughts occurred spontaneously without intention. Moreover, mind wandering and probabilistic learning were both associated with slow frequency neural activity, suggesting that mind wandering may reflect a transient, offline state facilitating rapid learning and memory consolidation
Impact de l'activation de Rac1 dans la dégranulation des éosinophiles au cours de l'asthme sévère
No full textInternational audienceAsthma is a chronic airway disease characterized by exacerbated inflammation, hyperresponsiveness, and associated bronchial remodeling. Despite innovative biotherapies, severe asthma remains largely uncontrolled, highlighting the need for new therapeutic approaches. Rac1 GTPase has recently been identified as a major contributor to bronchial hyperresponsiveness and remodeling. In this study, we demonstrate Rac1 overactivation in pulmonary eosinophils of asthmatic patients. Identifying the role of Rac1 GTPase in the molecular mechanisms of polymorphonuclear cells during allergic asthma could validate Rac1 as an innovative therapeutic target for severe asthma.L’asthme est une pathologie chronique des voies aériennes caractérisée par une inflammation exacerbée et une hyperréactivité associée à un remodelage bronchique. Malgré les biothérapies innovantes, l’asthme sévère reste, dans certains cas, incontrôlé et nécessite de nouvelles approches thérapeutiques. La GTPase Rac1 a été identifiée récemment comme acteur majeur dans l’hyperréactivité et le remodelage bronchique. Dans cette étude, nous mettons en évidence une suractivation de Rac1 dans les éosinophiles pulmonaires de patients asthmatiques. Identifier le rôle de la GTPase Rac1 dans les mécanismes moléculaires du polynucléaire au cours de l’asthme allergique permettrait de valider Rac1 comme cible thérapeutique innovante dans l’asthme sévère
Optimization and evaluation of new decontamination procedures inactivating human prions
No full textInternational audienceBackgroundPrions are protein-only infectious agents for which no prophylactic or curative treatment exists. Infectivity bioassays based on hamster-263K prions allowed to identify processes capable of inactivating prions on medical devices. However, a 2016 publication study revealed that detergent formulations effective against hamster strain had poor efficacy against human strains. Shortly after, three probable cases of accidental Creutzfeldt–Jakob disease underscored the risk for scientists, health workers, and patients exposed to contaminated materials. The governmental guidelines were modified and emphasizing the need for formulations effective against human prions and robust in vitro and in vivo evaluation protocols. Here, we aimed to compare infectivity bioassays with those of their PMCA counterparts to propose a robust method for evaluating prionicide treatments against human prions.Methods: Stainless steel wires were contaminated with two humanized prion strains. The wires were then treated with different protocols based on a new formulation termed TFD Premium and WHO references. Residual prion seeding activity and infectivity on the wire and in wastewater were quantified using mb-PMCA and ad hoc bioassays. For vCJD, PMCA compared humanized prions and a human-derived prion isolate.Findings: TFD Premium proved more efficient at decontaminating humanized prions than 1 N NaOH for 1 hour at room temperature. Tg650-sCJD-VV2 were more resistant to inactivation than vCJD prions. For vCJD, strain from both sources shown similar resistant profile against TFD Premium. Finally, there was perfect alignment between the highly sensitive PMCA cell-free assay and the bioassays
Joint-likelihood Bayesian model for urban heat island inference with two crowdsourced datasets
No full textInternational audienceHeat stress is a growing public health concern in cities as urban dwellers are exposed to combined effect of global warming and urban heat islands. We develop a cuttingedge Bayesian Hierarchical Model that incorporates data from connected vehicles and citizen weather stations to draw hourly urban air temperature maps at hectometric resolution. To overpass the uncertainty of opportunistic observations, we set priors on the measurement error into two separate likelihoods, one per each data source. The model with joint-likelihoods is compared to two single models, one for the onboard thermometers and the other for citizen weather stations. All models, inferred with the INLA-SPDE approach, are evaluated against an independent professional network in the French city of Dijon. The maps are consistent with the reference network. The performance of the joint-likelihood model with both data sources exceeds the other two. Its Root Mean Square Error is less than 1 • C for more than 75% of the 714 hourly maps. These results open up new perspectives in urban climatology and for the post-processing of numerical weather forecasts on cities. They will also support research on urban heat exposure and all actors involved in sustainable urban planning. Bayesian hierarchical model, connected vehicles, crowdsourcing, integrated nested Laplace approximate (INLA), personal weather stations, urban heat islan
Interleukin 17-producing C-C motif chemokine receptor 6 + conventional CD4+ T cells are arthritogenic in an animal model of spondyloarthritis
No full textInternational audienceObjective: Spondyloarthritis (SpA) is a group of chronic inflammatory disorders associated with the human leukocyte antigen (HLA) class I allele HLA-B27. Transgenic rats expressing HLA-B27 and human β2-microglobulin (B27 rats) develop clinical manifestations resembling SpA called rat SpA. IL-17 and TNF are key proinflammatory cytokines implicated in both human and rat SpA. We aimed to determine which T cell subset(s) produce IL-17 and TNF during rat SpA, characterize their tissue distribution and tested their pathogenicity in vivo. Methods: Cytokine production by T cell subsets was evaluated in target tissues and lymphoid organs during rat SpA. Pathogenicity of purified IL-17+ cells was assessed in vivo by cell transfer. Blood samples were used to translate B27 rats findings to SpA patients. Results: Conventional CD4+ T cells (Foxp3-; Tconv) and γδ T cells were the main producers of both IL-17 and TNF in B27 rats. IL-17-producing Tconv and γδ T cells were expanded in the colon of premorbid 3-weeks-old B27 rats. C-C motif chemokine receptor 6 (CCR6) allowed the isolation of IL-17+ Tconv (Th17) in rat. Transfer of B27 rat IL-17-producing CCR6+ Tconv but not of γδ T cells into disease-free nude B27 rats induced arthritis, directly demonstrating for the first time the arthritogenic potential of Th17 cells in SpA. Finally, a CCR6+ IL-17+ Tconv expansion enriched for IL-17F production was evidenced in SpA patients. Conclusion: Our study demonstrates that IL-17+TNF+CCR6+ Th17 cells and IL-17+ γδ T cells are expanded preceding SpA onset in B27 rats and that only IL-17+TNF+CCR6+ Th17 cells can trigger arthritis
La sorcellerie se transmet-elle génétiquement ?
No full textInternational audienceThe genogram is regularly used in transcultural consultations. These are offered as a second line of treatment to migrant families whose care is stagnant or complicated by cultural issues. The contribution of a genogram can be illustrated through the situation of Sandra, a 32-year-old patient of Cape Verdean origin with a chronic anxiety disorder. Her anxiety fixation concerns her inability to perceive the presence of the dead, unlike the rest of her family, who possess this gift. She says she feels isolated from her family, especially as she feels acculturated.Le génogramme est régulièrement utilisé dans le cadre des consultations transculturelles. Celles-ci sont proposées en seconde intention à des familles migrantes dont la prise en charge en soins est stagnante ou complexifiée par des questions culturelles. Les apports d’un génogramme peuvent être illustrés à travers la situation de Sandra, patiente de 32 ans d’origine capverdienne qui présente un trouble anxieux chronicisé. Sa fixation anxieuse porte sur son incapacité à percevoir la présence des morts contrairement au reste de sa famille qui possède ce don. Elle dit d’ailleurs être isolée de sa famille, d’autant qu’elle se sent acculturée
The prion-family protein Doppel exerts a protective role during influenza virus infection
No full textInternational audienceThe cellular form of the prion protein (PrPC), known for its involvement as a misfolded isoform in transmissible spongiform encephalopathies, has recently been identified to exert a protective effect against viral infections. In this study, we explored the role of 2 other prion family members, Shadoo and Doppel, in protection against influenza A virus infection in mice. Lung expression levels of these genes revealed marked differences, with high expression of PrPC, low expression of Doppel, while Shadoo remained undetectable.Mice genetically knocked out for the genes encoding PrPC, Prnp−/− or Doppel, Prnd−/−, showed increased susceptibility to the virus, resulting in elevated morbidity compared with wild-type mice and mice knocked out for Shadoo, Sprn−/−. Unlike previous results observed in Prnp−/− mice, the absence of Doppel does not show enhancing effect on virus replication levels. Histological analysis of lung tissue from Prnd−/− mice revealed no difference in lesion size and severity compared with wild-type mice. However, transcriptomic analysis on day 7 postinfection revealed distinct signatures in Prnd−/− mice, highlighting the role of specific genes associated with polymorphonuclear neutrophil cells. Bronchoalveolar lavages confirmed a substantial neutrophil influx and increased inflammatory markers in the lungs of Prnd−/− mice. Neutrophil depletion experiments demonstrated a direct link between excessive neutrophil influx and increased susceptibility, mitigating pathology and partially restoring a wild-type phenotype in Prnd−/− mice. These findings underscore the complex role of Doppel in modulating the host immune response to influenza virus infection, particularly in regulating neutrophil recruitment and its implications on disease outcomes
Systemic treatment among frail older patients with cancer: An observational cohort
No full textInternational audienceIntroduction: In the past, certain oncological therapies were not offered to frail older patients. However, the advancement of geriatric oncology, tailored chemotherapy regimens, the introduction of new treatments, and the optimization of supportive care have contributed to enhancing the therapeutic margin. We aimed to evaluate the benefit of systemic treatment among older adults by assessing the three-month survival of older frail patients with metastatic cancer.Materials and methods: This retrospective cohort study included patients aged 70 and over with metastatic cancer who underwent pre-therapeutic geriatric assessment at Gustave Roussy Hospital between May 2020 and May 2022 and were categorized as "frail" according to the SIOG-1 classification, whether they received systemic treatment (ST group) or exclusive supportive care (SC group).Results: The ST group included 77 patients, and the SC group included 44 patients. Patients in the ST group had a median age of 80.6 years (82.7 years in SC group). The three-month overall survival rate was 81.8 % [95 % Confidence Interval (CI) 71.8; 88.9] in the ST group. The median survival rate was 10.6 months [95 % CI 6.3; 12.6] in the ST group. In multivariate analysis within the ST group, loss of autonomy assessed by activity of daily living (ADL) (HR 2.16 [1.09; 4.28]) and more frailty factors (HR 1.40 [1.01; 1.95]) were associated with lower three-month survival.Discussion: Older frail patients with metastatic cancer may benefit from systemic oncologic treatment. The introduction of such treatment for patients with loss of autonomy in ADL or cumulative frailty factors should be considered only with caution
