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Association Between Metabolic Syndrome, Obesity, and Cognitive Performances in Individuals With Bipolar Disorders: Cross‐Sectional and Longitudinal Analyses in the FACE ‐ BD Cohort
No full textInternational audienceIntroduction: Metabolic syndrome (MetS) has been suggested to be associated with cognitive impairments in bipolar disorder (BD); however, studies are limited by small sample sizes or cross-sectional design. Our objective is to evaluate the cross-sectional and longitudinal associations between MetS and cognitive performances in a large cohort of individuals with BD.Methods: 1175 individuals with a DSM-IV diagnosis of BD were included from the FACE-BD cohort, assessed with a standardized battery of clinical and neuropsychological tests and followed up with a cognitive retest at 2 years for a subsample (n = 367). A global cognitive index was created by using a Principal Component Analysis. Associations between MetS and cognitive performances at baseline were explored using multiple analyses of covariance and linear mixed models were used for longitudinal data.Results: The prevalence of MetS was 21.5% in this sample. Multivariable analyses identified associations between MetS and poorer cognitive performance in the cross-sectional analysis, independently of age, gender, education level, psychotropic treatments, and comorbidities. Specifically, individuals with MetS showed poorer results (global cognitive index, cognitive flexibility, inhibition, and verbal memory). After adjustment, the longitudinal analysis showed no change in the global cognitive index at year 2 and no time × metabolic syndrome interaction.Conclusions: Our results suggest that MetS is cross-sectionally, but not longitudinally, associated with poorer cognitive performances in BD. This study highlights the importance of systematically and accurately screening for metabolic abnormalities in individuals with BD, and screening for cognitive deficit especially in individuals with MetS. Our results suggest that MetS is not a risk factor for cognitive decline during the follow-up, but further longitudinal studies are required
Amaryllidaceae Alkaloids and Phenolic Acids Identification in Leucojum aestivum L. Plant Cultures Exposed to Different Temperature Conditions
No full textInternational audienceAmaryllidaceae alkaloids are of notable pharmacological relevance. For instance, galanthamine is used in the treatment of Alzheimer’s disease, while other alkaloids (lycorine, crinine, etc.) derived from Amaryllidaceae plants are also of great interest because they exhibit antitumour, antiviral, antibacterial, antifungal, antimalarial, analgesic and cytotoxic properties. Phenolic acids comprise a group of natural bioactive substances that have commercial value in the cosmetic, food and medicinal industries due to their antioxidant, anticancer, anti-inflammatory and cardioprotective potential. In the present study, the effect of temperature (15, 20, 25 and 30 °C) on Amaryllidaceae alkaloid and phenolic acid biosynthesis in Leucojum aestivum in vitro plant cultures was investigated. The highest diversity of alkaloids (i.e., galanthamine, crinan-3-ol, demethylmaritidine, crinine, 11-hydroxyvitattine, lycorine, epiisohaemanthamine, chlidanthine) was noted in plants cultured at 30 °C. By contrast, ismine and tazettine were only present in plants cultured at 15 °C. Temperatures of 20 °C and 30 °C were found to stimulate galanthamine accumulation. The highest lycorine content was noted in plants grown at temperatures of 15 and 30 °C, and it was negatively correlated with the expression of the gene that encodes the cytochrome P450 96T (CYP96T) enzyme which catalyses a key step in the biosynthesis of different types of Amaryllidaceae alkaloids. This observation may reflect temperature-induced shifts in metabolic flux among different branches of Amaryllidaceae alkaloid biosynthesis. The observed stimulating effect of a 15 °C temperature on the chlorogenic, caffeic, p-coumaric, sinapic, ferulic and isoferulic acid content was in line with the highest expression of a gene that encodes the tyrosine decarboxylase (TYDC) enzyme, which is involved in plant stress response mechanisms. At 30 °C, however, the highest content of the caffeic, vanillic, p-coumaric and isoferulic acids was noted
A novel glutathione transferase harboring an FMN redox cofactor
No full textInternational audienceGlutathione transferases (GSTs) constitute a widespread superfamily of multifunctional enzymes with roles in cellular detoxification and secondary metabolism. We report that the poorly characterized Iota‐class enzymes (GSTIs) are mainly found in photosynthetic prokaryotes and eukaryotes, excluding Spermatophyta, and in a few fungi of the order Chytridiomycota. GSTIs are distinguished from other GSTs by the presence of N‐ and C‐terminal extensions of unknown function flanking the central GST domain. Focusing on the GSTI enzyme (SynGSTI1) of the model cyanobacterium Synechocystis sp. PCC 6803 ( S.6803 ), we showed that recombinant SynGSTI1 protein purified from Escherichia coli and S.6803 exhibited thiol‐transferase and dehydroascorbate reductase activities consistent with the presence of a CPYC catalytic motif in its GST domain. SynGSTI1 was found to be monomeric and to exhibit a spectrophotometric signature between 300 and 500 nm, which was attributed to a flavin mononucleotide (FMN). The C‐terminal domain of SynGSTI1 contained a conserved PRDM/L motif involved in the binding of an FMN ligand and showed a structure similar to that of the α‐subunit of phycoerythrin components of the light‐harvesting antenna of some cyanobacteria, most red algae and some cryptophytes. The deletion of the SynGSTI1 encoding gene in S.6803 (i) caused a slight decrease in the photosynthetic pigment content without impairing growth in standard photoautotrophic conditions; (ii) increased sensitivity to moderate and high light intensities; (iii) reduced glutathione levels and consistently; (iv) decreased tolerance to oxidative and metal stresses triggered by H 2 O 2 , diamide and cobalt. Thus, SynGSTI1 defines a unique GST subclass with critical roles in redox homeostasis and stress tolerance
Frictions, alignements et engagement dans les dispositifs hybrides : Analyse croisée des perceptions et des pratiques enseignantes et étudiantes
No full textInternational audienceCette communication s’inscrit dans le Work Package 2 (WP2) du projet international HyPES, qui vise à décrire et comprendre les transformations des pratiques d’apprentissage des étudiants en lien avec les caractéristiques techno-pédagogiques des dispositifs hybrides de formation auxquels ils participent. Cette recherche prolonge les travaux du projet européen HySUP (Deschryver & Charlier, 2012 ; Peraya, 2010) en adoptant une approche qualitative et longitudinale, plus à même de rendre compte de la complexité et des dynamiques évolutives de l’expérience étudiante dans les formations hybrides. Alors que HySUP reposait principalement sur des questionnaires fermés centrés sur les perceptions, HyPES développe une méthodologie d’enquête fondée notamment sur le recueil de récits d’expériences, croisés avec ceux des enseignants impliqués dans les mêmes dispositifs.Le cadre conceptuel mobilisé dans ce WP2 articule trois ensembles théoriques. Le premier concerne les travaux de Vermunt et Verloop (1999) sur la congruence et la friction entre enseignement et apprentissage. Ce modèle, enrichi par les travaux de Chaker (2024), permet d’analyser les tensions entre les stratégies pédagogiques proposées par les enseignants et les pratiques effectives des étudiants, en tenant compte de leurs dimensions cognitives, sociales et affectives, mais aussi de leur inscription temporelle et située. Le deuxième ensemble repose sur la notion d’environnement personnel d’apprentissage (EPA), défini comme un système évolutif d’artefacts (outils, médias, ressources humaines, valeurs, stratégies cognitives et métacognitives, connaissances et compétences) choisis et articulés par l’étudiant pour apprendre dans une situation donnée (Väljataga & Laanpere, 2010 ; Roland & Talbot, 2014 ; Felder, 2019). Le troisième ensemble s’appuie sur un modèle systémique de la co-construction des dispositifs hybrides, tel que proposé par Charlier et Peltier (2024), qui met l’accent sur les interactions dynamiques entre les caractéristiques des étudiants, celles des dispositifs et des représentations et les stratégies d’apprentissage construites par les étudiants.L’enquête se déploie dans 15 programmes de formation, identifiés dans différents établissements partenaires du projet. Chaque terrain comprend le suivi longitudinal de cinq étudiants et de deux enseignants, sur trois semestres consécutifs. Les formations concernées relèvent de champs variés (éducation, santé, ingénierie, etc.) et mobilisent des formes d’hybridation différenciées (blended, HyFlex, synchrone hybride, flipped). Le dispositif méthodologique repose sur des entretiens individuels approfondis, d’une durée de 120 minutes, réalisés à partir d’un guide structuré selon trois temps : le récit de deux expériences significatives d’apprentissage, la description d’un objet métaphorique de l’expérience étudiante, et la réponse au questionnaire proposé par le WP1 afin de caractériser les représentations qu’ont les étudiants des dispositifs de formation choisis. Ces recueils de données (répétés trois fois avec le même étudiant au cours de trois semestres consécutifs) sont à chaque fois complétés par un recueil auprès de leurs enseignants leur demandant de compléter le questionnaire du WP1 (point de vue enseignant).L’analyse des données est réalisée selon la méthode MEPA (Felder, 2019), mise en œuvre avec le logiciel YEPA®. Cette méthode permet de modéliser les EPA en identifiant quatre types d’artefacts (techniques, didactiques, pédagogiques, sociaux) et en les reliant à un schème représentant l’intention d’apprentissage. Ces modélisations offrent une visualisation des pratiques d’apprentissage individuelles, tout en permettant des comparaisons dans le temps (entre semestres), entre dispositifs (synchronique) et entre étudiants (intra- et inter-cas). Elles rendent visibles les ajustements, les continuités et les ruptures dans les pratiques d’apprentissage, en lien avec les évolutions des contextes, des contenus et des formes d’accompagnement.Le symposium sera l’occasion de proposer des analyses de cas contrastés portant sur les premiers recueils de données réalisés. Les analyses chercheront à identifier et à comprendre les dynamiques de transformation des pratiques d’apprentissage d’un même étudiant confronté à deux dispositifs différents. Ces analyses permettront de mieux comprendre comment les étudiants orchestrent leurs apprentissages à partir d’une pluralité de ressources, au-delà notamment de celles prévues par le cadre institutionnel.À travers cette contribution, le WP2 entend participer à la construction d’un modèle développemental évolutif de la qualité des dispositifs hybrides, en lien étroit avec les analyses typologiques du WP1 et les analyses systémiques du WP3. Il met en lumière les conditions d’un engagement effectif dans les apprentissages hybrides, ainsi que les leviers et les obstacles à la construction des pratiques d’apprentissage. Il souligne l’importance d’une hybridation contextualisée, négociée et accompagnée, qui tienne compte de la diversité des parcours, des expériences et des aspirations des étudiants. Ce travail, encore en cours, amènera dans ses phases ultérieures à une analyse plus approfondie des relations entre dispositifs, pratiques et contextes, en vue de proposer des principes de conception et d’évaluation pour des dispositifs hybrides de qualité, au service d’une amélioration continue de l’expérience d’apprentissage dans l’enseignement supérieur
Supportive cancer care and patient satisfaction: international prospective longitudinal study – secondary data analysis
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Mixed Ni/Cu-sandwich dawson polyoxotungstates: Electrochemistry and DFT insights
No full textInternational audienceGiven the established electrocatalytic potential of Ni(II)-and Cu(II)-containing tungsten-based POMs, the primary objective of this work was to create a unique molecular architecture combining both active metal centres in the two Dawson sandwich POMs, [(CuOH 2 ) 2 Ni 2 (As 2 W 15 O 56 ) 2 ] 16-and [(NiOH 2 ) 2 Cu 2 (As 2 W 15 O 56 ) 2 ] 16-. This aims to exploit potential synergistic effects for enhanced catalytic performance and to deepen the understanding of redox mechanisms in these mixed-metal systems. A detailed electrochemical study of the two POMs in solution, compared to their homometallic analogues containing only Ni(II) or only Cu(II) centres, was conducted using cyclic voltammetry (CV), also coupled to quartz crystal microbalance in order to monitor Cu deposition/ desorption phenomena, and controlled potential coulometry, enabling unambiguous identification and differentiation. X-ray photoelectron spectroscopy (XPS) unequivocally corroborated these findings. Furthermore, density functional theory (DFT) calculations provide additional insights that are relevant to rationalise the electrochemical measurements. The molecular orbital sequence, energies and shapes provide relevant supporting information to the experimental facts. Combined evidence establishes that Na/Ni compounds maintain the Wonly electrochemical fingerprint, whereas new CV features appear when Cu(II) is part of the structure, modulated by the rest of the equatorial composition. Protonation has been explored and its effects on the redox chemistry examined at the theoretical level
The DIGIT-HF trial and the Mihai Gheorghiade legacy: time to reconsider cardiac glycosides as effective therapy in HFrEF
No full textInternational audienceCardiac glycosides have been used for more than two centuries in patients with heart failure with reduced ejection fraction (HFrEF), but their use has steadily declined in recent decades, largely due to safety concerns raised by observational studies and the availability of outcomemodifying therapies with more favorable safety profiles. Evidence from earlier randomized trials suggested that digoxin improves symptoms and reduces heart-failure hospitalizations without affecting survival, but these studies were conducted before the widespread adoption of contemporary guideline-directed medical therapy (GDMT).Digitoxin is a cardiac glycoside that differs from digoxin through its hepatic clearance and more stable pharmacokinetics, diminishing the impact of renal dysfunction and serum concentration fluctuations, thereby improving safety and facilitating long-term use in routine care. Here, we critically discuss in the context of available evidence the findings of the recently published DIGIT-HF (Digitoxin to Improve Outcomes in Patients with Advanced Chronic Heart Failure) trial, which for the first time evaluated the efficacy and safety of digitoxin in contemporary patients with HFrEF.</div
The Zermelo Navigation Problem on the 2-Sphere of Revolution: An Optimal Control Perspective with Applications to Micromagnetism
No full textInternational audienceThis article presents geometric optimal control techniques for analyzing geodesics in time-optimal Zermelo navigation problems on 2-spheres of revolution. We classify the problem by analyzing the pair , which represents the current (or wind) and the Riemannian metric. Using the maximum principle, the dynamics of geodesics are described by a Hamiltonian vector field on the cotangent bundle . Our primary motivation is the application to micromagnetism, specifically spin magnetization reversal in ferromagnetic ellipsoidal samples. This model depends on four parameters and the amplitude of the applied magnetic field. The problem is formulated as a Zermelo navigation on the 2-sphere, where geodesics are classified as elliptic, hyperbolic, or abnormal. We demonstrate that the transition set , which separates weak and strong current domains, is critical for understanding optimality. A key result shows that abnormal geodesics intersect this set with semi-cubical cusp singularities, a phenomenon we term the Landau–Lifshitz billiard. The analysis of the transition set's connected components is complex and complemented by algebraic geometry and symbolic computations. We further reveal that hyperbolic geodesics lose optimality at their second intersection with the abnormal arc. Our numerical simulations complement this analysis by computing conjugate and cut loci, wavefronts, and accessibility sets, providing new insights into optimal magnetization switching under bounded control