Adaptations cardiovasculaires et inconfort lors du maintien d'une posture debout prolongée

Au Québec, 58% des travailleurs passent la majorité de leur temps de travail en posture debout. Selon des études épidémiologiques, une posture debout prolongée est associée à des problèmes de santé tels que des troubles de circulation sanguine veineuse, des problèmes d'athérosclérose, des complications lors de la grossesse, de la douleur aux membres inférieurs et au dos. La littérature rapporte que la posture debout occasionne des changements physiologiques tels que l'accumulation de sang dans les membres inférieurs ou de l'enflure. Cependant, ce n'est pas clair si ces changements sont associés à l'inconfort. La présente étude a comme but d'étudier les associations possibles entre l'inconfort au niveau des membres inférieurs et divers paramètres physiologiques, sous différentes conditions en laboratoire. Huit sujets ayant un emploi où la majorité du temps de travail est passé en posture debout et étant en parfaite santé ont participé à l'étude. Pour chaque sujet, des mesures de température cutanée, d'indice de saturation d'oxygène tissulaire (TOI), de fréquence cardiaque, de variabilité du rythme cardiaque, de pression artérielle, d'analyse du centre de pression et d'inconfort ont été prises durant trois conditions expérimentales d'une durée de 31 minutes chacune: A-posture statique sans possibilité de bouger les pieds; B-posture statique durant 9 minutes et piétinement durant une minute, répété 3 fois; C-posture statique durant 9 minutes et marche durant une minute, répété 3 fois. Les résultats obtenus démontrent que la posture statique provoque un inconfort au niveau des membres inférieurs et que les périodes de mobilité diminuent cet inconfort. Les mesures de température cutanée, du TOI et de la fréquence cardiaque ont été affectées par l'une ou l'autre des conditions expérimentales mais aucun lien entre ces mesures et l'inconfort n'a pu être établi. D'autres études sont nécessaires avec davantage de sujets et comportant une analyse de différents mécanismes pouvant être impliqués dans la présence d'inconfort. Les mesures de TOI, d'oedème sous-cutané, de pressions mécaniques sur les tissus, de composition biochimique du sang pourraient être de bonnes mesures à utiliser dans de futures études. De plus, il serait important de réaliser des études sur le sujet dans de vrais milieux de travail puisque c'est à ce niveau que la problématique prend tout son sens. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Posture debout, Inconfort, Membres inférieurs, Laboratoire, Indicateurs physiologiques

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Analyse de l’implantation d’un programme d’accompagnement des enseignants pour favoriser l’inclusion des adolescents présentant des troubles du comportement

Cet article présente les résultats d’une recherche portant sur l’évaluation d’un programme d’accompagnement collaboratif des enseignants du secondaire afin de faciliter l’inclusion scolaire d’élèves présentant des troubles du comportement, en particulier les perceptions des acteurs concernant les conditions d’efficacité du programme. Des entretiens semi-dirigés ont été réalisés auprès de 42 enseignants ayant été accompagnés, onze accompagnateurs et huit directions d’école. Selon l’analyse qualitative des résultats, le programme peut facilement être mis en place auprès des enseignants qui oeuvrent dans les écoles secondaires afin de faciliter l’intégration des élèves présentant des troubles du comportement. L’élément clé du programme semble être les activités de résolution de problème basées sur une évaluation fonctionnelle des comportements problématiques.This article presents some results of the evaluative research that was conducted on a collaborative school consulting program to facilitate integration of adolescents with behavior disorders in mainstream classes of secondary schools. It examines particularly the stakeholders’ perceptions regarding the conditions of program effectiveness. Semi-structured interviews were conducted with teachers (N = 42), resource persons accompanying individuals or groups (N = 11) and school managers (N = 8). According to qualitative analysis of the interviews, the program should be easily implemented with secondary teachers in order to facilitate the integration of EBD students. The problem solving process seems the core element of the program.Este artículo presenta los resultados de una investigación sobre la evaluación de un programa de acompañamiento colaborativo de maestros de secundaria, con el objetivo de facilitar la inclusión escolar de alumnos con problemas de comportamiento y, en particular, sobre las percepciones de los actores en lo que se refiere a las condiciones de eficacia del programa. Se llevaron a cabo entrevistas semi-dirigidas con 42 maestros que habían sido acompañados, once acompañantes y ocho direcciones de escuela. Según el análisis cualitativo de los resultados, el programa puede desarrollarse fácilmente con maestros que trabajan en escuelas secundarias, de forma que se facilite la integración de los alumnos con problemas de comportamiento. El elemento clave del programa parece ser las actividades de resolución de problemas basadas en una evaluación funcional de los comportamientos problemáticos

Finding an Appropriate Mouse Model to Study the Impact of a Treatment for Friedreich Ataxia on the Behavioral Phenotype

Friedreich ataxia (FRDA) is a progressive neurodegenerative disease caused by a GAA repeat in the intron 1 of the frataxin gene (FXN) leading to a lower expression of the frataxin protein. The YG8sR mice are Knock-Out (KO) for their murine frataxin gene but contain a human frataxin transgene derived from an FRDA patient with 300 GAA repeats. These mice are used as a FRDA model but even with a low frataxin concentration, their phenotype is mild. We aimed to find an optimized mouse model with a phenotype comparable to the human patients to study the impact of therapy on the phenotype. We compared two mouse models: the YG8sR injected with an AAV. PHP.B coding for a shRNA targeting the human frataxin gene and the YG8-800, a new mouse model with a human transgene containing 800 GAA repeats. Both mouse models were compared to Y47R mice containing nine GAA repeats that were considered healthy mice. Behavior tests (parallel rod floor apparatus, hanging test, inverted T beam, and notched beam test) were carried out from 2 to 11 months and significant differences were noticed for both YG8sR mice injected with an anti-FXN shRNA and the YG8-800 mice compared to healthy mice. In conclusion, YG8sR mice have a slight phenotype, and injecting them with an AAV-PHP.B expressing an shRNA targeting frataxin does increase their phenotype. The YG8-800 mice have a phenotype comparable to the human ataxic phenotype

Increased Stiffness in Aged Skeletal Muscle Impairs Muscle Progenitor Cell Proliferative Activity

<div><p>Background</p><p>Skeletal muscle aging is associated with a decreased regenerative potential due to the loss of function of endogenous stem cells or myogenic progenitor cells (MPCs). Aged skeletal muscle is characterized by the deposition of extracellular matrix (ECM), which in turn influences the biomechanical properties of myofibers by increasing their stiffness. Since the stiffness of the MPC microenvironment directly impacts MPC function, we hypothesized that the increase in muscle stiffness that occurs with aging impairs the behavior of MPCs, ultimately leading to a decrease in regenerative potential.</p><p>Results</p><p>We showed that freshly isolated individual myofibers from aged mouse muscles contain fewer MPCs overall than myofibers from adult muscles, with fewer quiescent MPCs and more proliferative and differentiating MPCs. We observed alterations in cultured MPC behavior in aged animals, where the proliferation and differentiation of MPCs were lower and higher, respectively. These alterations were not linked to the intrinsic properties of aged myofibers, as shown by the similar values for the cumulative population-doubling values and fusion indexes. However, atomic force microscopy (AFM) indentation experiments revealed a nearly 4-fold increase in the stiffness of the MPC microenvironment. We further showed that the increase in stiffness is associated with alterations to muscle ECM, including the accumulation of collagen, which was correlated with higher hydroxyproline and advanced glycation end-product content. Lastly, we recapitulated the impaired MPC behavior observed in aging using a hydrogel substrate that mimics the stiffness of myofibers.</p><p>Conclusions</p><p>These findings provide novel evidence that the low regenerative potential of aged skeletal muscle is independent of intrinsic MPC properties but is related to the increase in the stiffness of the MPC microenvironment.</p></div

MPCs in aged myofibers display decreased myogenic activity.

<p><b>(A</b>) Histograms showing the total number of MPCs per myofiber on 5–109 freshly isolated and cultured (6 days) myofibers from adult and aged mice (<i>n</i> = 5 mice per group). <b>(B, C)</b> Histograms showing the percentage of quiescent SCs (Pax7⁺MyoD⁻) and proliferating (Pax7⁺MyoD⁺) and differentiating MPCs (Pax7⁻MyoD⁺) per myofiber on intact <b>(B)</b> and damaged <b>(C)</b> myofibers. The Pax7 and MyoD proteins were immunostained as shown in the photomicrograph on the right. The count includes all parts and depths of the myofibers. The representative image on the right shows that Pax7 and MyoD proteins are expressed at lower levels in aged myofibers. **<i>p</i><0.01 and ***<i>p</i><0.0001 versus adult. ^†††<i>p</i><0.001 versus intact counterparts. All data are expressed as means ± SEM.</p

Damaged myofibers from aged mice display robust stiffness that impairs MPC activity.

<p>Graphs showing Young’s modulus values (kPa) and stiffness measurements of freshly isolated (<b>A</b>) and cultured intact and damaged myofibers (<b>B</b>) from adult (<i>n</i> = 3) and aged (<i>n</i> = 5) muscles. One measurement (three force-indentation curves collected for each measurement) per myofiber was performed on 6–50 myofibers. **<i>p</i><0.01; ***<i>p</i><0.0001 versus adult counterpart. ^†††<i>p</i><0.001 versus intact counterpart. All data are expressed as means ± SEM.</p

Molecular basis for the methylation specificity of ATXR5 for histone H3

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