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Le développement de thérapies efficaces pour la sclérose latérale amyotrophique (SLA) est urgent et est dépendant de la compréhension des mécanismes moléculaires sous-jacents à la pathologie. La délocalisation de TDP-43 du noyau vers le cytoplasme est un événement observé dans la majorité des cas de SLA et nous avons démontré que la déplétion nucléaire de TDP-43 induit l’accumulation d’une isoforme alternative de Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), nommé hnRNP A1B. La protéine hnRNP A1B diffère de hnRNP A1 par l’inclusion de l’exon 7B qui allonge son domaine intrinsèquement désordonné de 52 acides aminés. HNRNPA1 est muté dans certains cas de SLA familiale et la présence de mutations augmente les propriétés d’agrégation de la protéine. Par contre, la contribution des agrégats à la pathogenèse n’est pas totalement comprise dû au manque de connaissances sur les fonctions de hnRNP A1B. L’isoforme hnRNP A1 est quant à elle très bien étudiée et est un membre important du métabolisme de l’ARN. Étonnamment, on connaît très peu l’isoforme hnRNP A1B. Nous avons donc examiné l’expression spatiotemporelle et la fonction de hnRNP A1B pour comprendre sa contribution à la biologie cellulaire et aux pathologies. Dans la première partie, nous avons découvert que l’expression de la protéine hnRNP A1B est plus restreinte au système nerveux central (SNC) comparé à hnRNP A1. Dans le SNC, hnRNP A1B peut aussi former un dimère résistant au SDS. De plus, nous avons démontré que l’expression de hnRNP A1B devient progressivement restreinte aux neurones moteurs dans la corne ventrale de la moelle épinière. Contrairement à hnRNP A1 qui est exprimée globalement. Nous avons aussi découvert que hnRNP A1B est présente dans le noyau et le cytoplasme des neurones moteurs alors que la protéine hnRNP A1 est nucléaire. De plus, hnRNP A1B forme des puncta dans les neurites. Dans la seconde partie, nous avons caractérisé l’interactome de hnRNP A1B dans la moelle épinière. Nous avons identifié et validé l’interaction de hnRNP A1B avec des protéines motrices. Nous avons démontré que les granules de hnRNP A1B contenaient des ARN messagers (ARNm) et des protéines nouvellement synthétisées. Ce résultat soutient le rôle de hnRNP A1B comme adaptateur dans le transport neuronal et régulateur de la traduction locale. Nos résultats démontrent que les deux isoformes de HNRNPA1 sont différentiellement exprimées dans les tissus et ont des localisations cellulaires distinctes. Ces résultats suggèrent que les deux isoformes ont des fonctions cellulaires spécifiques. Ainsi, nous proposons que hnRNP A1B joue une fonction cytoplasmique neuronale dans le transport des ARNm, qui n’est pas partagé par hnRNP A1. Les isoformes de HNRNPA1 peuvent donc contribuer distinctement dans la progression des pathologies., The development of an effective treatment for amyotrophic lateral sclerosis (ALS) is urgent and is expected to be informed by a better understanding of the molecular mechanisms underlying the pathology. TDP-43 mislocalization from the nucleus to the cytoplasm is observed in the majority of ALS cases and we have discovered that TDP-43 nuclear depletion drives the accumulation of an alternatively spliced variant of heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), termed hnRNP A1B. hnRNP A1B differs by the inclusion of the 7B exon that elongates its intrinsically disorder region by 52 amino acids. HNRNPA1 is mutated in rare cases of familial ALS and these diseaseassociated mutations drive aggregation, but their contribution to the pathogenesis is not clearly understood due to the lack of information about hnRNP A1B functions. hnRNP A1 is well studied and is a major player in RNA metabolism, but surprisingly little is known about the spliced variant hnRNP A1B. We then aim to investigate the spatiotemporal regulation and function of hnRNP A1B to understand its contribution to physiology and pathology. In the first part, we have found that hnRNP A1B’s expression is more restricted to the central nervous system (CNS) compared to hnRNP A1, and that it can form an SDSresistant dimer enriched in the CNS. Also, hnRNP A1B expression becomes progressively restricted to motor neurons in the ventral horn of the spinal cord, compared to hnRNP A1 which is more broadly expressed. We also demonstrate that hnRNP A1B is present in the nucleus and in the soma of motoneurons compared to hnRNP A1 which is nuclear. In addition, hnRNP A1B forms puncta in neuronal processes. In the second part, we have characterized hnRNP A1B’s interactome in the spinal cord. We have identified and validated the interactions between hnRNP A1B and cytoskeletal motor proteins. We have demonstrated that hnRNP A1B granules in neuronal process contains messenger RNA (mRNA) and contains nascent proteins which support the role for hnRNP A1B as an RNA adaptor in mRNA transport and a regulator of local translation. Our results demonstrate that both isoforms of HNRNPA1 are differentially expressed across tissues and have distinct localization profiles, suggesting that the two isoforms may have specific subcellular functions. Those finding support that hnRNP A1B may have a cytosolic function in neurons, RNA transport, that is not shared with hnRNP A1. Indeed, HNRNPA1 isoforms can uniquely contribute to disease progression.

AIM: The aim of the present study was to identify systematically the measurement properties of patient‐reported outcome instruments (PROs) that evaluate adherence to inhaled maintenance medication in adults with asthma. METHODS: We conducted a systematic review of six databases. Two reviewers independently included studies on the measurement properties of PROs that evaluated adherence in asthmatic participants aged ≥18 years. Based on the COnsensus‐based Standards for the selection of health Measurement INstruments (COSMIN), the reviewers: (i) extracted data on internal consistency, reliability, measurement error, content validity, structural validity, hypotheses testing, cross‐cultural validity, criterion validity and responsiveness; (ii) assessed the methodological quality of the included studies; (iii) assessed the quality of the measurement properties (positive or negative); and (iv) summarized the level of evidence (limited, moderate or strong). RESULTS: We screened 6068 records and included 15 studies (14 PROs). No studies evaluated measurement error or responsiveness. Based on methodological and measurement property quality assessments, we found limited positive evidence of: (i) internal consistency of the Adherence Questionnaire, Refined Medication Adherence Reason (MAR) scale, Medication Adherence Report Scale for Asthma (MARS‐A) and Test of the Adherence to Inhalers (TAI); (ii) reliability of the TAI; and (iii) structural validity of the adherence questionnaire, MAR scale, MARS‐A and TAI. We also found limited negative evidence of: (i) hypotheses testing of the Adherence Questionnaire; (ii) reliability of the MARS‐A; and (iii) criterion validity of the MARS‐A and TAI. CONCLUSIONS: Our results highlighted the need to conduct further high‐quality studies to evaluate the reliability, validity and responsiveness of the available PROs.

Questionnaire on attendees’ learning. The questionnaire on attendees’ learning comprises eight open-ended questions aligned with the CE activity specific objectives. A professional translator translated the items from French to English. (DOCX 46 kb)

Le contexte scolaire actuel au Québec, et particulièrement à Montréal, amène les enseignants à développer des pratiques différenciées pour répondre aux besoins de leurs élèves. En effet, l’intégration des élèves handicapés ou en difficulté d’adaptation ou d’apprentissage ainsi que les différences socioéconomiques et culturelles sont des manifestations de l’hétérogénéité qui sont présentes simultanément dans leurs classes. Des études menées au Québec semblent toutefois indiquer que certaines pratiques différenciées demeurent méconnues et peu utilisées. Il semble que, d’une part, la gestion de classe soit un déterminant de l’implantation des pratiques différenciées et, d’autre part, que cette bonne gestion de classe soit tributaire d’un haut niveau de sentiment d’efficacité personnelle à gérer la classe. Cette recherche mixte vise à explorer les relations entre les pratiques différenciées et le sentiment d’efficacité à gérer la classe chez des enseignants au primaire de Montréal. Pour ce faire, un questionnaire a été rempli par 154 enseignants de la CSDM et un groupe de discussion a été organisé auprès de 6 d’entre eux. Nos résultats tendent à confirmer la corrélation entre le SEP à gérer la classe et la fréquence d’utilisation de pratiques différenciées. Plus précisément, ils indiquent que les relations sociales en classe, dont celles entre les élèves et l’enseignant sont un prédicteur d’une utilisation plus fréquente de la différenciation pédagogique. Finalement, même si les enseignants du groupe de discussion définissent le contexte montréalais comme possédant des caractéristiques particulières requérant des pratiques différenciées fréquentes et variées, selon eux, la gestion de classe n’y requiert pas d’interventions distinctes., The current school context in Quebec, especially in Montreal, leads teachers to develop differentiated pedagogies to meet the needs of all. The integration of students with special needs, socio-economic and cultural differences are examples of manifestations of heterogeneity to be observed in teaching. Yet, few teachers adopted such practices. Moreover, we know that, classroom management is a key to the implementation of differentiated practices and, good classroom management depends on a high level of self-efficacy of classroom management. This article presents a mixed method design study that explore relationships between frequency of differentiated practices and self-efficacy of classroom management of elementary teachers. First, a questionnaire was completed by 154 teachers of the CSDM. Then, a focus-group was organized with 6 of them. Our results tend to confirm the correlation between the SEP to manage the class and the frequency of differentiated practices. Specifically, they suggest that relationships in class, including those between students and the teacher, is a predictor of increased use of differentiated instruction. Finally, even if teachers in the focus-group define the Montreal context as having special characteristics requiring frequent and varied differentiated practices, according to them, classroom management do not require different interventions.

Objective: Based on the Knowledge-to-Action Cycle, we assessed the self-reported implementation and perception of asthma clinical practice guideline (CPG) recommendations in primary care physicians (PCPs), along with the barriers and facilitators to CPG use in primary care. Methods: We conducted a cross-sectional study. Using the extended Asthma Physicians' Practice Assessment Questionnaire©, PCPs self-reported the following: their knowledge of 15 key asthma CPG recommendations, the perceived usefulness of each of these recommendations, their motivation to apply these recommendations, and their agreement with the content of these recommendations. Participants also reported the barriers and facilitators to CPG use in primary care. Results: Out of the 46 potential participants, 43 physicians completed the questionnaire (response rate: 93%). Results underlined care gaps regarding the provision of asthma education and written action plans, inhaler technique demonstrations, and assessment of patients' concerns. Results showed that the majority of physicians knew the key asthma CPG recommendations, but their motivation to implement them and the perceived usefulness of these recommendations varied from one proposal to another. Main barriers to the implementation of these recommendations were related to time and resources. PCPs stressed the importance of teamwork for enhancing the use of asthma CPGs in primary care. Conclusions: Our results suggest that the implementation of asthma CPGs remains suboptimal in primary care. Interventions addressing the identified barriers and providing facilitators to asthma CPG implementation, such as continuing education, could be implemented and evaluated to sustain asthma CPG use in primary care settings.