Peripheral thickening of the sarcomeres and pointed end elongation of the thin filaments are both promoted by SALS and its formin interaction partners.

During striated muscle development the first periodically repeated units appear in the premyofibrils, consisting of immature sarcomeres that must undergo a substantial growth both in length and width, to reach their final size. Here we report that, beyond its well established role in sarcomere elongation, the Sarcomere length short (SALS) protein is involved in Z-disc formation and peripheral growth of the sarcomeres. Our protein localization data and loss-of-function studies in the Drosophila indirect flight muscle strongly suggest that radial growth of the sarcomeres is initiated at the Z-disc. As to thin filament elongation, we used a powerful nanoscopy approach to reveal that SALS is subject to a major conformational change during sarcomere development, which might be critical to stop pointed end elongation in the adult muscles. In addition, we demonstrate that the roles of SALS in sarcomere elongation and radial growth are both dependent on formin type of actin assembly factors. Unexpectedly, when SALS is present in excess amounts, it promotes the formation of actin aggregates highly resembling the ones described in nemaline myopathy patients. Collectively, these findings helped to shed light on the complex mechanisms of SALS during the coordinated elongation and thickening of the sarcomeres, and resulted in the discovery of a potential nemaline myopathy model, suitable for the identification of genetic and small molecule inhibitors.

The effects of different types of organisational workplace mental health interventions on mental health and wellbeing in healthcare workers: a systematic review.

OBJECTIVE: To determine if and which types of organisational interventions conducted in small and medium size enterprises (SMEs) in healthcare are effective on mental health and wellbeing. METHODS: Following PRISMA guidelines, we searched six scientific databases, assessed the methodological quality of eligible studies using QATQS and grouped them into six organisational intervention types for narrative synthesis. Only controlled studies with at least one follow-up were eligible. RESULTS: We identified 22 studies (23 articles) mainly conducted in hospitals with 16 studies rated of strong or moderate methodological quality. More than two thirds (68%) of the studies reported improvements in at least one primary outcome (mental wellbeing, burnout, stress, symptoms of depression or anxiety), most consistently in burnout with eleven out of thirteen studies. We found a strong level of evidence for the intervention type "Job and task modifications" and a moderate level of evidence for the types "Flexible work and scheduling" and "Changes in the physical work environment". For all other types, the level of evidence was insufficient. We found no studies conducted with an independent SME, however five studies with SMEs attached to a larger organisational structure. The effectiveness of workplace mental health interventions in these SMEs was mixed. CONCLUSION: Organisational interventions in healthcare workers can be effective in improving mental health, especially in reducing burnout. Intervention types where the change in the work environment constitutes the intervention had the highest level of evidence. More research is needed for SMEs and for healthcare workers other than hospital-based physicians and nurses.

Implementing a complex mental health intervention in occupational settings: process evaluation of the MENTUPP pilot study.

BACKGROUND: According to the Medical Research Council (MRC) framework, the theorisation of how multilevel, multicomponent interventions work and the understanding of their interaction with their implementation context are necessary to be able to evaluate them beyond their complexity. More research is needed to provide good examples following this approach in order to produce evidence-based information on implementation practices. OBJECTIVES: This article reports on the results of the process evaluation of a complex mental health intervention in small and medium enterprises (SMEs) tested through a pilot study. The overarching aim is to contribute to the evidence base related to the recruitment, engagement and implementation strategies of applied mental health interventions in the workplace. METHOD: The Mental Health Promotion and Intervention in Occupational Settings (MENTUPP) intervention was pilot tested in 25 SMEs in three work sectors and nine countries. The evaluation strategy of the pilot test relied on a mixed-methods approach combining qualitative and quantitative research methods. The process evaluation was inspired by the RE-AIM framework and the taxonomy of implementation outcomes suggested by Proctor and colleagues and focused on seven dimensions: reach, adoption, implementation, acceptability, appropriateness, feasibility and maintenance. RESULTS: Factors facilitating implementation included the variety of the provided materials, the support provided by the research officers (ROs) and the existence of a structured plan for implementation, among others. Main barriers to implementation were the difficulty of talking about mental health, familiarisation with technology, difficulty in fitting the intervention into the daily routine and restrictions caused by COVID-19. CONCLUSIONS: The results will be used to optimise the MENTUPP intervention and the theoretical framework that we developed to evaluate the causal mechanisms underlying MENTUPP. Conducting this systematic and comprehensive process evaluation contributes to the enhancement of the evidence base related to mental health interventions in the workplace and it can be used as a guide to overcome their contextual complexity. TRIAL REGISTRATION NUMBER: ISRCTN14582090.