Molecular regulation of myocyte fusion.

Myocyte fusion is a pivotal process in the development and regeneration of skeletal muscle. Failure during fusion can lead to a range of developmental as well as pathological consequences. This review aims to comprehensively explore the intricate processes underlying myocyte fusion, from the molecular to tissue scale. We shed light on key players, such as the muscle-specific fusogens - Myomaker and Myomixer, in addition to some lesser studied molecules contributing to myocyte fusion. Conserved across vertebrates, Myomaker and Myomixer play a crucial role in driving the merger of plasma membranes of fusing myocytes, ensuring the formation of functional muscle syncytia. Our multiscale approach also delves into broader cell and tissue dynamics that orchestrate the timing and positioning of fusion events. In addition, we explore the relevance of muscle fusogens to human health and disease. Mutations in fusogen genes have been linked to congenital myopathies, providing unique insights into the molecular basis of muscle diseases. We conclude with a discussion on potential therapeutic avenues that may emerge from manipulating the myocyte fusion process to remediate skeletal muscle disorders.

The COVID-19 pandemic's impact on all-cause mortality disparities in Medicare: By race, income, chronic health, mental/behavioral health, disability.

BACKGROUND: The Medicare-enrolled population is heterogeneous across race, ethnicity, age, dual eligibility, and a breadth of chronic health, mental and behavioral health, and disability-related conditions, which may be differentially impacted by the COVID-19 pandemic. OBJECTIVE: To quantify changes in all-cause mortality prior-to and in the first year of the COVID-19 pandemic across Medicare's different sociodemographic and health-condition subpopulations. METHODS: This observational, population-based study used stratified bivariate regression to investigate Medicare fee-for-service subpopulation differences in pre-pandemic (i.e., 2019 versus 2016) and pandemic-related (2020 versus 2019) changes in all-cause mortality. RESULTS: All-cause mortality in the combined Medicare-Advantage (i.e., managed care) and fee-for-service beneficiary population improved by a relative 1% in the ten years that preceded the COVID-19 pandemic, but then escalated by a relative 15.9% in 2020, the pandemic's first year. However, a closer look at Medicare's fee-for-service subpopulations reveals critical differences. All-cause mortality had actually been worsening prior to the pandemic among most psychiatric and disability-related condition groups, all race and ethnicity groups except White Non-Hispanic, and Medicare-Medicaid dual-eligible (i.e., low-income) beneficiaries. Many of these groups then experienced all-cause mortality spikes in 2020 that were over twice that of the overall Medicare fee-for-service population. Of all 61 chronic health conditions studied, beneficiaries with schizophrenia were the most adversely affected, with all-cause mortality increasing 38.4% between 2019 and 2020. CONCLUSION: This analysis reveals subpopulation differences in all-cause mortality trends, both prior to and in year-one of the COVID-19 pandemic, indicating that the events of 2020 exacerbated preexisting health-related inequities.

The Relationship Between Physical Activity and Health-Related Quality of Life in People With Dementia: An Observational Study.

Recent research suggests the positive effect of physical activity on health-related quality of life in people with dementia may be mediated through improved activities of daily living and reduced depressive symptoms. One hundred and twenty-four people with dementia and their informal carers were recruited from the South East of England for this observational study. A subset of participants wore an accelerometer for 30 days. A series of bivariate analyses were completed, alongside mediation analyses. In people with mild to moderate severity dementia, weak positive associations were widely reported between physical activity indices and health-related quality of life, though only a single association reached statistical significance (rs = .25, p = .03). Mediation analysis revealed no significant indirect effects across the models after controlling for cognition. Future research needs to explore such relationships with a greater emphasis on the modality and psychosocial components of physical activity rather than just frequency, duration, and intensity.

Barriers, motivators and facilitators of physical activity in people with dementia and their family carers in England: dyadic interviews.

INTRODUCTION: Physical activity may have a number of physical and mental health benefits for people with dementia and their carers. However, there is limited evidence about factors that influence physical activity participation in these groups. This study therefore looks at the barriers, facilitators and motivators of physical activity in people with dementia, from both the perspective of the person with dementia and their carer. METHOD: Thirty participants (15 sets of community-dwelling people with dementia and their family carers) were recruited from the South East of England. The participants took part in semi-structured dyadic interviews about their views of physical activity. Interviews were analysed using inductive thematic analysis at an individual level and comparisons were made between the groups. RESULTS: Common motivator themes across persons with dementia and family carers were emotional and physical wellbeing, and social connectedness. Physical health was seen as a common barrier in both groups. Physical activity in the person with dementia was encouraged and supported by the family carer. For the carer, their caring role, and limited time acted as barriers to their participation. CONCLUSION: Themes such as social connectedness, positive emotion and health were seen as key motivators to physical activity, which indicate that people with dementia and carers use physical activity as a means to maintain and improve their quality of life. Supporting family members to better facilitate such activities could encourage physical activity in people with dementia.

Validation of a low-cost, carbon dioxide-based cryoablation system for percutaneous tumor ablation.

Breast cancer rates are rising in low- and middle-income countries (LMICs), yet there is a lack of accessible and cost-effective treatment. As a result, the cancer burden and death rates are highest in LMICs. In an effort to meet this need, our work presents the design and feasibility of a low-cost cryoablation system using widely-available carbon dioxide as the only consumable. This system uses an 8-gauge outer-diameter needle and Joule-Thomson expansion to percutaneously necrose tissue with cryoablation. Bench top experiments characterized temperature dynamics in ultrasound gel demonstrated that isotherms greater than 2 cm were formed. Further, this system was applied to mammary tumors in an in vivo rat model and necrosis was verified by histopathology. Finally, freezing capacity under a large heat load was assessed with an in vivo porcine study, where volumes of necrosis greater than 1.5 cm in diameter confirmed by histopathology were induced in a highly perfused liver after two 7-minute freeze cycles. These results demonstrate the feasibility of a carbon-dioxide based cryoablation system for improving solid tumor treatment options in resource-constrained environments.

Acceptability and feasibility of wearing activity monitors in community-dwelling older adults with dementia.

OBJECTIVES: Measuring physical activity is complicated particularly in people with dementia, where activity levels are low and subjective measures are susceptible to inaccurate recall. Activity monitors are increasingly being used within research; however, it is unclear how people with dementia view wearing such devices and what aspects of the device effect wear time. The aim of the study was to evaluate the acceptability and feasibility of people with dementia wearing activity monitors. METHODS: Twenty-six, community-dwelling, people with mild dementia were asked to wear an activity monitor (GENEactiv Original) over a 1-month period. Perceptions of the device were measured using the Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) 2.0, alongside qualitative interviews. Device diary and activity monitor data were used to assess compliance. RESULTS: Participants tended to find wearing the activity monitors acceptable, with only three participants (12%) withdrawing prior to the study end date. Participants were generally satisfied with wearing the devices as measured by the QUEST (Mdn = 4.4, IQR = 1.1). Four themes were identified that influenced perceptions of wearing the device: external influences, design, routine, and perceived benefits. DISCUSSION: Asking people with dementia to wear a wrist-worn activity monitor for prolonged periods appears to be both feasible and acceptable. Researchers need to consider the needs and preferences of the sample population prior to selecting activity monitors.