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Proper temporal and spatial activation of stem cells relies on highly coordinated cell signaling. The primary cilium is the sensory organelle that is responsible for transmitting extracellular signals into a cell. Primary cilium size, architecture, and assembly-disassembly dynamics are under rigid cell cycle-dependent control. Using mouse incisor tooth epithelia as a model, we show that ciliary dynamics in stem cells require the proper functions of a cholesterol-binding membrane glycoprotein, Prominin-1 (Prom1/CD133), which controls sequential recruitment of ciliary membrane components, histone deacetylase, and transcription factors. Nuclear translocation of Prom1 and these molecules is particularly evident in transit amplifying cells, the immediate derivatives of stem cells. The absence of Prom1 impairs ciliary dynamics and abolishes the growth stimulation effects of sonic hedgehog (SHH) treatment, resulting in the disruption of stem cell quiescence maintenance and activation. We propose that Prom1 is a key regulator ensuring appropriate response of stem cells to extracellular signals, with important implications for development, regeneration, and diseases.

This study identified evidence and considerations for allied health clinicians in providing group interventions for people with cognitive impairment. A scoping review was conducted by searching the MEDLINE (Ovid), CINHAL (EBSCOhost), Scopus (Elsevier), Embase (Ovid) and TROVE databases from 2016. Articles of any study design in which group interventions were performed by an allied health professional with participants with cognitive impairment were included. Data on physical, cognitive, psychological, and quality of life measures were extracted from the selected articles. Standardised mean changes (SMC) were calculated. Ten articles were included in the study. No article directly compared group interventions versus one‐to‐one interventions. The results of the meta‐analysis showed significant improvements after the intervention in the physical (SMC = 0.42, P = 0.013), cognitive (SMC = 0.43, P = 0.005), psychological (SMC = 0.14, P = 0.005), and quality of life domains (SMC = 0.28, P = 0.002). This review identified considerations for clinicians when developing group interventions for people with cognitive impairments, including specific participant criteria, increasing support, modifications to intervention difficulty, and environmental considerations. Group intervention for people with cognitive impairments demonstrated moderate effectiveness in improving physical and cognitive domains and a small effect in improving psychological and quality of life domains. Specific considerations are recommended when clinicians provide group interventions for people with cognitive impairments. [ABSTRACT FROM AUTHOR]

Objectives: To understand the nature and effectiveness of interventions aimed at improving informal stroke caregiver burden, stress, and strain. Data sources: In line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search of CENTRAL, CINAHL, MEDLINE, Embase, APA PsycInfo, and Web of Science was conducted in May 2022. Review methods: Studies were eligible if they included an intervention designed for informal stroke caregivers, reported on caregiver burden, strain, or stress, were published in English, and used a randomized controlled trial design. An updated search was conducted in June 2024. The methodological quality of studies was appraised using the Cochrane risk-of-bias tool for randomized trials. The data were pooled, and a meta-analysis was completed for caregiver burden and strain outcomes. Results: Nineteen studies met inclusion criteria and were meta-analyzed. Interventions ranged from 4 days to 12 months. Most studies incorporated educational and/or support components. Meta-analyses revealed nonsignificant effects on caregiver burden or strain. Significant between-group differences for caregiver strain and burden were, however, found in seven studies. Conclusion: Limited studies, small sample sizes, and conflicting results made definitive conclusions on the most effective intervention characteristics for improving caregiver outcomes difficult. Of the 19 studies, seven found significant between-group differences for caregiver outcomes postintervention, and these tended to incorporate educational components and comprised between seven and nine sessions. Further high-quality research is required to identify optimal format, duration, and frequency for improving caregiver outcomes. [ABSTRACT FROM AUTHOR]

Background: The sudden nature of stroke onset does not provide carers with sufficient time to prepare for the demands associated with caring. Healthcare professionals can have a vital role in providing carers with support and training, which may reduce carer stress and strain, and allow for better health and rehabilitation outcomes for the stroke survivor. The experiences of healthcare professionals on supporting carers in stroke care, however, remain unclear. Objective: To understand the experiences and perceptions of healthcare professionals working in stroke care on implementing resources and support to informal stroke carers. Methods: Semi-structured interviews were conducted with 11 healthcare professionals (5 occupational therapists, 5 physiotherapists, 1 psychologist) with at least 12 months' experience in working with stroke survivors. Interviews ranged from 25–70 minutes in duration, and were recorded, transcribed, and analysed using thematic analysis. Results: Three overarching categories that were explored were: (1) Experiences of working in stroke care and supporting carers; (2) Recommendations for a program designed for carers; and (3) Future priorities in stroke care. Participants discussed a variety of strategies they utilised to support carers including collaborating with other healthcare professionals and utilising skills and experience. Healthcare professionals highlighted the need for additional resources that are designed specifically for carers and explored key topics including carer stress and fatigue, support services, stroke education, and how to look after oneself. Participants identified priorities for stroke care including additional professional training and resource availability. Conclusion: This study provided a unique insight from the perspectives of healthcare professionals on supporting carers. Participants identified the need for additional training and resources to equip healthcare professionals to better support carers. Future programs designed for carers should be informed by the needs and experiences of both informal carers and healthcare professionals. [ABSTRACT FROM AUTHOR]

Introduction: Inpatient rehabilitation is the best time window to improve patient performance post-stroke. Little is known about the type and effectiveness of activity interventions. This study aims to review activities of daily living interventions and evaluate their effectiveness on activity performance for stroke inpatients. Method: MEDLINE, Embase, CINAHL and Web of Science were searched. Randomised controlled trials investigating the effects of activities of daily living interventions for stroke inpatients were included. Two reviewers independently selected the studies and extracted data. Meta-analysis was conducted on relevant data with a random effect model with 95% CI. Results: Fourteen randomised controlled trials involving 602 stroke inpatients, were included. Both experimental and control groups offered activities of daily living interventions. Thirteen experimental groups offered added components, such as imagery and repetitive practice. Five studies reported significant improvement in activity performance within experimental and control groups. A meta-analysis of 12 randomised controlled trials with 512 participants revealed non-significant results for activity performance between the two groups. Conclusion: Both experimental and control groups in the included studies provided activities of daily living interventions. Added components were included in 13 out of 14 experimental groups. Meta-analysis revealed no significant difference between the two groups as they both offered activities of daily living interventions. [ABSTRACT FROM AUTHOR]

Introduction: Occupational therapists have vital roles in inpatient rehabilitation to focus on independence in activities of daily living. Occupational therapy interventions are uniquely designed to address goals of service users and can be delivered individually or in group formats. Group interventions promote service users' mutual support and enable therapists to increase frequency and intensity of service provision. Student‐led programs have become an attractive model, benefiting students while providing positive treatment outcomes for service users. There is an emerging body of literature that explores service users' and students' satisfaction with student‐led group models of practice within inpatient rehabilitation and occupational performance outcomes of service users participating in student‐led programs. This study aimed to explore the satisfaction of service users and students in addition to the self‐reported occupational performance outcomes of a student‐led activities of daily living group program in inpatient rehabilitation. Methods: Data from 33 service users and seven students were collected retrospectively. The intervention involved a student‐led activities of daily living group program, consisting of three groups: breakfast, morning tea, and home readiness group. All service users and students completed unique satisfaction surveys at the conclusion of their participation in the student‐led program. Service users completed a self‐reported activities of daily living performance measure pre‐ and post‐program. Findings were reported in descriptive statistics, and pre‐ and post‐program data were compared with the Wilcoxon signed‐rank test. Results: All students were satisfied with the student‐led program. Majority of service users were satisfied with all components of the student‐led program. Median scores for self‐reported performance increased significantly following the student‐led program (P < 0.001). Conclusion: This study highlighted that service users and students were satisfied with the service delivery of a student‐led activities of daily living group program. The program was effective in addressing self‐reported performance for service users in inpatient rehabilitation. The findings from this study have potential to inform clinical practice on the implementation of student‐led programs in occupational therapy settings. [ABSTRACT FROM AUTHOR]

VOICE-a phase 2B, placebo-controlled, randomized trial testing daily use of an antiretroviral tablet (tenofovir or Truvada) or daily use of tenofovir gel in 5029 women from South Africa, Uganda, and Zimbabwe-found none of the drug regimens effective in reducing HIV-1 acquisition in the intent-to-treat analysis. More than half of women assigned to active products in a case cohort sample had no drug detected in any plasma specimens tested during the trial. Yet, in response to questions asked of participants during the trial, ≥90 % of doses were reportedly taken. To explore factors associated with low adherence, a behavioral termination visit questionnaire was developed after early closure of the oral tenofovir and vaginal gel arms. We hypothesized that participants would be more forthcoming about nonuse after they exited the trial than during monthly/quarterly follow-up visits. Comparison of adherence reporting at routine follow-up visits with reporting at trial termination, however, indicates that disclosure of product nonadherence did not increase at the termination visit as anticipated. In resource-limited settings where women value the ancillary benefits provided by trial participation and are concerned that disclosure of nonuse may jeopardize trial participation, objective measures of adherence may yield more meaningful data regarding the inability or reluctance to use than measures of product use derived from self-report.

Objective: To understand the experiences of informal carers and the impact of role and activity changes on their health and wellbeing. Methods: A systematic search of CINHAL, MEDLINE, Embase, APA PsycInfo, and Web of Science was conducted. Studies were eligible if they included informal stroke carers (≥18 years), used a qualitative methodology, explored the roles and valued activities of stroke carers, and were published in English. The 10-item Critical Appraisal Skills Programme checklist for qualitative studies was used to assess methodological quality. The results of the included studies were thematically synthesised. Results: A total of 36 qualitative studies were included and four overarching themes were identified: (1) Life adjustment; (2) Changing role and identity; (3) Changing activities: From meaningful to purposeful; and (4) Understanding and supporting carers. Conclusion: The sudden nature of stroke requires major readjustment in the carers life that has implications on their relationships, roles, and activities, subsequently impacting on their health and wellbeing. Health professionals and researchers should collaborate with stroke carers to identify their valued activities and implement realistic strategies to maintain these activities. Future interventions designed for carers should implement education about the importance of participating in valued activities and strategies to maintain these activities. [ABSTRACT FROM AUTHOR]

Rab3 interacting molecules (RIMs) are evolutionarily conserved scaffolding proteins that are located at presynaptic active zones. In the mammalian nervous system, RIMs have two major activities that contribute to the fidelity of baseline synaptic transmission: they concentrate calcium channels at the active zone and facilitate synaptic vesicle docking/priming. Here we confirm that RIM has an evolutionarily conserved function at the Drosophila neuromuscular junction and then define a novel role for RIM during homeostatic synaptic plasticity. We show that loss of RIM disrupts baseline vesicle release, diminishes presynaptic calcium influx, and diminishes the size of the readily-releasable pool (RRP) of synaptic vesicles, consistent with known activities of RIM. However, loss of RIM also completely blocks the homeostatic enhancement of presynaptic neurotransmitter release that normally occurs after inhibition of postsynaptic glutamate receptors, a process termed synaptic homeostasis. It is established that synaptic homeostasis requires enhanced presynaptic calcium influx as a mechanism to potentiate vesicle release. However, despite a defect in baseline calcium influx in rim mutants, the homeostatic modulation of calcium influx proceeds normally. Synaptic homeostasis is also correlated with an increase in the size of the RRP of synaptic vesicles, although the mechanism remains unknown. Here we demonstrate that the homeostatic modulation of the RRP is blocked in the rim mutant background. Therefore, RIM-dependent modulation of the RRP is a required step during homeostatic plasticity. By extension, homeostatic plasticity appears to require two genetically separable processes, the enhancement of presynaptic calcium influx and a RIM-dependent modulation of the RRP.

Musculoskeletal geometry and muscle volumes vary widely in the population and are intricately linked to the performance of tasks ranging from walking and running to jumping and sprinting. As an alternative to experimental approaches, where it is difficult to isolate factors and establish causal relationships, simulations can be used to independently vary musculoskeletal geometry and muscle volumes, and develop a fundamental understanding. However, our ability to understand how these parameters affect task performance has been limited due to the high computational cost of modelling the necessary complexity of the musculoskeletal system and solving the requisite multi-dimensional optimization problem. For example, sprinting and running are fundamental to many forms of sport, but past research on the relationships between musculoskeletal geometry, muscle volumes, and running performance has been limited to observational studies, which have not established cause-effect relationships, and simulation studies with simplified representations of musculoskeletal geometry. In this study, we developed a novel musculoskeletal simulator that is differentiable with respect to musculoskeletal geometry and muscle volumes. This simulator enabled us to find the optimal body segment dimensions and optimal distribution of added muscle volume for sprinting and marathon running. Our simulation results replicate experimental observations, such as increased muscle mass in sprinters, as well as a mass in the lower end of the healthy BMI range and a higher leg-length-to-height ratio in marathon runners. The simulations also reveal new relationships, for example showing that hip musculature is vital to both sprinting and marathon running. We found hip flexor and extensor moment arms were maximized to optimize sprint and marathon running performance, and hip muscles the main target when we simulated strength training for sprinters. Our simulation results provide insight to inspire future studies to examine optimal strength training. Our simulator can be extended to other athletic tasks, such as jumping, or to non-athletic applications, such as designing interventions to improve mobility in older adults or individuals with movement disorders. Author summary: Our study addresses the challenge of determining optimal musculoskeletal parameters for tasks like sprinting and marathon running. Existing research has been limited to observational studies and simplified simulations. To overcome these limitations, we developed a differentiable musculoskeletal simulator to optimize running performance. We replicated past findings and uncovered new insights. We confirmed the benefits of increased muscle mass for sprinters and identified key factors for marathon runners, such a mass in the lower end of the healthy BMI range and an increased leg-length-to-height ratio. Hip musculature was found to be critical for both sprinting and marathon running. Our simulation results have practical implications. They can inform customized strength training for sprinters and marathon runners. Additionally, the simulator can be extended to other athletic tasks, benefiting various sporting events. Beyond athletics, our open-source simulator has broader applications. It can determine minimal strength requirements for daily activities, guide strength training in the elderly, and estimate the effects of simulated musculoskeletal surgery. [ABSTRACT FROM AUTHOR]