Restoration of SMN in Schwann cells reverses myelination defects and improves neuromuscular function in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein, primarily affecting lower motor neurons. Recent evidence from SMA and related conditions suggests that glial cells can influence disease severity. Here, we investigated the role of glial cells in the peripheral nervous system by creating SMA mice selectively overexpressing SMN in myelinating Schwann cells (Smn(−/−);SMN2(tg/0);SMN1(SC)). Restoration of SMN protein levels restricted solely to Schwann cells reversed myelination defects, significantly improved neuromuscular function and ameliorated neuromuscular junction pathology in SMA mice. However, restoration of SMN in Schwann cells had no impact on motor neuron soma loss from the spinal cord or ongoing systemic and peripheral pathology. This study provides evidence for a defined, intrinsic contribution of glial cells to SMA disease pathogenesis and suggests that therapies designed to include Schwann cells in their target tissues are likely to be required in order to rescue myelination defects and associated disease symptoms

A mixed methods systematic review of digital interventions to support the psychological health and well-being of people living with dermatological conditions

Background: Dermatological conditions can have a substantial impact on psychological as well as physical health yet dedicated face-to-face psychological support for patients is lacking. Thus, individuals may require additional support to self-manage dermatological conditions effectively. Digital technology can contribute to long-term condition management, but knowledge of the effectiveness of digital interventions addressing psychological (cognitive, emotional, and behavioural) aspects of dermatological conditions is limited. Objectives: To identify, determine the effectiveness, and explore people’s views and experiences of digital interventions supporting the psychological health of people with dermatological conditions. Methods: A mixed methods systematic review informed by JBI methodology. The protocol was registered on PROSPERO. Eight electronic databases were searched for papers written between January 2002 and October 2021. Data screening and extraction were conducted in Covidence. The methodological quality of studies were scrutinised against JBI critical appraisal tools. Intervention characteristics were captured using the Template for Intervention Description and Replication checklist and guide. Data were synthesised using a convergent segregated approach. The results were reported in a narrative summary. Results: Twenty-three papers were identified from 4,883 references, including 15 randomised controlled trials. Nineteen interventions were condition-specific, 13 were delivered online, 16 involved an educational component, and 7 endorsed established, evidence-based therapeutic approaches. Improvements in knowledge, mood, quality of life, the therapeutic relationship, and reduced disease severity in the short to medium term, were reported, although there was substantial heterogeneity within the literature. Thirteen studies captured feedback from users, who considered various digital interventions as convenient and helpful for improving knowledge, emotion regulation, and personal control, but technical and individual barriers to use were reported. Use of established qualitative methodologies was limited and, in some cases, poorly reported. Conclusion: Some web-based digital psychological interventions seem to be acceptable to people living with mainly psoriasis and eczema. Whilst some digital interventions benefitted cognitive and emotional factors, heterogeneity and inconsistencies in the literature meant definitive statements about their effectiveness could not be drawn. Interdisciplinary and patient-centred approaches to research are needed to develop and test quality digital interventions supporting the psychological health of adults living with common and rare dermatological conditions

School playgrounds and physical activity policies as predictors of school and home time activity

<p>Abstract</p> <p>Background</p> <p>Previous work has suggested that the number of permanent play facilities in school playgrounds and school-based policies on physical activity can influence physical activity in children. However, few comparable studies have used objective measures of physical activity or have had little adjustment for multiple confounders.</p> <p>Methods</p> <p>Physical activity was measured by accelerometry over 5 recess periods and 3 full school days in 441 children from 16 primary schools in Dunedin, New Zealand. The number of permanent play facilities (swing, fort, slide, obstacle course, climbing wall etc) in each school playground was counted on three occasions by three researchers following a standardized protocol. Information on school policies pertaining to physical activity and participation in organized sport was collected by questionnaire.</p> <p>Results</p> <p>Measurement of school playgrounds proved to be reliable (ICC 0.89) and consistent over time. Boys were significantly more active than girls (P < 0.001), but little time overall was spent in moderate-vigorous physical activity (MVPA). Boys engaged in MVPA for 32 (SD 17) minutes each day of which 17 (10) took place at school compared with 23 (14) and 11 (7) minutes respectively in girls. Each additional 10-unit increase in play facilities was associated with 3.2% (95% CI 0.0-6.4%) more total activity and 8.3% (0.8-16.3%) more MVPA during recess. By contrast, school policy score was not associated with physical activity in children.</p> <p>Conclusion</p> <p>The number of permanent play facilities in school playgrounds is associated with higher physical activity in children, whereas no relationship was observed for school policies relating to physical activity. Increasing the number of permanent play facilities may offer a cost-effective long-term approach to increasing activity levels in children.</p

Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy

Acknowledgments Blood biochemistry analysis and serum analysis were performed by the Easter Bush Pathology Department, University of Edinburgh. Animal husbandry was performed by Centre for Integrative Physiology bio-research restructure technical staff, University of Edinburgh. Assistance with intravenous injections was provided by Ian Coldicott (University of Sheffield) and Hannah Shorrock (University of Edinburgh). Human blood cDNA was a gift to GH from Kathy Evans, University of Edinburgh. Imaging was performed at the IMPACT imaging facility, University of Edinburgh, with technical assistance from Anisha Kubasik-Thayil. The authors would also like to thank Lyndsay Murray for technical discussions relating to qRT-PCR analysis. This work was supported by funding from the SMA Trust and the Anatomical Society (via grants to THG); the Euan MacDonald Centre for Motor Neurone Disease Research (via grants to THG and SHP); the Wellcome Trust (via grants to EJNG and THG); Muscular Dystrophy UK (via grants to THG and CGB); a Elphinstone Scholarship from the University of Aberdeen (to SHP); and The French Muscular Dystrophy Association (via grants to CM and JC).Peer reviewedPublisher PD

The consumption of protein-rich foods in older adults: An exploratory focus group study

Objective: Many older adults consume inadequate protein for their needs. This study explored the factors associated with the consumption of high-protein foods in older adults. Methods: Participants over the age of 65 years (n = 28) took part in 1 of 4 focus group discussions on meat, fish, eggs, dairy products, nuts, and pulses. Discussions were audio taped, transcribed, and analyzed using thematic analysis. Results: Numerous and various reasons for the consumption and non-consumption of high-protein foods were reported. Many of these reasons result from reductions in chemosensory, dental and physical abilities, and changes in living situation in the older population, and have impact specifically on high-protein foods because of their often hard, perishable and need-to-be-cooked nature, and high cost. Conclusions and Implications: Further work is required to establish the importance of each of thesereasons in relation to protein intakes, to prioritize those of likely greatest impact for increasing intakes. © 2013 Society for Nutrition Education and Behavior

Regulation of meiotic prophase arrest in mouse oocytes by GPR3, a constitutive activator of the Gs G protein

The arrest of meiotic prophase in mouse oocytes within antral follicles requires the G protein Gs and an orphan member of the G protein–coupled receptor family, GPR3. To determine whether GPR3 activates Gs, the localization of Gαs in follicle-enclosed oocytes from Gpr3+/+ and Gpr3−/− mice was compared by using immunofluorescence and GαsGFP. GPR3 decreased the ratio of Gαs in the oocyte plasma membrane versus the cytoplasm and also decreased the amount of Gαs in the oocyte. Both of these properties indicate that GPR3 activates Gs. The follicle cells around the oocyte are also necessary to keep the oocyte in prophase, suggesting that they might activate GPR3. However, GPR3-dependent Gs activity was similar in follicle-enclosed and follicle-free oocytes. Thus, the maintenance of prophase arrest depends on the constitutive activity of GPR3 in the oocyte, and the follicle cell signal acts by a means other than increasing GPR3 activity

Addressing the Supportive Transportation Challenges of Community-Residing Older Adults

The ability to get to where you want to go, when you want to go there is a key factor for aging-in-place in our communities. It is often taken for granted until that ability is compromised. The informal network of family and friends, if it exists, is not likely to be a sustainable transportation alternative for persons with cognitive impairment or for older adults with limitations that may not fit eligibility criteria for senior transportation services, where they exist. The purpose of this study was to investigate the potential of communities to address the specialized supportive mobility needs of community-residing older adults. A major conclusion to emerge from the research is the connection of mobility to healthcare

Motivational interviewing for screening and feedback and encouraging lifestyle changes to reduce relative weight in 4-8 year old children: design of the MInT study

<p>Abstract</p> <p>Background</p> <p>Because parental recognition of overweight in young children is poor, we need to determine how best to inform parents that their child is overweight in a way that enhances their acceptance and supports motivation for positive change. This study will assess 1) whether weight feedback delivered using motivational interviewing increases parental acceptance of their child's weight status and enhances motivation for behaviour change, and 2) whether a family-based individualised lifestyle intervention, delivered primarily by a MInT mentor with limited support from "expert" consultants in psychology, nutrition and physical activity, can improve weight outcomes after 12 and 24 months in young overweight children, compared with usual care.</p> <p>Methods/Design</p> <p>1500 children aged 4-8 years will be screened for overweight (height, weight, waist, blood pressure, body composition). Parents will complete questionnaires on feeding practices, physical activity, diet, parenting, motivation for healthy lifestyles, and demographics. Parents of children classified as overweight (BMI ≥ CDC 85^th) will receive feedback about the results using Motivational interviewing or Usual care. Parental responses to feedback will be assessed two weeks later and participants will be invited into the intervention. Additional baseline measurements (accelerometry, diet, quality of life, child behaviour) will be collected and families will be randomised to Tailored package or Usual care. Parents in the Usual care condition will meet once with an advisor who will offer general advice regarding healthy eating and activity. Parents in the Tailored package condition will attend a single session with an "expert team" (MInT mentor, dietitian, physical activity advisor, clinical psychologist) to identify current challenges for the family, develop tailored goals for change, and plan behavioural strategies that best suit each family. The mentor will continue to provide support to the family via telephone and in-person consultations, decreasing in frequency over the two-year intervention. Outcome measures will be obtained at baseline, 12 and 24 months.</p> <p>Discussion</p> <p>This trial offers a unique opportunity to identify effective ways of providing feedback to parents about their child's weight status and to assess the efficacy of a supportive, individualised early intervention to improve weight outcomes in young children.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry ACTRN12609000749202</p

What were the information voids? A qualitative analysis of questions asked by Dear Pandemic readers between august 2020-august 2021

In the current infodemic, how individuals receive information (channel), who it is coming from (source), and how it is framed can have an important effect on COVID-19 related mitigation behaviors. In light of these challenges presented by the infodemic, Dear Pandemic (DP) was created to directly address persistent questions related to COVID-19 and other health topics in the online environment. This is a qualitative analysis of 3806 questions that were submitted by DP readers to a question box on the Dear Pandemic website between August 30, 2020 and August 29, 2021. Analyses resulted in four themes: the need for clarification of other sources; lack of trust in information; recognition of possible misinformation; and questions on personal decision-making. Each theme reflects an unmet informational need of Dear Pandemic readers, which may be reflective of the broader informational gaps in our science communication efforts.This study highlights the role of an ad hoc risk communication platform in the current environment and uses questions submitted to the Dear Pandemic question box to identify informational needs of DP readers over the course of the COVID-19 pandemic. These findings may help clarify how organizations addressing health misinformation in the digital space can contribute to timely, responsive science communication and improve future communication efforts