'HeART of Stroke (HoS)', a community-based Arts for Health group intervention to support self-confidence and psychological well-being following a stroke: protocol for a randomised controlled feasibility study

Introduction Over 152 000 people in the UK have strokes annually and a third experience residual disability. Low mood also affects a third of stroke survivors; yet psychological support is poor. While Arts for Health interventions have been shown to improve well-being in people with mild-to-moderate depression post-stroke, their role in helping people regain sense of self, well-being and confidence has yet to be evaluated. The main aim of this study is to explore the feasibility of conducting a pragmatic multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of an Arts for Health group intervention (‘HeART of Stroke’ (HoS)) for stroke survivors. HoS is a 10-session artist-facilitated group intervention held in the community over 14 weeks. It offers a non-judgemental, supportive environment for people to explore sense of self, potentially enhancing well-being and confidence. Methods and analysis Sixty-four people, up to 2 years post-stroke, recruited via secondary care research staff or community stroke/rehabilitation teams in two UK centres will be randomised to either HoS plus usual care or usual care only. Self-reported outcomes, measured at baseline and approximately 5 months postrandomisation, will include stroke-related, well-being, mood, self-esteem, quality of life and process measures. Analyses will focus on estimating key feasibility parameters (eg, rates of recruitment, retention, intervention attendance). We will develop outcome and resource use data collection methods to inform an effectiveness and cost-effectiveness analysis in the future trial. Interviews, with a sample of participants, will explore the acceptability of the intervention and study processes, as well as experiences of the HoS group. Ethics and dissemination National Health Service (NHS), Research and Development and University ethical approvals have been obtained. Two peer-reviewed journal publications are planned plus one service user led publication. Findings will be disseminated at key national conferences, local stakeholder events and via institutional websites.This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0212-27054)

The AP-3 Adaptor Complex Is Essential for Cargo-Selective Transport to the Yeast Vacuole

AbstractThree distinct adaptor protein (AP) complexes involved in protein trafficking have been identified. AP-1 and AP-2 mediate protein sorting at the trans-Golgi network and plasma membrane, respectively, whereas the function of AP-3 has not been defined. A screen for factors specifically involved in transport of alkaline phosphatase (ALP) from the Golgi to the vacuole/lysosome has identified Apl6p and Apl5p of the yeast AP-3 complex. Deletion of each of the four AP-3 subunits results in selective mislocalization of ALP and the vacuolar t-SNARE, Vam3p (but not CPS and CPY), while deletion of AP-1 and AP-2 subunits has no effect on vacuolar protein delivery. This study, therefore, provides evidence that the AP-3 complex functions in cargo-selective protein transport from the Golgi to the vacuole/lysosome

Osmotic stress–induced increase of phosphatidylinositol 3,5-bisphosphate requires Vac14p, an activator of the lipid kinase Fab1p

Phosphatidylinositol 3,5-bisphosphate (PtdIns[3,5]P2) was first identified as a nonabundant phospholipid whose levels increase in response to osmotic stress. In yeast, Fab1p catalyzes formation of PtdIns(3,5)P2 via phosphorylation of PtdIns(3)P. We have identified Vac14p, a novel vacuolar protein that regulates PtdIns(3,5)P2 synthesis by modulating Fab1p activity in both the absence and presence of osmotic stress. We find that PtdIns(3)P levels are also elevated in response to osmotic stress, yet, only the elevation of PtdIns(3,5)P2 levels are regulated by Vac14p. Under basal conditions the levels of PtdIns(3,5)P2 are 18–28-fold lower than the levels of PtdIns(3)P, PtdIns(4)P, and PtdIns(4,5)P2. After a 10 min exposure to hyperosmotic stress the levels of PtdIns(3,5)P2 rise 20-fold, bringing it to a cellular concentration that is similar to the other phosphoinositides. This suggests that PtdIns(3,5)P2 plays a major role in osmotic stress, perhaps via regulation of vacuolar volume. In fact, during hyperosmotic stress the vacuole morphology of wild-type cells changes dramatically, to smaller, more highly fragmented vacuoles, whereas mutants unable to synthesize PtdIns(3,5)P2 continue to maintain a single large vacuole. These findings demonstrate that Vac14p regulates the levels of PtdIns(3,5)P2 and provide insight into why PtdIns(3,5)P2 levels rise in response to osmotic stress