Exogenous MPP3 is Sufficient to Induce Excitatory Synapse Formation

Brain-derived neurotrophic factor (BDNF) is a secreted growth factor critical for the establishment and maintenance of central nervous system (CNS) synapses. However, the precise mechanisms that allow BDNF signaling to regulate synapse formation are unknown. Interestingly, MAGUK scaffold proteins, a family of proteins critical for organizing the molecular architecture of the synapse, have altered gene expression in the brains of BDNF mutant mice. This suggests that BDNF’s in vivo regulation of MAGUK proteins may be important for the process of BDNF-induced synapse formation. Two MAGUKs with the most significantly decreased expression are membrane protein, palmitoylated 3 (MPP3) and postsynaptic density 95 (PSD95). PSD95 is a well-established mediator of synapse formation as demonstrated by PSD95’s colocalization with postsynaptic proteins, sufficiency to increase synapse density, and trafficking to synapses in a BDNF-dependent manner. However, little is known about the role of MPP3 in synapse formation. The specific objective for this research project was to determine if MPP3 positively regulates synapse development and to determine the requirement of MPP3 in BDNF-induced excitatory synapse formation. To test the role of MPP3 in synapse formation two MPP3 expression constructs and three short-hairpin RNAs (shRNAs) were created and transfected in neuronal cultures. The neuronal cultures were fixed and stained for excitatory synaptic markers, VGlut1 and PSD95, and finally imaged using laser scanning confocal microscopy to highlight synapses on these neurons. This methodology was used in order to determine if MPP3 1) localizes to postsynaptic areas, 2) is sufficient to increase synapse density, and 3) is required for BDNF-induced synapse formation. Based on our findings, MPP3 localizes to potential postsynaptic regions and is sufficient to increase excitatory synapse formation

Construing the cultural other and the self: A Personal Construct analysis of English and Italian perceptions of national character

How we perceive other cultures is arguably of increasing importance in contemporary society, impacting on realms such as international relations, business and tourism. The qualitative research reported in this paper was carried out in the UK and in Italy and adopted a Personal Construct Psychology approach. It aimed to explore intercultural perceptions in a sample of people who had some degree of experience with the ‘other’ culture, and a unique feature of the research is that it asked how those perceptions might be affected if people from both cultures are given access to each other’s perceptions. There was considerable commonality in the perceptions of the English and Italian participants, and each culture envied some of the qualities of the other. However, they initially struggled to accommodate how they were seen by the other and endeavoured to resolve difference by construing at a more superordinate level. The findings also suggest that national identity is rooted in the construing of others’ constructions, achieved through relationship and comparison

Interventions for reducing sedentary behaviour in people with stroke

BACKGROUND: Stroke survivors are often physically inactive as well as sedentary,and may sit for long periods of time each day. This increases cardiometabolic risk and has impacts on physical and other functions. Interventions to reduce or interrupt periods of sedentary time, as well as to increase physical activity after stroke, could reduce the risk of secondary cardiovascular events and mortality during life after stroke. OBJECTIVES: To determine whether interventions designed to reduce sedentary behaviour after stroke, or interventions with the potential to do so, can reduce the risk of death or secondary vascular events, modify cardiovascular risk, and reduce sedentary behaviour. SEARCH METHODS: In December 2019, we searched the Cochrane Stroke Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, Conference Proceedings Citation Index, and PEDro. We also searched registers of ongoing trials, screened reference lists, and contacted experts in the field. SELECTION CRITERIA: Randomised trials comparing interventions to reduce sedentary time with usual care, no intervention, or waiting‐list control, attention control, sham intervention or adjunct intervention. We also included interventions intended to fragment or interrupt periods of sedentary behaviour. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and performed 'Risk of bias' assessments. We analyzed data using random‐effects meta‐analyses and assessed the certainty of the evidence with the GRADE approach. MAIN RESULTS: We included 10 studies with 753 people with stroke. Five studies used physical activity interventions, four studies used a multicomponent lifestyle intervention, and one study used an intervention to reduce and interrupt sedentary behaviour. In all studies, the risk of bias was high or unclear in two or more domains. Nine studies had high risk of bias in at least one domain. The interventions did not increase or reduce deaths (risk difference (RD) 0.00, 95% confidence interval (CI) ‐0.02 to 0.03; 10 studies, 753 participants; low‐certainty evidence), the incidence of recurrent cardiovascular or cerebrovascular events (RD ‐0.01, 95% CI ‐0.04 to 0.01; 10 studies, 753 participants; low‐certainty evidence), the incidence of falls (and injuries) (RD 0.00, 95% CI ‐0.02 to 0.02; 10 studies, 753 participants; low‐certainty evidence), or incidence of other adverse events (moderate‐certainty evidence). Interventions did not increase or reduce the amount of sedentary behaviour time (mean difference (MD) +0.13 hours/day, 95% CI ‐0.42 to 0.68; 7 studies, 300 participants; very low‐certainty evidence). There were too few data to examine effects on patterns of sedentary behaviour. The effect of interventions on cardiometabolic risk factors allowed very limited meta‐analysis. AUTHORS' CONCLUSIONS: Sedentary behaviour research in stroke seems important, yet the evidence is currently incomplete, and we found no evidence for beneficial effects. Current World Health Organization (WHO) guidelines recommend reducing the amount of sedentary time in people with disabilities, in general. The evidence is currently not strong enough to guide practice on how best to reduce sedentariness specifically in people with stroke. More high‐quality randomised trials are needed, particularly involving participants with mobility limitations. Trials should include longer‐term interventions specifically targeted at reducing time spent sedentary, risk factor outcomes, objective measures of sedentary behaviour (and physical activity), and long‐term follow‐up

You’ll never walk alone: supportive social relations in a football and mental health project

Football can bring people together in acts of solidarity and togetherness. This spirit is most evocatively illustrated in the world renowned football anthem You’ll Never Walk Alone (YNWA). In this paper we argue that this spirit can be effectively harnessed in nursing and mental health care. We draw on data from qualitative interviews undertaken as part of evaluating a football and mental health project to explore the nature of supportive social relations therein. We use some of the lyrics from YNWA as metaphor to frame our thematic analysis. We are especially interested in the interactions between the group facilitators and group members, but also address aspects of peer support within the groups. A contrast is drawn between the flexible interpersonal boundaries and self-disclosure evident in the football initiative and the reported more distant relations with practitioners in mainstream mental health services. Findings suggest scope for utilising more collective, solidarity enhancing initiatives and attention to alliances and boundaries to maximise engagement and therapeutic benefits within routine practice

Mesenchymal stromal cell-mediated neuroprotection and functional preservation of retinal ganglion cells in a rodent model of glaucoma

Background aims: Glaucoma is a leading cause of irreversible blindness involving loss of retinal ganglion cells (RGC). Mesenchymal stromal cells (MSC) have shown promise as a paracrine-mediated therapy for compromised neurons. It is, however, unknown whether dental pulp stem cells (DPSC) are effective as a cellular therapy in glaucoma and how their hypothesized influence compares with other more widely researched MSC sources. The present study aimed to compare the efficacy of adipose-derived stem cells, bone marrow-derived MSC (BMSC) and DPSC in preventing the loss of RGC and visual function when transplanted into the vitreous of glaucomatous rodent eyes. Methods: Thirty-five days after raised intraocular pressure (IOP) and intravitreal stem cell transplantation, Brn3a+ RGC numbers, retinal nerve fibre layer thickness (RNFL) and RGC function were evaluated by immunohistochemistry, optical coherence tomography and electroretinography, respectively. Results: Control glaucomatous eyes that were sham-treated with heat-killed DPSC had a significant loss of RGC numbers, RNFL thickness and function compared with intact eyes. BMSC and, to a greater extent, DPSC provided significant protection from RGC loss and RNFL thinning and preserved RGC function. Discussion: The study supports the use of DPSC as a neuroprotective cellular therapy in retinal degenerative disease such as glaucoma

Blacklisting and its legacy in the UK construction industry: employment relations in the aftermath of exposure of the Consulting Association

This paper explores responses to the exposure of blacklisting in the UK construction industry in the period following the closure of the Consulting Association (CA) in 2009. It asks whether employer collusion to blacklist in this way has been terminated and concludes that it is now largely of historical interest although other forms of anti-union activity continue. It highlights particularly the historic and continuing importance of ‘double breasting’ and reports on divergent employer paths in the aftermath of the exposure and subsequent closure of the activities of the CA

Feasibility study of the effects of art as a creative engagement intervention during stroke rehabilitation on improvement of psychosocial outcomes: Study protocol for a single blind randomized controlled trial: The ACES study

BackgroundBenefits of art participation after stroke are becoming increasingly recognized. Qualitative studies suggest that participation in visual arts creative engagement interventions (CEIs) during rehabilitation after stroke may improve mood, self-esteem, hope and some aspects of physical recovery. This study examines the feasibility of undertaking a randomized controlled trial of a CEI delivered by artists within in-patient stroke rehabilitation to test effectiveness.Methods/DesignThis trial is a two arm, single-blind, randomized controlled feasibility trial within in-patient stroke rehabilitation. We will recruit 80 patients receiving stroke rehabilitation in two stroke units in a health board area of Scotland (40 patients in each arm). Intervention arm participants will receive a visual-arts based CEI facilitated by experienced artists. Artists will follow an intervention protocol with specific components that enable participants to set, achieve and review artistic goals. Participants will receive up to eight intervention sessions, four within a group and four one-to-one with the artist. Control group participants will receive usual care only.Data collection will occur at baseline, post-intervention and three-month follow-up. Stroke-related health status is the primary outcome; mood, self-esteem, self-efficacy, perceived recovery control and hope are secondary outcomes. Semi-structured interviews will be conducted with purposively selected patients, artists and healthcare staff to elicit views and experiences of the intervention and feasibility and acceptability of trial processes. Recruitment rates, retention rates and patient preference for art participation will also be collected. Data will indicate, with confidence intervals, the proportion of patients choosing or refusing participation in the CEI and will allow calculation of recruitment rates for a future definitive trial. Summary data will indicate potential variability, magnitude and direction of difference between groups. Findings will inform sample size calculations for a definitive trial. Thematic analysis of qualitative data will be managed using the Framework Approach. Framework is an analytical approach for qualitative data, commonly used in policy and medical research.DiscussionIf shown to demonstrate effects, this intervention has the potential to address aspects of stroke recovery previously. Not routinely addressed in rehabilitation.Trial registrationRegistered with Clinical Trials.Gov: NCT02085226 on 6th March 2014

Gaussian process assisted stochastic dynamic analysis with applications to near-periodic structures

This paper characterizes the stochastic dynamic response of periodic structures by accounting for manufacturing variabilities. Manufacturing variabilities are simulated through a probabilistic description of the structural material and geometric properties. The underlying uncertainty propagation problem has been efficiently carried out by functional decomposition in the stochastic space with the help of Gaussian Process (GP) meta-modelling. The decomposition is performed by projected the response onto the eigenspace and involves a nominal number of actual physics-based function evaluations (the eigenvalue analysis). This allows the stochastic dynamic response evaluation to be solved with low computational cost. Two numerical examples, namely an analytical model of a damped mechanical chain and a finite-element model of multiple beam-mass systems, are undertaken. Two key findings from the results are that the proposed GP based approximation scheme is capable of (i) capturing the stochastic dynamic response in systems with well-separated modes in the presence of high levels of uncertainties (up to 20), and (ii) adequately capturing the stochastic dynamic response in systems with multiple sets of identical modes in the presence of 5–10 uncertainty. The results are validated by Monte Carlo simulations

Prevalence of severe childhood obesity in England:2006-2013

BACKGROUND: International evidence shows that severe paediatric obesity results in an increased risk of ill health and may require specialised weight management strategies, yet there remains a lack of data on the extent of the problem. OBJECTIVE: To examine the prevalence of severe obesity in children aged 4-5 and 10-11 years, attending English schools between 2006/2007 and 2012/2013. DESIGN: A retrospective analysis of National Child Measurement Programme (NCMP) data. SETTING: Maintained schools in England. PARTICIPANTS: All children aged 4-5 and 10-11 years included in the NCMP dataset. MAIN OUTCOME MEASURES: Prevalence of severe childhood obesity, defined using the 99.6th centile of the British 1990 (UK90) growth reference for body mass index (BMI), analysed by sex, geography, ethnic group and deprivation. RESULTS: The key findings show that in 2012/2013, severe obesity (BMI ≥UK90 99.6th centile) was found in 1.9% of girls and 2.3% of boys aged 4-5 years, and 2.9% of girls and 3.9% of boys aged 10-11 years. Severe obesity prevalence varies geographically and is more prevalent in children from deprived areas, and among those from black ethnic groups. CONCLUSIONS: The findings from this study should help to raise awareness of the prevalence of severe obesity and support the provision of adequate treatment and prevention services both to support children who are already severely obese and reduce the prevalence of extreme weight in the future