'Walk this way': results from a pilot randomised controlled trial of a health coaching intervention to reduce sedentary behaviour and increase physical activity in people with serious mental illness.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of premature death among people with serious mental illness (SMI). Sedentary behaviour (SB) is an independent risk factor for CVD and mortality and people with SMI are highly sedentary. We developed a health coaching intervention called 'Walk this Way' to reduce SB and increase physical activity (PA) in people with SMI and conducted a pilot randomised controlled trial (RCT) to test its feasibility and acceptability. METHODS: We randomised people with SMI from three community mental health teams into either the WTW intervention or treatment as usual. The WTW intervention lasted 17 weeks and included an initial education session, fortnightly coaching, provision of pedometers and access to a weekly walking group. Objective SB and PA were measured with accelerometers. Cardiometabolic risk factors and wellbeing measures were collected. RESULTS: We recruited 40 people of whom 33 (82.5%) were followed up. 13/20 (65%) of participants allocated to the coaching intervention completed it. In the intervention group SB decreased by 56 min and total PA increased by 32 min per day on average which was sustained 6 months later. There was no change in PA or SB in the control group. When interviewed, participants in the intervention found the intervention helpful and acceptable. No adverse events were reported from the intervention. CONCLUSIONS: The intervention was feasible and acceptable to participants. Preliminary results were encouraging with improvement seen in both SB and PA. A larger study is needed to assess the effectiveness of the intervention and address any implementation challenges. TRIAL REGISTRATION: ISRCTN Registry identifier: ISRCTN37724980 , retrospectively registered 25 September 2015.

Single-Cell Analyses of Prostate Cancer Liquid Biopsies Acquired by Apheresis.

Purpose: Circulating tumor cells (CTCs) have clinical relevance, but their study has been limited by their low frequency.Experimental Design: We evaluated liquid biopsies by apheresis to increase CTC yield from patients suffering from metastatic prostate cancer, allow precise gene copy-number calls, and study disease heterogeneity.Results: Apheresis was well tolerated and allowed the separation of large numbers of CTCs; the average CTC yield from 7.5 mL of peripheral blood was 167 CTCs, whereas the average CTC yield per apheresis (mean volume: 59.5 mL) was 12,546 CTCs. Purified single CTCs could be isolated from apheresis product by FACS sorting; copy-number aberration (CNA) profiles of 185 single CTCs from 14 patients revealed the genomic landscape of lethal prostate cancer and identified complex intrapatient, intercell, genomic heterogeneity missed on bulk biopsy analyses.Conclusions: Apheresis facilitated the capture of large numbers of CTCs noninvasively with minimal morbidity and allowed the deconvolution of intrapatient heterogeneity and clonal evolution. Clin Cancer Res; 24(22); 5635-44. ©2018 AACR.

Halting of Caspase Activity Protects Tau from MC1-Conformational Change and Aggregation.

Intracellular neurofibrillary tangles (NFTs) are the hallmark of Alzheimer's disease and other tauopathies in which tau, a microtubule-associated protein, loses its ability to stabilize microtubules. Several post-translational modifications including phosphorylation and truncation increase tau's propensity to aggregate thus forming NFTs; however, the mechanisms underlying tau conformational change and aggregation still remain to be defined. Caspase activation and subsequent proteolytic cleavage of tau is thought to be a potential trigger of this disease-related pathological conformation. The aim of this work was to investigate the link between caspase activation and a disease-related conformational change of tau in a neuroblastoma cell-based model of spontaneous tau aggregation. We demonstrated that caspase induction initiates proteolytic cleavage of tau and generation of conformationally altered and aggregated tau recognized by the MC1 conformational antibody. Most importantly, these events were shown to be attenuated with caspase inhibitors. This implies that therapeutics aimed at inhibiting caspase-mediated tau cleavage may prove beneficial in slowing cleavage and aggregation, thus potentially halting tau pathology and disease progression.

The effect of a specialist seating assessment clinic on the skin management of individuals with spinal cord injury.

OBJECTIVE: To evaluate the specialist seating clinic's effectiveness in improving skin management knowledge and independence, represented by the Needs Assessment Checklist (NAC). DESIGN: Longitudinal, between subjects design, with two intervention groups and one control. SETTING: Tertiary care, spinal cord injury centre (National Spinal Injuries Centre), Stoke Mandeville Hospital, United Kingdom. METHOD: This study assessed the skin management ability of three groups. Group 1 consisted of individuals who had attended a specialist seating assessment (SSA) clinic before their first needs assessment, group 2 had attended SSA between their first and second needs assessment, and group 3 (control) had not attended at all. Patient skin management ability was assessed using the skin management subscale of the NAC, a measure of rehabilitation outcome, at two time points. RESULTS: Significant differences were identified between group 3 and group 1 at both the first (t = 2.36, degrees of freedom (df) = 37, p < 0.05) and second (t = 2.84, df = 37, p < 0.01) needs assessment. Significant improvements were also observed within each group between the first and second needs assessment time points in all seating assessment categories. CONCLUSION: Skin management achievement scores were significantly higher for patients who had attended a SSA clinic before their first NAC (group 1) at both time points, supporting the use of SSA as a proactive intervention to improve patient independence, knowledge and awareness, and potentially reduce pressure ulcer incidence.