An App to Help Young People Self-Manage When Feeling Overwhelmed (ReZone): Protocol of a Cluster Randomized Controlled Trial

Background: The association between behavioral difficulties and academic attainment is well established. Recent policy advising schools on managing behavior has promoted the early identification of behavioral difficulties. There is also increasing research into mHealth interventions to provide support for emotional and behavioral difficulties for young people. Objective: The primary aim of the proposed research is to examine the effectiveness of an mHealth intervention, ReZone, in reducing emotional and behavioral difficulties in young people. Methods: The protocol is a cluster trial of 12 classes with N=120 students with classes randomized to ReZone or management as usual. Multilevel modeling will be used to compare ReZone versus management as usual accounting for classroom-level variation. Results: Baseline data collection started in February 2017 and ended in April 2017. Follow-up data collection started in April 2017 and ended in June 2017. Conclusions: The proposed research will provide evidence as to whether ReZone is effective at helping young people to self-manage when feeling overwhelmed

Interactions among mitochondrial proteins altered in glioblastoma

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein–protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology

Rheumatoid Arthritis is an Autoimmune Disease Triggered by Proteus Urinary Tract Infection

Rheumatoid arthritis (RA) is a chronic and disabling polyarthritic disease, which affects mainly women in middle and old age

Collision activity during training increases total energy expenditure measured via doubly labelled water

Purpose: Collision sports are characterised by frequent high intensity collisions that induce substantial muscle damage, potentially increasing the energetic cost of recovery. Therefore, this study investigated the energetic cost of collision-based activity for the first time across any sport. Methods: Using a randomised crossover design, six professional young male rugby league players completed two different five-day pre-season training microcycles. Players completed either a collision (COLL; 20 competitive one-on-one collisions) or non-collision (nCOLL; matched for kinematic demands, excluding collisions) training session on the first day of each microcycle, exactly seven days apart. All remaining training sessions were matched and did not involve any collision-based activity. Total energy expenditure was measured using doubly labelled water, the literature gold standard. Results: Collisions resulted in a very likely higher (4.96 ± 0.97 MJ; ES = 0.30 ±0.07; p=0.0021) total energy expenditure across the five-day COLL training microcycle (95.07 ± 16.66 MJ) compared with the nCOLL training microcycle (90.34 ± 16.97 MJ). The COLL training session also resulted in a very likely higher (200 ± 102 AU; ES = 1.43 ±0.74; p=0.007) session rating of perceived exertion and a very likely greater (-14.6 ± 3.3%; ES = -1.60 ±0.51; p=0.002) decrease in wellbeing 24h later. Conclusions: A single collision training session considerably increased total energy expenditure. This may explain the large energy expenditures of collision sport athletes, which appear to exceed kinematic training and match demands. These findings suggest fuelling professional collision-sport athletes appropriately for the "muscle damage caused” alongside the kinematic “work required”. Key words: Nutrition, Recovery, Contact, Rugb

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

BACKGROUND: Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. METHODS: The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. DISCUSSION: The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.MRC Funding: MC_UP_1302/3 NIHR Funding: RP-PG-0610-1006

Strengthening and stretching for rheumatoid arthritis of the hand (SARAH):Design of a randomised controlled trial of a hand and upper limb exercise intervention-ISRCTN89936343

Background: Rheumatoid Arthritis (RA) commonly affects the hands and wrists with inflammation, deformity, pain, weakness and restricted mobility leading to reduced function. The effectiveness of exercise for RA hands is uncertain, although evidence from small scale studies is promising. The Strengthening And Stretching for Rheumatoid Arthritis of the Hand (SARAH) trial is a pragmatic, multi-centre randomised controlled trial evaluating the clinical and cost effectiveness of adding an optimised exercise programme for hands and upper limbs to best practice usual care for patients with RA.Methods/design: 480 participants with problematic RA hands will be recruited through 17 NHS trusts. Treatments will be provided by physiotherapists and occupational therapists. Participants will be individually randomised to receive either best practice usual care (joint protection advice, general exercise advice, functional splinting and assistive devices) or best practice usual care supplemented with an individualised exercise programme of strengthening and stretching exercises. The study assessors will be blinded to treatment allocation and will follow participants up at four and 12 months. The primary outcome measure is the Hand function subscale of the Michigan Hand Outcome Questionnaire, and secondary outcomes include hand and wrist impairment measures, quality of life, and resource use. Economic and qualitative studies will also be carried out in parallel.Discussion: This paper describes the design and development of a trial protocol of a complex intervention study based in therapy out-patient departments. The findings will provide evidence to support or refute the use of an optimised exercise programme for RA of the hand in addition to best practice usual care.Trial registration: Current Controlled Trials ISRCTN89936343Keywords: Randomised controlled trial, Rheumatoid arthritis, Exercise, Hand, Rehabilitatio

The effect of prior walking on coronary heart disease risk markers in South Asian and European men.

Purpose: Heart disease risk is elevated in South Asians possibly due to impaired postprandial metabolism. Running has been shown to induce greater reductions in postprandial lipaemia in South Asian than European men but the effect of walking in South Asians is unknown. Methods: Fifteen South Asian and 14 White European men aged 19-30 years completed two, 2-d trials in a randomised crossover design. On day 1, participants rested (control) or walked for 60 min at approximately 50% maximum oxygen uptake (exercise). On day 2, participants rested and consumed two high fat meals over a 9h period during which 14 venous blood samples were collected. Results: South Asians exhibited higher postprandial triacylglycerol (geometric mean (95% confidence interval) 2.29(1.82 to 2.89) vs. 1.54(1.21 to 1.96) mmol·L-1·hr-1), glucose (5.49(5.21 to 5.79) vs. 5.05(4.78 to 5.33) mmol·L-1·hr-1), insulin (32.9(25.7 to 42.1) vs. 18.3(14.2 to 23.7) µU·mL-1·hr-1) and interleukin-6 (2.44(1.61 to 3.67) vs. 1.04(0.68 to 1.59) pg·mL-1·hr-1) than Europeans (all ES ≥ 0.72, P≤0.03). Between-group differences in triacylglycerol, glucose and insulin were not significant after controlling for age and percentage body fat. Walking reduced postprandial triacylglycerol (1.79(1.52 to 2.12) vs. 1.97(1.67 to 2.33) mmol·L-1·hr-1) and insulin (21.0(17.0 to 26.0) vs. 28.7(23.2 to 35.4) µU·mL-1·hr-1) (all ES ≥ 0.23. P≤0.01), but group differences were not significant. Conclusions: Healthy South Asians exhibited impaired postprandial metabolism compared with White Europeans, but these differences were diminished after controlling for potential confounders. The small-moderate reduction in postprandial triacylglycerol and insulin after brisk walking was not different between the ethnicities