Remote ischemic conditioning for stroke: A critical systematic review

Remote ischemic conditioning (RIC) is the application of brief periods of ischemia to an organ or tissue with the aim of inducing protection from ischemia in a distant organ. It was first developed as a cardioprotective strategy but has been increasingly investigated as a neuroprotective intervention. The mechanisms by which RIC achieves neuroprotection are incompletely understood. Preclinical studies focus on the hypothesis that RIC can protect the brain from ischemia reperfusion (IR) injury following the restoration of blood flow after occlusion of a large cerebral artery. However, increasingly, a role of chronic RIC (CRIC) is being investigated as a means of promoting recovery following an ischemic insult to the brain. The recent publication of two large, randomized control trials has provided promise that RIC could improve functional outcomes after acute ischemic stroke, and that there may be a role for CRIC in the prevention of recurrent stroke. Although less developed, there is also proof-of-concept to suggest that RIC may be used to reduce vasospasm after subarachnoid hemorrhage or improve cognitive outcomes in vascular dementia. As a cheap, well-tolerated and almost universally applicable intervention, the motivation for investigating possible benefit of RIC in patients with cerebrovascular disease is great. In this review, we shall review the current evidence for RIC as applied to cerebrovascular disease

Creatinine and myoglobin are poor predictors of anaerobic threshold in colorectal cancer and health

Aims Myoglobin is a haem protein produced in skeletal muscles. Serum concentrations of myoglobin have been proposed as a surrogate marker of muscle mass and function in both cachectic cancer patients and healthy non-cancer individuals. Creatinine, a metabolite of creatine phosphate, an energy store found in skeletal muscle, is produced at a constant rate from skeletal muscle. Urinary and plasma creatinine have been used in clinical practice as indicators of skeletal muscle mass in health and disease. Our study aimed to test the hypothesis that plasma myoglobin and creatinine concentration could accurately predict skeletal muscle mass and aerobic capacity in colorectal cancer (CRC) patients and matched healthy controls and thereby an indicative of aerobic performance. Methods We recruited 47 patients with CRC and matching number of healthy volunteers for this study. All participants had their body composition measured by dual-energy X-ray absorptiometry scan, aerobic capacity measured to anaerobic threshold (AT) by cardiopulmonary exercise testing and filled in objective questionnaires to assess the qualitative functions. This study was carried out in accordance with the Declaration of Helsinki, after approval by the local National Health Service (NHS) Research Ethics Committee. Results Age-matched groups had similar serum myoglobin and creatinine concentrations in spite of differences in their aerobic capacity. AT was significantly lower in the CRC group compared with matched controls (1.18 ± 0.44 vs. 1.41 ± 0.71 L/min; P < 0.01). AT had significant correlation with lean muscle mass (LMM) among these groups, but myoglobin and creatinine had poor correlation with LMM and AT. Conclusions Serum myoglobin is a poor predictor of muscle mass, and serum myoglobin and creatinine concentrations do not predict aerobic performance in CRC patients or healthy matched controls

Short-Term Impact of Point-Source Enrichment on the Behavior of Gestating Sows Housed in Groups

Environmental enrichment is an important strategy to improve the welfare of farm animals. However, relatively little is known about enrichment for gestating sows, especially those raised on farms with slatted floors and for which provision of straw may be difficult. The objective of this study was therefore to investigate the short-term (4 d) impact of a point-source enrichment object on the behavior of gestating sows housed in group pens. Four pens of gestating sows on a university research farm were randomly allocated to receive either enrichment or no enrichment (control) in a 2 by 2 crossover design. Time budgets were established by video recording focal sows' behaviors (n = 10 focals per pen) every 15 min between 0800 and 1500 every day. Enrichment use was further characterized by continuous behavior sampling for a 1 h interval between 0830 and 0930 each day. The impact of parity, lameness and presence of stereotypical behavior such as sham chewing on enrichment use was evaluated. Over the course of the study, focal sows spent approximately 73% of observations inactive [either lying down (70%), standing (2%), or sitting (1%)]. Within the remaining observations, sows were most commonly observed sham-chewing (16%), followed by 3% exploring, 2% feeding, 2% walking and 1% interacting with the enrichment when it was available. Low-parity sows, moderately-lame sows, and sows observed sham chewing at baseline displayed more consistent enrichment use over the course of the study (p = 0.02, p < 0.01, p = 0.04, respectively). While no adverse behavioral effects (increased agonism or sham chewing) due to provision or removal of the enrichment object were observed and while 85% of sows were observed to interact with enrichment at least once, interest declined sharply after the first day. We conclude that further research is needed to identify effective and sustainable enrichment strategies for gestating sows

Surgical resection of primary tumour improves aerobic performance in colorectal cancer

Background Colorectal cancer is the third most common cancer in the UK, with patients suffering declines in muscle mass and aerobic function. We hypothesised that tumour removal in non-metastatic colorectal cancer would lead to a restoration of lean muscle mass and increases in objective and subjective measures of aerobic performance. Methods We recruited two groups: patients with colorectal cancer (n = 30, 65.3 (51–77) y, body mass index 27.67 (4.83) kg m−2) and matched controls (n = 30, 64.6 (42–77) y, BMI 27.14 (3.51) kg m−2). Controls underwent a single study while colorectal cancer patients were studied before and 10 months after tumour resection. Aerobic performance was assessed via cardiopulmonary exercise testing and activity questionnaires. Lean muscle mass was measured via dual-energy X-ray absorptiometry. Results Lean muscle mass was not different between groups (control: 47.82 (8.23); pre-resection: 52.41 (10.59); post-resection: 52.38 (10.52), kg). Anaerobic threshold was lower in pre-operative patients compared to controls (14.40 (3.23) vs. 19.67 (5.81) ml kg−1 min−1, p < 0.0001), increasing significantly post-resection (17.00 (3.56) ml kg−1 min−1 p < 0.0001). Self reported maximal physical activity was lower after resection compared to preoperatively (pre-resection 6.0 (6.5–5 IQR), post-resection 3.75 (4–3 IQR), p < 0.0001). Conclusion In colorectal cancer, anaerobic threshold is reached more rapidly than in matched controls, returning toward normal with tumour resection. Self-reported measures of activity do not mirror this objective change, cardiopulmonary exercise testing may therefore allow for a more accurate evaluation of pre and postoperative performance capability. The variance between objective and subjective measures of exercise capacity may be important in determining return to normal activities

Enriching a protein drink with leucine augments muscle protein synthesis after resistance exercise in young and older men

Maximizing anabolic responses to feeding and exercise is crucial for muscle maintenance and adaptation to exercise training. We hypothesized that enriching a protein drink with leucine would improve anabolic responses to resistance exercise (RE: 6×8 knee-extension repetitions at 75% of 1-RM) in both young and older adults. Groups (n=9) of young (24±6 y, BMI 23±2kg.m-2) and older men (70±5 y, BMI 25±2 kg.m-2) were randomized to either: (i) RE followed by Slim-Fast Optima (SFO 10 g PRO; 24 g CHO) with 4.2 g of leucine (LEU) or, (ii) RE+SFO with 4.2 g of alanine (ALA; isonitrogenous control). Muscle biopsies were taken before, immediately after, and 1, 2 and 4 h after RE and feeding. Muscle protein synthesis (MPS) was measured by incorporation of [1, 2-13C2] leucine into myofibrillar proteins and the phosphorylation of p70S6K1 by immunoblotting. In young men, both area under the curve (AUC; FSR 0-4 h P<0.05) and peak FSR (0.11 vs. 0.08%.h.-1; P<0.05) were greater in the SFO+LEU than in the SFO+ALA group, after RE. Similarly, in older men, AUC analysis revealed that post-exercise anabolic responses were greater in the SFO+LEU than SFO+ALA group, after RE (AUC; FSR 0-4 h P<0.05). Irrespective of age, increases in p70S6K1 phosphorylation were evident in response to both SFO+LEU and SFO+ALA, although greater with leucine supplementation than alanine (fold-change 2.2 vs. 3.2; P<0.05), specifically in the older men. We conclude that addition of Leucine to a sub-maximal PRO bolus improves anabolic responses to RE in young and older men

Breast cancer risk prediction using a polygenic risk score in the familial setting: a prospective study from the Breast Cancer Family Registry and kConFab.

PURPOSE: This study examined the utility of sets of single-nucleotide polymorphisms (SNPs) in familial but non-BRCA-associated breast cancer (BC). METHODS: We derived a polygenic risk score (PRS) based on 24 known BC risk SNPs for 4,365 women from the Breast Cancer Family Registry and Kathleen Cuningham Consortium Foundation for Research into Familial Breast Cancer familial BC cohorts. We compared scores for women based on cancer status at baseline; 2,599 women unaffected at enrollment were followed-up for an average of 7.4 years. Cox proportional hazards regression was used to analyze the association of PRS with BC risk. The BOADICEA risk prediction algorithm was used to measure risk based on family history alone. RESULTS: The mean PRS at baseline was 2.25 (SD, 0.35) for affected women and was 2.17 (SD, 0.35) for unaffected women from combined cohorts (P < 10-6). During follow-up, 205 BC cases occurred. The hazard ratios for continuous PRS (per SD) and upper versus lower quintiles were 1.38 (95% confidence interval: 1.22-1.56) and 3.18 (95% confidence interval: 1.84-5.23) respectively. Based on their PRS-based predicted risk, management for up to 23% of women could be altered. CONCLUSION: Including BC-associated SNPs in risk assessment can provide more accurate risk prediction than family history alone and can influence recommendations for cancer screening and prevention modalities for high-risk women.Genet Med 19 1, 30-35.National Institutes of HealthThis is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/gim.2016.4

Planning and optimising a digital intervention to protect older adults' cognitive health.

BackgroundBy 2050, worldwide dementia prevalence is expected to triple. Affordable, scalable interventions are required to support protective behaviours such as physical activity, cognitive training and healthy eating. This paper outlines the theory-, evidence- and person-based development of 'Active Brains': a multi-domain digital behaviour change intervention to reduce cognitive decline amongst older adults.MethodsDuring the initial planning phase, scoping reviews, consultation with PPI contributors and expert co-investigators and behavioural analysis collated and recorded evidence that was triangulated to inform provisional 'guiding principles' and an intervention logic model. The following optimisation phase involved qualitative think aloud and semi-structured interviews with 52 older adults with higher and lower cognitive performance scores. Data were analysed thematically and informed changes and additions to guiding principles, the behavioural analysis and the logic model which, in turn, informed changes to intervention content.ResultsScoping reviews and qualitative interviews suggested that the same intervention content may be suitable for individuals with higher and lower cognitive performance. Qualitative findings revealed that maintaining independence and enjoyment motivated engagement in intervention-targeted behaviours, whereas managing ill health was a potential barrier. Social support for engaging in such activities could provide motivation, but was not desirable for all. These findings informed development of intervention content and functionality that appeared highly acceptable amongst a sample of target users.ConclusionsA digitally delivered intervention with minimal support appears acceptable and potentially engaging to older adults with higher and lower levels of cognitive performance. As well as informing our own intervention development, insights obtained through this process may be useful for others working with, and developing interventions for, older adults and/or those with cognitive impairment

The Active Brains Digital Intervention to Reduce Cognitive Decline in Older Adults: Protocol for a Feasibility Randomized Controlled Trial.

BACKGROUND: Increasing physical activity, improving diet, and performing brain training exercises are associated with reduced cognitive decline in older adults. OBJECTIVE: In this paper, we describe a feasibility trial of the Active Brains intervention, a web-based digital intervention developed to support older adults to make these 3 healthy behavior changes associated with improved cognitive health. The Active Brains trial is a randomized feasibility trial that will test how accessible, acceptable, and feasible the Active Brains intervention is and the effectiveness of the study procedures that we intend to use in the larger, main trial. METHODS: In the randomized controlled trial (RCT), we use a parallel design. We will be conducting the intervention with 2 populations recruited through GP practices (family practices) in England from 2018 to 2019: older adults with signs of cognitive decline and older adults without any cognitive decline. Trial participants were randomly allocated to 1 of 3 study groups: usual care, the Active Brains intervention, or the Active Brains website plus brief support from a trained coach (over the phone or by email). The main outcomes are performance on cognitive tasks, quality of life (using EuroQol-5D 5 level), Instrumental Activities of Daily Living, and diagnoses of dementia. Secondary outcomes (including depression, enablement, and health care costs) and process measures (including qualitative interviews with participants and supporters) will also be collected. The trial has been approved by the National Health Service Research Ethics Committee (reference 17/SC/0463). RESULTS: Results will be published in peer-reviewed journals, presented at conferences, and shared at public engagement events. Data collection was completed in May 2020, and the results will be reported in 2021. CONCLUSIONS: The findings of this study will help us to identify and make important changes to the website, the support received, or the study procedures before we progress to our main randomized phase III trial. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number 23758980; http://www.isrctn.com/ISRCTN23758980. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18929