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Abstract Background Ageing leads to decreased physical function, which can impact independent living and raise health risks, increasing demand on healthcare resources. Finding affordable and accessible exercise to improve physical function is necessary for a population seemingly resistant to strength and balance training in leisure settings. This review aimed to evaluate whether unsupervised home-based exercises improve lower extremity function in older adults. Methods We systematically searched for randomised controlled trials (RCTs) and cluster RCTs investigating unsupervised home-based exercises’ effects on physical function in older adults through English and Mandarin databases. Studies’ methodological quality was assessed using the Cochrane’s Risk of Bias Tool. Meta-analyses were conducted on lower extremity functions outcomes. Results Of the 6791 identified articles, 10 English studies (907 participants) were included, 8 studies (839 participants) were used for final meta-analysis, with no Mandarin studies. Studies were largely based in Europe with mostly moderate risk of bias. Most interventions were multicomponent lasting 10–40 min/session, 3 times/week. Meta-analysis showed no statistically significant differences in 5 sit-to-stand (p = 0.05; I2 = 0%), maximal knee extension strength (p = 0.61; I2 = 71%), 10 m maximal walking speed (p = 0.22; I2 = 30%), timed-up-to-go (p = 0.54; I2 = 0%), and short physical performance battery (p = 0.32; I2 = 98%) between exercise and control groups. Conclusions This meta-analysis suggests that unsupervised home-based exercise programmes have little impact on lower extremity functions in older adults. This review is limited by the small number of included studies, sample sizes, and high heterogeneity. There is a need to understand why this format lacks efficacy, and design more beneficial home-based exercise programmes.

Abstract The aim of this work is to determine the effect of upper‐body high intensity interval training (HIIT) on cardiometabolic risks in individuals with chronic paraplegia. Twenty‐seven individuals (14 females, 13 males, mean ± SD age: 46 ± 9 years) with chronic paraplegia (spinal cord injury between T2 and L5 >1‐year post‐injury) took part in a randomized controlled trial and were included in the final analysis. Participants in the HIIT group (n = 18) performed ∼30 min of arm crank exercise (60 s intervals at 80%–90% peak heart rate) four times per week, for 6 weeks. Participants in the control (CON) group (n = 9) were asked to maintain their habitual diet and physical activity patterns over the study period. Outcome measures were taken at baseline and follow‐up. The primary outcome measures were fasting insulin, peak power output (PPO) and peak aerobic capacity (V̇O2peak). Secondary outcome measures included body composition, postprandial glycaemic control, fasting blood lipids, inflammatory biomarkers and resting blood pressure. Differences between groups were assessed by ANCOVA, using baseline values as a covariate. PPO was higher in the HIIT (101 W, 97–106) compared to the CON (90 W, 83–96) group at follow‐up (P = 0.006). There were no differences in fasting insulin (P = 0.415) or relative V̇O2peak (P = 0.417). Postprandial Matsuda insulin sensitivity index (ISIMatsuda) was higher in the HIIT (5.42, 4.69–6.15) compared to the CON (3.75, 2.46–5.04) group at follow‐up (P = 0.036). Six weeks of upper‐body HIIT increased PPO and ISIMatsuda, with no other beneficial effect on cardiometabolic component risks in persons with chronic paraplegia. Highlights What is the central question of this study? What is the effect of upper‐body high intensity interval training (HIIT) on cardiometabolic component risks in individuals with chronic paraplegia? What is the main finding and its importance? Six weeks of upper‐body HIIT increased PPO and improved insulin sensitivity, but had no beneficial effect on other cardiometabolic component risks in persons with chronic paraplegia. The large effect size observed for insulin sensitivity may be important in terms of reducing the risk of type‐2 diabetes in this population.

Abstract The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants’ habitual diets, yet a self‐report and replication method can be flawed by under‐reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash‐out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between‐ or within‐participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts.

Background and objectivesSome patients with chronic knee pain experience an increase in knee pain following a single bout of exercise involving their knee joint, which can negatively affect exercise adherence and thus result in reduced overall health and lack of disease management. We want to determine whether a single bout of upper-body (UB) aerobic arm-ergometry exercise is effective in reducing the experience of pain in those with chronic knee pain compared with lower-body (LB) aerobic leg ergometry exercise.MethodsA total of 19 individuals (women = 11, men = 8; age = 63 ± 8 years; body mass index = 24 ± 3 kg/m2) who suffered from chronic knee pain for ≥3 months took part in this study. Arm-ergometry and cycle-ergometry exercises were performed for 30 min at a moderate intensity, separated by 7 days. Pain intensity was assessed by means of a visual analogue scale (VAS) pre- and post-exercise and for 7 days post-exercise. Pressure pain threshold (PPT) and mechanical detection threshold (MDT) were measured pre- and post-exercise at both local and distal anatomical sites. Data are presented as mean ± SD.ResultsVAS pain was significantly reduced (p = 0.035) at 1 day post-exercise following the UB exercise trial (−1.4 ± 0.8) when compared with the LB exercise trial (+0.1 ± 2.1). Both UB and LB exercises were effective in reducing local and distal PPT. MDT responses were heterogeneous, and no differences between the UB and LB exercise conditions were noted.ConclusionAn acute bout of upper-body aerobic arm-ergometry exercise evoked a significant decrease in the affected knee joint pain in individuals with chronic knee pain of up to 24 h/1 day post-exercise compared with lower-body aerobic exercise. While the exact mechanisms remain unclear, upper-body exercise may offer a viable, novel therapeutic treatment for patients with chronic knee pain.

Introduction Patients diagnosed with coronary artery disease (CAD) are currently treated with medications and lifestyle advice to reduce the likelihood of disease progression and risk of future major adverse cardiovascular events (MACE). Where obstructive disease is diagnosed, revascularisation may be considered to treat refractory symptoms. However, many patients with coexistent cardiovascular risk factors, particularly those with metabolic syndrome (MetS), remain at heightened risk of future MACE despite current management.Cardiac rehabilitation is offered to patients post-revascularisation, however, there is no definitive evidence demonstrating its benefit in a primary prevention setting. We propose that an intensive lifestyle intervention (Super Rehab, SR) incorporating high-intensity exercise, diet and behavioural change techniques may improve symptoms, outcomes, and enable CAD regression.This study aims to examine the feasibility of delivering a multicentre randomised controlled trial (RCT) testing SR for patients with CAD, in a primary prevention setting.Methods and analysis This is a multicentre randomised controlled feasibility study of SR versus usual care in patients with CAD. The study aims to recruit 50 participants aged 18–75 across two centres. Feasibility will be assessed against rates of recruitment, retention and, in the intervention arm, attendance and adherence to SR. Qualitative interviews will explore trial experiences of study participants and practitioners. Variance of change in CAD across both arms of the study (assessed with serial CT coronary angiography) will inform the design and power of a future, multi-centre RCT.Ethics and dissemination Ethics approval was granted by South West—Frenchay Research Ethics Committee (reference: 21/SW/0153, 18 January 2022). Study findings will be disseminated via presentations to relevant stakeholders, national and international conferences and open-access peer-reviewed research publications.Trial registration number ISRCTN14603929.

Abstract Background Type 2 diabetes mellitus (T2DM) and its associated complications puts considerable strain on healthcare systems. With the global incidence of T2DM increasing, effective disease management is essential. Physical activity (PA) is a key component of T2DM management; however, rates of PA engagement are low in this population. Developing effective and sustainable interventions that encourage PA is a high priority. Electrically assisted bicycles are becoming increasingly popular and may increase PA in healthy adults. This study aimed to provide evidence of the feasibility of conducting a randomized controlled trial to evaluate the efficacy of an e-cycling intervention to increase PA and improve health in individuals with T2DM. Methods A parallel-group two-arm randomized, waitlist-controlled pilot study was conducted. Individuals were randomized to either an e-bike intervention or standard care. The intervention incorporated two one-to-one e-bike skills training and behavioural counselling sessions delivered by a community-based cycling charity, followed by a 12-week e-bike loan with two further sessions with the instructors. Feasibility was assessed via measures related to recruitment, retention and intervention implementation. Post-intervention interviews with instructors and participants explored the acceptability of the study procedures and intervention. Clinical, physiological and behavioural outcomes were collected at baseline and post-intervention to evaluate the intervention’s potential. Results Forty participants (M age = 57) were randomized, of which 34 were recruited from primary care practices. Thirty-five participants were retained in the trial. The intervention was conducted with high fidelity (> 80% content delivered). E-bike training provided participants with the skills, knowledge and confidence needed to e-bike independently. Instructors reported being more confident delivering the skills training than behavioural counselling, despite acknowledging its importance. The study procedures were found to be acceptable to participants. Between-group differences in change during the intervention were indicative of the interventions potential for improving glucose control, health-related quality of life and cardiorespiratory fitness. Increases in overall device measured moderate-to-vigorous PA behaviour following the intervention were found, and there was evidence that this population self-selected to e-cycle at a moderate intensity. Conclusions The study’s recruitment, retention, acceptability and potential efficacy support the development of a definitive trial subject to identified refinements. Trial registration ISRCTN, ISRCTN67421464 . Registered 17/12/2018.

Introduction: Exercise “snacking” and Tai-chi ‘snacking’ protocols are designed to overcome typical barriers to older adults’ participation in muscle strength and balance exercise, using short bouts of home-based exercise. This study aimed to investigate the acceptability of homebred exercise- and Tai-chi snacking in British and Taiwanese older adults of high and low physical function.Methods: Thirty-three British and Thirty Taiwanese older adults took part in semi-structured interviews, after trying 1-week of exercise- and Tai-chi snacking. The interview schedule and deductive framework analysis was based on the seven components of the Theoretical Framework of Acceptability (TFA). Differences between the Taiwanese and United Kingdom participants and those considered high versus low physical function were also analysed.Results: Both snacking regimes were found to be convenient and easy to implement. Participants reported that no activity had to be given up, and considered the programmes would be beneficial to their physical and mental health. Interestingly, more UK-based participants preferred the elegant and relaxing movements of Tai-chi snacking, yet participants with low physical function experienced difficulties when mastering Tai-chi movements. A few high physical function participants perceived exercise snacking to be tedious.Discussion: Overall, the snacking exercise was found to be acceptable and useful. Personal affective attitude and different cultural backgrounds may affect exercise participation. Nevertheless, it is important to consider individuals’ physical function when designing exercise regime. The findings indicate that making Tai-chi snacking easier to master initially, building in progression and adding some upper body movements in the exercise snacking may further enhance acceptability.

Methods: We examined whether immune cell profiles differ between healthy women (n = 38) and breast cancer survivors (n = 27) within 2 years of treatment, and whether any group-differences were influenced by age, cytomegalovirus infection, cardiorespiratory fitness and body composition. Using flow cytometry, CD4+ and CD8+ T cell subsets, including naïve (NA), central memory (CM) and effector cells (EM and EMRA) were identified using CD27/CD45RA. Activation was measured by HLA-DR expression. Stem cell-like memory T cells (TSCMs) were identified using CD95/CD127. B cells, including plasmablasts, memory, immature and naïve cells were identified using CD19/CD27/CD38/CD10. Effector and regulatory Natural Killer cells were identified using CD56/CD16.Results: Compared to healthy women, CD4+ CM were +Δ21% higher among survivors (p = 0.028) and CD8+ NA were −Δ25% lower (p = 0.034). Across CD4+ and CD8+ subsets, the proportion of activated (HLA-DR+) cells was +Δ31% higher among survivors: CD4+ CM (+Δ25%), CD4+ EM (+Δ32%) and CD4+ EMRA (+Δ43%), total CD8+ (+Δ30%), CD8+ EM (+Δ30%) and CD8+ EMRA (+Δ25%) (p < 0.046). The counts of immature B cells, NK cells and CD16+ NK effector cells were higher among survivors (+Δ100%, +Δ108% and +Δ143% respectively, p < 0.04). Subsequent analyses examined whether statistically significant differences in participant characteristics, influenced immunological differences between groups. Compared to healthy women, survivors were older (56 ± 6 y vs. 45 ± 11 y), had lower cardiorespiratory fitness (V̇O2max mL kg−1 min−1: 28.8 ± 5.0 vs. 36.2 ± 8.5), lower lean mass (42.3 ± 5.0 kg vs. 48.4 ± 15.8 kg), higher body fat (36.3% ± 5.3% vs. 32.7% ± 6.4%) and higher fat mass index (FMI kg/m2: 9.5 ± 2.2 vs. 8.1 ± 2.7) (all p < 0.033). Analysis of covariance revealed divergent moderating effects of age, CMV serostatus, cardiorespiratory fitness and body composition on the differences in immune cell profiles between groups, depending on the cell type examined. Moreover, across all participants, fat mass index was positively associated with the proportion of HLA-DR+ CD4+ EMRA and CD8+ EM/EMRA T cells (Pearson correlation: r > 0.305, p < 0.019). The association between fat mass index and HLA-DR+ CD8+ EMRA T cells withstood statistical adjustment for all variables, including age, CMV serostatus, lean mass and cardiorespiratory fitness, potentially implicating these cells as contributors to inflammatory/immune-dysfunction in overweight/obesity.

MethodsThis study examined the effects of exercise training for 8 weeks on blood immune cell characteristics among 20 breast cancer survivors (age 56 ± 6 years, Body Mass Index 25.4 ± 3.0 kg m2) within two years of treatment. Participants were randomly allocated to a partly-supervised or a remotely-supported exercise group (n = 10 each). The partly supervised group undertook 2 supervised (laboratory-based treadmill walking and cycling) and 1 unsupervised session per week (outdoor walking) progressing from 35 to 50 min and 55% to 70% V˙O2max. The remotely-supported group received weekly exercise/outdoor walking targets (progressing from 105 to 150 min per week 55% to 70% V˙O2max) via weekly telephone calls discussing data from a fitness tracker. Immune cell counts were assessed using flow cytometry: CD4+ and CD8+ T cells (Naïve, NA; Central memory, CM; and Effector cells, EM and EMRA; using CD27/CD45RA), Stem cell-like memory T cells (TSCMs; using CD95/CD127), B cells (plasmablasts, memory, immature and naïve cells using CD19/CD27/CD38/CD10) and Natural Killer cells (effector and regulatory cells, using CD56/CD16). T cell function was assessed by unstimulated HLA-DR expression or interferon gamma (IFN-γ) production with Enzyme-linked ImmunoSpot assays following stimulation with virus or tumour-associated antigens.ResultsTotal leukocyte counts, lymphocytes, monocytes and neutrophils did not change with training (p > 0.425). Most CD4+ and CD8+ T cell subtypes, including TSCMs, and B cell and NK cell subtypes did not change (p > 0.127). However, across groups combined, the CD4+ EMRA T cell count was lower after training (cells/µl: 18 ± 33 vs. 12 ± 22, p = 0.028) and these cells were less activated on a per cell basis (HLA-DR median fluorescence intensity: 463 ± 138 vs. 420 ± 77, p = 0.018). Furthermore, the partly-supervised group showed a significant decrease in the CD4+/CD8+ ratio (3.90 ± 2.98 vs. 2.54 ± 1.29, p = 0.006) and a significant increase of regulatory NK cells (cells/µl: 16 ± 8 vs. 21 ± 10, p = 0.011). T cell IFN-γ production did not change with exercise training (p > 0.515).DiscussionIn summary, most immune cell characteristics are relatively stable with 8 weeks of exercise training among breast cancer survivors. The lower counts and activation of CD4+ EMRA T cells, might reflect an anti-immunosenescence effect of exercise.

Background: Wearable technologies offer new opportunities to address in-school physical inactivity. However, children are often excluded from discussing issues which directly impact them, including the use of wearable technologies in a school setting. Thus, the aim of this study is to understand primary school pupils' experiences and perceptions of using wearable physical activity monitoring technologies within schools. Methods: Nine semi-structured focus groups were conducted with 41 Year 5 and 6 pupils (19 girls, 22 boys) from 5 primary schools in the South West of England. Focus group transcripts were analyzed using a reflective thematic approach. Results: Pupils made valuable contributions to discussions around wearable technologies, considering both advantages and disadvantages. Most importantly, when discussing use in schools, pupils were mindful that while they wanted to see their own activity and saw benefit in teachers knowing their activity, they felt comparisons in classes could lead to negative emotions for some pupils. Conclusion: The findings from this study can contribute to a more detailed understanding of pupils' perspectives, which can help inform school-based interventions which aim to address physical inactivity and associated inequalities. Instead of using wearable devices for individual pupil ownership, schools should access data-insights with the intention of changing school practices.

Abstract Background Wearable technologies are being used to provide personalised feedback across multiple physical activity dimensions in countries such as the UK, but their feasibility has not been tested in South Asia, where physical inactivity is increasing. This study assessed the understanding, acceptability, and relevance of personalised multidimensional physical activity feedback in urban dwellers in Colombo, Sri Lanka. Methods A qualitative feasibility study was conducted among 35 adults to assess a community-based approach to provide multidimensional physical activity feedback. Healthy adults, adults at risk of non-communicable diseases and community-based primary healthcare professionals wore a physical activity monitor for 7 days and were then guided through their personalised multidimensional physical activity feedback. One-to-one interviews were conducted, transcribed verbatim and analysed using framework analysis. Results Four themes were generated: understanding of personalised physical activity feedback, perceived novelty of the feedback, motivation, and consideration of the multidimensional nature of physical activity. A majority of participants required guidance initially to understand the feedback, following which most were quickly able to interpret the data shown, and were willing to use the feedback as a basis for identifying goals to improve physical activity. Participants perceived the feedback and its delivery as novel because it provided new knowledge about physical activity guidelines and awareness on their own behaviour through graphics. Comparisons of personal performance against recommended physical activity levels and information on sedentary time were the most commonly motivating aspects of the feedback, prompting talk about behaviour change. All three groups showed poor planning on goal achievement, with some noticeable differences between those with and without health risk of non-communicable diseases. Following the feedback, most participants understood that physical activity is composed of several dimensions, while around half could recognise more suitable options to change behaviour. Of the physical activity dimensions, calorie burn received more attention than others. Conclusions Multidimensional physical activity feedback was considered understandable and acceptable and has the potential to support behaviour change among urban Sri Lankans with or without identified health risk. These findings highlight the feasibility of this technology-enabled approach as a personalised intervention to improve knowledge and motivation for physical activity behaviour.

Abstract Background Technological progress has enabled the provision of personalised feedback across multiple dimensions of physical activity that are important for health. Whether this multidimensional approach supports physical activity behaviour change has not yet been examined. Our objective was to examine the effectiveness of a novel digital system and app that provided multidimensional physical activity feedback combined with health trainer support in primary care patients identified as at risk of chronic disease. Methods MIPACT was a parallel-group, randomised controlled trial that recruited patients at medium (≥10 and minimum clinically important difference, MCID). However, there was profound physical activity multidimensionality, and only a small proportion (5%) of patients had consistently low physical activity across all dimensions. Conclusion In patients at risk of cardiovascular disease and/or type II diabetes, MIPACT did not increase mean physical activity. Using a sophisticated multidimensional digital approach revealed enormous heterogeneity in baseline physical activity in primary care patients, and practitioners may need to screen for low physical activity across dimensions rather than rely on disease-risk algorithms that are heavily influenced by age. Trial registration This trial is registered with the ISRCTN registry ( ISRCTN18008011 ; registration date 31 July 2013).

BackgroundIncreasing physical activity (PA) behavior remains a public health priority, and wearable technology is increasingly being used to support behavior change efforts. Using wearables to capture and provide comprehensive, visually persuasive, multidimensional feedback with real-time support may be a promising way of increasing PA in inactive individuals. ObjectiveThis study aims to explore whether a 6-week self-monitoring intervention using composite web-based multidimensional PA feedback with real-time daily feedback supports increased PA in adults. MethodsA 6-week, mixed methods, 2-armed exploratory randomized controlled trial with 6-week follow-up was used, whereby low to moderately active (PA level [PAL]

BackgroundDespite reforming health policies to create more enabling environments, insufficient physical activity in Sri Lanka remains a major public health issue. Socio-culture specific determinants underlying the physical activity of adults living in such environments need to be identified. The aim of this study was to explore the barriers and facilitators for physical activity, as perceived by adult urban dwellers in activity-friendly environments in Colombo District, Sri Lanka.MethodsA qualitative study using in-depth interviews was conducted among adults aged 20-60 years living in an urban area which has been recently re-designed for recreational and rejuvenating purposes in Sri Lanka. Recruitment targeted varying socio-economic status and risk of non-communicable diseases; and was continued until the data saturation point was reached. Interviews were conducted in homes, primary healthcare units and fitness centres, and were transcribed verbatim and analysed using framework analysis.ResultsA total of 31 eligible and consenting adults were interviewed. Of the reported barriers to physical activity, lack of time was very common. Other frequently reported barriers included unpleasant experiences following exercise and misconceptions about exercise, whereas physical environmental factors, weather and road safety were reported less frequently. All participants reported at least one facilitator for engaging in exercise. Expectations of preventing diseases, improving health, physical fitness, psycho-social wellbeing, optimising body functions and increasing lifespan were frequently cited as reasons to be active, while social factors such as positive attitudes of family members and the influence of peers were found to be motivating.ConclusionsThe study showed that while participants valued the health benefits of physical activity and refurbished activity-friendly urban environments, these were not sufficient to support them to overcome key perceived barriers to being physically active.

Background: Many children are not engaging in sufficient physical activity and there are substantial between-children physical activity inequalities. In addition to their primary role as educators, teachers are often regarded as being well-placed to make vital contributions to inclusive visions of physical activity promotion. With the dramatic increase in popularity of wearable technologies for physical activity promotion in recent years, there is a need to better understand teachers' perspectives about using such devices, and the data they produce, to support physical activity promotion in schools.Method: Semi-structured interviews were conducted with 26 UK-based primary school teachers, exploring their responses to children's physical activity data and their views about using wearable technologies during the school day. Interview discussions were facilitated by an elicitation technique whereby participants were presented with graphs illustrating children's in-school physical activity obtained from secondary wearable technology data. Interview transcripts were thematically analyzed.Results: Most teachers spoke positively about the use of wearable technologies specifically designed for school use, highlighting potential benefits and considerations. Many teachers were able to understand and critically interpret data showing unequal physical activity patterns both within-and between-schools. Being presented with the data prompted teachers to provide explanations about observable patterns, emotional reactions—particularly about inequalities—and express motivations to change the current situations in schools.Conclusion: These findings suggest that primary school teachers in the UK are open to integrating wearable technology for measuring children's physical activity into their practices and can interpret the data produced by such devices. Visual representations of physical activity elicited strong responses and thus could be used when working with teachers as an effective trigger to inform school practices and policies seeking to address in-school physical inactivity and inequalities.

Introduction Lifestyle modification is the mainstay of gestational diabetes mellitus (GDM) prevention. However, clinical trials evaluating the safety and efficacy of diet or physical activity (PA) in low-income and middle-income settings such as Africa and India are lacking. This trial aims to evaluate the efficacy of yoghurt consumption and increased PA (daily walking) in reducing GDM incidence in high-risk pregnant women.Methods and analysis The study is a 2×2 factorial, open-labelled, multicentre randomised controlled trial to be conducted in Vellore, South India and The Gambia, West Africa. ‘High-risk’ pregnant women (n=1856) aged ≥18 years and ≤16 weeks of gestational age, with at least one risk factor for developing GDM, will be randomised to either (1) yoghurt (2) PA (3) yoghurt +PA or (4) standard antenatal care. Participants will be followed until 32 weeks of gestation with total active intervention lasting for a minimum of 16 weeks. The primary endpoint is GDM incidence at 26–28 weeks diagnosed using International Association of the Diabetes and Pregnancy Study Groups criteria or elevated fasting glucose (≥5.1 mmol/L) at 32 weeks. Secondary endpoints include absolute values of fasting plasma glucose concentration at 32 weeks gestation, maternal blood pressure, gestational weight gain, intrapartum and neonatal outcomes. Analysis will be both by intention to treat and per-protocol. Continuous outcome measurements will be analysed using multiple linear regression and binary variables by logistic regression.Ethics and dissemination The study is approved by Oxford Tropical Research Ethics Committee (44–18), ethics committees of the Christian Medical College, Vellore (IRB 11367) and MRCG Scientific Coordinating Committee (SCC 1645) and The Gambia Government/MRCG joint ethics committee (L2020.E15). Findings of the study will be published in peer-reviewed scientific journals and presented in conferences.Trial registration number ISRCTN18467720.

Breast cancer is the most common malignancy among women worldwide. Over the last four decades, diagnostic and therapeutic procedures have improved substantially, giving patients with localized disease a better chance of cure, and those with more advanced cancer, longer periods of disease control and survival. However, understanding and managing heterogeneity in the clinical response exhibited by patients remains a challenge. For some treatments, biomarkers are available to inform therapeutic options, assess pathological response and predict clinical outcomes. Nevertheless, some measurements are not employed universally and lack sensitivity and specificity, which might be influenced by tissue-specific alterations associated with aging and lifestyle. The first part of this article summarizes available and emerging biomarkers for clinical use, such as measurements that can be made in tumor biopsies or blood samples, including so-called liquid biopsies. The second part of this article outlines underappreciated factors that could influence the interpretation of these clinical measurements and affect treatment outcomes. For example, it has been shown that both adiposity and physical activity can modify the characteristics of tumors and surrounding tissues. In addition, evidence shows that inflammaging and immunosenescence interact with treatment and clinical outcomes and could be considered prognostic and predictive factors independently. In summary, changes to blood and tissues that reflect aging and patient characteristics, including lifestyle, are not commonly considered clinically or in research, either for practical reasons or because the supporting evidence base is developing. Thus, an aim of this article is to encourage an integrative phenomic approach in oncology research and clinical management.

Abstract Background Short-term overfeeding combined with reduced physical activity impairs metabolic function and alters the expression of key genes within adipose tissue. We have shown that daily vigorous-intensity running can prevent these changes independent of any net effect on energy imbalance. However, which type, intensity and/or duration of exercise best achieves these benefits remains to be ascertained. Methods/design Forty-eight healthy young men will be recruited and randomly allocated to one of four experimental conditions for 1 week: (1) to ingest 50% more energy than normal by over-consuming their habitual diet whilst simultaneously restricting their physical activity below 4000 steps day−1 (i.e. energy surplus; SUR group); (2) the same regimen but with a daily 45-min bout of vigorous-intensity arm crank ergometry at 70% of maximum oxygen uptake (SUR + ARM group); (3) the same regimen but with a daily 45-min bout of moderate-intensity treadmill walking at 50% of maximum oxygen uptake (SUR + MOD group); (4) the same regimen but with the addition of intermittent short bouts of walking during waking hours (SUR + BREAKS group). Critically, all exercise groups will receive additional dietary energy intake to account for the energy expended by exercise, thus maintaining a matched energy surplus. At baseline and follow-up, fasted blood samples, abdominal subcutaneous adipose tissue and skeletal muscle biopsies will be obtained and oral glucose tolerance tests conducted. Discussion This study will establish the impact of different forms of daily exercise on metabolic function at the whole-body level as well as within adipose tissue and skeletal muscle in the context of a standardised energy surplus. Trial registration ISRCTN, ISRCTN18311163. Registered on 24 June 2015.

Abstract Background Prior studies have shown that intermittent fasting is capable of producing improvements in body weight and fasted health markers. However, the extent to which intermittent fasting incurs compensatory changes in the components of energy balance and its impact on postprandial metabolism are yet to be ascertained. Methods A total of 30–36 lean participants and 30–36 overweight/obese participants will be recruited to provide two separate study groups who will undergo the same protocol. Following an initial assessment of basic anthropometry and key health markers, measurements of habitual energy intake (weighed food and fluid intake) and physical activity energy expenditure (combined heart rate and accelerometry) will be obtained over 4 weeks under conditions of energy balance. Participants will then be randomly allocated to one of three experimental conditions for 20 days, namely (1) daily calorie restriction (reduce habitual daily energy intake by 25%), (2) intermittent fasting with calorie restriction (alternate between 24-hour periods of fasting and feeding to 150% of habitual daily energy intake), (3) intermittent fasting without calorie restriction (alternate between 24-hour periods of fasting and feeding to 200% of habitual daily energy intake). In addition to continued monitoring of energy intake and physical activity during the intervention, participants will report for laboratory-based assessments of various metabolic parameters both before and after the intervention. Specifically, fasting and postprandial measurements of resting metabolic rate, substrate oxidation, appetite, food preference, and plasma concentrations of key metabolites and hormones will be made, in addition to subcutaneous abdominal adipose tissue biopsies in the fasted state and an assessment of body composition via dual-energy x-ray absorptiometry. Discussion Comparing observed changes in these measures across the three intervention arms in each group will establish the impact of intermittent fasting on postprandial metabolism and the components of energy balance in both lean and overweight/obese populations. Furthermore, this will be benchmarked against current nutritional interventions for weight management and the relative contributions of negative energy balance and fasting-dependent mechanisms in inducing any observed effects will be elucidated. Trial registration Trial retrospectively registered at clinicaltrials.gov under reference number NCT02498002 (version: IMF-02, date: July 6, 2015).

Abstract Background Despite obesity being highly prevalent in persons with spinal cord injury (SCI), our current understanding of the interactions between energy balance components, which may contribute to this, is limited. The primary aim of this study is to identify the intra-individual variability of physical activity dimensions across days and suggest an appropriate monitoring time frame for these constructs in adults with SCI. The secondary aim is to examine these parameters with regard to energy intake and dietary macronutrient composition. Methods Participants [33 men and women with chronic (> 1 year post injury) paraplegia; age = 44 ± 9 years (mean ± S.D.] wore an Actiheart™ PA monitor and completed a weighed food diary for 7 consecutive days. Spearman-Brown Prophecy Formulae, based on Intraclass Correlations of .80 (acceptable reliability), were used to predict the number of days required to measure energy balance components. Linear mixed-effects analyses and magnitude-based inferences were performed for all energy intake, expenditure and physical activity dimensions. Adjustments were made for age, injury level, wear time, sex, day of the week and measurement order as fixed effects. Results To reliably measure energy expenditure components; 1 day [total energy expenditure (TEE)], 2 days [physical activity energy expenditure (PAEE), light-intensity activity, moderate-to-vigorous PA (MVPA)], 3 days [physical activity level (PAL)] and 4 days (sedentary behaviour) are necessary. Device wear time (P 1 year) paraplegia and propose suitable measurement durations to achieve acceptable reliability in outcome measures. Device wear time and measurement order play a role in the quality of energy expenditure and intake data, respectively, and should be considered when designing and analysing studies of energy balance components in persons with SCI. Trial registration N/A

Background: Promotion of physical activity in primary care has had limited success. Wearable technology presents an opportunity to support healthcare practitioners (HCPs) in providing personalised feedback to their patients. Aim: To explore the differing thoughts and feelings of both HCPs and at-risk patients provided with personalised multidimensional physical activity feedback. Design & setting: Qualitative study with HCPs (n = 15) and patients at risk of cardiovascular disease or type 2 diabetes (n = 29), recruited from primary care. Method: HCPs and patients wore a physical activity monitor for 7 days and were subsequently shown their personalised multidimensional feedback, including sedentary time, calorie burn, short (1-minute) or long (>10-minute) bouts of moderate-to-vigorous activity during semi-structured interviews. Transcripts were analysed thematically with comparisons made between individuals of high (n = 21) and low (n = 23) physical activity levels as to their cognitive–affective responses to their data. Results: Personalised feedback elicited positive emotional responses for highly active participants and negative emotional responses for those with low activity. However, individuals with low activity demonstrated largely positive coping mechanisms. Some low active participants were in denial over feedback, but the majority valued it as an opportunity to think of ways to improve physical activity (cognitive reappraisal) and started forming action plans (problem-focused coping). Around half of all participants also sought to validate their feedback against peers. Conclusion: Personalised, visual feedback elicits immediate emotional and coping responses in participants of high and low physical activity levels. Further studies should explore whether multidimensional feedback could help practitioners explore diverse ways for lifestyle change with patients.

Circadian regulation of transcriptional processes has a broad impact on cell metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle conducted on serial muscle biopsies in vivo with profiles of human skeletal myotubes synchronized in vitro. More extensive rhythmic transcription was observed in human skeletal muscle compared to in vitro cell culture as a large part of the in vivo mRNA rhythmicity was lost in vitro. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. Moreover, basal and insulin-stimulated glucose uptake were significantly reduced upon CLOCK depletion. Our findings suggest an essential role for the circadian coordination of skeletal muscle glucose homeostasis and lipid metabolism in humans.

Ageing, like obesity, is often associated with alterations in metabolic and inflammatory processes resulting in morbidity from diseases characterised by poor metabolic control, insulin insensitivity, and inflammation. Ageing populations also exhibit a decline in immune competence referred to as immunosenescence, which contributes to, or might be driven by chronic, low-grade inflammation termed “inflammageing”. In recent years, animal and human studies have started to uncover a role for immune cells within the stromal fraction of adipose tissue in driving the health complications that come with obesity, but relatively little work has been conducted in the context of immunometabolic adipose function in ageing. It is now clear that aberrant immune function within adipose tissue in obesity—including an accumulation of pro-inflammatory immune cell populations—plays a major role in the development of systemic chronic, low-grade inflammation, and limiting the function of adipocytes leading to an impaired fat handling capacity. As a consequence, these changes increase the chance of multiorgan dysfunction and disease onset. Considering the important role of the immune system in obesity-associated metabolic and inflammatory diseases, it is critically important to further understand the interplay between immunological processes and adipose tissue function, establishing whether this interaction contributes to age-associated immunometabolic dysfunction and inflammation. Therefore, the aim of this article is to summarise how the interaction between adipose tissue and the immune system changes with ageing, likely contributing to the age-associated increase in inflammatory activity and loss of metabolic control. To understand the potential mechanisms involved, parallels will be drawn to the current knowledge derived from investigations in obesity. We also highlight gaps in research and propose potential future directions based on the current evidence.

Physical activity is considered crucial in attenuating losses in strength and power associated with ageing. However, in well-functioning, active older adults the relationship between habitual physical activity and muscle function is surprisingly unclear. Leg press velocity, force, and power, were compared between 50 older and 30 younger healthy individuals, and associations with habitual physical activity explored. An incremental power test was performed on a pneumatic leg press, with theoretical maximum velocity, force, and power calculated. Vastus lateralis muscle thickness was measured by ultrasound, and participants wore a combined accelerometer and heart rate monitor for 6-days of free-living. Older individuals produced lower absolute maximum velocity, force, and power, than younger individuals. When accounting for smaller muscle size, older individual's maximum force and power remained markedly lower. Both groups were active, however using age specific thresholds for classifying physical activity, the older individuals engaged in twice the amount of moderate-to-vigorous physical activity in comparison to the younger individuals. There were no associations between any characteristics of muscle function and physical activity. These data support that the ability to generate force and power deteriorates with age, however habitual physical activity levels do not explain inter-individual differences in muscle function in active older individuals.

Wearable physical activity monitors are growing in popularity and provide the opportunity for large numbers of the public to self-monitor physical activity behaviours. The latest generation of these devices feature multiple sensors, ostensibly similar or even superior to advanced research instruments. However, little is known about the accuracy of their energy expenditure estimates. Here, we assessed their performance against criterion measurements in both controlled laboratory conditions (simulated activities of daily living and structured exercise) and over a 24 hour period in free-living conditions. Thirty men (n = 15) and women (n = 15) wore three multi-sensor consumer monitors (Microsoft Band, Apple Watch and Fitbit Charge HR), an accelerometry-only device as a comparison (Jawbone UP24) and validated research-grade multi-sensor devices (BodyMedia Core and individually calibrated Actiheart™). During discrete laboratory activities when compared against indirect calorimetry, the Apple Watch performed similarly to criterion measures. The Fitbit Charge HR was less consistent at measurement of discrete activities, but produced similar free-living estimates to the Apple Watch. Both these devices underestimated free-living energy expenditure (-394 kcal/d and -405 kcal/d, respectively; P

To assess the validity of two accelerometer devices, at two different anatomical locations, for the prediction of physical activity energy expenditure (PAEE) in manual wheelchair users (MWUs).Seventeen MWUs (36 ± 10 yrs, 72 ± 11 kg) completed ten activities; resting, folding clothes, propulsion on a 1% gradient (3,4,5,6 and 7 km·hr-1) and propulsion at 4km·hr-1 (with an additional 8% body mass, 2% and 3% gradient) on a motorised wheelchair treadmill. GT3X+ and GENEActiv accelerometers were worn on the right wrist (W) and upper arm (UA). Linear regression analysis was conducted between outputs from each accelerometer and criterion PAEE, measured using indirect calorimetry. Subsequent error statistics were calculated for the derived regression equations for all four device/location combinations, using a leave-one-out cross-validation analysis.Accelerometer outputs at each anatomical location were significantly (p < .01) associated with PAEE (GT3X+-UA; r = 0.68 and GT3X+-W; r = 0.82. GENEActiv-UA; r = 0.87 and GENEActiv-W; r = 0.88). Mean ± SD PAEE estimation errors for all activities combined were 15 ± 45%, 14 ± 50%, 3 ± 25% and 4 ± 26% for GT3X+-UA, GT3X+-W, GENEActiv-UA and GENEActiv-W, respectively. Absolute PAEE estimation errors for devices varied, 19 to 66% for GT3X+-UA, 17 to 122% for GT3X+-W, 15 to 26% for GENEActiv-UA and from 17.0 to 32% for the GENEActiv-W.The results indicate that the GENEActiv device worn on either the upper arm or wrist provides the most valid prediction of PAEE in MWUs. Variation in error statistics between the two devices is a result of inherent differences in internal components, on-board filtering processes and outputs of each device.

BACKGROUND:Innovative physical activity monitoring technology can be used to depict rich visual feedback that encompasses the various aspects of physical activity known to be important for health. However, it is unknown whether patients who are at risk of chronic disease would understand such sophisticated personalised feedback or whether they would find it useful and motivating. The purpose of the present study was to determine whether technology-enabled multidimensional physical activity graphics and visualisations are comprehensible and usable for patients at risk of chronic disease. METHOD:We developed several iterations of graphics depicting minute-by-minute activity patterns and integrated physical activity health targets. Subsequently, patients at moderate/high risk of chronic disease (n=29) and healthcare practitioners (n=15) from South West England underwent full 7-days activity monitoring followed by individual semi-structured interviews in which they were asked to comment on their own personalised visual feedback Framework analysis was used to gauge their interpretation and of personalised feedback, graphics and visualisations. RESULTS:We identified two main components focussing on (a) the interpretation of feedback designs and data and (b) the impact of personalised visual physical activity feedback on facilitation of health behaviour change. Participants demonstrated a clear ability to understand the sophisticated personal information plus an enhanced physical activity knowledge. They reported that receiving multidimensional feedback was motivating and could be usefully applied to facilitate their efforts in becoming more physically active. CONCLUSION:Multidimensional physical activity feedback can be made comprehensible, informative and motivational by using appropriate graphics and visualisations. There is an opportunity to exploit the full potential created by technological innovation and provide sophisticated personalised physical activity feedback as an adjunct to support behaviour change.

Recently, there has been some discussion of whether it is possible to score highly in one dimension of physical activity behaviour (e.g., moderate intensity exercise) whilst also scoring poorly in another (e.g., sedentary time). Interestingly, direct empirical observations to support these proposals are lacking. New technologies now enable the capture of physical activity thermogenesis on a minute-by-minute basis and over a sustained period. We used one of the best available technologies to explore whether individuals can score differently in various physiologically-important physical activity dimensions. We determined minute-by-minute physical activity energy expenditure over 7 days in 100 men aged 28 ± 9 years. We used combined accelerometry and heart rate with branched equation modelling to estimate energy expenditure and extracted data for key physical activity outcomes and descriptors. Although some physical activity outcomes were tightly correlated, the attainment of one threshold for a given physical activity dimension did not automatically predict how well an individual scored in another dimension (with bivariate correlations ranging from 0.05 to 0.96). In one illustrative example of this heterogeneity, although 41 men showed a relatively low Physical Activity Level (total energy expenditure/resting energy expenditure ≤ 1.75), only 17% (n=7) of these men showed consistently low physical activity across other dimensions (moderate intensity activity, vigorous intensity activity, and sedentary time). Thus, physical activity is highly heterogeneous and there is no single outcome measure that captures all the relevant information about a given individual. We propose that future studies need to capture (rather than ignore) the different physiologically-important dimensions of physical activity via generation of integrated, multidimensional physical activity 'profiles'.

BackgroundPhysical activity (including exercise) is prescribed for health and there are various recommendations that can be used to gauge physical activity status. The objective of the current study was to determine whether twelve commonly-used physical activity recommendations similarly classified middle-aged men as sufficiently active for general health.Methods and findingsWe examined the commonality in the classification of physical activity status between twelve variations of physical activity recommendations for general health in ninety men aged 45-64 years. Physical activity was assessed using synchronised accelerometry and heart rate. Using different guidelines but the same raw data, the proportion of men defined as active ranged from to 11% to 98% for individual recommendations (median 73%, IQR 30% to 87%). There was very poor absolute agreement between the recommendations, with an intraclass correlation coefficient (A,1) of 0.24 (95% CI, 0.15 to 0.34). Only 8% of men met all 12 recommendations and would therefore be unanimously classified as active and only one man failed to meet every recommendation and would therefore be unanimously classified as not sufficiently active. The wide variability in physical activity classification was explained by ostensibly subtle differences between the 12 recommendations for thresholds related to activity volume (time or energy), distribution (e.g., number of days of the week), moderate intensity cut-point (e.g., 3 vs. 4 metabolic equivalents or METs), and duration (including bout length).ConclusionsPhysical activity status varies enormously depending on the physical activity recommendation that is applied and even ostensibly small differences have a major impact. Approximately nine out of every ten men in the present study could be variably described as either active or not sufficiently active. Either the effective dose or prescription that underlies each physical activity recommendation is different or each recommendation is seeking the same prescriptive outcome but with variable success.