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It is unknown if adult human skeletal muscle has an epigenetic memory of earlier encounters with growth. We report, for the first time in humans, genome-wide DNA methylation (850,000 CpGs) and gene expression analysis after muscle hypertrophy (loading), return of muscle mass to baseline (unloading), followed by later hypertrophy (reloading). We discovered increased frequency of hypomethylation across the genome after reloading (18,816 CpGs) versus earlier loading (9,153 CpG sites). We also identified AXIN1, GRIK2, CAMK4, TRAF1 as hypomethylated genes with enhanced expression after loading that maintained their hypomethylated status even during unloading where muscle mass returned to control levels, indicating a memory of these genes methylation signatures following earlier hypertrophy. Further, UBR5, RPL35a, HEG1, PLA2G16, SETD3 displayed hypomethylation and enhanced gene expression following loading, and demonstrated the largest increases in hypomethylation, gene expression and muscle mass after later reloading, indicating an epigenetic memory in these genes. Finally, genes; GRIK2, TRAF1, BICC1, STAG1 were epigenetically sensitive to acute exercise demonstrating hypomethylation after a single bout of resistance exercise that was maintained 22 weeks later with the largest increase in gene expression and muscle mass after reloading. Overall, we identify an important epigenetic role for a number of largely unstudied genes in muscle hypertrophy/memory.

High intensity interval training (HIIT) is a time-efficient exercise modality to improve cardiorespiratory fitness, and has recently been popularised by social media influencers. However, little is known regarding acute physiological and perceptual responses to these online protocols compared to HIIT protocols used within research. The aim was to investigate acute physiological, perceptual and motivational responses to two HIIT protocols popular on social media, and compare these to two evidence-based protocols. Twenty-seven recreationally active (>1 exercise session /week) participants (Age: 22±3y, BMI: 24.3±2.4) completed a randomised cross-over study, whereby each participant completed four HIIT protocols, two already established in research (Ergo-60:60 (cycling 10x60s at 100%Wmaxwith 60s rest), BW-60:60 (body-weight exercises 10x60swith 60s rest)) and two promoted on social media (SM-20:10 (body-weight exercises 20x20swith 10s rest) and SM-40:20 (body-weight exercises 15x40s with 20s rest)). Blood lactate, heart rate (HR), feeling scale (FS), felt arousal scale (FSA), enjoyment and perceived competence were measured in response to each protocol. Significant differences were observed between BW-60:60 and SM-20:10 for the proportion of intervals meeting the ACSM high-intensity exercise criterion (>80% of HRmax) (BW-60:60 93±10%, SM-20:10 74±20%, P = 0.039) and change in lactate (BW-60:60 +7.8±3.7mmol/L, SM-20:10 +5.5±2.6mmol/L, P = 0.001). The percentage of time spent above the criterion HR was also significantly lower in SM-20:10 compared to all other protocols (Ergo-60:60 13.9±4.9min, BW-60:60 13.5±3.5min, SM-40:20 12.1±2.4min, SM-20:10 7.7±3.1, P<0.05). No differences were observed in lowest reported FS between protocols (P = 0.268), but FS decreased linearly throughout Ergo-60:60 and BW-60:60 (first vs. last interval P<0.05), but not in SM-20:10 or SM-40:20 (P>0.05). Enjoyment was higher upon completion of BW-60:60 compared to Ergo-60:60 and SM-40:20 (P<0.05). This study shows that HIIT protocols available on social media offer an interesting real-world alternative for promoting exercise participation. Future studies should continue to investigate these highly popular and practical HIIT protocols.

IntroductionCardiac rehabilitation (CR) can reduce cardiovascular mortality and improve health-related quality of life. In the United Kingdom, patient uptake of CR remains low (52%), falling well short of the target in the 2019 National Health Service long-term plan (85%). Mobile health (mHealth) technologies, offering biometric data to patients and healthcare professionals, may bridge the gap between supervised exercise and physical activity advice, enabling patients to engage in regular long-term physically active lifestyles. This randomised controlled trial (RCT) will evaluate the feasibility of mHealth technology when incorporated into a structured home-based walking intervention, in people with recent myocardial infarction.Methods and analysisThis is a feasibility, assessor blinded, parallel group RCT. Participants will be allocated to either CR standard care (control group) or CR standard care+mHealth supported exercise counselling (mHealth intervention group). Feasibility outcomes will include the number of patients approached, screened and eligible; the percentage of patients who decline CR (including reasons for declining), agree to CR and consent to being part of the study; the percentage of patients who enrol in standard CR and reasons for drop out; and the percentage of participants who complete clinical, physical and psychosocial outcomes to identify a suitable primary outcome for a future definitive trial.Ethics and disseminationThe trial was approved in the UK by the Northwest—Greater Manchester East Research Ethics Committee (22/NW/0301) and is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Results will be published in peer-reviewed journals and presented at national and international scientific meetings.Trial registration numbers NCT05774587

Exercise during pregnancy presents many benefits for the mother and baby. Yet, pregnancy is characterised by a decrease in exercise. Studies have reported barriers to antenatal exercise. The coronavirus (COVID-19) pandemic may have further exacerbated barriers to antenatal exercise as pregnant females faced many challenges. Rich, in-depth exploration into pregnant female’s perceived barriers to antenatal exercise during COVID-19 is imperative. Questionnaires reporting physical activity levels were completed by all participants (n = 14). Semi-structured interviews were conducted between November 2020 and May 2021 in the UK. Interviews were analysed using thematic analysis and revealed four main themes: ‘Perceptions of being an active person shaping activity levels in pregnancy’, ‘How do I know what is right? Uncertainty, seeking validation and feeling informed’, ‘Motivators to antenatal exercise’ and ‘A process of adaptations and adjustment’. Findings indicate that the COVID-19 pandemic exacerbated barriers to antenatal exercise and highlight the importance of direct psychosocial support and clear, trustworthy information. Findings also support the fundamental need for better education amongst healthcare professionals regarding antenatal exercise.

Whereas many cities in Europe experience a continuous process of urban growth, a considerable number of others have experienced long periods of urban shrinkage over recent decades. In many such cities this process is ongoing. However, in between these two poles of growth or shrinkage, there are cities with less pronounced trajectories. One such type is cities that underwent a phase of shrinkage but have more recently seen a recovery in population numbers. This 'turnaround' from shrinkage towards a stabilization, or even re-growth, has been increasingly reflected in the literature in recent years. Set against this background, the paper discusses and analyses the urban development trajectories of two European cities - Leipzig in Germany and Liverpool in the UK - cities of a similar size that underwent a phase of long-term shrinkage from the 1930s until the late 1990s (Leipzig), and even the 2000s (Liverpool). Recently, while both cities have stabilized their populations, and have seen a modest growth of some thousand people per year, this success has been heavily dependent on external public investment and cannot be explained simply by the assertions of popular urban development models.

ObjectivesAssess the feasibility of a mobile health (mHealth)-supported home-delivered physical activity (PA) intervention (MOTIVATE-T2D) in people with recently diagnosed type 2 diabetes (T2D).DesignFeasibility multicentre, parallel group, randomised controlled trial (RCT).SettingParticipants were recruited from England and Canada using a decentralised design.ParticipantsAdults (40–75 years) recently diagnosed with T2D (5–24 months).InterventionsParticipants were randomised 1:1 to intervention (MOTIVATE-T2D) or active control groups. Participants codesigned 6month- home-delivered, personalised, progressive PA programmes supported by virtual behavioural counselling. MOTIVATE-T2D used biofeedback from wearable technologies to support the programme. The active control group received the same intervention without wearables.OutcomesThe primary outcomes were recruitment rate, retention and adherence to purposeful exercise. Clinical data on effectiveness were collected as exploratory outcomes at baseline, 6 and 12 months, with HbA1c and systolic blood pressure (BP) proposed as primary outcomes for a future full RCT.Resultsn=135 eligible participants expressed an interest in the trial, resulting in 125 participants randomised (age 55±9 years, 48% female, 81% white), a recruitment rate of 93%. Retention at 12 months was 82%. MOTIVATE-T2D participants were more likely to start (OR 10.4, CI 3.4 to 32.1) and maintain purposeful exercise at 6 (OR 7.1, CI 3.2 to 15.7) and 12 months (OR 2.9, CI 1.2 to 7.4). Exploratory clinical outcomes showed a potential effect in favour of MOTIVATE-T2D, including proposed primary outcomes HbA1c and systolic BP (between-group mean differences: HbA1c: 6 months: −5% change from baseline, CI −10 to 2: 12 months: −2% change from baseline, CI −8 to −4; systolic BP: 6 months: −1 mm Hg, CI −5 to 3: 12 months: −4 mm Hg, CI −8 to 1).ConclusionsOur findings support the feasibility of delivering the MOTIVATE-T2D mHealth-supported PA intervention for people with recently diagnosed T2D and progression to a full RCT to examine its clinical and cost-effectiveness.Trial registration numberISRCTN: 14335124; ClinicalTrials.gov: NCT0465353.

IntroductionSLE is a chronic autoimmune disease that results in sustained hyperactivation of innate and adaptive immune cells and widespread inflammatory damage. Regular exercise reduces SLE symptoms including fatigue and joint pain and improves patient quality of life. However, most individuals with SLE are not sufficiently active to achieve these benefits, and guidance on the optimal approach to exercise is limited. EXCEL will examine the feasibility of conducting a large-scale randomised controlled trial comparing the effects of a remotely monitored, home-based, exercise programme with standard of care for individuals with SLE.Methods and analysis30 females with SLE will be recruited, and those randomised into Exercise (SLE-Ex) will codesign a progressive training plan with support from the research team. The aim of each 12-week plan will be to complete 150 min of moderate (60–70% heart rate max, HRmax) or 90 min of vigorous exercise (>70% HRmax) per week. SLE-Ex will be encouraged to exercise independently (without support) from weeks 13–18. Participants with SLE that are randomised into Control (SLE-Con) will maintain habitual activity without support for 18 weeks. Measures of feasibility and acceptability will be reported, and peripheral blood will be collected at weeks 0, 12 and 18 to explore whether the frequency, phenotype and metabolic profile of lymphocyte subsets has changed. Biomarkers of SLE activity, and self-reported measures of fatigue, sleep quality and health-related quality of life will also be monitored at these timepoints. Blood and self-reported measures will be compared with a healthy control (HC) group (n=15, age and body mass index matched) at baseline only.Ethics and disseminationA favourable ethical opinion was given by South East Scotland Research Ethics Committee (22/SS/0082). Findings will be disseminated at conferences and published in peer-reviewed journals.Trial registration numberISRCTN72757645.

IntroductionExercise and physical activity (PA) are fundamental to the treatment of type 2 diabetes. Current exercise and PA strategies for newly diagnosed individuals with type 2 diabetes are either clinically effective but unsuitable in routine practice (supervised exercise) or suitable in routine practice but clinically ineffective (PA advice). Mobile health (mHealth) technologies, offering biometric data to patients and healthcare professionals, may bridge the gap between supervised exercise and PA advice, enabling patients to engage in regular long-term physically active lifestyles. This feasibility randomised controlled trial (RCT) will evaluate the use of mHealth technology when incorporated into a structured home-based exercise and PA intervention, in those recently diagnosed with type 2 diabetes.Methods and analysisThis feasibility multicentre, parallel group RCT will recruit 120 individuals with type 2 diabetes (diagnosis within 5–24 months, aged 40–75 years) in the UK (n=60) and Canada (n=60). Participants will undertake a 6-month structured exercise and PA intervention and be supported by an exercise specialist (active control). The intervention group will receive additional support from a smartwatch and phone app, providing real-time feedback and enabling improved communication between the exercise specialist and participant. Primary outcomes are recruitment rate, adherence to exercise and loss to follow-up. Secondary outcomes include a qualitative process evaluation and piloting of potential clinical outcome measures for a future RCT.Ethics and disseminationThe trial was approved in the UK by the South East Scotland Research Ethics Committee 01 (20/SS/0101) and in Canada by the Clinical Research Ethics Board of the University of British Columbia (H20-01936), and is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Results will be published in peer-reviewed journals and presented at national and international scientific meetings.Trial registration numbersISRCTN14335124; ClinicalTrials.gov: NCT04653532.

Introduction Adherence to unsupervised exercise is poor, yet unsupervised exercise interventions are utilised in most healthcare settings. Thus, investigating novel ways to enhance adherence to unsupervised exercise is essential. This study aimed to examine the feasibility of two mobile health (mHealth) technology–supported exercise and physical activity (PA) interventions to increase adherence to unsupervised exercise. Methods Eighty-six participants were randomised to online resources (n = 44, females n = 29) or MOTIVATE (n = 42, females n = 28). The online resources group had access to booklets and videos to assist in performing a progressive exercise programme. MOTIVATE participants received exercise counselling sessions supported via mHealth biometrics which allowed instant participant feedback on exercise intensity, and communication with an exercise specialist. Heart rate (HR) monitoring, survey-reported exercise behaviour and accelerometer-derived PA were used to quantify adherence. Remote measurement techniques were used to assess anthropometrics, blood pressure, HbA1c and lipid profiles. Results HR–derived adherence rates were 22 ± 34% and 113 ± 68% in the online resources and MOTIVATE groups, respectively. Self-reported exercise behaviour demonstrated moderate (Cohen's d = 0.63, CI = 0.27 to 0.99) and large effects (Cohen's d = 0.88, CI = 0.49 to 1.26) in favour of online resources and MOTIVATE groups, respectively. When dropouts were included, 84% of remotely gathered data were available, with dropouts removed data availability was 94%. Conclusion Data suggest both interventions have a positive impact on adherence to unsupervised exercise but MOTIVATE enables participants to meet recommended exercise guidelines. Nevertheless, to maximise adherence to unsupervised exercise, future appropriately powered trials should explore the effectiveness of the MOTIVATE intervention.

Abstract Background Although major improvements are achieved after cure of Cushing syndrome (CS), fatigue and decreased quality of life persist. This is the first study to measure aerobic exercise capacity in patients in remission of CS for more than 4 years in comparison with matched controls, and to investigate whether the reduction in exercise capacity is related to alterations in muscle tissue. Methods Seventeen patients were included. A control individual, matched for sex, estrogen status, age, body mass index, smoking, ethnicity, and physical activity level was recruited for each patient. Maximal aerobic capacity (VO2peak) was assessed during incremental bicycle exercise to exhaustion. In 8 individually matched patients and controls, a percutaneous muscle biopsy was obtained and measures were made of cross-sectional areas, capillarization, and oxphos complex IV (COXIV) protein content as an indicator of mitochondrial content. Furthermore, protein content of endothelial nitric oxide synthase (eNOS) and eNOS phosphorylated on serine1177 and of the NAD(P)H-oxidase subunits NOX2, p47phox, and p67phox were measured in the microvascular endothelial layer. Findings Patients showed a lower mean VO2peak (SD) (28.0 [7.0] vs 34.8 [7.9] ml O2/kg bw/min, P < .01), maximal workload (SD) (176 [49] vs 212 [67] watt, P = .01), and oxygen pulse (SD) (12.0 [3.7] vs 14.8 [4.2] ml/beat, P < .01) at VO2peak. No differences were seen in muscle fiber type–specific cross-sectional area, capillarization measures, mitochondrial content, and protein content of eNOS, eNOS-P-ser1177, NOX2, p47phox, and p67phox. Interpretation Because differences in muscle fiber and microvascular outcome measures are not statistically significant, we hypothesize that cardiac dysfunction, seen in active CS, persists during remission and limits blood supply to muscles.