Mobile health biometrics to prescribe immediate remote physical activity for enhancing uptake to cardiac rehabilitation (MOTIVATE-CR+): protocol for a randomised controlled feasibility trial.

INTRODUCTION: Cardiac 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 ANALYSIS: This 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 DISSEMINATION: The 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.

People with obesity exhibit losses in muscle proteostasis that are partly improved by exercise training.

This pilot experiment examines if a loss in muscle proteostasis occurs in people with obesity and whether endurance exercise positively influences either the abundance profile or turnover rate of proteins in this population. Men with (n = 3) or without (n = 4) obesity were recruited and underwent a 14-d measurement protocol of daily deuterium oxide (D2 O) consumption and serial biopsies of vastus lateralis muscle. Men with obesity then completed 10-weeks of high-intensity interval training (HIIT), encompassing 3 sessions per week of cycle ergometer exercise with 1 min intervals at 100% maximum aerobic power interspersed by 1 min recovery periods. The number of intervals per session progressed from 4 to 8, and during weeks 8-10 the 14-d measurement protocol was repeated. Proteomic analysis detected 352 differences (p < 0.05, false discovery rate < 5%) in protein abundance and 19 (p < 0.05) differences in protein turnover, including components of the ubiquitin-proteasome system. HIIT altered the abundance of 53 proteins and increased the turnover rate of 22 proteins (p < 0.05) and tended to benefit proteostasis by increasing muscle protein turnover rates. Obesity and insulin resistance are associated with compromised muscle proteostasis, which may be partially restored by endurance exercise.

Adherence to unsupervised exercise in sedentary individuals: A randomised feasibility trial of two mobile health interventions.

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.

Remote maintenance cardiac rehabilitation (MAINTAIN): A protocol for a randomised feasibility study.

Background: Long-term adherence to exercise is often poor for people with coronary heart disease (CHD) who have completed supervised, centre-based cardiac rehabilitation. The aim of this study is to assess the feasibility of a remotely prescribed, delivered and monitored cardiac rehabilitation intervention using a wearable device to support long-term adherence to exercise and physical activity during maintenance of cardiac rehabilitation. Methods: After completing cardiac rehabilitation, 30 participants with CHD, will be randomised (1:1) to an intervention (n = 15) or a usual care group (n = 15) in a 12-month feasibility randomised controlled trial (RCT). The intervention will comprise of an exercise consultation, personalised exercise prescription delivered via a wearable activity monitor using biometric feedback, regular monitoring via check-ins, and feedback text-messages for 6-months. Participants will be assessed at baseline (following completion of cardiac rehabilitation) and at three-, six-, and 12-months post-randomisation. The primary outcome will be feasibility, including assessment of eligibility, recruitment, adherence, and acceptability. Secondary outcomes will include exercise capacity, physical activity behaviours, cardiovascular disease risk and quality of life. Semi-structured interviews will be conducted at three-, six-, and 12-months post-randomisation (and with those who drop-out) to explore the acceptability of the study intervention and procedures. A questionnaire will be offered to those who decline participation. Discussion: The MAINTAIN study will evaluate the feasibility of conducting a future definitive multi-centre RCT testing a remotely prescribed and monitored long-term mHealth maintenance exercise programme, versus usual care, for people with CHD who have completed cardiac rehabilitation. Trial registration number: ClinicalTrials.gov, NCT05292287. Registered on 22/03/2022.

Ex Vivo treatment of coronary artery endothelial cells with serum post-exercise training offers limited protection against in vitro exposure to FEC-T chemotherapy.

Background: Chemotherapy treatment for breast cancer associates with well-documented cardiovascular detriments. Exercise has shown promise as a potentially protective intervention against cardiac toxicity. However, there is a paucity of evidence for the benefits of exercise on the vasculature. Objectives: This study aimed to determine the effects of chemotherapy on the vascular endothelium; and if there are protective effects of serological alterations elicited by an exercise training intervention. Methods and Results: 15 women participated in a 12-week home-based exercise intervention consisting of three high-intensity interval sessions per week. Human coronary artery endothelial cells (HCAEC) were exposed to physiological concentrations of 5-fluorouracil, epirubicin, cyclophosphamide (FEC) and docetaxel to determine a dose-response. Twenty-4 hours prior to FEC and docetaxel exposure, HCAECs were preconditioned with serum collected pre- and post-training. Annexin V binding and cleaved caspase-3 were assessed using flow cytometry and wound repair by scratch assays. Chemotherapy exposure increased HCAEC Annexin V binding, cleaved caspase-3 expression in a dose-dependent manner; and inhibited wound repair. Compared to pre-training serum, conditioning HCAECs with post-training serum, reduced Annexin V binding (42% vs. 30%, p = 0.01) when exposed to FEC. For docetaxel, there were no within-group differences (pre-vs post-exercise) for Annexin V binding or cleaved caspase-3 expression. There was a protective effect of post-training serum on wound repair for 5-flurouracil (p = 0.03) only. Conclusion: FEC-T chemotherapy drugs cause significant damage and dysfunction of endothelial cells. Preconditioning with serum collected after an exercise training intervention, elicited some protection against the usual toxicity of FEC-T, when compared to control serum.

Home-Based HIIT and Traditional MICT Prescriptions Improve Cardiorespiratory Fitness to a Similar Extent Within an Exercise Referral Scheme for At-Risk Individuals.

Exercise referral schemes (ERS) are used to promote physical activity within primary care. Traditionally, ERS are conducted in a gym or leisure-center setting, with exercise prescriptions based on moderate-intensity continuous training (MICT). Home-based high-intensity interval training (Home-HIIT) has the potential to reduce perceived barriers to exercise, including lack of time and access to facilities, compared to traditional MICT prescription used with ERS and improve health related outcomes. We hypothesized that Home-HIIT would mediate greater improvement in cardiorespiratory fitness (CRF) by virtue of greater adherence and compliance to the exercise prescription, compared to MICT. Methods: Patients enrolled on an ERS (Liverpool, United Kingdom) were recruited for a pragmatic trial. Participants self-selected either 12 weeks of MICT (45-135 min/week at 50-70% HRmax) or Home-HIIT (4-9 min × 1 min intervals at ≥80% of HRmax, interspersed with 1 min rest). The primary outcome was the change in CRF (VO2 peak) at post-intervention (12 weeks) and follow-up (3-month post intervention), using intention-to-treat analysis. Results: 154 participants (age 48 ± 10y; BMI 30.5 ± 6.1 kg/m2) were recruited between October 2017 and March 2019, 87 (56%) participants chose Home-HIIT and 67 (44%) MICT. VO2 peak increased post-intervention in both groups (MICT 3.9 ± 6.0 ml.kg-1.min-1, Home-HIIT 2.8 ± 4.5 ml.kg-1.min-1, P < 0.001), and was maintained at follow-up (P < 0.001). Fat mass was only reduced post MICT (MICT -1.5 ± 6.3 kg, P < 0.05, Home-HIIT -0.2 ± 2.0 kg, P = 1.00), but the reduction was not maintained at follow-up (MICT -0.6 ± 5.1 kg, Home-HIIT 0.0 ± 2.2 kg, P > 0.05). Adherence to the prescribed programs was similar (MICT 48 ± 35%, Home-HIIT 39 ± 36%, P = 0.77). Conclusion: This is the first study to evaluate the use of Home-HIIT for individuals in a primary care setting. Contrary to our hypothesis, adherence to both exercise prescriptions was poor, and CRF improved to a similar extent in both groups with improvements maintained at 3-month follow-up. We provide evidence that, although not superior, Home-HIIT could be an effective and popular additional exercise choice for patients within primary care based ERS. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04553614].

Mobile Health Biometrics to Enhance Exercise and Physical Activity Adherence in Type 2 Diabetes (MOTIVATE-T2D): protocol for a feasibility randomised controlled trial.

INTRODUCTION: Exercise 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 ANALYSIS: This 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 DISSEMINATION: The 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 NUMBERS: ISRCTN14335124; ClinicalTrials.gov: NCT04653532.

Evidence-based vs. social media based high-intensity interval training protocols: Physiological and perceptual responses.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Reliability of Protein Abundance and Synthesis Measurements in Human Skeletal Muscle.

The repeatability of dynamic proteome profiling (DPP), which is a novel technique for measuring the relative abundance (ABD) and fractional synthesis rate (FSR) of proteins in humans, is investigated. LC-MS analysis is performed on muscle samples taken from male participants (n = 4) that consumed 4 × 50 mL doses of deuterium oxide (2 H2 O) per day for 14 days. ABD is measured by label-free quantitation and FSR is calculated from time-dependent changes in peptide mass isotopomer abundances. One-hundred one proteins have at least one unique peptide and are used in the assessment of protein ABD. Fifty-four of these proteins meet more stringent criteria and are used in the assessment of FSR data. The median (M), lower-, (Q1 ) and upper-quartile (Q3 ) values for protein FSR (%/d) are M = 1.63, Q1  = 1.07, and Q3  = 3.24, respectively. The technical CV of ABD data has a median value of 3.6% (Q1 1.7% to Q3 6.7%), whereas the median CV of FSR data is 10.1% (Q1 3.5% to Q3 16.5%). These values compare favorably against other assessments of technical repeatability of proteomics data, which often set a CV of 20% as the upper bound of acceptability.

Passive heat therapy in sedentary humans increases skeletal muscle capillarization and eNOS content but not mitochondrial density or GLUT4 content.

Passive heat therapy (PHT) has been proposed as an alternative intervention to moderate-intensity continuous training (MICT) in individuals who are unable or unwilling to exercise. This study aimed to make the first comparison of the effect of PHT and MICT on 1) skeletal muscle capillarization and endothelial-specific endothelial nitric oxide synthase (eNOS) content and 2) mitochondrial density, glucose transporter 4 (GLUT4), and intramuscular triglyceride (IMTG) content. Twenty young sedentary males (21 ± 1 yr, body mass index 25 ± 1 kg/m2) were allocated to either 6 wk of PHT (n = 10; 40-50 min at 40°C in a heat chamber, 3×/wk) or MICT (n = 10; time-matched cycling at ~65% V̇o2peak). Muscle biopsies were taken from the vastus lateralis muscle before and after training. Immunofluorescence microscopy was used to assess changes in skeletal muscle mitochondrial density (mitochondrial marker cytochrome c oxidase subunit 4), GLUT4, and IMTG content, capillarization, and endothelial-specific eNOS content. V̇o2peak and whole body insulin sensitivity were also assessed. PHT and MICT both increased capillary density (PHT 21%; MICT 12%), capillary-fiber perimeter exchange index (PHT 15%; MICT 12%) (P < 0.05), and endothelial-specific eNOS content (PHT 8%; MICT 12%) (P < 0.05). However, unlike MICT (mitochondrial density 40%; GLUT4 14%; IMTG content 70%) (P < 0.05), PHT did not increase mitochondrial density (11%, P = 0.443), GLUT4 (7%, P = 0.217), or IMTG content (1%, P = 0.957). Both interventions improved aerobic capacity (PHT 5%; MICT 7%) and whole body insulin sensitivity (PHT 15%; MICT 36%) (P < 0.05). Six-week PHT in young sedentary males increases skeletal muscle capillarization and eNOS content to a similar extent as MICT; however, unlike MICT, PHT does not affect skeletal muscle mitochondrial density, GLUT4, or IMTG content. NEW & NOTEWORTHY The effect of 6-wk passive heat therapy (PHT) compared with moderate-intensity continuous training (MICT) was investigated in young sedentary males. PHT induced similar increases in skeletal muscle capillarization and endothelial-specific endothelial nitric oxide synthase content to MICT. Unlike MICT, PHT did not improve skeletal muscle mitochondrial density, glucose transporter 4, or intramuscular triglyceride content. These microvascular adaptations were paralleled by improvements in V̇o2peak and insulin sensitivity, suggesting that microvascular adaptations may contribute to functional improvements following PHT.