Development of the intelligent knee osteoarthritis lifestyle app: a person-based approach.

BACKGROUND: Knee osteoarthritis is one of the most prevalent long term health conditions globally. Exercise and physical activity are now widely recognised to significantly reduce joint pain, improve physical function and quality of life in patients with knee osteoarthritis. However, prescribed exercise without regular contact with a healthcare professional often results in lower adherence and poorer health outcomes. Digital mobile health (mHealth) technologies offer great potential to support people with long-term conditions such as knee osteoarthritis more efficiently and effectively and with relatively lower cost than existing interventions. However, there are currently very few mHealth interventions for the self-management of knee osteoarthritis. The aim of the present study was to describe the development process of a mHealth app to extend the support for physical activity and musculoskeletal health beyond short-term, structured rehabilitation through self-management, personalised physical activity, education, and social support. METHODS: The development of the intelligent knee osteoarthritis lifestyle application intervention involved an iterative and interconnected process comprising intervention 'planning' and 'optimisation' informed by the person-based approach framework for the development of digital health interventions. The planning phase involved a literature review and collection of qualitative data obtained from focus groups with individuals with knee osteoarthritis (n = 26) and interviews with relevant physiotherapists (n = 5) to generate 'guiding principles' for the intervention. The optimisation phase involved usability testing (n = 7) and qualitative 'think aloud' sessions (n = 6) with potential beneficiaries to refine the development of the intervention. RESULTS: Key themes that emerged from the qualitative data included the need for educational material, modifying activities to suit individual abilities and preferences as well as the inclusion of key features such as rehabilitation exercises. Following a user-trial further changes were made to improve the usability of the application. CONCLUSIONS: Using a systematic person-based, development approach, we have developed the intelligent knee osteoarthritis lifestyle application to help people maintain physical activity behaviour. The app extends the support for physical activity and musculoskeletal health beyond short-term, structured rehabilitation through personalised physical activity guidance, education, and social support.

Influence of the intelligent knee osteoarthritis lifestyle app (iKOALA) on knee joint pain.

BACKGROUND: The intelligent knee osteoarthritis lifestyle app (iKOALA) has been co-developed with target users to extend the support for physical activity (PA) and musculoskeletal health, beyond short-term structured rehabilitation, using personalised PA guidance, education, and social support. The purpose of this study was to assess the preliminary effectiveness and usability of the iKOALA digital intervention on indices of musculoskeletal (MSK) health, symptoms, and physical activity levels in a broad range of individuals with knee osteoarthritis (KOA) over 12 weeks to inform the design of a larger randomised controlled trial. METHODS: Thirty-eight (33 female) participants living in the UK with a mean (SD) age of 58 (± 9) years diagnosed radiographically or clinically with KOA completed a 12-week user trial of the iKOALA. Participants completed an in-app physical activity questionnaire which intelligently recommended suitable strengthening and aerobic based activities to individuals. Throughout the trial, participants wore a physical activity monitor and were given access to functions within the app (physical activity (PA) reminders, information and education, symptom and PA tracking as well as social support forums) to support them in maintaining their PA plan. Participants completed a MSK questionnaire for chronic symptoms and quality of life (MSK-HQ) as well as an acute iKOALA symptoms questionnaire (confidence, fatigue, mood, pain during the day/night, sleep and ability to walk) in the week prior to starting and following completion of the trial. RESULTS: Physical activity levels were consistent over the 12 weeks with total daily steps of 9102 (± 3514) in week 1, 9576 (± 4214) in week 6 and 9596 (± 3694) in week 12. Group mean changes in all iKOALA MSK symptom scores and the total MSK-HQ (pre 33.1 (7.6) vs. post 40.2 (7.6)) score improved significantly (p < .001, 95% CI [-8.89, -5.16]) over the 12-week period. CONCLUSIONS: Physical activity levels were maintained at a high level throughout the 12 weeks. Significant improvements in mean MSK symptom scores and the total MSK-HQ score were also observed. Efforts to ensure more generalised reach amongst sex and socioeconomic status of the digital intervention in a randomised controlled clinical trial are warranted.

Serum osmolality measured in fingertip capillary blood is comparable to serum osmolality measured in venous blood.

Blood osmolality is considered the gold standard hydration assessment, but has limited application for technical and invasive reasons. Paired antecubital-venous blood and fingertip-capillary blood were collected pre- and 30 min post-drinking 600 mL water in 55 male/female participants. No bias (0.2 mOsmo/kg, limits of agreement = -2.5 to 2.8 mOsmo/kg) was found between sampling methods, with high linear correlation (Spearman's r = 0.95, P < 0.001). Capillary blood sampling offers an accurate less-invasive method for determining serum osmolality than venous blood sampling.

The effects of upper- vs. lower-body aerobic exercise on perceived pain in individuals with chronic knee pain: a randomised crossover trial.

Background and objectives: Some 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. Methods: A 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. Results: VAS 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. Conclusion: An 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.

ADAPTations to low load blood flow restriction exercise versus conventional heavier load resistance exercise in UK military personnel with persistent knee pain: protocol for the ADAPT study, a multi-centre randomized controlled trial.

BACKGROUND: Muscle atrophy, muscle weakness and localised pain are commonly reported following musculoskeletal injury (MSKI). To mitigate this risk and prepare individuals to return to sport or physically demanding occupations, resistance training (RT) is considered a vital component of rehabilitation. However, to elicit adaptations in muscle strength, exercise guidelines recommend lifting loads ≥ 70% of an individual's one repetition maximum (1-RM). Unfortunately, individuals with persistent knee pain are often unable to tolerate such high loads and this may negatively impact the duration and extent of their recovery. Low load blood flow restriction (LL-BFR) is an alternative RT technique that has demonstrated improvements in muscle strength, hypertrophy, and pain in the absence of high mechanical loading. However, the effectiveness of high-frequency LL-BFR in a residential rehabilitation environment remains unclear. This study will compare the efficacy of high frequency LL-BFR to 'conventional' heavier load resistance training (HL-RT) on measures of physical function and pain in adults with persistent knee pain. METHODS: This is a multicentre randomised controlled trial (RCT) of 150 UK service personnel (aged 18-55) admitted for a 3-week residential rehabilitation course with persistent knee pain. Participants will be randomised to receive: a) LL-BFR delivered twice daily at 20% 1-RM or b) HL-RT three-times per week at 70% 1-RM. Outcomes will be recorded at baseline (T1), course discharge (T2) and at three-months following course (T3). The primary outcome will be the lower extremity functional scale (LEFS) at T2. Secondary outcomes will include patient reported perceptions of pain, physical and occupational function and objective measures of muscle strength and neuromuscular performance. Additional biomechanical and physiological mechanisms underpinning both RT interventions will also be investigated as part of a nested mechanistic study. DISCUSSION: LL-BFR is a rehabilitation modality that has the potential to induce positive clinical adaptations in the absence of high mechanical loads and therefore could be considered a treatment option for patients suffering significant functional deficits who are unable to tolerate heavy load RT. Consequently, results from this study will have a direct clinical application to healthcare service providers and patients involved in the rehabilitation of physically active adults suffering MSKI. TRIAL REGISTRATION: ClinicalTrials.org reference number, NCT05719922.

Influence of traumatic lower-limb amputation on physical activity, body composition, and cardiometabolic risks: A descriptive preliminary study.

BACKGROUND: Following traumatic lower-limb amputation (LLA), humans are predisposed to numerous unfavorable changes in health, including the development of secondary chronic health conditions such as metabolic disorders and cardiovascular disease. OBJECTIVE: To determine within and between group differences in cardiometabolic component risks, body composition, and physical activity (PA) in individuals with traumatic unilateral and bilateral LLA, compared to noninjured controls. DESIGN: Prospective observational cohort study. SETTING: A military complex trauma rehabilitation center. PARTICIPANTS: Sixteen males with traumatic LLA (8 unilateral, mean age 30 ± 5 years and 8 bilateral, mean age 29 ± 3 years). Thirteen active age-matched males with no LLA (28 ± 5 years) acted as controls and performed habitual activities of daily living. INTERVENTION: Participants with LLA attended two 4-week periods of inpatient rehabilitation, separated by two 6-week periods of home-based recovery. MAIN OUTCOME MEASURES: Venous blood samples were taken prior to and following a 75 g oral glucose load, for determination of biomarkers, including insulin and glucose, at baseline and 20 weeks. Body composition (dual X-ray absorptiometry) was measured at baseline, 10 weeks, and 20 weeks. Daily PA was recorded using a triaxial accelerometer for 7 days during inpatient rehabilitation and while at home. Energy expenditure was estimated using population-specific equations. RESULTS: Individuals with bilateral LLA demonstrated more unfavorable mean body composition values, lower PA, and increased cardiometabolic health risk compared to controls. Cardiometabolic syndrome was identified in 63% of individuals with bilateral LLA. No statistically significant differences in cardiometabolic component risk factors, body composition, and estimated daily PA were reported between unilateral LLA and control groups (p > .05). While at home, mean PA counts.day-1 reduced by 17% (p = .018) and 42% (p = .001) in the unilateral and bilateral LLA groups, respectively. CONCLUSIONS: Despite extensive inpatient rehabilitation, cardiometabolic component risks are elevated in individuals with bilateral LLA but are comparable between unilateral LLA and active noninjured control groups. Innovative strategies that improve/support the long-term PA and cardiometabolic health of severely injured individuals with bilateral LLA are warranted.

Post-exercise skimmed milk, but not a sucrose beverage decreases energy intake at the next meal compared to a placebo beverage in active males.

This study compared the appetite and energy intake effects of three post-exercise beverages at a subsequent post-exercise meal. On three occasions, ten active males: (mean ± sd) age 21.3 ± 1.2 y, V˙ O2peak 58 ± 5 mL/kg/min) performed 30-min cycling at ∼60% V˙ O2peak and five 4-min intervals at 85% V˙ O2peak. Post-exercise, placebo (PLA: 57 kJ), skimmed milk (MILK: 1002 kJ) or sucrose (CHO: 1000 kJ) beverages (615 mL) were consumed. Sixty min post-beverage, subjects consumed an ad-libitum pasta lunch in a 30 min eating period. Subjective appetite and plasma acylated ghrelin and plasma glucose were determined pre-exercise, post-exercise and pre-meal, with sensory characteristics of beverages rated. Ad-libitum energy intake in MILK (6746 ± 2035) kJ) was lower than CHO (7762 ± 1921) kJ) (P = 0.038; dz = 0.98; large effect) and tended to be lower than PLA (7672 (2005) kJ) (P = 0.078; dz = 0.76; medium effect). Including energy consumed in beverages, energy intake was greater in CHO than PLA (P = 0.010; dz = 1.24; large effect) or MILK (P = 0.026; dz = 0.98; large effect), with PLA and MILK not different (P = 0.960; dz = 0.02; trial effect). Plasma ghrelin, plasma glucose and appetite were not different between trials. MILK was perceived thicker than CHO (P = 0.020; dz = 1.11; large effect) and creamier than PLA (P = 0.026; dz = 1.06; large effect). These results suggest that when energy balance is important for an exerciser, post-exercise skimmed milk ingestion reduces energy intake compared to a sucrose beverage and might therefore help facilitate recovery/adaptation without affecting energy balance.

Portions selected to stave off hunger are reduced when food is presented in an 'unusual' food-to-mealtime context: An implication for implicit satiety drivers.

Research suggests that the role of expected satiety in influencing portion-size selection is reduced when food is presented in unusual food-to-mealtime contexts; however, the underlying mechanism has not been explored. Other research has revealed that different implicit satiety drivers (e.g., to stop momentary hunger or obtain complete fullness) are associated with different perceived levels of stomach fullness, portion-size selections and can change on instruction. The current study explored whether changes in expected satiety and ideal portions in congruous vs incongruous contexts can be explained by changes in implicit satiety drivers. Another aim was to investigate a previous exploratory finding suggesting that portions selected to stave off hunger are reduced when foods are presented in unusual food-to-mealtime contexts. At two trials (breakfast/lunch), participants (n = 40) selected a portion of typical lunch (pasta) and breakfast (porridge) foods via a psychophysical computer-based method 1) to stave off hunger for 5 h, and 2) as an ideal portion. Participants also indicated their perceived level of stomach fullness associated with 1) each portion, and 2) five implicit satiety drivers. Results revealed that a smaller average portion was selected to stave off hunger in incongruous (vs congruous) food-to-mealtime contexts (531 ± 229 vs 575 ± 236 kcal) (p = 0.008). This suggests that expected satiety is influenced by momentary context; foods are perceived to be more satiating when consumed in unusual (vs usual) contexts. Results also showed that implicit satiety drivers are malleable in regard to the portion size associated with a perceived level of stomach fullness and that this can vary contextually. These findings provide initial evidence to explain the psychological mechanism underlying the contextual differences observed in portion-size selections. Future work should explore longer-term impacts of consuming foods in unusual contexts.

Current appetite influences relative differences in the expected satiety of foods for momentary, but not hypothetical, expected satiety assessments.

Research has shown that expected satiety is highly associated with portion-size selection and can vary (kcal-for-kcal) significantly between foods. However, research has not adequately investigated whether current appetite influences relative differences in the expected satiety of foods. This is important to explore to better understand how current motivational state influences food choice and portion selection. This study used 'hypothetical' and 'momentary' expected-satiety assessments to understand whether methods requiring a reflection on current motivational state [momentary] versus more hypothetical considerations when assessing expected satiety can influence the interpretation of results. It was hypothesised that current appetite would only influence relative differences in expected satiety between foods for momentary, but not hypothetical, expected satiety assessments. Participants (n = 54) were shown images of twelve foods, once when hungry and once when full. In each case, they selected a portion for each food to 1) match the expected satiety of a fixed-portion 'standard' food [hypothetical], and 2) stave off hunger until their next meal [momentary]. Results showed that the relative between-food comparison of expected satiety was stable for hypothetical (p=.73) but not momentary assessments (p<.001) suggesting that while current motivational state may influence food choice and portion selection in the moment, more generalised comparisons of the satiating abilities of foods (learned over a longer period) remain stable. This is important 1) for methods in future studies, as immediate dietary intake does not appear to influence hypothetical expected satiety, thus dietary control is not necessary before participants undertake these assessments, and 2) as it confirms that difficulties associated with dietary regulation may not be due to inaccurate hypothetical judgements about foods, but instead appear to be influenced by contextual nuances that occur in the moment.

Metabolic Profiling of Mice with Deletion of the Orphan G Protein-Coupled Receptor, GPR37L1.

Understanding the neurogenic causes of obesity may reveal novel drug targets to counter the obesity crisis and associated sequelae. Here, we investigate whether the deletion of GPR37L1, an astrocyte-specific orphan G protein-coupled receptor, affects whole-body energy homeostasis in mice. We subjected male Gpr37l1-/- mice and littermate wildtype (Gpr37l1+/+, C57BL/6J background) controls to either 12 weeks of high-fat diet (HFD) or chow feeding, or to 1 year of chow diet, with body composition quantified by EchoMRI, glucose handling by glucose tolerance test and metabolic rate by indirect calorimetry. Following an HFD, Gpr37l1-/- mice had similar glucose handling, body weight and fat mass compared with wildtype controls. Interestingly, we observed a significantly elevated respiratory exchange ratio in HFD- and chow-fed Gpr37l1-/- mice during daylight hours. After 1 year of chow feeding, we again saw no differences in glucose and insulin tolerance or body weight between genotypes, nor in energy expenditure or respiratory exchange ratio. However, there was significantly lower fat mass accumulation, and higher ambulatory activity in the Gpr37l1-/- mice during night hours. Overall, these results indicate that while GPR37L1 may play a minor role in whole-body metabolism, it is not a viable clinical target for the treatment of obesity.

Prior arm-crank exercise has no effect on postprandial lipaemia in nondisabled adults.

A single bout of cycling or running performed in the evening can reduce postprandial lipaemia (PPL) the following morning, although this is currently unknown for upper-body exercise. The aim of this study was to determine if a bout of arm-crank exercise (high-intensity interval [HIIE] or moderate-intensity continuous [MICE]), can attenuate PPL in noninjured individuals. Eleven healthy and recreationally active participants (eight males, three females; age: 27 ± 7 years; body mass index: 23.5 ± 2.5 kg·m-2) volunteered to participate in three trials: HIIE (10 × 60 s at 80% peak power output), MICE (50% peak power output of isocaloric duration), and a no-exercise control condition. Each exercise bout was performed at 18:00, and participants consumed a standardised evening meal at 20:00. Following an overnight fast, a 5-h mixed-macronutrient tolerance test was performed at 08:00. There were no significant differences in triglyceride incremental area under the curve between HIIE (192 ± 94 mmol·L-1 per 300 min), MICE (184 ± 111 mmol·L-1 per 300 min), and the no-exercise condition (175 ± 90 mmol·L-1 per 300 min) (P = 0.46). There were no significant differences in incremental area under the curve for glucose (P = 0.91) or insulin (P = 0.59) between conditions. Upper-body MICE and HIIE performed in the evening do not influence PPL the following morning, in normotriglyceridemic individuals. Clinical Trials Registration: NCT04277091. Novelty: Arm-crank exercise has no effect on PPL when performed the evening prior to a mixed-macronutrient meal test. Upper-body sprint interval exercise should be investigated as a potential solution to reduce PPL.

Cost-effectiveness of a physical activity and behaviour maintenance programme on functional mobility decline in older adults: an economic evaluation of the REACT (Retirement in Action) trial.

BACKGROUND: Mobility limitations in older populations have a substantial impact on health outcomes, quality of life, and social care costs. The Retirement in Action (REACT) randomised controlled trial assessed a 12-month community-based group physical activity and behaviour maintenance intervention to help prevent decline in physical functioning in older adults at increased risk of mobility limitation. We aimed to do an economic evaluation of the REACT trial to investigate whether the intervention is cost-effective. METHODS: In this health economic evaluation, we did cost-effectiveness and cost-utility analyses of the REACT programme versus standard care on the basis of resource use, primary outcome, and health-related quality-of-life data measured in the REACT trial. We also developed a decision analytic Markov model that forecasts the mobility of recipients beyond the 24-month follow-up of the trial and translated this into future costs and potential benefit to health-related quality of life using the National Health Service and Personal Social Services perspective. Participants completed questionnaire booklets at baseline, and at 6, 12, and 24 months after randomisation, which included a resource use questionnaire and the EQ-5D-5L and 36-item short-form survey (SF-36) health-related quality-of-life instruments. The cost of delivering the intervention was estimated by identifying key resources, such as REACT session leader time, time of an individual to coordinate the programme, and venue hire. EQ-5D-5L and SF-36 responses were converted to preference-based utility values, which were used to estimate quality-adjusted life-years (QALYs) over the 24-month trial follow-up using the area-under-the-curve method. We used generalised linear models to examine the effect of the REACT programme on costs and QALYs and adjust for baseline covariates. Costs and QALYs beyond 12 months were discounted at 3·5% per year. This is a pre-planned analysis of the REACT trial; the trial itself is registered with ISRCTN (ISRCTN45627165). FINDINGS: The 12-month REACT programme was estimated to cost £622 per recipient to deliver. The most substantial cost components are the REACT session leader time (£309 per participant), venue hire (£109), and the REACT coordinator time (£80). The base-case analysis of the trial-based economic evaluation showed that reductions in health and social care usage due to the REACT programme could offset the REACT delivery costs (£3943 in the intervention group vs £4043 in the control group; difference: -£103 [95% CI -£695 to £489]) with a health benefit of 0·04 QALYs (0·009-0·071; 1·354 QALYs in the intervention group vs 1·314 QALYs in the control group) within the 24-month timeframe of the trial. INTERPRETATION: The REACT programme could be considered a cost-effective approach for improving the health-related quality of life of older adults at risk of mobility limitations. FUNDING: National Institute for Health Research Public Health Research Programme.

Effect of a physical activity and behaviour maintenance programme on functional mobility decline in older adults: the REACT (Retirement in Action) randomised controlled trial.

BACKGROUND: Mobility limitations in old age can greatly reduce quality of life, generate substantial health and social care costs, and increase mortality. Through the Retirement in Action (REACT) trial, we aimed to establish whether a community-based active ageing intervention could prevent decline in lower limb physical functioning in older adults already at increased risk of mobility limitation. METHODS: In this pragmatic, multicentre, two-arm, single-blind, parallel-group, randomised, controlled trial, we recruited older adults (aged 65 years or older and who are not in full-time employment) with reduced lower limb physical functioning (Short Physical Performance Battery [SPPB] score 4-9) from 35 primary care practices across three sites (Bristol and Bath; Birmingham; and Devon) in England. Participants were randomly assigned to receive brief advice (three healthy ageing education sessions) or a 12-month, group-based, multimodal physical activity (64 1-h exercise sessions) and behavioural maintenance (21 45-min sessions) programme delivered by charity and community or leisure centre staff in local communities. Randomisation was stratified by site and adopted a minimisation approach to balance groups by age, sex, and SPPB score, using a centralised, online, randomisation algorithm. Researchers involved in data collection and analysis were masked but participants were not because of the nature of the intervention. The primary outcome was change in SPPB score at 24 months, analysed by intention to treat. This trial is registered with ISRCTN, ISRCTN45627165. FINDINGS: Between June 20, 2016, and Oct 30, 2017, 777 participants (mean age 77·6 [SD 6·8] years; 66% female; mean SPPB score 7·37 [1·56]) were randomly assigned to the intervention (n=410) and control (n=367) groups. Primary outcome data at 24 months were provided by 628 (81%) participants (294 in the control group and 334 in the intervention group). At the 24-month follow-up, the SPPB score (adjusted for baseline SPPB score, age, sex, study site, and exercise group) was significantly greater in the intervention group (mean 8·08 [SD 2·87]) than in the control group (mean 7·59 [2·61]), with an adjusted mean difference of 0·49 (95% CI 0·06-0·92; p=0·014), which is just below our predefined clinically meaningful difference of 0·50. One adverse event was related to the intervention; the most common unrelated adverse events were heart conditions, strokes, and falls. INTERPRETATION: For older adults at risk of mobility limitations, the REACT intervention showed that a 12-month physical activity and behavioural maintenance programme could help prevent decline in physical function over a 24-month period. FUNDING: National Institute for Health Research Public Health Research Programme (13/164/51).

Backward Double Integration is a Valid Method to Calculate Maximal and Sub-Maximal Jump Height.

The backward double integration method uses one force plate and could calculate jump height for countermovement jumping, squat jumping and drop jumping by analysing the landing phase instead of the push-off phase. This study compared the accuracy and variability of the forward double integration (FDI), backwards double integration (BDI) and Flight Time + Constant (FT+C) methods, against the marker-based rigid-body modelling method. It was hypothesised that the jump height calculated using the BDI method would be equivalent to the FDI method, while the FT+C method would have reduced accuracy and increased variability during sub-maximal jumping compared to maximal jumping. Twenty-four volunteers performed five maximal and five sub-maximal countermovement jumps, while force plate and motion capture data were collected. The BDI method calculated equivalent mean jump heights compared to the FDI method, with only slightly higher variability (2-3 mm), and therefore can be used in situations where FDI cannot be employed. The FT+C method was able to account for reduced heel-lift distance, despite employing an anthropometrically scaled heel-lift constant. However, across both sub-maximal and maximal jumping, it had increased variability (1.1 cm) compared to FDI and BDI and should not be used when alternate methods are available.

Involvement of GPR37L1 in murine blood pressure regulation and human cardiac disease pathophysiology.

Multiple mouse lines lacking the orphan G protein-coupled receptor, GPR37L1, have elicited disparate cardiovascular phenotypes. The first Gpr37l1 knockout mice study to be published reported a marked elevation in systolic blood pressure (SBP; ∼60 mmHg), revealing a potential therapeutic opportunity. The phenotype differed from our own independently generated knockout line, where male mice exhibited equivalent baseline blood pressure to wild type. Here, we attempted to reproduce the first study by characterizing the cardiovascular phenotype of both the original knockout and transgenic lines alongside a C57BL/6J control line, using the same method of blood pressure measurement. The present study supports the findings from our independently developed Gpr37l1 knockout line, finding that SBP and diastolic blood pressure (DBP) are not different in the original Gpr37l1 knockout male mice (SBP: 130.9 ± 5.3 mmHg; DBP: 90.7 ± 3.0 mmHg) compared with C57BL/6J mice (SBP: 123.1 ± 4.1 mmHg; DBP: 87.0 ± 2.7 mmHg). Instead, we attribute the apparent hypertension of the knockout line originally described to comparison with a seemingly hypotensive transgenic line (SBP 103.7 ± 5.0 mmHg; DBP 71.9 ± 3.7 mmHg). Additionally, we quantified myocardial GPR37L1 transcript in humans, which was suggested to be downregulated in cardiovascular disease. We found that GPR37L1 has very low native transcript levels in human myocardium and that expression is not different in tissue samples from patients with heart failure compared with sex-matched healthy control tissue. These findings indicate that cardiac GPR37L1 expression is unlikely to contribute to the pathophysiology of human heart failure.NEW & NOTEWORTHY This study characterizes systolic blood pressure (SBP) in a Gpr37l1 knockout mouse line, which was previously reported to have ∼60 mmHg higher SBP compared with a transgenic line. We observed only a ∼27 mmHg SBP difference between the lines. However, when compared with C57BL/6J mice, knockout mice showed no difference in SBP. We also investigated GPR37L1 mRNA abundance in human hearts and observed no difference between healthy and failing heart samples.

Neither Postabsorptive Resting Nor Postprandial Fat Oxidation Are Related to Peak Fat Oxidation in Men With Chronic Paraplegia.

The peak rate of fat oxidation (PFO) achieved during a graded exercise test is an important indicator of metabolic health. In healthy individuals, there is a significant positive association between PFO and total daily fat oxidation (FO). However, conditions resulting in metabolic dysfunction may cause a disconnect between PFO and non-exercise FO. Ten adult men with chronic thoracic spinal cord injury (SCI) completed a graded arm exercise test. On a separate day following an overnight fast (≥ 10 h), they rested for 60 min before ingesting a liquid mixed meal (600 kcal; 35% fat, 50% carbohydrate, 15% protein). Expired gases were collected and indirect calorimetry data used to determine FO at rest, before and after feeding, and during the graded exercise test. Participants had "good" cardiorespiratory fitness (VO2peak: 19.2 ± 5.2 ml/kg/min) based on normative reference values for SCI. There was a strong positive correlation between PFO (0.30 ± 0.08 g/min) and VO2peak (r = 0.86, p = 0.002). Additionally, postabsorptive FO at rest was significantly and positively correlated with postprandial peak FO (r = 0.77, p = 0.01). However, PFO was not significantly associated with postabsorptive FO at rest (0.08 ± 0.02 g/min; p = 0.97), postprandial peak FO (0.10 ± 0.03 g/min; p = 0.43), or incremental area under the curve postprandial FO (p = 0.22). It may be advantageous to assess both postabsorptive FO at rest and PFO in those with SCI to gain a more complete picture of their metabolic flexibility and long-term metabolic health.

Recommendations for Face Coverings While Exercising During the COVID-19 Pandemic.

In an effort to reduce transmission and number of infections of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) virus, governments and official bodies around the world have produced guidelines on the use of face masks and face coverings. While there is a growing body of recommendations for healthcare professionals and the wider population to use facial protection in "enclosed spaces" where minimal distancing from other individuals is not possible, there is a dearth of clear guidelines for individuals undertaking exercise and sporting activity. The present viewpoint aims to propose recommendations for face coverings while exercising during the COVID-19 pandemic that consider physical distancing, the environment, the density of active cases associated with the specific sports activity, and the practical use of face coverings in order to reduce potential viral transmission. Recommendations are provided on the basis of very limited available evidence in conjunction with the extensive collective clinical experience of the authors and acknowledging the need to consider the likelihood of the presence of the SARS-CoV-2 in the general population. We recommend that face coverings should be used in any environment considered to be of a high or moderate transmission risk, where tolerated and after individual risk assessment. In addition, as national caseloads fluctuate, individual sporting bodies should consider up to date guidance on the use of face coverings during sport and exercise, alongside other preventative measures.

Effect of high-intensity interval training on cardiometabolic component risks in persons with paraplegia: Protocol for a randomized controlled trial.

Individuals with a spinal cord injury (SCI) are at an increased risk of developing cardiovascular disease and present with a multitude of elevated cardiometabolic component risks. Although upper-body exercise appears an effective strategy to improve some of these outcomes, the effectiveness of high-intensity interval training (HIIT) has yet to be determined for this population. Therefore, a randomized controlled trial will be conducted to determine the effectiveness of a 6 week home-based upper-body HIIT intervention on biomarkers of cardiometabolic health in persons with spinal cord injury, in comparison to a control (CON) group. We will recruit 40 individuals with chronic (>1 year post-injury) paraplegia (spinal cord lesion between the second thoracic and second lumbar vertebrae), aged between 18 and 65 years. After baseline testing, participants will be assigned randomly, using a 2:1 allocation, to the home-based exercise intervention (HIIT, n = 26) or control group (CON, n = 14). The HIIT intervention will consist of 30 min of arm crank-based HIIT (60 s intervals at 80-90% peak heart rate) four times per week. Participants in the CON group will be asked to maintain their habitual diet and physical activity patterns over the study period. Baseline and follow-up assessments will be made for determination of body composition, postprandial glycaemic control, fasting blood lipids and systemic inflammation, aerobic capacity, physical activity and energy intake, resting metabolic rate, resting blood pressure, and subjective measures of health and well-being. ClinicalTrials.gov, ID: NCT04397250. Registered on 21 May 2020.