Biventricular responses to exercise and their relation to cardiorespiratory fitness in pediatric pulmonary hypertension.

Despite exercise intolerance being predictive of outcomes in pulmonary arterial hypertension (PAH), its underlying cardiac mechanisms are not well described. The aim of the study was to explore the biventricular response to exercise and its associations with cardiorespiratory fitness in children with PAH. Participants underwent incremental cardio-pulmonary exercise testing and simultaneous exercise echocardiography on a recumbent cycle ergometer. Linear mixed models were used to assess cardiac function variance and associations between cardiac and metabolic parameters during exercise. Eleven participants were included with a mean age 13.4 ±2.9 years. Right ventricle (RV) systolic pressure (RVsp) increased from a mean of 59 ±25 mmHg at rest to 130 ±40 mmHg at peak exercise (p<0.001), while RV fractional area change (RV-FAC) and RV free wall longitudinal strain (RVFW-Sl) worsened (35.2% vs 27%, p=0.09 and -16.6% vs -14.6%, p=0.1, respectively). At low and moderate intensity exercise, RVsp was positively associated with stroke volume and O2 pulse (p<0.1). At high intensity exercise RV-FAC, RVFW-Sl and left ventricular longitudinal strain were positively associated with oxygen uptake and O2 pulse (p<0.1), while stroke volume decreased towards peak (p=0.04). In children with PAH, the increase of pulmonary pressure alone does not limit peak exercise, but rather the concomitant reduced RV functional reserve, resulting in RV-PA uncoupling, worsening of inter-ventricular interaction and LV dysfunction. A better mechanistic understanding of PAH exercise physiopathology can inform stress testing and cardiac rehabilitation in this population.

Increased adiposity is associated with altered skeletal muscle energetics.

The objective of this pilot study was to characterize relationships between skeletal muscle energy metabolism and body composition in healthy adults with varied amounts and distribution of adipose tissue. In vivo muscle energetics were quantified using dynamic 31P magnetic resonance spectroscopy with knee extension exercise standardized to subject lean body mass. Spearman's correlation analysis examined relationships between muscle metabolism indices and measures of adiposity including body mass index (BMI), total body fat, and quadriceps intermuscular adipose tissue (IMAT). Post hoc partial correlations were examined controlling for additional body composition measures. Kruskal-Wallis tests with Dunn-Sidak post hoc comparisons evaluated group differences in energy metabolism based on body composition profiles (i.e., lean, normal-weight obese, and overweight-obese) and IMAT tertiles. BMI negatively correlated with end-exercise muscle pH after correcting for IMAT and total body fat (r = -0.46, P = 0.034). Total adiposity negatively correlated with maximum oxidative capacity after correcting for IMAT (r = -0.54, P = 0.013). IMAT positively correlated with muscle proton buffering capacity after correcting for total body fat (r = 0.53, P = 0.023). Body composition groups showed differences in end-exercise fall in [PCr] with normalized workload (P = 0.036; post hoc: overweight-obese < lean, P = 0.029) and maximum oxidative capacity (P = 0.021; post hoc: normal-weight obese < lean, P = 0.016). IMAT tertiles showed differences in end-exercise fall in [PCr] with normalized workload (P = 0.035; post hoc: 3rd < 1st, P = 0.047). Taken together, these results support increased adiposity is associated with reduced muscle energetic efficiency with more reliance on glycolysis, and when accompanied with reduced lean mass, is associated with reduced maximum oxidative capacity.NEW & NOTEWORTHY Skeletal muscle energy production is influenced by both lean body mass and adipose tissue but the effect of their distribution on energy metabolism is unclear. This study examined variations in quadriceps muscle energy metabolism in healthy adults with varied relative amounts of lean and adipose tissue. Results suggest increased adiposity is associated with reduced muscle energetic efficiency with more reliance on glycolysis, and when accompanied with reduced lean mass, is associated with reduced maximum oxidative capacity.

The Exeter Activity Unlimited statement on physical activity and exercise for cystic fibrosis: methodology and results of an international, multidisciplinary, evidence-driven expert consensus.

BACKGROUND: The roles of physical activity (PA) and exercise within the management of cystic fibrosis (CF) are recognised by their inclusion in numerous standards of care and treatment guidelines. However, information is brief, and both PA and exercise as multi-faceted behaviours require extensive stakeholder input when developing and promoting such guidelines. METHOD: On 30th June and 1st July 2021, 39 stakeholders from 11 countries, including researchers, healthcare professionals and patients participated in a virtual conference to agree an evidence-based and informed expert consensus about PA and exercise for people with CF. This consensus presents the agreement across six themes: (i) patient and system centred outcomes, (ii) health benefits, iii) measurement, (iv) prescription, (v) clinical considerations, and (vi) future directions. The consensus was achieved by a stepwise process, involving: (i) written evidence-based synopses; (ii) peer critique of synopses; (iii) oral presentation to consensus group and peer challenge of revised synopses; and (iv) anonymous voting on final proposed synopses for adoption to the consensus statement. RESULTS: The final consensus document includes 24 statements which surpassed the consensus threshold (>80% agreement) out of 30 proposed statements. CONCLUSION: This consensus can be used to support health promotion by relevant stakeholders for people with CF.

Physiological stress reactivity in pediatric cancer survivors treated with chemotherapy.

Children who experience early life stress demonstrate changes to their stress responses, which may modulate long-term health. Childhood cancer presents significant stress during diagnosis, treatment, and survivorship. We hypothesized that children who have completed chemotherapy treatment for ALL will demonstrate altered hormone patterns in response to a stressor compared with healthy controls. Twelve pediatric ALL survivors and 12 healthy controls completed the Trier Social Stress Test. Salivary samples, heart rate, and self-report ratings of stress were collected at baseline, pretest, and posttest. Between group comparison showed baseline (interleukin [IL]-8) was significantly higher in the survivor group versus controls (survivors: 89.9, 40.1-544.9 pg ml-1 ; controls: 30.7, 5.6-241.9 pg ml-1 , p = .001) as was peak (IL-8) (survivors: 147.1, 71.6-1177.6 pg ml-1 ; controls: 75.5, 28.6-698.6 pg ml-1 ). Peak salivary alpha-amylase (sAA) concentration was significantly lower in the survivor group (survivors: 69.3, 19.4-195.5 U ml-1 ; controls: 91.2, 27.7-213.7 U ml-1 ; p = .04). Repeated measures ANOVA revealed significant main effects for time on cortisol (F(2.35, 50.81)  = 5.9, p < .01), sAA (F(1.56, 33.17)  = 6.6, p < .01), stress ratings (F(3.42, 88.14)  = 53.4, p < .001), and heart rate (F(8, 83)  = 16.8, p < .05). Significant main effects for group were observed for IL-8 (F(1, 23)  = 8.2, p < .01) and tumor necrosis factor-α (F(1, 23)  = 6.8, p < .05). Significant interaction effects for group × time were found for sAA (F(5, 106)  = 2.8, p < .05). Our results indicate that childhood ALL survivors have similar responses to stress as healthy controls, but lower sympatho-adrenal-medullary reactivity. Therefore, altered stress regulation may present a pathway modulating long-term health in this population.

Sex differences in the relationships between body composition, fat distribution, and mitochondrial energy metabolism: a pilot study.

BACKGROUND: Adiposity and mitochondrial dysfunction are related factors contributing to metabolic disease development. This pilot study examined whether in vivo and ex vivo indices of mitochondrial metabolism were differentially associated with body composition in males and females. METHODS: Thirty-four participants including 19 females (mean 27 yr) and 15 males (mean 29 yr) had body composition assessed by dual energy x-ray absorptiometry and magnetic resonance (MR) imaging. Monocyte reserve capacity and maximal oxygen consumption rate (OCR) were determined ex vivo using extracellular flux analysis. In vivo quadriceps mitochondrial function was measured using 31P-MR spectroscopy based on post-exercise recovery kinetics (τPCr). The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin levels. Variables were log-transformed, and Pearson correlations and partial correlations were used for analyses. RESULTS: Mitochondrial metabolism was similar between sexes (p > 0.05). In males only, higher fat mass percent (FM%) was correlated with lower reserve capacity (r = - 0.73; p = 0.002) and reduced muscle mitochondrial function (r = 0.58, p = 0.02). Thigh subcutaneous adipose tissue was inversely related to reserve capacity in males (r = - 0.75, p = 0.001), but in females was correlated to higher maximal OCR (r = 0.48, p = 0.046), independent of FM. In females, lean mass was related to greater reserve capacity (r = 0.47, p = 0.04). In all participants, insulin (r = 0.35; p = 0.04) and HOMA-IR (r = 0.34; p = 0.05) were associated with a higher τPCr. CONCLUSIONS: These novel findings demonstrate distinct sex-dependent associations between monocyte and skeletal muscle mitochondrial metabolism with body composition. With further study, increased understanding of these relationships may inform sex-specific interventions to improve mitochondrial function and metabolic health.

Peripheral Skeletal Muscle Impairment in Children After Treatment for Leukemia and Lymphoma.

Exercise intolerance is a common adverse effect of childhood cancer, contributing to impaired health and well-being. While reduced aerobic fitness has been attributed to central cardiovascular deficiencies, the involvement of peripheral musculature has not been investigated. We studied peripheral muscle function in children following cancer treatment using noninvasive phosphorus-31 magnetic resonance spectroscopy. Ten acute lymphoblastic leukemia (ALL) and 1 lymphoma patient 8 to 18 years of age who completed treatment 6 to 36 months prior and 11 healthy controls participated in the study. Phosphorus-31 magnetic resonance spectroscopy was used to characterize muscle bioenergetics at rest and following an in-magnet knee-extension exercise. Exercise capacity was evaluated using a submaximal graded treadmill test. Both analysis of variance and Cohen d were used as statistical methods to determine the statistical significance and magnitude of differences, respectively, on these parameters between the patient and control groups. The patients treated for ALL and lymphoma exhibited lower anaerobic function ( P =0.14, d =0.72), slower metabolic recovery ( P =0.08, d =0.93), and lower mechanical muscle power ( d =1.09) during exercise compared with healthy controls. Patients demonstrated lower estimated VO 2peak (41.61±5.97 vs. 47.71±9.99 mL/min/kg, P =0.11, d =0.76), lower minutes of physical activity (58.3±35.3 vs. 114.8±79.3 min, P =0.12, d =0.99) and higher minutes of inactivity (107.3±74.0 vs. 43.5±48.3 min, d =1.04, P <0.05). Children treated for ALL and lymphoma exhibit altered peripheral skeletal muscle metabolism during exercise. Both deconditioning and direct effects of chemotherapy likely contribute to exercise intolerance in this population.

Exercise intolerance in cystic fibrosis-the role of CFTR modulator therapies.

Exercise intolerance is common in people with CF (pwCF), but not universal among all individuals. While associated with disease prognosis, exercise intolerance is not simply a reflection of the degree of lung disease. In people with severe CF, respiratory limitations may contribute more significantly to impaired exercise capacity than in those with mild-moderate CF. At all levels of disease severity, there are peripheral factors e.g., abnormal macro- and micro-vascular function that impair blood flow and reduce oxygen extraction, and mitochondrial defects that diminish metabolic efficiency. We discuss advances in understanding the central and peripheral mechanisms underlying exercise intolerance in pwCF. Exploring both the central and peripheral factors that contribute to exercise intolerance in CF can help inform the development of new therapeutic targets, as well as help define prognostic criteria.

The Psychoneuroimmunology of Stress Regulation in Pediatric Cancer Patients.

Stress is a ubiquitous experience that can be adaptive or maladaptive. Physiological stress regulation, or allostasis, can be disrupted at any point along the regulatory pathway resulting in adverse effects for the individual. Children with cancer exhibit significant changes to these pathways in line with stress dysregulation and long-term effects similar to those observed in other early-life stress populations, which are thought to be, in part, a result of cytotoxic cancer treatments. Children with cancer may have disruption to several steps in the stress-regulatory pathway including cognitive-affective function, neurological disruption to stress regulatory brain regions, altered adrenal and endocrine function, and disrupted tissue integrity, as well as lower engagement in positive coping behaviours such as physical activity and pro-social habits. To date, there has been minimal study of stress reactivity patterns in childhood illness populations. Nor has the role of stress regulation in long-term health and function been elucidated. We conclude that consideration of stress regulation in childhood cancer may be crucial in understanding and treating the disease.

The Impact of Moderate and High Intensity Cardiovascular Exertion on Sub-Elite Soccer Referee's Cognitive Performance: A Lab-Based Study.

Soccer referees represent a specialized population who are required to perform decisional or perceptual tasks during physical exertion. Recent studies have demonstrated that submaximal acute exercise has a positive impact on cognitive performance. However, less is known about the impact of more strenuous exertion on cognitive performance. This study assessed the effect of moderate and maximal intensity exercise exertion on a cognitive performance in sub-elite soccer referees. Twelve experienced soccer referees (4 female, 8 male) were recruited. Data were collected on 2 separate days. Baseline fitness level was assessed by a standardized aerobic capacity test (VO2max Test) on Day 1, along with practice trials of the Stroop Color Word Test (Stroop Test) for evaluating cognitive performance. On Day 2, cognitive performance was assessed before, during, and after an incremental intensity exercise protocol based on the Fédération International de Football Association (FIFA) referee fitness test. Relative to results obtained at rest performance on the Stroop Test improved at moderate exertion and at maximal exertion during the modified FIFA fitness test (F = 18.97, p = .005). Mean time to completion (in seconds) of the interference Stroop task significantly improved (p < .05) between rest and moderate exertion [-3.0 ± 3.0 seconds] and between rest and maximal exertion [-4.8 ± 2.6 seconds]. In summary, we observed that cognitive performance was found to improve when sub-elite soccer referees performed moderate and maximal exercise relative to results obtained at rest. It is possible that referees focus their attention to improve goal-oriented processing in the brain during physical exertion.

The Effect of Creatine Supplementation on Muscle Function in Childhood Myositis: A Randomized, Double-blind, Placebo-controlled Feasibility Study.

OBJECTIVE: To evaluate the feasibility of studying creatine in juvenile dermatomyositis (JDM). Secondary objectives were to determine the effect of creatine on muscle function and metabolism, aerobic capacity, fatigue, physical activity, and quality of life (QOL), as well as its safety. METHODS: We conducted a 6-month, double-blind, randomized, multiple-baseline design; patients were assigned to creatine or placebo. Feasibility was assessed using attended study visits, completed study procedures, and adherence. Muscle function, aerobic capacity, and muscle strength were assessed with standardized exercise tests. Muscle metabolism was assessed using a 31-Phosphorus Magnetic Resonance Spectroscopy protocol. Fatigue, physical activity, and QOL were assessed by questionnaires. Statistical significance was estimated using a randomization (permutation) test. Changes in outcome measures taken at baseline and end-of-study were calculated using paired t-tests. RESULTS: Median (range) adherence to the study drug was 88.5% (20.5-95.5%) and the proportion of subjects with 80% adherence or higher was 76.9%. There were no missed study visits. There were no statistically significant changes in muscle function, strength, aerobic capacity, disease activity, fatigue, physical activity, or QOL while subjects were receiving creatine compared to placebo. There were statistically significant adaptations in muscle metabolism (e.g., decrease in change in muscle pH following exercise, and decrease in phosphate/phosphocreatine ratio) at the end-of-study compared to baseline. There were no significant adverse effects. CONCLUSION: Creatine supplementation in children with JDM is feasible to study, and is safe and well-tolerated; it may lead to improvements in muscle metabolism.

Massage Therapy Modulates Inflammatory Mediators Following Sprint Exercise in Healthy Male Athletes.

Massage therapy is a common postexercise muscle recovery modality; however, its mechanisms of efficacy are uncertain. We evaluated the effects of massage on systemic inflammatory responses to exercise and postexercise muscle performance and soreness. In this crossover study, nine healthy male athletes completed a high-intensity intermittent sprint protocol, followed by massage therapy or control condition. Inflammatory markers were assessed pre-exercise; postexercise; and at 1, 2, and 24 h postexercise. Muscle performance was measured by squat and drop jump, and muscle soreness on a Likert scale. Significant time effects were observed for monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNFα), drop jump performance, squat jump performance, and soreness. No significant effects for condition were observed. However, compared with control, inflammatory marker concentrations (IL-8, TNFα, and MCP-1) returned to baseline levels earlier following the massage therapy condition (p < 0.05 for all). IL-6 returned to baseline levels earlier following the control versus massage therapy condition (p < 0.05). No differences were observed for performance or soreness variables. MCP-1 area under the curve (AUC) was negatively associated with squat and drop jump performance, while IL-10 AUC was positively associated with drop jump performance (p < 0.05 for all). In conclusion, massage therapy promotes resolution of systemic inflammatory signaling following exercise but does not appear to improve performance or soreness measurements.

Uterine artery and umbilical vein blood flow are unaffected by moderate habitual physical activity during pregnancy.

OBJECTIVE: This study aims to noninvasively quantify blood flow in the uterine arteries (UTAs) and umbilical vein (UV) using phase-contrast magnetic resonance imaging (PC-MRI) and test whether these correlate with maternal fitness parameters. METHOD: Resting UTA and UV flows were measured in 23 healthy 30 ± 3-year-old women who engaged in moderate-intensity physical activity during pregnancy. Participant fitness was characterized in the second and third trimesters using the submaximal oxygen uptake (VO2 ) test measuring heart rate (HR), VO2 , ventilation (ventilatory equivalent [VE]/VO2 ), and the Borg rating of perceived exertion (respiratory quotient [RQ]). Linear regression models were used to determine the associations between blood flow and maternal fitness measures. RESULTS: Blood flows in the UTA (957 ± 241 mL/min) and UV (132 ± 38 mL/min/kg) were successfully measured in 20 (87%) participants. Neither was associated with any physical fitness parameters (HR, VO2 , VE/VO2 , and RQ) nor with any second-to-third trimester change in these parameters. CONCLUSION: PC-MRI can be used to noninvasively measure blood flow in the UTA and UV. Neither resting UTA nor UV flow is associated with maternal fitness parameters. This is the first MRI-based study to provide novel hemodynamic data suggesting decoupling between maternal moderate fitness level and the maternal-placental-fetal hemodynamic system in healthy, normal body mass index (BMI) pregnancies.

Skeletal Muscle Dysfunction and Exercise Intolerance in Children Treated with Haematopoietic Stem Cell Transplant-A Pilot Feasibility Study.

Haematopoietic stem cell transplant (HSCT) is an intensive therapy for some pediatric hematological illnesses. Survivors are at risk for adverse effects including exercise intolerance. Peripheral tissue dysfunction may contribute to exercise intolerance; therefore, we examined the feasibility of a magnetic resonance spectroscopy (MRS) protocol to evaluate skeletal muscle metabolism in children post-HSCT. We measured demographic characteristics, aerobic exercise capacity (YMCA protocol), and skeletal muscle function in response to exercise (MRS; Siemens 3T MRI) in five children post-allogeneic HSCT and five age/body mass index-matched healthy controls (HCs). The mean age (± standard deviation) of the HSCT group and HC group were 11 ± 1.2 and 12.8 ± 2.4 years, respectively. Children post-HSCT had a lower peak aerobic exercise capacity compared to HCs (27.8 ± 3.4 vs. 40.3 ± 8.1 mL kg-1 min-1, respectively; p = 0.015). Exercise MRS testing protocols were successfully completed by all HSCT and HC participants; however, MRS-derived skeletal muscle metabolism variables were not different between the two groups. In conclusion, the use of exercise protocols in conjunction with MRS to assess peripheral skeletal muscle metabolism was achievable in children post-HSCT. In the future, larger studies should determine if skeletal muscle function is associated with exercise capacity in children post-HSCT.

Physical activity for children with chronic disease; a narrative review and practical applications.

BACKGROUND: Physical activity (PA) is associated with a diverse range of health benefits. International guidelines suggest that children should be participating in a minimum of 60 min of moderate to vigorous intensity PA per day to achieve these benefits. However, current guidelines are intended for healthy children, and thus may not be applicable to children with a chronic disease. Specifically, the dose of PA and disease specific exercise considerations are not included in these guidelines, leaving such children with few, if any, evidence-based informed suggestions pertaining to PA. Thus, the purpose of this narrative review was to consider current literature in the area of exercise as medicine and provide practical applications for exercise in five prevalent pediatric chronic diseases: respiratory, congenital heart, metabolic, systemic inflammatory/autoimmune, and cancer. METHODS: For each disease, we present the pathophysiology of exercise intolerance, summarize the pediatric exercise intervention research, and provide PA suggestions. RESULTS: Overall, exercise intolerance is prevalent in pediatric chronic disease. PA is important and safe for most children with a chronic disease, however exercise prescription should involve the entire health care team to create an individualized program. CONCLUSIONS: Future research, including a systematic review to create evidence-based guidelines, is needed to better understand the safety and efficacy of exercise among children with chronic disease.

A wearable activity tracker intervention for promoting physical activity in adolescents with juvenile idiopathic arthritis: a pilot study.

BACKGROUND: Children and adolescents with juvenile idiopathic arthritis (JIA) are less physically active than their healthy peers and are at high risk of missing out on the general health benefits of physical activity. Wearable activity trackers are a promising option for intervening in this population with potential advantages over traditional exercise prescriptions. The objectives of this study were to: (1) determine the feasibility of a wearable activity tracker intervention in adolescents with JIA; and (2) estimate the variability in response to a wearable activity tracker intervention on the physical activity levels of adolescents with JIA. METHODS: Participants aged 12-18 years with JIA were recruited during their routine rheumatology clinic visits at a tertiary care hospital. Participants completed the 3-Day Physical Activity Recall self-reported questionnaire at baseline, 1 week and 5 week follow-up. At the 1 week follow up, participants were instructed to start wearing an activity tracker for 28 consecutive days. Participants completed a feasibility questionnaire at their end of study visit. Participant demographics, adherence rates and feasibility outcomes were summarized using descriptive statistics. The effect of wearing a tracker on moderate-to-vigorous physical activity (MVPA) and total metabolic equivalents (METs) per day were analyzed using a paired t-test. RESULTS: Twenty-eight participants (74% female; median age 15.1, range 12.8-18.6) were included in the analysis. All of the participants were able to synchronize the activity tracker to a supported device, use the activity tracker correctly and complete the study measurements. On average, participants had activity logged on their smartphone application for 72% of the intervention period. The standard deviation of the change in mean METs/day was 12.148 and for mean MVPA blocks/day was 3.143 over the study period. CONCLUSION: Wrist worn activity tracking is a feasible intervention for adolescent patients with JIA. More research is needed to examine the effect of activity tracking on physical activity levels. TRIAL REGISTRATION: Not an applicable clinical device trial as per the criteria listed on ClinicalTrials.gov as the primary objective is feasibility.

The reproducibility of measuring trabecular bone parameters using a commercially available high-resolution magnetic resonance imaging approach: A pilot study.

Bone imaging is currently the best non-invasive way to assess changes to bone associated with aging or chronic disease. However, common imaging techniques such as dual energy x-ray absorptiometry are associated with limitations. Magnetic resonance imaging (MRI) is a radiation-free technique that can measure bone microarchitecture. However, published MRI bone assessment protocols use specialized MRI coils and sequences and therefore have limited transferability across institutions. We developed a protocol on a Siemens 3 Tesla MRI machine, using a commercially available coil (Siemens 15 CH knee coil), and manufacturer supplied sequences to acquire images at the tibia. We tested the reproducibility of the FSE and the GE Axial sequences and hypothesized that both would generate reproducible trabecular bone parameters. Eight healthy adults (age 25.5 ±â€¯5.4 years) completed three measurements of each MRI sequence at the tibia. Each of the images was processed for 8 different bone parameters (such as volumetric bone volume fraction). We computed the coefficient of variation (CV) and intraclass correlation coefficients (ICC) to assess reproducibility and reliability. Both sequences resulted in trabecular parameters that were reproducible (CV <5% for most) and reliable (ICC >80% for all). Our study is one of the first to report that a commercially available MRI protocol can result in reproducible data, and is significant as MRI may be an accessible method to measure bone microarchitecture in clinical or research environments. This technique requires further testing, including validation and evaluation in other populations.

Skeletal Muscle Metabolic Dysfunction in Patients With Malignant Hyperthermia Susceptibility.

BACKGROUND: Malignant hyperthermia (MH), a pharmacogenetic disorder of skeletal muscle, presents with a potentially lethal hypermetabolic reaction to certain anesthetics. However, some MH-susceptible patients experience muscle weakness, fatigue, and exercise intolerance in the absence of anesthetic triggers. The objective of this exploratory study was to elucidate the pathophysiology of exercise intolerance in patients tested positive for MH with the caffeine-halothane contracture test. To this end, we used phosphorus magnetic resonance spectroscopy, blood oxygen level-dependent functional magnetic resonance imaging (MRI), and traditional exercise testing to compare skeletal muscle metabolism in MH-positive patients and healthy controls. METHODS: Skeletal muscle metabolism was assessed using phosphorus magnetic resonance spectroscopy and blood oxygen level-dependent functional MRI in 29 MH-positive patients and 20 healthy controls. Traditional measures of physical capacity were employed to measure aerobic capacity, anaerobic capacity, and muscle strength. RESULTS: During 30- and 60-second exercise, MH-positive patients had significantly lower ATP production via the oxidative pathway compared to healthy controls. MH-positive patients also had a longer recovery time with blood oxygen level-dependent functional MRI compared to healthy controls. Exercise testing revealed lower aerobic and anaerobic capacity in MH-positive patients compared to healthy controls. CONCLUSIONS: Results of this exploratory study suggest that MH-positive patients have impaired aerobic metabolism compared to healthy individuals. This could explain the exercise intolerance exhibited in MH-susceptible patient population.

Neuromuscular adaptations to sprint interval training and the effect of mammalian omega-3 fatty acid supplementation.

PURPOSE: Sprint interval training (SIT) stimulates rapid metabolic adaptations within skeletal muscle but the nature of neuromuscular adaptions is unknown. Omega-3 polyunsaturated fatty acids (N-3 PUFA) are suggested to enhance neuromuscular adaptations to exercise. METHODS: We measured the neuromuscular adaptations to SIT (Study-1) and conducted a placebo-controlled randomized double blinded study to determine the effect of N-3 PUFA supplementation on neuromuscular adaptations to SIT (Study-2). In Study-1, seven active men (24.4 ± 2.6 years, VO2 peak 43.8 ± 8.7 ml kg min-1) completed 2-weeks of SIT with pre- and post-training 10 km cycling time trials (TT). In Study-2, 30 active men (24.5 ± 4.2 years, VO2 peak 41.0 ± 5.1 ml kg min-1) were randomly assigned to receive N-3 PUFA (2330 mg day-1) (n = 14) or olive oil (n = 16) during 2-weeks of SIT with pre- and post-training TTs. Four week post-training, a SIT session and TT were also performed. Change in neuromuscular function was assessed from resting twitches, quadriceps maximal voluntary contraction (MVC) force, and potentiated twitch force (Q tw). RESULTS: Study-1 showed that SIT did not elicit significant neuromuscular adaptations. Study-2 showed that N-3 PUFA supplementation had no significant effect on neuromuscular adaptations. Training caused lower MVC force [mean ± SD; N-3 PUFA -9 ± 11%, placebo -9 ± 13% (p < 0.05 time)] and Q tw peripheral fatigue [N-3 PUFA -10 ± 19%, placebo -14 ± 13% (p < 0.05 time)]. TT time was lower after training in all groups [Study-1 -10%, Study-2 N-3 PUFA -8%, placebo -12% (p < 0.05 time)]. CONCLUSION: Two weeks of SIT improved TT performance in the absence of measurable neuromuscular adaptations. N-3 PUFA supplementation had no significant effect on SIT training adaptations.

The association among skeletal muscle phosphocreatine recovery, adiposity, and insulin resistance in children.

BACKGROUND: Obesity is associated with cardiometabolic disturbances, which may have significant implications for musculoskeletal health and exercise tolerance. OBJECTIVE: We sought to determine the association between muscle structure, function, and metabolism in adolescents across the weight spectrum. METHODS: This cross-sectional case-control study included overweight and obese participants (n = 24) 8-18 years of age with a body mass index (BMI) ≥ 85th percentile for age and gender, and non-obese participants (n = 24) with a BMI < 85th percentile. Body composition, physical activity, peak aerobic capacity, cardiometabolic blood markers and insulin resistance (measured by the homeostatic model assessment of insulin resistance, HOMA-IR), skeletal muscle mitochondrial oxidative capacity (via 31 Phosphorous-Magnetic Resonance Spectroscopy, 31 P-MRS, to assess phosphocreatine (PCr) recovery after exercise), and extramyocellular and intramyocellular lipid (IMCL) levels (via 1 Hydrogen-MRS) were assessed. Stepwise regression was performed to examine the factors associated with oxidative capacity. RESULTS: bese and overweight patients had similar age, height, and physical activity to non-obese controls, but obese and overweight participants exhibited higher insulin resistance. Obese and overweight participants had longer PCr recovery than non-obese controls following 5x30s of moderate-intensity exercise (51.2 ± 20.1 s vs. 23.9 ± 7.5 s, p = 0.004). In univariate correlation analysis, impaired PCr recovery was associated with a higher BMI z-score (rs = 0.51, p < 0.001), circulating triglycerides (rs = 0.41, p = 0.005), and HOMA-IR (rs = 0.46, p = 0.001). In stepwise multivariate regression analysis, impaired PCr recovery was associated with a higher BMI z-score (ß = 0.47, p = 0.002), but not insulin resistance (ß = 0.07, p = 0.07) or circulating triglycerides (ß = 0.16 p = 0.33). CONCLUSION: A slower phosphocreatine recovery following aerobic exercise is strongly associated with increasing adiposity. A slower metabolic recovery following aerobic exercise stress suggests that endurance exercise training in obese adolescents may be an optimal strategy to target exercise intolerance in this cohort.

Cortical Thickness Changes and Their Relationship to Dual-Task Performance following Mild Traumatic Brain Injury in Youth.

Mild traumatic brain injury (mTBI) is common in youth, especially in those who participate in sport. Recent investigations from our group have shown that asymptomatic children and adolescents with mTBI continue to exhibit alterations in neural activity and cognitive performance compared with those without a history of mTBI. This is an intriguing finding, given that current return-to-learn and return-to-play protocols rely predominately on subjective symptom reports, which may not be sensitive enough to detect subtle injury-related changes. As a result, youth may be at greater risk for re-injury and long-term consequences if they are cleared for activity while their brains continue to be compromised. It is currently unknown whether mTBI also affects brain microstructure in the developing brain, particularly cortical thickness, and whether such changes are also related to cognitive performance. The present study examined cortical thickness in 13 asymptomatic youth (10-14 years old) who had sustained an mTBI 3-8 months prior to testing compared with 14 age-matched typically developing controls. Cortical thickness was also examined in relation to working memory performance during single and dual task paradigms. The results show that youth who had sustained an mTBI had thinner cortices in the left dorsolateral prefrontal region and right anterior and posterior inferior parietal lobes. Additionally, cortical thinning was associated with slower reaction time during the dual-task condition in the injured youth only. The results also point to a possible relationship between functional and structural alterations as a result of mTBI in youth, and lend evidence for neural changes beyond symptom resolution.