Translational Medicine: Exercise Physiology Applied to Metabolic Myopathies The relevance of translational medicine (bringing basic science methods “to the bed of patients”) is universally recognized. Too often, however, the tools to be applied translationally are thought to derive only from the “-omics” (genomics, proteomics, transcriptomics, metabolomics, etc.) world. The failures of this “reductionist” approach are widely recognized. In the review, we discuss studies demonstrating that scientifically sound mechanistic insights into diseases, relevant both in terms of basic science and clinically, and very well suited to be utilized within a translational medicine approach, can be obtained from the established field of exercise physiology. Methods originally aimed toward basic physiological mechanisms, and applied for the functional evaluation of athletes and sport performance, can have a valuable translational application in patients with metabolic myopathies; such as myophosphorylase deficiency (McArdle disease) or mitochondrial myopathies, diseases which share the common denominator of an impaired skeletal muscle oxidative metabolism. Several variables can yield pathophysiological insights, can identify and quantify the metabolic impairment and the effects on exercise tolerance (one of the main determinants of the patients’ clinical picture and quality of life), and can offer diagnostic clues: the impaired capacity of O2 extraction by skeletal muscle, evaluated by near-infrared spectroscopy; the “exaggerated” cardiovascular response to exercise; the slower speed of adjustment of oxidative metabolism during metabolic transitions; the “slow component” of pulmonary O2 uptake kinetics and the associated reduced efficiency and fatigue; the impaired intramuscular matching between O2 delivery and O2 utilization. The proposed methods are noninvasive, and therefore facilitate repeated or serial evaluations. They provide support for a simple message: physiology and physiological research remain the essential link between genes, molecules, and clinical care.

High-Intensity Interval Training Is Feasible in Women at High Risk for Breast Cancer Purpose This trial aimed to demonstrate the feasibility of high-intensity interval training (HIIT) in postmenopausal, overweight/obese women at high risk of invasive breast cancer and to explore HIIT on changes in cardiorespiratory fitness (CRF), body weight, and body mass index (BMI) compared with moderate-intensity continuous training (MICT) and usual care (UC). Methods Forty-four women were randomized to HIIT, MICT, or UC for a 12-wk, thrice weekly, supervised exercise intervention. HIIT included a 5-min warm-up at 50%–70% HRpeak, four cycles of 4 min at 90%–100% HRpeak, followed by 3 min at 50%–70% HRpeak. MICT consisted of 41 min at 60%–70% HRpeak. Feasibility was assessed by consent, adherence, compliance, and retention rates. CRF, body weight, and BMI were measured at baseline and end of study. Repeated-measures linear mixed models were used to assess within- and between-group differences. Results Average age was 63.9 ± 8.8 yr. BMI was 30.9 ± 5.7 kg·m−2. Participants completed 90% and 89% of HIIT and MICT workouts, respectively, with 100% compliance to the exercise prescriptions. No serious adverse events were reported. Compared with MICT and UC, HIIT exhibited improvements in change in treadmill time (101 s greater than MICT, and 125 s greater than UC, respectively, P < 0.001). Compared with UC, HIIT exhibited improvement in changes in absolute and relative V˙O2peak (a 0.15-L·min−1 increase, P = 0.005, and a 2.3-mL·kg−1⋅min−1 increase, P = 0.004). There were no significant differences between groups for body weight or BMI (P > 0.05). Conclusions HIIT is feasible, safe, and seems to promote greater improvements in CRF compared with MICT and UC in women at high risk for breast cancer.

The Effect of Growth Restriction on Voluntary Physical Activity Engagement in Mice Introduction The purpose of this study was to determine the effect of growth restriction on the biological regulation of physical activity. Methods Using a cross-fostering, protein-restricted nutritive model, mice were growth-restricted during either gestation (GUN; N = 3 litters) or postnatal life (PUN; N = 3 litters). At 21 d of age, all mice pups were weaned and fed a nonrestrictive healthy diet for the remainder of the study. At 45 d of age, mice were individually housed in cages with free moving running wheels to assess physical activity engagement. At day 70, mice were euthanized, and the nucleus accumbens was analyzed for dopamine receptor 1 expression. Skeletal muscle fiber type and cross-sectional area of the soleus, extensor digitorom longus, and diaphragm were analyzed by immunohistochemistry. The soleus from the other hindleg was evaluated for calsequestrin 1 and annexin A6 expression. Results The PUN female mice (15,365 ± 8844 revolutions per day) had a reduction (P = 0.0221) in wheel revolutions per day as compared with the GUN (38,667 ± 8648 revolutions per day) and CON females (36,421.0 ± 6700 revolutions per day). The PUN female mice also expressed significantly higher dopamine receptor 1 compared (P = 0.0247) to the other groups. The PUN female soleus had a higher expression of calsequestrin 1, along with more type IIb fibers (P = 0.0398). Conclusions Growth restriction during lactation reduced physical activity in female mice by reducing the central drive to be active and displayed a more fatigable skeletal muscle phenotype.

Aerobic Training and Green Tea Extract Protect against N-methyl-N-nitrosourea–induced Prostate Cancer Introduction Aerobic training and green tea extract can be used to reduce the risk of prostate cancer. The goal of this study was to evaluate the effects of 8-wk aerobic exercise training and administration of green tea extract on the level of nuclear factor kappa B (NF-kB), cyclooxygenase-2 (COX-2) and p53 tumor suppressor protein (p53) in prostate of rats which were stimulated by N-methyl-N-nitrosourea to induce the prostate cancer. Methods Sixty adult male Wistar rats were assigned into six groups including healthy control, cancer control (CCt), cancer training (CTr: 45 min·d−1 at low to moderate intensity, five times per week, 8 wk), cancer extract (CEx: 1.34 mL of green tea extract, three times per week, 8 wk), cancer training+ cancer extract (CTr + CEx) and sham groups. Rats were sacrificed 48 h after the last intervention session, and the prostate tissue was isolated to measure the levels of NF-kB, COX-2, and p53. Results The NF-kB level in CCt group was increased significantly compared to the healthy control (P = 0.02). In the CTr group, NF-kB level was decreased significantly compared to the CCt and CEx groups (P = 0.001 and 0.05, respectively). In addition, the levels of P53 protein were reduced in CTr, CEx, and CTr + CEx groups compared to CCt group (P = 0.001, 0.02 and 0.004, respectively). No significant changes were found in the level of COX-2 between groups. Conclusions These results suggest that a long-term exercise training combined with the intake of green tea extract may reduce levels of NF-kB and p53 in rats with prostate cancer. Given the importance of recognizing complementary therapies in this regard, future studies are warranted.

Community-Level Sports Group Participation and the Risk of Cognitive Impairment Purpose Community-level group participation is a structural aspect of social capital that may have a contextual influence on individual health. We investigated the contextual effect of community-level prevalence of sports group participation on the risk of cognitive impairment among older individuals. Methods We analyzed prospective cohort data from the Japan Gerontological Evaluation Study, a nationwide survey of 40,308 functionally independent older individuals from 346 communities. Cognitive impairment was assessed by the nationally standardized dementia scale proposed by the Ministry of Health, Labour and Welfare of Japan. Participation in a sports group 1 d per month or more frequently was defined as “participation.” We applied a two-level multilevel survival analysis to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results The cumulative incidence of cognitive impairment during the 6-yr follow-up period was 9.8%. The mean proportion of sports group participation was 25.2% (range, 0.0%–56.5%). Higher prevalence of community-level sports group participation was associated with a lower risk of cognitive impairment (HR, 0.92; 95% CI, 0.86–0.99, estimated by 10 percentage points of participation proportion) after adjusting for individual-level sports group participation, sex, age, disease, obesity, social isolation, alcohol, smoking, education, income, depression, daily walking time, population density, and sunlight hours. We found cross-level interaction between individual- and community-level sports group participation (HR, 0.87; 95% CI, 0.76–0.99). Conclusions We found a contextual preventive effect of community-level sports group participation on developing cognitive impairment among older individuals. Furthermore, the benefit may favor sports group participants. Therefore, promoting sports groups in a community setting may be effective as a population-based strategy for the prevention of dementia.

Optimal Approach to Load Progressions during Strength Training in Older Adults Progressive resistance training (RT) is one of the most effective interventions for reducing age-related deficits in muscle mass and functional capacity. Purpose To compare four approaches to load progressions in RT for older adults to determine if an optimal method exists. Methods Eighty-two healthy community-dwelling older adults (71.8 ± 6.2 yr) performed 11 wk of structured RT (2.5 d·wk−1) in treatment groups differing only by the method used to increase training loads. These included percent one repetition maximum (%1RM): standardized loads based on a percentage of the one repetition maximum (1RM); rating of perceived exertion (RPE): loads increased when perceived difficulty falls below 8/10 on the OMNI-Resistance Exercise Scale perceived exertion scale; repetition maximum (RM): loads increased when a target number of repetitions can be completed with a given load; repetitions in reserve (RiR): identical to RM except subjects must always maintain ≥1 “repetition in reserve,” thus avoiding the possibility of training to temporary muscular failure. Results Multiple analyses of covariance indicated no significant between-group differences on any strength (chest press 1RM; leg press 1RM) or functional performance outcome (usual walking speed, maximum walking speed, 8-ft timed up-and-go, gallon jug transfer test, 30 s sit-to-stand). The RPE group found the exercise to be significantly more tolerable and enjoyable than subjects in the RiR, RM, and %1RM groups. Conclusion Given the RM, RPE, %1RM, and RiR methods appear equally effective at improving muscular strength and functional performance in an older population, we conclude that the RPE method is optimal because it is likely to be perceived as the most tolerable and enjoyable, which are two important factors determining older adults’ continued participation in RT.

High-Intensity Single-Leg Cycling Improves Cardiovascular Disease Risk Factor Profile Introduction Regular exercise can reduce the risk of developing cardiovascular disease through risk factor modification, with high-intensity exercise and more recently small muscle mass training providing alternatives to moderate-intensity exercise. Methods This study randomly assigned 53 healthy middle-age adults (age, 62 ± 6 yr) to complete 24 sessions (8 wk; 3 d·wk−1) of exercise training, using either high-intensity double-leg cycling (n = 17; HITDL), high-intensity single-leg cycling (n = 18; HITSL), or moderate-intensity double-leg cycling (n = 18; MCTDL). Biomarkers of cardiovascular risk (total cholesterol, triglycerides, HDL-c, LDL-c, apo-B48, and glucose), anthropometry measures (body mass, body mass index, waist circumference, and waist-to-hip ratio), resting blood pressure, and aerobic capacity were assessed pre- and postintervention. Results Total work completed was greater (P < 0.01) in MCTDL (5938 ± 1462 kJ) compared with the HITDL (3462 ± 1063 kJ) and HITSL (4423 ± 1875 kJ). Pre- to posttraining differences were observed for waist-to-hip ratio (0.84 ± 0.09 vs 0.83 ± 0.09; P < 0.01), resting systolic blood pressure (129 ± 11 vs 124 ± 12 mm Hg; P < 0.01), total cholesterol (5.87 ± 1.17 vs 5.55 ± 0.98 mmol·L−1; P < 0.01), and LDL-c (3.70 ± 1.04 vs 3.44 ± 0.84 mmol·L−1; P < 0.01), with no differences between conditions. In addition, aerobic capacity increased after training (22.3 ± 6.4 vs 24.9 ± 7.6 mL·kg−1·min−1; P < 0.01), with no differences between conditions. Conclusion These findings suggest that all three modes of exercise can be prescribed to achieve cardiovascular risk reduction in an aging population.

Quantification of Cardiorespiratory Fitness in Children with Obesity Purpose Without consideration for the effects of fat mass, there could be an underestimation of cardiorespiratory fitness in children with obesity leading to a clinical diagnosis of deconditioning and resulting in unrealistic training goals and limitation of physical activities. The purpose of this study was to identify methods of quantifying cardiorespiratory fitness that were less influenced by fat mass. Methods Fifty-three children, 27 with obesity (10.9 ± 1.0 yr) and 26 without obesity (11.0 ± 1.0 yr), volunteered for this study. Maximal oxygen uptake, an indicator of cardiorespiratory fitness, was referenced to lean body mass, body mass, and predicted body mass at the 50th and 85th body mass index percentiles. Results Children with obesity carried 18 kg more fat mass and 7 kg more lean body mass compared with children without obesity. Cardiorespiratory fitness based on lean body mass, body mass, and predicted body mass at the 85th percentile was lower in children with obesity compared with children without obesity (P < 0.001). Differences in cardiorespiratory fitness based on predicted body mass at the 50th percentile between children with and without obesity did not reach statistical significance (P = 0.84). Fat mass influenced cardiorespiratory fitness least when referenced to lean body mass or predicted body mass at the 50th percentile (R2 < 0.26) in contrast to when it was referenced to body mass or predicted body mass at the 85th percentile (R2 > 0.37). Conclusion Quantifying cardiorespiratory fitness based on lean body mass or predicted body mass at the 50th percentile could be useful for estimating fitness levels in children with obesity.

Validity of Cardiorespiratory Fitness Measured with Fitbit Compared to V˙O2max Purpose Cardiorespiratory fitness (CRF), broadly defined as the body’s ability to utilize oxygen, is a well-established prognostic marker of health, but it is not routinely measured. This may be due to the difficulty of acquiring high-quality CRF measures. The purpose of this study was to independently determine the validity of the Fitbit Charge 2’s measure of CRF (Fitbit CRF). Methods Sixty-five healthy adults between the ages of 18 and 45 yr (55% female, 45% male) were recruited to undergo gold standard V˙O2max testing and wear a Fitbit Charge 2 continuously for 1 wk during which they were instructed to complete a qualifying outdoor run to derive the Fitbit CRF (units: mL·kg−1·min−1). This measure was compared with V˙O2max measures (units: mL·kg−1·min−1) epoched at 15 and 60 s. Results Bland–Altman analyses revealed that Fitbit CRF had a positive bias of 1.59 mL·kg−1·min−1 compared with laboratory data epoched at 15 s and 0.30 mL·kg−1·min−1 compared with data epoched at 60 s (n = 60). F statistics (2.09; 0.08) and P values (0.133; 0.926) from Bradley–Blackwood tests for the concordance of Fitbit CRF with 15- and 60-s laboratory data, respectively, support the null hypothesis of equal means and variances, indicating there is concordance between the two measures. Mean absolute percentage error was less than 10% for each comparison. Conclusions The Fitbit Charge 2 provides an acceptable level of validity when measuring CRF in young, healthy, and fit adults who are able to run. Further research is required to determine if it is a potentially useful tool in clinical practice and epidemiological research to quantify, categorize, and longitudinally track risk for adverse outcomes.

Estimating Tibial Stress throughout the Duration of a Treadmill Run Introduction Stress fractures of the tibia are a problematic injury among runners of all levels. Quantifying tibial stress using a modeling approach provides an alternative to invasive assessments that may be used to detect changes in tibial stress during running. This study aimed to assess the repeatability of a tibial stress model and to use this model to quantify changes in tibial stress that occur throughout the course of a 40-min prolonged treadmill run. Methods Synchronized force and kinematic data were collected during prolonged treadmill running from 14 recreational male rearfoot runners on two separate occasions. During each session, participants ran at their preferred speed for two consecutive 20-min runs, separated by a 2-min pause. The tibia was modeled as a hollow ellipse and bending moments and stresses at the distal third of the tibia were estimated using beam theory combined with inverse dynamics and musculoskeletal modeling. Results Intraclass correlation coefficients indicated good-to-excellent repeatability for peak stress values between sessions. Peak anterior and posterior stresses increased after 20 min of prolonged treadmill running and were 15% and 12% greater, respectively, after 40 min of running compared with the start of the run. Conclusion The hollow elliptical tibial model presented is a repeatable tool that can be utilized to assess within-participant changes in peak tibial stress during running. The increased stresses observed during a prolonged treadmill run may have implications for the development of tibial stress fracture.