Medicine & Science in Sports & Exercise

Resistance Exercise-induced Changes in Muscle Metabolism are Load-dependent Introduction Lower-load (LL), higher-repetition resistance exercise training (RET) can increase muscle mass similar degree as higher-load (HL), lower-repetition RET. However, little is known about how LL and HL RET modulate other aspects of the RET phenotype such as satellite cells, myonuclei, and mitochondrial proteins. We aimed to investigate changes in muscle mass, muscle strength, satellite cell activity, myonuclear addition, and mitochondrial protein content following prolonged RET with LL and HL RET. Methods We recruited 21 young men and randomly assigned them to perform 10 weeks RET (leg press, leg extension and leg curl) three times per week with the following conditions: 80FAIL (80% one repetition maximum performed [1RM] to volitional fatigue), 30WM (30%1RM with volume matched to 80FAIL), and 30FAIL (30%1RM to volitional fatigue). Skeletal muscle biopsies were taken from the vastus lateralis pre- and post-RET intervention. Results After 10 weeks of RET, only 30FAIL and 80FAIL showed an increase in peak torque and type I fiber cross-sectional area (CSA) (p<0.05). Moreover, only 30FAIL resulted in a significant decrease in the myonuclear domain of type II muscle fibers and an increase in mitochondrial proteins related to autophagy, fission and fusion (all p<0.05). Conclusion We discovered that LL RET was effective at increasing the content of a number of mitochondrial proteins. Similar to previous research, we found that changes in muscle mass and strength were independent of load when repetitions were performed to volitional fatigue. Author for correspondence Prof. Chang Keun Kim, Ph.D. Human physiology, Korea National Sport University, 88-15 Oryun-dong, Songpa-gu, Seoul South Korea T: +82-2-410-6815 E: ckkim@knsu.ac.kr No research grant was received for this study. CONFLICT OF INTEREST. The authors declare that the results of the study are presented clearly, honestly and without fabrication, falsification or inappropriate data manipulation. The results of the present investigation do not constitute endorsement by ACSM. No conflict of interest or financial are declared by the authors. Accepted for Publication: 17 June 2019 © 2019 American College of Sports Medicine

Correlates of Children’s Physical Activity: A Canadian Multisite Study Purpose To inform future physical activity (PA) interventions among children, we investigated the correlates of PA among 8- to 12-year-olds in three regions of Canada: Ottawa, Trois-Rivières, and Vancouver. Methods We recruited 1,699 children (55.0% girls) in 37 schools located in urban, suburban, and rural areas that differed in socioeconomic status. Children wore a sealed SC-StepRx pedometer capable of measuring moderate-to-vigorous physical activity (MVPA) for 7 consecutive days. Children and one of their parents/guardians completed a questionnaire that captured multiple potential PA correlates. Publicly-available data on weather and neighbourhood walkability were obtained. Multiply-imputed gender-stratified linear mixed models were used to examine the correlates of daily step counts and MVPA while controlling for age, site, type of urbanization, and area-level socioeconomic status. Results Each additional hour spent outdoors was associated with higher PA in boys (+769 steps/day; +3.7 min MVPA/day) and girls (+596 steps/day; +3.5 min/day). Boys’ PA declined with age (-500 steps/day; -3.7 min/day). Boys were less active if they had a long-standing injury/illness (-1862 steps/day; -3.7 min/day) or their parents reported driving to work (-835 steps/day; -4.4 min/day), were worried about traffic (-982 steps/day; -6.4 min/day) or about other people in their neighbourhood (-1250 steps/day). Girls speaking neither English nor French at home were less active (-620 steps/day; -3.7 min/day). In girls, each °C increase in morning temperature was associated with 77 additional steps/day and each km increase in active school travel distance was associated with 0.5 more MVPA min/day. Conclusion Consistent with previous studies, our results suggest that PA interventions should aim to increase outdoor time. The observed gender differences in PA correlates suggest the need for a gender-sensitized approach to PA promotion. Corresponding author: Richard Larouche, PhD Assistant Professor, University of Lethbridge 4401 University Drive, office M3049 Lethbridge, Alberta, Canada, T1K 3M4 Phone 403-332-4439 Fax 403-329-2668 Email Richard.larouche@uleth.ca The ATIM study was sponsored by a grant-in-aid from the Heart and Stroke Foundation of Canada (grant number: G-15-0009021). Guy Faulkner holds a Canadian Institutes of Health Research- Public Health Agency of Canada (CIHR- PHAC) Chair in Applied Public Health. Conflicts of interest: Richard Larouche receives royalties from Elsevier for his book, Children’s Active Transportation, which is not cited in the present manuscript. The results of the present study do not constitute endorsement by ACSM. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 8 July 2019 © 2019 American College of Sports Medicine

Risk Estimates for Diabetes and Hypertension with Different Physical Activity Methods Purpose To estimate risks of incident Type 2 Diabetes (T2D) and Stage 2 and greater hypertension associated with self-reported and accelerometer-determined moderate-vigorous physical activity (MVPA) separately and adjusted for each other. Methods The sample included 2,291 black and white men and women, ages 38-50, in the CARDIA (Coronary Artery Risk Development in Young Adults) Fitness Study, conducted during the Year 20 core CARDIA exam. Accelerometer-determined (Actigraph, LLC. model 7164) MVPA (MVPA-Acc), assessed at Year 20, was defined as mins/day of counts >2020/min. Self-reported MVPA (MVPA-SR) was assessed at Year 20 using the CARDIA Physical Activity History. Incident T2D was ascertained at Years 25 and 30 from fasting glucose, 2 hr GTT, HbA1c or diabetes medication; incident hypertension was ascertained at those same times from measured blood pressure or use of antihypertensive medications. Modified Poisson regression models estimated relative risk (RR) of incident (Years 25 and 30) T2D or hypertension, associated with middle and high tertiles of Year 20 MVPA-Acc alone, Year 20 MVPA-SR alone, and both, adjusted for each other, relative to bottom tertile. Results In men, MVPA-Acc, but not MVPA-SR, was associated with a 37-67% decreased risk of incident T2D in a dose response relation that persisted with adjustment for BMI, Similar associations were observed in women, although the risk reduction was similar in the second and third tertiles, relative to the bottom tertile. In both men and women, MVPA-Acc was marginally associated with reduced risk of incident Stage 2 and greater hypertension, but only after adjustment for BMI, while MVPA-SR was not associated in either sex. Conclusions Accelerometer-determined MVPA may provide more consistent risk estimates for incident diabetes than self-reported MVPA. ADDRESS FOR CORRESPONDENCE: Barbara Sternfeld, PhD, Emeritus, Division of Research, Kaiser Permanente, 270 Purdue Ave., Kensington, CA 94708, bsternfeld@gmail.com. 510-847-6246 The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I & HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I). Accelerometer data collection was supported by grants R01 HL078972 from the NHLBI. This manuscript has been reviewed by CARDIA for scientific content. CONFLICT OF INTEREST: The authors have no conflicts to declare. The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM. Accepted for Publication: 24 June 2019. © 2019 American College of Sports Medicine

Impact of Exercise and Activity on Weight Regain and Musculoskeletal Health PostOVX The purpose of this study was to determine whether obesity and/or exercise training alters weight regain and musculoskeletal health after ovariectomy (OVX). Female rats were fed high fat diet (HFD) to reveal Obesity-Prone (OP) and Obesity-Resistant (OR) phenotypes. OP and OR exercising (EX) and sedentary (SED) rats were calorically restricted to lose 15% of body weight using medium fat diet (MFD). Rats were then maintained in energy balance for 8 weeks before OVX. Following OVX and a brief calorically limited phase, rats were allowed to eat ad libitum until body weight plateaued. Starting at weight loss, EX ran 1 h/d, 6 d/week, 15 m/min. Energy intake (EI), spontaneous physical activity (SPA), and total energy expenditure were evaluated at the end of weight maintenance preOVX, and at three time points postOVX: before weight regain, during early regain, and after regain. Data are presented as mean±SE. Exercise attenuated weight regain after OVX in OP only (OP-EX: 123±10g; OP-SED: 165±12g; OR-EX 121±6g; OR-SED: 116±6g), which was primarily an attenuation of fat gain. The early postOVX increase in EI explained much of the weight regain, and was similar across groups. EX improved bone strength, as did maintaining SPA. Group differences in muscle mitochondrial respiration were not significant. The large decrease in SPA due to OVX was persistent, but early weight regain was dependent on decreased SPA. In conclusion, leanness and exercise do not necessarily protect from OVX-induced weight gain. Exercise prevented weight gain in obese rats, but loss of SPA was the greatest contributor to postOVX weight gain. Thus, understanding the mechanisms resulting in reduction in SPA following ovarian hormone loss is critical in the prevention of menopause-associated metabolic dysfunction. Corresponding Author: Vanessa Sherk, PhD, Assistant Professor, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado School of Medicine, 12800 East 19th Avenue, Aurora, CO 80045, 303-724-0731. Vanessa.sherk@ucdenver.edu Funding Sources: P50 HD073063 (PSM, VDS), T32 DK007658 (VDS), KL2TR002534 (VDS), U54 AG062319 (PSM), P30 48520 (NORC), K99/R00 CA169430 (EDG), UL1TR002535 (JAH) TL1TR002533 (RF, DP). Disclosures: No conflicts of interest, financial or otherwise, are declared by the authors. Results of the study do not constitute endorsement by the American College of Sports Medicine. Accepted for Publication: 26 June 2019. © 2019 American College of Sports Medicine

Improving the Diagnosis of Nonfunctional Overreaching and Overtraining Syndrome Introduction This study aimed to simplify and optimize the distinction between non – functional overreaching (NFO) and overtraining syndrome (OTS) by developing a multivariate approach (discriminant analysis, DA) including hormonal and psychological changes measured during the Training Optimization (TOP) test. Methods Sensitivity of previously defined cut-off values for hypothalamic–pituitary–adrenal axis (HPA) hormonal changes were recalculated on a larger database (n=100). DA including hormonal and psychological variables measured during the TOP test was used to discriminate between NFO and OTS and predict the diagnosis of new cases. Results Adrenocorticotrophic hormone (ACTH) and prolactin (PRL) responses to the 2nd exercise test were most sensitive to NFO and OTS. Cut-off values for ACTH and PRL response to the 2nd test (NFO > cut-off value (200 %) > OTS), showed a sensitivity of 67% for ACTH and 93% for PRL in case of OTS and 74% for both ACTH and PRL in case of NFO. A DA including hormonal and psychological changes measured during the TOP test, resulted in the accurate diagnosis of NFO and OTS with 98% sensitivity. ACTH and PRL responses to the 1st and 2nd exercise test and feeling of fatigue were the most discriminating variables. Conclusion ACTH and PRL responses during the TOP test are the most sensitive markers to discriminate between NFO and OTS. DA including hormonal and psychological responses during the TOP test, can be used to optimize the diagnosis of NFO and OTS. Luk Buyse and Lieselot Decroix contributed equally to this paper. Corresponding author: Romain Meeusen, Pleinlaan 2, 1050 Elsene, Belgium, Romain.meeusen@vub.be. +32 (0) 2 629 27 32 The results of the present study do not constitute endorsement by ACSM. All authors confirm that they do not have any financial and personal relationships with other people or organizations that could inappropriately influence (bias) this work. No conflicts of interest to declare. The results are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. No source of funding to declare. Accepted for Publication: 30 June 2019. © 2019 American College of Sports Medicine

Load Carriage and Physical Exertion Influence Cognitive Control in Military Scenarios INTRODUCTION Physical exertion has both beneficial and detrimental effects on cognitive performance, particularly cognitive control. Research into physical exertion under conditions of load carriage is particularly important given that military personnel and first responders must perform optimally under such combinatorial physical stressors. The present work sought to characterize cognitive control as a function of physical exertion and load carriage in a military operational scenario. METHODS Thirty-one active-duty Soldiers underwent a four-hour operationally relevant and fatiguing scenario that included two one-hour foot marches under load carriage conditions of 8.8, 47.2, 50.7 kg on each of three separate days. During each foot march they completed five five-minute blocks of an auditory go/no-go task of response inhibition. RESULTS Results showed that response inhibition declined with increasing load carriage and physical exertion, as evidenced by lower proportion of correct responses, higher proportion of false alarms, and lower response sensitivity between all three load conditions, particularly upon successive foot marches and time blocks within each foot march. CONCLUSIONS The results support previous laboratory-based work on load carriage and physical exertion, and suggest that deteriorations in cognitive control witnessed in lab settings are more pronounced within realistic operational scenarios akin to those encountered by military personnel and first responders. Corresponding author: Grace E. Giles, US Army Combat Capabilities Development Command Soldier Center (CCDC Soldier Center), 10 General Greene Avenue, Natick, MA 01760. grace.e.giles4.civ@mail.mil This work was funded by the United States Army. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Conflicts of Interest. The authors have declared that no conflicts of interest exist. The opinions expressed herein are those of the authors and not necessarily of the United States Army. The results of the present study do not constitute endorsement by ACSM. Accepted for Publication: 29 June 2019. © 2019 American College of Sports Medicine

Feasibility of Two High-Intensity Interval Training Protocols in Cancer Survivors Purpose High-intensity interval training (HIIT) is a time-efficient and promising tool for enhancing physical fitness. However, there is lack of research concerning safety and feasibility of HIIT in cancer survivors. Therefore, two different HIIT protocols were investigated in terms of safety, feasibility, and acute exercise responses. Methods Forty cancer survivors (20 breast and 20 prostate cancer survivors, 62.9±9.2 years, BMI 27.4±3.9 kg·m-2, 6-52 weeks after the end of primary therapy) completed a maximal cardiopulmonary exercise test (CPET) and two HIIT protocols on a cycle ergometer: 10x1 min at peak power output (10x1) and 4x4 min at 85–95% peak heart rate (HR) (4x4). Safety (adverse events, AEs), acute physiological responses (HR; blood lactate concentration, bLa) and acute psychological responses (ratings of perceived exertion, RPE; enjoyment) were recorded. Results No major but three minor AEs occurred. Ninety-five percent of participants were able to complete each HIIT protocol. Estimated energy expenditure (159±15 vs. 223±45 kcal, p<0.001), HR (128±20 vs. 139±18 bpm; p<0.001), bLa (5.4±1.0 vs. 5.9±1.9 mmol·l-1; p=0.035) and RPE legs/breathing (13.8±2.0/13.1±2.0 vs. 14.6±2.1/14.3±2.0; p=0.038/0.003) were significantly higher in the 4x4. Enjoyment did not differ between protocols (p=0.301). Conclusions The two HIIT protocols as single sessions appear safe and in the vast majority of breast and prostate cancer survivors after the end of primary therapy also feasible and enjoyable. The 4x4 elicited higher energy expenditure and higher cardio-circulatory and metabolic strain and might therefore be preferred if a high training stimulus is intended. Corresponding author: Prof. Dr. Friederike Rosenberger, Working Group Exercise Oncology, Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany, Phone: 06221-56-35681, Fax: 06221-56-7109, Email: friederike.rosenberger@nct-heidelberg.de We thank the Dietmar Hopp Foundation for funding the study. Furthermore, we thank the German Cancer Research Center (DKFZ) for the study assessment support. Conflict of Interest disclosure: The authors declare no conflicts of interest. The results of the present study do not constitute endorsement by ACSM. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 24 June 2019 © 2019 American College of Sports Medicine

Exercise Intensity Matters in Chronic Nonspecific Low Back Pain Rehabilitation Introduction Exercise therapy (ET) is advocated as a treatment for chronic nonspecific low back pain (CNSLBP). However, therapy effect sizes remain low. In other chronic disorders, training at higher intensity has resulted in greater improvements on both general health related and disease specific outcomes compared to lower intensity ET. Possibly, high intensity training also improves effect sizes in CNSLBP. Objective To compare the effects of a high intensity ET program with a similar moderate intensity ET program on disability, pain, function, exercise capacity, and abdominal/back muscle strength in persons with CNSLBP. Methods In a randomized controlled trial, persons with CNSLBP performed a 12-week ET program (24 sessions, 1.5hours/session, 2x/week) at high (HIT) or moderate intensity (MIT). Questionnaires to assess disability (Modified Oswestry Index (MODI)), pain intensity (Numeric Pain Rating Scale (NPRS)), and function (Patient Specific Functioning Scale (PSFS)), a cardiopulmonary exercise test to assess exercise capacity (VO2max, cycling time), and a maximum isometric muscle strength test to assess abdominal/back muscle strength (maximum muscle torque) were administered at baseline and after the training program. Results Thirty-eight participants (HIT: n=19, MIT: n=19) were included (mean age: 44.1y, SD=9.8, 12 males). Groups did not differ at baseline. Between group differences (p<0.01) in favor of HIT were found for MODI, VO2max, and cycling time. Within group improvements (p<0.01) were found in both groups on MODI (HIT:-64%, MIT:-33%), NPRS (HIT:-56%, MIT:-39%), PSFS (HIT:+37%, MIT:+39%), VO2max (HIT:+14, MIT:+4%), cycling time (HIT:+18%, MIT:+13%), and back muscle strength (HIT:+10%, MIT:+14%). Conclusion HIT proved to be a feasible, well tolerated, and effective therapy modality in CNSLBP. Moreover, it shows greater improvements on disability and exercise capacity than a similar ET performed at moderate intensity. Corresponding author: Jonas Verbrugghe, Hasselt University, Faculty of Rehabilitation Sciences, REVAL, Gebouw A, Agoralaan 5, 3590, Diepenbeek, Belgium, Tel: +003211269239, jonas.verbrugghe@uhasselt.be This project is funded by the UHasselt research fund BOF New initiatives (project number R-5211). This funding source had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results. The authors would like to thank all the persons with CNSLBP that participated in this study. Conflict of Interest. The authors report no conflict of interest. Accepted for Publication: 24 June 2019 © 2019 American College of Sports Medicine

Lower Trapezius Weakness and Shoulder Complex Biomechanics during the Tennis Serve PURPOSE This study aimed to assess the effect of lower trapezius (LT) weakness on humeral and scapular kinematics and shoulder muscle activity during the tennis serve. METHODS Fifteen competitive male tennis players (age: 23.8 ± 3.4 years; height: 182.8 ± 6.7 cm; mass: 76.6 ± 8.7 kg; tennis experience: 15.6 ± 4.9 years) performed two tennis serves before and after selective fatigue of the LT (25-min electric muscle stimulation). During each tennis serve, racket, humeral and scapular kinematics and the activity of 13 shoulder muscles were recorded using an optoelectronic system synchronized with indwelling and surface electromyography. The serve was split into five phases, i.e., early and late cocking, acceleration, early and late follow-through. RESULTS Selective fatigue led to a 22.5 ± 10.4% strength decrease but did not alter maximum racket speed and humerothoracic joint kinematics. However, increased scapular upward rotation was observed in the acceleration (p=0.02) and early follow-through (p=0.01) phases. Decreased muscular activity was observed during the early cocking phase for the LT (p=0.01), during the acceleration phase for the LT (p=0.01), anterior deltoid (p=0.03), pectoralis major (p=0.04) and subscapularis (p=0.03), and during the early follow-through phase for the anterior deltoid (p=0.03) and LT (p=0.04). CONCLUSION LT weakness altered neither serve velocity nor humerothoracic joint kinematics, but impaired scapulothoracic kinematics and anterior shoulder muscle activation. Such alterations may reduce the subacromial space and jeopardize humeral head stability. These findings shed new light on the consequences of LT weakness, highlighting the importance of monitoring and strengthening this muscle in overhead athletes. Corresponding author: Isabelle Rogowski, UCB Lyon 1 – UFRSTAPS, 27-29, bd du 11 novembre 1918, 69622 Villeurbanne Cedex France, E-mail: isabelle.rogowski@univ-lyon1.fr This study was supported by Auvergne-Rhône-Alpes with the explora’doc program and by Mitacs with the globalink program. Conflict of interest. The authors declare no conflict of interest. Accepted for Publication: 21 June 2019 © 2019 American College of Sports Medicine

Reduced Active Muscle Stiffness after Intermittent Submaximal Isometric Contractions Purpose Whether muscle stiffness is influenced by fatigue remains unclear. Classical methods used to assess muscle stiffness provide a global measure at the joint level. As fatigue may selectively affect specific muscles, a joint-level approach may not be sensitive enough to detect potential changes in muscle stiffness. Taking advantage of ultrasound shear wave elastography, this study aimed to determine the influence of a fatiguing protocol involving intermittent submaximal isometric contractions on muscle shear modulus (an index of stiffness). Methods Shear modulus was measured on either the vastus lateralis (VL; n=9) or the abductor digiti minimi (ADM; n=10) before and after 15-mins of intermittent submaximal isometric contractions at 60% of maximal voluntary contraction (MVC; 4 s ON, 4 s OFF). An index of active muscle stiffness was estimated PRE and POST-fatigue as the slope of the linear regression established between shear modulus and absolute joint force up to 60% MVC. Results After the fatiguing exercise, MVC was significantly decreased by 22 ± 7 % and 32 ± 15 % for knee extension and little finger abduction, respectively (p<0.001). When compared to PRE-fatigue, the index of active muscle stiffness was 12 ± 15 % lower for the VL (p < 0.031) and 44 ± 19 % lower for the ADM (p < 0.001) POST-fatigue. Conclusion Although the present results cannot clearly determine the involved mechanisms, they demonstrate a decreased active muscle stiffness after a fatiguing task involving intermittent submaximal isometric contractions. Further studies should now determine whether this change in stiffness affects performance and risk of injury. CORRESPONDING AUTHOR: Thomas LAPOLE, Laboratoire Interuniversitaire de Biologie de la Motricité, Bâtiment IRMIS, 10 rue de la Marandière, 42270 Saint Priest en Jarez, thomas.lapole@univ-st-etienne.fr The authors declare they have no conflict of interest. The authors did not receive any funding for this study. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM. Accepted for Publication: 21 June 2019 © 2019 American College of Sports Medicine