Increasing Students’ Activity in Physical Education: Results of the SELF-FIT Trial Purpose To examine the effects of the SELF-FIT intervention on students’ moderate-to-vigorous physical activity (MVPA) and motivation in physical education (PE). Methods In a clustered randomized controlled trial, 667 students (mean age = 14.4 years, SD = 0.78) from 26 schools (i.e., clusters) were randomized into either an experimental group or a wait-list control group. Students in the experimental group received the SELF-FIT intervention, a school-based intervention designed to infuse fitness and game-like elements into PE using self-determination theory principles, while those in the control continued their classes using usual practices. Intervention content was provided by teachers who received training from the research team. The primary outcome was percentage of time spent in MVPA during PE. Secondary outcomes included basic psychological need satisfaction, motivation towards PE, leisure-time MVPA, and mental well-being. Data were analyzed using multi-level regression analyses and pre-specified interactions were tested (i.e., group*time*sex). Results Positive intervention effects were found on MVPA during PE (B = 4.00, 95% CI [2.96, 5.04], d = 0.36). Regarding the participants’ competence and autonomy need satisfaction, and autonomous motivation, the intervention effects were stronger in girls, compared to boys. Conclusions Fitness infusion and game-like elements, employed according to self-determination theory principles, can enhance students’ physical activity and motivation towards PE. This low-cost intervention has the potential to be scaled-up and disseminated in secondary schools. Corresponding author: Amy S Ha, Mailing address: Kwok Sports Building, The Chinese University of Hong Kong, Shatin, Hong Kong, Telephone: +852-39436083, Fax: +852-39421013, Email: sauchingha@cuhk.edu.hk This study was supported by the General Research Fund, University Grants Committee, Hong Kong (Project number: 14403214). The results of the study are presented honestly, and without fabrication, falsification, or inappropriate data manipulation. The results also do not constitute endorsement by ACSM. The authors have no potential conflict of interest to declare. Accepted for Publication: 11 September 2019 © 2019 American College of Sports Medicine

Physical Activity and Genome-wide DNA Methylation: The REGICOR Study Introduction DNA methylation may be one of the biological mechanisms underlying the health benefits of physical activity (PA). Our objective was to determine the association between PA and genome-wide DNA methylation at CpG level. Methods We designed a two-stage epigenome wide association study. In the discovery stage, we used 619 individuals from the REGICOR cohort. Next, we validated the CpGs suggestively associated with PA (p-value <10-5) in two independent populations (n=1,735 and 190, respectively). PA was assessed with validated questionnaires and classified as light (LPA), moderate (MPA), vigorous (VPA), moderate-vigorous (MVPA) and total PA (TPA). We examined linear and non-linear associations and meta-analyzed the results in the three populations. The linear associations were meta-analyzed with a fixed-effects model and the p-values of the non-linear associations with the Stouffer and Fisher methods. We established a p-value threshold that fulfilled Bonferroni criteria over the number of CpGs analyzed (0.05/421,940=1.185·10-7). Results In the meta-analyses, two CpG sites had a statistically significant non-linear association with MVPA. cg24155427 (p-value=1.19·10-9), located in an intergenic region in chromosome 1, has been previously associated with smoking, lupus and aging. cg09565397 (p-value=1.59·10-7), located within DGAT1 in chromosome 8, encodes an enzyme involved in triacylglycerol synthesis and has been associated with body mass index. Conclusion This population-based study identified two new, differentially methylated CpG sites with a non-linear dose-response relationship to MVPA. These associations must be additionally validated and may be considered for further research on the biological mechanisms underlying health benefits of PA. Author for correspondence: Roberto Elosua, MD, PhD, IMIM, Hospital del Mar Medical Research Institute, Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain, Telephone: (+34) 933 160800; Email: relosua@imim.es This project was funded by the Carlos III Health Institute–European Regional Development Fund (FIS PI12/00232; FIS PI15/00051, CIBERCV, CIBERESP, CIBERONC), and the Government of Catalonia through the Agency for Management of University and Research Grants (2014SGR240). S. Sayols-Baixeras was funded by the Instituto de Salud Carlos III-Fondos FEDER (IFI14/00007). A. Fernández-Sanlés was funded by the Spanish Ministry of Economy and Competitiveness (BES-2014–069718). The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195 and HHSN268201500001I). This manuscript was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or NHLBI. Additional funding for SABRe was provided by Division of Intramural Research, NHLBI, and Center for Population Studies, NHLBI. CONFLICT OF INTEREST: No conflict of interest to declare. The results of the present study do not constitute endorsement by the American College of Sports Medicine. The authors declare that the results of the study are presented clearly and honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 18 June 2019 © 2019 American College of Sports Medicine

Exertional Rhabdomyolysis: A Retrospective Population-based Study PURPOSE To evaluate the incidence and characteristics of exertional rhabdomyolysis (ER) in a population-based cohort. METHODS A retrospective cohort study was performed in Olmsted County, Minnesota, from 2003-2015. Incident ER cases were ascertained through the Rochester Epidemiology Project (REP) medical record linkage system through electronic searches of ICD-9 codes and clinical note text. Population incidence rate was calculated using corresponding calendar-year- and sex specific REP census populations. Descriptive statistics were used. RESULTS 431 cases in 430 patients met inclusion criteria for rhabdomyolysis; 4.9% of cases (n= 20; males n=18; Caucasian n=17) were ER, with one recurrence. There were no deaths secondary to ER. The age and sex adjusted incidence rate of ER was 1.06 ± 0.24 (95% CI 0.59-1.52) per 100,000 person-years. Endurance activity (n=7), manual labor (n=5), and weight lifting (n=4) were common causes. Complications included kidney injury (n=5), mild electrolyte abnormalities (n=10), elevated transaminases (n=12), and minor electrocardiographic abnormalities (n=4). A majority of patients were hospitalized (n=16) for a median of two days, had mild abnormalities in renal and liver function, and electrolytes; and were discharged without sequelae. CONCLUSION ER in the civilian population occurs at a much lower incidence than the military population. The most common causes were endurance exercise, manual labor, and weight lifting. The majority of cases were treated conservatively with intravenous fluid resuscitation during a brief hospital stay, and all were discharged without sequela. Only one case of recurrence occurred in this cohort, indicating the recurrence rate was low. Send correspondence to: Jonathan T. Finnoff, DO, Mayo Clinic Sports Medicine Center, 600 Hennepin Ave, #310, Minneapolis, MN 55403, 612-313-0526, Fax 612-313-0522, Finnoff.jonathan@mayo.edu The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. CONFLICTS OF INTEREST AND SOURCES OF FUNDING: Dr. Finnoff is on the Medical Advisory Boards for COVR Medical, Sanofi, and Aim Specialty Health; and receives royalties from Demos Publishing and Up to Date. No funding was required for this study. This study was made possible using the resources of the Rochester Epidemiology Project, which is supported by the National Institute on Aging of the National Institutes of Health under Award Number R01AG034676. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The results do not constitute endorsement by ACSM. Accepted for Publication: 17 September 2019 © 2019 American College of Sports Medicine

The Basics of Training for Muscle Size and Strength: A Brief Review on the Theory The periodization of resistance exercise is often touted as the most effective strategy for optimizing muscle size and strength adaptations. This narrative persists despite a lack of experimental evidence to demonstrate its superiority. In addition, the general adaptation syndrome, which provides the theoretical framework underlying periodization, does not appear to provide a strong physiological rationale that periodization is necessary. Hans Selye conducted a series of rodent studies which used toxic stressors to facilitate the development of the general adaptation syndrome. To our knowledge, normal exercise in humans has never been shown to produce a general adaptation syndrome. We question whether there is any physiological rationale that a periodized training approach would facilitate greater adaptations compared to non-periodized approaches employing progressive overload. The purpose of this paper is to briefly review currently debated topics within strength and conditioning and provide some practical insight regarding the implications these re-evaluations of the literature may have for resistance exercise and periodization. In addition, we provide some suggestions for the continued advancement within the field of strength and conditioning. Corresponding Author: Jeremy Paul Loenneke, PhD, P.O. Box 1848. University, MS 38677, Phone: (662) 915-5567, Fax: (662) 915-5525, Email: jploenne@olemiss.edu No sources of funding were used to assist in the preparation of this article. Authors declare that they have no conflicts of interest relevant to the content of this review. The results and data presented in this review are done so honestly, and without fabrication, falsification, or inappropriate data manipulation, and statement that results of the present study do not constitute endorsement by ACSM. Accepted for Publication: 16 September 2019 © 2019 American College of Sports Medicine

Accelerometer-measured Physical Activity, Reproductive Hormones, and DNA Methylation Introduction/Purpose Limited studies have examined the association of physical activity with reproductive hormones, DNA methylation, and pubertal status among adolescents. Methods Among 248 boys and 271 girls, we estimated daily physical activity levels based on 7 days of wrist-worn accelerometer data. We used an isotemporal substitution paradigm and sex-stratified regression models to examine the association of physical activity levels with 1) testosterone, cortisol, progesterone and androstenedione concentrations; 2) DNA methylation of long interspersed nucleotide (LINE-1) repeats, and the genes H19, hydroxysteroid (11-Beta) dehydrogenase 2 (HSD11B2) and peroxisome proliferator-activated receptor alpha (PPARA) from blood leukocytes; and 3) Tanner stages, adjusted for age, BMI and socioeconomic status. Results In boys, substituting 30 minutes of moderate physical activity for 30 minutes of sedentary behavior per day was associated with 29% (-49%, 0%) of lower testosterone, and 29% (4%, 61%) of higher progesterone. Substituting 30 minutes of light physical activity for sedentary behavior was associated with 13% (-22%, -2%) of lower progesterone. Among girls, 30 minutes of additional sedentary behavior was associated with 8% (-15%, 0%) of lower testosterone, and 24% (8%, 42%) of higher progesterone concentrations. Substituting 30 minutes of moderate physical activity for sedentary behavior was associated with 15% (0%, 31%) of higher cortisol, while substituting the same amount of light physical activity for sedentary behavior was associated with 22% (-39%, 0%) of lower progesterone. Substituting 30 minutes of vigorous physical activity for sedentary behavior per day was associated with almost six times higher levels (5.83 (1.79, 9.86)) of HSD11B2 methylation in boys. Conclusions Accelerometer-measured daily physical activity was associated with reproductive hormones and HSD11B2 DNA methylation, differed by sex and activity intensity levels. Corresponding author: Karen E. Peterson, Sc.D., 1415 Washington Heights, I-1867, Ann Arbor, Michigan 48109-2029, Email: karenep@umich.edu The authors acknowledge the research staff at participating hospitals and the American British Cowdray Hospital in Mexico City provide facilities used for this research. We thank the mothers and children for participating in the study. This work was supported by U.S. Environmental Protection Agency (US EPA) grants RD834800 and RD83543601 and National Institute for Environmental Health Sciences (NIEHS) grants P20 ES018171, P01 ES02284401, R01 ES007821, R01 ES014930, R01 ES013744, and P30 ES017885. This study was also supported and partially funded by the National Institute of Public Health/Ministry of Health of Mexico. The contents of this publication are solely the responsibility of the grantee and do not necessarily represent the official views of the US EPA or the NIH. Further, the US EPA does not endorse the purchase of any commercial products or services mentioned in the publication. Accepted for Publication: 10 September 2019 © 2019 American College of Sports Medicine

Impact of Exercise–Nutritional State Interactions in Patients with Type 2 Diabetes Introduction This study examines the role of nutritional status during exercise training in patients with type 2 diabetes mellitus by investigating the impact of endurance-type exercise training in the fasted versus the fed state on clinical outcome measures, glycemic control, and skeletal muscle characteristics in male type 2 diabetes patients. Methods Twenty-five male patients (HbA1c 57±3 mmol/mol (7.4±0.3%)) participated in a randomized 12-week supervised endurance-type exercise intervention, with exercise being performed in an overnight fasted state (FastEx, n=13) or after consuming breakfast (FedEx, n=12). Patients were evaluated for glycemic control, blood lipid profiles, body composition and physical fitness, and skeletal muscle gene expression. Results Exercise training was well tolerated without any incident of hypoglycemia. Exercise training significantly decreased whole-body fat mass (-1.6kg) and increased HDL concentrations (+2mg*dL-1), physical fitness (+1.7mL*min-1*kg-1) and fat oxidation during exercise in both groups (PTIME<0.05), with no between group differences (PTIME*GROUP>0.05). HbA1c concentrations significantly decreased after exercise training (PTIME<0.001), with a significant greater reduction in FedEx (-0.30±0.06%) compared to FastEx (-0.08±0.06%; mean difference 0.21%; PTIME*GROUP=0.016). No interaction effects were observed for skeletal muscle genes related to lipid metabolism or oxidative capacity. Conclusion Endurance-type exercise training in the fasted or fed state do not differ in their efficacy to reduce fat mass, increase fat oxidation capacity, increase cardiorespiratory fitness and HDL concentrations or their risk of hypoglycemia in male patients with type 2 diabetes. Glycated haemoglobin seems to be improved more with exercise performed in the post-prandial compared with the post-absorptive state. Corresponding author: Kenneth Verboven, PhD, Hasselt University, Faculty of Rehabilitation Sciences; Agoralaan, Building A, 3590 Diepenbeek, Belgium; e-mail: kenneth.verboven@uhasselt.be; tel. +32-11-286949 Shared last authors: Patrick Calders, Dominique Hansen Grant acknowledgement: Yvonne and Jacques Francois de Meurs grant (King Baudouin Fund, 2013). The authors declare that they have no conflict of interest in relation to this work. The results of the present study do not constitute endorsement by ACSM. The results presented are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 9 September 2019 © 2019 American College of Sports Medicine

Daily Changes of Resting Metabolic Rate in Elite Rugby Union Players INTRODUCTION Preparation for competitive contact sport has been extensively researched. There are, however, limited data to guide players as to how the demands of their sport affect the energy requirements of recovery. We aimed to provide novel data on changes in resting metabolic rate (RMR) in contact sport athletes and relate these to the physical demands of training and competition. METHODS 22 Elite professional Premiership Rugby Union players were recruited to the study. Indirect calorimetry (Vyntus CPX canopy, CareFusion) was used to measure RMR each morning of the competitive game week, in a fasted, rested state. External loads for training and game play were monitored and recorded using global positioning systems (Catapult Innovations, Australia), whilst internal loads were tracked using rate of perceived exertion scales. Collisions were reviewed and recorded by expert video analysts for contacts in general play (breakdown and tackle area) or the set piece (scrum or maul). RESULTS There were significant (p=0.005) mean increases in RMR of ≈231kcal the morning after (GD+1) and 3 days after the game (GD+3), compared with the day before the game (GD-1). The players were exposed to internal and external loads during the training week comparable to that of a match day, however, despite the equivocal loads between training and game play, there were no significant increases in RMR following training. CONCLUSION The collisions experienced in rugby match play are likely to be responsible for the significant increases in RMR at GD+1 and GD+3. Consequently, the measurement of RMR via indirect calorimetry may provide a novel non-invasive measure of the effects of collisions. This study provides a novel insight to the energy requirements of recovering from contact sport. Address for correspondence: Professor Graeme L. Close, Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Tom Reilly Building, Bryom St Campus, Liverpool, L3 3AF, UK, g.l.close@ljmu.ac.uk The research was funded by the rugby club as part of the post graduate work of JH. The authors report no potential conflict of interest. The results of the current study do not constitute endorsement by ACSM. All results presented here are done so clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 14 September 2019 © 2019 American College of Sports Medicine

Cardiovascular Testing Detects Underlying Dysfunction in Childhood Leukemia Survivors Purpose Childhood leukemia survivors commonly develop late-onset cardiovascular disease following treatment with anthracyclines. Resting echocardiogram is the standard procedure for monitoring cardiac health but this method may not be sensitive enough to detect subclinical injury. Exercise echocardiography may provide a viable alternative. Methods: Nineteen (9 male; age, 19±3 years) anthracycline-treated survivors of childhood leukemia and 17 (8 male) healthy individuals of similar age (22±2 years) were recruited. All survivors had normal resting echocardiography upon recruitment. Exercise echocardiography was performed using contemporary imaging techniques. Flow mediated dilation (FMD), body composition, and cardiorespiratory fitness (V[Combining Dot Above]O2peak) were assessed to determine predisposition to additional disease. Results: Mitral valve peak flow velocity in late diastole (interaction, p=0.007) increased from rest in survivors (p=0.023) and controls (p=0.020) immediately post exercise but did not recover again in the survivors (exercise-recovery, p=0.784) following recuperation. Consequently, E/A ratio (interaction, p<0.001) was lower in the survivors at recovery (p<0.001). Survivors had reduced FMD (7.88±1.70 vs. 9.65±2.83; p=0.030), maximal and recovery heart rates (p=0.001;p<0.001), minute ventilation (p<0.001), and V[Combining Dot Above]O2peak (absolute, 2.64±0.62 vs. 3.14±0.74 L·min-1, p=0.034; relative, 36.78±11.49 vs. 45.14±6.80 ml·kg-1·min-1; p=0.013) compared to controls. They also had higher total body fat (percentage, p=0.034; mass, p=0.024) and fat mass in the central (p=0.050), peripheral (p=0.039) and visceral (p<0.001) regions. Survivors matched controls with regards to height (173.0±7.8 cm vs. 173.8±9.1 cm; p=0.796), body mass (76.16±19.05 kg vs. 70.07±13.96 kg; p=0.287) and body mass index (25.2±5.1 vs. 22.9±2.7; p=0.109). Conclusion: Exercise echocardiography unmasked subclinical diastolic dysfunction that may indicate late anthracycline toxicity in apparently-healthy survivors of childhood leukemia. Presence of secondary risk-factors indicates increased predisposition to comorbidities and highlights the importance of assessing cardiovascular health during follow-up. Treya M Long (Corresponding Author): 305/30 The Circus, Burswood WA 6100, AUSTRALIA. Phone: (+61) 0407 690 629. Email: treya.long@research.uwa.edu.au This work was supported by The Heart Foundation Vanguard Grant (LHN) award number 101412. The results of the present study do not constitute endorsement by ACSM and are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. There are no other conflicts of interest to acknowledge. Accepted for Publication: 28 August 2019 © 2019 American College of Sports Medicine

Cachexia Disrupts Diurnal Regulation of Activity, Feeding, and Muscle mTORC1 in Mice Introduction Cancer cachexia is characterized by severe skeletal muscle mass loss, which is driven by decreased muscle protein synthesis and increased protein degradation. Daily physical activity and feeding behaviors exhibit diurnal fluctuations in mice that can impact the systemic environment and skeletal muscle signaling. Purpose We investigated the effect of cancer cachexia on the diurnal regulation of feeding, physical activity, and skeletal muscle mTORC1 signaling in tumor bearing mice. We also examined the impact of increased physical activity on diurnal behaviors and skeletal muscle mTROC1 signaling in the cancer environment. Methods Physical activity and feeding behaviors were measured for 4 consecutive days prior to sacrifice in male C57BL/6 (B6; N=24) and ApcMin/+ (MIN; N=22) mice at 7:00AM and 7:00PM under ad libitum condition. A subset of B6 (N=16) and MIN (N=19) mice were given wheel access for 2-weeks prior to diurnal behavior measurements. Gastrocnemius muscle protein expression was examined. Results MIN mice demonstrated altered diurnal fluctuations in feeding and activity, compared to the B6. Interestingly, cachexia did not alter MIN total food intake, but dramatically reduced cage physical activity. As a measurement of mTORC1 activity, 4E-BP1 phosphorylation increased following the dark cycle in B6 and pre-cachectic MIN mice, while rpS6 phosphorylation was only increased following the dark cycle in MIN mice. MIN 4E-BP1 phosphorylation at the end of the light cycle was significantly correlated with cachexia progression and reduced physical activity. Voluntary wheel running increased light cycle MIN 4E-BP1 phosphorylation and attenuated muscle mass loss. Conclusion The cancer environment can alter diurnal feeding and physical activity behaviors in tumor bearing mice, which are linked to the progression of cachexia and muscle wasting. Furthermore, suppressed physical activity during cachexia is associated with decreased skeletal muscle mTORC1 signaling. Corresponding Author: James A. Carson, Ph.D., College of Health Professions, University of Tennessee Health Science Center, 630 Madison Avenue, Suite 633, Memphis, TN 38163. Office Phone: 901-448-5588. Email: jcarso16@uthsc.edu This work was supported by National Institute of Health Grants RO1 CA-121249 (NCI) to J.A. Carson; SPARC Graduate Research Grant from the Office of the Vice President for Research at the University of South Carolina to B.R. Counts. 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. Conflict of Interest: The authors have no conflicts of interest to report. Accepted for Publication: 27 August 2019 © 2019 American College of Sports Medicine

Effects of Exergaming on Cognition and Gait in Older Adults at Risk for Falling Purpose To test whether an 8-week exergaming (EG) program would improve cognition and gait characteristics compared to a traditional physical exercise (TPE) program in older adults at risk for falling. Methods A pilot quasi-experimental study was conducted in adults aged ≥ 65 years at risk for falls, living in senior communities. Participants enrolled (N=35) in either exercise program offered twice weekly for 8 weeks. Cognition and single-task and dual-task gait characteristics were measured before and after the 8-week exercise intervention. For each outcome, a repeated measure ANCOVA adjusted for age, gender, and exercise intensity (ratings of perceived exertion, RPE) was used to examine the Group x Time interaction. Results Twenty-nine participants (aged 77±7 yrs) completed either the EG program (n=15) or the TPE program (n=14). Statistically significant Group x Time interactions were observed in Trail Making Test Part A (TMT-A, p<0.05) and single-task gait speed, stride length, swing time percentage, and double support percentage (all p<0.05) and marginal group differences were observed in Mini-Mental State Examination (MMSE, p=0.07), all favoring the EG program. There were no statistically significant group differences in dual-task gait measurements except for swing time percentage and double support percentage, favoring the EG program. Conclusions An 8-week EG program for older adults at risk for falls contributed to modest improvements in a number of cognitive measures and single-task but limited improvements in dual-task gait measures, compared to TPE. These findings support the need for larger trials to determine cognitive and mobility benefits related to exergaming. Corresponding Author: Tongjian You, PhD, Department of Exercise and Health Sciences, College of Nursing and Health Sciences, University of Massachusetts Boston, Boston, MA 02125, USA. Telephone: 617-287-5934. Email: tongjian.you@umb.edu The study was funded by a Doctoral Dissertation Research Grant from the University of Massachusetts Boston. The authors declare no conflict of interest. The results of the study do not constitute endorsement by the American College of Sports Medicine. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 10 September 2019 © 2019 American College of Sports Medicine