Medicine & Science in Sports & Exercise

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 82 healthy community-dwelling older adults (71.8 + 6.2 y) performed 11 weeks of structured RT (2.5 days/week) in treatment groups differing only by the method used to increase training loads. These included percent 1RM (%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 RES 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 foot timed up-and-go, gallon jug transfer test, 30 second 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. Corresponding author: Dr. Andrew N.L. Buskard, Laboratory of Neuromuscular Research and Active Aging, Department of Kinesiology and Sport Sciences, University of Miami, 1507 Levante Avenue, Coral Gables, Florida, 33146, USA, Tel: +1 305 284 3105, Fax: +1 305 284 3003, E-mail: andrewbuskard@miami.edu No outside funding was obtained for this study, but equipment and laboratory support were provided by the University of Miami under the auspices of graduate research support for the first author's PhD in exercise physiology. The authors have no professional relationships with companies or manufacturers who will benefit from the results of the study. The results of this study do not constitute an endorsement by the American College of Sports Medicine (ACSM). The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 8 May 2019 © 2019 American College of Sports Medicine

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 days of age, all mice pups were weaned and fed a non-restrictive healthy diet for the remainder of the study. At 45 days 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 hind leg was evaluated for calsequestrin 1 and annexin A6 expression. RESULTS The PUN female mice (15,365 ±8,844 revolutions·day-1) had a reduction (P=0.0221) in wheel revolutions per day as compared to the GUN (38,667±8648 revolutions·day-1) and CON females (36,421.0± 6,700 revolutions·day-1). PUN female mice also expressed significantly higher Drd1compared (P=0.0247) to the other groups. PUN female soleus had a higher expression of calsequestrin 1, along with more Type IIb fibers (P=0.0398). CONCLUSION 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. Address for correspondence: David P. Ferguson, 308 W. Circle Dr. Room 27S, East Lansing, MI, 48824, 517-355-4763, Fergu312@msu.edu This project was funded by Michigan State University Department of Kinesiology Start up funds. The authors have no conflicts of interest to report, and the results of this study are not endorsed by the ACSM. The results of this study are also presented clearly and honestly, without inappropriate data manipulation, fabrication, or falsification. Accepted for Publication: 4 May 2019 © 2019 American College of Sports Medicine

The Longitudinal Associations of Fitness and Motor Skills with Academic Achievement PURPOSE This study aimed to examine both independent and dependent longitudinal associations of physical fitness (PF) components with academic achievement. METHODS 954 4th-7th graders (9-15y [Mage=12.5y], 52% girls) from nine schools throughout Finland participated in a two-year follow-up study. Register-based academic achievement scores (grade point average [GPA]) and PF were assessed in the spring of 2013-2015. Aerobic fitness was measured with a maximal 20-m shuttle run test, muscular fitness with curl-up and push-up tests, and motor skills with a 5-leaps test and a throwing-catching combination test. Structural equation modelling was applied to examine the longitudinal associations adjusting for age, gender, pubertal stage, body fat percentage, learning difficulties and mother’s education. RESULTS The change in aerobic and muscular fitness were positively associated with the change in GPA (B=0.27, 99% confidence interval CI=0.06-0.48; B=0.36, CI=0.11-0.63, respectively), while the change in motor skills were not associated with the change in GPA. Better motor skills in year 2 predicted better GPA a year later (B=0.06, CI=0.00-0.11; B=0.06, CI=0.01-0.11), while aerobic and muscular fitness did not predict GPA. GPA in year 1 predicted both aerobic (B=0.08, CI=0.01-0.15) and muscular (B=0.08, CI=0.02-0.15) fitness, and motor skills (B=0.08, CI=0.02-0.15) a year later. CONCLUSION The changes in both aerobic and muscular fitness were positively associated with change in academic achievement during adolescence, while the change in motor skills had only borderline significant association. However, better motor skills, although not systematically, independently predicted better academic achievement one year later, while aerobic or muscular fitness did not. Better academic achievement predicted better motor skills, aerobic and muscular fitness. Developmental changes in adolescence may induce parallel and simultaneous changes in academic achievement and PF. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Corresponding author: Heidi J. Syväoja, LIKES Research Centre for Physical Activity and Health, Jyväskylä, Finland, Rautpohjankatu 8, FI-40700, Finland, tel. +358 (0)400248133, fax +358207629501, heidi.syvaoja@likes.fi This study was funded by the Academy of Finland (grant 273971) and the Finnish Ministry of Education and Culture (OKM/92/626/2013). The authors declare that there are no conflicts of interest. The results of the present study do not constitute endorsement by ACSM. The Authors declare that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for publication: 26 April 2019. © 2019 American College of Sports Medicine

Estimating Tibial Stress throughout the Duration of a Treadmill Run Introduction Stress fractures of the tibia are a problematic injury amongst runners of all levels. Quantifying tibial stress using a modelling 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-minute prolonged treadmill run. Methods Synchronised force and kinematic data were collected during prolonged treadmill running from fourteen recreational male rearfoot runners on two separate occasions. During each session, participants ran at their preferred speed for two consecutive 20-minute runs, separated by a 2-minute pause. The tibia was modelled as a hollow ellipse and bending moments and stresses at the distal 1/3 of the tibia were estimated using beam theory combined with inverse dynamics and musculoskeletal modelling. Results Intraclass correlation coefficients indicated good-to-excellent repeatability for peak stress values between sessions. Peak anterior and posterior stresses increased following 20 minutes of prolonged treadmill running and were 15% and 12% greater respectively after 40 minutes of running compared with the start of the run. Conclusion The hollow elliptical tibial model presented is a repeatable tool that can be utilised 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. Corresponding author: Hannah Rice, PhD, Sport and Health Sciences, Richards Building, St Luke’s Campus, Heavitree Road, Exeter, EX1 2LU, UK, H.Rice@exeter.ac.uk This research was supported by Brooks Running Company, Seattle, WA, USA. The authors declare no conflicts of interest. 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: 8 May 2019 © 2019 American College of Sports Medicine

Myocardial Adaptations to Competitive Swim Training Purpose Swim training is performed in the prone or supine position and obligates water immersion, factors which may augment cardiac volume-loading more than other endurance sports. At present, prospective data defining the cardiac responses to swim training are lacking. We therefore studied myocardial adaptations among competitive swimmers in order to establish a causal relationship between swim training and left ventricular (LV) remodeling. Methods Collegiate swimmers were studied before and after a 90-day period of training intensification. Transthoracic echocardiography was used to examine LV structural and functional adaptations under resting conditions and during an acute LV afterload challenge generated by isometric handgrip testing (IHGT). A sedentary control population was identically studied with IHGT. Results In response to a discrete period of swim training intensification, athletes (n=17, 47% female, 19±0.4 years old) experienced eccentric LV remodeling, characterized by proportionally more chamber dilation than wall thickening, with attendant enhancements of resting LV systolic (LV twist) and diastolic (early and late phase tissue velocities) function. Compared to baseline and controls, athletes post training demonstrated greater systolic twist impairment during IHGT. However, training induced LV dilation coupled with gains in diastolic function offset this acquired systolic susceptibility to acute afterload resulting in relative preservation of stroke volume during IHGT. Conclusion Swim training, a sport characterized by unique cardiac loading conditions, stimulates eccentric LV remodeling with concomitant augmentation of systolic twist and diastolic relaxation. This volume mediated cardiac remodeling appears to result in greater systolic susceptibility to acute afterload challenge. Further work is required to establish how training-induced changes in function translate to human performance and whether these are accompanied by physiologic trade-offs with relevance to common forms of heart disease. Address for correspondence: Aaron Baggish, M.D. Cardiovascular Performance Program Massachusetts General Hospital 55 Fruit Street, Yawkey 5B Boston, MA, 02114 Email: abaggish@partners.org This study was funded in part by a research grant from the American Heart Association FTF2220328 (A.L.B.). 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 the ACSM. CONFLICTS OF INTEREST: The authors have no conflicts of interest to report. Accepted for publication: 22 April 2019. © 2019 American College of Sports Medicine

The Physiological Roles of Carnosine and β-Alanine in Exercising Human Skeletal Muscle Carnosine (β-alanyl-L-histidine) plays an important role in exercise performance and skeletal muscle homeostasis. Dietary supplementation with the rate-limiting precursor β-alanine leads to an increase in skeletal muscle carnosine content, which further potentiates its effects. There is significant interest in carnosine and β-alanine across athletic and clinical populations. Traditionally, attention has been given to performance outcomes with less focus on the underlying mechanism(s). Putative physiological roles in human skeletal muscle include acting as an intracellular pH buffer, modulating energy metabolism, regulating Ca2+ handling and myofilament sensitivity, and scavenging of reactive species. Emerging evidence shows that carnosine could also act as a cytoplasmic Ca2+–H+ exchanger and form stable conjugates with exercise-induced reactive aldehydes. The enigmatic nature of carnosine means there is still much to learn regarding its actions and applications in exercise, health and disease. In this review, we examine the research relating to each physiological role attributed to carnosine, and its precursor β-alanine, in exercising human skeletal muscle. Corresponding Author: Prof. Craig Sale, Nottingham Trent University, Erasmus Darwin Building, Clifton Lane, Nottingham, United Kingdom, NG11 8NS. Tel: 0115 8483505, craig.sale@ntu.ac.uk No funding was received for writing this manuscript. GGA has been supported financially by Fundação de Amparo à Pesquisa do Estado de São Paulo (FASESP; grant number: 2014/11948-8). MDT has received a British Council award to support a studentship focused on research into carnosine (grant number: 209524711). JJM, GGA, and MDT collectively declare that they have no competing interests. CS has received β-alanine supplements free of charge from Natural Alternatives International (NAI) for use in experimental investigations; NAI have also supported open access page charges for some manuscripts. The review is presented honestly, and without fabrication, falsification, or inappropriate data manipulation. The viewpoints expressed in the review do not constitute endorsement by the American College of Sports Medicine. Accepted for Publication: 29 April 2019 © 2019 American College of Sports Medicine

Effects of Instrument-assisted Soft Tissue Mobilization on Musculoskeletal Properties Purpose Instrument-assisted soft tissue mobilization (IASTM) has been reported to improve joint range of motion (flexibility). However, it is not clear whether this change in the joint range of motion is accompanied by any alterations in the mechanical and/or neural properties. This study aimed to investigate the effects of IASTM in plantar flexors and Achilles tendon on the mechanical and neural properties of them. Methods This randomized, controlled, crossover study included 14 healthy volunteers (11 men and 3 women, 21–32 y). IASTM was performed on the skin over the posterior part of the lower leg for 5 min and targeted the soft tissues (gastrocnemii, soleus, and tibialis posterior muscles; overlying deep fascia; and Achilles tendon). As a control condition, the same participants rested for 5 min between pre and post measurements without IASTM on a separate day. The maximal ankle joint dorsiflexion angle (dorsiflexion range of motion), peak passive torque (stretch tolerance), and ankle joint stiffness (slope of the relationship between passive torque and ankle joint angle) during measurement of dorsiflexion range of motion and muscle stiffness of the triceps surae (using shear wave elastography) were measured before and immediately after the interventions. Results Following IASTM, the dorsiflexion range of motion significantly increased by 10.7 ± 10.8% and ankle joint stiffness significantly decreased by -6.2 ± 10.1%. However, peak passive torque and muscle stiffness did not change. All variables remained unchanged in the repeated measurements of controls. Conclusion IASTM can improve joint range of motion, without affecting the mechanical and neural properties of the treated muscles. Corresponding author: Naoki Ikeda, Faculty of Sport Sciences, Waseda University, Mikajima 2-579-15, Tokorozawa, Saitama 359-1192, Japan, Phone: +81-4-2947-6766, Fax: +81-4-2947-6766, E-mail: n.ikeda2@kurenai.waseda.jp This study was supported by JSPS KAKENHI (grant number 16H01870). The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation, and the results of the present study do not constitute endorsement by the American College of Sports Medicine. The authors declare no conflict of interest. None of the authors has a professional relationship with any company or manufacturer who will benefit from the results of the present study. Accepted for Publication: 8 April 2019 © 2019 American College of Sports Medicine

Low-Carbohydrate Training Increases Protein Requirements of Endurance Athletes Introduction Training with low-carbohydrate (CHO) availability enhances markers of aerobic adaptation and has become popular to periodize throughout an endurance-training program. However, exercise-induced amino acid oxidation is increased with low muscle glycogen, which may limit substrate availability for post-exercise protein synthesis. We aimed to determine the impact of training with low-CHO availability on estimates of dietary protein requirements. Methods Eight endurance-trained males (27±4y, 75±10kg, 67±10ml·kg body mass-1·min-1) completed two trials matched for energy and macronutrient composition but with differing CHO periodization. In the low-CHO availability trial (LOW), participants consumed 7.8g CHO·kg-1 prior to evening high-intensity interval training (HIIT; 10 x 5 min at 10-km race pace, 1 min rest) and subsequently withheld CHO post-exercise (0.2g·kg-1). In the high-CHO availability trial (HIGH), participants consumed 3g CHO·kg-1during the day before HIIT, and consumed 5g CHO·kg-1that evening to promote muscle glycogen resynthesis. A 10km run (~80% HRmax) was performed the following morning, fasted (LOW) or 1h after consuming 1.2g CHO·kg-1 (HIGH). Whole-body phenylalanine flux (PheRa) and oxidation (PheOx) were determined over 8h of recovery via oral [13C]phenylalanine ingestion, according to standard indicator amino acid oxidation methodology, while consuming sufficient energy, 7.8g CHO·kg-1·d-1, and suboptimal protein (0.93g·kg-1·d-1). Results Fat oxidation (indirect calorimetry) during the 10-km run was higher in LOW compared to HIGH (0.99±0.35 vs. 0.60±0.26 g·min-1, p<0.05). PheRa during recovery was not different between trials (p>0.05) whereas PheOX (reciprocal of protein synthesis) was higher in LOW compared to HIGH (8.8±2.7 vs. 7.9±2.4 umol·kg-1·h-1, p<0.05), suggesting a greater amino acid requirement to support rates of whole-body protein synthesis. Conclusion Our findings suggest that performing endurance exercise with low-CHO availability increases protein requirements of endurance athletes. Address for Correspondence: Daniel R. Moore, Assistant Professor, Faculty of Kinesiology and Physical Education, University of Toronto, 100 Devonshire Place Toronto, ON M5S 2C9, CANADA, Tel:416-946-4088, Email: dr.moore@utoronto.ca This study was supported by grants to DRM from Ajinomoto Innovation Alliance Program, Canadian Foundations for Innovation and Ontario Research Fund. JBG held a Canadian Institutes of Health Research Postdoctoral Fellowship. 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. The authors report no conflicts of interest. Accepted for Publication: 6 May 2019 © 2019 American College of Sports Medicine

One Week of Step Reduction Lowers Myofibrillar Protein Synthesis Rates in Young Men PURPOSE Across the lifespan, physical activity levels decrease and time spent sedentary typically increases. However, little is known about the impact that these behavioural changes have on skeletal muscle mass regulation. The primary aim of this study was to use a step reduction model to determine the impact of reduced physical activity and increased sedentary time on daily myofibrillar protein synthesis rates in healthy young men. METHODS Eleven men (22±2 y) completed 7 days of habitual physical activity (HPA) followed by 7 days of step reduction (SR). Myofibrillar protein synthesis rates were determined during HPA and SR using the deuterated water (2H2O) method combined with the collection of skeletal muscle biopsies and daily saliva samples. Gene expression of selected proteins related to muscle mass regulation and oxidative metabolism were determined via real time RT-qPCR. RESULTS Daily step count was reduced by approximately 91% during SR (from 13054±2763 to 1192±330 steps·d-1; P<0.001) and this led to an increased contribution of sedentary time to daily activity (73±6 to 90±3%; P<0.001). Daily myofibrillar protein synthesis decreased by approximately 27% from 1.39±0.32 %·d-1 during HPA to 1.01±0.38 %·d-1 during SR (P<0.05). MAFbx and myostatin mRNA expression were up-regulated whereas mTOR, p53 and PDK4 mRNA expression were down-regulated following SR (P<0.05). CONCLUSION One week of reduced physical activity and increased sedentary time substantially lowers daily myofibrillar protein synthesis rates in healthy young men. Corresponding author: Dr Gareth A. Wallis, School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston, B15 2TT, UK. Phone: +44(0) 121 414 4129. Email: g.a.wallis@bham.ac.uk B.J.S is funded by a University of Birmingham ‘Exercise as Medicine’ PhD studentship. None of the authors have any conflicts of interest or financial disclosures to declare. The results of the present study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation and do not constitute endorsement by the American College of Sports Medicine. Accepted for publication: 2 May 2019. © 2019 American College of Sports Medicine

Protein Supplementation Does Not Augment Adaptations to Endurance Exercise Training Introduction Recently, it has been speculated that protein supplementation may further augment the adaptations to chronic endurance exercise training. We assessed the impact of protein supplementation during chronic endurance exercise training on whole-body oxidative capacity (VO2max) and endurance exercise performance. Methods In this double-blind, randomized, parallel placebo-controlled trial, sixty recreationally active males (age: 27±6 y; BMI: 23.8±2.6 kg·m-2; VO2max: 47±6 mL·min-1·kg-1) were subjected to 12 weeks of triweekly endurance exercise training. After each session and each night before sleep, participants ingested either a protein supplement (PRO; 28.7 g casein protein) or an isoenergetic carbohydrate placebo (PLA). Before and after the 12 weeks of training, VO2max and endurance exercise performance (~10-km time-trial) were assessed on a cycle ergometer. Muscular endurance (total workload achieved during 30 reciprocal isokinetic contractions) was assessed by isokinetic dynamometry and body composition by DXA. Mixed-model ANOVA was applied to assess whether training adaptations differed between groups. Results Endurance exercise training induced an 11±6% increase in VO2max (time effect, P<0.0001), with no differences between groups (PRO: 48±6 to 53±7 mL·min-1·kg-1; PLA: 46±5 to 51±6 mL·min-1·kg-1; time×treatment interaction, P=0.50). Time to complete the time-trial was reduced by 14±7% (time effect, P<0.0001), with no differences between groups (time×treatment interaction, P=0.15). Muscular endurance increased by 6±7% (time effect, P<0.0001), with no differences between groups (time×treatment interaction, P=0.84). Leg lean mass showed an increase following training (P<0.0001), which tended to be greater in PRO compared with PLA (0.5±0.7 vs 0.2±0.6 kg, respectively; time×treatment interaction, P=0.073). Conclusion Protein supplementation after exercise and before sleep does not further augment the gains in whole-body oxidative capacity and endurance exercise performance following chronic endurance exercise training in recreationally active, healthy young males. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. These authors contributed equally to this work, Kristin L. Jonvik, Kevin J.M. Paulussen Address for correspondence: Dr. Jan-Willem van Dijk, Institute of Sports and Exercise Studies, HAN University of Applied Sciences, PO Box 6960, 6503 GL Nijmegen, The Netherlands, Tel: +(31) 6 55227849, Email: janwillem.vandijk@han.nl This project was funded by the Dutch Ministry of Economic Affairs (Topsector Agri&Food), award number: AF16501 (PPS Allowance). KLJ, KJMP, SLD and IJMC declare that they have no conflict of interest. FCW, LJCvL and JWvD have received research grants, consulting fees, and/or speaking honoraria from FrieslandCampina. LJCvL has received research grants, consulting fees, and speaking honoraria from Pepsico/Gatorade. AMHH is an employee at FrieslandCampina. Accepted for Publication: 22 April 2019 © 2019 American College of Sports Medicine