Skeletal muscle adaptations to high-intensity, low-volume concurrent resistance and interval training in recreationally active men and women.

This study compared the structural and cellular skeletal muscle factors underpinning adaptations in maximal strength, power, aerobic capacity, and lean body mass to a 12-week concurrent resistance and interval training program in men and women. Recreationally active women and men completed three training sessions per week consisting of high-intensity, low-volume resistance training followed by interval training performed using a variety upper and lower body exercises representative of military occupational tasks. Pre- and post-training vastus lateralis muscle biopsies were analyzed for changes in muscle fiber type, cross-sectional area, capillarization, and mitochondrial biogenesis marker content. Changes in maximal strength, aerobic capacity, and lean body mass (LBM) were also assessed. Training elicited hypertrophy of type I (12.9%; p = 0.016) and type IIa (12.7%; p = 0.007) muscle fibers in men only. In both sexes, training decreased type IIx fiber expression (1.9%; p = 0.046) and increased total PGC-1α (29.7%, p < 0.001) and citrate synthase (11.0%; p < 0.014) content, but had no effect on COX IV content or muscle capillarization. In both sexes, training increased maximal strength and LBM but not aerobic capacity. The concurrent training program was effective at increasing strength and LBM but not at improving aerobic capacity or skeletal muscle adaptations underpinning aerobic performance.

Acute Resistance Exercise Modifies Extracellular Vesicle miRNAs Targeting Anabolic Gene Pathways: A Prospective Cohort Study.

BACKGROUND: Resistance training confers numerous health benefits that are mediated in part by circulating factors. Towards an enhanced molecular understanding, there is growing interest in a class of signaling biomarkers called extracellular vesicles (EVs). Extracellular vesicles support physiological adaptations to exercise by transporting their cargo (e.g., microRNA [miRNA]) to target cells. Previous studies of changes in EV cargo have focused on aerobic exercise, with limited data examining the effects of resistance exercise. We examined the effect of acute resistance exercise on circulating EV miRNAs and their predicted target pathways. METHODS: Ten participants (5 men; age: 26.9 ± 5.5 y, height: 1.7 ± 0.1 m, body mass: 74.0 ± 11.1 kg, body fat: 25.7 ± 11.6 %) completed an acute heavy resistance exercise test (AHRET) consisting of six sets of 10 repetitions of back squats using 75% one-repetition maximum. Pre-/post-AHRET, EVs were isolated from plasma using size exclusion chromatography, and RNA sequencing was performed. Differentially expressed (DE) miRNAs between pre- and post-AHRET EVs were analyzed using Ingenuity Pathway Analysis to predict target messenger RNAs and their target biological pathways. RESULTS: Overall, 34 miRNAs were altered by AHRET (p < 0.05), targeting 4,895 mRNAs, with enrichment of 175 canonical pathways (p < 0.01), including 12 related to growth/metabolism (p53, IGF-I, STAT3, PPAR, JAK/STAT, growth hormone, WNT/ß-catenin, ERK/MAPK, AMPK, mTOR, and PI3K/AKT) and eight to inflammation signaling (TGF-ß, IL-8, IL-7, IL-3, IL-6, IL-2, IL-17, IL-10). CONCLUSIONS: Acute resistance exercise alters EV miRNAs targeting pathways involved in growth, metabolism, and immune function. Circulating EVs may serve as significant adaptive signaling molecules influenced by exercise training.

Effect of acute resistance exercise on bone turnover in young adults before and after concurrent resistance and interval training.

Weight-bearing physical activity can stimulate bone adaptation. This investigation explored the effect of an acute bout of resistance exercise before and after resistance+interval training on circulating biomarkers of bone metabolism and muscle-bone crosstalk. Healthy young male and female participants (n = 21 male, 28 ± 4 years; n = 17 female, 27 ± 5 years) performed a 6 × 10 squat test (75% 1RM) before and after a 12-week resistance+interval training program. Before and after completion of the training program, blood samples were collected at rest, immediately postexercise, and 2 h postexercise. Blood samples were analyzed for ßCTX, P1NP, sclerostin, osteocalcin, IGF-1, and irisin. Significant effects of acute exercise (main effect of time) were observed as increases in concentrations of IGF-1, irisin, osteocalcin, and P1NP from rest to postexercise. A sex*time interaction indicated a greater decline in ßCTX concentration from rest to 2 h postexercise and a greater increase in sclerostin concentration from rest to immediately postexercise in male compared with female participants. Sex differences (main effect of sex) were also observed for irisin and P1NP concentrations. In summary, changes in concentrations of biochemical markers of bone metabolism and muscle-bone crosstalk were observed in males and females after an acute bout of resistance exercise and following 12 weeks of resistance+interval training.

Comparison of physiological outcomes after dynamic exertion between athletes at return to sport from concussion and controls: Preliminary findings.

OBJECTIVES: Compare physiological (heart rate, heart rate variability, and blood pressure), performance (change-of-direction task completion time and errors), and clinical (symptoms and rating of perceived exertion) outcomes during dynamic exertion between athletes at return to sport after concussion to healthy athlete controls. DESIGN: Case control. METHODS: A sample of 23 (Female = 10; 43.5 %) athletes at medical clearance to play/activity from concussion (CONCUSS) and 23 sex-, age-, and sport-matched healthy athletes (CONTROLS) completed a 5-min seated rest before and after the dynamic exertion test. Independent sample t-tests were used to compare CONCUSS and CONTROLS for completion time, heart rate, and blood pressure; and Mann-Whitney U tests for symptoms, perceived exertion, and errors. A series of ANOVAs were conducted to compare heart rate variability between groups across pre- and post-exercise rest periods. RESULTS: There were no differences in heart rate, blood pressure, symptoms, perceived exertion, and errors. CONCUSS were faster on Zig Zag (p = .048) and Pro Agility (p = .018) tasks, reported lower symptom severity (p = .019), and had lower post-EXiT HRV (p < .049) than CONTROLS. CONCLUSIONS: Performance, symptoms, perceived exertion, and blood pressure outcomes from dynamic exertion were equivocal between athletes at medical clearance from concussion and healthy controls, which provide empirical support for dynamic exercise to inform medical clearance clinical decision making for sport-related concussion. However, differences in autonomic nervous system functioning indicate that additional research is needed to examine temporal changes in heart rate variability and other physiological outcomes following dynamic exertion.

Hydrodynamic Flow Characteristics of a Recirculating Pool: Examining the Ecological Validity for Training and Testing.

ABSTRACT: Krajewski, KT, Beethe, AZ, Dever, DE, Johnson, CD, Nindl, BC, Lovalekar, MT, Flanagan, SD, and Connaboy, C. Hydrodynamic flow characteristics of a recirculating pool: examining the ecological validity for training and testing. J Strength Cond Res 37(10): 2023-2031, 2023-Recirculating swimming flumes (RSFs) with elliptical multifeature designs have grown in popularity due to their multifunctionality for rehabilitation and training. Because of their smaller footprint, laboratories have adopted their use to investigate swimming and underwater treadmill running. However, little is known about the hydrodynamic characteristics of these RSFs and how they might influence outcomes. The purpose was to determine hydrodynamic flow characteristics of an RSF at the manufacturers' set "speeds" around the centroid of flow projection. Hydrodynamic velocity profiles were collected through a 3D profiling velocimeter, sampling at 200 Hz in an RSF. Data were collected 0.5 and 1.5 m from the projection channel at designated flume "speeds" of 30-95 (+99) in 5-unit increments. Velocity data were collected for 1 minute per trial (location × speed) to determine mean flow velocity (MFV) for 10, 20, 30, and 40 cm2 cross-sectional areas (CSAs). A two-way ANOVA was conducted comparing CSAs from the surface by distance from the current channel (4 × 2). Separate ANOVAs were conducted to assess differences in MFV across each CSA. Significant differences between flow CSAs indicated that MFV is less for a larger area at the same speed, indicative of variable and turbulent flow characteristics across the respective CSAs. Mean flow velocity was further diminished by distance from the flow channel as supported by the main effect, thus exposing an individual to variant flow velocities simultaneously. Limited stability of the flow velocity centroid could affect swim mechanics making the movement pattern no longer analogous to traditional pool and open water swimming, rather resembling swimming upstream in a river with turbulent flow.

Twelve weeks of concurrent resistance and interval training improves military occupational task performance in men and women.

In the British Army, ground close combat roles have opened to women, however, they must pass the newly developed, gender-neutral Role Fitness Tests for Soldiers (RFT(S)). Due to physiological differences between sexes, training that optimally prepares both sexes for military occupational demands and the RFT(S) is needed. The purpose of this study was to determine the efficacy of a 12-week periodized strength and power programme with concurrent interval training on RFT(S) performance and determine if performance adaptations differed between sexes. 39 recruit-aged (18-35 yrs) participants, including 21 men (29 ± 1 yrs) and 18 women (27 ± 1 yrs), completed the study. Participants performed 3 training sessions per week that included strength and power resistance training followed by interval training. Pre- to post-training, improvements were observed for seated medicine ball throw (4.5%, p < 0.001), casualty drag (29.8%, p < 0.001), single lift (8.9%, p < 0.001), water can carry (13.8%, p = 0.012), repeated lift and carry (6.5%, p < 0.001), 2-km load carriage (7.2%, p < 0.001) and 2-km run (3.2%, p = 0.021). Pre- to post-training improvements were also observed for maximal squat (27.0%, p < 0.001), bench press (8.9%, p < 0.001) and deadlift (24.6%, p < 0.001) maximal strength, but not upper body power or aerobic capacity. No differences in RFT(S) improvements were observed between sexes, however men performed better than women in all RFT(S) and physical performance measures. Concurrent resistance and interval training improves military occupational performance in men and women; however, women may need more training than men to pass the gender-neutral RFT(S).

Twelve weeks of concurrent resistance and interval training improved seated medicine ball throw, casualty drag, single lift, water can carry, repeated lift and carry, 2-km load carriage and 2-km run performance, military occupational performance measures that comprise the British Army Role Fitness Test for Soldiers (RFT(S)).Men and women demonstrated similar military occupational performance improvements from pre- to post-training, however, men performed better than women in all measures.Simple linear regression analyses between improvements in RFT(S) tasks and measures of physical fitness (one-repetition maximal strength, upper body power, lower body power, aerobic capacity) demonstrated limited significant associations suggesting that military occupational performance improvement relies on simultaneous development of multiple fitness domains.

Monitoring cognitive function in the fatigued warfighter: A rapid review of cognitive biomarkers.

OBJECTIVES: Decreases in cognitive function impair occupational performance, reduce occupational safety, and increase musculoskeletal injury risk. The aim of this paper was to identify measures that may be used to monitor cognitive function in the warfighter. DESIGN: A rapid review. METHODS: A rapid search of Academic Search Complete, MEDLINE, PsycINFO, and SPORTSDiscus databases was conducted. ELIGIBILITY CRITERIA: original peer reviewed research articles, written in English, published between 2002 and 2022, and using human participants with no health issues in military training environments or active service. RESULTS: Of the 248 articles screened, 58 full-text articles were assessed for eligibility and 29 included in the review. Of these, 16 papers presented data from multi-stressor military training environments, or experimental studies where simulated military tasks were being performed. Thirteen papers focused on an aspect of military work and the implications for cognitive function (i.e., physical load, periods of extended wakefulness or fatigue, and hypoxic conditions). The domains of cognitive function that were assessed (i.e. vigilance, reaction time, working memory, situational awareness, and decision-making) were somewhat consistent among studies. CONCLUSIONS: Prolonged exposure to high-stress military environments compromises multiple aspects of cognitive function. These findings highlight the need for a suite of biomarkers to monitor cognitive function and assess the ability of military personnel to attend to and process mission-critical information and make appropriate decisions on the battlefield and other high-stress environments. Our findings suggest that a suite of common tests may provide useful information about cognitive function in the warfighter.

Recruit-aged adults may preferentially weight task goals over deleterious cost functions during short duration loaded and imposed gait tasks.

Optimal motor control that is stable and adaptable to perturbation is reflected in the temporal arrangement and regulation of gait variability. Load carriage and forced-marching are common military relevant perturbations to gait that have been implicated in the high incidence of musculoskeletal injuries in military populations. We investigated the interactive effects of load magnitude and locomotion pattern on motor variability, stride regulation and spatiotemporal complexity during gait in recruit-aged adults. We further investigated the influences of sex and task duration. Healthy adults executed trials of running and forced-marching with and without loads at 10% above their gait transition velocity. Spatiotemporal parameters were analyzed using a goal equivalent manifold approach. With load and forced-marching, individuals used a greater array of motor solutions to execute the task goal (maintain velocity). Stride-to-stride regulation became stricter as the task progressed. Participants exhibited optimal spatiotemporal complexity with significant but not meaningful differences between sexes. With the introduction of load carriage and forced-marching, individuals relied on a strategy that maximizes and regulates motor solutions that achieve the task goal of velocity specifically but compete with other task functions. The appended cost penalties may have deleterious effects during prolonged execution, potentially increasing the risk of musculoskeletal injuries.

Military tactical adaptive decision making during simulated military operational stress is influenced by personality, resilience, aerobic fitness, and neurocognitive function.

Laboratory-based studies designed to mimic combat or military field training have consistently demonstrated deleterious effects on warfighter's physical, cognitive, and emotional performance during simulated military operational stress (SMOS). Purpose: The present investigation sought to determine the impact of a 48-h simulated military operational stress (SMOS) on military tactical adaptive decision making, and the influence of select psychological, physical performance, cognitive, and physiological outcome measures on decision making performance. Methods: Male (n = 48, 26.2 ± 5.5 years, 177.7 ± 6.6 cm, 84.7 ± 14.1 kg.) subjects currently serving in the U.S. military were eligible to participate in this study. Eligible subjects completed a 96-h protocol that occurred over five consecutive days and four nights. Day 2 (D2) and day 3 (D3) consisted of 48-h of SMOS wherein sleep opportunity and caloric needs were reduced to 50%. Differences in SPEAR total block score from baseline to peak stress (D3 minus D1) were calculated to assess change in military tactical adaptive decision making and groups were stratified based on increase (high adaptors) or decrease (low adaptors) of the SPEAR change score. Results: Overall, military tactical decision-making declined 1.7% from D1 to D3 (p < 0.001). High adaptors reported significantly higher scores of aerobic capacity (p < 0.001), self-report resilience (p = 0.020), extroversion (p < 0.001), and conscientiousness (p < 0.001). at baseline compared to low adaptors, while low adaptors reported greater scores in Neuroticism (p < 0.001). Conclusion: The present findings suggest that service members whose adaptive decision making abilities improved throughout SMOS (i.e., high adaptors) demonstrated better baseline psychological/self-reported resilience and aerobic capacity. Further, changes in adaptive decision-making were distinct from those of lower order cognitive functions throughout SMOS exposure. With the transition of future military conflicts placing higher priority on enhancing and sustaining cognitive readiness and resiliency, data presented here demonstrates the importance of measuring and categorizing baseline measures inherent to military personnel, in order to change and train one's ability to suffer less of a decline during high stress conditions.

Test-Retest, Interrater Reliability, and Minimal Detectable Change of the Dynamic Exertion Test (EXiT) for Concussion.

BACKGROUND: The Dynamic Exertion Test (EXiT) was developed to inform return-to-play (RTP) decision-making following clinical recovery from sport-related concussion (SRC). The purpose of the current study was to document intrarater and test-retest reliability and minimal detectable change (MDC) scores for physiological [heart rate (HR) and blood pressure], performance (change-of-direction task completion time and errors), and clinical outcomes (endorsed symptoms, perceived exertion) of EXiT, and interrater reliability of performance outcomes. HYPOTHESIS: Healthy athletes would exhibit stable physiological responses to the EXiT across visits, demonstrate consistent change-of-direction task completion time between consecutive trials at each visit, and the fastest time (of 2 trials) across visits, and endorse equivocal symptoms and effort across visits. STUDY DESIGN: Cross-sectional, test-retest. LEVEL OF EVIDENCE: Level 3. METHODS: Seventy-nine (female: 34 [43%], 19.6 ± 5.0 years) athletes completed the EXiT at 2 study visits (8.7 ± 4.7 days between visits). Two-way, mixed, intraclass correlation coefficients (ICCs) were used to evaluate intrarater and test-retest reliability. Cronbach's alpha was used to document the internal consistency of symptoms at each visit, and MDC scores were calculated on the physiological, performance, and clinical outcomes. RESULTS: Measured and percentage of age-estimated maximum HR were reliable following EXiT (ICC = 0.579-0.618). Change-of-direction task completion time (MDC range = 0.75-8.70 s) had good-to-excellent test-retest (ICC = 0.703-0.948) and interrater (ICC = 0.932-0.965) reliability. Symptoms had a high internal consistency at visits 1 (α = 0.894) and 2 (α = 0.805) and were reliable across visits (ICC = 0.588). CONCLUSION: The current investigation established test-retest reliability in addition to MDC scores of an objective dynamic exercise assessment among healthy adolescent and adult athletes. The EXiT may be an objective approach to inform RTP decision-making following SRC recovery. CLINICAL RELEVANCE: The EXiT is a clinically feasible exertion-based assessment that can be readily administered in a variety of outpatient clinical settings.

Prevention of Lower Extremity Musculoskeletal Injuries in Tactical and First Responder Populations: A Systematic Review and Meta-Analysis of Randomized Trials From 1955 to 2020.

ABSTRACT: Sinnott, AM, Krajewski, KT, LaGoy, AD, Beckner, ME, Proessl, F, Canino, MC, Nindl, BC, Turner, RL, Lovalekar, MT, Connaboy, C, and Flanagan, SD. Prevention of lower extremity musculoskeletal injuries in tactical and first responder populations: A systematic review and meta-analysis of randomized trials from 1955 to 2020. J Strength Cond Res 37(1): 239-252, 2023-Lower extremity musculoskeletal injuries (LEMSIs) impose a significant burden on tactical and first responder populations. To determine the effectiveness of LEMSI prevention strategies, we performed a systematic review and meta-analysis of randomized controlled trials published in English from 1955 to 2020 (PROSPERO: CRD42018081799). MEDLINE, EMBASE, Cochrane, CINAHL, ProQuest, and DTIC databases were searched for trials that assigned military service members, police, firefighters, or paramedics to LEMSI prevention interventions with a minimum surveillance period of 12 weeks. Evidence was synthesized as odds ratios (OR) for LEMSI occurrence between individuals assigned to interventions and those assigned to standard activities. Risk of bias was assessed with the Cochrane Risk of Bias tool 2.0. Random-effects meta-analyses were conducted for (a) physical training and (b) footwear modifications to reduce LEMSI and (c) footwear modifications to reduce stress fractures specifically. Certainty in the body of evidence was determined with the GRADE approach. Of 28,499 records, 18 trials comprised of more than 11,000 subjects were synthesized. Interventions included physical training (8, N = 6,838), footwear modifications (8, N = 3,792), nutritional supplementation (1, N = 324), and training modifications (1, N = 350). Overall risk of bias was generally moderate ( N = 7 of 18) or high ( N = 9 of 18). Physical training (OR = 0.87, 95% CI [0.71, 1.08], p = 0.22, I 2 = 58.4%) and footwear modification (OR = 1.13, 95% CI [0.85, 1.49], p = 0.42, I 2 = 0.0%) did not reduce LEMSI or stress fractures (OR = 0.76, 95% CI [0.45, 1.28], p = 0.30, I 2 = 70.7%). Our results indicate that there is weak evidence to support current LEMSI prevention strategies. Future efforts will benefit from longer surveillance periods, assessment of women and nonmilitary populations, improved methodological rigor, and a greater breadth of approaches.

Less daytime sleepiness and slow wave activity during sleep predict better physical readiness in military personnel.

BACKGROUND: Military personnel must maintain physical performance despite exposure to operational stressors such as sleep loss, caloric restriction and high cognitive load. Habitual sleep and specific sleep features are positively associated with fitness and may contribute to physical performance in operational settings. Further, by affecting muscle recovery, sleep may contribute to the ability to maintain performance across multiple days of exposure to operational stressors. OBJECTIVES: We examined the role of individual differences in baseline sleep on baseline physical performance and on change in physical performance throughout exposure to simulated military operational stress (SMOS). METHODS: Military personnel (36 male, 9 female, 26.3 ± 5.3 years) completed a 5-day SMOS protocol during which they completed a tactical mobility test daily. Sleep questionnaires were administered at intake and sleep was monitored each night with polysomnography. Lasso regressions were used to identify meaningful predictors of physical performance at baseline and of change in physical performance across SMOS. RESULTS: Better aerobic fitness, lower daytime sleepiness (Epworth Sleepiness Scale), and lower absolute slow wave activity (0.5-4 Hz) predicted better physical performance at baseline (66.1% of variance explained), but did not relate to changes in performance. CONCLUSIONS: Collectively, higher daytime sleepiness and slow wave activity may reflect more chronic exposure to insufficient sleep and higher baseline sleep drive, which in turn led to compromised physical performance. The findings suggest that low self-report sleepiness and low objective slow wave activity may reflect two quantifiable markers of healthy sleep behaviors that have implications for operational performance.

Combined effects of time-of-day and simulated military operational stress on perception-action coupling performance.

Perception-action coupling, the ability to 'read and react' to the environment, is essential for military personnel to operate within complex and unpredictable environments. Exposure to military operational stressors (e.g., caloric restriction, sleep loss, physical exertion), including around-the-clock operations, may compromise perception-action coupling, thereby impacting performance and safety. We examined the combined effects of simulated military operational stress (SMOS) and time-of-day on perception-action coupling. Fifty-seven active duty and reservist military personnel (45 M; 26.4 ± 5.6 years) completed a 5-day SMOS protocol that included two consecutive days of caloric restriction, and sleep restriction, and disruption. Participants completed a tablet-based perception-action coupling task (PACT) that involves perceiving whether virtual balls fit through virtual apertures. Familiarization occurred on day 0. Eight trials across day 1 (18:00, 22:00), 2 (04:00, 18:00, 22:00) and 3 (04:00, 18:00, 22:00) were analyzed. Mixed models were run to examine the interactive and main effects of day, and time-of-day on PACT response speed and accuracy outcomes. PACT response speed and accuracy outcomes improved at 18:00 and 22:00, whereas performance at 04:00 deteriorated across days. Perception-action coupling performance was resilient to SMOS, except in the early morning when the circadian drive for sleep is high, and the effects of sleep loss are more prominent.

Resistance exercise differentially alters extracellular vesicle size and subpopulation characteristics in healthy men and women: an observational cohort study.

Extracellular vesicles (EVs) are established mediators of adaptation to exercise. Currently, there are no published data comparing changes in EVs between men and women after resistance exercise. We tested the hypothesis that EV profiles would demonstrate a sex-specific signature following resistance exercise. Ten men and 10 women completed an acute heavy resistance exercise test for back squats using 75% of their one-repetition maximum. Blood was drawn before and immediately after exercise. EVs were isolated from plasma using size exclusion chromatography and stained with antibodies associated with exosomes (CD63), microvesicles (VAMP3), apoptotic bodies (THSD1), and a marker for skeletal muscle EVs (SGCA). CD63+ EV concentration and proportion of total EVs increased 23% (P = 0.006) and 113% (P = 0.005) in both sexes. EV mean size declined in men (P = 0.020), but not in women, suggesting a relative increase in small EVs in men. VAMP3+ EV concentration and proportion of total EVs increased by 93% (P = 0.025) and 61% (P = 0.030) in men and women, respectively. SGCA+ EV concentration was 69% higher in women compared with men independent of time (P = 0.007). Differences were also observed for CD63, VAMP3, and SGCA median fluorescence intensity, suggesting altered surface protein density according to sex and time. There were no significant effects of time or sex on THSD1+ EVs or fluorescence intensity. EV profiles, particularly among exosome-associated and muscle-derived EVs, exhibit sex-specific differences in response to resistance exercise which should be further studied to understand their relationship to training adaptations.

Insulin-like growth factor-I biocompartmentalization across blood, interstitial fluid and muscle, before and after 3 months of chronic resistance exercise.

This investigation examined the influence of 12-week ballistic resistance training programs on the IGF-I system in circulation, interstitial fluid, and skeletal muscle, at rest and in response to acute exercise. Seventeen college-aged subjects (11 women/6 men; 21.7 ± 3.7 yr) completed an acute ballistic exercise bout before and after the training program. Blood samples were collected pre-, mid-, and postexercise and analyzed for serum total IGF-I, free IGF-I, and IGF binding proteins (IGFBPs) 1-4. Dialysate and interstitial free IGF-I were analyzed in vastus lateralis (VL) interstitial fluid collected pre- and postexercise via microdialysis. Pre- and postexercise VL muscle biopsies were analyzed for IGF-I protein expression, IGF-I receptor phosphorylation (p-IGF-IR), and AKT phosphorylation (p-AKT). Following training, basal serum IGF-I, free IGF-I, IGFBP-2, and IGFBP-3 decreased whereas IGFBP-1 and IGFBP-4 increased. Training reduced basal dialysate and interstitial free IGF-I but had no effect on basal skeletal muscle IGF-I, p-IGF-IR, or p-AKT. Acute exercise elicited transient changes in IGF-I system concentrations and downstream anabolic signaling both pre- and posttraining; training did not affect this acute exercise response. Posttraining, acute exercise-induced changes in dialysate/interstitial free IGF-I were strongly correlated with the changes in intramuscular IGF-I expression, p-IGF-IR, and p-AKT. The divergent influence of resistance training on circulating/interstitial and skeletal muscle IGF-I demonstrates the importance of concurrent, multiple biocompartment analysis when examining the IGF-I system. As training elicited muscle hypertrophy, these findings indicate that IGF-I's anabolic effects on skeletal muscle are mediated by local, rather than systemic mechanisms.NEW & NOTEWORTHY In the first investigation to assess resistance training's effects on the IGF-I system in serum, interstitial fluid, and skeletal muscle, training decreased basal circulating and interstitial IGF-I but did not alter basal intramuscular IGF-I protein activity. Posttraining, acute exercise-induced interstitial IGF-I increases were strongly correlated with intramuscular IGF-I expression and signaling. These findings highlight the importance of multibiocompartment measurement when analyzing IGF-I and suggest that IGF-I's role in hypertrophic adaptations is locally mediated.

Neuroendocrine, inflammatory, and extracellular vesicle responses during the Navy Special Warfare Screener Selection Course.

Military operational stress is known to increase adrenal hormones and inflammatory cytokines, while decreasing hormones associated with the anabolic milieu and neuroendocrine system. Less is known about the role of extracellular vesicles (EVs), a form of cell-to-cell communication, in military operational stress and their relationship to circulating hormones. The purpose of this study was to characterize the neuroendocrine, cytokine, and EV response to an intense. 24-h selection course known as the Naval Special Warfare (NSW) Screener and identify associations between EVs and cytokines. Blood samples were collected the morning of and following the NSW Screener in 29 men (18-26 yr). Samples were analyzed for concentrations of cortisol, insulin-like growth factor I (IGF-I), neuropeptide-Y (NPY), brain-derived neurotrophic factor (BDNF), α-klotho, tumor necrosis factor-α (TNFα), and interleukins (IL) -1ß, -6, and -10. EVs stained with markers associated with exosomes (CD63), microvesicles (VAMP3), and apoptotic bodies (THSD1) were characterized using imaging flow cytometry and vesicle flow cytometry. The selection event induced significant changes in circulating BDNF (-43.2%), IGF-I (-24.6%), TNFα (+17.7%), and IL-6 (+13.6%) accompanied by increases in intensities of THSD1+ and VAMP3+ EVs (all P < 0.05). Higher concentrations of IL-1ß and IL-10 were positively associated with THSD1+ EVs (P < 0.05). Military operational stress altered the EV profile. Surface markers associated with apoptotic bodies were positively correlated with an inflammatory response. Future studies should consider a multiomics assessment of EV cargo to discern canonical pathways that may be mediated by EVs during military stress.

Utility of extracellular vesicles as a potential biological indicator of physiological resilience during military operational stress.

Extracellular vesicles (EVs) transport biological content between cells to mediate physiological processes. The association between EVs and resilience, the ability to cope with stress, is unknown. Using unbiased machine learning approaches, we aimed to identify a biological profile of resilience. Twenty servicemen (27.8 ± 5.9 years) completed the Connor Davidson Resilience (CD-RISC) questionnaire and were exposed to daily physical and cognitive exertion with 48-hr sleep and caloric restriction. Blood samples from baseline and the second day of stress were analyzed for neuroendocrine biomarkers impacted by military stress. EVs were isolated from plasma and stained with antibodies associated with exosomes (CD63), microvesicles (VAMP3), and apoptotic bodies (THSD1). Individuals were separated into high (n = 10, CD-RISC > 90) and low (n = 10, CD-RISC < 79) resilience. EV features were stratified by size, then down-selected using regression trees and compared between groups. Diagnostic accuracy was assessed using receiver operating characteristic curves. Compared to low resilience, high resilience demonstrated a greater increase in variability of THSD1 local bright spot intensities among large-sized EVs in response to stress (p = 0.002, Hedges' g = 1.59). Among medium-sized EVs, high resilience exhibited a greater decrease in side scatter intensity (p = 0.014, Hedges' g = 1.17). Both features demonstrated high to moderate diagnostic accuracy for high resilience (AUC = 0.90 and 0.79). In contrast, neuroendocrine biomarker concentrations were similar between groups. The increase in variability among THSD1 + EVs in high, but not low, resilient individuals following stress may suggest high resilience is accompanied by stress-triggered apoptotic adaptations to the environment that are not detected in neuroendocrine biomarkers.

Men and women display distinct extracellular vesicle biomarker signatures in response to military operational stress.

Extracellular vesicles (EVs) are mediators of physiological changes that occur during physical exertion. This study examined the effects of physical exertion with and without sleep and caloric restriction on EV size, concentration, and surface proteins in men and women. Twenty participants (10 men) completed a 5-day simulated military operational stress protocol with daily physical exertion. Blood was drawn before and immediately after exertion at baseline (D1) and following 48-h of sleep and caloric restriction (D3). EV size and concentration were assessed using nanoparticle tracking analysis. EVs were identified with markers associated with exosomes (CD63), microvesicles (VAMP3), apoptotic bodies (THSD1), and skeletal muscle-derived EVs (SGCA) and quantified using imaging flow cytometry. Interactive and main effects of sex, day, and time on EVs were assessed using three-way ANOVAs. EV concentration declined pre to postexertion in women on D1 and D3 but was stable in men. EV size increased from pre to postexertion and from D1 to D3 in men and women. Physical exertion following sleep and caloric restriction increased CD63+ EV concentration, proportion of total EVs, and CD63 surface protein expression regardless of sex. The proportion of SGCA+ EVs increased in men and women following exertion and from D1 to D3 but was higher in women than in men. No differences were observed in VAMP3+ and THSD1+ EVs. This study identified sexually dimorphic EV profiles in response to various stressors. Further investigations are necessary to determine if dimorphic EV responses affect health and performance outcomes during stress.NEW & NOTEWORTHY Sex is understudied in EV research, and most studies limit EV analysis to single stress conditions such as exercise. Multistress conditions consisting of physical exertion and sleep and caloric restriction are common in real-world settings. We demonstrate that physical exertion results in sex-specific EV signatures and that EV profiles vary according to single versus multistress conditions. Our data highlight important biological and ecological characteristics that should be considered in EV research.

The Role of Age, Sex, Body Mass Index, and Sport Type on the Dynamic Exertion Test in Healthy Athletes: A Cross-Sectional Study.

BACKGROUND: The dynamic exertion test (EXiT) was developed to help inform return to play after sport-related concussion, but some factors may threaten the internal validity of EXiT and affect clinical interpretation. OBJECTIVE: To compare age, sex, BMI, and sport types across EXiT physiological [pre-EXiT and post-EXiT percentage of maximum heart rate (HR %max) and blood pressure (BP)], performance (change-of-direction task completion time and committed errors), and clinical [symptoms and rating of perceived exertion (RPE)] outcomes among healthy adolescents and adults. STUDY DESIGN: Cross-sectional. METHODS: Eighty-seven participants ( F = 55, 37.4%) reported symptoms and RPE during the EXiT, which consists of a 12-minute treadmill running protocol, and the dynamic circuit, ball toss, box shuffle (SHUF) and carioca (CAR), zig zag (ZZ), proagility (PA), and arrow agility (AA) tasks. Independent samples t tests were conducted for pre-EXiT and post-EXiT HR %max and BP and change-of-direction task completion time and Mann-Whitney U tests for errors, symptoms, and RPE. A series of 1-way analysis of variance (ANOVAs) and Kruskal-Wallis H tests were conducted to compare collision, contact, and noncontact sport types. RESULTS: Adolescents had lower completion time across AA ( P = 0.01) and male athletes lower than female athletes on CAR, ZZ, PA, and AA ( P < 0.04). Male athletes reported greater RPE after the SHUF, CAR, and AA ( P < 0.03). HR %max , errors, and symptoms were equivocal across all subgroups ( P > 0.05). CONCLUSION: Age and sex should be considered in the interpretation of performance and clinical, but not physiological, EXiT outcomes. The EXiT is a standardized exercise assessment and generalizable to healthy athletes.