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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.

Cutaneous melanoma (CM) survival is assessed using averaged data from the American Joint Committee on Cancer 8th edition (AJCC8). However, subsets of AJCC8 stages I-III have better or worse survival than the predicted average value. The objective of this study was to determine if the 31-gene expression profile (31-GEP) test for CM can further risk-stratify melanoma-specific mortality within each AJCC8 stage. This retrospective multicenter study of 901 archival CM samples obtained from patients with stages I-III CM assessed 31-GEP test predictions of 5-year melanoma-specific survival (MSS) using Kaplan-Meier and Cox proportional hazards. In stage I-III CM population, patients with a Class 2B result had a lower 5-year MSS (77.8%) than patients with a Class 1A result (98.7%) and log-rank testing demonstrated significant stratification of MSS [χ2 (2df, n = 901) = 99.7, P0.001). Within each stage, 31-GEP data provided additional risk stratification, including in stage I [χ2 (2df, n = 415) = 11.3, P = 0.004]. Cox regression multivariable analysis showed that the 31-GEP test was a significant predictor of melanoma-specific mortality (MSM) in patients with stage I-III CM [hazard ratio: 6.44 (95% confidence interval: 2.61-15.85), P0.001]. This retrospective study focuses on Class 1A versus Class 2B results. Intermediate results (Class 1B/2A) comprised 21.6% of cases with survival rates between Class 1A and 2B, and similar to 5-year MSS AJCC stage values. Data from the 31-GEP test significantly differentiates MSM into lower (Class 1A) and higher risk (Class 2B) groups within each AJCC8 stage. Incorporating 31-GEP results into AJCC8 survival calculations has the potential to more precisely assess survival and enhance management guidance.

Simulated military operational stress (SMOS) provides a useful model to better understand resilience in humans as the stress associated with caloric restriction, sleep deficits, and fatiguing exertion degrades physical and cognitive performance. Habitual physical activity may confer resilience against these stressors by promoting favorable use-dependent neuroplasticity, but it is unclear how physical activity, resilience, and corticospinal excitability (CSE) relate during SMOS. To examine associations between corticospinal excitability, physical activity, and physical performance during SMOS. Fifty-three service members (age: 26 ± 5 yr, 13 women) completed a 5-day and -night intervention composed of familiarization, baseline, SMOS (2 nights/days), and recovery days. During SMOS, participants performed rigorous physical and cognitive activities while receiving half of normal sleep (two 2-h blocks) and caloric requirements. Lower and upper limb CSE were determined with transcranial magnetic stimulation (TMS) stimulus-response curves. Self-reported resilience, physical activity, military-specific physical performance (TMT), and endocrine factors were compared in individuals with high (HIGH) and low CSE based on a median split of lower limb CSE at baseline. HIGH had greater physical activity and better TMT performance throughout SMOS. Both groups maintained physical performance despite substantial psychophysiological stress. Physical activity, resilience, and TMT performance were directly associated with lower limb CSE. Individual differences in physical activity coincide with lower (but not upper) limb CSE. Such use-dependent corticospinal excitability directly relates to resilience and physical performance during SMOS. Future studies may use noninvasive neuromodulation to clarify the interplay among CSE, physical activity, and resilience and improve physical and cognitive performance. NEW & NOTEWORTHY We demonstrate that individual differences in physical activity levels coincide with lower limb corticospinal excitability. Such use-dependent corticospinal excitability directly relates to resilience and physical performance during a 5-day simulation of military operational stress with caloric restriction, sleep restriction and disruption, and heavy physical and cognitive exertion.

Adaptation to military operational stress is a complex physiological response that calls upon the sympathetic nervous system (SNS), hypothalamic pituitary adrenal (HPA) axis and immune system, to create a delicate balance between anabolism and catabolism and meet the demands of an ever-changing environment. As such, resilience, the ability to withstand and overcome the negative impact of stress on military performance, is likely grounded in an appropriate biological adaptation to encountered stressors. Neuroendocrine [i.e. cortisol, epinephrine (EPI), norepinephrine (NE), neuropeptide-Y (NPY), and brain derived neurotropic factor (BDNF)], inflammatory [i.e. interleukin 6 (IL-6), IL-1β, IL-4, IL-10 and tumour necrosis factor (TNF)-α], as well as growth and anabolic [i.e. insulin-like growth factor-I (IGF-I), testosterone, and dehydroepiandrosterone (DHEA)] biomarkers independently and interactively function in stress adaptations that are associated with a soldier's physical and psychological performance. In this narrative review, we detail biomarkers across neuroendocrine, inflammatory, and growth stimulating domains to better elucidate the biological basis of a resilient soldier. The findings from the reviewed studies indicate that military readiness and resiliency may be enhanced through better homeostatic control, better regulated inflammatory responses, and balanced anabolic/catabolic processes. It is unlikely that one class of biomarkers is better for assessing physiological resilience. Therefore, a biomarker panel that can account for appropriate balance across these domains may be superior in developing monitoring frameworks. Real-time physiological monitoring to assess biomarkers associated with resilience will be possible pending more sophisticated technologies and provide a field-expedient application for early identification and intervention of at-risk soldiers to improve military resiliency.

Purpose. To examine whether growth in visits to Public Health Dental Hygiene Practitioners (PHDHPs) providing preventative dental services at a pediatric hospital clinic was predominantly among children receiving public insurance and children of minority background from 2013 to 2017. Methods. Longitudinal descriptive data analysis from electronic health records for 6,856 children under age 18 years who visited PHDHPs co-located at a hospital clinic in Pittsburgh, PA, from 2013 to 2017. We compared visits between white versus non-white children and between children with public, private, and no or missing insurance by year. Results. Visit volume doubled from 2013 (n=811) to 2017 (n=1868). The proportion of PHDHP visits with non-white children increased from 77% (n=625) in 2013 to 87% (n=1,472) in 2017 (P

Conkright, WR, Beckner, ME, Sinnott, AM, Eagle, SR, Martin, BJ, Lagoy, AD, Proessl, F, Lovalekar, M, Doyle, TLA, Agostinelli, P, Sekel, NM, Flanagan, SD, Germain, A, Connaboy, C, and Nindl, BC. Neuromuscular performance and hormonal responses to military operational stress in men and women. J Strength Cond Res XX(X): 000-000, 2021-Women have recently been integrated into ground close combat positions; however, there are limited data in women in these roles. We aimed to test the hypothesis that there would be no sex-specific neuromuscular responses, but hormonal signaling would be differentially impacted when exposed to simulated military operational stress (SMOS). Neuromuscular performance was assessed daily using a tactical mobility test (TMT) in 54 male and 15 female military members. Blood was drawn before/after TMT. Mood states were assessed each morning. Unloaded 300-m shuttle time increased 6% in both sexes and remained 7% higher after 1 day of recovery compared with baseline (p 0.05). Growth hormone increased in men, but not women, before to after TMT (p < 0.001 vs. p = 0.086). Women experienced a greater decline in insulin-like growth factor-I across days compared with men (ηp2 = 0.778 vs. 0.209, respectively, p < 0.001). Brain-derived neurotrophic factor increased significantly in men only from before to after TMT on day 1 (men: +107% vs. women: +10%) but no difference on days 3 or 4. Cortisol increased 69% from before to after TMT when averaged by sex and day. Negative mood states (depression, tension, and anger) and altered hormonal concentrations were associated with poorer TMT performance. Acute SMOS differentially impacted circulating hormonal milieu in men and women, but no differences in physical performance responses. Unloaded 300-m shuttle was negatively impacted while other fitness domains were maintained. Relationships between performance and mood/endocrine signaling highlight the potential for self-report measures and biomarkers to serve as indicators of performance change.

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.

Objectives The purpose of this study was to evaluate whether Public Health Dental Hygiene Practitioner (PHDHP) referrals to pediatric dentists were more successful for children younger than 3 years old and those with dental caries. Methods We reviewed the electronic health records of 1,450 children, age 1 to 12 years, who completed a dental visit with a PHDHP in 2017 at UPMC Children's Hospital of Pittsburgh's (CHP) Primary Care Center. We tracked whether children who visited the onsite PHDHP accepted a referral to CHP pediatric dentists, and if so, whether they successfully completed the referral. Results Of the 1,450 children who visited the PHDHP, 67 percent (n = 973) accepted a referral to CHP pediatric dentists. Of these referrals, 32 percent (312/973) were successfully fulfilled. The proportions of accepted and fulfilled referrals were significantly higher for children older than 3 years old and those with dental caries. After controlling for child age, gender, and insurance status, children with dental caries had 5.7 times greater odds of successful referral from the PHDHP to the pediatric dentist compared to children without dental caries (95 percent CI 4.1-7.9). Conclusions PHDHPs were more successful referring children older than 3 years old and those with dental caries to pediatric dentists. PHDHPs are allied dental health professionals that can be effective at referring children to pediatric dentists when they have dental caries. Additional strategies are needed to enhance the success rate of dental referrals for young children under 3 years old.

Beckner, ME, Pihoker, AA, Darnell, ME, Beals, K, Lovalekar, M, Proessl, F, Flanagan, SD, Arciero, PJ, Nindl, BC, and Martin, BJ. Effects of multi-ingredient preworkout supplements on physical performance, cognitive performance, mood state, and hormone concentrations in recreationally active men and women. J Strength Cond Res XX(X): 000-000, 2020-Performance enhancement supplement research has primarily focused on the effectiveness of individual ingredients, rather than the combination. This study investigated the acute effects of 2 multi-ingredient preworkout supplements (MIPS), with beta-alanine and caffeine (BAC) and without (NBAC), compared with placebo (PLA) on anaerobic performance, endurance capacity, mood state, cognitive function, vascular function, and anabolic hormones. Thirty exercise-trained individuals (24.4 ± 4.9 years, 15 men and 15 women) completed a fatiguing exercise protocol on 3 separate occasions, 30 minutes after ingestion of BAC, NBAC, or PLA. Outcomes were analyzed using one-way or two-way repeated-measures analysis of variance, as appropriate (alpha = 0.05). Anaerobic power was greater when supplementing with NBAC (10.7 ± 1.2 W·kg) and BAC (10.8 ± 1.4 W·kg) compared with PLA (10.4 ± 1.2 W·kg) (p = 0.014 and p = 0.022, respectively). BAC improved V[Combining Dot Above]O2peak time to exhaustion (p = 0.006), accompanied by an increase in blood lactate accumulation (p < 0.001), compared with PLA. Both NBAC and BAC demonstrated improved brachial artery diameter after workout (p = 0.041 and p = 0.005, respectively), but PLA did not. L-arginine concentrations increased from baseline to postsupplement consumption of BAC (p = 0.017). Reaction time significantly decreased after exercise for all supplements. There was no effect of supplement on mood states. Exercise-trained individuals looking to achieve modest improvements in power and endurance may benefit from consuming MIPS before exercise.

BACKGROUND: While patients with localized cutaneous melanoma (CM) generally have good five-year melanoma-specific survival rates, identifying patients with localized disease at a high risk of recurrence could allow them access to additional follow-up or surveillance. OBJECTIVE: We sought to examine the prognostic value of the 31-gene expression profile (31-GEP) test for the risk of recurrence in stage I CM patients according to 31-GEP main class (low risk: Class 1 vs. high-risk: Class 2) and the lowest and highest risk 31-GEP subclasses (Class 1A vs. Class 2B). METHODS: Data from a previously described meta-analysis detailing the 31-GEP results for patients with stage I CM (N = 623) were re-analyzed to determine 31-GEP accuracy. RESULTS: Patients with stage I CM and a Class 1 31-GEP result were less likely to have a recurrence (15/556; 2.7% vs. 6/67; 9.0%; p=0.018) than patients with a Class 2 result and had a higher five-year recurrence-free survival (RFS) (96% vs. 85%). Patients with a Class 2 result were 2.8 times as likely to experience a recurrence (positive likelihood ratio: 2.82; 95% confidence interval: 1.38–5.77). In a subset of patients with stage I CM stratified further into 31-GEP subclasses (n = 206), patients with a Class 1A result had a higher five-year RFS than those with a Class 2B result (98% vs. 73%). Patients with a Class 2B result were also 6.5 times as likely to experience a recurrence (positive likelihood ratio: 6.45; 95% confidence interval: 2.44–17.00) than those with a Class 1A result, and the 31-GEP had a negative predictive value of 96.3% (95% confidence interval: 92.3%–98.4%). CONCLUSION: The 31-GEP test significantly differentiates between low and high recurrence risk in patients with stage I CM.

Nutritional fitness, which comprises food choices, meal timing, and dietary intake behaviors, is an important component of military service member health and performance that has garnered recent attention. This study utilized generalized linear mixed effects modeling (GLMM) to investigate changes in eating pathology symptoms in men and women during initial military training (Marine Corps Officer Candidates School (OCS)). Associations among eating pathology, musculoskeletal injury risk and BMI were also assessed. This investigation includes data from the Eating Pathology Symptoms Inventory (EPSI) and BMI at the start of OCS (n = 598: Male n = 469, Female n = 129) and end of the 10-week program (n = 413: Male n = 329, Female n = 84), and injury surveillance throughout. At baseline, female candidates presented with greater body dissatisfaction, binge eating, purging, and restricting, but lower negative attitudes toward obesity compared to male candidates (p 0.001). Eating symptoms changed during military training indicated by decreased body dissatisfaction in women (p = 0.003), decreased excessive exercise and negative attitudes toward obesity in men (p 0.001), decreased cognitive restraint (p 0.001), restricting (p 0.001), purging (p = 0.013), and muscle building (p 0.001) and increased binge eating (p 0.001) in both sexes. Changes in restricting were significantly related to changes in BMI during training (p 0.05). The likelihood of future injury was 108 % higher in female candidates than males and decreased by 5 % for each unit increase in excessive exercise. Eating attitudes and behaviors change during military training environments and are associated with military health and readiness outcomes including BMI and injury risk.

The legs of 9 men (age 21 ± 2 years, 45 ± 4 mL/(kg·min)) were randomly assigned to complete 6 sessions of high-intensity exercise training, involving either one or four 5-min bouts of counterweighted, single-leg cycling. Needle biopsies from vastus lateralis revealed that citrate synthase maximal activity increased after training in the 4-bout group (p = 0.035) but not the 1-bout group (p = 0.10), with a significant difference between groups post-training (13%, p = 0.021). Novelty Short-term training using brief intense exercise requires multiple bouts per session to increase mitochondrial content in human skeletal muscle.

Background Chronic kidney disease (CKD) is characterized by dysbiosis, elevated levels of uremic toxins, systemic inflammation, and increased markers of oxidative stress. These factors lead to an increased risk of cardiovascular disease (CVD) which is common among CKD patients. Supplementation with high amylose maize resistant starch type 2 (RS-2) can change the composition of the gut microbiota, and reduce markers of inflammation and oxidative stress in patients with end-stage renal disease. However, the impact of RS-2 supplementation has not been extensively studied in CKD patients not on dialysis. Aerobic exercise training lowers certain markers of inflammation in CKD patients. Whether combining aerobic training along with RS-2 supplementation has an additive effect on the aforementioned biomarkers in predialysis CKD patients has not been previously investigated. Methods The study is being conducted as a 16-week, double-blind, placebo controlled, parallel arm, randomized controlled trial. Sixty stage 3–4 CKD patients (ages of 30–75 years) are being randomized to one of four groups: RS-2 & usual care, RS-2 & aerobic exercise, placebo (cornstarch) & usual care and placebo & exercise. Patients attend four testing sessions: Two baseline (BL) sessions with follow up visits 8 (wk8) and 16 weeks (wk16) later. Fasting blood samples, resting brachial and central blood pressures, and arterial stiffness are collected at BL, wk8 and wk16. A stool sample is collected for analysis of microbial composition and peak oxygen uptake is assessed at BL and wk16. Blood samples will be assayed for p-cresyl sulphate and indoxyl sulphate, c-reactive protein, tumor necrosis factor α, interleukin 6, interleukin 10, monocyte chemoattractant protein 1, malondialdehyde, 8-isoprostanes F2a, endothelin-1 and nitrate/nitrite. Following BL, subjects are randomized to their group. Individuals randomized to conditions involving exercise will attend three supervised moderate intensity (55–65% peak oxygen uptake) aerobic training sessions (treadmills, bikes or elliptical machine) per week for 16 weeks. Discussion This study has the potential to yield information about the effect of RS-2 supplementation on key biomarkers believed to impact upon the development of CVD in patients with CKD. We are examining whether there is an additive effect of exercise training and RS-2 supplementation on these key variables. Trial registration Clinicaltrials.gov Trial registration#NCT03689569. 9/28/2018, retrospectively registered.

Introduction Alertness, essential for optimal performance, may be modulated by acute stressors including: sleep loss, caloric restriction, cognitive load, and physical exertion. Prior sleep may attenuate sleep loss-related alertness decrements, thereby influencing performance and safety. We examined the effects of prior sleep and changes in alertness throughout the day and across days during a simulated military operational stress (SMOS) protocol. Methods As part of a 5-day SMOS protocol, fifty-eight active-duty or recently-separated military personnel (45 men; 26±6 years) completed subjective (Profile of Mood States, Vigor subscale) and objective (3-minute Psychomotor Vigilance Task; PVT) alertness assessments each morning (~0900) and evening (~2200). PVT outcomes included median reaction time (RT) and lapses. Day 2 (D2) reflected baseline testing, in which participants received an 8-hour sleep opportunity (2300-0700) and 100% of their estimated caloric need. Day 4 (D4) reflected peak stress, after two nights of participants receiving two 2-hour sleep opportunities (0100-0300, 0500-0700) and 50% of their estimated caloric need. Mixed effects ANOVAs were used to assess the effects of day (D2, D4) and time (Morning, Evening) on alertness. D2 and D4 reflected alertness at baseline and peak stress, respectively. Separate ANOVAs were performed to assess the effects of prior sleep: the Pittsburgh Sleep Quality Index (PSQI) assessed at intake, baseline polysomnography-measured sleep efficiency (SE), and baseline frontal slow wave activity (SWA; 0.5-4Hz). All analyses controlled for age. Results No significant interaction or main effects of day and time were found for Vigor or PVT lapses. Participants with higher PSQI scores reported lower Vigor (p=.01, η_p^2=.11). A significant interaction was found for PVT RT (p=.04, η_p^2=.07); morning RT was slower on D4 than D2, while evening RT did not differ across days. SE and SWA did not significantly influence alertness. Conclusion SMOS led to objective alertness deficits in the morning but not evening. Subjective alertness did not change during SMOS but was influenced by prior sleep quality (PSQI). Thus, both circadian and prior sleep-related factors influence performance during operational stress. Fatigue mitigation strategies delivered before and during military operations may support performance and safety. Support (if any) Department of Defense Award #W81XWH-17-2-0070

Healthy aging results in cardiac structural and electrical remodeling that increases susceptibility to cardiovascular diseases. Relaxin, an insulin-like hormone, suppresses atrial fibrillation, inflammation and fibrosis in aged rats but the mechanisms-of-action are unknown. Here we show that relaxin treatment of aged rats reverses pathological electrical remodeling (increasing Nav1.5 expression and localization of Connexin43 to intercalated disks) by activating canonical Wnt signaling. In isolated adult ventricular myocytes, relaxin upregulated Nav1.5 (EC50 = 1.3 nM) by a mechanism inhibited by the addition of Dickkopf-1. Furthermore, relaxin increased the levels of connexin43, Wnt1, and cytosolic and nuclear β-catenin. Treatment with Wnt1 or CHIR-99021 (a GSK3β inhibitor) mimicked the relaxin effects. In isolated fibroblasts, relaxin blocked TGFβ-induced collagen elevation in a Wnt dependent manner. These findings demonstrate a close interplay between relaxin and Wnt-signaling resulting in myocardial remodeling and reveals a fundamental mechanism of great therapeutic potential.

Purpose To study the impact of 48 h of simulated military operational stress (SMOS) on executive function, in addition to the role of trait resilience (RES) and aerobic fitness (FIT) on executive function performance. Associations between executive function and neuropeptide-Y (NPY), brain-derived neurotropic factor (BDNF), insulin-like growth factor-I (IGF-I), oxytocin, and α-klotho (klotho) were assessed to elucidate potential biomarkers that may contribute to cognitive performance during a multi-factorial stress scenario. Methods: Fifty-four service members (SM) (26.4 ± 5.4 years, 178.0 ± 6.5 cm, 85.2 ± 14.0 kg) completed the 5-day protocol, including daily physical exertion and 48 h of restricted sleep and caloric intake. Each morning subjects completed a fasted blood draw followed by Cognition, a 10-part cognitive test battery assessing executive function. SMs were grouped into tertiles [low (L-), moderate (M-), high (H-)] based on Connor Davidson Resilience Score (RES) and V ˙ O2peak (FIT). Repeated measures ANOVA were run to analyze the effect of day on cognitive performance and biomarker concentration. Separate two-way mixed ANOVAs were run to determine the interaction of group by day on cognitive function. Friedman test with Bonferroni-corrected pairwise comparisons were used if assumptions for ANOVA were not met. Associations between changes in biomarkers and cognitive performance were analyzed using parametric and non-parametric correlation coefficients. Results: SMOS reduced SM vigilance –11.3% (p 0.05). Vigilance was compromised during SMOS in L - and M-RES (p = 0.007 and p = 0.001, respectively) as well as L - and M-FIT (p = 0.001 and p = 0.031, respectively). SMOS reduced circulating concentrations of α-klotho -7.2% (p = 0.004), NPY -6.4% (p = 0.001), and IGF-I -8.1% (p 0.05). Several modest associations between neuroendocrine biomarkers and cognitive performance were identified. Conclusion: This study demonstrates H-FIT and H-RES may buffer the impact of SMOS on vigilance. SMOS negatively impacted circulating neuroendocrine biomarkers. While BDNF returned to baseline concentrations by the end of the 5 d protocol, NPY, IGF-I, and α-klotho may require a longer recovery period. These data suggest that the military may benefit by training and/or selection processes targeting at augmenting trait resilience and aerobic fitness for increased readiness.

New Findings What is the central question of this study? Are there sex-based differences in the acute skeletal muscle response to sprint interval training (SIT)? What is the main finding and its importance? In response to a SIT protocol that involved three 20 s bouts of ‘all-out’ cycling, the expression of multiple genes associated with mitochondrial biogenesis, metabolic control and structural remodelling was largely similar between men and women matched for fitness. Our findings cannot explain previous reports of sex-based differences in the adaptive response to SIT and suggest that the mechanistic basis for these differences remains to be elucidated. A few studies have reported sex-based differences in response to several weeks of sprint interval training (SIT). These findings may relate to sex-specific responses to an acute session of SIT. We tested the hypothesis that the acute skeletal muscle response to SIT differs between sexes. Sedentary but healthy men (n = 10) and women (n = 9) were matched for age (22 ± 3 versus 22 ± 3 years old) and cardiorespiratory fitness [45 ± 7 versus 43 ± 10 ml O2 (kg fat-free mass)−1 min−1], with women tested in the mid-follicular phase of their menstrual cycles. Subjects performed three 20 s ‘all-out’ cycling efforts against a resistance of 5% of body mass, interspersed with 2 min of recovery. Relative mean power outputs [7.6 ± 0.5 versus 7.5 ± 0.9 W (kg fat-free mass)−1] were similar between men and women (P > 0.05). Furthermore, there were no differences in the exercise-induced changes in mRNA expression of PGC-1α, PRC, PPARD, SIRT1, RIP140, HSL, HKII, PDK4, PDP1, FOXO3, MURF-1, Myf5, MyoD and VEGFA at 3 h of recovery versus rest (P

We reported that supplementation with green tea extract (GTE) lowered the glycemic response to an oral glucose load following exercise, but via an unknown mechanism (Martin BJ, MacInnis MJ, Gillen JB, Skelly LE, Gibala MJ. Appl Physiol Nutr Metab 41: 1057–1063, 2016. Here we examined the effect of supplementation with GTE on plasma glucose kinetics on ingestion of a glucose beverage during exercise recovery. Eleven healthy, sedentary men (21 ± 2 yr old; body mass index = 23 ± 4 kg/m2, peak O2 uptake = 38 ± 7 ml·kg−1·min−1; means ± SD) ingested GTE (350 mg) or placebo (PLA) thrice daily for 7 days in a double-blind, crossover design. In the fasted state, a primed constant infusion of [U-13C6]glucose was started, and 1 h later, subjects performed a graded exercise test (25 W/3 min) on a cycle ergometer. Immediately postexercise, subjects ingested a 75-g glucose beverage containing 2 g of [6,6-2H2]glucose, and blood samples were collected every 10 min for 3 h of recovery. The rate of carbohydrate oxidation was lower during exercise after GTE vs. PLA (1.26 ± 0.34 vs. 1.48 ± 0.51 g/min, P = 0.04). Glucose area under the curve (AUC) was not different between treatments after drink ingestion (GTE = 1,067 ± 133 vs. PLA = 1,052 ± 91 mM/180 min, P = 0.91). Insulin AUC was lower after GTE vs. PLA (5,673 ± 2,153 vs. 7,039 ± 2,588 µIU/180 min, P = 0.05), despite similar rates of glucose appearance (GTE = 0.42 ± 0.16 vs. PLA = 0.43 ± 0.13 g/min, P = 0.74) and disappearance (GTE = 0.43 ± 0.14 vs. PLA = 0.44 ± 0.14 g/min, P = 0.57). We conclude that short-term GTE supplementation did not affect glucose kinetics following ingestion of an oral glucose load postexercise; however, GTE was associated with attenuated insulinemia. These findings suggest GTE lowers the insulin required for a given glucose load during postexercise recovery, which warrants further mechanistic studies in humans.

Key points A classic unresolved issue in human integrative physiology involves the role of exercise intensity, duration and volume in regulating skeletal muscle adaptations to training. We employed counterweighted single-leg cycling as a unique within-subject model to investigate the role of exercise intensity in promoting training-induced increases in skeletal muscle mitochondrial content. Six sessions of high-intensity interval training performed over 2 weeks elicited greater increases in citrate synthase maximal activity and mitochondrial respiration compared to moderate-intensity continuous training matched for total work and session duration. These data suggest that exercise intensity, and/or the pattern of contraction, is an important determinant of exercise-induced skeletal muscle remodelling in humans. Abstract We employed counterweighted single-leg cycling as a unique model to investigate the role of exercise intensity in human skeletal muscle remodelling. Ten young active men performed unilateral graded-exercise tests to measure single-leg VO2, peak and peak power (Wpeak). Each leg was randomly assigned to complete six sessions of high-intensity interval training (HIIT) [4 × (5 min at 65% Wpeak and 2.5 min at 20% Wpeak)] or moderate-intensity continuous training (MICT) (30 min at 50% Wpeak), which were performed 10 min apart on each day, in an alternating order. The work performed per session was matched for MICT (143 ± 8.4 kJ) and HIIT (144 ± 8.5 kJ, P > 0.05). Post-training, citrate synthase (CS) maximal activity (10.2 ± 0.8 vs. 8.4 ± 0.9 mmol kg protein−1 min−1) and mass-specific [pmol O2•(s•mg wet weight)−1] oxidative phosphorylation capacities (complex I: 23.4 ± 3.2 vs. 17.1 ± 2.8; complexes I and II: 58.2 ± 7.5 vs. 42.2 ± 5.3) were greater in HIIT relative to MICT (interaction effects, P 0.05). In whole muscle, the protein content of COXIV (24%), NDUFA9 (11%) and mitofusin 2 (MFN2) (16%) increased similarly across groups (training effects, P 0.05). Single-leg VO2, peak was also unaffected by training (P > 0.05). In summary, single-leg cycling performed in an interval compared to a continuous manner elicited superior mitochondrial adaptations in human skeletal muscle despite equal total work.

Introduction The ability to adapt actions to perceptions of environmental constraints, perception-action coupling, may be compromised by military operational stress (caloric restriction, sleep disruption, physical exertion). Differences in sleep may influence susceptibility to these stressors. We investigated perception-action coupling during simulated military operational stress and the influence of sleep on perception-action coupling. Methods During a 5-day simulated military operational stress protocol, thirty-six (6 female) service members (25.8 ± 4.7 years) completed three trials of a perception-action coupling task (PACT) in the evening after a night of baseline sleep (BASE), two nights of sleep restriction (T1) and a night of recovery sleep (T2). Participants had 8-hr for baseline and recovery sleep (2300-0700) and 4-hr disturbed sleep on sleep restriction nights (0100-0300 and 0500-0700). Polysomnography was used to determine time spent in different sleep stages: stage 2 (N2), slow wave (SWS) and rapid-eye movement (REM). The tablet-based PACT requires participants make quick, accurate perceptual judgments and responses about the ability of virtual balls to fit through virtual apertures. Linear mixed models were used to assess interaction and main effects of study day and prior sleep on PACT response time (RT) and accuracy (ACC). Results No significant sleep x time interactions or significant main effect of time were found for RT or ACC. A significant main effect of SWS was found for RT (F1,88.307 = 4.331, p = .04). Higher SWS was related to lower (faster) RT. No significant main effects of other sleep stages were found. Conclusion Perception-action coupling was maintained during simulated military operational stress. Participants with more SWS across the study responded faster during the PACT but N2 and REM sleep did not relate to perception-action coupling performance, suggesting a specific effect of SWS on perception-action coupling abilities and behaviors. Support Department of Defense Award #W81XWH-17-2-0070 (PI: Nindl)

Objective To characterize the influence of mode (aerobic/resistance) and volume of exercise (moderate/high) on circulating GH immediately post-exercise as well as following the onset of sleep. Design This study used repeated measures in which subjects randomly completed 5 separate conditions: control (no exercise), moderate volume resistance exercise (MR), high-volume resistance exercise (HR), moderate volume aerobic exercise (MA), and high volume aerobic exercise (HA). Methods Subjects had two overnight stays on each of the 5 iterations. Serial blood draws began as soon as possible after the completion of the exercise session. Blood was obtained every 20 min for 24-h. GH was measured using a chemiluminescent immunoassay. Pooled samples representing post exercise (PE) and first nocturnal pulse (NP) were divided into two aliquots. One of these aliquots was chemically reduced by adding 10 mM glutathione (GSH) to break down disulfide-linked aggregates. Results No differences were observed when pooling GH response at post-exercise (2.02 ± 0.21) and nocturnal pulse (2.63 ± 0.51; p = .32). Pairwise comparisons revealed main effect differences between controls (1.19 ± 0.29) and both MA (2.86 ± 0.31; p = .009) and HA (3.73 ± 0.71; p = .001). Both MA (p = .049) and HA (p = .035) responses were significantly larger than the MR stimulus (1.96 ± 0.28). With GSH reduction, controls significantly differed from MA (p = .018) and HA (p = .003) during PE, but only differed from HA (p = .003) during NP. Conclusions This study demonstrated similar GH responses to exercise and nocturnal pulse, indicating that mode and intensity of exercise does not proportionately affect GH dimeric isoform concentration.

We tested the hypothesis that ingestion of sodium bicarbonate (NaHCO3) prior to an acute session of high-intensity interval training (HIIT) would augment signaling cascades and gene expression linked to mitochondrial biogenesis in human skeletal muscle. On two occasions separated by ∼1 wk, nine men (mean ± SD: age 22 ± 2 yr, weight 78 ± 13 kg, V̇o2 peak 48 ± 8 ml·kg−1·min−1) performed 10 × 60-s cycling efforts at an intensity eliciting ∼90% of maximal heart rate (263 ± 40 W), interspersed with 60 s of recovery. In a double-blind, crossover manner, subjects ingested a total of 0.4 g/kg body weight NaHCO3 before exercise (BICARB) or an equimolar amount of a placebo, sodium chloride (PLAC). Venous blood bicarbonate and pH were elevated at all time points after ingestion ( P < 0.05) in BICARB vs. PLAC. During exercise, muscle glycogen utilization (126 ± 47 vs. 53 ± 38 mmol/kg dry weight, P < 0.05) and blood lactate accumulation (12.8 ± 2.6 vs. 10.5 ± 2.8 mmol/liter, P < 0.05) were greater in BICARB vs. PLAC. The acute exercise-induced increase in the phosphorylation of acetyl-CoA carboxylase, a downstream marker of AMP-activated protein kinase activity, and p38 mitogen-activated protein kinase were similar between treatments ( P > 0.05). However, the increase in PGC-1α mRNA expression after 3 h of recovery was higher in BICARB vs. PLAC (approximately sevenfold vs. fivefold compared with rest, P < 0.05). We conclude that NaHCO3 before HIIT alters the mRNA expression of this key regulatory protein associated with mitochondrial biogenesis. The elevated PGC-1α mRNA response provides a putative mechanism to explain the enhanced mitochondrial adaptation observed after chronic HIIT supplemented with NaHCO3 in rats.

What is the central question of this study? Are there sex-based differences in the acute skeletal muscle response to sprint interval training (SIT)? What is the main finding and its importance? In response to a SIT protocol that involved three 20 s bouts of 'all-out' cycling, the expression of multiple genes associated with mitochondrial biogenesis, metabolic control and structural remodelling was largely similar between men and women matched for fitness. Our findings cannot explain previous reports of sex-based differences in the adaptive response to SIT and suggest that the mechanistic basis for these differences remains to be elucidated. A few studies have reported sex-based differences in response to several weeks of sprint interval training (SIT). These findings may relate to sex-specific responses to an acute session of SIT. We tested the hypothesis that the acute skeletal muscle response to SIT differs between sexes. Sedentary but healthy men (n = 10) and women (n = 9) were matched for age (22 ± 3 versus 22 ± 3 years old) and cardiorespiratory fitness [45 ± 7 versus 43 ± 10 ml O

Green tea extract (GTE) ingestion improves glucose homeostasis in healthy and diabetic humans, but the interactive effect of GTE and exercise is unknown. The present study examined the effect of short-term GTE supplementation on the glycemic response to an oral glucose load at rest and following an acute bout of exercise, as well as substrate oxidation during exercise. Eleven sedentary, overweight men with fasting plasma glucose (FPG) ≥5.6 mmol·L−1 (age, 34 ± 13 years; body mass index = 32 ± 5 kg·m−2; FPG = 6.8 ± 1.0; mean ± SD) ingested GTE (3× per day, 1050 mg·day–1 total) or placebo (PLA) for 7 days in a double-blind, crossover design. The effects of a 75-g glucose drink were assessed on 4 occasions during both GTE and PLA treatments: On days 1 and 5 at rest, and again following an acute bout of exercise on days 3 and 8. The glycemic response was assessed via an indwelling continuous glucose monitor (CGM) and venous blood draws. At rest, 1-h CGM glucose area under the curve was not different (P > 0.05), but the postexercise response was lower after GTE versus PLA (330 ± 53 and 393 ± 65 mmol·L−1·min−1, main effect of treatment, P < 0.05). The 1-h postprandial peaks in venous blood glucose (8.6 ± 1.6 and 9.8 ± 2.2 mmol·L−1) and insulin (96 ± 59 and 124 ± 68 μIU·ml−1) were also lower postexercise with GTE versus PLA (time × treatment interactions, P < 0.05). In conclusion, short-term GTE supplementation did not affect postprandial glucose at rest; however, GTE was associated with an attenuated glycemic response following a postexercise oral glucose load. These data suggest that GTE might alter skeletal muscle glucose uptake in humans.

Astorino, TA, Martin, BJ, Schachtsiek, L, Wong, K, and Ng, K. Minimal effect of acute caffeine ingestion on intense resistance training performance. J Strength Cond Res XX(X): 000–000, 2010—The primary aim of the study was to determine the efficacy of acute caffeine intake to enhance intense resistance training performance. Fourteen resistance-trained men (age and body mass = 23.1 6 1.1 years and 83.4 6 13.2 kg, respectively) who regularly consumed caffeine ingested caffeine (6 mgkg 21 ) or placebo 1 hour before completion of 4 sets of barbell bench press, leg press, bilateral row, and barbell shoulder press to fatigue at 70–80% 1-repetition maximum. Two minutes of rest was allotted between sets. Saliva samples were obtained to assess caffeine concentration. The number of repetitions completed per set and total weight lifted were recorded as indices of performance. Two-way analysis of variance with repeated measures was used to examine differences in performance across treatment and sets. Compared to placebo, there was a small but significant effect (p , 0.05) of acute caffeine intake on repetitions completed for the leg press but not for upper-body exercise (p . 0.05). Total weight lifted across sets was similar (p . 0.05) with caffeine (22,409.5 6 3,773.2 kg) vs. placebo (21,185.7 6 4,655.4 kg), yet there were 9 responders to caffeine, represented by a meaningful increase in total weight lifted with caffeine vs. placebo. Any ergogenic effect of caffeine on performance of fatiguing, total-body resistance training appears to be of limited practical significance. Additional research is merited to elucidate interindividual differences in caffeine-mediated improvements in performance.