Acetaminophen influences musculoskeletal signaling but not adaptations to endurance exercise training.

Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6-week, low-dose ACE regimen on muscle and bone adaptations in exercising and non-exercising rats. Nine-week-old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% incline for 2 min at 15 cm/s, 2 min at 20 cm/s, and 26 min at 25 cm/s. A human equivalent dose of ACE was administered (379 mg/kg body weight) in drinking water and adjusted each week based on body weight. Food, water intake, and body weight were measured daily. At the beginning of week 6, animals in the exercise group completed a maximal treadmill test. At the end of week 6, rats were euthanized, and muscle cross-sectional area (CSA), fiber type, and signaling pathways were measured. Additionally, three-point bending and microcomputer tomography were measured in the femur. Follow-up experiments in human primary muscle cells were used to explore supra-physiological effects of ACE. Data were analyzed using a two-way ANOVA for treatment (ACE or placebo) and condition (exercise or non-exercise) for all animal outcomes. Data for cell culture experiments were analyzed via ANOVA. If omnibus significance was found in either ANOVA, a post hoc analysis was completed, and a Tukey's adjustment was used. ACE did not alter body weight, water intake, food intake, or treadmill performance (p > .05). There was a treatment-by-condition effect for Young's Modulus where placebo exercise was significantly lower than placebo control (p < .05). There was no treatment by condition effects for microCT measures, muscle CSA, fiber type, or mRNA expression. Phosphorylated-AMPK was significantly increased with exercise (p < .05) and this was attenuated with ACE treatment. Furthermore, phospho-4EBP1 was depressed in the exercise group compared to the control (p < .05) and increased in the ACE control and ACE exercise group compared to placebo exercise (p < .05). A low dose of ACE did not influence chronic musculoskeletal adaptations in exercising rodents but acutely attenuated AMPK phosphorylation and 4EBP1 dephosphorylation post-exercise.

Exogenous ketone esters as a potential therapeutic for treatment of sarcopenic obesity.

Identifying effective treatment(s) for sarcopenia and sarcopenic obesity is of paramount importance as the global population advances in age and obesity continues to be a worldwide concern. Evidence has shown that a ketogenic diet can be beneficial for the preservation of muscle quality and function in older adults, but long-term adherence is low due in part to the high-fat (≥80%), very low carbohydrate (<5%) composition of the diet. When provided in adequate amounts, exogenous ketone esters (KEs) can increase circulating ketones to concentrations that exceed those observed during prolonged fasting or starvation without significant alterations in the diet. Ketone esters first emerged in the mid-1990s and their use in preclinical and clinical research has escalated within the past 10-15 years. We present findings from a narrative review of the existing literature for a proposed hypothesis on the effects of exogenous ketones as a therapeutic for preservation of skeletal muscle and function within the context of sarcopenic obesity and future directions for exploration. Much of the reviewed literature herein examines the mechanisms of the ketone diester (R,S-1,3-butanediol diacetoacetate) on skeletal muscle mass, muscle protein synthesis, and epigenetic regulation in murine models. Additional studies are needed to further examine the key regulatory factors producing these effects in skeletal muscle, examine convergent and divergent effects among different ketone ester formulations, and establish optimal frequency and dosing regimens to translate these findings into humans.

A single, maximal dose of celecoxib, ibuprofen, or flurbiprofen does not reduce the muscle signalling response to plyometric exercise in young healthy adults.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) possess analgesic and anti-inflammatory properties by inhibiting cyclooxygenase (COX) enzymes. Conflicting evidence exists on whether NSAIDs influence signaling related to muscle adaptations and exercise with some research finding a reduction in muscle protein synthesis signaling via the AKT-mTOR pathway, changes in satellite cell signaling, reductions in muscle protein degradation, and reductions in cell proliferation. In this study, we determined if a single maximal dose of flurbiprofen (FLU), celecoxib (CEL), ibuprofen (IBU), or a placebo (PLA) affects the short-term muscle signaling responses to plyometric exercise. METHODS: This was a block randomized, double-masked, crossover design, where 12 participants performed four plyometric exercise bouts consisting of 10 sets of 10 plyometric jumps at 40% 1RM. Two hours before exercise, participants consumed a single dose of celecoxib (CEL 200 mg), IBU (800 mg), FLU (100 mg) or PLA with food. Muscle biopsy samples were collected before and 3-h after exercise from the vastus lateralis. Data were analyzed using a repeated measures (RM) ANOVA, ANOVA, or a Friedman test. Significance was considered at p < 0.05. RESULTS: We found no treatment effects on the mRNA expression of PTSG1, PTSG2, MYC, TBP, RPLOP, MYOD1, Pax7, MYOG, Atrogin-1, or MURF1 (all, p > 0.05). We also found no treatment effects on AKT-mTOR signaling or MAPK signaling measured through the phosphorylation status of mTORS2441, mTORS2448, RPS6 235/236, RPS 240/244, 4EBP1, ERK1/2, p38 T180/182 normalized to their respective total abundance (all, p > 0.05). However, we did find a significant difference between MNK1 T197/202 in PLA compared to FLU (p < .05). CONCLUSION: A single, maximal dose of IBU, CEL, or FLU taken prior to exercise did not affect the signaling of muscle protein synthesis, protein degradation, or ribosome biogenesis three hours after a plyometric training bout.

What About Water? Implications for Body Composition Assessment in Military Personnel.

ABSTRACT: Sergi, TE, Roberts, BM, and Heileson, JL. What About Water? Implications for Body Composition Assessment in Military Personnel. J Strength Cond Res 38(9): e534-e540, 2024-Body composition standards ensure service members maintain physical fitness, wellness, and support mission readiness. Anthropometric techniques (i.e., height/mass, circumference-based "tape test") have been the primary screening and percent body fat (%BF) assessment method in military personnel for about 4 decades. Recently, the Army and Marine Corps have implemented more advanced body composition assessment methods, such as air displacement plethysmography (ADP), multifrequency bioelectrical impedance analysis (MF-BIA), and dual-energy x-ray absorptiometry (DXA), to serve as supplemental %BF assessment after failing the tape test. Although supplemental assessments are intended to improve on the accuracy and precision of the tape test, preassessment standardization, specifically regarding acute water ingestion (AWI), is lacking. Thus, the purpose of this narrative review was to (a) summarize the available literature regarding the influence of AWI on body composition estimates derived from ADP, MF-BIA, and DXA and (b) provide evidence-based recommendations for researchers and practitioners. Studies indicate that AWI increases %BF estimates with ADP (4 of 6 [4/6] observations) and MF-BIA (6/7), whereas AWI increases muscle mass (6/6) and likely decreases %BF (2/3) when obtained by DXA. In conclusion, ADP, MF-BIA, and DXA are susceptible to confounding from AWI, leading to inaccurate body composition estimates that may negatively affect the careers of military personnel. Based on the findings from this narrative review, military practitioners and researchers should (a) follow manufacturer guidelines for calorie intake [food and fluid] and exercise avoidance, (b) conduct urine-specific gravity testing [if possible], and (c) limit AWI to <250 ml before assessment.

Sex Does Not Affect Changes in Body Composition and Insulin-Like Growth Factor-I During US Army Basic Combat Training.

ABSTRACT: Roberts, BM, Staab, JS, Caldwell, AR, Sczuroski, CE, Staab, JE, Lutz, LJ, Reynoso, M, Geddis, AV, Taylor, KM, Guerriere, KI, Walker, LA, Hughes, JM, and Foulis, SA. Sex does not affect changes in body composition and insulin-like growth factor-I during US Army basic combat training. J Strength Cond Res 38(6): e304-e309, 2024-Insulin-like growth factor 1 (IGF-I) has been implicated as a biomarker of health and body composition. However, whether changes in body composition are associated with changes in IGF-I is unclear. Therefore, we examined the relationship between body composition changes (i.e., fat mass and lean mass) and total serum IGF-I levels in a large cohort of young men ( n = 809) and women ( n = 397) attending US Army basic combat training (BCT). We measured body composition using dual energy x-ray absorptiometry and total serum IGF-I levels during week 1 and week 9 of BCT. We found that pre-BCT lean mass ( r = 0.0504, p = 0.082) and fat mass ( r = 0.0458, p = 0.082) were not associated with pre-BCT IGF-I. Body mass, body mass index, body fat percentage, and fat mass decreased, and lean mass increased during BCT (all p < 0.001). Mean (± SD ) IGF-I increased from pre-BCT (176 ± 50 ng·ml -1 ) to post-BCT (200 ± 50 ng·ml -1 , p < 0.001). Inspection of the partial correlations indicated that even when considering the unique contributions of other variables, increases in IGF-I during BCT were associated with both increased lean mass ( r = 0.0769, p = 0.023) and increased fat mass ( r = 0.1055, p < 0.001) with no sex differences. Taken together, our data suggest that although changes in IGF-I weakly correlated with changes in body composition, IGF-I, in isolation, is not an adequate biomarker for predicting changes in body composition during BCT in US Army trainees.

A Narrative Review of Performance and Health Research in US Army Rangers.

ABSTRACT: Roberts, BM, Mantua, J, Naylor, JA, and Ritland, BM. A narrative review of performance and health research in US army rangers. J Strength Cond Res 37(5): 1157-1161, 2023-The 75th Ranger Regiment (75RR) is an elite airborne infantry unit that is prepared to deploy on short notice and is resourced to maintain exceptional proficiency and readiness through prolonged deployments. Soldiers must be airborne qualified and pass a number of physical and psychological tests during training to become a member of 75RR. Rangers must maintain a level of physical performance comparable to high-level athletes while also handling operational stressors that include a negative-energy balance, high-energy expenditure, sleep restriction, and completing missions in extreme environments, all of which increase their chance of illness or infection. There are also situations of heighted injury risk, such as parachuting and repelling, which are routinely required in combat operations. Thus far, only one screening tool to assess injury risk has been developed. There are also physical training programs to enhance performance for Rangers in 75RR. This narrative review aims to evaluate the body of literature surrounding performance and health-related research in US Army Rangers to understand how Rangers are impacted during training or operations, to inform future training recommendations, and to identify areas of future research that are warranted and could potentially optimize the health and performance of Rangers during future training or operation events.

Metabolic Adaptations to Weight Loss: A Brief Review.

ABSTRACT: Martínez-Gómez, MG and Roberts, BM. Metabolic adaptations to weight loss: A brief review. J Strength Cond Res 36(10): 2970-2981, 2022-As the scientific literature has continuously shown, body mass loss attempts do not always follow a linear fashion nor always go as expected even when the intervention is calculated with precise tools. One of the main reasons why this tends to happen relies on our body's biological drive to regain the body mass we lose to survive. This phenomenon has been referred to as "metabolic adaptation" many times in the literature and plays a very relevant role in the management of obesity and human weight loss. This review will provide insights into some of the theoretical models for the etiology of metabolic adaptation as well as a quick look into the physiological and endocrine mechanisms that underlie it. Nutritional strategies and dietetic tools are thus necessary to confront these so-called adaptations to body mass loss. Among some of these strategies, we can highlight increasing protein needs, opting for high-fiber foods or programming-controlled diet refeeds, and diet breaks over a large body mass loss phase. Outside the nutritional aspects, it might be wise to increase the physical activity and thus the energy flux of an individual when possible to maintain diet-induced body mass loss in the long term. This review will examine these protocols and their viability in the context of adherence and sustainability for the individual toward successful body mass loss.

Does HMB Enhance Body Composition in Athletes? A Systematic Review and Meta-analysis.

ABSTRACT: Holland, BM, Roberts, BM, Krieger, JW, and Schoenfeld, BJ. Does HMB enhance body composition in athletes? A systematic review and meta-analysis. J Strength Cond Res 36(2): 585-592, 2022-The purpose of this article was to systematically review and meta-analyze the current literature to determine the effects of HMB on body composition in athletes. Studies were deemed eligible for inclusion if they met the following criteria: (a) were an experimental design published in a peer-reviewed, English-language journal; (b) included human athletic populations; (c) assessed body mass (BM), fat mass (FM), or fat-free mass (FFM) using a validated measure; (d) and had a minimum supplementation period of 4 weeks. Separate analyses were performed for BM, FM, and FFM using robust variance random-effects meta-regression for multilevel data structures, with adjustments for small samples. The final analysis of BM comprised a total of 208 subjects from 7 studies. Analysis of FFM and FM encompassed 5 studies comprising 161 subjects and 5 studies comprising 128 subjects, respectively. The principal finding of this analysis suggests HMB may have a small, positive impact on FFM in athletes (0.30 ± 0.13; 95% confidence interval [CI]: -0.07 to 0.68; p = 0.08), although this seems specific to when protein intake is suboptimal (<1.6 g·kg-1·d-1). Consistent with previous research on athletes, HMB demonstrated no significant effect on BM (-0.02 ± 0.04; 95% CI: -0.14 to 0.10; p = 0.70) and a small, nonsignificant effect on FM (-0.33 ± 0.23; 95% CI: -0.96 to 0.31; p = 0.22). More research is required to establish HMB's influence on FFM in athletes. It is also important to consider the dosage of HMB and training parameters of athletes because these will likely influence the efficacy of supplementation.

A dietary ketone ester mitigates histological outcomes of NAFLD and markers of fibrosis in high-fat diet fed mice.

Nutritional ketosis as a therapeutic tool has been extended to the treatment of metabolic diseases, including obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to determine whether dietary administration of the ketone ester (KE) R,S-1,3-butanediol diacetoacetate (BD-AcAc2) attenuates markers of hepatic stellate cell (HSC) activation and hepatic fibrosis in the context of high-fat diet (HFD)-induced obesity. Six-week-old male C57BL/6J mice were placed on a 10-wk ad libitum HFD (45% fat, 32% carbohydrates, 23% proteins). Mice were then randomized to one of three groups (n = 10 per group) for an additional 12 wk: 1) control (CON), continuous HFD; 2) pair-fed (PF) to KE, and 3) KE (HFD + 30% energy from BD-AcAc2, KE). KE feeding significantly reduced histological steatosis, inflammation, and total NAFLD activity score versus CON, beyond improvements observed for calorie restriction alone (PF). Dietary KE supplementation also reduced the protein content and gene expression of profibrotic markers (α-SMA, COL1A1, PDGF-ß, MMP9) versus CON (P < 0.05), beyond reductions observed for PF versus CON. Furthermore, KE feeding increased hepatic markers of anti-inflammatory M2 macrophages (CD163) and also reduced proinflammatory markers [tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and cellular communication network factor 1 (CCN1)] versus CON and PF (P ≤ 0.05), in the absence of changes in markers of total hepatic macrophage content (F4/80 and CD68; P > 0.05). These data highlight that the dietary ketone ester BD-AcAc2 ameliorates histological NAFLD and inflammation and reduces profibrotic and proinflammatory markers. Future studies to further explore potential mechanisms are warranted.NEW & NOTEWORTHY To our knowledge, this is the first study focusing on hepatic outcomes in response to dietary ketone ester feeding in male mice with HFD-induced NAFLD. Novel findings include that dietary ketone ester feeding ameliorates NAFLD outcomes via reductions in histological steatosis and inflammation. These improvements were beyond those observed for caloric restriction alone. Furthermore, dietary ketone ester feeding was associated with greater reductions in markers of hepatic fibrogenesis and inflammation compared with control and calorie-restricted mice.

The Importance of Resistance Exercise Training to Combat Neuromuscular Aging.

Older adults undergoing age-related decrements in muscle health can benefit substantially from resistance exercise training, a potent stimulus for whole muscle and myofiber hypertrophy, neuromuscular performance gains, and improved functional mobility. With the use of advancing technologies, research continues to elucidate the mechanisms of and heterogeneity in adaptations to resistance exercise training beyond differences in exercise prescription. This review highlights the current knowledge in these areas and emphasizes knowledge gaps that require future attention of the field.

Sex Differences in Resistance Training: A Systematic Review and Meta-Analysis.

Roberts, BM, Nuckols, G, and Krieger, JW. Sex differences in resistance training: A systematic review and meta-analysis. J Strength Cond Res 34(5): 1448-1460, 2020-The purpose of this study was to determine whether there are different responses to resistance training for strength or hypertrophy in young to middle-aged males and females using the same resistance training protocol. The protocol was pre-registered with PROSPERO (CRD42018094276). Meta-analyses were performed using robust variance random effects modeling for multilevel data structures, with adjustments for small samples using package robumeta in R. Statistical significance was set at P < 0.05. The analysis of hypertrophy comprised 12 outcomes from 10 studies with no significant difference between males and females (effect size [ES] = 0.07 ± 0.06; P = 0.31; I = 0). The analysis of upper-body strength comprised 19 outcomes from 17 studies with a significant effect favoring females (ES = -0.60 ± 0.16; P = 0.002; I = 72.1). The analysis of lower-body strength comprised 23 outcomes from 23 studies with no significant difference between sexes (ES = -0.21 ± 0.16; P = 0.20; I = 74.7). We found that males and females adapted to resistance training with similar effect sizes for hypertrophy and lower-body strength, but females had a larger effect for relative upper-body strength. Given the moderate effect size favoring females in the upper-body strength analysis, it is possible that untrained females display a higher capacity to increase upper-body strength than males. Further research is required to clarify why this difference occurs only in the upper body and whether the differences are due to neural, muscular, motor learning, or are an artifact of the short duration of studies included.

HDAC1 activates FoxO and is both sufficient and required for skeletal muscle atrophy.

The Forkhead box O (FoxO) transcription factors are activated, and necessary for the muscle atrophy, in several pathophysiological conditions, including muscle disuse and cancer cachexia. However, the mechanisms that lead to FoxO activation are not well defined. Recent data from our laboratory and others indicate that the activity of FoxO is repressed under basal conditions via reversible lysine acetylation, which becomes compromised during catabolic conditions. Therefore, we aimed to determine how histone deacetylase (HDAC) proteins contribute to activation of FoxO and induction of the muscle atrophy program. Through the use of various pharmacological inhibitors to block HDAC activity, we demonstrate that class I HDACs are key regulators of FoxO and the muscle-atrophy program during both nutrient deprivation and skeletal muscle disuse. Furthermore, we demonstrate, through the use of wild-type and dominant-negative HDAC1 expression plasmids, that HDAC1 is sufficient to activate FoxO and induce muscle fiber atrophy in vivo and is necessary for the atrophy of muscle fibers that is associated with muscle disuse. The ability of HDAC1 to cause muscle atrophy required its deacetylase activity and was linked to the induction of several atrophy genes by HDAC1, including atrogin-1, which required deacetylation of FoxO3a. Moreover, pharmacological inhibition of class I HDACs during muscle disuse, using MS-275, significantly attenuated both disuse muscle fiber atrophy and contractile dysfunction. Together, these data solidify the importance of class I HDACs in the muscle atrophy program and indicate that class I HDAC inhibitors are feasible countermeasures to impede muscle atrophy and weakness.

Genome-wide identification of FoxO-dependent gene networks in skeletal muscle during C26 cancer cachexia.

BACKGROUND: Evidence from cachectic cancer patients and animal models of cancer cachexia supports the involvement of Forkhead box O (FoxO) transcription factors in driving cancer-induced skeletal muscle wasting. However, the genome-wide gene networks and associated biological processes regulated by FoxO during cancer cachexia are unknown. We hypothesize that FoxO is a central upstream regulator of diverse gene networks in skeletal muscle during cancer that may act coordinately to promote the wasting phenotype. METHODS: To inhibit endogenous FoxO DNA-binding, we transduced limb and diaphragm muscles of mice with AAV9 containing the cDNA for a dominant negative (d.n.) FoxO protein (or GFP control). The d.n.FoxO construct consists of only the FoxO3a DNA-binding domain that is highly homologous to that of FoxO1 and FoxO4, and which outcompetes and blocks endogenous FoxO DNA binding. Mice were subsequently inoculated with Colon-26 (C26) cells and muscles harvested 26 days later. RESULTS: Blocking FoxO prevented C26-induced muscle fiber atrophy of both locomotor muscles and the diaphragm and significantly spared force deficits. This sparing of muscle size and function was associated with the differential regulation of 543 transcripts (out of 2,093) which changed in response to C26. Bioinformatics analysis of upregulated gene transcripts that required FoxO revealed enrichment of the proteasome, AP-1 and IL-6 pathways, and included several atrophy-related transcription factors, including Stat3, Fos, and Cebpb. FoxO was also necessary for the cancer-induced downregulation of several gene transcripts that were enriched for extracellular matrix and sarcomere protein-encoding genes. We validated these findings in limb muscles and the diaphragm through qRT-PCR, and further demonstrate that FoxO1 and/or FoxO3a are sufficient to increase Stat3, Fos, Cebpb, and the C/EBPß target gene, Ubr2. Analysis of the Cebpb proximal promoter revealed two bona fide FoxO binding elements, which we further establish are necessary for Cebpb promoter activation in response to IL-6, a predominant cytokine in the C26 cancer model. CONCLUSIONS: These findings provide new evidence that FoxO-dependent transcription is a central node controlling diverse gene networks in skeletal muscle during cancer cachexia, and identifies novel candidate genes and networks for further investigation as causative factors in cancer-induced wasting.

Diaphragm and ventilatory dysfunction during cancer cachexia.

Cancer cachexia is characterized by a continuous loss of locomotor skeletal muscle mass, which causes profound muscle weakness. If this atrophy and weakness also occurs in diaphragm muscle, it could lead to respiratory failure, which is a major cause of death in patients with cancer. Thus, the purpose of the current study was to determine whether colon-26 (C-26) cancer cachexia causes diaphragm muscle fiber atrophy and weakness and compromises ventilation. All diaphragm muscle fiber types were significantly atrophied in C-26 mice compared to controls, and the atrophy-related genes, atrogin-1 and MuRF1, significantly increased. Maximum isometric specific force of diaphragm strips, absolute maximal calcium activated force, and maximal specific calcium-activated force of permeabilized diaphragm fibers were all significantly decreased in C-26 mice compared to controls. Further, isotonic contractile properties of the diaphragm were affected to an even greater extent than isometric function. Ventilation measurements demonstrated that C-26 mice have a significantly lower tidal volume compared to controls under basal conditions and, unlike control mice, an inability to increase breathing frequency, tidal volume, and, thus, minute ventilation in response to a respiratory challenge. These data demonstrate that C-26 cancer cachexia causes profound respiratory muscle atrophy and weakness and ventilatory dysfunction.

The dose-response effects of flurbiprofen, indomethacin, ibuprofen, and naproxen on primary skeletal muscle cells.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, flurbiprofen, naproxen sodium, and indomethacin are commonly employed for their pain-relieving and inflammation-reducing qualities. NSAIDs work by blocking COX-1 and/or COX-2, enzymes which play roles in inflammation, fever, and pain. The main difference among NSAIDs lies in their affinity to these enzymes, which in turn, influences prostaglandin secretion, and skeletal muscle growth and regeneration. The current study investigated the effects of NSAIDs on human skeletal muscle cells, focusing on myoblast proliferation, differentiation, and muscle protein synthesis signaling. METHODS: Using human primary muscle cells, we examined the dose-response impact of flurbiprofen (25-200 µM), indomethacin (25-200 µM), ibuprofen (25-200 µM), and naproxen sodium (25-200 µM), on myoblast viability, myotube area, fusion, and prostaglandin production. RESULTS: We found that supraphysiological concentrations of indomethacin inhibited myoblast proliferation (-74 ± 2% with 200 µM; -53 ± 3% with 100 µM; both p < 0.05) compared to control cells and impaired protein synthesis signaling pathways in myotubes, but only attenuated myotube fusion at the highest concentrations (-18 ± 2% with 200 µM, p < 0.05) compared to control myotubes. On the other hand, ibuprofen had no such effects. Naproxen sodium only increased cell proliferation at low concentrations (+36 ± 2% with 25 µM, p < 0.05), and flurbiprofen exhibited divergent impacts depending on the concentration whereby low concentrations improved cell proliferation (+17 ± 1% with 25 µM, p < 0.05) but high concentrations inhibited cell proliferation (-32 ± 1% with 200 µM, p < 0.05). CONCLUSION: Our findings suggest that indomethacin, at high concentrations, may detrimentally affect myoblast proliferation and differentiation via an AKT-dependent mechanism, and thus provide new understanding of NSAIDs' effects on skeletal muscle cell development.

Non-Steroidal Anti-Inflammatory Drugs Do Not Affect the Bone Metabolic Response to Exercise.

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAID) are associated with increased stress fracture risk, potentially due to inhibiting the adaptive bone formation responses to exercise. This study investigated if a single, maximal dose of three different NSAIDs alters bone formation biomarker response to strenuous exercise. METHODS: In a randomized, counter-balanced order, 12 participants (10 male, 2 female), performed four bouts of plyometric jumps, each separated by at least one week. Two hours before exercise, participants consumed either placebo (PLA) or NSAID: Ibuprofen (IBU, 800 mg), celecoxib (CEL, 200 mg), flurbiprofen (FLU, 100 mg). Blood was collected before (PRE), and at 0, 15, 60, 120, and 240 minutes post-exercise. Parathyroid hormone (PTH), ionized calcium (iCa), procollagen type 1 N-terminal propeptide (P1NP), bone alkaline phosphatase (BAP), osteocalcin (OCN), C-terminal telopeptide of type 1 collagen (CTX), tartrate resistant acid phosphatase (TRAP5b), and sclerostin (SCL) were measured. Prostaglandin E2 metabolite (PGE2M) and creatinine (Cr) were measured in urine. Data were analyzed using repeated measures ANOVA and area under the curve analysis (AUC). Data are mean ± SD. RESULTS: There was an exercise effect for P1NP, BAP, OCN, CTX, TRAP5b, SCL, OPG, PTH, and iCa (all p < 0.05), but no NSAID treatment effect for any biomarker (all p > 0.05). AUC analyses were not different for any biomarker (p > 0.05). PGE2M was higher during the PLA trial (322 ± 153 pg/mg Cr, p < 0.05) compared to IBU (135 ± 83 pg/mg), CEL (202 ± 107 pg/mg), and FLU (159 ± 74 pg/mg). CONCLUSIONS: Plyometric exercise induced changes in bone metabolism, but the responses were unaltered by consuming NSAIDs two hours before exercise.

Evaluation of the Effectiveness of ROTC Army Cadet Exercise Training for the Army Combat Fitness Test.

The Army Combat Fitness Test (ACFT) is used to evaluate the fitness level of potential Cadets for military readiness. The purpose of this study was to evaluate the effectiveness of the exercise training program implemented by an Army Reserve Officers' Training Corps (ROTC) program to gauge the performance metrics of the ACFT. METHODS: Twenty-six student Cadets of the ROTC at the University of Alabama at Birmingham (UAB) program participated in the study. Over an 8-month period, the ROTC Cadets trained on campus three days per week. Training was performed in a circuit training format and each participant cycled through each of the four training stations (Strength, Conditioning, Core, and Endurance) for 15 minutes each session (for a total training time of 60 minutes). Each Cadet had body mass and body composition assessed as well as each component of the ACFT [maximum dead lift (MDL), standing power throw (SPT), hand release push-up (HRP), sprint-drag-carry (SDC), leg tuck/plank (LTK/PLK), and 2-mile run (2MR)]. Each variable was evaluated at three time points (pre-, mid-, and post-training program). RESULTS: There was a significant difference in the 2MR score between time points [F(2,50) = 4.530, p = .016, η2 = 0.153] with a significant difference between time point at pre- and post-training (p = .02). No other variables displayed a significant change: body mass (p = .741), body fat percentage (p = .238), MDL (p = .061), SPT (p = .308), HRP (p = .126), SDC (p = 0.132), LTK/PLK (p = 0.583). CONCLUSION: The results of this study suggest that the short-term training program used improves 2MR, but not other components of the ACFT over the course of an academic year.

NSAIDs do not prevent exercise-induced performance deficits or alleviate muscle soreness: A placebo-controlled randomized, double-blinded, cross-over study.

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently consumed by athletes to manage muscle soreness, expedite recovery, or improve performance. Despite the prevalence of NSAID use, their effects on muscle soreness and performance, particularly when administered prophylactically, remain unclear. This randomized, double-blind, counter-balanced, crossover study examined the effect of consuming a single dose of each of three NSAIDs (celecoxib, 200 mg; ibuprofen, 800 mg; flurbiprofen, 100 mg) or placebo 2 h before on muscle soreness and performance following an acute plyometric training session. Twelve healthy adults, aged 18-42 years, completed a standardized plyometric exercise session consisting of 10 sets of 10 repetitions at 40 % 1-repetition maximum (1RM) on a leg press device. During exercise, total work, rating of perceived exertion, and heart rate were measured. Maximum voluntary contraction force (MVC), vertical jump height, and muscle soreness were measured before exercise and 4-h and 24-h post-exercise. We found no significant differences in total work, heart rate, or rating of perceived exertion between treatments. Additionally, no significant differences in muscle soreness or vertical jump were observed between treatments. Ibuprofen and flurbiprofen did not prevent decrements in MVC, but celecoxib attenuated decreases in MVC 4-h post exercise (p < 0.05). This study suggests that athletes may not benefit from prophylactic ibuprofen or flurbiprofen treatment to prevent discomfort or performance decrements associated with exercise, but celecoxib may mitigate short-term performance decrements.

Sex Differences in Body Composition and Fitness Scores in Military Reserve Officers' Training Corps Cadets.

INTRODUCTION: The cadets in the U.S. Army Reserve Officers' Training Corps (ROTC) consist of students from varied backgrounds. As part of collegiate ROTC programs, cadets must pass fitness tests and adhere to body composition standards in addition to completing their education. The previous fitness test of record was the Army Physical Fitness Test (APFT), but it was recently changed to the Army Combat Fitness Test (ACFT) to better test soldiers for combat capabilities. As part of the standardized scoring, the ACFT is no longer separated by sex or age as in the APFT, but rather by job duty. The purpose of this study was to characterize the modern ROTC cadet based on body composition measures and APFT and ACFT scores and then determine how those factors are related. MATERIALS AND METHODS: We calculated body mass index (BMI), fat mass, fat-free mass (FFM), fat-free mass index (FFMI), and fat mass index (FMI) (n = 68, 42 males, 26 females). We used Pearson correlations to compare the scores to body composition assessments and Student's t-tests to determine if there were differences between sexes. We hypothesized that those with higher FFM and FFMI will have a higher passing rate on the ACFT and that males would perform better on the ACFT because of having more FFM. RESULTS: We found that cadets, regardless of sex, were borderline overweight using BMI standards and that BMI did not correlate with any fitness tests. When comparing sexes, both males and females had high passing rates on the APFT, but females struggled to pass the ACFT mostly because of the leg tuck. We also found that ACFT scores were strongly correlated with FFM and FFMI, yet no body composition measures were correlated with APFT scores. CONCLUSIONS: It is clear from our data that structured training programs and nutrition guidance are needed with an emphasis on changing body composition to increase lean mass and strength to increase the performance of ROTC cadets on the ACFT.

Differential activation of AKT isoforms by growth factors in human myotubes.

AKT signaling plays a crucial role in muscle physiology, and is activated by stimuli, including insulin, growth factors, and exercise. Three AKT isoforms have been identified in mammals, and they possess both distinct and redundant functions. However, it is currently unknown what the predominant AKT isoform is in primary human skeletal myotubes, and very little is known regarding the effects of insulin and insulin-like growth factor-I (IGF-I) on AKT isoforms activation in human myotubes. Thus, we sought to determine the abundances of each AKT isoform in primary human skeletal myotubes and their responses to insulin or IGF-I. Analysis of protein lysates by liquid chromatography-parallel reaction monitoring/mass spectrometry revealed that AKT1 was the most abundant AKT isoform and AKT3 was the least-abundant isoform. Next, myotubes were treated with either 100 nM insulin or 10 nM IGF-I for 5, 20, 45, or 60 min. In response to insulin, there was a significant treatment effect on phosphorylation of AKT1 and AKT2, but not AKT3 (p < 0.01). In response to IGF-I, there was a significant treatment effect on phosphorylation of pan-AKT at all timepoints compared to control (p < 0.01). Next, we determined how much of the total AKT isoform pool was phosphorylated. For insulin stimulation, AKT1 was significantly higher than AKT2 at 5 min and 60 min posttreatment (p < 0.05 both) and significantly different than AKT3 at all timepoints (p < 0.05). For IGF-I stimulation, AKT1 was significantly higher than AKT2 at 45 and 60 min posttreatment (p < 0.05 both) and significantly higher than AKT3 at all timepoints (p < 0.05). Our findings reveal the differential phosphorylation patterns among the AKT isoforms and suggest a potential explanation for the regulatory role of AKT1 in skeletal muscle.