Structural and Functional Properties of Lower Extremity Tendons in Men.

ABSTRACT: Comstock, BA, Flanagan, SD, Denegar, CR, Newton, RU, Häkkinen, K, Volek, JS, Maresh, CM, Kraemer, WJ. Structural and functional properties of lower extremity tendons in men. J Strength Cond Res XX(X): 000-000, 2024-The purpose of this study was to understand further patellar and Achilles tendon structure and function, body composition, and serum collagen turnover biomarkers in young men who performed heavy resistance training (RT, n = 13, age: 22.2 ± 1.4 years) compared with recreationally active men who were not resistance-trained (NR, n = 13, age: 22.8 ± 2.2 years). Tendon properties were measured at rest and during maximal voluntary isometric efforts using ultrasonography and dynamometry. Lean body mass (LBM) and bone mineral density (BMD) were assessed with dual X-ray absorptiometry. Serum collagen turnover markers were analyzed and related to tendon measures. Resistance-trained men had significantly (p ≤ 0.05) greater LBM and BMD compared with recreationally active men. Resistance-trained men also showed significantly greater patellar tendon (PT) stiffness (45%) and Young's modulus (36%), though the PT cross-sectional area (CSA) did not differ significantly between groups. Achilles tendon CSA was significantly larger in resistance-trained men. Still, other properties such as stiffness and modulus did not differ significantly between the groups. Serum collagen turnover markers showed no significant differences between groups and were not correlated to any tendon or bone biomarkers. The findings support that resistance-trained men have greater LBM and BMD. However now, it reveals that tendon adaptations differ, as not all measures were similarly affected in both tendons. The blood biomarkers did not show any obvious roles in explaining the differential changes in tendons. Heavy RT induces differential tendon changes potentially due to complex interactions of training variables.

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.

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.

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.

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.

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.

Effects of Multi-ingredient Preworkout Supplements on Physical Performance, Cognitive Performance, Mood State, and Hormone Concentrations in Recreationally Active Men and Women.

ABSTRACT: 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 36(9): 2493-2501, 2022-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 -1 ) and BAC (10.8 ± 1.4 W·kg -1 ) compared with PLA (10.4 ± 1.2 W·kg -1 ) ( p = 0.014 and p = 0.022, respectively). BAC improved V̇ o2 peak 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.

Differences in brain structure and theta burst stimulation-induced plasticity implicate the corticomotor system in loss of function after musculoskeletal injury.

Traumatic musculoskeletal injury (MSI) may involve changes in corticomotor structure and function, but direct evidence is needed. To determine the corticomotor basis of MSI, we examined interactions among skeletomotor function, corticospinal excitability, corticomotor structure (cortical thickness and white matter microstructure), and intermittent theta burst stimulation (iTBS)-induced plasticity. Nine women with unilateral anterior cruciate ligament rupture (ACL) 3.2 ± 1.1 yr prior to the study and 11 matched controls (CON) completed an MRI session followed by an offline plasticity-probing protocol using a randomized, sham-controlled, double-blind, cross-over study design. iTBS was applied to the injured (ACL) or nondominant (CON) motor cortex leg representation (M1LEG) with plasticity assessed based on changes in skeletomotor function and corticospinal excitability compared with sham iTBS. The results showed persistent loss of function in the injured quadriceps, compensatory adaptations in the uninjured quadriceps and both hamstrings, and injury-specific increases in corticospinal excitability. Injury was associated with lateralized reductions in paracentral lobule thickness, greater centrality of nonleg corticomotor regions, and increased primary somatosensory cortex leg area inefficiency and eccentricity. Individual responses to iTBS were consistent with the principles of homeostatic metaplasticity; corresponded to injury-related differences in skeletomotor function, corticospinal excitability, and corticomotor structure; and suggested that corticomotor adaptations involve both hemispheres. Moreover, iTBS normalized skeletomotor function and corticospinal excitability in ACL. The results of this investigation directly confirm corticomotor involvement in chronic loss of function after traumatic MSI, emphasize the sensitivity of the corticomotor system to skeletomotor events and behaviors, and raise the possibility that brain-targeted therapies could improve recovery.NEW & NOTEWORTHY Traumatic musculoskeletal injuries may involve adaptive changes in the brain that contribute to loss of function. Our combination of neuroimaging and theta burst transcranial magnetic stimulation (iTBS) revealed distinct patterns of iTBS-induced plasticity that normalized differences in muscle and brain function evident years after unilateral knee ligament rupture. Individual responses to iTBS corresponded to injury-specific differences in brain structure and physiological activity, depended on skeletomotor deficit severity, and suggested that corticomotor adaptations involve both hemispheres.

Network Analysis of Research on Mild Traumatic Brain Injury in US Military Service Members and Veterans During the Past Decade (2010-2019).

OBJECTIVE: To evaluate trends in the extant literature on mild traumatic brain injury (mTBI) in military service members and veterans using network analysis based on a comprehensive search of original, peer-reviewed research articles involving human participants published between January 1, 2010, and December 31, 2019. Specifically, we employed network analysis to evaluate associations in the following areas: (1) peer-reviewed journals, (2) authors, (3) organizations/institutions, and (4) relevant key words. PARTICIPANTS: Included studies were published in peer-reviewed journals available on Web of Science database, using US military service members or veterans. DESIGN: Bibliometric network analytical review. MAIN MEASURES: Outcomes for each analysis included number of articles, citations, total link strength, and clusters. RESULTS: The top publishing journals were (1) Journal of Head Trauma and Rehabilitation, (2) Military Medicine, (3) Brain Injury, (4) Journal of Neurotrauma, and (5) Journal of Rehabilitation Research and Development. The top publishing authors were (1) French, (2) Lange, (3) Cooper, (4) Vanderploeg, and (5) Brickell. The top research institutions were (1) Defense and Veterans Brain Injury Center, (2) Uniformed Services University of the Health Sciences, (3) University of California San Diego, (4) Walter Reed National Military Medical Center, and (5) Boston University. The top co-occurring key words in this analysis were (1) posttraumatic stress disorder (PTSD), (2) persistent postconcussion symptoms (PPCS), (3) blast injury, (4) postconcussion syndrome (PCS), and (5) Alzheimer's disease. CONCLUSIONS: The results of this network analysis indicate a clear focus on veteran health, as well as investigations on chronic effects of mTBI. Research in civilian mTBI indicates that delaying treatment for symptoms and impairments related to mTBI may not be the most precise treatment strategy. Increasing the number of early, active, and targeted treatment trials in military personnel could translate to meaningful improvements in clinical practices for managing mTBI in this population.

Increases in Load Carriage Magnitude and Forced Marching Change Lower-Extremity Coordination in Physically Active, Recruit-Aged Women.

The objective was to examine the interactive effects of load magnitude and locomotion pattern on lower-extremity joint angles and intralimb coordination in recruit-aged women. Twelve women walked, ran, and forced marched at body weight and with loads of +25%, and +45% of body weight on an instrumented treadmill with infrared cameras. Joint angles were assessed in the sagittal plane. Intralimb coordination of the thigh-shank and shank-foot couple was assessed with continuous relative phase. Mean absolute relative phase (entire stride) and deviation phase (stance phase) were calculated from continuous relative phase. At heel strike, forced marching exhibited greater (P < .001) hip flexion, knee extension, and ankle plantar flexion compared with running. At mid-stance, knee flexion (P = .007) and ankle dorsiflexion (P = .04) increased with increased load magnitude for all locomotion patterns. Forced marching (P = .009) demonstrated a "stiff-legged" locomotion pattern compared with running, evidenced by the more in-phase mean absolute relative phase values. Running (P = .03) and walking (P = .003) had greater deviation phase than forced marching. Deviation phase increased for running (P = .03) and walking (P < .001) with increased load magnitude but not for forced marching. With loads of >25% of body weight, forced marching may increase risk of injury due to inhibited energy attenuation up the kinetic chain and lack of variability to disperse force across different supportive structures.

Utility of a novel perceptual-motor control test for identification of sport-related concussion beyond current clinical assessments.

Clinically feasible metrics, that can inform the concussion recovery decision making process by evaluating a unique domain beyond current testing domains (e.g., balance, neurocognition, symptoms, vestibular/ocular function) are still in need. The purpose of this study was to compare perceptual-motor control in adolescent athletes ≤21 days of sport-related concussion and healthy controls and evaluate the association of perceptual-motor control to the outcomes of commonly-used sport-related concussion clinical assessments. Athletes (age: 12-18 years) with sport-related concussion (n = 48) and healthy controls (n = 24) completed the Perception-Action Coupling Task (PACT), whose outcomes are mean reaction, movement, initiation, response time, and accuracy. ImPACT outcomes are verbal/visual memory scores, motor processing speed, and reaction time. Vestibular-Ocular Motor Screen (VOMS) outcomes are symptoms from: smooth pursuit, horizontal/vertical saccades, near-point of convergence, horizontal/vestibular ocular-reflex, and visual motion sensitivity. CONCUSSED demonstrated ~5% deficit in overall perceptual-motor accuracy during PACT compared to CONTROLS (p = 0.03). PACT accuracy negatively correlated with smooth pursuits(r = -0.29), and horizontal (r = -0.35)/vertical (r = -0.30) saccades. The C5.0 decision tree determined PACT accuracy was the most relevant predictor of sport-related concussion when no visual motion sensitivity symptoms were reported and Visual Memory was >66. Perceptual-motor control tests may complement current sport-related concussion assessments when neurocognition and vestibular/ocular motor system are not grossly impaired.

Effects of Short-Term Unilateral Strength Training on Measures of Postural Control When Wearing "Operationally Relevant" Backpack Loads.

Krajewski, KT, Bansbach, HM, McLean, L, McKenzie, C, Rawcliffe, A, Graham, SM, Flanagan, SD, Pourmoghaddam, A, Dettmer, M, and Connaboy, C. Effects of short-term unilateral strength training on measures of postural control when wearing "operationally relevant" backpack loads. J Strength Cond Res 34(10): 2743-2750, 2020-To examine the effects of "operationally relevant" loads on postural stability and to determine the effects of unilateral and bilateral strength training programs on postural stability in healthy, recruit-aged men. Fifteen subjects were randomly assigned to either a unilateral (UL; n = 7) or bilateral (BL; n = 8) strength training group, which performed strength training 3 times a week for 4 weeks. Subjects completed the following pretest and post-test assessments: 1 repetition maximum in bilateral (1RM-BL) and unilateral (1RM-UL) stance positions and bilateral and unilateral balance tasks with eyes open and eyes closed. Balance tasks were performed over 3 loading conditions: body mass (BM), 50% BM, and 70% BM. Sample entropy (SE) and root mean square (RMS) were calculated from the center of pressures collected during each balance assessment. The UL strength training group showed significant improvement after training in both 1RM-UL (p < 0.01) and 1RM-BL (p < 0.01). The BL strength training group only showed significant improvement in 1RM-BL (p = 0.01). There was a significant main effect of load on RMS (p < 0.05) across all balance tasks with RMS increasing with increasing load. Sample entropy was found to decrease with increasing load in the unilateral eyes open and bilateral stance tasks. Significant increases in strength (∼10 to -29%) were observed; however, increased strength alone is not enough to mitigate the effects of load carriage on the postural control, even when training is performed in stance positions that are posturally challenging. Therefore, "operationally relevant" loads negatively impact postural stability in novice load carriers when assessing nonlinear measures.

Compromised Dynamic Postural Stability Under Increased Load Carriage Magnitudes.

Warfighter performance may be compromised through the impact of load carriage on dynamic postural stability. Men and women may experience this impact to differing extents due to postural stability differences. Therefore, the authors investigated the effect of load magnitude on dynamic postural stability in men and women during a landing and stabilization task. Dynamic postural stability of 32 subjects (16 women) was assessed during the unilateral landing of submaximal jumps under 3 load conditions: +0%, +20%, and +30% body weight. Dynamic postural stability was measured using the dynamic postural stability index, which is calculated from ground reaction force data sampled at 1200 Hz. Two-way mixed-measures analysis of variance compared dynamic postural stability index scores between sexes and loads. Dynamic postural stability index scores were significantly affected by load (P = .001) but not by sex or by the sex by load interaction (P > .05). Dynamic postural stability index scores increased between the 0% (0.359 ± 0.041), 20% (0.396 ± 0.034), and 30% (0.420 ± 0.028) body weight conditions. Increased load negatively affects dynamic postural stability with similar performance decrements displayed by men and women. Men and women warfighters may experience similar performance decrements under load carriage conditions of similar relative magnitudes.

Effects of Tedizolid Phosphate on Survival Outcomes and Suppression of Production of Staphylococcal Toxins in a Rabbit Model of Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia.

The protective efficacy of tedizolid phosphate, a novel oxazolidinone that potently inhibits bacterial protein synthesis, was compared to those of linezolid, vancomycin, and saline in a rabbit model of Staphylococcus aureus necrotizing pneumonia. Tedizolid phosphate was administered to rabbits at 6 mg/kg of body weight intravenously twice daily, which yielded values of the 24-h area under the concentration-time curve approximating those found in humans. The overall survival rate was 83% for rabbits treated with 6 mg/kg tedizolid phosphate twice daily and 83% for those treated with 50 mg/kg linezolid thrice daily (P = 0.66 by the log-rank test versus the results obtained with tedizolid phosphate). These survival rates were significantly greater than the survival rates of 17% for rabbits treated with 30 mg/kg vancomycin twice daily (P = 0.003) and 17% for rabbits treated with saline (P = 0.002). The bacterial count in the lungs of rabbits treated with tedizolid phosphate was significantly decreased compared to that in the lungs of rabbits treated with saline, although it was not significantly different from that in the lungs of rabbits treated with vancomycin or linezolid. The in vivo bacterial production of alpha-toxin and Panton-Valentine leukocidin, two key S. aureus-secreted toxins that play critical roles in the pathogenesis of necrotizing pneumonia, in the lungs of rabbits treated with tedizolid phosphate and linezolid was significantly inhibited compared to that in the lungs of rabbits treated with vancomycin or saline. Taken together, these results indicate that tedizolid phosphate is superior to vancomycin for the treatment of S. aureus necrotizing pneumonia because it inhibits the bacterial production of lung-damaging toxins at the site of infection.

Characterization of the haematological profile of 21 days of tedizolid in healthy subjects.

OBJECTIVES: Tedizolid is a novel oxazolidinone antibacterial. Oxazolidinones carry concerns for time-dependent myelosuppression. To further explore tedizolid's haematological tolerability, we analysed data from a 21 day study comparing safety and pharmacokinetics of tedizolid and linezolid. METHODS: This was a Phase 1 study in healthy volunteers comparing five treatments (each n = 8) over 21 days: tedizolid at 200, 300 or 400 mg once daily; linezolid at 600 mg twice daily; and placebo. Routine laboratory haematological parameters (platelet, absolute neutrophil, white blood cell, red blood cell and reticulocyte counts) were compared between groups. Adverse haematological outcomes were pre-specified as any parameter below the standard lower limits of normal (LLN), substantially abnormal (<50% LLN for neutrophils; <75% LLN for other parameters) or ≥50% below baseline (platelets only). ClinicalTrials.gov identifier: NCT00671814. RESULTS: During the 21 day study period, pre-specified adverse platelet outcomes were observed in the linezolid (n = 2), tedizolid 300 mg (n = 1) and tedizolid 400 mg (n = 3) groups. Mean platelet counts decreased over time in a dose-dependent manner for tedizolid, with higher doses being similar to linezolid. The magnitude of platelet count decreases from baseline was influenced by unbound drug trough plasma concentrations, which were generally higher in subjects with at least a 20% decrease in platelet count. Substantially abnormal haematological parameters were only observed with linezolid and tedizolid 400 mg. One linezolid and two tedizolid 400 mg subjects discontinued due to meeting criteria for pre-specified adverse haematological outcomes. CONCLUSIONS: Although limited to small groups of healthy volunteers, these exploratory results support clinical study of extended treatment durations with tedizolid at 200 mg once daily.

The Effects of Nitrate-Rich Supplementation on Neuromuscular Efficiency during Heavy Resistance Exercise.

OBJECTIVE: Nitrate-rich (NR) supplements can enhance exercise performance by improving neuromuscular function and the aerobic cost of exercise. However, little is known about the effects of nitrate on dynamic, multijoint resistance exercise. METHODS: Fourteen resistance-trained men (age, 21.1 ± 0.9 years; height, 173.2 ± 2.9 cm: body mass, 77.6 ± 4.3 kg; squat one-repetition maximum [1RM], 127.5 ± 18.8 kg) participated in a randomized, double-blind, crossover experiment. Subjects consumed an NR or nitrate-poor (NP) supplement for 3 days, performed a bout of heavy resistance exercise, completed a washout, and then repeated the procedures with the remaining supplement. Before, during, and after exercise, individual and gross motor unit efficiency was assessed during isometric and dynamic muscle contractions. In addition, we compared physical performance, heart rate, lactate, and oxygen consumption (VO2). RESULTS: Nitrate-rich supplementation resulted in lower initial muscle firing rates at rest and lower mean and maximum firing rates over the course of fatiguing exercise. Nitrate-poor supplementation was accompanied by increased mean and maximum firing rates by the end of exercise and lower initial firing rates. In addition, NR supplementation resulted in higher mean peak electromyography (EMG) amplitudes. Heart rate, lactate, and physical performance did not differ by treatment, but oxygen consumption increased more frequently when the NP supplement was consumed. CONCLUSION: Supplementation with an NR beetroot extract-based supplement provided neuromuscular advantages during metabolically taxing resistance exercise.

Physiological Effects of Nucleotide Supplementation on Resistance Exercise Stress in Men and Women.

Nucleotide supplementation can reduce postexercise immunosuppression and hypothalamic-pituitary axis (HPA) axis activation in endurance exercise models. Nucleotide supplementation may aid recovery from other exercise modalities, such as heavy resistance exercise. Thus, the purpose of this investigation was to investigate the effects of nucleotide supplementation on the acute cortisol and immune responses to heavy resistance exercise and its effects on recovery. A double-blinded, crossover, mixed methods design with 10 men and 10 women was used. Each performed an acute heavy resistance exercise protocol (AHREP) after a loading period with a nucleotide or placebo supplement. Before and after the AHREP, and at 24, 48, and 72 hours post, blood samples were analyzed for cortisol, myeloperoxidase (MPO), and absolute neutrophil, lymphocyte, and monocyte counts. Creatine kinase (CK) was analyzed before and 24, 48, and 72 hours after the AHREP. Performance measures, including peak back squat isometric force and peak countermovement jump power were also analyzed. Nucleotide supplementation resulted in significant (p ≤ 0.05) decreases in cortisol and MPO immediately after the AHREP, and significantly lower CK values 24 hours later. The AHREP significantly affected leukocyte counts; however, no treatment effects were observed. Greater isometric force was observed immediately after AHREP and at 24 hours and 48 hours with nucleotide supplementation. Nucleotide supplementation seems to attenuate muscle damage, HPA axis and immune system activation, and performance decrements after heavy resistance exercise.

Electromyographical and Perceptual Responses to Different Resistance Intensities in a Squat Protocol: Does Performing Sets to Failure With Light Loads Produce the Same Activity?

This investigation examined peak motor unit activity during sets that differed in resistance (50, 70, or 90% 1 repetition maximum [1RM]). Ten resistance-trained men (age, 23 ± 3 years; height, 187 ± 7 cm; body mass, 91.5 ± 6.9 kg; squat 1RM, 141 ± 28 kg) were assessed by electromyography (EMG) on the vastus lateralis and vastus medialis muscles in a randomized within-subject experiment consisting of 2 test visits: a drop-set day and a single-set day using only the 50% of 1RM intensity performed to failure. At the start of each day, subjects performed 2 submaximal repetition sets (50% 1RM × 10 repetitions and 70% 1RM × 7 repetitions). On the drop-set day, subjects performed 3 consecutive maximal repetition sets at 90%, 70%, and 50% 1RM to failure with no rest periods in between. On the single-set day, subjects performed a maximal repetition set at 50% 1RM to failure. Overall, the maximal repetition sets to failure at 50% and 70% 1RM resulted in higher peak EMG amplitude than during submaximal repetition sets with the same resistance. However, peak EMG amplitude was significantly (p ≤ 0.05) greater in the maximal 90% 1RM set than all other sets performed. When sets were performed to failure, ratings of perceived exertion (CR-10) did not differ over the intensity range of loads and suggests that perception is not capable of accurately detecting the actual amount of motor unit activation. The results of this investigation indicate that using higher external resistance is a more effective means of increasing motor unit activity than increasing the number of repetitions performed with lighter weights even when the end point is muscular failure. Accordingly, previous recommendations for the use of heavier loads during resistance training programs to stimulate the maximal development of strength and hypertrophy are further supported.

The addition of beta-hydroxy-beta-methylbutyrate and isomaltulose to whey protein improves recovery from highly demanding resistance exercise.

OBJECTIVE: This study evaluated whether a combination of whey protein (WP), calcium beta-hydroxy-beta-methylbutyrate (HMB), and carbohydrate exert additive effects on recovery from highly demanding resistance exercise. METHODS: Thirteen resistance-trained men (age: 22.6 ± 3.9 years; height: 175.3 ± 12.2 cm; weight: 86.2 ± 9.8 kg) completed a double-blinded, counterbalanced, within-group study. Subjects ingested EAS Recovery Protein (RP; EAS Sports Nutrition/Abbott Laboratories, Columbus, OH) or WP twice daily for 2 weeks prior to, during, and for 2 days following 3 consecutive days of intense resistance exercise. The workout sequence included heavy resistance exercise (day 1) and metabolic resistance exercise (days 2 and 3). The subjects performed no physical activity during day 4 (+24 hours) and day 5 (+48 hours), where recovery testing was performed. Before, during, and following the 3 workouts, treatment outcomes were evaluated using blood-based muscle damage markers and hormones, perceptual measures of muscle soreness, and countermovement jump performance. RESULTS: Creatine kinase was lower for the RP treatment on day 2 (RP: 166.9 ± 56.4 vs WP: 307.1 ± 125.2 IU · L(-1), p ≤ 0.05), day 4 (RP: 232.5 ± 67.4 vs WP: 432.6 ± 223.3 IU · L(-1), p ≤ 0.05), and day 5 (RP: 176.1 ± 38.7 vs 264.5 ± 120.9 IU · L(-1), p ≤ 0.05). Interleukin-6 was lower for the RP treatment on day 4 (RP: 1.2 ± 0.2 vs WP: 1.6 ± 0.6 pg · ml(-1), p ≤ 0.05) and day 5 (RP: 1.1 ± 0.2 vs WP: 1.6 ± 0.4 pg · ml(-1), p ≤ 0.05). Muscle soreness was lower for RP treatment on day 4 (RP: 2.0 ± 0.7 vs WP: 2.8 ± 1.1 cm, p ≤ 0.05). Vertical jump power was higher for the RP treatment on day 4 (RP: 5983.2 ± 624 vs WP 5303.9 ± 641.7 W, p ≤ 0.05) and day 5 (RP: 5792.5 ± 595.4 vs WP: 5200.4 ± 501 W, p ≤ 0.05). CONCLUSIONS: Our findings suggest that during times of intense conditioning, the recovery benefits of WP are enhanced with the addition of HMB and a slow-release carbohydrate. We observed reductions in markers of muscle damage and improved athletic performance.