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1.
Eur J Sport Sci ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967991

RESUMEN

Challenges for some women meeting the physical employment standards (PES) for ground close combat (GCC) roles stem from physical fitness and anthropometric characteristics. The purpose of this study was to identify the modifiable and nonmodifiable characteristics predictive of passing GCC-based PES tasks and determine the modifiable characteristics suitable to overcome nonmodifiable limitations. 107 adults (46 women) underwent multiday testing assessing regional and total lean mass (LM), percent body fat (BF%), aerobic capacity (V̇O2peak), strength, power, and PES performance. Predictors with p-value <0.200 were included in stepwise logistic regression analysis or binary logistic regression when outcomes among sexes were insufficient. Relative and absolute arm LM (OR: 4.617-8.522, p < 0.05), leg LM (OR: 2.463, p < 0.05), and upper body power (OR: 2.061, p < 0.05) predicted medicine ball chest throw success. Relative and absolute arm LM (OR: 3.734-11.694, p < 0.05), absolute trunk LM (OR: 2.576, p < 0.05), and leg LM (OR: 2.088, p < 0.05) predicted casualty drag success. Upper body power (OR: 3.910, p < 0.05), absolute trunk LM (OR: 2.387, p < 0.05), leg LM (OR: 2.290, p < 0.05), and total LM (OR: 1.830, p < 0.05) predicted maximum single lift success. Relative and absolute arm LM (OR: 3.488-7.377, p < 0.05), leg LM (OR: 1.965, p < 0.05), and upper body power (OR: 1.957, p < 0.05) predicted water can carry success. %BF (OR: 0.814, p = 0.007), V̇O2peak (OR: 1.160, p = 0.031), and lower body strength (OR: 1.059, p < 0.001) predicted repeated lift and carry success. V̇O2peak (OR: 1.540, p < 0.001) predicted 2-km ruck march success. Modifiable characteristics were the strongest predictors for GCC-based PES task success to warrant their improvement for enhancing PES performance for women.

2.
Pharmacotherapy ; 44(6): 435-443, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38840536

RESUMEN

INTRODUCTION: Rezafungin is a second-generation, once-weekly echinocandin antifungal approved for the treatment of invasive candidiasis, including candidemia. In phase II/III studies of rezafungin versus caspofungin, patients with severe hepatic impairment were excluded due to lack of caspofungin data in this population. This open-label, single-dose, phase I study evaluated the pharmacokinetics (primary objective) and safety of rezafungin in subjects with moderate or severe hepatic impairment versus matched, healthy subjects with normal hepatic function. METHODS: Eight subjects each with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment were matched 1:1 with healthy subjects for age, sex, and body mass index. Each subject received a single 400-mg, intravenous, 1-h infusion of rezafungin. Plasma pharmacokinetic sampling was performed at various time points through 336 h postdose. Pharmacokinetic parameters were derived by non-compartmental analysis. Safety was assessed throughout. RESULTS: All 32 subjects received study treatment and were included in all analyses. Despite overlapping distributions of total plasma concentrations, based on geometric least-squares (LS) mean ratios, the area under the plasma concentration-time curve from time zero (prior to the start of infusion) to infinity (AUC0-∞) was 32% lower in subjects with moderate (LS mean ratio, 67.55; 90% confidence interval [CI]: 53.91, 84.65) and severe (LS mean ratio, 67.84; 90% CI: 57.49, 80.05) hepatic impairment versus matched healthy subjects. The maximum plasma concentration (Cmax) was 12% lower in moderate hepatic impairment and 28% lower in severe hepatic impairment groups. Linear regression showed no significant trend in the degree of hepatic impairment (based on Child-Pugh score) on AUC0-∞ or Cmax (p > 0.05). Treatment-emergent adverse events were reported in seven subjects (21.9%; three subjects in each of the hepatic impairment groups, and one healthy subject), none of which were severe, serious, or resulted in withdrawal. CONCLUSIONS: Rezafungin is well tolerated and can be administered to patients with moderate or severe hepatic impairment without the need for dose adjustment. The modest reduction in exposures in subjects with hepatic impairment is not clinically meaningful and is unlikely to impact efficacy.


Asunto(s)
Antifúngicos , Equinocandinas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Antifúngicos/farmacocinética , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Equinocandinas/farmacocinética , Equinocandinas/efectos adversos , Equinocandinas/administración & dosificación , Adulto , Anciano , Hepatopatías , Infusiones Intravenosas , Área Bajo la Curva , Índice de Severidad de la Enfermedad , Estudios de Casos y Controles
3.
Med Sci Sports Exerc ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38758530

RESUMEN

PURPOSE: Optimize a dMS-based urinary proteomic technique and evaluate the relationship between urinary proteome content and adaptive changes in bone microarchitecture during BCT. METHODS: Urinary proteomes were analyzed with an optimized dMS technique in two groups of 13 recruits (n = 26) at the beginning (Pre) and end (Post) of BCT. Matched by age (21 ± 4 yr), sex (16 W), and baseline tibial trabecular bone volume fractions (Tb.BV/TV), these groups were distinguished by the most substantial (High) and minimal (Low) improvements in Tb.BV/TV. Differential protein expression was analyzed with mixed permutation ANOVA and false discovery proportion-based adjustment for multiple comparisons. RESULTS: Tibial Tb.BV/TV increased from pre- to post-BCT in High (3.30 ± 1.64%, p < 0.0001) but not Low (-0.35 ± 1.25%, p = 0.4707). The optimized dMS technique identified 10,431 peptides from 1,368 protein groups that represented 165 integrative biological processes. 74 urinary proteins changed from pre- to post-BCT (p = 0.0019) and neutrophil mediated immunity was the most prominent ontology. Two proteins (Immunoglobulin heavy constant gamma 4 and C-type lectin domain family 4 member G) differed from pre- to post-BCT in High and Low (p = 0.0006). CONCLUSIONS: The dMS technique can identify more than 1000 urinary proteins. At least 74 proteins are responsive to BCT, and other principally immune system-related proteins show differential expression patterns that coincide with adaptive bone formation.

4.
Sci Rep ; 14(1): 9542, 2024 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664550

RESUMEN

The introduction of women into U.S. military ground close combat roles requires research into sex-specific effects of military training and operational activities. Knee osteoarthritis is prevalent among military service members; its progression has been linked to occupational tasks such as load carriage. Analyzing tibiofemoral arthrokinematics during load carriage is important to understand potentially injurious motion and osteoarthritis progression. The study purpose was to identify effects of load carriage on knee arthrokinematics during walking and running in recruit-aged women. Twelve healthy recruit-aged women walked and ran while unloaded (bodyweight [BW]) and carrying additional + 25%BW and + 45%BW. Using dynamic biplane radiography and subject-specific bone models, tibiofemoral arthrokinematics, subchondral joint space and center of closest contact location between subchondral bone surfaces were analyzed over 0-30% stance (separate one-way repeated measures analysis of variance, load by locomotion). While walking, medial compartment contact location was 5% (~ 1.6 mm) more medial for BW than + 45%BW at foot strike (p = 0.03). While running, medial compartment contact location was 4% (~ 1.3 mm) more lateral during BW than + 25%BW at 30% stance (p = 0.04). Internal rotation was greater at + 45%BW compared to + 25%BW (p < 0.01) at 30% stance. Carried load affects tibiofemoral arthrokinematics in recruit-aged women. Prolonged load carriage could increase the risk of degenerative joint injury in physically active women.


Asunto(s)
Articulación de la Rodilla , Caminata , Soporte de Peso , Humanos , Femenino , Soporte de Peso/fisiología , Caminata/fisiología , Articulación de la Rodilla/fisiología , Adulto , Carrera/fisiología , Personal Militar , Fenómenos Biomecánicos , Fémur/fisiología , Fémur/diagnóstico por imagen , Osteoartritis de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/etiología , Tibia/fisiología , Tibia/diagnóstico por imagen , Adulto Joven
5.
Physiol Rep ; 12(6): e15953, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38490811

RESUMEN

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


Asunto(s)
Músculo Esquelético , Entrenamiento de Fuerza , Masculino , Humanos , Femenino , Músculo Esquelético/metabolismo , Fibras Musculares Esqueléticas/fisiología , Músculo Cuádriceps , Ejercicio Físico/fisiología , Terapia por Ejercicio , Fuerza Muscular
6.
Med Sci Sports Exerc ; 56(7): 1225-1232, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38377006

RESUMEN

BACKGROUND: Resistance training confers numerous health benefits that are mediated in part by circulating factors. Toward an enhanced molecular understanding, there is growing interest in a class of signaling biomarkers called extracellular vesicles (EV). EVs support physiological adaptations to exercise by transporting their cargo (e.g., microRNA (miRNA)) to target cells. Previous studies of changes in EV cargo have focused on aerobic exercise, with limited data examining the effects of resistance exercise. We examined the effect of acute resistance exercise on circulating EV miRNAs and their predicted target pathways. METHODS: Ten participants (5 men; age, 26.9 ± 5.5 yr; height, 173.4 ± 10.5 cm; body mass, 74.0 ± 11.1 kg; body fat, 25.7% ± 11.6%) completed an acute heavy resistance exercise test (AHRET) consisting of six sets of 10 repetitions of back squats using 75% one-repetition maximum. Pre-/post-AHRET, EVs were isolated from plasma using size exclusion chromatography, and RNA sequencing was performed. Differentially expressed miRNAs between pre- and post-AHRET EVs were analyzed using Ingenuity Pathway Analysis to predict target messenger RNAs and their target biological pathways. RESULTS: Overall, 34 miRNAs were altered by AHRET ( P < 0.05), targeting 4895 mRNAs, with enrichment of 175 canonical pathways ( P < 0.01), including 12 related to growth/metabolism (p53, IGF-I, STAT3, PPAR, JAK/STAT, growth hormone, WNT/ß-catenin, ERK/MAPK, AMPK, mTOR, and PI3K/AKT) and 8 to inflammation signaling (TGF-ß, IL-8, IL-7, IL-3, IL-6, IL-2, IL-17, IL-10). CONCLUSIONS: Acute resistance exercise alters EV miRNAs targeting pathways involved in growth, metabolism, and immune function. Circulating EVs may serve as significant adaptive signaling molecules influenced by exercise training.


Asunto(s)
Vesículas Extracelulares , MicroARNs , Entrenamiento de Fuerza , Humanos , Masculino , Vesículas Extracelulares/metabolismo , Adulto , Estudios Prospectivos , Femenino , MicroARNs/sangre , MicroARNs/metabolismo , Adulto Joven , Transducción de Señal , MicroARN Circulante/sangre
7.
Physiol Rep ; 12(3): e15906, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38296351

RESUMEN

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


Asunto(s)
Entrenamiento de Fuerza , Humanos , Masculino , Femenino , Adulto Joven , Factor I del Crecimiento Similar a la Insulina , Osteocalcina , Fibronectinas , Ejercicio Físico , Remodelación Ósea
8.
Cureus ; 15(10): e46794, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37954799

RESUMEN

Pulmonary sequestration is a congenital lung malformation characterized by a mass of nonfunctioning lung tissue that receives its arterial supply from an aberrant systemic artery. If symptomatic, most newborns present with respiratory distress. Recurrent infection is the most common presentation after the neonatal period. It is often diagnosed prenatally and is treated with elective surgical resection between ages six and twelve months. We present a case of an infant diagnosed with congenital pulmonary airway malformation prenatally revealed to be pulmonary sequestration at the age of six months, emphasizing the need for appropriate postnatal imaging.

9.
Antimicrob Agents Chemother ; 67(12): e0091623, 2023 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-38014945

RESUMEN

Rezafungin is a chemically and metabolically stable echinocandin with a longer half-life than other echinocandins, allowing for a once-weekly intravenous infusion versus a daily infusion. Rezafungin is approved in the US for the treatment of candidemia and/or invasive candidiasis and is in development for the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp. in immunosuppressed patients. A population pharmacokinetic (PPK) model was developed using data from five Phase 1, one Phase 2, and one Phase 3 study. The model found to best describe the available data was a three-compartment PPK model with first-order elimination characterized by the parameters clearance (CL), central volume (V1), peripheral volume (V23), intercompartmental clearance 1, and intercompartmental clearance 2. The variability model included correlated interindividual variability in CL, V1, and V23 and a proportional residual variability model. The following statistically significant covariates were identified: albumin concentrations on V23; body surface area (BSA) on CL, V1, and V23; and disease state on CL and V1. Disease states were defined as patients from the Phase 2 and Phase 3 studies and hepatically impaired subjects. Covariates of BSA, disease state, or albumin, included in the final model, were not associated with clinically meaningful changes in PK, nor were any other patient factors, indicating that a common dose regimen is adequate for all adult patients. Target attainment simulations were performed to estimate the probability of achieving PK/pharmacodynamic targets across the range of minimum inhibitory concentration values for six species of Candida.


Asunto(s)
Candidemia , Candidiasis Invasiva , Adulto , Humanos , Candidemia/tratamiento farmacológico , Antifúngicos/farmacología , Equinocandinas/farmacología , Candidiasis Invasiva/tratamiento farmacológico , Candida , Albúminas/uso terapéutico
10.
J Sci Med Sport ; 26(12): 682-687, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37793956

RESUMEN

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


Asunto(s)
Traumatismos en Atletas , Conmoción Encefálica , Deportes , Humanos , Femenino , Esfuerzo Físico , Volver al Deporte , Conmoción Encefálica/diagnóstico , Atletas , Traumatismos en Atletas/diagnóstico
11.
J Strength Cond Res ; 37(10): 2023-2031, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37729515

RESUMEN

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.


Asunto(s)
Hidrodinámica , Carrera , Humanos , Análisis de Varianza , Movimiento , Proteínas del Tejido Nervioso
12.
Cureus ; 15(6): e40409, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37456426

RESUMEN

Sudden sensorineural hearing loss (SSNHL) is considered an otolaryngologic emergency that must be treated within 72 hours. Failure to treat within that time frame typically results in permanent hearing loss. Here, we present a case of SSNHL confirmed by an audiogram that was treated as eustachian tube dysfunction. Aggressive management measures started at follow-up failed to improve the hearing loss. This case demonstrates the need for early recognition and ENT referral for SSNHL.

13.
Eur J Sport Sci ; 23(12): 2411-2424, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37517090

RESUMEN

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


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


Asunto(s)
Personal Militar , Entrenamiento de Fuerza , Femenino , Humanos , Masculino , Ejercicio Físico , Tolerancia al Ejercicio/fisiología , Fuerza Muscular , Aptitud Física/fisiología , Análisis y Desempeño de Tareas , Adolescente , Adulto Joven , Adulto
14.
J Sci Med Sport ; 26 Suppl 1: S54-S63, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37236820

RESUMEN

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


Asunto(s)
Cognición , Fatiga , Humanos , Tiempo de Reacción , Examen Físico , Biomarcadores
15.
Microbiol Spectr ; 11(3): e0133923, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37154682

RESUMEN

Rezafungin is a novel once-weekly echinocandin for intravenous injection currently in development for the treatment of Candida infections and the prevention of Candida, Aspergillus, and Pneumocystis infections in allogeneic blood and marrow transplant recipients. While in vitro data indicated that rezafungin exposure was unlikely to be affected by commonly prescribed medicines, interactions resulting in the altered systemic exposure of some drugs coadministered with rezafungin could not be excluded. Two phase 1 open label crossover studies, conducted in healthy subjects, examined drug interactions between rezafungin and multiple drug probe cytochrome P450 (CYP) substrates and/or transporter proteins, immunosuppressants, and cancer therapies. Statistical analysis compared the outcomes for drugs coadministered with rezafungin to those for the drugs administered alone. The geometric mean ratio was reported, and a default 90% confidence interval (CI) no-effect equivalence range of 80 to 125% was used for the maximal plasma concentration (Cmax), the area under the curve from time zero to the final sampling time point (AUC0-t), and the AUC from time zero to infinity (AUC0-∞). Most probes and concomitant drugs were within the equivalence range. For tacrolimus, ibrutinib, mycophenolic acid, and venetoclax, the AUC or Cmax was reduced (10 to 19%), with lower bounds of the 90% CI values falling outside the no-effect range. The rosuvastatin AUC and Cmax and the repaglinide AUC0-∞ were increased (12 to 16%), with the 90% CI being marginally above the upper bound. Overall, the in vitro and in vivo data demonstrated a low drug interaction potential with rezafungin via CYP substrate/transporter pathways and commonly prescribed comedications, suggesting that coadministration was unlikely to result in clinically significant effects. Treatment-emergent adverse events were typically mild, and rezafungin was generally well tolerated. IMPORTANCE Antifungal agents used to treat life-threatening infections are often associated with severe drug-drug interactions (DDIs) that may limit their usefulness. Rezafungin, a newly approved once-weekly echinocandin, has been shown to be free of DDIs based on extensive nonclinical and clinical testing described in this study.


Asunto(s)
Candidiasis , Equinocandinas , Humanos , Antifúngicos/efectos adversos , Candida , Candidiasis/tratamiento farmacológico , Interacciones Farmacológicas , Equinocandinas/efectos adversos , Ensayos Clínicos Fase I como Asunto , Estudios Cruzados
17.
Sci Rep ; 13(1): 4910, 2023 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-36966216

RESUMEN

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


Asunto(s)
Personal Militar , Carrera , Adulto , Humanos , Persona de Mediana Edad , Caminata/fisiología , Objetivos , Marcha/fisiología
18.
Front Psychol ; 14: 1102425, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36844343

RESUMEN

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

19.
Sports Health ; 15(3): 410-421, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-35678147

RESUMEN

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


Asunto(s)
Conmoción Encefálica , Deportes , Adulto , Adolescente , Humanos , Femenino , Esfuerzo Físico , Reproducibilidad de los Resultados , Estudios Transversales , Conmoción Encefálica/diagnóstico
20.
Sleep Health ; 9(1): 93-99, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36503874

RESUMEN

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


Asunto(s)
Trastornos de Somnolencia Excesiva , Personal Militar , Masculino , Humanos , Femenino , Somnolencia , Sueño/fisiología , Privación de Sueño/psicología
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