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The bromodomain and extra terminal (BET) family of bromodomain-containing proteins are important epigenetic regulators that elicit their effect through binding histone tail N-acetyl lysine (KAc) post-translational modifications. Recognition of such markers has been implicated in a range of oncology and immune diseases and, as such, small-molecule inhibition of the BET family bromodomain-KAc protein-protein interaction has received significant interest as a therapeutic strategy, with several potential medicines under clinical evaluation. This work describes the structure- and property-based optimization of a ligand and lipophilic efficient pan-BET bromodomain inhibitor series to deliver candidate I-BET787 (70) that demonstrates efficacy in a mouse model of inflammation and suitable properties for both oral and intravenous (IV) administration. This focused two-phase explore-exploit medicinal chemistry effort delivered the candidate molecule in 3 months with less than 100 final compounds synthesized.
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Administración Intravenosa , Animales , Administración Oral , Ratones , Relación Estructura-Actividad , Humanos , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/metabolismo , Estructura MolecularRESUMEN
The C-aryl-tetrahydropyran motif is prevalent in nature in a number of natural products with biological activity; however, this challenging architecture still requires novel synthetic approaches. We demonstrate the application of a stereoselective Heck redox-relay strategy for the synthesis of functionalized 2,6-trans-tetrahydropyrans in excellent selectivity in a single step from an enantiopure dihydropyranyl alcohol, proceeding through a novel exo-cyclic migration. The strategy has also been applied to the total synthesis of a trans-epimer of the natural product centrolobine in excellent yield and stereoselectivity.
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The purpose of this project was to examine the effect of a concurrent exercise program (sprint interval training and resistance exercise) on body composition in women with obesity and factors associated with continued exercise participation following the program. Twenty women (37.1 ± 7.4 y, height = 1.63 ± 0.09 m, weight = 98.22 ± 0.22 kg, BMI = 34.2 ± 2.50 kg/m2) participated in a 10-week exercise intervention consisting of a sprint interval treadmill protocol and resistance training three times a week totaling 30 sessions. Body composition was measured by dual-energy X-ray absorptiometry (iDXA) at pretest, 12 weeks, and six months post-intervention. Semi-structured interviews assessed participants' perception of the program at both 12 weeks and six months. Participants significantly reduced fat mass (p < 0.001), gynoid fat mass (p < 0.010), android fat mass (p = 0.003), and visceral fat mass (p = 0.003) at 12 weeks post-test. At six months, participants maintained their reductions in fat mass (p = 0.015), visceral fat (p = 0.040) and gynoid fat mass (p = 0.032). There were no significant main time effects in lean mass (p = 0.099) or caloric intake (p = 0.053) at 12 weeks or six months. Themes that emerged from the semi-structured interviews at 12 weeks reflected enjoyment in the training, increases in competence and knowledge, as well as apprehension of continuing training on their own. At six months, themes that emerged reflected overcoming barriers, competence regarding high-intensity training, and a lack of competence to engage in resistance training. Sprint interval training coupled with resistance training is a feasible exercise protocol for women with obesity and results in reduced fat mass over six months. Improving women's competence for training is imperative for continued participation.
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ABSTRACT: Wadsworth, DD, Rodriguez-Hernandez, M, Huffman, LS, McDonald, JR, Spring, KE, and Pascoe, DD. Adaptations to a concurrent exercise training program in inactive aging women. J Strength Cond Res 36(11): 3217-3223, 2022-This study assessed the effect of a 10-week, sprint interval concurrent exercise training program on body composition and muscular strength in aging women. Sixty-five inactive women (age, 40-64 years) were randomized into 2 sprint interval exercise programs, 0% incline and 6% incline. Sprint interval training was performed to achieve 95% of each subject's age-predicted maximal heart rate for a series of 40 seconds of work followed by 20 seconds of passive recovery. An undulating resistance training protocol, composed of 30 sessions, was performed by each group throughout the study. Dual-energy X-ray absorption scans were assessed body composition, and 1 repetition maximum was performed to assess muscular strength. Subjects in both groups significantly reduced fat mass by approximately 0.35 kg ( p = 0.002), and visceral adipose tissue by 0.05 kg ( p = 0.032). There were significant increases in lean body mass by approximately 0.50 kg ( p = 0.005), lower-body muscular strength by approximately 46.83 kg ( p < 0.001), and upper-body muscular strength by approximately 11.68 kg ( p < 0.001). No significant between-groups interactions were observed. A sprint interval training concurrent exercise training program is an effective strategy to improve body composition and muscular strength in inactive, aging women. Muscular strength improvements resulting from this intervention are particularly important because muscular strength losses are strong predictors of morbidity and mortality.
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Entrenamiento de Intervalos de Alta Intensidad , Entrenamiento de Fuerza , Humanos , Femenino , Adulto , Persona de Mediana Edad , Entrenamiento de Fuerza/métodos , Fuerza Muscular/fisiología , Ejercicio Físico/fisiología , Composición Corporal/fisiología , EnvejecimientoRESUMEN
CONTEXT: Slips, trips, and falls are leading causes of musculoskeletal injuries in firefighters. Researchers have hypothesized that heat stress is the major contributing factor to these fireground injuries. OBJECTIVE: To examine the effect of environmental conditions, including hot and ambient temperatures, and exercise on functional and physiological outcome measures, including balance, rectal temperature, and perceived exertion. DESIGN: Randomized controlled clinical trial. SETTING: Laboratory environmental chamber. PATIENTS OR OTHER PARTICIPANTS: A total of 13 healthy, active career firefighters (age = 26 ± 6 years [range = 19-35 years], height = 178.61 ± 4.93 cm, mass = 86.56 ± 16.13 kg). INTERVENTION(S): Independent variables consisted of 3 conditions (exercise in heat [37.41°C], standing in heat [37.56°C], and exercise in ambient temperature [14.24°C]) and 3 data-collection times (preintervention, postintervention, and postrecovery). Each condition was separated from the others by at least 1 week and lasted a maximum of 40 minutes or until the participant reached volitional fatigue or a rectal temperature of 40.0°C. MAIN OUTCOME MEASURE(S): Firefighting-specific functional balance performance index, rectal temperature, and rating of perceived exertion. RESULTS: Exercise in the heat decreased functional balance, increased rectal temperature, and altered the perception of exertion compared with the other intervention conditions. CONCLUSIONS: A bout of exercise in a hot, humid environment increased rectal temperature in a similar way to that reported in the physically active population and negatively affected measures of functional balance. Rather than independently affecting balance, the factors of exercise and heat stress appeared to combine, leading to an increased likelihood of slips, trips, and falls.
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Exposición a Riesgos Ambientales , Bomberos/estadística & datos numéricos , Trastornos de Estrés por Calor/fisiopatología , Calor/efectos adversos , Traumatismos Ocupacionales , Esfuerzo Físico/fisiología , Equilibrio Postural/fisiología , Adulto , Temperatura Corporal/fisiología , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Ejercicio Físico/fisiología , Humanos , Masculino , Traumatismos Ocupacionales/clasificación , Traumatismos Ocupacionales/fisiopatología , Evaluación de Resultado en la Atención de Salud , Rendimiento Físico FuncionalRESUMEN
PURPOSE: We investigated the effect of ischemic preconditioning (IPC) on performance of a 3 min maximal effort arm ergometer test in young women. METHODS: Twenty healthy women (23.1 (SD 3.3) years) performed a 3 min maximal effort arm cycling exercise, preceded by IPC on both arms or SHAM in a counterbalanced randomized crossover design. Both blood flow (via high resolution ultrasound; n = 17) and muscle oxygenation/deoxygenation (via near infrared spectroscopy; n = 5) were measured throughout the IPC/SHAM. Performance and perceptual/physiological (i.e., heart rate, blood lactate, rating of perceived exertion, and triceps brachialis oxygenation) parameters were recorded during the exercise test. RESULTS: Occlusion during IPC completely blocked brachial artery blood flow, decreased oxygenated hemoglobin/myoglobin (Δ[oxy(Hb + Mb)]), and increased deoxygenated Hb/Mb (Δ[deoxy(Hb + Mb)]). There were no differences (P > 0.797) in performance (peak, mean, and end power output) or in any perceptual/physiological variables during the 3 min all-out test between IPC/SHAM. During exercise, Δ[oxy(Hb + Mb)] initially decreased with no differences (P ≥ 0.296) between conditions and returned towards baseline by the completion of the test while Δ[deoxy(Hb + Mb)] increased with no differences between conditions and remained elevated until completion of the test (P ≥ 0.755). CONCLUSIONS: We verified the successful application of IPC via blood flow and NIRS measures but found no effects on performance of a 3 min maximal effort arm cranking test in young women.
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Brazo , Prueba de Esfuerzo/métodos , Precondicionamiento Isquémico , Músculo Esquelético/fisiología , Consumo de Oxígeno/fisiología , Adulto , Ejercicio Físico , Femenino , Humanos , Adulto JovenRESUMEN
Salom Huffman, L, Wadsworth, DD, McDonald, JR, Foote, SJ, Hyatt, H, and Pascoe, DD. Effects of a sprint interval and resistance concurrent exercise training program on aerobic capacity of inactive adult women. J Strength Cond Res 33(6): 1641-1648, 2019-The purpose of this investigation was to examine the effects of high-intensity concurrent exercise training (CET) consisting of sprint intervals (sprint interval training [SIT]) and resistance exercise (RET) protocols on aerobic capacity in recreationally active, adult women. A total of 53 participants were pair-matched according to preliminary maximal aerobic capacity (VO2max) Bruce protocol assessment into level-grade (SIT0) or 6% incline (SIT6) groups. This 12-week intervention consisted of 3 CET sessions per week. Sprint interval protocol consisted of 2 (weeks 1-6) then 3 (weeks 7-12) sets of three 40-second sprints at specific intensities to evoke responses equivalent to 95% of age-predicted maximal heart rate interspersed with 20 seconds of rest; with 1 minute of passive recovery between sets. An undulating periodization model consisting of lifts such as the back squat and bench press constituted the RET component. Protocol order alternated each session. Posttraining revealed significant improvements in both SIT0 and SIT6 (p ≤ 0.05) for VO2max (2.11 ± 0.390 to 2.29 ± 0.382 L·min; 2.03 ± 0.382 to 2.09 ± 0.561 L·min), Tmax (490.5 ± 102.3 to 542.7 ± 81.5 seconds; 503.2 ± 75.4 to 541.8 ± 77.0 seconds), and Vmax (5.1 ± 0.92 miles per hour [MPH] to 5.9 ± 0.90 MPH; 4.3 ± 0.68 MPH to 4.9 ± 0.64 MPH), respectively. No significant between-group interactions were detected for any of the variables. Our SIT-based CET intervention represents an effective strategy to induce significant cardiovascular adaptations in older women as evident by aerobic capacity improvements, beneficial to overall health and critical for functionality into old age; an important concern for aging women.
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Adaptación Fisiológica , Tolerancia al Ejercicio/fisiología , Entrenamiento de Intervalos de Alta Intensidad , Consumo de Oxígeno , Entrenamiento de Fuerza , Prueba de Esfuerzo , Femenino , Entrenamiento de Intervalos de Alta Intensidad/métodos , Humanos , Persona de Mediana Edad , Distribución AleatoriaRESUMEN
For the author R. Mac Thompson, the first name should be R. Mac and the last name should be Thompson. On SpringerLink the name is listed correctly, but on PubMed he is listed as Mac Thompson R.
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PURPOSE: Betalains are indole-derived pigments found in beet root, and recent studies suggest that they may exert ergogenic effects. Herein, we examined if supplementation for 7 days with betalain-rich beetroot concentrate (BLN) improved cycling performance or altered hemodynamic and serum analytes prior to, during and following a cycling time trial (TT). METHODS: Twenty-eight trained male cyclists (29 ± 10 years, 77.3 ± 13.3 kg, and 3.03 ± 0.62 W/kg) performed a counterbalanced crossover study whereby BLN (100 mg/day) or placebo (PLA) supplementation occurred over 7 days with a 1-week washout between conditions. On the morning of day seven of each supplementation condition, participants consumed one final serving of BLN or PLA and performed a 30-min cycling TT with concurrent assessment of several physiological variables and blood markers. RESULTS: BLN supplementation improved average absolute power compared to PLA (231.6 ± 36.2 vs. 225.3 ± 35.8 W, p = 0.050, d = 0.02). Average relative power, distance traveled, blood parameters (e.g., pH, lactate, glucose, NOx) and inflammatory markers (e.g., IL-6, IL-8, IL-10, TNFα) were not significantly different between conditions. BLN supplementation significantly improved exercise efficiency (W/ml/kg/min) in the last 5 min of the TT compared to PLA (p = 0.029, d = 0.45). Brachial artery blood flow in the BLN condition, immediately post-exercise, tended to be greater compared to PLA (p = 0.065, d = 0.32). CONCLUSIONS: We report that 7 days of BLN supplementation modestly improves 30-min TT power output, exercise efficiency as well as post-exercise blood flow without increasing plasma NOx levels or altering blood markers of inflammation, oxidative stress, and/or hematopoiesis.
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Rendimiento Atlético/fisiología , Betalaínas/administración & dosificación , Ciclismo/fisiología , Suplementos Dietéticos , Consumo de Oxígeno/efectos de los fármacos , Sustancias para Mejorar el Rendimiento/administración & dosificación , Adulto , Estudios Cruzados , Método Doble Ciego , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: We sought to determine the effects of unilateral lower-limb external pneumatic compression (EPC) on bilateral lower-limb vascular reactivity and skin blood flow. METHODS: Thirty-two participants completed this two-aim study. In AIM1 (n = 18, age: 25.5 ± 4.7 years; BMI: 25.6 ± 3.5 kg/m2), bilateral femoral artery blood flow and reactivity (flow mediated dilation [FMD]) measurements were performed via ultrasonography at baseline (PRE) and immediately following 30-min of unilateral EPC treatment (POST). AIM2 (n = 14, age: 25.9 ± 4.5; BMI: 27.2 ± 2.7 kg/m2) involved 30-min unilateral EPC (n = 7) or sham (n = 7) treatment with thermographic bilateral lower-limb mean skin temperature (MST) measurements at baseline, 15-min of treatment (T15) and 0, 30 and 60-min (R0, R30, R60) following treatment. RESULTS: Comparative data herein are presented as mean ± 95% confidence interval. AIM1: No significant effects on total reactive hyperemia blood flow were observed for the treated (i.e., compressed) or untreated (i.e., non-compressed) leg. A significant effect of time, but no time*leg interaction, was observed for relative FMD indicating higher reactivity bilaterally with unilateral EPC treatment (FMD: +0.41 ± 0.09% across both legs; p < 0.05). AIM2: Unilateral EPC treatment was associated with significant increases in whole-leg MST from baseline during (T15: +0.63 ± 0.56 °C in the visible untreated/contralateral leg, p < 0.025) and immediately following treatment (i.e., R0) in both treated (+1.53 ± 0.59 °C) and untreated (+0.60 ± 0.45 °C) legs (p < 0.0125). Across both legs, MST remained elevated with EPC at 30-min post-treatment (+0.60 ± 0.45 °C; p < 0.0167) but not at 60-min post (+0.27 ± 0.46 °C; p = 0.165). Sham treatment was associated with a significant increase in the treated leg immediately post-treatment (+1.12 ± 0.31 °C; p < 0.0167), but not in the untreated leg (-0.27 ± 0.12 °C). MST in neither the treated or untreated leg were increased relative to baseline at R30 or R60 (p > 0.05). Finally, during treatment and at all post-treatment time points (i.e., R0, R30 and R60), independent of treatment group (EPC vs. sham), there was a significant effect of region. The maximum increase in MST was observed at the R0 time point and was significantly (p < 0.05) larger in the thigh region (+1.02 ± 0.31 °C) than the lower-leg (+0.47 ± 0.29 °C) region. However, similar rates of MST decline from R0 in the thigh and lower leg regions were observed at the R30 and R60 time points. DISCUSSION: Unilateral EPC may be an effective intervention for increasing skin blood flow and/or peripheral conduit vascular reactivity in the contralateral limb. While EPC was effective in increasing whole-leg MST bilaterally, there appeared to be a more robust response in the thigh compared to the lower-leg. Thus, proximity along the leg may be an important consideration in prospective treatment strategies.
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BACKGROUND: We sought to determine the effect of multiple walking breaks from sedentary behavior (SED) on glucose responses in sedentary obese women. MATERIALS AND METHODS: Ten women [aged = 36 (5) y, body mass index = 38.0 (1.6) kg/m2, body fat = 49.6 (1.4)%] completed 3 conditions (48-h "washout" in-between conditions) following a standardized meal in random order: 4-hour SED, 4-hour SED with 2 minutes of moderate-intensity walking every 30 minutes (SED + 2 min), and 4-hour SED with 5 minutes of moderate-intensity walking every 30 minutes (SED + 5 min). Measurements included continuous interstitial glucose concentration monitoring immediately before and during standardized conditions and accelerometry for physical activity patterns during and in-between the standardized conditions. Repeated-measures 1-way analyses of variance (α = .05) with Bonferroni correction for post hoc comparisons were performed. Effect sizes (d [95% confidence interval]) were calculated as mean difference from SED/pooled standard deviation. RESULTS: Sedentary time was similar in the 48 hours preceding each condition (P > .05). By design, sedentary time was different between conditions (P < .001). Compared with SED, 2-hour postprandial glucose positive incremental area under the curve was lower for SED + 5 minutes (P = .005; d = - 0.57 [-1.48, 0.40]), but not for SED + 2 minutes (P = .086; d = - 0.71 [-1.63, 0.27]). Four-hour postprandial glucose area under the curve was similar between conditions (P > .05). CONCLUSION: In sedentary obese women, 5 minutes of moderate-intensity walking breaks from SED each 30 minutes attenuate 2-hour postprandial glucose excursions.
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Glucemia/metabolismo , Ejercicio Físico/fisiología , Obesidad/terapia , Caminata/fisiología , Adulto , Femenino , Humanos , Conducta SedentariaRESUMEN
Recent evidence suggests that resistance training with light or heavy loads to failure results in similar adaptations. Herein, we compared how both training modalities affect the molecular, neuromuscular, and recovery responses following exercise. Resistance-trained males (mean ± SE: 22 ± 2 years, 84.8 ± 9.0 kg, 1.79 ± 0.06 m; n = 15) performed a crossover design of four sets of leg extensor exercise at 30% (light RE) or 80% (heavy RE) one repetition maximum (1RM) to repetition failure, and heavy RE or light RE 1 week later. Surface electromyography (EMG) was monitored during exercise, and vastus lateralis muscle biopsies were collected at baseline (PRE), 15 min (15mPOST), and 90 min following RE (90mPOST) for examination of molecular targets and fiber typing. Isokinetic dynamometry was also performed before (PRE), immediately after (POST), and 48 h after (48hPOST) exercise. Dependent variables were analyzed using repeated measures ANOVAs and significance was set at P ≤ 0.05. Repetitions completed were greater during light RE (P < 0.01), while EMG amplitude was greater during heavy RE (P ≤ 0.01). POST isokinetic torque was reduced following light versus heavy RE (P < 0.05). Postexercise expression of mRNAs and phosphoproteins associated with muscle hypertrophy were similar between load conditions. Additionally, p70s6k (Thr389) phosphorylation and fast-twitch fiber proportion exhibited a strong relationship after both light and heavy RE (r > 0.5). While similar mRNA and phosphoprotein responses to both modalities occurred, we posit that heavy RE is a more time-efficient training method given the differences in total repetitions completed, lower EMG amplitude during light RE, and impaired recovery response after light RE.
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Músculo Cuádriceps/fisiología , Entrenamiento de Fuerza/métodos , Humanos , Masculino , Contracción Muscular , Músculo Cuádriceps/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Entrenamiento de Fuerza/efectos adversos , Proteínas Quinasas S6 Ribosómicas 70-kDa/genética , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Adulto JovenRESUMEN
The importance of using infrared thermography (IRT) to assess skin temperature (tsk) is increasing in clinical settings. Recently, its use has been increasing in sports and exercise medicine; however, no consensus guideline exists to address the methods for collecting data in such situations. The aim of this study was to develop a checklist for the collection of tsk using IRT in sports and exercise medicine. We carried out a Delphi study to set a checklist based on consensus agreement from leading experts in the field. Panelists (n = 24) representing the areas of sport science (n = 8; 33%), physiology (n = 7; 29%), physiotherapy (n = 3; 13%) and medicine (n = 6; 25%), from 13 different countries completed the Delphi process. An initial list of 16 points was proposed which was rated and commented on by panelists in three rounds of anonymous surveys following a standard Delphi procedure. The panel reached consensus on 15 items which encompassed the participants' demographic information, camera/room or environment setup and recording/analysis of tsk using IRT. The results of the Delphi produced the checklist entitled "Thermographic Imaging in Sports and Exercise Medicine (TISEM)" which is a proposal to standardize the collection and analysis of tsk data using IRT. It is intended that the TISEM can also be applied to evaluate bias in thermographic studies and to guide practitioners in the use of this technique.
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Temperatura Cutánea , Termografía/métodos , Animales , Regulación de la Temperatura Corporal , Técnica Delphi , Ejercicio Físico , Terapia por Ejercicio/métodos , Humanos , Medicina Deportiva/métodosRESUMEN
PURPOSE: To compare the effects of external pneumatic compression (EPC) and sham when used concurrently with high intensity interval training (HIIT) on performance-related outcomes and recovery-related molecular measures. METHODS: Eighteen recreationally endurance-trained male participants (age: 21.6 ± 2.4 years, BMI: 25.7 ± 0.5 kg/m2, VO2peak: 51.3 ± 0.9 mL/kg/min) were randomized to balanced sham and EPC treatment groups. Three consecutive days of HIIT followed by EPC/sham treatment (Days 2-4) and 3 consecutive days of recovery (Days 5-7) with EPC/sham only on Days 5-6 were employed. Venipuncture, flexibility and pressure-to-pain threshold (PPT) measurements were made throughout. Vastus lateralis muscle was biopsied at PRE (i.e., Day 1), 1-h post-EPC/sham treatment on Day 2 (POST1), and 24-h post-EPC/sham treatment on Day 7 (POST2). 6-km run time trial performance was tested at PRE and POST2. RESULTS: No group × time interaction was observed for flexibility, PPT, or serum measures of creatine kinase (CK), hsCRP, and 8-isoprostane. However, there was a main effect of time for serum CK (p = 0.005). Change from PRE in 6-km run times at POST2 were not significantly different between groups. Significant between-groups differences existed for change from PRE in atrogin-1 mRNA (p = 0.018) at the POST1 time point (EPC: - 19.7 ± 8.1%, sham: + 7.7 ± 5.9%) and atrogin-1 protein concentration (p = 0.013) at the POST2 time point (EPC: - 31.8 ± 7.5%, sham: + 96.0 ± 34.7%). In addition, change from PRE in poly-Ub proteins was significantly different between groups at both the POST1 (EPC: - 26.0 ± 10.3%, sham: + 34.8 ± 28.5%; p = 0.046) and POST2 (EPC: - 33.7 ± 17.2%, sham: + 21.4 ± 14.9%; p = 0.037) time points. CONCLUSIONS: EPC when used concurrently with HIIT and in subsequent recovery days reduces skeletal muscle markers of proteolysis.
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Entrenamiento de Intervalos de Alta Intensidad/métodos , Aparatos de Compresión Neumática Intermitente/efectos adversos , Proteolisis , Adulto , Proteína C-Reactiva/metabolismo , Creatina Quinasa/sangre , Dinoprost/análogos & derivados , Dinoprost/sangre , Entrenamiento de Intervalos de Alta Intensidad/efectos adversos , Humanos , Masculino , Proteínas Musculares/metabolismo , Músculo Cuádriceps/irrigación sanguínea , Músculo Cuádriceps/metabolismo , Músculo Cuádriceps/fisiología , Proteínas Ligasas SKP Cullina F-box/metabolismo , UbiquitinaciónRESUMEN
BACKGROUND: We sought to determine if a pre-workout supplement (PWS), containing multiple ingredients thought to enhance blood flow, increases hyperemia associated with resistance training compared to placebo (PBO). Given the potential interaction with training loads/time-under-tension, we evaluated the hyperemic response at two different loads to failure. METHODS: Thirty males participated in this double-blinded study. At visit 1, participants were randomly assigned to consume PWS (Reckless™) or PBO (maltodextrin and glycine) and performed four sets of leg extensions to failure at 30% or 80% of their 1-RM 45-min thereafter. 1-wk. later (visit 2), participants consumed the same supplement as before, but exercised at the alternate load. Heart rate (HR), blood pressure (BP), femoral artery blood flow, and plasma nitrate/nitrite (NOx) were assessed at baseline (BL), 45-min post-PWS/PBO consumption (PRE), and 5-min following the last set of leg extensions (POST). Vastus lateralis near infrared spectroscopy (NIRS) was employed during leg extension exercise. Repeated measures ANOVAs were performed with time, supplement, and load as independent variables and Bonferroni correction applied for multiple post-hoc comparisons. Data are reported as mean ± SD. RESULTS: With the 30% training load compared to 80%, significantly more repetitions were performed (p < 0.05), but there was no difference in total volume load (p > 0.05). NIRS derived minimum oxygenated hemoglobin (O2Hb) was lower in the 80% load condition compared to 30% for all rest intervals between sets of exercise (p < 0.0167). HR and BP did not vary as a function of supplement or load. Femoral artery blood flow at POST was higher independent of exercise load and treatment. However, a time*supplement*load interaction was observed revealing greater femoral artery blood flow with PWS compared to PBO at POST in the 80% (+56.8%; p = 0.006) but not 30% load condition (+12.7%; p = 0.476). Plasma NOx was ~3-fold higher with PWS compared to PBO at PRE and POST (p < 0.001). CONCLUSIONS: Compared to PBO, the PWS consumed herein augmented hyperemia following multiple sets to failure at 80% of 1-RM, but not 30%. This specificity may be a product of interaction with local perturbations (e.g., reduced tissue oxygenation levels [minimum O2Hb] in the 80% load condition) and/or muscle fiber recruitment.
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Suplementos Dietéticos , Hiperemia/fisiopatología , Pierna/irrigación sanguínea , Pierna/fisiología , Músculo Esquelético/irrigación sanguínea , Entrenamiento de Fuerza , Fenómenos Fisiológicos en la Nutrición Deportiva , Adulto , Método Doble Ciego , Metabolismo Energético/fisiología , Arteria Femoral/efectos de los fármacos , Arteria Femoral/fisiología , Voluntarios Sanos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Fuerza Muscular/efectos de los fármacos , Fuerza Muscular/fisiología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiología , Consumo de Oxígeno/efectos de los fármacos , Consumo de Oxígeno/fisiología , Resistencia Física , Flujo Sanguíneo Regional/efectos de los fármacos , Resultado del Tratamiento , Adulto JovenRESUMEN
We sought to determine the effects of L-leucine (LEU) or different protein supplements standardized to LEU (~3.0 g/serving) on changes in body composition, strength, and histological attributes in skeletal muscle and adipose tissue. Seventy-five untrained, college-aged males (mean ± standard error of the mean (SE); age = 21 ± 1 years, body mass = 79.2 ± 0.3 kg) were randomly assigned to an isocaloric, lipid-, and organoleptically-matched maltodextrin placebo (PLA, n = 15), LEU (n = 14), whey protein concentrate (WPC, n = 17), whey protein hydrolysate (WPH, n = 14), or soy protein concentrate (SPC, n = 15) group. Participants performed whole-body resistance training three days per week for 12 weeks while consuming supplements twice daily. Skeletal muscle and subcutaneous (SQ) fat biopsies were obtained at baseline (T1) and ~72 h following the last day of training (T39). Tissue samples were analyzed for changes in type I and II fiber cross sectional area (CSA), non-fiber specific satellite cell count, and SQ adipocyte CSA. On average, all supplement groups including PLA exhibited similar training volumes and experienced statistically similar increases in total body skeletal muscle mass determined by dual X-ray absorptiometry (+2.2 kg; time p = 0.024) and type I and II fiber CSA increases (+394 µm² and +927 µm²; time p < 0.001 and 0.024, respectively). Notably, all groups reported increasing Calorie intakes ~600-800 kcal/day from T1 to T39 (time p < 0.001), and all groups consumed at least 1.1 g/kg/day of protein at T1 and 1.3 g/kg/day at T39. There was a training, but no supplementation, effect regarding the reduction in SQ adipocyte CSA (-210 µm²; time p = 0.001). Interestingly, satellite cell counts within the WPC (p < 0.05) and WPH (p < 0.05) groups were greater at T39 relative to T1. In summary, LEU or protein supplementation (standardized to LEU content) does not provide added benefit in increasing whole-body skeletal muscle mass or strength above PLA following 3 months of training in previously untrained college-aged males that increase Calorie intakes with resistance training and consume above the recommended daily intake of protein throughout training. However, whey protein supplementation increases skeletal muscle satellite cell number in this population, and this phenomena may promote more favorable training adaptations over more prolonged periods.
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Adiposidad , Proteínas en la Dieta/administración & dosificación , Suplementos Dietéticos , Leucina/administración & dosificación , Fuerza Muscular , Hidrolisados de Proteína/administración & dosificación , Músculo Cuádriceps/fisiología , Entrenamiento de Fuerza , Proteínas de Soja/administración & dosificación , Grasa Subcutánea/fisiología , Proteína de Suero de Leche/administración & dosificación , Absorciometría de Fotón , Alabama , Biopsia , Proteínas en la Dieta/efectos adversos , Suplementos Dietéticos/efectos adversos , Método Doble Ciego , Ingestión de Energía , Humanos , Leucina/efectos adversos , Masculino , Hidrolisados de Proteína/efectos adversos , Músculo Cuádriceps/citología , Músculo Cuádriceps/diagnóstico por imagen , Proteínas de Soja/efectos adversos , Grasa Subcutánea/citología , Grasa Subcutánea/diagnóstico por imagen , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía , Proteína de Suero de Leche/efectos adversos , Adulto JovenRESUMEN
Purpose: Translating exercise-science methodology for determination of muscle bioenergetics, we hypothesized that the temporal voice-use patterns for classroom and music teachers would indicate a reliance on the immediate energy system for laryngeal skeletal-muscle metabolism. It was hypothesized that the music-teacher group would produce longer voiced segments than the classroom teachers. Method: Using a between- and within-group multivariate analysis-of-variance design (5 classroom teachers; 7 music teachers), we analyzed fundamental-frequency data-collected via an ambulatory phonation monitor-for length (seconds) of voiced and nonvoiced intervals. Data were collected for 7.5 hr during the workday, over the course of several workdays for each teacher. Results: Descriptive analyses of voiced and nonvoiced intervals indicated that over 99% of voiced segments for both groups were no longer than 3.15 s, supporting the hypothesis of reliance on the immediate energy system for muscle bioenergetics. Significant differences were identified between and within the classroom- and music-teacher groups, with the music-teacher group producing longer voiced segments overall. Conclusions: Knowledge of probable intrinsic laryngeal skeletal-muscle bioenergetics requirements could inform new interdisciplinary considerations for voice habilitation and rehabilitation.
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Maestros , Voz , Adulto , Metabolismo Energético , Femenino , Humanos , Músculos Laríngeos/metabolismo , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Tiempo , Voz/fisiología , Entrenamiento de la Voz , Adulto JovenRESUMEN
PURPOSE: We sought to compare the effects of external pneumatic compression (EPC) and sham when used concurrently with resistance training on performance-related outcomes and molecular measures related to recovery. METHODS: Twenty (N = 20) resistance-trained male participants (aged 21.6±2.4 years) were randomized to balanced sham or EPC intervention groups. The protocol consisted of 3 consecutive days of heavy, voluminous back squat exercise followed by EPC/sham treatment (Days2-4) and 3 consecutive days of recovery (Days5-7) with EPC/sham only on Days5-6. On Day1 (PRE), and Days3-7, venipuncture, flexibility and pressure-to-pain threshold (PPT) measures were performed. Vastsus lateralis muscle tissue was biopsied at PRE, 1-h post-EPC/sham treatment on Day2 (POST1) and 24-h post-EPC/sham treatment on Day7 (POST2). Isokinetic peak torque was assessed at PRE and POST2. RESULTS: Peak isokinetic strength did not change from PRE to POST2 in either group. The PPT was significantly lower on Days3-6 with sham, indicating greater muscle soreness, though this was largely abolished in the EPC group. A significant decrease in flexibility with sham was observed on Day3 (+16.2±4.6% knee joint angle; P<0.01) whereas there was no change with EPC (+2.8±3.8%; P>0.01). Vastus lateralis poly-ubiquitinated proteins significantly increased at the POST2 time point relative to PRE with sham (+66.6±24.6%; P<0.025) and were significantly greater (P<0.025) than those observed with EPC at the same time point (-18.6±8.5%). 4-hydroxynonenal values were significantly lower at POST2 relative to PRE with EPC (-16.2±5.6%; P<0.025) and were significantly lower (P<0.025) than those observed with sham at the same time point (+11.8±5.9%). CONCLUSION: EPC mitigated a reduction in flexibility and PPT that occurred with sham. Moreover, EPC reduced select skeletal muscle oxidative stress and proteolysis markers during recovery from heavy resistance exercise.
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Entrenamiento de Fuerza/métodos , Transducción de Señal , Adulto , Humanos , Masculino , Adulto JovenRESUMEN
Background: We examined the acute effect of a red spinach extract (RSE) (1000 mg dose; ~90 mg nitrate (NO 3 - )) on performance markers during graded exercise testing (GXT). Methods: For this randomized, double-blind, placebo (PBO)-controlled, crossover study, 15 recreationally-active participants (aged 23.1 ± 3.3 years; BMI: 27.2 ± 3.7 kg/m²) reported >2 h post-prandial and performed GXT 65â»75 min post-RSE or PBO ingestion. Blood samples were collected at baseline (BL), pre-GXT (65â»75 min post-ingestion; PRE), and immediately post-GXT (POST). GXT commenced with continuous analysis of expired gases. Results: Plasma concentrations of NO 3 - increased PRE (+447 ± 294%; p < 0.001) and POST (+378 ± 179%; p < 0.001) GXT with RSE, but not with PBO (+3 ± 26%, -8 ± 24%, respectively; p > 0.05). No effect on circulating nitrite (NO 2 - ) was observed with RSE (+3.3 ± 7.5%, +7.7 ± 11.8% PRE and POST, respectively; p > 0.05) or PBO (-0.5 ± 7.9%, -0.2 ± 8.1% PRE and POST, respectively; p > 0.05). When compared to PBO, there was a moderate effect of RSE on plasma NO 2 - at PRE (g = 0.50 [-0.26, 1.24] and POST g = 0.71 [-0.05, 1.48]). During GXT, VO2 at the ventilatory threshold was significantly higher with RSE compared to PBO (+6.1 ± 7.3%; p < 0.05), though time-to-exhaustion (-4.0 ± 7.7%; p > 0.05) and maximal aerobic power (i.e., VO2 peak; -0.8 ± 5.6%; p > 0.05) were non-significantly lower with RSE. Conclusions: RSE as a nutritional supplement may elicit an ergogenic response by delaying the ventilatory threshold.
RESUMEN
Next-generation RNA sequencing was employed to determine the acute and subchronic impact of peristaltic pulse external pneumatic compression (PEPC) of different target inflation pressures on global gene expression in human vastus lateralis skeletal muscle biopsy samples. Eighteen (N = 18) male participants were randomly assigned to one of the three groups: (1) sham (n = 6), 2) EPC at 30-40 mmHg (LP-EPC; n = 6), and 3) EPC at 70-80 mmHg (MP-EPC; n = 6). One hour treatment with sham/EPC occurred for seven consecutive days. Vastus lateralis skeletal muscle biopsies were performed at baseline (before first treatment; PRE), 1 h following the first treatment (POST1), and 24 h following the last (7th) treatment (POST2). Changes from PRE in gene expression were analyzed via paired comparisons within each group. Genes were filtered to include only those that had an RPKM ≥ 1.0, a fold-change of ≥1.5 and a paired t-test value of <0.01. For the sham condition, two genes at POST1 and one gene at POST2 were significantly altered. For the LP-EPC condition, nine genes were up-regulated and 0 genes were down-regulated at POST1 while 39 genes were up-regulated and one gene down-regulated at POST2. For the MP-EPC condition, two genes were significantly up-regulated and 21 genes were down-regulated at POST1 and 0 genes were altered at POST2. Both LP-EPC and MP-EPC acutely alter skeletal muscle gene expression, though only LP-EPC appeared to affect gene expression with subchronic application. Moreover, the transcriptome response to EPC demonstrated marked heterogeneity (i.e., genes and directionality) with different target inflation pressures.