Caffeine Expectancy Does Not Influence the Physical Working Capacity at the Fatigue Threshold.

ABSTRACT: Ambrozy, CA, Hawes, NE, Hayden, OL, Sortzi, I, and Malek, MH. Caffeine expectancy does not influence the physical working capacity at the fatigue threshold. J Strength Cond Res 38(6): 1056-1062, 2024-The placebo effect occurs when a desired outcome is experienced due to the belief that a treatment is effective, even in the absence of an active ingredient. One explanation for this effect is based on a person's expectations of a drug or supplement. Although caffeine's effects on sports performance have been studied, little is known about how expectations of caffeine affect neuromuscular fatigue during continuous muscle action. The physical working capacity at the fatigue threshold (PWCFT) can be used to assess neuromuscular fatigue noninvasively using surface electromyography. Thus, the purpose of this study was to investigate whether caffeine expectancy influences PWCFT. We hypothesized that regardless of expectancy, caffeine consumption would delay neuromuscular fatigue. The study involved 8 healthy college-aged men (mean ± SEM: age, 25.6 ± 1.0 years) who visited the laboratory on 4 occasions, each separated by 7 days. The subjects completed 4 experimental conditions, in random order, where they were told that they were consuming caffeine or placebo and either received caffeine or placebo. After consuming the drink, the subjects remained in the laboratory for an hour and then performed an incremental exercise test. The results showed that the condition where subjects were told that they were consuming caffeine and received caffeine had significantly higher mean values for maximal power output (F(3, 21) = 11.75; p < 0.001), PWCFT (F(3, 21) = 12.28; p < 0.001), PWCFT (%maximal power output; F(3, 21) = 8.75; p < 0.001), and heart rate at end exercise (%predicted; F(3, 21) = 3.83; p = 0.025) compared with the 2 conditions where placebo was received. However, no statistically significant mean differences were found from the condition where subjects were told that they were consuming placebo but consuming caffeine. This suggests that a person's expectancy and potential somatic response may serve as a cue for how an ergogenic aid or placebo could affect subsequent performance.

Mitochondria Transplantation: Rescuing Innate Muscle Bioenergetic Impairment in a Model of Aging and Exercise Intolerance.

ABSTRACT: Arroum, T, Hish, GA, Burghardt, KJ, Ghamloush, M, Bazzi, B, Mrech, A, Morse, PT, Britton, SL, Koch, LG, McCully, JD, Hüttemann, M, and Malek, MH. Mitochondria transplantation: Rescuing innate muscle bioenergetic impairment in a model of aging and exercise intolerance. J Strength Cond Res 38(7): 1189-1199, 2024-Mitochondria, through oxidative phosphorylation, are crucial for energy production. Disease, genetic impairment, or deconditioning can harm muscle mitochondria, affecting energy production. Endurance training enhances mitochondrial function but assumes mobility. Individuals with limited mobility lack effective treatments for mitochondrial dysfunction because of disease or aging. Mitochondrial transplantation replaces native mitochondria that have been damaged with viable, respiration-competent mitochondria. Here, we used a rodent model selectively bred for low-capacity running (LCR), which exhibits innate mitochondrial dysfunction in the hind limb muscles. Hence, the purpose of this study was to use a distinct breed of rats (i.e., LCR) that display hereditary skeletal muscle mitochondrial dysfunction to evaluate the consequences of mitochondrial transplantation. We hypothesized that the transplantation of mitochondria would effectively alleviate mitochondrial dysfunction in the hind limb muscles of rats when compared with placebo injections. In addition, we hypothesized that rats receiving the mitochondrial transplantation would experience an improvement in their functional capacity, as evaluated through incremental treadmill testing. Twelve aged LCR male rats (18 months old) were randomized into 2 groups (placebo or mitochondrial transplantation). One LCR rat of the same age and sex was used as the donor to isolate mitochondria from the hindlimb muscles. Isolated mitochondria were injected into both hindlimb muscles (quadriceps femoris, tibialis anterior (TA), and gastrocnemius complex) of a subset LCR (n = 6; LCR-M) rats. The remaining LCR (n = 5; LCR-P) subset received a placebo injection containing only the vehicle without the isolated mitochondria. Four weeks after mitochondrial transplantation, rodents were euthanized and hindlimb muscles harvested. The results indicated a significant (p < 0.05) increase in mitochondrial markers for glycolytic (plantaris and TA) and mixed (quadricep femoris) muscles, but not oxidative muscle (soleus). Moreover, we found significant (p < 0.05) epigenetic changes (i.e., hypomethylation) at the global and site-specific levels for a key mitochondrial regulator (transcription factor A mitochondrial) between the placebo and mitochondrial transplantation groups. To our knowledge, this is the first study to examine the efficacy of mitochondrial transplantation in a rodent model of aging with congenital skeletal muscle dysfunction.

Listening to Music Pretask on Neuromuscular Fatigue During Exercise: Preferred vs. Nonpreferred Music.

ABSTRACT: Diehl, TL, Yu, JN, Storer, FM, and Malek, MH. Listening to music pretask on neuromuscular fatigue during exercise: preferred vs. nonpreferred music. J Strength Cond Res 37(7): 1537-1542, 2023-Studies indicate that listening to music can elicit various physiological responses ranging from distracting the subject from the sensation of fatigue to changes in specific regions of the brain. Indeed, the use of music, as an ergogenic aid, to improve human performance has been shown to be a powerful tool. Many studies on the effect of music on human performance have had subjects listen to music in-task (i.e., during the activity). There is, however, a growing interest to determine the role of listening to music pretask (i.e., before the activity) on exercise outcomes. In addition, it is important to consider the subject's music preference as that may influence the target outcome variable(s). Therefore, the purpose of this study was to determine whether listening to preferred music pretask influences the physical working capacity at the fatigue threshold (PWC FT ). We hypothesized that listening to preferred music pretask will increase the estimated PWC FT compared with the control condition, which is listening to nonpreferred music. Nine healthy college-aged men (mean ± SEM : age, 23.4 ± 0.4 years; body mass, 71.6 ± 2.5 kg; and height, 1.81 ± 0.02 m) volunteered for this study. Each subject visited the laboratory on 2 occasions separated by 7 days. In a randomized manner, subjects listened to their preferred music for 30 minutes before the exercise test for 1 visit, whereas for the other visit, subjects listened to their nonpreferred music 30 minutes before the exercise test. Exercise outcomes were recorded for both visits and analyzed using a paired-samples t test. The results indicated no significant ( p > 0.05) mean differences for maximal power output (mean ± SEM : 60 ± 4 W vs. 60 ± 4 W), PWC FT (25 ± 3 W vs. 29 ± 2 W), or heart rate at end exercise (153 ± 8 b·min -1 vs. 155 ± 7 b·min -1 ) between listening to nonpreferred vs. preferred music 30 minutes before the exercise activity. These findings suggest that listening to music pretask does not influence neuromuscular fatigue during the exercise workbout.

Sometimes less is more: inhibitory infrared light during early reperfusion calms hyperactive mitochondria and suppresses reperfusion injury.

Ischemic stroke affects over 77 million people annually around the globe. Due to the blockage of a blood vessel caused by a stroke, brain tissue becomes ischemic. While prompt restoration of blood flow is necessary to save brain tissue, it also causes reperfusion injury. Mitochondria play a crucial role in early ischemia-reperfusion injury due to the generation of reactive oxygen species (ROS). During ischemia, mitochondria sense energy depletion and futilely attempt to up-regulate energy production. When reperfusion occurs, mitochondria become hyperactive and produce large amounts of ROS which damages neuronal tissue. This ROS burst damages mitochondria and the cell, which results in an eventual decrease in mitochondrial activity and pushes the fate of the cell toward death. This review covers the relationship between the mitochondrial membrane potential (ΔΨm) and ROS production. We also discuss physiological mechanisms that couple mitochondrial energy production to cellular energy demand, focusing on serine 47 dephosphorylation of cytochrome c (Cytc) in the brain during ischemia, which contributes to ischemia-reperfusion injury. Finally, we discuss the use of near infrared light (IRL) to treat stroke. IRL can both stimulate or inhibit mitochondrial activity depending on the wavelength. We emphasize that the use of the correct wavelength is crucial for outcome: inhibitory IRL, applied early during reperfusion, can prevent the ROS burst from occurring, thus preserving neurological tissue.

Log-Transformed Electromyography Amplitude Power Output Relationship: Nondominant vs. Dominant Limb.

ABSTRACT: Boccomino, HL, Daoud, BT, Hudas, A, North, WA, and Malek, MH. Log-transformed electromyography amplitude power output relationship: nondominant vs. dominant limb. J Strength Cond Res 36(3): 851-856, 2022-Findings from studies that examine bilateral differences between the nondominant and dominant limb during whole-body (i.e., cycle ergometry) are equivocal. This may, in part, be because of the mode of exercise (i.e., whole-body) and how the data are analyzed. Surface electromyography (EMG) is a noninvasive method of examining motor unit recruitment and activation during exercise. The log-transformed electromyography amplitude power output relationship provides y-intercept and slope terms on a subject-by-subject basis that can therefore be statistically analyzed. The purpose of this study, therefore, was to identify potential differences in the muscle for the nondominant and dominant limb using the log-transformed EMG amplitude power output relationship for continuous exercise that isolates the quadricep femoris muscles. Nine healthy college-aged men (mean ± SEM: age, 22.6 ± 1.2 years; mass, 68.6 ± 10.4 kg; and height, 1.76 ± 0.03 m) volunteered as subjects for the current study. Each subject visited the laboratory on a single occasion, had EMG electrodes placed on their rectus femoris muscle for their nondominant and dominant limb, and performed an incremental double-leg knee-extensor ergometry to voluntary exhaustion. The subjects achieved a mean power output (75 ± 8 W) for the exercise test. In addition, a mean end-exercise heart rate (155 ± 8 b·min-1) corresponded to 79 ± 4% of the age-predicted heart rate using the formula 220-age. Separate paired t tests for the slope (t[8] = 0.929 p = 0.38) and y-intercept (t[8] = 0.368, p = 0.72) terms revealed no significant mean differences between the 2 limbs. The results of the present study indicate that there are no differences in muscle activation between the nondominant and dominant limbs for continuous exercise that isolates the muscle.

Perceived Consumption of a High-Dose Caffeine Drink Delays Neuromuscular Fatigue.

ABSTRACT: Elhaj, HM, Imam, O, Page, BW, Vitale, JM, and Malek, MH. Perceived consumption of a high-dose caffeine drink delays neuromuscular fatigue. J Strength Cond Res 36(5): 1185-1190, 2022-The placebo effect is a concept in which a desired outcome arises, mainly from the belief that the treatment (i.e., supplement or drug) was beneficial although no active ingredient was given. The results of studies related to the placebo effect primarily examine functional performance. What remains unanswered, however, is whether these changes in performance are associated with neuromuscular alterations in the exercised muscles. The purpose of the study, therefore, was to determine the influence of the placebo effect on the physical working capacity fatigue threshold (PWCFT) for a continuous exercise paradigm. To achieve this aim, subjects were told that they were participating in a study to determine the dosage response (low or high) of caffeine on neuromuscular fatigue when in fact no caffeine was given during the experiment. We hypothesized that the perceived consumption of the high-dose caffeine drink would result in a higher PWCFT than the perceived consumption of the low-dose caffeine drink and placebo. Secondarily, we hypothesized that the perceived consumption of the high-dose caffeine drink would result in a higher power output than the perceived consumption of the placebo. Nine healthy college-aged men (mean ± SEM: age, 25.7 ± 1.3 years; body mass, 84.4 ± 3.1 kg; and height: 1.82 ± 0.02 m) volunteered to be in the study. For each of the visits, subjects were given an 8 oz. bottle of water with dissolved crystal light. After the drink was consumed, subjects rested in the laboratory for 1 hour before performing the incremental single-leg knee-extensor ergometry. Immediately after the termination of the incremental single-leg knee-extensor ergometry, the subject was asked which caffeine dose (placebo, low, or high) they believed they consumed for that visit. There were no significant mean differences for maximal power output for the 3 perceived conditions (placebo: 62 ± 3, low-dose caffeine: 62 ± 4, and high-dose caffeine: 65 ± 3 W). When the subjects perceived consuming the high-dose caffeine drink, there were significant mean differences (all p-values < 0.01), for PWCFT, between the other conditions (mean ± SEM: placebo: 23 ± 3 W, low-dose caffeine: 26 ± 2 W, and high-dose caffeine: 42 ± 3 W). This corresponded to a significant mean difference (all p-values < 0.01) when the PWCFT was presented as a percentage of the maximal power output (mean ± SEM: placebo: 37 ± 5%, low-dose caffeine: 42 ± 3%, and high-dose caffeine: 64 ± 3%). The application of our results may indicate that the subject's expectancy, to caffeine consumption, plays a critical role in delaying the onset of neuromuscular fatigue despite not receiving any caffeine in their drinks.

Cytochrome c oxidase-modulatory near-infrared light penetration into the human brain: Implications for the noninvasive treatment of ischemia/reperfusion injury.

Near-infrared light (IRL) has been evaluated as a therapeutic for a variety of pathological conditions, including ischemia/reperfusion injury of the brain, which can be caused by an ischemic stroke or cardiac arrest. Strategies have focused on modulating the activity of mitochondrial electron transport chain (ETC) enzyme cytochrome c oxidase (COX), which has copper centers that broadly absorb IRL between 700 and 1,000 nm. We have recently identified specific COX-inhibitory IRL wavelengths that are profoundly neuroprotective in rodent models of brain ischemia/reperfusion through the following mechanism: COX inhibition by IRL limits mitochondrial membrane potential hyperpolarization during reperfusion, which otherwise causes reactive oxygen species (ROS) production and cell death. Prior to clinical application of IRL on humans, IRL penetration must be tested, which may be wavelength dependent. In the present study, four fresh (unfixed) cadavers and isolated cadaver tissues were used to examine the transmission of infrared light through human biological tissues. We conclude that the transmission of 750 and 940 nm IRL through 4 cm of cadaver head supports the viability of IRL to treat human brain ischemia/reperfusion injury and is similar for skin with different skin pigmentation. We discuss experimental difficulties of working with fresh cadavers and strategies to overcome them as a guide for future studies.

The Evolution of the Physical Work Capacity at the Fatigue Threshold Test: Past, Present, and Future.

ABSTRACT: Feldpausch, JE, Blok, AL, Frederick, EL, Coburn, JW, and Malek, MH. The evolution of the physical work capacity at the fatigue threshold test: past, present, and future. J Strength Cond Res 35(12): 3529-3536, 2021-The assessment of neuromuscular fatigue using surface electromyography has evolved over the past 40 years while maintaining some of the original key features. In this mini-review article, the goal will be to briefly present a history and systems of the physical working capacity at the fatigue threshold (PWCFT). In addition, we will discuss studies that have investigated the effect of different interventions such as supplementation, exercise, and cognitive fatigue to examine what stimuli influence the PWCFT. The latter section of this mini-review will discuss future studies that may provide additional information related to the underlying physiological mechanism(s) that influences the PWCFT. We will conclude with the practical application of PWCFT in health and sports settings.

Reduced Electromyographic Fatigue Threshold After Performing a Cognitive Fatiguing Task.

ABSTRACT: Ferris, JR, Tomlinson, MA, Ward, TN, Pepin, ME, and Malek, MH. Reduced electromyographic fatigue threshold after performing a cognitive fatiguing task. J Strength Cond Res 35(1): 267-274, 2021-Cognitive fatigue tasks performed before exercise may reduce exercise capacity. The electromyographic fatigue threshold (EMGFT) is the highest exercise intensity that can be maintained without significant increase in the electromyography (EMG) amplitude vs. time relationship. To date, no studies have examined the effect of cognitive fatigue on the estimation of the EMGFT. The purpose of this study, therefore, was to determine whether cognitive fatigue before performing exercise reduces the estimated EMGFT. Eight healthy college-aged men were recruited from a university student population and visited the laboratory on multiple occasions. In a randomized order, subjects performed either the cognitive fatigue task (AX continuous performance test) for 60 minutes on one visit (experimental condition) or watched a video on trains for 60 minutes on the other visit (control condition). After each condition, subjects performed the incremental single-leg knee-extensor ergometry test while the EMG amplitude was recorded from the rectus femoris muscle and heart rate was monitored throughout. Thereafter, the EMGFT was calculated for each subject for each visit and compared using paired samples t-test. For exercise outcomes, there were no significant mean differences for maximal power output between the 2 conditions (control: 51 ± 5 vs. fatigue: 50 ± 3 W), but there was a significant decrease in EMGFT between the 2 conditions (control: 31 ± 3 vs. fatigue: 24 ± 2 W; p = 0.013). Moreover, maximal heart rate was significantly different between the 2 conditions (control: 151 ± 5 vs. fatigue: 132 ± 6; p = 0.027). These results suggest that performing the cognitive fatiguing task reduces the EMGFT with a corresponding reduction in maximal heart rate response.

Pre-exhaustion Exercise Differentially Influences Neuromuscular Fatigue Based on Habitual Physical Activity History.

ABSTRACT: Harlan, KG, Merucci, RB, Weaver, JJ, Windle, TC, and Malek, MH. Pre-exhaustion exercise differentially influences neuromuscular fatigue based on habitual physical activity history. J Strength Cond Res 35(3): 739-745, 2021-Although there is anecdotal evidence of a potential physiological benefit of pre-exhaustion exercise to enhance muscular recruitment, few studies have systematically examined the effect on neuromuscular activity. Moreover, a subject's habitual physical activity history may, in part, contribute to the muscle's response on a subsequent workbout after a single pre-exhaustion workbout. To date, no studies have examined the effect of pre-exhaustion exercise on the electromyographic fatigue threshold (EMGFT). The purpose of this study, therefore, is to determine whether pre-exhaustion exercise influences the EMGFT. Specifically, we were interested in determining whether or not there is a dichotomous response to pre-exhaustion exercise based on the individual's habitual physical activity history. Thus, we hypothesized that healthy active subjects would have reduced EMGFT values, whereas elite runners would have increased EMGFT values as a result of the pre-exhaustion exercise. Eight healthy college-aged men (mean ± SEM, age = 24.5 ± 0.3 years; body mass = 83.1 ± 3.0 kg; and height = 1.80 ± 0.02 m) and 9 elite runners (mean ± SEM, age = 23.4 ± 0.7 years; body mass = 70.3 ± 2.7 kg; and height = 1.79 ± 0.03 m) participated in current study. Each subject visited the laboratory on 2 occasions separated by 7 days and performed the single-leg knee-extensor ergometry test. For one of the visits, the subjects performed the Thorstensson test (50 continuous, concentric knee extensions) before the single-leg knee-extensor ergometry. The EMGFT was measured on both visits for all subjects. For healthy subjects, we found that the EMGFT was significantly reduced after performing the 50 isokinetic knee extensions (control: 27 ± 6 W vs. Thorstensson: 21 ± 6.0 W; p = 0.001), whereas for elite runners, there was no significant mean differences between the 2 visits (control: 38 ± 3 W vs. Thorstensson: 39 ± 2 W; p = 0.813). These results suggest that 50 repetition of isokinetic muscle action, as a method of pre-exhausting the quadriceps femoris muscles, may be influenced by the subject's habitual exercise history.

Repeated Incremental Workbouts Separated by 1 Hour Increase the Electromyographic Fatigue Threshold.

ABSTRACT: Bremer, N, Peoples, G, Hasler, B, Litzenburg, R, Johnson, A, and Malek, MH. Repeated incremental workbouts separated by 1 hour increase the electromyographic fatigue threshold. J Strength Cond Res 35(5): 1397-1402, 2021-Studies examining the influence of priming, for continuous exercise, have mainly focused on improved exercise capacity related to oxygen uptake kinetics rather than on neuromuscular fatigue of the muscle. The purpose of this study, therefore, was to determine whether or not the electromyographic fatigue threshold (EMGFT) could be modulated by having subjects perform 2 incremental tests separated by 1 hour. We hypothesized that the EMGFT determined from the second incremental test would be higher than the EMGFT determined from the first incremental test. Nine healthy college-aged men (mean ± SEM: age: 23.8 ± 0.6 years; body mass: 79.5 ± 3.3 kg; height: 1.78 ± 0.02 m) were recruited from the university population. Each subject visited the laboratory on 1 occasion and performed 2 incremental single-leg knee-extensor ergometry to voluntary fatigue separated by 1 hour. The EMGFT was determined for each trial and statistically compared using paired-samples t-test. The results indicated significant mean differences between the EMGFT for the 2 trials (trial 1: 27 ± 1 W vs. trial 2: 34 ± 2 W; p = 0.001), whereas there were no significant mean differences for maximal power output (trial 1: 53 ± 2 W vs. trial 2: 57 ± 2; p = 0.09). These findings suggest that postactivation potentiation may, in part, explain the differences in EMGFT because the exercise mode used in the current study minimizes the cardiorespiratory responses to exercise.

Evaluating Subjective and Objective Fatigue Immediately Before and After Hemodialysis: A Within-Subjects' Design.

Change in fatigue within a hemodialysis (HD) session has not been established previously. A total of 55 cognitively intact adults on HD were included; individuals with mobility/hemodynamic issues were excluded. Measures included the Piper Fatigue Scale-12 (PFS-12), 6-Minute Walk Test (6MWT), demographic and clinical. Descriptive statistics, ANOVA, and stepwise regression were used. Mean age was 57 years. Mean change in PFS-12 was -4.56 ± 27.85. Mean change in walk distance was -16.26 ± 43.87 meters (p = 0.03). The change in the PFS-12 accounted for 47% quadratic trend in the change in 6MWD (p < 0.001). Both fatigue measures (PFS-12 and 6MWT) can be useful for examining changes in fatigue levels within an HD session. Our findings speak to the convergent validity of these two measures of fatigue.

Tissue-specific regulation of cytochrome c by post-translational modifications: respiration, the mitochondrial membrane potential, ROS, and apoptosis.

Cytochrome c (Cyt c) plays a vital role in the mitochondrial electron transport chain (ETC). In addition, it is a key regulator of apoptosis. Cyt c has multiple other functions including ROS production and scavenging, cardiolipin peroxidation, and mitochondrial protein import. Cyt c is tightly regulated by allosteric mechanisms, tissue-specific isoforms, and post-translational modifications (PTMs). Distinct residues of Cyt c are modified by PTMs, primarily phosphorylations, in a highly tissue-specific manner. These modifications downregulate mitochondrial ETC flux and adjust the mitochondrial membrane potential (ΔΨm), to minimize reactive oxygen species (ROS) production under normal conditions. In pathologic and acute stress conditions, such as ischemia-reperfusion, phosphorylations are lost, leading to maximum ETC flux, ΔΨm hyperpolarization, excessive ROS generation, and the release of Cyt c. It is also the dephosphorylated form of the protein that leads to maximum caspase activation. We discuss the complex regulation of Cyt c and propose that it is a central regulatory step of the mammalian ETC that can be rate limiting in normal conditions. This regulation is important because it maintains optimal intermediate ΔΨm, limiting ROS generation. We examine the role of Cyt c PTMs, including phosphorylation, acetylation, methylation, nitration, nitrosylation, and sulfoxidation and consider their potential biological significance by evaluating their stoichiometry.-Kalpage, H. A., Bazylianska, V., Recanati, M. A., Fite, A., Liu, J., Wan, J., Mantena, N., Malek, M. H., Podgorski, I., Heath, E. I., Vaishnav, A., Edwards, B. F., Grossman, L. I., Sanderson, T. H., Lee, I., Hüttemann, M. Tissue-specific regulation of cytochrome c by post-translational modifications: respiration, the mitochondrial membrane potential, ROS, and apoptosis.

Listening to Fast-Tempo Music Delays the Onset of Neuromuscular Fatigue.

Centala, J, Pogorel, C, Pummill, SW, and Malek, MH. Listening to fast-tempo music delays the onset of neuromuscular fatigue. J Strength Cond Res 34(3): 617-622, 2020-Studies determining the effect of music on physical performance have primarily focused on outcomes such as running time to exhaustion, blood lactate, or maximal oxygen uptake. The electromyographic fatigue threshold (EMGFT) is determined through a single incremental test and operationally defined as the highest exercise intensity that can be sustained indefinitely without an increase in EMG activity of the working muscle. To date, no studies have examined the role of fast-tempo music on EMGFT. The purpose of this investigation, therefore, was to determine whether fast-tempo music attenuates neuromuscular fatigue as measured by the EMGFT. We hypothesized that listening to fast-tempo music during exercise would increase the estimated EMGFT compared with the control condition. Secondarily, we hypothesized that maximal power output would also increase as a result of listening to fast-tempo music during the exercise workbout. Ten healthy college-aged men (mean ± SEM: age, 25.3 ± 0.8 years [range from 22 to 31 years]; body mass, 78.3 ± 1.8 kg; height: 1.77 ± 0.02 m) visited the laboratory on 2 occasions separated by 7 days. The EMGFT was determined from an incremental single-leg knee-extensor ergometer for each visit. In a randomized order, subjects either listened to music or no music for the 2 visits. All music was presented as instrumentals and randomized with a tempo ranging between 137 and 160 b·min. The results indicated that listening to fast-tempo music during exercise increased maximal power output (No Music: 48 ± 4; Music: 54 ± 3 W; p = 0.02) and EMGFT (No Music: 27 ± 3; Music: 34 ± 4 W; p = 0.008). There were, however, no significant mean differences between the 2 conditions (no music vs. music) for absolute and relative end-exercise heart rate as well as end-exercise rating of perceived exertion for the exercised leg. These findings suggest that listening to fast-tempo music increased overall exercise tolerance as well as the neuromuscular fatigue threshold. The results are applicable to both sport and rehabilitative settings.

Epigenetic Responses to Acute Resistance Exercise in Trained vs. Sedentary Men.

Bagley, JR, Burghardt, KJ, McManus, R, Howlett, B, Costa, PB, Coburn, JW, Arevalo, JA, Malek, MH, and Galpin, AJ. Epigenetic responses to acute resistance exercise in trained vs. sedentary men. J Strength Cond Res 34(6): 1574-1580, 2020-Acute resistance exercise (RE) alters DNA methylation, an epigenetic process that influences gene expression and regulates skeletal muscle adaptation. This aspect of cellular remodeling is poorly understood, especially in resistance-trained (RT) individuals. The study purpose was to examine DNA methylation in response to acute RE in RT and sedentary (SED) young men, specifically targeting genes responsible for metabolic, inflammatory, and hypertrophic muscle adaptations. Vastus lateralis biopsies were performed before (baseline), 30 minutes after, and 4 hours after an acute RE bout (3 × 10 repetitions at 70% 1 repetition maximum [1RM] leg press and leg extension) in 11 RT (mean ± SEM: age = 26.1 ± 1.0 years; body mass = 84.3 ± 0.2 kg; leg press 1RM = 412.6 ± 25.9 kg) and 8 SED (age = 22.9 ± 1.1 years; body mass = 75.6 ± 0.3 kg; leg press 1RM = 164.8 ± 22.5 kg) men. DNA methylation was analyzed through methylation sensitive high-resolution melting using real-time polymerase chain reaction. Separate 2 (group) × 3 (time) repeated-measures analyses of variance and analyses of covariance were performed to examine changes in DNA methylation for each target gene. Results showed that acute RE (a) hypomethylated LINE-1 (measure of global methylation) in RT but not SED, (b) hypermethylated metabolic genes (GPAM and SREBF2) in RT, while lowering SREBF2 methylation in SED, and (c) did not affect methylation of genes associated with inflammation (IL-6 and TNF-α) or hypertrophy (mTOR and AKT1). However, basal IL-6 and TNF-α were lower in SED compared with RT. These findings indicate the same RE stimulus can illicit different epigenetic responses in RT vs. SED men and provides a molecular mechanism underpinning the need for differential training stimuli based on subject training backgrounds.

Multiple Dimensions and Correlates of Fatigue in Individuals on Hemodialysis.

This study examined the severity, pattern, and correlates of fatigue among adults undergoing hemodialysis. Measures included the Piper Fatigue Scale (PFS-12), Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue, Charlson Comorbidity Index, and Six-Minute Walk Test (6MWT). Patients were excluded if mobility or cardiovascular issues prevented conducting the 6MWT. Participants were 86 cognitively intact adults (M = 61.7 years, SD = 13.81), predominantly male (58.1%), and African American (48.8%), with 80% reporting fatigue in the week prior to hemodialysis. Significant increases were noted in sensory and cognitive fatigue from pre- to post-dialysis, while the 6MWT distance decreased significantly pre- to post-dialysis. Factors significantly associated with pre-dialysis fatigue included low hemoglobin, younger age, and living with someone else, while comorbidities and dialysis inadequacy were trending to significant associations with fatigue.

Log-Transformed Electromyography Amplitude-Power Output Relationship: Single-Leg Knee-Extensor Versus Single-Leg Cycle Ergometry.

Noble, EB, Pilarski, JM, Vora, HK, Zuniga, JM, and Malek, MH. Log-transformed electromyography amplitude-power output relationship: single-leg knee-extensor versus single-leg cycle ergometry. J Strength Cond Res 33(5): 1311-1319, 2019-Comparing and contrasting motor unit recruitment and activation for the same muscles for multiple versus single-joint exercise may provide a better understanding of neuromuscular fatigue. The purpose of this study, therefore, is to compare the slope and y-intercept terms for the 3 superficial quadriceps femoris (QF) (vastus lateralis, rectus femoris, and vastus medialis) muscles derived from the log-transformed electromyography (EMG) amplitude-power output relationship between the single-leg knee-extensor ergometry (KE) and the single-leg cycle ergometry (CE). Ten healthy college-aged men who engaged in regular physical activity visited the laboratory on 2 occasions separated by 7 days to perform either single-leg CE or single-leg KE in a randomized order. For each visit, subjects performed incremental exercise until voluntary fatigue. Electromyography electrodes were placed on the superficial QF muscles. The slope and y-intercept terms, for each muscle, for the EMG amplitude versus power output relationship was examined using the log-transformed model for each subject's data. The results indicated no significant (p > 0.05) mean differences for either slope or y-intercept terms between exercise modes and across muscles. In addition, separate repeated-measures analyses of variance (ANOVAs) were used to determine mean differences for the slope and y-intercept values between the 3 muscles. In addition, separate 2 (mode: CE or KE) × intensity (intensity: 30, 60, and 90% of maximal workload) repeated-measures ANOVAs were conducted for each muscle. There was a significant (p < 0.05) mode × exercise intensity interaction for each muscle. Follow-up testing indicated that in most cases, the normalized EMG amplitude was significantly higher for single-leg KE than single-leg CE. These results indicated that incremental single-leg KE activates the superficial QF muscles significantly greater than single-leg CE.

Aerobic Exercise Preconception and During Pregnancy Enhances Oxidative Capacity in the Hindlimb Muscles of Mice Offspring.

Liu, J, Lee, I, Feng, H-Z, Galen, SS, Hüttemann, PP, Perkins, GA, Jin, J-P, Hüttemann, M, and Malek, MH. Aerobic exercise preconception and during pregnancy enhances oxidative capacity in the hindlimb muscles of mice offspring. J Strength Cond Res 32(5): 1391-1403, 2018-Little is known about the effect of maternal exercise on offspring skeletal muscle health. The purpose of this study, therefore, was to determine whether maternal exercise (preconception and during pregnancy) alters offspring skeletal muscle capillarity and mitochondrial biogenesis. We hypothesized that offspring from exercised dams would have higher capillarity and mitochondrial density in the hindlimb muscles compared with offspring from sedentary dams. Female mice in the exercise condition had access to a running wheel in their individual cage 30 days before mating and throughout pregnancy, whereas the sedentary group did not have access to the running wheel before mating and during pregnancy. Male offspring from both groups were killed when they were 2 months old, and their tissues were analyzed. The results indicated no significant (p > 0.05) mean differences for capillarity density, capillarity-to-fiber ratio, or regulators of angiogenesis such as VEGF-A and TSP-1. Compared with offspring from sedentary dams, however, offspring from exercised dams had an increase in protein expression of myosin heavy chain type I (MHC I) (∼134%; p = 0.009), but no change in MHC II. For mitochondrial morphology, we found significant (all p-values ≤ 0.0124) increases in mitochondrial volume density (∼55%) and length (∼18%) as well as mitochondria per unit area (∼19%). For mitochondrial enzymes, there were also significant (all p-values ≤ 0.0058) increases in basal citrate synthase (∼79%) and cytochrome c oxidase activity (∼67%) in the nonoxidative muscle fibers as well as increases in basal (ATP) (∼52%). Last, there were also significant mean differences in protein expression for regulators (FIS1, Lon protease, and TFAM) of mitochondrial biogenesis. These findings suggest that maternal exercise before and during pregnancy enhances offspring skeletal muscle mitochondria functionality, but not capillarity.

Revisiting the Single-Visit Protocol for Determining the Electromyographic Fatigue Threshold.

Khan, FL, Lawal, JM, Kapture, DO, Swingle, JD, and Malek, MH. Revisiting the single-visit protocol for determining the electromyographic fatigue threshold. J Strength Cond Res 31(12): 3503-3507, 2017-The electromyographic fatigue threshold (EMGFT) has been shown to demarcate between nonfatiguing and fatiguing exercise workloads. One potential limitation of incorporating the single EMGFT test in a clinical setting is the 2-minute stage increment inherit to the protocol. In most rehabilitation clinics, time with the client is limited, and any testing procedure needs to consider this factor. The purpose of this study, therefore, was to determine whether or not the estimation of the EMGFT is influenced by reducing the incremental stage to 1-minute intervals. We hypothesized that the 1-minute incremental protocol would provide similar estimates of the EMGFT as the traditional 2-minute incremental protocol. Nine college-aged men performed the single-leg knee-extensor ergometry at 1-minute (3 W) and 2-minute (6 W) stages in random order separated by 7 days. The exercise indices and the EMGFT were determined from the 2 protocols and analyzed using a paired samples t test. The EMG amplitude was assessed from the rectus femoris muscle. The results indicated significant differences between protocols for maximal power output (1 minute: 31.7 ± 2.2 W vs. 2 minutes: 38.0 ± 3.3 W, p = 0.016) and heart rate at end exercise (1 minute: 137 ± 5 b·min vs. 2 minutes: 148 ± 5 b·min, p = 0.024). There were, however, no significant mean differences for the EMGFT (1 minute: 19.8 ± 1.8 vs. 2 minutes: 20.3 ± 1.9 W, p = 0.63) and rating of perceived exertion (RPE) for the exercised leg (1 minute: 9 ± 0 vs. 2 minutes: 9 ± 1, p = 0.68). These results indicate that reducing the exercise protocol by 50% did not change the estimated EMGFT. The practical application of this finding resides in the potential use in sports or rehabilitative settings in which there is limited time with the client and no objective measures to determine neuromuscular fatigue for aerobic exercise.

Slow recovery of the impaired fatigue resistance in postunloading mouse soleus muscle corresponding to decreased mitochondrial function and a compensatory increase in type I slow fibers.

Unloading or disuse rapidly results in skeletal muscle atrophy, switching to fast-type fibers, and decreased resistance to fatigue. The recovery process is of major importance in rehabilitation for various clinical conditions. Here we studied mouse soleus muscle during 60 days of reloading after 4 wk of hindlimb suspension. Unloading produced significant atrophy of soleus muscle with decreased contractile force and fatigue resistance, accompanied by switches of myosin isoforms from IIa to IIx and IIb and fast troponin T to more low-molecular-weight splice forms. The total mass, fiber size, and contractile force of soleus muscle recovered to control levels after 15 days of reloading. However, the fatigue resistance showed a trend of worsening during this period with significant infiltration of inflammatory cells at days 3 and 7, indicating reloading injuries that were accompanied by active regeneration with upregulations of filamin-C, αB-crystallin, and desmin. The fatigue resistance partially recovered after 30-60 days of reloading. The expression of peroxisome proliferator-activated receptor γ coactivator 1α and mitofusin-2 showed changes parallel to that of fatigue resistance after unloading and during reloading, suggesting a causal role of decreased mitochondrial function. Slow fiber contents in the soleus muscle were increased after 30-60 days of reloading to become significantly higher than the normal level, indicating a secondary adaption to compensate for the slow recovery of fatigue resistance.