Preclinical Multi-Omic Assessment of Pioglitazone in Skeletal Muscles of Mice Implanted with Human HER2/neu Overexpressing Breast Cancer Xenografts.

Breast cancer (BC) is the most prevalent cancer worldwide and is accompanied by fatigue during both active disease and remission in the majority of cases. Our lab has measured fatigue in isolated muscles from treatment-naive BC patient-derived orthotopic xenograft (BC-PDOX) mice. Here, we conducted a preclinical trial of pioglitazone in BC-PDOX mice to determine its efficacy in ameliorating BC-induced muscle fatigue, as well as its effects on transcriptomic, metabolomic, and lipidomic profiles in skeletal muscle. Methods: The pioglitazone and vehicle groups were treated orally for 4 weeks upon reaching a tumor volume of 600 mm3. Whole-animal indirect calorimetry was used to evaluate systemic metabolic states. The transcriptome was profiled using short-read bulk RNA sequencing (RNA-seq). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to profile the metabolome and lipidome. Fast and slow skeletal muscle function were evaluated using isolated ex vivo testing. Results: Pioglitazone was associated with a significant overall decrease in metabolic rate, with no changes in substrate utilization. RNA-seq supported the downstream effects of pioglitazone on target genes and displayed considerable upregulation of mitochondrial bioenergetic pathways. Skeletal muscle metabolomic and lipidomic profiles exhibited dysregulation in response to BC, which was partially restored in pioglitazone-treated mice compared to vehicle-treated BC-PDOX mice. Despite molecular support for pioglitazone's efficacy, isolated muscle function was not affected by pioglitazone treatment. Conclusions: BC induces multi-omic dysregulation in skeletal muscle, which pioglitazone partially ameliorates. Future research should focus on profiling systemic metabolic dysfunction, identifying molecular biomarkers of fatigue, and testing alternative pioglitazone treatment regimens.

Sexual Dimorphism of Skeletal Muscle in a Mouse Model of Breast Cancer: A Functional and Molecular Analysis.

Breast cancer incidence in men is statistically rare; however, given the lack of screening in males, more advanced stages at initial diagnosis result in lower 5-year survival rates for men with breast cancer compared to women. A sexual dimorphism, with respect to the effect of tumor growth on cachexia incidence and severity, has also been reported across cancer types. The purpose of this study was to examine the sexual dimorphism of breast cancer as it pertains to skeletal muscle function and molecular composition. Using female and male transgenic PyMT mice, we tested the hypothesis that the isometric contractile properties and molecular composition of skeletal muscle would be differentially affected by breast tumors. PyMT tumor-bearing mice of each sex, corresponding to maximal tumor burden, were compared to their respective controls. RNA sequencing of skeletal muscle revealed different pathway alterations that were exclusive to each sex. Further, differentially expressed genes and pathways were substantially more abundant in female tumor mice, with only minimal dysregulation in male tumor mice, each compared to their respective controls. These differences in the transcriptome were mirrored in isometric contractile properties, with greater tumor-induced dysfunction in females than male mice, as well as muscle wasting. Collectively, these data support the concept of sexually dimorphic responses to cancer in skeletal muscle and suggest that these responses may be associated with the clinical differences in breast cancer between the sexes. The identified sex-dependent pathways within the muscle of male and female mice provide a framework to evaluate therapeutic strategies targeting tumor-associated skeletal muscle alterations.

Sexual Dimorphism of Skeletal Muscle in a Mouse Model of Breast Cancer: A Functional and Molecular Analysis.

Breast cancer incidence in men is statistically rare; however, given the lack of screening in males, more advanced stages at initial diagnosis results in lower 5-year survival rates for men with breast cancer compared to women. A sexual dimorphism, with respect to the effect of tumor growth on cachexia incidence and severity, has also been reported across cancer types. The purpose of this study was to examine the sexual dimorphism of breast cancer as it pertains to skeletal muscle function and molecular composition. Using female and male transgenic PyMT mice, we tested the hypothesis that isometric contractile properties and molecular composition of skeletal muscle would be differentially affected by breast tumors. PyMT tumor-bearing mice of each sex, corresponding to maximal tumor burden, were compared to their respective controls. RNA-sequencing of skeletal muscle revealed different pathway alterations that were exclusive to each sex. Further, differentially expressed genes and pathways were substantially more abundant in female tumor mice, with only minimal dysregulation in male tumor mice, each compared to their respective controls. These differences in the transcriptome were mirrored in isometric contractile properties, with greater tumor-induced dysfunction in females than male mice, as well as muscle wasting. Collectively, these data support the concept of sexually dimorphic responses to cancer in skeletal muscle and suggest these responses may be associated with the clinical differences in breast cancer between the sexes. The identified sex-dependent pathways within muscle of male and female mice provide a framework to evaluate therapeutic strategies targeting tumor-associated skeletal muscle alterations.

Full-Body Photobiomodulation Therapy Is Associated with Reduced Sleep Durations and Augmented Cardiorespiratory Indicators of Recovery.

Research is emerging on the use of Photobiomodulation therapy (PBMT) and its potential for augmenting human performance, however, relatively little research exists utilizing full-body administration methods. As such, further research supporting the efficacy of whole-body applications of PBMT for behavioral and physiological modifications in applicable, real-world settings are warranted. The purpose of this analysis was to observe cardiorespiratory and sleep patterns surrounding the use of full-body PBMT in an elite cohort of female soccer players. Members of a women's soccer team in a "Power 5 conference" of the National Collegiate Athletic Association (NCAA) were observed across one competitive season while wearing an OURA Ring nightly and a global positioning system (GPS) sensor during training. Within-subject comparisons of cardiorespiratory physiology, sleep duration, and sleep composition were evaluated the night before and after PBMT sessions completed as a standard of care for team recovery. Compared to pre-intervention, mean heart rate (HR) was significantly lower the night after a PBMT session (p = 0.0055). Sleep durations were also reduced following PBMT, with total sleep time (TST) averaging 40 min less the night after a session (p = 0.0006), as well as significant reductions in light sleep (p = 0.0307) and rapid eye movement (REM) sleep durations (p = 0.0019). Sleep durations were still lower following PBMT, even when controlling for daily and accumulated training loads. Enhanced cardiorespiratory indicators of recovery following PBMT, despite significant reductions in sleep duration, suggest that it may be an effective modality for maintaining adequate recovery from the high stress loads experienced by elite athletes.

Comparisons of Countermovement Jump Force-Time Characteristics Among National Collegiate Athletic Association Division I American Football Athletes: Use of Principal Component Analysis.

ABSTRACT: Merrigan, JJ, Rentz, LE, Hornsby, WG, Wagle, JP, Stone, JD, Smith, HT, Galster, SM, Joseph, M, and Hagen, JA. Comparisons of countermovement jump force-time characteristics among NCAA Division I American football athletes: use of principal component analysis. J Strength Cond Res 36(2): 411-419, 2022-This study aimed to reduce the dimensionality of countermovement jump (CMJ) force-time characteristics and evaluate differences among positional groups (skills, hybrid, linemen, and specialists) within National Collegiate Athletic Association (NCAA) division I American football. Eighty-two football athletes performed 2 maximal effort, no arm-swing, CMJs on force plates. The average absolute and relative (e.g., power/body mass) metrics were analyzed using analysis of variance and principal component analysis procedures (p < 0.05). Linemen had the heaviest body mass and produced greater absolute forces than hybrid and skills but had lower propulsive abilities demonstrated by longer propulsive phase durations and greater eccentric to concentric mean force ratios. Skills and hybrid produced the most relative concentric and eccentric forces and power, as well as modified reactive strength indexes (RSIMOD). Skills (46.7 ± 4.6 cm) achieved the highest jump height compared with hybrid (42.8 ± 5.5 cm), specialists (38.7 ± 4.0 cm), and linemen (34.1 ± 5.3 cm). Four principal components explained 89.5% of the variance in force-time metrics. Dimensions were described as the (a) explosive transferability to concentric power (RSIMOD, concentric power, and eccentric to concentric forces) (b) powerful eccentric loading (eccentric power and velocity), (c) countermovement strategy (depth and duration), and (d) jump height and power. The many positional differences in CMJ force-time characteristics may inform strength and conditioning program designs tailored to each position and identify important explanatory metrics to routinely monitor by position. The overwhelming number of force-time metrics to select from may be reduced using principal component analysis methods, although practitioners should still consider the various metric's applicability and reliability.

Contextual Variation in External and Internal Workloads across the Competitive Season of a Collegiate Women's Soccer Team.

As sports technology has continued to develop, monitoring athlete workloads, performance, and recovery has demonstrated boundless benefits for athlete and team success. Specifically, technologies such as global positioning systems (GPS) and heart rate (HR) monitors have granted the opportunity to delve deeper into performance contributors, and how variations may exist based upon context. A team of NCAA Division I women's soccer athletes were monitored during games throughout one competitive season. Individual athlete, positional groups, and team external and internal workloads were explored for differences based upon game location, opponent ranking, game result, and the final score differential. Game location and opponent ranking were found to have no effect on team-wide absolute or relative external workloads, whereas game result and score differential did. Internal workloads across the team tended to only vary by game half, independent of game context; however, the HR of defenders was determined to be higher during losses as compared to wins (p = 0.0256). Notably, the games that resulted in losses also represented the games with the fewest number of substitutions. These findings suggest high value in monitoring performance and workloads that are characteristic of varying, often multifaceted, contexts. It is hoped that this information can lead to more informed approaches to vital game-time and coaching decisions.

Reactive Task Performance Under Varying Loads in Division I Collegiate Soccer Athletes.

This study was conducted to identify whether team-wide or positional differences exist in simple or choice reactivity of collegiate soccer athletes when completed under various loads. Much research exists surrounding the assessment of reaction time in the general population, but given variations in training, little insight exists surrounding how unique and elite populations may differ based upon performance demands and task translatability to training. Reactive performance was assessed using the Dynavision D2 in 24 female soccer players (19.73 ± 1.05 years old) from a team within a power five conference of the National Collegiate Athletic Association. Evaluated loads included two conditions of simple reactivity (no additional load and with a concurrent lower body motor task) and three conditions of choice reactivity (no additional load, with a concurrent lower body motor task, and prolonged durations). Paired t-tests and ANOVAs were used to identify differences in task performance based upon load and positional group. No significant load-based or positional differences existed in measured simple reaction times. Performances in choice reaction tasks across the team were found to be slower when completed across extended durations (p < 0.0001) and faster when completed concurrent with an added balance task (p = 0.0108), as compared to performance under normal conditions. By assessment of positional differences, goalkeepers tended to be slower than other positions in reactivity during choice tasks, despite no differences existing in simple task performance. Given the unique population utilized herein, measured reactivity in different tasks suggests a strong relation to the training demands of soccer, as well as those of goalkeepers as compared to field positions. Findings suggest that sport and positional demands may be substantial contributors to population- and individual-based reactivity performance.

Deconstructing Commercial Wearable Technology: Contributions toward Accurate and Free-Living Monitoring of Sleep.

Despite prolific demands and sales, commercial sleep assessment is primarily limited by the inability to "measure" sleep itself; rather, secondary physiological signals are captured, combined, and subsequently classified as sleep or a specific sleep state. Using markedly different approaches compared with gold-standard polysomnography, wearable companies purporting to measure sleep have rapidly developed during recent decades. These devices are advertised to monitor sleep via sensors such as accelerometers, electrocardiography, photoplethysmography, and temperature, alone or in combination, to estimate sleep stage based upon physiological patterns. However, without regulatory oversight, this market has historically manufactured products of poor accuracy, and rarely with third-party validation. Specifically, these devices vary in their capacities to capture a signal of interest, process the signal, perform physiological calculations, and ultimately classify a state (sleep vs. wake) or sleep stage during a given time domain. Device performance depends largely on success in all the aforementioned requirements. Thus, this review provides context surrounding the complex hardware and software developed by wearable device companies in their attempts to estimate sleep-related phenomena, and outlines considerations and contributing factors for overall device success.

Evaluations of Commercial Sleep Technologies for Objective Monitoring During Routine Sleeping Conditions.

PURPOSE: The commercial market is saturated with technologies that claim to collect proficient, free-living sleep measurements despite a severe lack of independent third-party evaluations. Therefore, the present study evaluated the accuracy of various commercial sleep technologies during in-home sleeping conditions. MATERIALS AND METHODS: Data collection spanned 98 separate nights of ad libitum sleep from five healthy adults. Prior to bedtime, participants utilized nine popular sleep devices while concurrently wearing a previously validated electroencephalography (EEG)-based device. Data collected from the commercial devices were extracted for later comparison against EEG to determine degrees of accuracy. Sleep and wake summary outcomes as well as sleep staging metrics were evaluated, where available, for each device. RESULTS: Total sleep time (TST), total wake time (TWT), and sleep efficiency (SE) were measured with greater accuracy (lower percent errors) and limited bias by Fitbit Ionic [mean absolute percent error, bias (95% confidence interval); TST: 9.90%, 0.25 (-0.11, 0.61); TWT: 25.64%, -0.17 (-0.28, -0.06); SE: 3.49%, 0.65 (-0.82, 2.12)] and Oura smart ring [TST: 7.39%, 0.19 (0.04, 0.35); TWT: 36.29%, -0.18 (-0.31, -0.04); SE: 5.42%, 1.66 (0.17, 3.15)], whereas all other devices demonstrated a propensity to over or underestimate at least one if not all of the aforementioned sleep metrics. No commercial sleep technology appeared to accurately quantify sleep stages. CONCLUSION: Generally speaking, commercial sleep technologies displayed lower error and bias values when quantifying sleep/wake states as compared to sleep staging durations. Still, these findings revealed that there is a remarkably high degree of variability in the accuracy of commercial sleep technologies, which further emphasizes that continuous evaluations of newly developed sleep technologies are vital. End-users may then be able to determine more accurately which sleep device is most suited for their desired application(s).