Hypoxia treatment and resistance training alters microRNA profiling in rats skeletal muscle.

MicroRNAs (miRNAs) may play a crucial regulatory role in the process of muscle atrophy induced by high-altitude hypoxia and its amelioration through resistance training. However, research in this aspect is still lacking. Therefore, this study aimed to employ miRNA microarray analysis to investigate the expression profile of miRNAs in skeletal muscle from an animal model of hypoxia-induced muscle atrophy and resistance training aimed at mitigating muscle atrophy. The study utilized a simulated hypoxic environment (oxygen concentration at 11.2%) to induce muscle atrophy and established a rat model of resistance training using ladder climbing, with a total intervention period of 4 weeks. The miRNA expression profile revealed 9 differentially expressed miRNAs influenced by hypoxia (e.g., miR-341, miR-32-5p, miR-465-5p) and 14 differentially expressed miRNAs influenced by resistance training under hypoxic conditions (e.g., miR-338-5p, miR-203a-3p, miR-92b-3p) (∣log2(FC)∣ ≥ 1.5, p < 0.05). The differentially expressed miRNAs were found to target genes involved in muscle protein synthesis and degradation (such as Utrn, mdm2, eIF4E), biological processes (such as negative regulation of transcription from RNA polymerase II promoter, regulation of transcription, DNA-dependent), and signaling pathways (such as Wnt signaling pathway, MAPK signaling pathway, ubiquitin-mediated proteolysis, mTOR signaling pathway). This study provides a foundation for understanding and further exploring the molecular mechanisms underlying hypoxia-induced rats muscle atrophy and the mitigation of atrophy through resistance training.

Revealing myopathy spectrum: integrating transcriptional and clinical features of human skeletal muscles with varying health conditions.

Myopathy refers to a large group of heterogeneous, rare muscle diseases. Bulk RNA-sequencing has been utilized for the diagnosis and research of these diseases for many years. However, the existing valuable sequencing data often lack integration and clinical interpretation. In this study, we integrated bulk RNA-sequencing data from 1221 human skeletal muscles (292 with myopathies, 929 controls) from both databases and our local samples. By applying a method similar to single-cell analysis, we revealed a general spectrum of muscle diseases, ranging from healthy to mild disease, moderate muscle wasting, and severe muscle disease. This spectrum was further partly validated in three specific myopathies (97 muscles) through clinical features including trinucleotide repeat expansion, magnetic resonance imaging fat fraction, pathology, and clinical severity scores. This spectrum helped us identify 234 genuinely healthy muscles as unprecedented controls, providing a new perspective for deciphering the hallmark genes and pathways among different myopathies. The newly identified featured genes of general myopathy, inclusion body myositis, and titinopathy were highly expressed in our local muscles, as validated by quantitative polymerase chain reaction.

Monitoring Changes in TMS-Evoked EEG and EMG Activity During 1†Hz rTMS of the Healthy Motor Cortex.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique capable of inducing neuroplasticity as measured by changes in peripheral muscle electromyography (EMG) or electroencephalography (EEG) from pre-to-post stimulation. However, temporal courses of neuromodulation during ongoing rTMS are unclear. Monitoring cortical dynamics via TMS-evoked responses using EMG (motor-evoked potentials; MEPs) and EEG (transcranial-evoked potentials; TEPs) during rTMS might provide further essential insights into its mode of action - temporal course of potential modulations. The objective of this study was to first evaluate the validity of online rTMS-EEG and rTMS-EMG analyses, and second to scrutinize the temporal changes of TEPs and MEPs during rTMS. As rTMS is subject to high inter-individual effect variability, we aimed for single-subject analyses of EEG changes during rTMS. Ten healthy human participants were stimulated with 1,000 pulses of 1 Hz rTMS over the motor cortex, while EEG and EMG were recorded continuously. Validity of MEPs and TEPs measured during rTMS was assessed in sensor and source space. Electrophysiological changes during rTMS were evaluated with model fitting approaches on a group- and single-subject level. TEPs and MEPs appearance during rTMS was consistent with past findings of single pulse experiments. Heterogeneous temporal progressions, fluctuations or saturation effects of brain activity were observed during rTMS depending on the TEP component. Overall, global brain activity increased over the course of stimulation. Single-subject analysis revealed inter-individual temporal courses of global brain activity. The present findings are in favor of dose-response considerations and attempts in personalization of rTMS protocols.

Acetaminophen influences musculoskeletal signaling but not adaptations to endurance exercise training.

Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6-week, low-dose ACE regimen on muscle and bone adaptations in exercising and non-exercising rats. Nine-week-old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% incline for 2 min at 15 cm/s, 2 min at 20 cm/s, and 26 min at 25 cm/s. A human equivalent dose of ACE was administered (379 mg/kg body weight) in drinking water and adjusted each week based on body weight. Food, water intake, and body weight were measured daily. At the beginning of week 6, animals in the exercise group completed a maximal treadmill test. At the end of week 6, rats were euthanized, and muscle cross-sectional area (CSA), fiber type, and signaling pathways were measured. Additionally, three-point bending and microcomputer tomography were measured in the femur. Follow-up experiments in human primary muscle cells were used to explore supra-physiological effects of ACE. Data were analyzed using a two-way ANOVA for treatment (ACE or placebo) and condition (exercise or non-exercise) for all animal outcomes. Data for cell culture experiments were analyzed via ANOVA. If omnibus significance was found in either ANOVA, a post hoc analysis was completed, and a Tukey's adjustment was used. ACE did not alter body weight, water intake, food intake, or treadmill performance (p > .05). There was a treatment-by-condition effect for Young's Modulus where placebo exercise was significantly lower than placebo control (p < .05). There was no treatment by condition effects for microCT measures, muscle CSA, fiber type, or mRNA expression. Phosphorylated-AMPK was significantly increased with exercise (p < .05) and this was attenuated with ACE treatment. Furthermore, phospho-4EBP1 was depressed in the exercise group compared to the control (p < .05) and increased in the ACE control and ACE exercise group compared to placebo exercise (p < .05). A low dose of ACE did not influence chronic musculoskeletal adaptations in exercising rodents but acutely attenuated AMPK phosphorylation and 4EBP1 dephosphorylation post-exercise.

Carbon Monoxide Alleviates Post-ischemia-reperfusion Skeletal Muscle Injury and Systemic Inflammation.

Restoration of blood flow in skeletal muscle after a prolonged period of ischemia induces muscular ischemia-reperfusion injury, leading to local injury/dysfunction in muscles followed by systemic inflammatory responses. However, preventive/curative agents for skeletal muscle ischemia injury are unavailable in clinics to date. Increasing evidence has validated that carbon monoxide (CO) prevents the progression of ischemia-reperfusion injury in various organs owing to its versatile bioactivity. Previously, we developed a bioinspired CO donor, CO-bound red blood cells (CO-RBC), which mimics the dynamics of RBC-associated CO in the body. In the present study, we have tested the therapeutic potential of CO-RBC in muscular injury/dysfunction and secondary systemic inflammation induced by skeletal muscle ischemia-reperfusion. The results indicate that CO-RBC rather than RBC alone suppressed elevation of plasma creatine phosphokinase, a marker of muscular injury, in rats subjected to both hind limbs ischemia-reperfusion. In addition, the results of the treadmill walking test revealed a significantly decreased muscular motor function in RBC-treated rats subjected to both hind limbs ischemia-reperfusion than that in healthy rats, however, CO-RBC treatment facilitated sustained muscular motor functions after hind limbs ischemia-reperfusion. Furthermore, CO-RBC rather than RBC suppressed the production of tumour necrosis factor (TNF)-α and interleukin (IL)-6, which were upregulated by muscular ischemia-reperfusion. Interestingly, CO-RBC treatment induced higher levels of IL-10 compared to saline or RBC treatments. Based on these findings, we suggest that CO-RBC exhibits a suppressive effect against skeletal muscle injury/dysfunction and systemic inflammatory responses after skeletal muscle ischemia-reperfusion.

Effects of gait retraining using minimalist shoes on the medial gastrocnemius muscle-tendon unit behavior and dynamics during running.

The effects of a 12-week gait retraining program on the adaptation of the medial gastrocnemius (MG) and muscle-tendon unit (MTU) were investigated. 26 runners with a rearfoot strike pattern (RFS) were randomly assigned to one of two groups: gait retraining (GR) or control group (CON). MG ultrasound images, marker positions, and ground reaction forces (GRF) were collected twice during 9 km/h of treadmill running before and after the intervention. Ankle kinetics and the MG and MTU behavior and dynamics were quantified. Runners in the GR performed gradual 12-week gait retraining transitioning to a forefoot strike pattern. After 12-week, (1) ten participants in each group completed the training; eight participants in GR transitioned to non-RFS with reduced foot strike angles; (2) MG fascicle contraction length and velocity significantly decreased after the intervention for both groups, whereas MG forces increased after intervention for both groups; (3) significant increases in MTU stretching length for GR and peak MTU recoiling velocity for both groups were observed after the intervention, respectively; (4) no significant difference was found for all parameters of the series elastic element. Gait retraining might potentially influence the MG to operate at lower fascicle contraction lengths and velocities and produce greater peak forces. The gait retraining had no effect on SEE behavior and dynamics but did impact MTU, suggesting that the training was insufficient to induce mechanical loading changes on SEE behavior and dynamics.

[Clinical Efficacy of Modified Arthroscopic Revision Release of Gluteal Muscle Contracture With Residual Symptoms After Open Surgery]. / æ”¹è‰¯åŽçš„å ³èŠ‚é•œç¿»ä¿®æ¾è§£æœ¯å¯¹å¼€æ”¾æœ¯åŽæœ‰æ®‹ç•™ç—‡çŠ¶çš„è‡€è‚ŒæŒ›ç¼©ç—‡çš„ä¸´åºŠç–—æ•ˆ.

Objective: To investigate the clinical efficacy of modified arthroscopic revision release for patients who have gluteal muscle contracture and who have poor outcomes after traditional open surgery. Methods: The data of patients who underwent modified arthroscopic revision release for residual symptoms of gluteal muscle contracture after traditional open surgery were retrospectively collected and analyzed. All subjects underwent the procedure between December 2015 and December 2022. The surgical efficacy was assessed by evaluating improvements in specific symptoms, including bilateral lower extremity inequality, hip internal rotation and adduction mobility, squatting with both knees pressed together, and the ability to cross one's legs in supine position, as well as the preoperative and postoperative results for the gluteal muscle contracture functionality scale. Paired t-test was performed to examine whether the differences between preoperative and postoperative measurements were statistically significant. Results: A total of 36 patients were followed up systematically, with the mean follow-up period being (22.4±4.9) months. All patients had significantly higher scores for assessment with the gluteal muscle contracture functionality scale at the last follow-up than their preoperative assessment results, showing an increase from the preoperative scores of 40.2±5.5 to 78.4±4.9 (P<0.05). At the follow-up, all patients showed improvement in hip adduction and internal rotation mobility compared with their preoperative status and all patients were able to squat with both knees pressed together. Moreover, only 1 patient still had difficulty in crossing his legs. A total of 27 cases (75%) had preoperative leg length inequality, all of which improved to varying degrees at follow-up. Among all the patients (72 hips/cases), 8 cases had subcutaneous hematomas and incisional ecchymosis, which were resolved after conservative treatments such as hot compresses. 3 cases showed decreased hip abductor strength, but the muscle strength gradually recovered after postoperative exercise and rehabilitation. There were no complications such as subcutaneous exudate, neurovascular injury, or surgical site infection. Conclusion: Modified arthroscopic revision release of gluteus muscle contracture is suitable for cases with poor outcomes after conventional open surgery.

A Biomechanical Comparison of the Back Squat and Hexagonal Barbell Deadlift.

ABSTRACT: Stahl, CA, Regni, G, Tanguay, J, McElfresh, M, Trihy, E, Diggin, D, and King, DL. A biomechanical comparison of the back squat and hexagonal barbell deadlift. J Strength Cond Res 38(5): 815-824, 2024-Coaches often use different exercises to encourage similar strength adaptations and limit monotony. Anecdotally, the hexagonal barbell deadlift (HBD) exhibits similarities to the back squat (BS). To date, research has not examined the empirical differences between these exercises. This study examined kinematic and kinetic differences between the BS and the HBD across different loads. Sixteen resistance-trained individuals (6 men and 10 women) volunteered to participate. Subjects performed 1-repetition maximum (1RM) testing under BS and HBD conditions. Kinematic and kinetic data were collected during performance of both exercises at submaximal (warm-up sets) and maximal (1RM) loads using a 3D motion capture and force-plate system. Results showed that subjects lifted greater 1RM loads in the HBD relative to the BS (p < 0.05; d = -1.75). Kinematic data indicated that subjects exhibited greater maximum forward lean of the trunk and decreased maximum knee flexion while performing the HBD compared with the BS. The BS resulted in higher maximum extension moments at the hip joint than the HBD. Maximum extension moments at the knee joint showed no difference between the exercises. Data suggest that bar design and position facilitate balanced moment arm length at hip and knee joints during performance of the HBD. By contrast, bar position during performance of the BS increases moment arm length at the hip joint, making it a hip-dominant exercise. The present data have implications for the programming of both exercises. Future research should examine differences in muscle-activation strategies between the 2 exercises.

Do Muscle Mass and Body Fat Differ Between Elite and Amateur Natural Physique Athletes on Competition Day? A Preliminary, Cross-Sectional, Anthropometric Study.

ABSTRACT: González-Cano, H, Martín-Olmedo, JJ, Baz-Valle, E, Contreras, C, Schoenfeld, BJ, García-Ramos, A, Jiménez-Martínez, P, and Alix-Fages, C. Do muscle mass and body fat differ between elite and amateur natural physique athletes on competition day? A preliminary, cross-sectional, anthropometric study. J Strength Cond Res 38(5): 951-956, 2024-Natural physique athletes strive to achieve low body fat levels while promoting muscle mass hypertrophy for competition day. This study aimed to compare the anthropometric characteristics of natural amateur (AMA) and professional (PRO) World Natural Bodybuilding Federation (WNBF) competitors. Eleven male natural physique athletes (6 PRO and 5 AMA; age = 24.8 ± 2.3 years) underwent a comprehensive anthropometric evaluation following the International Society for the Advancement of Kinanthropometry protocol within a 24-hour time frame surrounding the competition. The 5-component fractionation method was used to obtain the body composition profile of the muscle, adipose, bone, skin, and residual tissues. Five physique athletes exceeded the 5.2 cutoff point of muscle-to-bone ratio (MBR) for natural athletes. Professional physique athletes were older than AMA physique athletes (p = 0.05), and they also presented larger thigh girths (p = 0.005) and bone mass (p = 0.019) compared with AMA physique athletes. Although no statistically significant between-group differences were observed in body mass, height, or body fat levels, PRO physique athletes exhibited a higher body mass index (BMI; AMA: 24.45 ± 0.12; PRO: 25.52 ± 1.01; p = 0.048), lean body mass (LBM; AMA: 64.49 ± 2.35; PRO: 69.80 ± 3.78; p = 0.024), fat-free mass (FFM; AMA: 71.23 ± 3.21; PRO: 76.52 ± 4.31; p = 0.05), LBM index (LBMI; AMA: 20.65 ± 0.52; PRO: 21.74 ± 0.85; p = 0.034), and fat-free mass index index (FFMI; AMA: 22.80 ± 0.22; PRO: 23.83 ± 0.90; p = 0.037) compared with AMA physique athletes. These findings highlight the unique characteristics and anthropometric differences between PRO and AMA natural physique athletes on competition day, emphasizing the significance of age, thigh girth, bone mass, BMI, LBM, FFM, and FFMI in distinguishing these 2 groups. Based on our findings, the established boundaries for muscle mass in natural physique athletes, based on FFMI and MBR, warrant reconsideration.

Comparison Between Traditional and Alternated Resistance Exercises on Blood Pressure, Acute Neuromuscular Responses, and Rating of Perceived Exertion in Recreationally Resistance-Trained Men.

ABSTRACT: Corrêa Neto, VG, Silva, DdN, Palma, A, de Oliveira, F, Vingren, JL, Marchetti, PH, da Silva Novaes, J, and Monteiro, ER. Comparison between traditional and alternated resistance exercises on blood pressure, acute neuromuscular responses, and rating of perceived exertion in recreationally resistance-trained men. J Strength Cond Res 38(5): e211-e218, 2024-The purpose of this study was to compare the acute effects of traditional and alternated resistance exercises on acute neuromuscular responses (maximum repetition performance, fatigue index, and volume load), rating of perceived exertion (RPE), and blood pressure (BP) in resistance-trained men. Fifteen recreationally resistance-trained men (age: 26.40 ± 4.15 years; height: 173 ± 5 cm, and total body mass: 78.12 ± 13.06 kg) were recruited and performed all 3 experimental conditions in a randomized order: (a) control (CON), (b) traditional (TRT), and (c) alternated (ART). Both conditions (TRT and ART) consisted of 5 sets of bilateral bench press, articulated bench press, back squat, and Smith back squat exercises at 80% 1RM until concentric muscular failure. The total number of repetitions performed across sets in the bench press followed a similar pattern for TRT and ART, with significant reductions between sets 3, 4, and 5 compared with set 1 (p < 0.05). There was a significant difference for set 4 between conditions with a lower number of repetitions performed in the TRT. The volume load was significantly higher for ART when compared with TRT. TRT showed significant reductions in BP after 10-, 40-, and 60-minute postexercise and when compared with CON after 40- and 60-minute postexercise. However, the effect size illustrated large reductions in systolic BP during recovery in both methods. Thus, it is concluded that both methods reduced postexercise BP.

The Effects of Anchoring a Fatiguing Forearm Flexion Task to a High vs. Low Rating of Perceived Exertion on Torque and Neuromuscular Responses.

ABSTRACT: Ortega, DG, Housh, TJ, Smith, RW, Arnett, JE, Neltner, TJ, Schmidt, RJ, and Johnson, GO. The effects of anchoring a fatiguing forearm flexion task to a high versus low rating of perceived exertion on torque and neuromuscular responses. J Strength Cond Res 38(5): e219-e225, 2024-This study examined the torque and neuromuscular responses following sustained, isometric, forearm flexion tasks anchored to 2 ratings of perceived exertion (RPE). Nine men (mean ± SD: age = 21.0 ± 2.4 years; height = 179.5 ± 5.1 cm; body mass = 79.6 ± 11.4 kg) completed maximal voluntary isometric contractions (MVIC) before and after sustained, isometric, forearm flexion tasks to failure anchored to RPE = 2 and RPE = 8. The amplitude (AMP) and mean power frequency (MPF) of the electromyographic (EMG) signal were recorded from the biceps brachii. Normalized torque was divided by normalized EMG AMP to calculate neuromuscular efficiency (NME). A dependent t-test was used to assess the mean difference for time to task failure (TTF). Repeated-measures analysis of variances was used to compare mean differences for MVIC and normalized neuromuscular parameters. There was no significant difference in TTF between RPE = 2 and RPE = 8 (p = 0.713). The MVIC decreased from pretest to posttest at RPE = 2 (p = 0.009) and RPE = 8 (p = 0.003), and posttest MVIC at RPE = 8 was less than that at RPE = 2 (p < 0.001). In addition, NME decreased from pretest to posttest (p = 0.008). There was no change in normalized EMG AMP or EMG MPF (p > 0.05). The current findings indicated that torque responses were intensity specific, but TTF and neuromuscular responses were not. Furthermore, normalized EMG AMP and EMG MPF remained unchanged but NME decreased, likely due to peripheral fatigue and excitation-contraction coupling failure. Thus, this study provides information regarding the neuromuscular responses and mechanisms of fatigue associated with tasks anchored to RPE, which adds to the foundational understanding of the relationship between resistance exercise and the perception of fatigue.

iMPAQT reveals that adequate mitohormesis from TFAM overexpression leads to life extension in mice.

Mitochondrial transcription factor A, TFAM, is essential for mitochondrial function. We examined the effects of overexpressing the TFAM gene in mice. Two types of transgenic mice were created: TFAM heterozygous (TFAM Tg) and homozygous (TFAM Tg/Tg) mice. TFAM Tg/Tg mice were smaller and leaner notably with longer lifespans. In skeletal muscle, TFAM overexpression changed gene and protein expression in mitochondrial respiratory chain complexes, with down-regulation in complexes 1, 3, and 4 and up-regulation in complexes 2 and 5. The iMPAQT analysis combined with metabolomics was able to clearly separate the metabolomic features of the three types of mice, with increased degradation of fatty acids and branched-chain amino acids and decreased glycolysis in homozygotes. Consistent with these observations, comprehensive gene expression analysis revealed signs of mitochondrial stress, with elevation of genes associated with the integrated and mitochondrial stress responses, including Atf4, Fgf21, and Gdf15. These found that mitohormesis develops and metabolic shifts in skeletal muscle occur as an adaptive strategy.

Imaging-based diagnosis of sarcopenia for transplant-free survival in primary sclerosing cholangitis.

BACKGROUND: Imaging-based assessment of sarcopenia is a well-validated prognostic tool for patients with chronic liver disease. However, little is known about its value in patients with primary sclerosing cholangitis (PSC). This cross-sectional study aimed to investigate the predictive value of the cross-sectional imaging-based skeletal muscle index (SMI) for transplant-free survival (TFS) in patients with PSC. METHODS: A total of 95 patients with PSC who underwent abdominal cross-sectional imaging between 2008 and 2022 were included in this retrospective study. SMI was measured at the third lumbar vertebra level (L3-SMI). The cut-off values to define sarcopenia were < 50 cm²/m² in male patients and < 39 cm²/m² in female patients. The primary outcome of this study was TFS, which was defined as survival without liver transplantation or death from any cause. RESULTS: Our study indicates that L3-SMI sarcopenia impairs TFS in patients with PSC (5-year TFS: 33.9% vs. 83.3%, p = 0.001, log-rank test). L3-SMI sarcopenia was independently associated with reduced TFS via multivariate Cox regression analysis (HR = 2.749; p = 0.028). Body mass index reduction > 10% at 12 months, which is used as MELD standard exception (SE) criterion in Eurotransplant (in Germany only until September 2023), was not significantly associated with TFS in the multivariate Cox regression analysis (HR = 1.417; p = 0.330). Substitution of BMI reduction with L3-SMI in the German SE criteria improved the predictive accuracy of TFS compared to the established SE criteria (multivariable Cox regression analysis: HR = 4.007, p < 0.001 vs. HR = 1.691, p = 0.141). CONCLUSION: Imaging-based diagnosis of sarcopenia via L3-SMI is associated with a low TFS in patients with PSC and may provide additional benefits as a prognostic factor in patient selection for liver transplantation.

The causal relationship of human blood metabolites with the components of Sarcopenia: a two-sample Mendelian randomization analysis.

BACKGROUND: Sarcopenia is a progressive loss of muscle mass and function. Since skeletal muscle plays a critical role in metabolic homeostasis, identifying the relationship of blood metabolites with sarcopenia components would help understand the etiology of sarcopenia. METHODS: A two-sample Mendelian randomization study was conducted to examine the causal relationship of blood metabolites with the components of sarcopenia. Summary genetic association data for 309 known metabolites were obtained from the Twins UK cohort and KORA F4 study (7824 participants). The summary statistics for sarcopenia components [hand grip strength (HGS), walking pace (WP), and appendicular lean mass (ALM)] were obtained from the IEU Open GWAS project (461,089 participants). The inverse variance weighted method was used, and the MR-Egger, weighted median, and MR-PRESSO were used for the sensitivity analyses. Metabolic pathways analysis was further performed. RESULTS: Fifty-four metabolites associated with sarcopenia components were selected from 275 known metabolites pool. Metabolites that are causally linked to the sarcopenia components were mainly enriched in amino sugar and nucleotide sugar metabolism, galactose metabolism, fructose and mannose metabolism, carnitine synthesis, and biotin metabolism. The associations of pentadecanoate (15:0) with ALM, and 3-dehydrocarnitine and isovalerylcarnitine with HGS were significant after Bonferroni correction with a threshold of P < 1.82 × 10- 4 (0.05/275). Meanwhile, the association of hyodeoxycholate and glycine with the right HGS, and androsterone sulfate with ALM were significant in the sensitivity analyses. CONCLUSION: Blood metabolites from different metabolism pathways were causally related to the components of sarcopenia. These findings might benefit the understanding of the biological mechanisms of sarcopenia and targeted drugs development for muscle health.

Relationship between sarcopenia and fatty liver in middle-aged and elderly patients with type 2 diabetes mellitus.

OBJECTIVE: In this study, we investigated the relationship between sarcopenia and fatty liver in middle-aged and elderly patients diagnosed with type 2 diabetes mellitus (T2DM) to provide a theoretical foundation for the prevention and treatment of sarcopenia. METHODS: A total of 282 patients diagnosed with T2DM aged 50 and older and were admitted to the Endocrinology Department of Xin Medical University First Affiliated Hospital between December 2021 and February 2023, were selected. Body mass index (BMI), and limb and trunk muscle mass of the patients were measured, and data were collected. Patients were grouped based on the sarcopenia diagnostic criteria. All study participants underwent the same physical examinations and laboratory tests. The relationship between the onset of sarcopenia and fatty liver in middle-aged and elderly patients diagnosed with T2DM was then investigated using statistical analysis. RESULTS: Comparing the sarcopenia group to the non-sarcopenia group revealed statistically significant variations in gender, BMI, fatty liver prevalence rate, uric acid (UA), alanine aminotransferase (ALT), blood glucose, blood lipid associated indicators, and limb skeletal muscle content. There were, however, no statistically significant differences in age, disease duration, hypertension, smoking, or alcohol intake. There was a positive correlation between BMI, UA, fasting c-peptide, and Appendicular Skeletal Muscle Index (ASMI). Higher levels of BMI, ASMI, and UA were identified as protective variables against sarcopenia by multifactorial logistic regression analysis. CONCLUSION: Higher levels of BMI, ASMI, and UA can greatly reduce skeletal muscle atrophy in patients with T2DM. Patients with a fatty liver may be less vulnerable to sarcopenia. There is little evidence, however, that a fatty liver works as a preventive factor against sarcopenia.

Dimorphic effect of TFE3 in determining mitochondrial and lysosomal content in muscle following denervation.

BACKGROUND: Muscle atrophy is a common consequence of the loss of innervation and is accompanied by mitochondrial dysfunction. Mitophagy is the adaptive process through which damaged mitochondria are removed via the lysosomes, which are regulated in part by the transcription factor TFE3. The role of lysosomes and TFE3 are poorly understood in muscle atrophy, and the effect of biological sex is widely underreported. METHODS: Wild-type (WT) mice, along with mice lacking TFE3 (KO), a transcriptional regulator of lysosomal and autophagy-related genes, were subjected to unilateral sciatic nerve denervation for up to 7 days, while the contralateral limb was sham-operated and served as an internal control. A subset of animals was treated with colchicine to capture mitophagy flux. RESULTS: WT females exhibited elevated oxygen consumption rates during active respiratory states compared to males, however this was blunted in the absence of TFE3. Females exhibited higher mitophagy flux rates and greater lysosomal content basally compared to males that was independent of TFE3 expression. Following denervation, female mice exhibited less muscle atrophy compared to male counterparts. Intriguingly, this sex-dependent muscle sparing was lost in the absence of TFE3. Denervation resulted in 45% and 27% losses of mitochondrial content in WT and KO males respectively, however females were completely protected against this decline. Decreases in mitochondrial function were more severe in WT females compared to males following denervation, as ROS emission was 2.4-fold higher. In response to denervation, LC3-II mitophagy flux was reduced by 44% in females, likely contributing to the maintenance of mitochondrial content and elevated ROS emission, however this response was dysregulated in the absence of TFE3. While both males and females exhibited increased lysosomal content following denervation, this response was augmented in females in a TFE3-dependent manner. CONCLUSIONS: Females have higher lysosomal content and mitophagy flux basally compared to males, likely contributing to the improved mitochondrial phenotype. Denervation-induced mitochondrial adaptations were sexually dimorphic, as females preferentially preserve content at the expense of function, while males display a tendency to maintain mitochondrial function. Our data illustrate that TFE3 is vital for the sex-dependent differences in mitochondrial function, and in determining the denervation-induced atrophy phenotype.

Effects of arousal and valence on center of pressure and ankle muscle activity during quiet standing.

Emotion affects postural control during quiet standing. Emotional states can be defined as two-dimensional models comprising valence (pleasant/unpleasant) and arousal (aroused/calm). Most previous studies have investigated the effects of valence on postural control without considering arousal. In addition, studies have focused on the center of pressure (COP) trajectory to examine emotional effects on the quiet standing control; however, the relationship between neuromuscular mechanisms and the emotionally affected quiet standing control is largely unknown. This study aimed to investigate the effects of arousal and valence on the COP trajectory and ankle muscle activity during quiet standing. Twenty-two participants were instructed to stand on a force platform and look at affective pictures for 72 seconds. The tasks were repeated six times, according to the picture conditions composed of arousal (High and Low) and valence (Pleasant, Neutral, and Unpleasant). During the task, the COP, electromyogram (EMG) of the tibialis anterior and soleus muscles, and electrocardiogram (ECG) were recorded. The heart rate calculated from the ECG was significantly affected by valence; the value was lower in Unpleasant than that in Neutral and Pleasant. The 95% confidence ellipse area and standard deviation of COP in the anterior-posterior direction were lower, and the mean power frequency of COP in the anterior-posterior direction was higher in Unpleasant than in Pleasant. Although the mean velocity of the COP in the medio-lateral direction was significantly lower in Unpleasant than in Pleasant, the effect was observed only when arousal was low. Although the EMG variables were not significantly affected by emotional conditions, some EMG variables were significantly correlated with the COP variables that were affected by emotional conditions. Therefore, ankle muscle activity may be partially associated with postural changes triggered by emotional intervention. In conclusion, both valence and arousal affect the COP variables, and ankle muscle activity may be partially associated with these COP changes.

A Biomechanical Comparison Between the Safety-Squat Bar and Traditional Barbell Back Squat.

ABSTRACT: Johansson, DG, Marchetti, PH, Stecyk, SD, and Flanagan, SP. A biomechanical comparison between the safety-squat bar and traditional barbell back squat. J Strength Cond Res 38(5): 825-834, 2024-The primary objectives for this investigation were to compare the kinematic and kinetic differences between performing a parallel back squat using a traditional barbell (TB) or a safety-squat bar (SSB). Fifteen healthy, recreationally trained male subjects (23 + 4 years of age) performed the back squat with a TB and an SSB at 85% of their respective 1 repetition maximum with each barbell while instrumented for biomechanical analysis. Standard inverse dynamics techniques were used to determine joint kinematic and kinetic measures. A 2 × 3 (exercise × joint) factorial analysis of variance with repeated measures was used to determine the kinetic and kinematic differences between the squats while using the different barbells. Fisher's least significant difference post hoc comparisons showed that the TB resulted in significantly greater maximum hip flexion angle (129.33 ± 11.8° vs. 122.11 ± 12.1°; p < 0.001; d = 1.80), peak hip net joint extensor torque (2.54 ± 0.4 Nm·kg -1 vs. 2.40 ± 0.4 Nm·kg -1 ; p = 0.001; d = 1.10), hip net extensor torque mechanical energy expenditure (MEE; 2.81 ± 0.5 Nm·kg -1 vs. 2.58 ± 0.6 Nm·kg -1 ; p = 0.002; d = 0.97), and ankle net joint plantar flexor torque MEE (0.32 ± 0.09 J·kg -1 vs. 0.28 ± 0.06 J·kg -1 ; p = 0.029; d = 0.63), while also lifting significantly (123.17 ± 20.8 kg vs. 117.17 ± 20.8 kg; p = 0.005; d = 0.858) more weight than the SSB. The SSB resulted in significantly higher maximum knee flexion angles (116.82 ± 5.8° vs. 115.65 ± 5.6°; p = 0.011; d = 0.75) than the TB, with no significant difference in kinetics at the knee. The TB may be preferred to the SSB for developing the hip extensors and lifting higher maximum loads. The SSB may be advantageous in situations where a more upright posture or a lower load is preferred while creating a similar demand for the knee joint.

Muscle Synergy Plasticity in Motor Function Recovery After Stroke.

In certain neurological disorders such as stroke, the impairment of upper limb function significantly impacts daily life quality and necessitates enhanced neurological control. This poses a formidable challenge in the realm of rehabilitation due to its intricate nature. Moreover, the plasticity of muscle synergy proves advantageous in assessing the enhancement of motor function among stroke patients pre and post rehabilitation training intervention, owing to the modular control strategy of central nervous system. It also facilitates the investigation of long-term alterations in remodeling of muscle functional performance among patients undergoing clinical rehabilitation, aiming to establish correlations between changes in muscle synergies and stroke characteristics such as type, stage, and sites. In this study, a three-week rehabilitation monitoring experiment was conducted to assess the motor function of stroke patients at different stages of rehabilitation based on muscle synergy performance. Additionally, we aimed to investigate the correlation between clinical scale scores, rehabilitation stages, and synergy performance in order to provide a more comprehensive understanding of stroke patient recovery. The results of 7 healthy controls and 16 stroke patients showed that high-functioning patients were superior to low-functioning patients in terms of motor function plasticity towards healthy individuals. Moreover, there was a high positive correlation between muscle synergies and clinical scale scores in high-functioning patients, and the significance gradually emerged with treatment, highlighting the potential of muscle synergy plasticity as a valuable tool for monitoring rehabilitation progress. The potential of this study was also demonstrated for elucidating the physiological mechanisms underlying motor function reconstruction within the central nervous system, which is expected to promote the further application of muscle synergy in clinical assessment.

A protocol for remote collection of skeletal muscle mass via D3-creatine dilution in community-dwelling postmenopausal women from the Women's Health Initiative.

BACKGROUND: There is emerging evidence that cancer and its treatments may accelerate the normal aging process, increasing the magnitude and rate of decline in functional capacity. This accelerated aging process is hypothesized to hasten the occurrence of common adverse age-related outcomes in cancer survivors, including loss of muscle mass and decrease in physical function. However, there is no data describing age-related loss of muscle mass and its relation to physical function in the long-term in cancer survivors. METHODS: This study protocol describes the use of a novel method of muscle mass measurement, D3-creatine dilution method (D3Cr), in a large sample (n~6000) of community dwelling postmenopausal women from the Women's Health Initiative (WHI). D3Cr will be used to obtain a direct measure of muscle mass remotely. Participants will be drawn from two sub-cohorts embedded within the WHI that have recently completed an in-home visit. Cancer survivors will be drawn from the Life and Longevity After Cancer (LILAC) cohort, and cancer-free controls will be drawn from the WHI Long Life Study 2. The overall objective of this study is to examine the antecedents and consequences of low muscle mass in cancer survivors. The study aims are to: 1) create age-standardized muscle mass percentile curves and z-scores to characterize the distribution of D3- muscle mass in cancer survivors and non-cancer controls, 2) compare muscle mass, physical function, and functional decline in cancer survivors and non- cancer controls, and 3) use machine learning approaches to generate multivariate risk-prediction algorithms to detect low muscle mass. DISCUSSION: The D3Cr method will transform our ability to measure muscle mass in large-scale epidemiologic research. This study is an opportunity to advance our understanding of a key source of morbidity among older and long-term female cancer survivors. This project will fill knowledge gaps, including the antecedents and consequences of low muscle mass, and use innovative methods to overcome common sources of bias in cancer research. The results of this study will be used to develop interventions to mitigate the harmful effects of low muscle mass in older adults and promote healthy survivorship in cancer survivors in the old (>65) and oldest-old (>85) age groups.