Exercise following joint distraction inhibits muscle wasting and delays the progression of post-traumatic osteoarthritis in rabbits by activating PGC-1α in skeletal muscle.

OBJECTIVE: Muscle wasting frequently occurs following joint trauma. Previous research has demonstrated that joint distraction in combination with treadmill exercise (TRE) can mitigate intra-articular inflammation and cartilage damage, consequently delaying the advancement of post-traumatic osteoarthritis (PTOA). However, the precise mechanism underlying this phenomenon remains unclear. Hence, the purpose of this study was to examine whether the mechanism by which TRE following joint distraction delays the progression of PTOA involves the activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), as well as its impact on muscle wasting. METHODS: Quadriceps samples were collected from patients with osteoarthritis (OA) and normal patients with distal femoral fractures, and the expression of PGC-1α was measured. The hinged external fixator was implanted in the rabbit PTOA model. One week after surgery, a PGC-1α agonist or inhibitor was administered for 4 weeks prior to TRE. Western blot analysis was performed to detect the expression of PGC-1α and Muscle atrophy gene 1 (Atrogin-1). We employed the enzyme-linked immunosorbent assay (ELISA) technique to examine pro-inflammatory factors. Additionally, we utilized quantitative real-time polymerase chain reaction (qRT-PCR) to analyze genes associated with cartilage regeneration. Synovial inflammation and cartilage damage were evaluated through hematoxylin-eosin staining. Furthermore, we employed Masson's trichrome staining and Alcian blue staining to analyze cartilage damage. RESULTS: The decreased expression of PGC-1α in skeletal muscle in patients with OA is correlated with the severity of OA. In the rabbit PTOA model, TRE following joint distraction inhibited the expressions of muscle wasting genes, including Atrogin-1 and muscle ring finger 1 (MuRF1), as well as inflammatory factors such as interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in skeletal muscle, potentially through the activation of PGC-1α. Concurrently, the production of IL-1ß, IL-6, TNF-α, nitric oxide (NO), and malondialdehyde (MDA) in the synovial fluid was down-regulated, while the expression of type II collagen (Col2a1), Aggrecan (AGN), SRY-box 9 (SOX9) in the cartilage, and superoxide dismutase (SOD) in the synovial fluid was up-regulated. Additionally, histological staining results demonstrated that TRE after joint distraction reduced cartilage degeneration, leading to a significant decrease in OARSI scores.TRE following joint distraction could activate PGC-1α, inhibit Atrogin-1 expression in skeletal muscle, and reduce C-telopeptides of type II collagen (CTX-II) in the blood compared to joint distraction alone. CONCLUSION: Following joint distraction, TRE might promote the activation of PGC-1α in skeletal muscle during PTOA progression to exert anti-inflammatory effects in skeletal muscle and joint cavity, thereby inhibiting muscle wasting and promoting cartilage regeneration, making it a potential therapeutic intervention for treating PTOA.

Prediction of lymph node metastasis in T1 colorectal cancer based on combination of body composition and vascular invasion.

OBJECTIVES: Lymph node metastasis (LNM) in colorectal cancer (CRC) patients is not only associated with the tumor's local pathological characteristics but also with systemic factors. This study aims to assess the feasibility of using body composition and pathological features to predict LNM in early stage colorectal cancer (eCRC) patients. METHODS: A total of 192 patients with T1 CRC who underwent CT scans and surgical resection were retrospectively included in the study. The cross-sectional areas of skeletal muscle, subcutaneous fat, and visceral fat at the L3 vertebral body level in CT scans were measured using Image J software. Logistic regression analysis were conducted to identify the risk factors for LNM. The predictive accuracy and discriminative ability of the indicators were evaluated using receiver operating characteristic (ROC) curves. Delong test was applied to compare area under different ROC curves. RESULTS: LNM was observed in 32 out of 192 (16.7%) patients with eCRC. Multivariate analysis revealed that the ratio of skeletal muscle area to visceral fat area (SMA/VFA) (OR = 0.021, p = 0.007) and pathological indicators of vascular invasion (OR = 4.074, p = 0.020) were independent risk factors for LNM in eCRC patients. The AUROC for SMA/VFA was determined to be 0.740 (p < 0.001), while for vascular invasion, it was 0.641 (p = 0.012). Integrating both factors into a proposed predictive model resulted in an AUROC of 0.789 (p < 0.001), indicating a substantial improvement in predictive performance compared to relying on a single pathological indicator. CONCLUSION: The combination of the SMA/VFA ratio and vascular invasion provides better prediction of LNM in eCRC.

Effects of high-intensity sprint exercise on neuromuscular function in sprinters: the countermovement jump as a fatigue assessment tool.

Background: High-intensity sprint exercises (HIS) are central to sprinter training and require careful monitoring of athlete muscle fatigue to improve performance and prevent injury. While the countermovement jump (CMJ) may be used to monitor neuromuscular fatigue (NMF), little is known about the specific effects from HIS. The purpose of this study is to investigate the effects of HIS on the CMJ to assess its utility for assessing NMF following HIS. Methods: Ten male collegiate 400 m sprinters completed a 400 m sprint fatigue protocol and underwent five CMJ-testing sessions (baseline, 3 minutes, 10 minutes, 1 hour and 24 hours) over two days. Three CMJ trials, performed on a force plate, were completed each trial, with rating of perceived exertion (RPE) recorded as a subjective fatigue measure. Changes in RPE, CMJ variables, force-time and power-time curves at baseline and post fatigue were assessed. Results: Significant changes were observed in most variables following the fatigue protocol. In particular, concentric mean power remained significantly lower after 24 hours compared to baseline. In addition, the force-time curves exhibited a significant reduction in all conditions following the fatigue protocol. This decline was most pronounced within 50-75%of the concentric phase relative to baseline measurements. Conclusion. Results indicate that the CMJ may be a useful tool for monitoring fatigue in at least 400 m sprinters. These data also indicate that HIS may disproportionately reduce force output in during concentric movement. These insights may improve training prescriptions and injury prevention strategies for sprint athletes.

Developmental dynamics of mitochondrial fission and fusion proteins in functionally divergent skeletal muscles of goat.

During skeletal muscle development, the intricate mitochondrial network formation relies on continuous fission and fusion. This process in larger mammals differs from rodents, the most used animal models. However, the expression pattern of proteins regulating mitochondrial dynamics in developing skeletal muscle remains unexplored in larger mammals. Therefore, we characterized the cellular expression and tissue-level distribution of these proteins during development taking goat as a model. We have performed histological and immunohistochemical analyses to study metabolic features in various muscles. Neonatal muscles display uniform distribution of mitochondrial activity. In contrast, adult muscles exhibit clear distinctions based on their function, whether dedicated for posture maintenance or facilitating locomotion. Mitochondrial fission proteins like DRP-1, MFF, and fusion proteins like MFN-1 and 2 are abundantly expressed in neonatal muscles. Fission proteins exhibit drastic downregulation with limited peripheral expression, whereas fusion proteins continue to express in a fiber-specific manner during adulthood. Locomotory muscles exhibit different fibers based on mitochondrial activity and peripheralization with high SDH activity. The proximity ligation assay between MFN1 and MFN2 demonstrates that their interaction is restricted to subsarcolemmal mitochondria in adult fibers while distributed evenly in neonatal fibers. These differences between postural and locomotory muscles suggest their physiological and metabolic properties are different.

Agent-based model demonstrates the impact of nonlinear, complex interactions between cytokinces on muscle regeneration.

Muscle regeneration is a complex process due to dynamic and multiscale biochemical and cellular interactions, making it difficult to identify microenvironmental conditions that are beneficial to muscle recovery from injury using experimental approaches alone. To understand the degree to which individual cellular behaviors impact endogenous mechanisms of muscle recovery, we developed an agent-based model (ABM) using the Cellular-Potts framework to simulate the dynamic microenvironment of a cross-section of murine skeletal muscle tissue. We referenced more than 100 published studies to define over 100 parameters and rules that dictate the behavior of muscle fibers, satellite stem cells (SSCs), fibroblasts, neutrophils, macrophages, microvessels, and lymphatic vessels, as well as their interactions with each other and the microenvironment. We utilized parameter density estimation to calibrate the model to temporal biological datasets describing cross-sectional area (CSA) recovery, SSC, and fibroblast cell counts at multiple timepoints following injury. The calibrated model was validated by comparison of other model outputs (macrophage, neutrophil, and capillaries counts) to experimental observations. Predictions for eight model perturbations that varied cell or cytokine input conditions were compared to published experimental studies to validate model predictive capabilities. We used Latin hypercube sampling and partial rank correlation coefficient to identify in silico perturbations of cytokine diffusion coefficients and decay rates to enhance CSA recovery. This analysis suggests that combined alterations of specific cytokine decay and diffusion parameters result in greater fibroblast and SSC proliferation compared to individual perturbations with a 13% increase in CSA recovery compared to unaltered regeneration at 28 days. These results enable guided development of therapeutic strategies that similarly alter muscle physiology (i.e. converting extracellular matrix [ECM]-bound cytokines into freely diffusible forms as studied in cancer therapeutics or delivery of exogenous cytokines) during regeneration to enhance muscle recovery after injury.

Skeletal muscle desmin alterations following revascularization in peripheral artery disease claudicants.

Peripheral artery disease (PAD) is characterized by varying severity of arterial stenosis, exercise induced claudication, malperfused tissue precluding normal healing and skeletal muscle dysfunction. Revascularization interventions improve circulation, but post-reperfusion changes within the skeletal muscle are not well characterized. This study investigates if revascularization enhanced hemodynamics increases walking performance with concurrent improvement of mitochondrial function and reverses abnormal skeletal muscle morphological features that develop with PAD. Fifty-eight patients completed walking performance testing and muscle biopsy before and 6 months after revascularization procedures. Muscle fiber morphology, desmin structure, and mitochondria respiration assessments before and after the revascularization were evaluated. Revascularization improved limb hemodynamics, walking function, and muscle morphology. Qualitatively not all participants recovered normal structural architecture of desmin in the myopathic myofibers after revascularization. Heterogenous responses in the recovery of desmin structure following revascularization may be caused by other underlying factors not reversed with hemodynamic improvements. Revascularization interventions clinically improve patient walking ability and can reverse the multiple subcellular functional and structural abnormalities in muscle cells. Further study is needed to characterize desmin structural remodeling with improvements in skeletal muscle morphology and function.

Integrated transcriptomics and metabolomics study of embryonic breast muscle of Jiaji ducks.

Because number of matured muscle fibers in poultry does not increase after birth, the meat yield is mainly determined during embryogenesis. We previously indicated breast muscle grew rapidly from 18th day after hatching (E18) to E27, and almost stopped from E27 to E34 of Jiaji ducks, while the mechanism is unclear. This study utilized RNA-seq to explore the related genes of muscle development and their relationship with small molecule metabolites at E18, E27 and E34 of Jiaji ducks. Several thousand differentially expressed genes (DEGs) were detected among E18, E27 and E34. DEGs expression profiles included 8 trend maps, among which trend 1 was opposite to and trend 6 was consistent with breast muscle development trend of Jiaji ducks. Through joint analysis between trend 1 of DEGs and trend 1 of differential metabolites (DEMs), protein digestion and absorption pathway stood out. The decrease of COL8A2 gene expression will lead to the decrease of arginine content, which will inhibit the development of breast muscle in embryonic Jiaji duck. Similarly, joint analysis between trend 6 of DEGs and trend 6 of DEMs indicated the increase of GAMT gene expression will cause the increase of proline content, and then promote the development of breast muscle of Jiaji duck in embryonic period. These results will be helpful for further understanding the mechanism of muscle yields of Jiaji ducks.

miR-27b-3p reduces muscle fibrosis during chronic skeletal muscle injury by targeting TGF-ßR1/Smad pathway.

BACKGROUND: Fibrosis is a significant pathological feature of chronic skeletal muscle injury, profoundly affecting muscle regeneration. Fibro-adipogenic progenitors (FAPs) have the ability to differentiate into myofibroblasts, acting as a primary source of extracellular matrix (ECM). the process by which FAPs differentiate into myofibroblasts during chronic skeletal muscle injury remains inadequately explored. METHOD: mouse model with sciatic nerve denervated was constructed and miRNA expression profiles between the mouse model and uninjured mouse were analyzed. qRT/PCR and immunofluorescence elucidated the effect of miR-27b-3p on fibrosis in vivo and in vitro. Dual-luciferase reporter identified the target gene of miR-27b-3p, and finally knocked down or overexpressed the target gene and phosphorylation inhibition of Smad verified the influence of downstream molecules on the abundance of miR-27b-3p and fibrogenic differentiation of FAPs. RESULT: FAPs derived from a mouse model with sciatic nerves denervated exhibited a progressively worsening fibrotic phenotype over time. Introducing agomiR-27b-3p effectively suppressed fibrosis both in vitro and in vivo. MiR-27b-3p targeted Transforming Growth Factor Beta Receptor 1 (TGF-ßR1) and the abundance of miR-27b-3p was negatively regulated by TGF-ßR1/Smad. CONCLUSION: miR-27b-3p targeting the TGF-ßR1/Smad pathway is a novel mechanism for regulating fibrogenic differentiation of FAPs. Increasing abundance of miR-27b-3p, suppressing expression of TGF-ßR1 and inhibiting phosphorylation of smad3 presented potential strategies for treating fibrosis in chronic skeletal muscle injury.

Discipline-specific Torque-Velocity Profiles and Musculotendinous Morphology in Athletes.

OBJECTIVES: The aim of this study was to compare torque-velocity profiles, muscle architecture, tendon dimensions, and bilateral-symmetry between competitive cyclists (CY), competitive runners (RN), ice-hockey players (IH), basketball players (BP), and physically-active individuals (CN) (n=10 for each group). METHODS: Vastus lateralis (VL) muscle and patellar tendon (PT) structures were determined with B-mode ultrasonography, and maximal knee extensor isokinetic torque was assessed at three different velocities. RESULTS: Optimal torque and velocity were lower in runners than CY, BP and IH (p<0.05). Maximal power was similar between the athlete groups but greater than CN (p<0.05). Furthermore, RN and BP reached their peak-torque at longer muscle lengths compared to IH and CY (p<0.05). RN had the lowest VL muscle thickness and the greatest fascicle length, while CY had the greatest pennation angle (p<0.05). CY had the greatest PT thickness, particularly at the proximal and medial sites, while BP at the distal point (p<0.05), with similar trends observed for PT cross-sectional-area. CONCLUSIONS: Our findings show that even if power generating capacity is similar between athletic disciplines, there are discipline-specific muscle adaptations, where particularly runners appear to have muscles adapted for speed rather than torque development, while in cyclists, velocity is sacrificed for torque development.

The Components of Lumbar Motor Control Are Not Inter-related.

OBJECTIVES: To verify the relationship between the indicators of components of lumbar motor control and determine the factors related to the indicators to each of these components. METHODS: Twenty-five healthy university students were included in the study. The lumbar spine and hip kinematic parameters of posterior/anterior pelvic tilt (mobility and smoothness), ball catching (reactivity), and forward/backward rocking (adaptive stability) were measured as indicators of lumbar motor control. Lumbar proprioception, trunk muscle strength, and lower trunk muscle thickness were also measured. Kinematic parameters of the lumbar spine and hip were measured using a small accelerometer. The data verified the relevance of indicators of lumbar motor control and the relationship with relevant factors. RESULTS: No significant correlations were found for most lumbar motor control indicators. Lumbar proprioception and rectus abdominis muscle thickness were identified as relevant indicators of lumbar motor control. CONCLUSIONS: Each component of lumbar motor control is independent and must be evaluated for the component whose function is required. Additionally, some components of lumbar motor control are associated with lumbar proprioception and rectus abdominis muscle thickness; thus, evaluation of these components is necessary when evaluating lumbar motor control.

Force Production Measurements During a Supine Medicine Ball Throw: a Reliability and Correlation Study.

OBJECTIVES: This study aimed to examine the reliability of supine medicine ball throw peak force and rate of force development (RFD) measurements. A secondary aim was to investigate the correlations between these measurements and vertical jump height. METHODS: Twenty young women (21±3 years) reported for experimental testing on two different occasions. Supine medicine ball throw assessments were performed during each testing session to assess peak force, RFDmax, and RFD at specific percentages of peak force (RFD30% and RFD40-80%). Vertical jumps were performed on a jump mat. The jump mat measured vertical jump height based on flight time. RESULTS: Good intraclass correlation coefficients (≥0.82) and coefficients of variation (≤14.0%) were observed between sessions for peak force, RFDmax, and RFD40-80%, but not for RFD30% (0.55, 27.2%). There were significant correlations between jump height and peak force (r=0.483, P=0.031), RFDmax (r=0.484, P=0.031), and RFD40-80% (r=0.491, P=0.028). There was no significant correlation between jump height and RFD30% (r=0.359, P=0.120). CONCLUSIONS: Our results showed that supine medicine ball throw peak force, RFDmax, and RFD40-80% were reliable measures for assessing upper-body explosive strength in young adults. These measurements were significantly associated with vertical jump height and therefore, may be effective predictors of one's athletic ability.

Neural Drive and Motor Unit Characteristics of the Serratus Anterior in Individuals With Scapular Dyskinesis.

OBJECTIVE: Scapular dyskinesis is one of the causes of shoulder disorders and involves muscle weakness in the serratus anterior. This study investigated whether motor unit (MU) recruitment and firing property, which are important for muscle exertion, have altered in serratus anterior of the individuals with scapular dyskinesis. METHODS: Asymptomatic adults with (SD) and without (control) scapular dyskinesis were analyzed. Surface electromyography (sEMG) waveforms were collected at submaximal voluntary contraction of the serratus anterior. The sEMG waveform was decomposed into MU action potential amplitude (MUAPAMP), mean firing rate (MFR), and recruitment threshold. MUs were divided into low, moderate, and high thresholds, and MU recruitment and firing properties of the groups were compared. RESULTS: High-threshold MUAPAMP was significantly smaller in the SD group than in the control group. The control group also exhibited recruitment properties that reflected the size principle, however, the SD group did not. Furthermore, the SD group had a lower MFR than the control group. CONCLUSIONS: Individuals with scapular dyskinesis exhibit altered MU recruitment properties and lower firing rates of the serratus anterior; this may be detrimental to muscle performance. Thus, it may be necessary to improve the neural drive of the serratus anterior when correcting scapular dyskinesis.

Force and Neuromuscular Responses During a Handgrip Hold to Failure Anchored to a Moderate Perceptual Intensity in Males.

OBJECTIVES: The current study investigated performance fatigability (PF) and time course of changes in force, electromyographic amplitude (EMG AMP) and frequency (EMG MPF), and neuromuscular efficiency (NME) during a sustained, isometric, handgrip hold to failure (HTF) using the rating of perceived exertion (RPE)-Clamp Model. METHODS: Twelve males performed a handgrip HTF anchored to RPE=5. The time to task failure (Tlim), force (N), EMG AMP and MPF, and NME (normalized force/ normalized EMG AMP) were recorded. Analyses included a paired samples t-test for PF at an alpha of p<0.05, 1-way repeated measures ANOVA across time and post-hoc t-tests (p<0.0025) for force, EMG AMP and MPF, and NME responses. RESULTS: The PF (pre- to post- maximal force % decline) was 38.2±11.5%. There were decreases in responses, relative to 0% Tlim, from 40% to 100% Tlim (force), at 30%, 60%, and 100% Tlim (EMG AMP), from 10% to 100% Tlim(EMP MPF), and from 50% to 65%, and 80% to 100% Tlim (NME) (p<0.0025). CONCLUSIONS: The RPE-Clamp Model in this study demonstrated that pacing strategies may be influenced by the integration of anticipatory, feedforward, and feedback mechanisms, and provided insights into the relationship between neuromuscular and perceptual responses, and actual force generating capacity.

Effects of Bilateral or Unilateral Plyometric Training of Lower Limbs on the Bilateral Deficit During Explosive Efforts.

OBJECTIVES: Bilateral Deficit (BLD) occurs when the force generated by both limbs together is smaller than the sum of the forces developed separately by the two limbs. BLD may be modulated by physical training. Here, were investigated the effects of unilateral or bilateral plyometric training on BLD and neuromuscular activation during lower limb explosive extensions. METHODS: Fourteen young males were randomized into the unilateral (UL_) or bilateral (BL_) training group. Plyometric training (20 sessions, 2 days/week) was performed on a sled ergometer, and consisted of UL or BL consecutive, plyometric lower limb extensions (3-to-5 sets; 8-to-10 repetitions). Before and after training, maximal explosive efforts with both lower limbs or with each limb separately were assessed. Electromyography of representative lower limb muscles was measured. RESULTS: BL_training significantly and largely decreased BLD (p=0.003, effect size=1.63). This was accompanied by the reversion from deficit to facilitation of the electromyography amplitude of knee extensors during bilateral efforts (p=0.007). Conversely, UL_training had negligible effects on BLD (p=0.781). Also, both groups showed similar improvements in their maximal explosive power generated after training. CONCLUSIONS: Bilateral plyometric training can mitigate BLD, and should be considered for training protocols focused on improving bilateral lower limb motor performance.

Multimodal sensorimotor assessment of hand and forearm asymmetries: a reliability and correlational study.

Background: Effective rehabilitation of upper limb musculoskeletal disorders requires multimodal assessment to guide clinicians' decision-making. Furthermore, a comprehensive assessment must include reliable tests. Nevertheless, the interrelationship among various upper limb tests remains unclear. This study aimed to evaluate the reliability of easily applicable upper extremity assessments, including absolute values and asymmetries of muscle mechanical properties, pressure pain threshold, active range of motion, maximal isometric strength, and manual dexterity. A secondary aim was to explore correlations between different assessment procedures to determine their interrelationship. Methods: Thirty healthy subjects participated in two experimental sessions with 1 week between sessions. Measurements involved using a digital myotonometer, algometer, inclinometer, dynamometer, and the Nine-Hole Peg test. Intraclass correlation coefficients, standard error of the mean, and minimum detectable change were calculated as reliability indicators. Pearson's correlation was used to assess the interrelationship between tests. Results: For the absolute values of the dominant and nondominant sides, reliability was 'good' to 'excellent' for muscle mechanical properties, pressure pain thresholds, active range of motion, maximal isometric strength, and manual dexterity. Similarly, the reliability for asymmetries ranged from 'moderate' to 'excellent' across the same parameters. Faster performance in the second session was consistently found for the Nine-Hole Peg test. No systematic inter-session errors were identified for the values of the asymmetries. No significant correlations were found between tests, indicating test independence. Conclusion: These findings indicate that the sensorimotor battery of tests is reliable, while monitoring asymmetry changes may offer a more conservative approach to effectively tracking recovery of upper extremity injuries.

The Validity of Muscle Ultrasound in the Diagnostic Workup of Sarcopenia Among Older Adults: A Scoping Review.

Purpose: Muscle ultrasound has emerged as a promising method in the diagnostic work-up of sarcopenia. The objective of this scoping review was to explore the validity of muscle ultrasound against the latest sarcopenia definitions among older adults. Methods: We adhered to the PRISMA guidelines for scoping reviews. A systematic search of databases was performed by two independent reviewers. All articles comparing the performance of ultrasound to an internationally acknowledged sarcopenia definition among older adults (≥60 years) and published between 2019/01/01 (the year updated sarcopenia definitions were introduced) and 2023/11/15 were included. Data were extracted and collated by muscle and muscle parameters. Results: Out of 2290 articles screened, six studies comprising 24 validity tests among a total of 1619 older adults (mean age 74.1 years, 52.2% female) were included. The validity tests investigated the rectus femoris (n = 7), biceps brachii (n = 5), gastrocnemius medialis (n = 4), tibialis anterior (n = 4), soleus (n = 3), and rectus abdominis (n = 1). The parameter muscle thickness (MT) (n = 14) was most commonly measured. The latest European and Asian sarcopenia definitions (EWGSOP2, AWGS2) were applied as reference standards in four validity tests each. None of the studies used the Sarcopenia Definition and Outcome Consortium (SDOC) criteria. The highest area under the curve AUC (0.92, 95% confidence interval [CI] 0.89-0.94) was found for the muscle thickness of the rectus femoris muscle. Due to substantial heterogeneity among the studies, pooling of data using a meta-analytic approach was not feasible. Conclusion: Limited number of studies have examined the validity of muscle ultrasound for diagnosing sarcopenia based on recent definitions among older adults. Thereby, muscle thickness of the rectus femoris showed promising results regarding validity. Further studies are needed to investigate the validity of key muscles and to validate muscle ultrasound among older hospitalized patients.

Progressive sarcopenia and myosteatosis predict prognosis of advanced HCC patients treated with immune checkpoint inhibitors.

Background: Immunotherapy stands as a pivotal modality in the therapeutic landscape for the treatment of advanced hepatocellular carcinoma, yet responses vary among patients. This study delves into the potential impact of sarcopenia, myosteatosis and adiposity indicators, as well as their changes during immunotherapy, on treatment response and prognosis in patients with advanced hepatocellular carcinoma treated with immune checkpoint inhibitors. Methods: In this retrospective analysis, 116 patients with advanced hepatocellular carcinoma receiving immune checkpoint inhibitors were recruited. Skeletal muscle, intramuscular, subcutaneous, and visceral adipose tissue were assessed by computed tomography at the level of the third lumbar vertebrae before and after 3 months of treatment. Sarcopenia and myosteatosis were evaluated by skeletal muscle index and mean muscle density using predefined threshold values. Patients were stratified based on specific baseline values or median values, along with alterations observed during the treatment course. Overall survival (OS) and progression-free survival (PFS) were compared using the log-rank test and a multifactorial Cox proportional risk model. Results: A total of 116 patients were recruited and divided into two cohorts, 81 patients for the training set and 35 patients for the validating set. In the overall cohort, progressive sarcopenia (P=0.021) and progressive myosteatosis (P=0.001) were associated with objective response rates, whereas progressive myosteatosis (P<0.001) was associated with disease control rates. In the training set, baseline sarcopenia, myosteatosis, and subcutaneous and visceral adipose tissue were not significantly associated with PFS and OS. In multivariate analysis adjusting for sex, age, and other factors, progressive sarcopenia(P=0.002) and myosteatosis (P=0.018) remained independent predictors of PFS. Progressive sarcopenia (P=0.005), performance status (P=0.006) and visceral adipose tissue index (P=0.001) were all independent predictors of OS. The predictive models developed in the training set also had good feasibility in the validating set. Conclusion: Progressive sarcopenia and myosteatosis are predictors of poor clinical outcomes in patients with advanced hepatocellular carcinoma receiving immune checkpoint inhibitors, and high baseline visceral adiposity is associated with a poorer survival.

A therapeutic leap: how myosin inhibitors moved from cardiac interventions to skeletal muscle myopathy solutions.

The myosin inhibitor mavacamten has transformed the management of obstructive hypertrophic cardiomyopathy (HCM) by targeting myosin ATPase activity to mitigate cardiac hypercontractility. This therapeutic mechanism has proven effective for patients with HCM independent of having a primary gene mutation in myosin. In this issue of the JCI, Buvoli et al. report that muscle hypercontractility is a mechanism of pathogenesis underlying muscle dysfunction in Laing distal myopathy, a disorder characterized by mutations altering the rod domain of ß myosin heavy chain. The authors performed detailed physiological, molecular, and biomechanical analyses and demonstrated that myosin ATPase inhibition can correct a large extent of muscle abnormalities. The findings offer a therapeutic avenue for Laing distal myopathy and potentially other myopathies. This Commentary underscores the importance of reevaluating myosin activity's role across myopathies in general for the potential development of targeted myosin inhibitors to treat skeletal muscle disorders.

Highly stretchable and customizable microneedle electrode arrays for intramuscular electromyography.

Stretchable three-dimensional (3D) penetrating microelectrode arrays have potential utility in various fields, including neuroscience, tissue engineering, and wearable bioelectronics. These 3D microelectrode arrays can penetrate and conform to dynamically deforming tissues, thereby facilitating targeted sensing and stimulation of interior regions in a minimally invasive manner. However, fabricating custom stretchable 3D microelectrode arrays presents material integration and patterning challenges. In this study, we present the design, fabrication, and applications of stretchable microneedle electrode arrays (SMNEAs) for sensing local intramuscular electromyography signals ex vivo. We use a unique hybrid fabrication scheme based on laser micromachining, microfabrication, and transfer printing to enable scalable fabrication of individually addressable SMNEA with high device stretchability (60 to 90%). The electrode geometries and recording regions, impedance, array layout, and length distribution are highly customizable. We demonstrate the use of SMNEAs as bioelectronic interfaces in recording intramuscular electromyography from various muscle groups in the buccal mass of Aplysia.

Predictive value of adductor pollicis muscle thickness for ultrasound-based sarcopenia in older adults.

BACKGROUND: The adductor pollicis muscle thickness (APMT) is least affected by subcutaneous adipose tissue and can be measured externally. The aim of this study is to identify the predictive value of APMT for the diagnosis of ultrasonography-based sarcopenia. METHODS: A total of 245 outpatients who were aged ≥65 years (49 with sarcopenia and 196 without sarcopenia) were included in this cross-sectional study. Patients with knee or hip replacement, advanced dementia, cerebrovascular disease, neurodegenerative disease, or decompensated heart failure and those using drugs that affect muscle functions, such as steroids, were excluded. Comprehensive geriatric assessments and anthropometric measurements of the patients were performed. APMT was assessed with a skinfold caliper. The diagnosis of sarcopenia was based on a low Sonographic Thigh Adjustment Ratio (STAR) index (anterior thigh muscle thickness by ultrasonography/body mass index [BMI] ratio, cutoff points are <1.4 for men and <1.0 for women) and low handgrip strength. The predictive ability of APMT for ultrasound-based sarcopenia diagnosis was examined. RESULTS: There was no significant difference in terms of arm and calf circumference and BMI between the sarcopenic and nonsarcopenic groups. APMT, handgrip strength, anterior thigh muscle thickness, and gait speed were significantly lower in the patients with sarcopenia. The best cutoff points of APMT for sarcopenia were ≤16.5 for women and ≤21.5 for men with areas under the curve of 0.70 and 0.66, respectively, and negative predictive values of 91.2 and 94.3, respectively (P < 0.001). CONCLUSION: APMT can be a useful anthropometric marker for ultrasound-based sarcopenia diagnosis.