A comprehensive review of the mechanisms on fish stress affecting muscle qualities: Nutrition, physical properties, and flavor.

Fish inevitably face numerous stressors in growth, processing, and circulation. In recent years, stress-related change in fish muscle quality has gradually become a research hotspot. Thus, the understanding of the mechanism regarding the change is constantly deepening. This review introduces the physiological regulation of fish under stress, with particular attention devoted to signal transduction, gene expression, and metabolism, and changes in the physiological characteristics of muscular cells. Then, the influences of various stressors on the nutrition, physical properties, and flavor of the fish muscle are sequentially described. This review emphasizes recent advances in the mechanisms underlying changes in muscle quality, which are believed to be involved mainly in physiological regulation under stress. In addition, studies are also introduced on improving muscle quality by mitigating fish stress.

Organ preservation in muscle-invasive urothelial bladder cancer.

PURPOSE OF REVIEW: The most common definitive treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy. However, removing the bladder and surrounding organs poses risks of morbidity that can reduce quality of life, and raises the risk of death. Treatment strategies that preserve the organs can manage the local tumor and mitigate the risk of distant metastasis. Recent data have demonstrated promising outcomes in several bladder-preservation strategies. RECENT FINDINGS: Bladder preservation with trimodality therapy (TMT), combining maximal transurethral resection of the bladder tumor, chemotherapy, and radiotherapy (RT), was often reserved for nonsurgical candidates for radical cystectomy. Recent meta-analyses show that outcomes of TMT and radical cystectomy are similar. More recent bladder-preservation approaches include combining targeted RT (MRI) and immune checkpoint inhibitors (ICIs), ICIs and chemotherapy, and selecting patients based on genomic biomarkers and clinical response to systemic therapies. These are all promising strategies that may circumvent the need for radical cystectomy. SUMMARY: MIBC is an aggressive disease with a high rate of systemic progression. Current management includes neoadjuvant cisplatin-based chemotherapy and radical cystectomy with lymph node dissection. Novel alternative strategies, including TMT approaches, combinations with RT, chemotherapy, and/or ICIs, and genomic biomarkers, are in development to further advance bladder-preservation options for patients with MIBC.

Is bulbospongiosus muscle botox injection safe and effective in treating lifelong premature ejaculation? Randomized controlled study.

PURPOSE: To evaluate the safety and efficacy of botulinum-A toxin injections into the bulbospongiosus muscle for cases of lifelong drug-resistant premature ejaculation (PE). METHODS: Ninety-eight outpatients diagnosed with lifelong PE were randomly assigned to two groups: the botulinum-A toxin group comprising forty-nine patients and the placebo (saline) group also consisting of forty-nine patients. A 100 U botulinum-A toxin was diluted into 10 cc of saline, with 5 cc injected into one side of the muscle (botulinum-A toxin group) guided by ultrasound to distribute across most muscle fibers. The same technique was applied using the same volume of saline injected into the bulbospongiosus muscle. Intravaginal ejaculatory latency time (IELT), scores from the premature ejaculation profile (PEP), Premature Ejaculation Diagnostic Tool (PEDT), International Index of Erectile Function (IIEF), and recording of any complications were obtained. Follow-ups occurred at 1-, 3-, and 6-month post-procedure. RESULTS: Cases receiving injections of botulinum-A toxin into the bulbospongiosus muscle showed notably extended intravaginal ejaculatory latency times compared to their initial performance after treatment. In addition, there were enhancements in PEP scores, and notably, no significant complications were reported. Conversely, the bilateral injection of saline into the bulbospongiosus muscle did not demonstrate any impact on ejaculation latencies. CONCLUSION: Our study demonstrated that the injection of botulinum-A toxin into the bulbospongiosus muscle can serve as a safe and effective option for treating PE. Nonetheless, its clinical application warrants further studies involving larger sample sizes and longer follow-up periods.

A deep learning approach for fast muscle water T2 mapping with subject specific fat T2 calibration from multi-spin-echo acquisitions.

This work presents a deep learning approach for rapid and accurate muscle water T2 with subject-specific fat T2 calibration using multi-spin-echo acquisitions. This method addresses the computational limitations of conventional bi-component Extended Phase Graph fitting methods (nonlinear-least-squares and dictionary-based) by leveraging fully connected neural networks for fast processing with minimal computational resources. We validated the approach through in vivo experiments using two different MRI vendors. The results showed strong agreement of our deep learning approach with reference methods, summarized by Lin's concordance correlation coefficients ranging from 0.89 to 0.97. Further, the deep learning method achieved a significant computational time improvement, processing data 116 and 33 times faster than the nonlinear least squares and dictionary methods, respectively. In conclusion, the proposed approach demonstrated significant time and resource efficiency improvements over conventional methods while maintaining similar accuracy. This methodology makes the processing of water T2 data faster and easier for the user and will facilitate the utilization of the use of a quantitative water T2 map of muscle in clinical and research studies.

[Current and Future Status of Muscle Pathology: The Position of Muscle Pathology Diagnosis in the Future].

Many muscle disease names are mostly based on muscle pathology findings. Naturally, muscle pathology is important in the diagnosis of muscle diseases. Moreover, in recent years, extensive genetic analysis and autoantibody testing for myositis have been applied clinically, although muscle biopsies are less performed. However, muscle pathology should be proactively considered when a single gene presents multiple phenotypes, when variants of unknown pathological significance are detected, or in cases of autoimmune myositis that may be misdiagnosed as muscular dystrophy.

Severe fibromyalgia alleviated by the unique muscle relaxation method of applying low force: A case report.

RATIONALE: Fibromyalgia (FM) is characterized by idiopathic persistent chronic pain in the ligaments or musculoskeletal system, and more than half of the patients with FM might have migraine headaches. Direct musculoskeletal intervention could be a non-pharmacological management to relieve symptoms. However, patients with severe FM often have intense pain from only a soft touch, thereby rendering musculoskeletal intervention challenging. PATIENT CONCERNS: A 47-year-old man had progressing intense pain, and this affected his everyday life. There were no abnormal physical findings on laboratory examination such as levels of complement, antinuclear antibodies, and C-reactive protein, which were within normal limits. Magnetic resonance imaging did not indicate abnormalities. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: The patient satisfied the American College of Rheumatology criteria. Finally, we made a final diagnosis of fibromyalgia. The therapeutic intervention of Kanshoho, the unique muscle relaxation technique with low force, relieved his pain. LESSONS: If Kanshoho is carefully applied in a state of hospitalization under surveillance by an experienced physician, it could be a promising muscle relaxation method. Relaxing the trapezius muscle and reducing its intramuscular pressure might be key in treating patients with severe FM. However, it needs elucidation of its mechanism.

Scaling of buccal mass growth and muscle activation determine the duration of feeding behaviours in the marine mollusc Aplysia californica.

The mechanical forces experienced during movement and the time constants of muscle activation are important determinants of the durations of behaviours, which may both be affected by size-dependent scaling. The mechanics of slow movements in small animals are dominated by elastic forces and are thus quasistatic (i.e. always near mechanical equilibrium). Muscular forces producing movement and elastic forces resisting movement should scale identically (proportional to mass2/3), leaving the scaling of the time constant of muscle activation to play a critical role in determining behavioural duration. We tested this hypothesis by measuring the duration of feeding behaviours in the marine mollusc Aplysia californica whose body sizes spanned three orders of magnitude. The duration of muscle activation was determined by measuring the time it took for muscles to produce maximum force as A. californica attempted to feed on tethered inedible seaweed, which provided an in vivo approximation of an isometric contraction. The timing of muscle activation scaled with mass0.3. The total duration of biting behaviours scaled identically, with mass0.3, indicating a lack of additional mechanical effects. The duration of swallowing behaviour, however, exhibited a shallower scaling of mass0.17. We suggest that this was due to the allometric growth of the anterior retractor muscle during development, as measured by micro-computed tomography (micro-CT) scans of buccal masses. Consequently, larger A. californica did not need to activate their muscles as fully to produce equivalent forces. These results indicate that muscle activation may be an important determinant of the scaling of behavioural durations in quasistatic systems.

MIR145 Core Promoter Methylation in Pretreatment Cell-Free DNA: A Liquid Biopsy Tool for Muscle-Invasive Bladder Cancer Treatment Outcome.

PURPOSE: The lack of personalized management of bladder cancer (BlCa) results in patients' lifelong post-treatment monitoring with invasive interventions, underlying the urgent need for tailored and minimally invasive health care services. On the basis of our previous findings on miR-143/145 cluster methylation in bladder tumors, we evaluated its clinical significance in pretreatment cell-free DNA (cfDNA) of patients with BlCa. MATERIALS AND METHODS: Methylation analysis was performed in our screening cohort (120 patients with BlCa; 20 age-matched healthy donors) by bisulfite-based pyrosequencing. Tumor recurrence/progression for patients with non-muscle-invasive bladder cancer, and progression and mortality for patients with muscle-invasive bladder cancer (MIBC) were used as clinical end point events in survival analysis. Bootstrap analysis was applied for internal validation of Cox regression models and decision curve analysis for assessment of clinical benefit on disease prognosis. RESULTS: Decreased methylation of MIR145 core promoter in pretreatment cfDNA was associated with short-term disease progression (multivariate Cox: hazard ratio [HR], 2.027 [95% CI, 1.157 to 3.551]; P = .010) and poor overall survival (multivariate Cox: HR, 2.098 [95% CI, 1.154 to 3.817]; P = .009) of patients with MIBC after radical cystectomy (RC). Multivariate models incorporating MIR145 promoter methylation in cfDNA with tumor stage clearly ameliorated patients' risk stratification, highlighting superior clinical benefit in MIBC prognostication. CONCLUSION: Reduced pretreatment cfDNA methylation of MIR145 core promoter was markedly correlated with increased risk for short-term progression and worse survival of patients with MIBC after RC and adjuvant therapy, supporting modern personalized and minimally invasive prognosis. Methylation profiling of MIR145 core promoter in pretreatment cfDNA could serve as a minimally invasive and independent predictor of MIBC treatment outcome and emerge as a promising marker for blood-based test in BlCa.

Estimation of lower back muscle force in a lifting task using wearable IMUs.

Low back pain is commonly reported in occupational settings due to factors such as heavy lifting and poor ergonomic practices, often resulting in significant healthcare expenses and lowered productivity. Assessment tools for human motion and ergonomic risk at the workplace are still limited. Therefore, this study aimed to assess lower back muscle and joint reaction forces in laboratory conditions using wearable inertial measurement units (IMUs) during weight lifting, a frequently high-risk workplace task. Ten able-bodied participants were instructed to lift a 28 lbs. box while surface electromyography sensors, IMUs, and a camera-based motion capture system recorded their muscle activity and body motion. The data recorded by IMUs and motion capture system were used to estimate lower back muscle and joint reaction forces via musculoskeletal modeling. Lower back muscle patterns matched well with electromyography recordings. The normalized mean absolute differences between muscle forces estimated based on measurements of IMUs and cameras were less than 25 %, and the statistical parametric mapping results indicated no significant difference between the forces estimated by both systems. However, abrupt changes in motion, such as lifting initiation, led to significant differences (p < 0.05) between the muscle forces. Furthermore, the maximum L5-S1 joint reaction force estimated using IMU data was significantly lower (p < 0.05) than those estimated by cameras during weight lifting and lowering. The study showed how kinematic errors from IMUs propagated through the musculoskeletal model and affected the estimations of muscle forces and joint reaction forces. Our findings showed the potential of IMUs for in-field ergonomic risk evaluations.

Automatic segmentation of lower limb muscles from MR images of post-menopausal women based on deep learning and data augmentation.

Individual muscle segmentation is the process of partitioning medical images into regions representing each muscle. It can be used to isolate spatially structured quantitative muscle characteristics, such as volume, geometry, and the level of fat infiltration. These features are pivotal to measuring the state of muscle functional health and in tracking the response of the body to musculoskeletal and neuromusculoskeletal disorders. The gold standard approach to perform muscle segmentation requires manual processing of large numbers of images and is associated with significant operator repeatability issues and high time requirements. Deep learning-based techniques have been recently suggested to be capable of automating the process, which would catalyse research into the effects of musculoskeletal disorders on the muscular system. In this study, three convolutional neural networks were explored in their capacity to automatically segment twenty-three lower limb muscles from the hips, thigh, and calves from magnetic resonance images. The three neural networks (UNet, Attention UNet, and a novel Spatial Channel UNet) were trained independently with augmented images to segment 6 subjects and were able to segment the muscles with an average Relative Volume Error (RVE) between -8.6% and 2.9%, average Dice Similarity Coefficient (DSC) between 0.70 and 0.84, and average Hausdorff Distance (HD) between 12.2 and 46.5 mm, with performance dependent on both the subject and the network used. The trained convolutional neural networks designed, and data used in this study are openly available for use, either through re-training for other medical images, or application to automatically segment new T1-weighted lower limb magnetic resonance images captured with similar acquisition parameters.

JAK/STAT mediated insulin resistance in muscles is essential for effective immune response.

BACKGROUND: The metabolically demanding nature of immune response requires nutrients to be preferentially directed towards the immune system at the expense of peripheral tissues. We study the mechanisms by which this metabolic reprograming occurs using the parasitoid infection of Drosophila larvae. To overcome such an immune challenge hemocytes differentiate into lamellocytes, which encapsulate and melanize the parasitoid egg. Hemocytes acquire the energy for this process by expressing JAK/STAT ligands upd2 and upd3, which activates JAK/STAT signaling in muscles and redirects carbohydrates away from muscles in favor of immune cells. METHODS: Immune response of Drosophila larvae was induced by parasitoid wasp infestation. Carbohydrate levels, larval locomotion and gene expression of key proteins were compared between control and infected animals. Efficacy of lamellocyte production and resistance to wasp infection was observed for RNAi and mutant animals. RESULTS: Absence of upd/JAK/STAT signaling leads to an impaired immune response and increased mortality. We demonstrate how JAK/STAT signaling in muscles leads to suppression of insulin signaling through activation of ImpL2, the inhibitor of Drosophila insulin like peptides. CONCLUSIONS: Our findings reveal cross-talk between immune cells and muscles mediates a metabolic shift, redirecting carbohydrates towards immune cells. We emphasize the crucial function of muscles during immune response and show the benefits of insulin resistance as an adaptive mechanism that is necessary for survival.

Beyond surgery: bladder preservation and the role of systemic treatment in localised muscle-invasive bladder cancer.

Over the last two to three decades the non-surgical curative management of bladder cancer has significantly progressed. Increasing evidence supports the use of bladder preservation as an alternative to radical cystectomy (RC) for localised muscle-invasive bladder cancer (MIBC). Radiosensitisation with chemotherapy or hypoxia modification improves the efficacy of radiotherapy. Systemic treatments play an important role in the management of localised MIBC with the benefit of neoadjuvant chemotherapy prior to radical treatment well established. The use of immune checkpoint inhibitors (ICIs) in the radical treatment of bladder cancer, their safe combination with radical radiotherapy regimens and whether the addition of ICIs improve rates of cure are outstanding questions beginning to be answered by ongoing clinical trials. In this narrative review, we discuss the current evidence for bladder preservation and the role of systemic treatments for localised MIBC.

Successful application of modified crude DNA extraction from muscle tissues for various types of PCR amplifications.

BACKGROUND: One of the most challenging aspects of nucleic acid amplification tests is the extraction of genomic DNA. However, achieving satisfactory quality and quantity of genomic DNA is not always easy, while the demand for rapid, low-cost and less laborious DNA isolation methods is ever-increasing. METHODS AND RESULTS: We have developed a rapid (⁓2 min) crude DNA extraction method leading to direct-PCR that requires minimum reagents and laboratory equipment. It was developed by eliminating the time-consuming purification steps of DNA extraction, by processing the sample in optimized amounts of Taq KCl PCR buffer and DNARelease Additive/Proteinase K in only two minutes and carrying out amplification using conventional Taq DNA polymerase. The DNA preparation method was validated on muscle tissue samples from 12 different species as well as 48 cooked meat samples. Its compatibility was also successfully tested with different types of PCR amplification platforms extensively used for genetic analysis, such as simplex PCR, PCR-RFLP (Restriction Fragment Length Polymorphism), multiplex PCR, isothermal amplification, real-time PCR and DNA sequencing. CONCLUSIONS: The developed protocol provides sufficient amount of crude DNA from muscle tissues of different species for PCR amplifications to identify species-of-origin via different techniques coupled with PCR. The simplicity and robustness of this protocol make nucleic acid amplification assays more accessible and affordable to researchers and authorities for both laboratory and point-of-care tests.

Natural zeolite for heavy metal, ammonia removal, and physiological responses in European sea bass (Dicentrarchus labrax) juveniles tanks with different densities.

The present study aims to investigate the influence of zeolite usage and stocking densities on various parameters, including ammonia removal from water, accumulation of heavy metals in fish organs, water quality, growth performance, feed efficiency, muscle composition, as well as hematological and biochemical parameters in European seabass (Dicentrarchus labrax) over a 90-day duration. A total of 2400 D. labrax with an initial weight of 9.83 ± 2.02 g and initial length of 9.37 ± 0.32 cm were distributed among 24 tanks. The research involved six distinct treatment groups, with two different zeolite levels (0 and 15 ppt) and three stocking density levels (50, 100, and 150 fish/m3), each replicated four times. The results of the research demonstrate a statistically significant improvement (p < 0.05) in water quality measures with the introduction of zeolite. The successful implementation of this amendment mitigated the adverse effects of fish density on water quality parameters. Higher stocking density negatively impacted European sea bass growth, feed utilization, and hemato-biochemical indicators. Zeolite use effectively alleviated these adverse effects, particularly on performance, feed utilization, hematological, and biochemical parameters. The study's results indicate that the utilization of zeolite has shown to be efficacious in mitigating the accumulation of heavy metals in both water and fish organs, while concurrently augmenting fish attributes. However, the increase in density led to a significant decrease in the accumulation of heavy metals in both water and fish organs. The present study highlights the capacity of natural zeolites to mitigate the negative consequences associated with water quality concerns. The efficiency of these zeolites in limiting the accessibility of heavy metals in polluted water is shown, hence minimizing their accumulation in fish organs. In addition, the improvement of fish performance has the capacity to have a beneficial influence on both the well-being and efficiency of fish in aquaculture. Additional research is essential to fully understand the complex molecular pathways involved in utilizing natural zeolite under different fish densities.

col1a2+ fibroblasts/muscle progenitors finetune xanthophore countershading by differentially expressing csf1a/1b in embryonic zebrafish.

Animals evolve diverse pigment patterns to adapt to the natural environment. Countershading, characterized by a dark-colored dorsum and a light-colored ventrum, is one of the most prevalent pigment patterns observed in vertebrates. In this study, we reveal a mechanism regulating xanthophore countershading in zebrafish embryos. We found that csf1a and csf1b mutants altered xanthophore countershading differently: csf1a mutants lack ventral xanthophores, while csf1b mutants have reduced dorsal xanthophores. Further study revealed that csf1a is expressed throughout the trunk, whereas csf1b is expressed dorsally. Ectopic expression of csf1a or csf1b in neurons attracted xanthophores into the spinal cord. Blocking csf1 signaling by csf1ra mutants disrupts spinal cord distribution and normal xanthophores countershading. Single-cell RNA sequencing identified two col1a2+ populations: csf1ahighcsf1bhigh muscle progenitors and csf1ahighcsf1blow fibroblast progenitors. Ablation of col1a2+ fibroblast and muscle progenitors abolished xanthophore patterns. Our study suggests that fibroblast and muscle progenitors differentially express csf1a and csf1b to modulate xanthophore patterning, providing insights into the mechanism of countershading.

The Prognostic Value of the Combination of the Prognostic Nutritional Index and the Lymphocyte:Monocyte Ratio for the Prediction of Patients with Muscle-Invasive Bladder Cancer.

OBJECTIVE: To explore the efficacy of combining the prognostic nutritional index (PNI) and the lymphocyte:monocyte ratio (LMR) for patients with muscle-invasive bladder cancer (MIBC). METHODS: Of 172 patients who were diagnosed with MIBC in our hospital, 94 were eligible for the study. The clinical data of the 94 patients with MIBC were collected. The patients were divided according to the optimal cut-off values for the preoperative PNI and LMR into a low-PNI subgroup (PNI <44.15, 52 patients), a high-PNI subgroup (PNI ≥44.15, 42 patients), a low-LMR subgroup (LMR <2.98, 50 patients) and a high-LMR subgroup (LMR ≥2.98, 44 patients). The area under the receiver operating characteristic (ROC) curve (AUC) was used to analyse the efficacy of the PNI and the LMR in predicting the prognosis of patients with MIBC. Univariate and multivariate logistic regression analyses were performed to evaluate prognostic factors for patients with MIBC. Kaplan-Meier (K‒M) survival analysis was used for overall survival (OS) analysis to explore the ability of the PNI combined with the LMR to predict the prognosis of patients with MIBC. RESULTS: The optimal cut-off values for the preoperative PNI and the preoperative LMR were 44.15 and 2.98, respectively, on the basis of ROC curves. ROC curve analysis revealed that the PNI (AUC = 0.720, sensitivity 65.9%, specificity 74.50%, Youden index 0.399) and the LMR (AUC = 0.724, sensitivity 65.9%, specificity 70.0%, Youden index 0.395) both had good prognostic efficacy for patients with MIBC. The results of univariate and multivariate logistic regression analyses showed that preoperative PNI <44.15 was an independent risk factor for OS in patients with MIBC (p = 0.027). Based on K‒M survival curve analysis, patients with PNI <44.15 and LMR <2.98 had the shortest OS (p = 0.00002). CONCLUSIONS: Low preoperative PNI and LMR values are indicative of poor prognosis in patients with MIBC. The efficacy of their combination was better than that of the factors independently.

Fibrin Glue Coating Limits Scar Tissue Formation around Peripheral Nerves.

Scar tissue formation presents a significant barrier to peripheral nerve recovery in clinical practice. While different experimental methods have been described, there is no clinically available gold standard for its prevention. This study aims to determine the potential of fibrin glue (FG) to limit scarring around peripheral nerves. Thirty rats were divided into three groups: glutaraldehyde-induced sciatic nerve injury treated with FG (GA + FG), sciatic nerve injury with no treatment (GA), and no sciatic nerve injury (Sham). Neural regeneration was assessed with weekly measurements of the visual static sciatic index as a parameter for sciatic nerve function across a 12-week period. After 12 weeks, qualitative and quantitative histological analysis of scar tissue formation was performed. Furthermore, histomorphometric analysis and wet muscle weight analysis were performed after the postoperative observation period. The GA + FG group showed a faster functional recovery (6 versus 9 weeks) compared to the GA group. The FG-treated group showed significantly lower perineural scar tissue formation and significantly higher fiber density, myelin thickness, axon thickness, and myelinated fiber thickness than the GA group. A significantly higher wet muscle weight ratio of the tibialis anterior muscle was found in the GA + FG group compared to the GA group. Our results suggest that applying FG to injured nerves is a promising scar tissue prevention strategy associated with improved regeneration both at the microscopic and at the functional level. Our results can serve as a platform for innovation in the field of perineural regeneration with immense clinical potential.

The Effect of Cold-Water Swimming on Energy Metabolism, Dynamics, and Mitochondrial Biogenesis in the Muscles of Aging Rats.

Our study aimed to explore the potential positive effects of cold water exercise on mitochondrial biogenesis and muscle energy metabolism in aging rats. The study involved 32 male and 32 female rats aged 15 months, randomly assigned to control sedentary animals, animals training in cold water at 5 ± 2 °C, or animals training in water at thermal comfort temperature (36 ± 2 °C). The rats underwent swimming training for nine weeks, gradually increasing the duration of the sessions from 2 min to 4 min per day, five days a week. The results demonstrated that swimming in thermally comfortable water improved the energy metabolism of aging rat muscles (increased metabolic rates expressed as increased ATP, ADP concentration, TAN (total adenine nucleotide) and AEC (adenylate energy charge value)) and increased mRNA and protein expression of fusion regulatory proteins. Similarly, cold-water swimming improved muscle energy metabolism in aging rats, as shown by an increase in muscle energy metabolites and enhanced mitochondrial biogenesis and dynamics. It can be concluded that the additive effect of daily activity in cold water influenced both an increase in the rate of energy metabolism in the muscles of the studied animals and an intensification of mitochondrial biogenesis and dynamics (related to fusion and fragmentation processes). Daily activity in warm water also resulted in an increase in the rate of energy metabolism in muscles, but at the same time did not cause significant changes in mitochondrial dynamics.

Comparative Efficacy of Different Protein Supplements on Muscle Mass, Strength, and Physical Indices of Sarcopenia among Community-Dwelling, Hospitalized or Institutionalized Older Adults Undergoing Resistance Training: A Network Meta-Analysis of Randomized Controlled Trials.

Aging-related sarcopenia exerts harmful impacts on muscle mass, strength, and physical mobility. Protein supplementation has been demonstrated to augment efficacy of resistance training (RT) in elderly. This study compared the relative effects of different protein supplements on muscle mass, strength, and mobility outcomes in middle-aged and older individuals undergoing RT. A comprehensive search of online databases was performed to identify randomized controlled trials (RCTs) examining the efficacy of protein supplement plus RT in untrained community-dwelling adults, hospitalized, or institutionalized residents who suffered acute or chronic health conditions. Network meta-analysis (NMA) was performed using a frequentist method for all analyses. Treatment effects for main outcomes were expressed as standard mean difference (SMD) with 95% confidence interval (CI). We used the surface-under-the cumulative-ranking (SUCRA) scores to rank probabilities of effect estimation among all identified treatments. Meta-regression analyses were performed to identify any relevant moderator of the treatment efficacy and results were expressed as ß with 95% credible interval (CrI). We finally included 78 RCTs (5272 participants) for analyses. Among the six protein sources identified in this NMA, namely whey, milk, casein, meat, soy, and peanut, whey supplement yielded the most effective treatments augmenting efficacy of RT on muscle mass (SMD = 1.29, 95% CI: 0.96, 1.62; SUCRA = 0.86), handgrip strength (SMD = 1.46, 95% CI: 0.92, 2.00; SUCRA = 0.85), and walking speed (SMD = 0.73, 95% CI: 0.39, 1.07; SUCRA = 0.84). Participant's health condition, sex, and supplementation dose were significant factors moderating the treatment efficacy on muscle mass (ß = 0.74; 95% CrI: 0.22, 1.25), handgrip strength (ß = -1.72; 95% CrI: -2.68, -0.77), and leg strength (ß = 0.76; 95% CrI: 0.06, 1.47), respectively. Our findings suggest whey protein yields the optimal supplements to counter sarcopenia in older individuals undergoing RT.

State-dependent binding of cholesterol and an anionic lipid to the muscle-type Torpedo nicotinic acetylcholine receptor.

The ability of the Torpedo nicotinic acetylcholine receptor (nAChR) to undergo agonist-induced conformational transitions requires the presence of cholesterol and/or anionic lipids. Here we use recently solved structures along with multiscale molecular dynamics simulations to examine lipid binding to the nAChR in bilayers that have defined effects on nAChR function. We examine how phosphatidic acid and cholesterol, lipids that support conformational transitions, individually compete for binding with phosphatidylcholine, a lipid that does not. We also examine how the two lipids work synergistically to stabilize an agonist-responsive nAChR. We identify rapidly exchanging lipid binding sites, including both phospholipid sites with a high affinity for phosphatidic acid and promiscuous cholesterol binding sites in the grooves between adjacent transmembrane α-helices. A high affinity cholesterol site is confirmed in the inner leaflet framed by a key tryptophan residue on the MX α-helix. Our data provide insight into the dynamic nature of lipid-nAChR interactions and set the stage for a detailed understanding of the mechanisms by which lipids facilitate nAChR function at the neuromuscular junction.