Muscle Resistance Research Articles

TLR13 contributes to skeletal muscle atrophy by increasing insulin resistance in chronic kidney disease.

ObjectivesInsulin resistance in chronic kidney disease (CKD) stimulates muscle wasting, but the molecular processes behind the resistance are undetermined. However, inflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia. Toll‐like receptors (TLRs) are known to regulate local innate immune responses, and microarray data have shown that Tlr13 is upregulated in the muscles of mice with CKD, but the relevance is unknown.Materials and MethodsWe performed in vitro experiments in C2C12 myotubes and constructed a CKD murine model using subtotal nephrectomy to conduct experiments in vivo.Results Tlr13 expression was stimulated in C2C12 myotubes treated with uremic serum. The expression of Tlr13 was also upregulated in the tibialis anterior muscles of mice with CKD. Tlr13 knockdown with siRNAs in skeletal muscle cells decreased insulin resistance despite the inclusion of uremic serum. This led to increased levels of p‐AKT and suppression of protein degradation. Using immunofluorescence staining and coimmunoprecipitation assay, we found that TLR13 recruits IRF3, which activates Irf3 expression, resulting in decreased AKT activity. Moreover, insulin resistance and proteolysis are re‐induced by Irf3 overexpression under Tlr13 deletion.ConclusionsOur results indicate that TLR13 is involved in CKD‐mediated insulin resistance in muscle. In catabolic conditions where insulin signaling is impaired, targeting TLR13 may improve insulin sensitivity and prevent muscle atrophy.

The acute effects of different hamstring muscle stretching techniques on reducing muscle resistance to movement by ultrasound elastography

ObjectiveMany stretching methods are applied on the hamstring muscles for reducing muscle resistance on movement. The aim of our study to investigate the acute effects of static stretching and the Mulligan traction straight leg raise (TSLR) technique administered to the hamstring muscles on reducing its resistance to movement. MethodsThe study included 22 healthy male volunteers (19.5 ± 0.98 years). After the individuals were randomly divided into two groups, static stretching was administered to the hamstring muscles in the first group and the Mulligan TSLR technique was administered on the same muscle in the second group. Active knee extension angles of the individuals were evaluated by a digital goniometer and muscle strain was assessed by ultrasound elastography. ResultsWhile there was a significant difference in all parameters in both groups after the treatment, the changes in the active knee extension angle and the strain index value of the biceps femoris musculotendinous junction were higher in the Mulligan TSLR group compared to the static stretching group (p < 0.05). ConclusionIt was concluded that, static stretching and the Mulligan TSLR technique administered to the hamstring muscles are effective ways to increase the range of motion. The Mulligan TSLR technique, however, can be opted in healthy individuals and patients since it is painless and more effective in reducing muscle resistance to movement and range of motion.

CRISPR/Cas9 editing of directly reprogrammed myogenic progenitors restores dystrophin expression in a mouse model of muscular dystrophy.

SummaryGenetic mutations in dystrophin manifest in Duchenne muscular dystrophy (DMD), the most commonly inherited muscle disease. Here, we report on reprogramming of fibroblasts from two DMD mouse models into induced myogenic progenitor cells (iMPCs) by MyoD overexpression in concert with small molecule treatment. DMD iMPCs proliferate extensively, while expressing myogenic stem cell markers including Pax7 and Myf5. Additionally, DMD iMPCs readily give rise to multinucleated myofibers that express mature skeletal muscle markers; however, they lack DYSTROPHIN expression. Utilizing an exon skipping-based approach with CRISPR/Cas9, we report on genetic correction of the dystrophin mutation in DMD iMPCs and restoration of protein expression in vitro. Furthermore, engraftment of corrected DMD iMPCs into the muscles of dystrophic mice restored DYSTROPHIN expression and contributed to the muscle stem cell reservoir. Collectively, our findings report on a novel in vitro cellular model for DMD and utilize it in conjunction with gene editing to restore DYSTROPHIN expression in vivo.

Diverse myopathological features in the congenital myasthenia syndrome with GFPT1 mutation.

IntroductionMutations in the GFPT1 gene are associated with a particular subtype of congenital myasthenia syndrome (CMS) called limb‐girdle myasthenia with tubular aggregates. However, not all patients show tubular aggregates in muscle biopsy, suggesting the diversity of myopathology should be further investigated.MethodsIn this study, we reported two unrelated patients clinically characterized by easy fatigability, limb‐girdle muscle weakness, positive decrements of repetitive stimulation, and response to pyridostigmine. The routine examinations of myopathology were conducted. The causative gene was explored by whole‐exome screening. In addition, we summarized all GFPT1‐related CMS patients with muscle biopsy in the literature.ResultsPathogenic biallelic GFPT1 mutations were identified in the two patients. In patient one, muscle biopsy indicated vacuolar myopathic changes and atypical pathological changes of myofibrillar myopathy characterized by desmin deposits, Z‐disc disorganization, and electronic dense granulofilamentous aggregation. In patient two, muscle biopsy showed typical myopathy with tubular aggregates. Among the 51 reported GFPT1‐related CMS patients with muscle biopsy, most of them showed tubular aggregates myopathy, while rimmed vacuolar myopathy, autophagic vacuolar myopathy, mitochondria‐like myopathy, neurogenic myopathy, and unspecific myopathic changes were also observed in some patients. These extra‐synaptic pathological changes might be associated with GFPT1‐deficiency hypoglycosylation and altered function of muscle‐specific glycoproteins, as well as partly responsible for the permanent muscle weakness and resistance to acetylcholinesterase inhibitor therapy.ConclusionsMost patients with GFPT1‐related CMS had tubular aggregates in the muscle biopsy, but some patients could show great diversities of the pathological change. The myopathological findings might be a biomarker to predict the prognosis of the disease.

Alteração postural, dor lombar e a resistência dos músculos do tronco em jovens universitárias

Abstract Introduction: Low back pain, the most prevalent musculoskeletal disorder, is common in individuals with postural changes and has a high incidence in university students. Trunk muscle instability and weakness can contribute to the presence of low back pain. However, no research has investigated the relationship between low back pain in conjunction with postural changes and the resistance of the trunk stabilizing muscles. Objective: To analyze the correlation between postural alterations and muscular resistance of the trunk of women with and without low back pain. Methods: Forty university women were recruited and divided into a group with low back pain (n = 20; 20.85 ± 1.69 years) and a group without low back pain (n = 20; 20.05 ± 2.54 years). On the first day, the postural assessment was carried out by photogrammetry with Kinovea software. On the second day, the resistance tests of the trunk flexor and extensor muscles, lateral and ventral plank, bridge, and lumbar traction were performed through the traction dynamometer. Pearson's correlation test was applied to verify the relationship between the analyzed variables, Student's T test was used for comparison between groups, and a significance level of p &lt; 0.05 was adopted. Results: There was no correlation between the variables related to postural changes and muscle resistance tests (p &gt; 0.05). There was a difference between the groups only for the bridge exercise test (p = 0.04) and vertical alignment of the head, left lateral view (p = 0.041), and right lateral view (p = 0.034). Conclusion: This study did not show a direct and significant relationship between postural changes in young university students with and without complaints of low back pain and resistance of the trunk-stabilizing muscles.

Implication of the hepatokine, fibrinogen-like protein 1 in liver diseases, metabolic disorders and cancer: The need to harness its full potential.

Fibrinogen-like protein 1 (FGL1) is a novel hepatokine that forms part of the fibrinogen superfamily. It is predominantly expressed in the liver under normal physiological conditions. When the liver is injured by external factors, such as chemical drugs and radiation, FGL1 acts as a protective factor to promote the growth of regenerated cells. However, elevated hepatic FGL1 under high fat conditions can cause lipid accumulation and inflammation, which in turn trigger the development of non-alcoholic fatty liver disease, diabetes, and obesity. FGL1 is also involved in the regulation of insulin resistance in adipose tissues and skeletal muscles as a means of communication between the liver and other tissues. In addition, the abnormally changed FGL1 levels in the plasma of cancer patients make it a potential predictor of cancer incidence in clinical practice. FGL1 was recently identified as a major functional ligand of the immune inhibitory receptor, lymphocyte-activation gene 3 (LAG3), thus making it a promising target for cancer immunotherapy except for the classical programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) axis. Despite the potential of FGL1 as a new cancer biomarker and therapeutic target, there are few related studies and much of what has been reported are superficial and lack depth and particularity. Therefore, elucidating the role and underlying mechanisms of FGL1 could be crucial for the development of promising diagnostic and therapeutic strategies for related diseases. Here, we provide a comprehensive review of the cellular mechanisms and clinical prospects of FGL1 in the prevention and treatment of liver diseases, metabolic disorders and cancer, and proffer suggestions for future studies.

The quality of handling and extended the shelf life and preservation of lagoon mullets fish (Mugil cephalus)

The deterioration of fish by microorganisms is very quickly, because it’s a highly perishable foods and short shelf life, for this reason the handling and stored condition very important to slow down and extend the shelf life and its quality. There are a number of strategies used as traditional methods to extend the shelf life of fishes included: chilling, freezing, icing, drying, smoking and salting. From the innovative processing technologies using of icing system with organic acids is considered to be a preservative method and delaying the changing in the fish and able to guarantee the quality with extension of their shelf-life. The present study provides the addition of organic acid as lactic acid (0.1%), propylene glycol (7%), potassium sorbate (1000 ppm) and mixture of potassium sorbate (1000 ppm) + sodium benzoate (0.2%) to fresh water and dipping the mullet fish in it then preserved in fresh water crushed ice medium containing the same concentration of organic acids. Different parameters were determined to limit the quality and safety of mullet during storage periods as total volatile nitrogen base, trimethylamine, thiobarbituric acid-value, refractive index of the muscle fluids, electrical resistance of the fish muscles, organoleptic evaluations and in addition to total viable count of bacteria and psychrophilic bacteria. The mixture of potassium sorbate and sodium benzoate using icing system method extended the shelf life of mullet fish up to 17-19 days of storage period in comparison with control and other organic acids.

The Correlation between Gross Motor Function Classification System and Spasticity in Children with Cerebral Palsy

Gross Motor Function Classification System (GMFCS) was used as a criterion to classify motor function in children with cerebral palsy. Spasticity is an increase in muscle resistance to passive stretching, which is an involuntary muscle activity associated with upper motor neuron paralysis that occurs in CP children so that it interferes with their activities. The purpose of this study was to determine the relationship between GMFCS and the level of spasticity assessed by the Ashworth scale in children with cerebral palsy. The analytical research method was observational with a cross sectional approach, the independent variable was assessed on the functional scale using the GMFCS and the dependent variable was assessed for spasticity using the Ashworth scale. The research sample was CP children at YPAC Semarang city. The results of this study are that the highest GMFCS level in children with cerebral palsy at SLB YPAC Semarang City is level III and IV as much as 25.0% while the assessment of spasticity using the ashworth scale obtained ashworth level 3 as much as 58.3% while the results of the calculation of the non-parametric Spearman correlation test were obtained. p value = 0.000 (p &lt; 0.05) with a value of r = 0.837. Therefore, it can be concluded that there is a positive correlation between GMFCS and the level of spasticity assessed using the Ashworth scale in children with cerebral palsy.

Spexin ameliorates skeletal muscle insulin resistance through activation of GAL2 receptor

Skeletal muscle is a principal tissue involved in energy expenditure and glucose metabolism. Although the results of our and other studies show that spexin could decrease food intake and obesity, the specific metabolic effect of spexin on glucose metabolism of skeletal muscle is still unclear. The aim of this study is to investigate whether spexin might mitigate obesity-induced insulin resistance in skeletal muscles and to explore its underlying mechanisms. The high fat diet-fed mice were treated with 50 μg/kg/d spexin for 21 consecutive days, and the differentiated myotubes of L6 were treated with spexin (200, 400, 800 nM) in the absence or presence of M871 (800 nM) for 12 h respectively. Besides, the galanin type 2 (GAL2) receptor knockdown myotubes were treated with 800 nM spexin for 12 h in this study. The present findings showed that spexin reversed hyperglycemia and glucose intolerance as well as insulin intolerance and insulin resistance in the mice fed with high fat diet. Furthermore, spexin markedly augmented the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) expression and deacetylation, and further triggered glucose transporter 4 (GLUT4) expression and trafficking in myotubes through p38 mitogen-activated protein kinase (P38MAPK) and protein kinase B (AKT) activation. More importantly, the elevation of glucose consumption related genes by spexin were abolished by GAL2 receptor antagonist or silencing of GAL2 receptor in myotubes. In conclusion, our findings provide a novel insight that spexin can protect against insulin resistance and increase glucose consumption in skeletal muscles mainly through activation of GAL2/GLUT4 signal pathway. Spexin might therefore be a novel therapeutic target for hyperglycemia and insulin resistance in clinic.

Stevioside Attenuates Insulin Resistance in Skeletal Muscle by Facilitating IR/IRS-1/Akt/GLUT 4 Signaling Pathways: An In Vivo and In Silico Approach.

Type-2 diabetes mellitus (T2DM), the leading global health burden of this century majorly develops due to obesity and hyperglycemia-induced oxidative stress in skeletal muscles. Hence, developing novel drugs that ameliorate these pathological events is an immediate priority. The study was designed to analyze the possible role of Stevioside, a characteristic sugar from leaves of Stevia rebaudiana (Bertoni) on insulin signaling molecules in gastrocnemius muscle of obesity and hyperglycemia-induced T2DM rats. Adult male Wistar rats rendered diabetic by administration of high fat diet (HFD) and sucrose for 60 days were orally administered with SIT (20 mg/kg/day) for 45 days. Various parameters were estimated including fasting blood glucose (FBG), serum lipid profile, oxidative stress markers, antioxidant enzymes and expression of insulin signaling molecules in diabetic gastrocnemius muscle. Stevioside treatment improved glucose and insulin tolerances in diabetic rats and restored their elevated levels of FBG, serum insulin and lipid profile to normalcy. In diabetic gastrocnemius muscles, Setvioside normalized the altered levels of lipid peroxidase (LPO), hydrogen peroxide (H2O2) and hydroxyl radical (OH*), antioxidant enzymes (CAT, SOD, GPx and GSH) and molecules of insulin signaling including insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and Akt mRNA levels. Furthermore, Stevioside enhanced glucose uptake (GU) and oxidation in diabetic muscles by augmenting glucose transporter 4 (GLUT 4) synthesis very effectively in a similar way to metformin. Results of molecular docking analysis evidenced the higher binding affinity with IRS-1 and GLUT 4. Stevioside effectively inhibits oxidative stress and promotes glucose uptake in diabetic gastrocnemius muscles by activating IR/IRS-1/Akt/GLUT 4 pathway. The results of the in silico investigation matched those of the in vivo study. Hence, Stevioside could be considered as a promising phytomedicine to treat T2DM.

Physical activity program using active video games with sedentary adolescents

Objective: the aim of our study was to assess the effect of a physical activity that uses active video games in body composition, physical fitness, cardiovascular and biochemical parameters with sedentary adolescents. Methods: a non-controlled clinical trial design with a convenience sample of adolescents, separately, from ages ten to 17, of both genders. The intervention protocol consisted of physical activity with active video games (AVG), lasting two months, in 24 sessions, evolving into three levels (basic, intermediate and advanced) according to the maximum heart rate of the individuals. The adolescents’ body composition, physical fitness, cardiovascular and biochemical parameters were assessed. Data analysis was performed with a 95% confidence interval. Results: among the 14 adolescents that completed the physical training, we observed a improvement of muscle resistance (Δ= 8.26; p= 0.02) and decrease in post-exercise heart rate and systolic blood pressure (p&lt; 0.01). However, were found a non-significant decrease in body fat percentage (Δ= -3.83; p= 0.24) and strength (Δ= 4.26; p= 0.57). A high level of satisfaction with the proposed activity was identified. Conclusion: a physical activity program based on AVG can reduce cardiovascular risk factors and improve muscle resistance in sedentary adolescents.

Human and mouse muscle transcriptomic analyses identify insulin receptor mRNA downregulation in hyperinsulinemia-associated insulin resistance.

Hyperinsulinemia is commonly viewed as a compensatory response to insulin resistance, yet studies have demonstrated that chronically elevated insulin may also drive insulin resistance. The molecular mechanisms underpinning this potentially cyclic process remain poorly defined, especially on a transcriptome‐wide level. Transcriptomic meta‐analysis in >450 human samples demonstrated that fasting insulin reliably and negatively correlated with INSR mRNA in skeletal muscle. To establish causality and study the direct effects of prolonged exposure to excess insulin in muscle cells, we incubated C2C12 myotubes with elevated insulin for 16 h, followed by 6 h of serum starvation, and established that acute AKT and ERK signaling were attenuated in this model of in vitro hyperinsulinemia. Global RNA‐sequencing of cells both before and after nutrient withdrawal highlighted genes in the insulin receptor (INSR) signaling, FOXO signaling, and glucose metabolism pathways indicative of ‘hyperinsulinemia’ and ‘starvation’ programs. Consistently, we observed that hyperinsulinemia led to a substantial reduction in Insr gene expression, and subsequently a reduced surface INSR and total INSR protein, both in vitro and in vivo. Bioinformatic modeling combined with RNAi identified SIN3A as a negative regulator of Insr mRNA (and JUND, MAX, and MXI as positive regulators of Irs2 mRNA). Together, our analysis identifies mechanisms which may explain the cyclic processes underlying hyperinsulinemia‐induced insulin resistance in muscle, a process directly relevant to the etiology and disease progression of type 2 diabetes.

Reversible insulin resistance in muscle and fat unrelated to the metabolic syndrome in patients with acromegaly.

SummaryBackgroundPatients with active acromegaly exhibit insulin resistance despite a lean phenotype whereas controlled disease improves insulin sensitivity and increases fat mass. The mechanisms underlying this paradox remain elusive, but growth hormone (GH)-induced lipolysis plays a central role. The aim of the study was to investigative the molecular mechanisms of insulin resistance dissociated from obesity in patients with acromegaly.MethodsIn a prospective study, twenty-one patients with newly diagnosed acromegaly were studied at diagnosis and after disease control obtained by either surgery alone (n=10) or somatostatin analogue (SA) treatment (n=11) with assessment of body composition (DXA scan), whole body and tissue-specific insulin sensitivity and GH and insulin signalling in adipose tissue and skeletal muscle.FindingsDisease control of acromegaly significantly reduced lean body mass (p<0.001) and increased fat mass (p<0.001). At diagnosis, GH signalling (pSTAT5) was constitutively activated in fat and enhanced expression of GH-regulated genes (CISH and IGF-I) were detected in muscle and fat. Insulin sensitivity in skeletal muscle, liver and adipose tissue increased after disease control regardless of treatment modality. This was associated with enhanced insulin signalling in both muscle and fat including downregulation of phosphatase and tensin homolog (PTEN) together with reduced signalling of GH and lipolytic activators in fat.InterpretationIn conclusion, the study support that uncontrolled lipolysis is a major feature of insulin resistance in active acromegaly, and is characterized by upregulation of PTEN and suppression of insulin signalling in both muscle and fat.FundingThis work was supported by a grant from the Independent Research Fund, Denmark (7016-00303A) and from the Alfred Benzon Foundation, Denmark.

BLOOD GLUCOSE TEST FOR DM TYPE 2

Indonesia is one of the countries with a high prevalence of diabetes, with total cases of diabetes in adults reaching 10 million cases, 6.2% of the total adult population. Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia due to defects in insulin secretion, insulin action, or both. Insulin resistance in muscle and liver cells and pancreatic beta-cell failure has been recognized as the pathophysiology of major damage of type 2 diabetes. The blood glucose test is an important laboratory examination that can be used to diagnose, screen, and monitor DM type 2. There are several types of blood glucose levels, including random blood glucose tests, fasting blood glucose tests, post prandial blood glucose tests, oral Glucose Tolerance Test (OGTT), and HbA1c. Type 2 DM is often called the silent killer because sufferers are often late for self-examination and treatment so that complications arise early. Early symptoms of type 2 diabetes can be identified through blood sugar examination and risk factor screening. Screening for type 2 DM can detect abnormalities as early as possible so that interventions can start as early as possible to minimize the complication rate so that the quality of life can be maintained or better.

Experimental and finite element analysis studies of a reduction-force reducing traction method for pelvic fracture surgeries

Pelvic fracture is among the most complicated fractures in traumatic orthopedics, with high mortality and morbidity rates. The main difficulty associated with the reduction surgery is significant muscle resistance. It then becomes necessary to decrease the reduction force against this strong muscle resistance, for improving surgical safety. Here, we propose a novel traction method for decreasing the reduction force during pelvic reduction, and investigate the performance of the elastic traction method on decreasing the reduction force using experimental tests and simulation-based analyses. From the experimental results, the reduction force decreased by 59.2% when 10 ​kg of elastic traction was applied. We also establish a musculoskeletal model of the pelvic fracture reduction, for analyzing the muscle resistance and the optimal traction force applied in reduction surgeries. The elastic traction method can counteract the muscle resistance increase in the non-traction direction owing to its flexibility. We conclude that the optimal traction force applied should be in the 10–15 ​kg range, and recommend adopting a dynamic traction strategy rather than continuous traction in clinical settings. Elastic traction is very promising for various surgeries that require traction, including pelvic reduction. It significantly reduces force, which can significantly reduce the physical exertion of the operating surgeon, the possibility of additional injuries to the operated patient, and promotes robot-assisted reduction surgeries.

Polygonatum sibiricum polysaccharides (PSP) improve the palmitic acid (PA)-induced inhibition of survival, inflammation, and glucose uptake in skeletal muscle cells

ABSTRACT Polygonatum sibiricum polysaccharides (PSP) can decrease the levels of fasting blood glucose, total cholesterol, and triglyceride (TG) in hyperlipidemic and diabetic animals. It can also reduce inflammatory cytokines and promote glucose uptake in adipocytes. However, the underlying molecular mechanisms of PSP in improving insulin resistance (IR) in skeletal muscle remain unclear. In this study, palmitic acid (PA) induced an IR model in L6 myotubes. After treatment, cell proliferation was measured using the CCK8. miR-340-3p, glucose transporter 4 (GLUT-4), and interleukin-1 receptor-associated kinase 3 (IRAK3) expression was measured by qRT-PCR. IRAK3 protein levels were measured by Western blotting. Glucose in the cell supernatant, TG concentration in L6 myotubes, and the levels of IL-1β, IL-6, and TNF-α were measured by an ELISA. We found that cell survival, glucose uptake, and GLUT-4 expression in L6 myotubes were significantly suppressed, while lipid accumulation and inflammatory factor levels were enhanced by PA stimulation. Furthermore, PSP treatment markedly alleviated these effects. Interestingly, PSP also significantly reduced the upregulated expression of miR-340-3p in the L6 myotube model of IR. Furthermore, overexpression of miR-340-3p reversed the beneficial effects of PSP in the same IR model. miR-340-3p can bind to the 3′-untranslated regions of IRAK3. Additionally, PA treatment inhibited IRAK3 expression, whereas PSP treatment enhanced IRAK3 expression in L6 myotubes. Additionally, miR-340-3p also inhibited IRAK3 expression in L6 myotubes. Taken together, PSP improved inflammation and glucose uptake in PA-treated L6 myotubes by regulating miR-340-3p/IRAK3, suggesting that PSP may be suitable as a novel therapeutic agent for IR.

Smart Drain for Post–Cardiac Surgery Left Ventricular Volumes Evaluated in Large Animal Models

BackgroundOpen heart surgeries for coronary arterial bypass graft and valve replacements are performed on 400,000 Americans each year. Unexplained hypotension during recovery causes morbidity and mortality through cerebral, kidney, and coronary hypoperfusion. An early detection method that distinguishes between hypovolemia and decreased myocardial function before onset of hypotension is desirable. We hypothesized that admittance measured from a modified pericardial drain can detect changes in left ventricular end-systolic, end-diastolic, and stroke volumes. MethodsAdmittance was measured from 2 modified pericardial drains placed in 7 adult female dogs using an open chest preparation, each with 8 electrodes. The resistive and capacitive components of the measured admittance signal were used to distinguish blood and muscle components. Admittance measurements were taken from 12 electrode configurations in each experiment. Left ventricular preload was reduced by inferior vena cava occlusion. Physiologic response to vena cava occlusion was measured by aortic pressure, aortic flow, left ventricle diameter, left ventricular wall thickness, and electrocardiogram. ResultsAdmittance successfully detected a drop in left ventricular end-diastolic volume (P < .001), end-systolic volume (P < .001), and stroke volume (P < .001). Measured left ventricular muscle resistance correlated with crystal-derived left ventricular wall thickness (R2 = 0.96), validating the method’s ability to distinguish blood from muscle components. ConclusionsAdmittance measured from chest tubes can detect changes in left ventricular end-systolic, end-diastolic, and stroke volumes and may therefore have diagnostic value for unexplained hypotension.

The Association between Trajectories of Anthropometric Variables and Risk of Diabetes among Prediabetic Chinese.

In order to explore the association between trajectories of body mass index (BMI) and mid-upper arm circumference (MUAC) and diabetes and to assess the effectiveness of the models to predict diabetes among Chinese prediabetic people, we conducted this study. Using a national longitudinal study, 1529 cases were involved for analyzing the association between diabetes and BMI trajectories or MUAC trajectories. Growth mixture modeling was conducted among the prediabetic Chinese population to explore the trajectories of BMI and MUAC, and logistic regression was applied to evaluate the association between these trajectories and the risk of diabetes. The receiver operating characteristic curve (ROC) and the area under the curve (AUC) were applied to assess the feasibility of prediction. BMI and MUAC were categorized into 4-class trajectories, respectively. Statistically significant associations were observed between diabetes in certain BMI and MUAC trajectories. The AUC for trajectories of BMI and MUAC to predict diabetes was 0.752 (95% CI: 0.690–0.814). A simple cross-validation using logistic regression indicated an acceptable efficiency of the prediction. Diabetes prevention programs should emphasize the significance of body weight control and maintaining skeletal muscle mass and resistance training should be recommended for prediabetes.

Isometric training improves fatigue resistance in dystrophin-deficient muscle

Eccentric contractions, in which the muscle is stretched during contraction, cause substantially greater damage than isometric (ISO) contractions, in which the length of the muscle does not change during contraction. Here, we tested the hypothesis that ISO training improves fatigue resistance in skeletal muscle from dystrophin-deficient mdx52 mice (15-22 wk old). ISO training (100 Hz stimulation frequency, 0.25-s contractions every 0.5 s, 6 sets of 60 contractions) was performed on the left plantar flexor muscles in vivo with supramaximal electrical stimulation every other day for 4 wk. Compared with the normal control muscle, resistance to fatigue was reduced in the nontrained muscle from mdx52 mice, which was accompanied by a reduction in citrate synthase activity and the LC3BII/I ratio and an increase in the phosphorylation levels of Akt Ser473 and the expression levels of p62. ISO training restored these alterations and markedly increased in vivo fatigue resistance and PGC-1α expression in mdx52 muscles. Moreover, an increased number of Evans Blue dye-positive fibers was significantly reduced by ISO training in mdx52 muscles. In contrast, ISO training did not restore a reduction in the amount of SH3 and cysteine-rich domain 3 in mdx muscles. Thus, our data suggest that mitochondrial function is impaired in dystrophin-deficient muscles, which is likely to be induced by the defective autophagy due to persistent activation of Akt. ISO training inhibits the aberrant activation of Akt presumably by up-regulating the PGC-1α expression, which results in improved mitochondrial function and thus fatigue resistance in dystrophin-deficient muscles.

Possible mechanisms underlying the dynamic assembly of calcium entry units: The role of temperature and pH

Skeletal muscle function is regulated by intracellular Ca2+ levels. Two main mechanisms control movements of Ca2+ ions from intracellular stores (i.e., the sarcoplasmic reticulum; SR) and from extracellular space: (1) excitation-contraction (EC) coupling and (2) store-operated Ca2+ entry (SOCE). SOCE allows recovery of extracellular Ca2+ during prolonged muscle activity, when the SR undergoes depletion. We recently discovered that prolonged exercise leads to formation of calcium entry units (CEUs), intracellular junctions located at the I band that are formed by two distinct elements: SR stacks and transverse tubules (TTs). Assembly of CEUs during exercise promotes the interaction between STIM1 and Orai1, the two main proteins that mediate SOCE, and increases muscle resistance to fatigue in the presence of extracellular Ca2+. The molecular mechanisms underlying the exercise-dependent remodeling of SR and TT leading to CEU assembly remain to be fully elucidated. Here, we first verified whether CEUs can assemble ex vivo (in the absence of blood supply and innervation), subjecting excised EDL muscles from mice to an ex vivo incremental fatigue protocol (80 Hz tetanus stimulation lasting 45 min): the data collected demonstrate that CEUs can assemble ex vivo in isolated EDL muscles. We then evaluated if intracellular parameters that are affected by exercise, such as temperature and pH, may influence the assembly of CEUs. We found that higher temperature (36°C versus 25°C) and lower pH (7.2 versus 7.4) promotes formation of CEUs increasing the percentage of fibers containing SR stacks, the number of SR stacks/area, and the elongation of TTs at the I band. Importantly, increased assembly of CEUs at higher temperature (36°C) or at lower pH (7.2) correlated with increased fatigue resistance of EDL muscles in the presence of extracellular Ca2+, suggesting that CEUs assembled ex vivo are functional.