ResearchPad - muscles https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Relationship between maximal incremental and high-intensity interval exercise performance in elite athletes]]> https://www.researchpad.co/article/elastic_article_13822 This descriptive study aimed to explore the physiological factors that determine tolerance to exertion during high-intensity interval effort. Forty-seven young women (15–28 years old) were enrolled: 23 athletes from Taiwan national or national reserve teams and 24 moderately active females. Each participant underwent a maximal incremental INC (modified Bruce protocol) cardiopulmonary exercise test on the first day and high-intensity interval testing (HIIT) on the second day, both performed on a treadmill. The HIIT protocol involved alternation between 1-min effort at 120% of the maximal speed, at the same slope reached at the end of the INC, and 1-min rest until volitional exhaustion. Gas exchange, heart rate (HR), and muscle oxygenation at the right vastus lateralis, measured by near-infrared spectroscopy, were continuously recorded. The number of repetitions completed (Rlim) by each participant was considered the HIIT tolerance index. The results showed a large difference in the Rlim (range, 2.6–12.0 repetitions) among the participants. Stepwise linear regression revealed that the variance in the Rlim within the cohort was related to the recovery rates of oxygen consumption (V˙O2), HR at the second minute after INC, and muscle tissue saturation index at exhaustion (R = 0.644). In addition, age was linearly correlated with Rlim (adjusted R = −0.518, p < 0.0001). In conclusion, the recovery rates for V˙O2 and HR after the incremental test, and muscle saturation index at exhaustion, were the major physiological factors related to HIIT performance. These findings provide insights into the role of the recovery phase after maximal INC exercise testing. Future research investigating a combination of INC and HIIT testing to determine training-induced performance improvement is warranted.

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<![CDATA[Falls Risk in Relation to Activity Exposure in High-Risk Older Adults]]> https://www.researchpad.co/article/elastic_article_10135 Physical activity is linked to many positive health outcomes, stimulating the development of exercise programs. However, many falls occur while walking and so promoting activity might paradoxically increase fall rates, causing injuries, and worse quality of life. The relationship between activity exposure and fall rates remains unclear. We investigated the relationship between walking activity (exposure to risk) and fall rates before and after an exercise program (V-TIME).MethodsOne hundred and nine older fallers, 38 fallers with mild cognitive impairment (MCI), and 128 fallers with Parkinson’s disease (PD) were randomly assigned to one of two active interventions: treadmill training only or treadmill training combined with a virtual reality component. Participants were tested before and after the interventions. Free-living walking activity was characterized by volume, pattern, and variability of ambulatory bouts using an accelerometer positioned on the lower back for 1 week. To evaluate that relationship between fall risk and activity, a normalized index was determined expressing fall rates relative to activity exposure (FRA index), with higher scores indicating a higher risk of falls per steps taken.ResultsAt baseline, the FRA index was higher for fallers with PD compared to those with MCI and older fallers. Walking activity did not change after the intervention for the groups but the FRA index decreased significantly for all groups (p ≤ .035).ConclusionsThis work showed that V-TIME interventions reduced falls risk without concurrent change in walking activity. We recommend using the FRA index in future fall prevention studies to better understand the nature of intervention programs. ]]> <![CDATA[Unraveling the Association Between Gait and Mortality—One Step at a Time]]> https://www.researchpad.co/article/elastic_article_10129 Slowness of walking is one of the very first signs of aging and is considered a marker for overall health that is strongly associated with mortality risk. In this study, we sought to disentangle the clinical drivers of the association between gait and mortality.MethodsWe included 4,490 participants of the Rotterdam Study who underwent a gait assessment between 2009 and 2015 and were followed-up for mortality until 2018. Gait was assessed with an electronic walkway and summarized into the domains Rhythm, Phases, Variability, Pace, Tandem, Turning, and Base of Support. Cox models adjusted for age, sex, and height were built and consecutively adjusted for six categories of health indicators (lifestyle, musculoskeletal, cardiovascular, pulmonary, metabolic, and neurological). Analyses were repeated in comorbidity-free individuals.ResultsMultiple gait domains were associated with an increased risk of mortality, including Pace (hazard ratio (HR) per SD worse gait, adjusted for other domains: 1.34 [1.19–1.50]), Rhythm (HR: 1.12 [1.02–1.23]) and Phases (HR: 1.12 [1.03–1.21]). Similarly, a 0.1 m/s decrease in gait speed was associated with a 1.21 (1.15–1.27) times higher hazard of mortality (HR fully adjusted: 1.14 [1.08–1.20]). In a comorbidity-free subsample, the HR per 0.1 m/s decrease in gait speed was 1.25 (1.09–1.44). Cause-specific mortality analyses revealed an association between gait speed and multiple causes of death.ConclusionsSeveral gait domains were associated with mortality risk, including Pace which primarily represents gait speed. The association between gait speed and mortality persisted after an extensive adjustment for covariates, suggesting that gait is a marker for overall health. ]]> <![CDATA[Uncontrolled Diabetes as an Associated Factor with Dynapenia in Adults Aged 50 Years or Older: Sex Differences]]> https://www.researchpad.co/article/elastic_article_10127 Epidemiological studies demonstrate an association between diabetes and low neuromuscular strength (NMS). However, none have grouped participants into nondiabetics (ND), undiagnosed diabetics (UDD), controlled diabetics (CD), and uncontrolled diabetics (UCD) or investigated what glycated hemoglobin levels (HbA1c) are associated with low NMS (dynapenia) by sex.MethodsWe analyzed the association between UDD, CD, and UCD and dynapenia, the extent to which the different groupings of these individuals modifies this association and the association between HbA1c levels and NMS, by sex, in a cross-sectional study involving 5,290 participants ≥50 years from the ELSA study. In the first two analyses, logistic regression models were used with dynapenia (grip strength <26 kg in men and <16 kg in women) as outcome and diabetes (ND, UDD, CD, and UCD) as exposure. Next, linear regression was performed with grip strength as the outcome, and the participants were classified based on HbA1c level as exposure. The models were adjusted by sociodemographic, behavioral, and clinical characteristics.ResultsCompared to ND, only UCD was associated with dynapenia (men OR = 2.37 95% CI 1.36–4.14; women OR = 1.67 95% CI 1.01–2.79). This association was less clear, particularly in women, when CD and UCD groups were merged. HbA1c ≥6.5% in men and ≥8.0% in women were associated with lower NMS.ConclusionsUCD increases the chance of dynapenia in both sexes. The different groupings based on diabetes status modify the association between UCD and dynapenia. The threshold of HbA1c associated with reduced NMS is lower in men compared to women. ]]> <![CDATA[Is postural dysfunction related to sarcopenia? A population-based study]]> https://www.researchpad.co/article/elastic_article_7695 Postural dysfunction is one of the most common community health symptoms and frequent chief complaints in hospitals. Sarcopenia is a syndrome characterized by degenerative loss of skeletal muscle mass, muscle quality, and muscle strength, and is the main contributor to musculoskeletal impairment in the elderly. Previous studies reported that loss of muscle mass is associated with a loss of diverse functional abilities. Meanwhile, there have been limited studies concerning postural dysfunction among older adults with sarcopenia. Although sarcopenia is primarily a disease of the elderly, its development may be associated with conditions that are not exclusively seen in older persons. Also, recent studies recognize that sarcopenia may begin to develop earlier in life. The objective of this paper was to investigate the association between the prevalence of sarcopenia and postural dysfunction in a wide age range of adults using data from a nationally representative cohort study in Korea. Korean National Health & Nutrition Exhibition Survey V (KNHANES V, 2010–2012) data from the fifth cross-sectional survey of the South Korean population performed by the Korean Ministry of Health and Welfare were used. Appendicular skeletal muscle mass (ASM)/height (ht)2 was used to define sarcopenia, and the Modified Romberg test using a foam pad (“foam balance test”) was performed to evaluate postural dysfunction. ASM/ht2 was lower in women and significantly decreased with age in men. Subjects with sarcopenia were significantly more likely to fail the foam balance test, regardless of sex and age. Regression analysis showed a significant relationship between sarcopenia and postural dysfunction (OR: 2.544, 95% CI: 1.683–3.846, p<0.001). Multivariate regression analysis revealed that sarcopenia (OR: 1.747, 95% CI: 1.120–2.720, p = 0.014) and age (OR: 1.131, 95% CI: 1.105–1.158, p<0.001) are independent risk factors for postural instability. In middle age subjects, the adjusted OR for sarcopenia was 3.344 (95% CI: 1.350–8.285) (p = 0.009). The prevalence of postural dysfunction is higher in sarcopenia patients, independent of sex and age.

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<![CDATA[Low relative muscle volume: Correlation with prevalence of venous thromboembolism following total knee arthroplasty]]> https://www.researchpad.co/article/5c8823ced5eed0c484639081

Background

There have been many efforts to find modifiable risk factors for venous thromboembolism (VTE) in the perioperative period of total knee arthroplasty (TKA), while no study has investigated the relationship between the muscle mass and deep vein thrombosis (DVT) or pulmonary embolism frequency following TKA. This study aimed to evaluate the relationship between muscle volume and the prevalence of symptomatic and radiologically confirmed venous thromboembolism (VTE) after total knee arthroplasty (TKA).

Methods

A total of 261 consecutive patients who underwent primary TKA between 2013 and 2015 were enrolled. Computed tomographic venography with pulmonary angiography (CTVPA) was performed between the 5th and 7th postoperative days to assess the presence of VTE. Four parameters of muscle volume at three levels were evaluated on CTVPA: (i) the cross-sectional area of all skeletal muscles (skeletal muscle index) and total psoas area at the level of the third lumbar vertebrae; (ii) the vastus lateralis muscle at the thigh level; and (iii) the posterior crural muscle at the lower leg level. The relationship between the muscle volume at each level and the prevalence of VTE after TKA was evaluated with multivariate adjusted logistic regression models.

Results

The CTVPA scan showed no proximal DVT, and all thrombi were located in muscular, peroneal, and posterior tibial veins. In unilateral TKA, patients with lower muscle volume of the vastus lateralis at the thigh level in the nonoperated limb had significantly higher prevalence of distal DVT in the operated limb (adjusted OR: 2.97 at subclinical DVT revealed by CTVPA and adjusted OR: 2.68 at symptomatic DVT). This finding was also discovered in patients who underwent simultaneous bilateral TKA (adjusted OR: 1.73–2.97 at subclinical DVT and adjusted OR:1.76–1.86 at symptomatic DVT).

Conclusions

The relative muscle volume of the vastus lateralis at the thigh level was negatively associated with the prevalence of symptomatic and radiologically confirmed DVT, suggesting that low thigh muscle mass is an independent risk factor for VTE in the postoperative period of TKA.

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<![CDATA[Functional analysis finds differences on the muscle transcriptome of pigs fed an n-3 PUFA-enriched diet with or without antioxidant supplementations]]> https://www.researchpad.co/article/5c76fe15d5eed0c484e5b456

Supplementing pig diets with n-3 polyunsaturated fatty acids (n-3 PUFA) may produce meat products with an increased n-3 fatty acid content, and the combined antioxidants addition could prevent lipid oxidation in the feed. However, to date, the effects of these bioactive compounds at the molecular level in porcine skeletal muscle are mostly unknown. This study aimed to analyse changes in the Longissimus thoracis transcriptome of 35 pigs fed three diets supplemented with: linseed (L); linseed, vitamin E and Selenium (LES) or linseed and plant-derived polyphenols (LPE). Pigs were reared from 80.8 ± 5.6 kg to 151.8 ± 9.9 kg. After slaughter, RNA-Seq was performed and 1182 differentially expressed genes (DEGs) were submitted to functional analysis. The L vs LES comparison did not show differences, while L vs LPE showed 1102 DEGs and LES vs LPE 80 DEGs. LPE compared to the other groups showed the highest number of up-regulated genes involved in preserving muscle metabolism and structure. Results enlighten that the combined supplementation of bioactive lipids (n-3 PUFA from linseed) with plant extracts as a source of polyphenols increases, compared to the only addition of linseed, the expression of genes involved in mRNA metabolic processes and transcriptional regulation, glucose uptake and, finally, in supporting muscle development and physiology. These results improve the knowledge of the biological effect of bioactive compounds in Longissimus thoracis muscle, and sustain the growing interest over their use in pig production.

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<![CDATA[The associations of fat tissue and muscle mass indices with all-cause mortality in patients undergoing hemodialysis]]> https://www.researchpad.co/article/5c6dc9bbd5eed0c48452a0c8

Protein-energy wasting, which involves loss of fat and muscle mass, is prevalent and is associated with mortality in hemodialysis (HD) patients. We investigated the associations of fat tissue and muscle mass indices with all-cause mortality in HD patients. The study included 162 patients undergoing HD. The fat tissue index (FTI) and skeletal muscle mass index (SMI), which represent respective tissue masses normalized to height squared, were measured by bioimpedance analysis after dialysis. Patients were divided into the following four groups according to the medians of FTI and SMI values: group 1 (G1), lower FTI and lower SMI; G2, higher FTI and lower SMI; G3, lower FTI and higher SMI; and G4, higher FTI and higher SMI. The associations of the FTI, SMI, and body mass index (BMI) with all-cause mortality were evaluated. During a median follow-up of 2.5 years, 29 patients died. The 5-year survival rates were 48.6%, 76.1%, 95.7%, and 87.4% in the G1, G2, G3, and G4 groups, respectively (P = 0.0002). The adjusted hazard ratio values were 0.34 (95% confidence interval [CI] 0.10–0.95, P = 0.040) for G2 vs. G1, 0.13 (95%CI 0.01–0.69, P = 0.013) for G3 vs. G1, and 0.25 (95%CI 0.07–0.72, P = 0.0092) for G4 vs. G1, respectively. With regard to model discrimination, on adding both FTI and SMI to a model with established risk factors, the C-index increased significantly when compared with the value for a model with BMI (0.763 vs. 0.740, P = 0.016). Higher FTI and/or higher SMI values were independently associated with reduced risks of all-cause mortality in HD patients. Moreover, the combination of the FTI and SMI may more accurately predict all-cause mortality when compared with BMI. Therefore, these body composition indicators should be evaluated simultaneously in this population.

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<![CDATA[Nr2f-dependent allocation of ventricular cardiomyocyte and pharyngeal muscle progenitors]]> https://www.researchpad.co/article/5c63393fd5eed0c484ae6300

Multiple syndromes share congenital heart and craniofacial muscle defects, indicating there is an intimate relationship between the adjacent cardiac and pharyngeal muscle (PM) progenitor fields. However, mechanisms that direct antagonistic lineage decisions of the cardiac and PM progenitors within the anterior mesoderm of vertebrates are not understood. Here, we identify that retinoic acid (RA) signaling directly promotes the expression of the transcription factor Nr2f1a within the anterior lateral plate mesoderm. Using zebrafish nr2f1a and nr2f2 mutants, we find that Nr2f1a and Nr2f2 have redundant requirements restricting ventricular cardiomyocyte (CM) number and promoting development of the posterior PMs. Cre-mediated genetic lineage tracing in nr2f1a; nr2f2 double mutants reveals that tcf21+ progenitor cells, which can give rise to ventricular CMs and PM, more frequently become ventricular CMs potentially at the expense of posterior PMs in nr2f1a; nr2f2 mutants. Our studies reveal insights into the molecular etiology that may underlie developmental syndromes that share heart, neck and facial defects as well as the phenotypic variability of congenital heart defects associated with NR2F mutations in humans.

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<![CDATA[Characteristics of mitral valve leaflet length in patients with pectus excavatum: A single center cross-sectional study]]> https://www.researchpad.co/article/5c6b266dd5eed0c484289a7e

The mitral valve morphology in patients with pectus excavatum (PE) has not been fully investigated. Thirty-five patients with PE, 46 normal controls, and patients with hypertrophic cardiomyopathy (HCM) who underwent 2 leaflet length measurements of Carpentier classification P2 and A2 using a transthoracic echocardiography were retrospectively investigated. The coaptation lengths and depths, papillary muscle tethering length, and mitral annular diameters were also measured. The P2 and A2 lengths were separately compared between 2 groups: older than 16 years and 16 years or younger. Furthermore, the correlations between actual P2 or A2 lengths and Haller computed tomography index, an index of chest deformity, were investigated in patients with PE exclusively. Among subjects older than 16 years, patients with PE had significantly shorter P2, longer A2, shorter copatation depth, and longer papillary muscle tethering length compared with normal controls. Similarly, patients with PE had significantly shorter P2 and shorter coaptation depth even compared with patients with HCM, while no significant difference was found in A2 length and papillary muscle tethering length. The same tendency was noted between 4 normal controls and 7 age- and sex-matched patients with PE ≤ 16 years old. No significant difference regarding A2/P2 ratio was found between patients with PE older and younger than 16 years. No significant correlation between the Haller computed tomography index and actual mitral leaflet lengths in patients with PE older than 16 years was noted; the same was observed for A2/P2 in all patients with PE. In conclusion, the characteristic features of the shorter posterior mitral leaflet, the longer anterior mitral leaflet, the shorter coaptation depth, and the longer papillary muscle tethering length in patients with PE was demonstrated. This finding might provide a clue regarding the etiology of mitral valve prolapse in PE at its possible earliest form.

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<![CDATA[Morphological and mechanical properties of the human triceps surae aponeuroses taken from elderly cadavers: Implications for muscle-tendon interactions]]> https://www.researchpad.co/article/5c6730e1d5eed0c484f3829d

The human triceps surae (two gastrocnemii and soleus) has aponeuroses in the proximal and distal aspects, the latter of which insert into the calcaneus by sharing the common Achilles tendon. These tendinous tissues are known to have elasticity and upon muscle contraction the aponeurosis is stretched both longitudinally (along the muscle’s line of action) and transversely. Higher aponeurosis transverse deformability has been documented, but there is a paucity of information on the morphology and mechanical properties of human aponeurosis. This study aimed to identify morphological and mechanical characteristics of the human triceps surae aponeuroses. Twenty-five triceps surae muscle-tendon units were procured from 13 human donors (formalin fixed, 6 males, 7 females) aged 67–91 years. Specimens of aponeuroses were excised from the eight regions (posterior and anterior regions of the gastrocnemius medialis and lateralis, medial and lateral parts of soleus; proximal, middle, and distal sites each, 2–4 cm × 2–4 cm). Aponeurosis thickness was measured using a digital caliper. Uniaxial tensile tests were implemented to determine the mechanical properties of specimens loaded longitudinally (along the muscle’s line of action) and transversely. The aponeurosis thickness showed significant differences between muscles and sites, while Young’s modulus showed direction-dependent (longitudinal vs. transverse) differences within sites. Results show different morphology and mechanical properties of aponeuroses between synergist muscles. The reason for site-dependent differences in stiffness is due to a reduced aponeurosis thickness rather than a reduction in the material property. The anisotropic elastic feature (differences between longitudinal and transverse directions) of the aponeuroses was more pronounced than previous in vivo findings, suggesting inherent material design of the aponeurosis that matches three-dimensional contractile behavior of muscle fibers.

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<![CDATA[Patterns of muscle coordination during dynamic glenohumeral joint elevation: An EMG study]]> https://www.researchpad.co/article/5c6730d6d5eed0c484f381e4

The shoulder relies heavily on coordinated muscle activity for normal function owing to its limited osseous constraint. However, previous studies have failed to examine the sophisticated interrelationship between all muscles. It is essential for these normal relationships to be defined as a basis for understanding pathology. Therefore, the primary aim of the study was to investigate shoulder inter-muscular coordination during different planes of shoulder elevation. Twenty healthy subjects were included. Electromyography was recorded from 14 shoulder girdle muscles as subjects performed shoulder flexion, scapula plane elevation, abduction and extension. Cross-correlation was used to examine the coordination between different muscles and muscle groups. Significantly higher coordination existed between the rotator cuff and deltoid muscle groups during the initial (Pearson Correlation Coefficient (PCC) = 0.79) and final (PCC = 0.74) stages of shoulder elevation compared to the mid-range (PCC = 0.34) (p = 0.020–0.035). Coordination between the deltoid and a functional adducting group comprising the latissimus dorsi and teres major was particularly high (PCC = 0.89) during early shoulder elevation. The destabilising force of the deltoid, during the initial stage of shoulder elevation, is balanced by the coordinated activity of the rotator cuff, latissimus dorsi and teres major. Stability requirements are lower during the mid-range of elevation. At the end-range of movement the demand for muscular stability again increases and higher coordination is seen between the deltoid and rotator cuff muscle groups. It is proposed that by appreciating the sophistication of normal shoulder function targeted evidence-based rehabilitation strategies for conditions such as subacromial impingement syndrome or shoulder instability can be developed.

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<![CDATA[Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease]]> https://www.researchpad.co/article/5c59febed5eed0c484135375

Snakebite is a major neglected tropical health issue that affects over 5 million people worldwide resulting in around 1.8 million envenomations and 100,000 deaths each year. Snakebite envenomation also causes innumerable morbidities, specifically loss of limbs as a result of excessive tissue/muscle damage. Snake venom metalloproteases (SVMPs) are a predominant component of viper venoms, and are involved in the degradation of basement membrane proteins (particularly collagen) surrounding the tissues around the bite site. Although their collagenolytic properties have been established, the molecular mechanisms through which SVMPs induce permanent muscle damage are poorly understood. Here, we demonstrate the purification and characterisation of an SVMP from a viper (Crotalus atrox) venom. Mass spectrometry analysis confirmed that this protein is most likely to be a group III metalloprotease (showing high similarity to VAP2A) and has been referred to as CAMP (Crotalus atrox metalloprotease). CAMP displays both collagenolytic and fibrinogenolytic activities and inhibits CRP-XL-induced platelet aggregation. To determine its effects on muscle damage, CAMP was administered into the tibialis anterior muscle of mice and its actions were compared with cardiotoxin I (a three-finger toxin) from an elapid snake (Naja pallida) venom. Extensive immunohistochemistry analyses revealed that CAMP significantly damages skeletal muscles by attacking the collagen scaffold and other important basement membrane proteins, and prevents their regeneration through disrupting the functions of satellite cells. In contrast, cardiotoxin I destroys skeletal muscle by damaging the plasma membrane, but does not impact regeneration due to its inability to affect the extracellular matrix. Overall, this study provides novel insights into the mechanisms through which SVMPs induce permanent muscle damage.

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<![CDATA[Association of skeletal muscle and serum metabolites with maximum power output gains in response to continuous endurance or high-intensity interval training programs: The TIMES study – A randomized controlled trial]]> https://www.researchpad.co/article/5c6b2666d5eed0c484289a04

Background

Recent studies have begun to identify the molecular determinants of inter-individual variability of cardiorespiratory fitness (CRF) in response to exercise training programs. However, we still have an incomplete picture of the molecular mechanisms underlying trainability in response to exercise training.

Objective

We investigated baseline serum and skeletal muscle metabolomics profile and its associations with maximal power output (MPO) gains in response to 8-week of continuous endurance training (ET) and high-intensity interval training (HIIT) programs matched for total units of exercise performed (the TIMES study).

Methods

Eighty healthy sedentary young adult males were randomized to one of three groups and 70 were defined as completers (> 90% of sessions): ET (n = 30), HIIT (n = 30) and control (CO, n = 10). For the CO, participants were asked to not exercise for 8 weeks. Serum and skeletal muscle samples were analyzed by 1H-NMR spectroscopy. The targeted screens yielded 43 serum and 70 muscle reproducible metabolites (intraclass > 0.75; coefficient of variation < 25%). Associations of baseline metabolites with MPO trainability were explored within each training program via three analytical strategies: (1) correlations with gains in MPO; (2) differences between high and low responders to ET and HIIT; and (3) metabolites contributions to the most significant pathways related to gains in MPO. The significance level was set at P < 0.01 or false discovery rate of 0.1.

Results

The exercise programs generated similar gains in MPO (ET = 21.4 ± 8.0%; HIIT = 24.3 ± 8.5%). MPO associated baseline metabolites supported by all three levels of evidence were: serum glycerol, muscle alanine, proline, threonine, creatinine, AMP and pyruvate for ET, and serum lysine, phenylalanine, creatine, and muscle glycolate for HIIT. The most common pathways suggested by the metabolite profiles were aminoacyl-tRNA biosynthesis, and carbohydrate and amino acid metabolism.

Conclusion

We suggest that MPO gains in both programs are potentially associated with metabolites indicative of baseline amino acid and translation processes with additional evidence for carbohydrate metabolism in ET.

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<![CDATA[Identification of qPCR reference genes suitable for normalizing gene expression in the mdx mouse model of Duchenne muscular dystrophy]]> https://www.researchpad.co/article/5c5b525fd5eed0c4842bc6fe

The mdx mouse is the most widely-used animal model of the human disease Duchenne muscular dystrophy, and quantitative PCR analysis of gene expression in the muscles of this animal plays a key role in the study of pathogenesis and disease progression and in evaluation of potential therapeutic interventions. Normalization to appropriate stably-expressed reference genes is essential for accurate quantitative measurement, but determination of such genes is challenging: healthy and dystrophic muscles present very different transcriptional environments, further altering with disease progression and muscle use, raising the possibility that no single gene or combination of genes may be stable under all experimental comparative scenarios. Despite the pedigree of this animal model, this problem remains unaddressed. The aim of this work was therefore to comprehensively assess reference gene suitability in the muscles of healthy and dystrophic mice, identifying reference genes appropriate for specific experimental comparisons, and determining whether an essentially universally-applicable set of genes exists. Using a large sample collection comprising multiple muscles (including the tibialis anterior, diaphragm and heart muscles) taken from healthy and mdx mice at three disease-relevant ages, and a panel of sixteen candidate reference genes (FBXO38, FBXW2, MON2, ZFP91, HTATSF1, GAPDH, ACTB, 18S, CDC40, SDHA, RPL13a, CSNK2A2, AP3D1, PAK1IP1, B2M and HPRT1), we used the geNorm, BestKeeper and Normfinder algorithms to identify genes that were stable under multiple possible comparative scenarios. We reveal that no single gene is stable under all conditions, but a normalization factor derived from multiple genes (RPL13a, CSNK2A2, AP3D1 and the widely-used ACTB) appears suitable for normalizing gene expression in both healthy and dystrophic mouse muscle regardless of muscle type or animal age. We further show that other popular reference genes, including GAPDH, are markedly disease- or muscle-type correlated. This study demonstrates the importance of empirical reference gene identification, and should serve as a valuable resource for investigators wishing to study gene expression in mdx mice.

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<![CDATA[Characterization of a novel microRNA, miR-188, elevated in serum of muscular dystrophy dog model]]> https://www.researchpad.co/article/5c5b525dd5eed0c4842bc6ee

MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression at the post-transcriptional level. Several miRNAs are exclusively expressed in skeletal muscle and participate in the regulation of muscle differentiation by interacting with myogenic factors. These miRNAs can be found at high levels in the serum of patients and animal models for Duchenne muscular dystrophy, which is expected to be useful as biomarkers for their clinical conditions. By miRNA microarray analysis, we identified miR-188 as a novel miRNA that is elevated in the serum of the muscular dystrophy dog model, CXMDJ. miR-188 was not muscle-specific miRNA, but its expression was up-regulated in skeletal muscles associated with muscle regeneration induced by cardiotoxin-injection in normal dogs and mice. Manipulation of miR-188 expression using antisense oligo and mimic oligo RNAs alters the mRNA expression of the myogenic regulatory factors, MRF4 and MEF2C. Our results suggest that miR-188 is a new player that participates in the gene regulation process of muscle differentiation and that it may serve as a serum biomarker reflecting skeletal muscle regeneration.

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<![CDATA[Reproducibility and validity of a novel invasive method of assessing peripheral microvascular vasomotor function]]> https://www.researchpad.co/article/5c57e6ddd5eed0c484ef3ffe

In healthy arteries, blood flow is regulated by microvascular tone assessed by changes in blood flow volume and vascular resistance to endothelium-dependent and -independent vasodilators. We developed a novel method of using intravascular ultrasound (IVUS) and a Doppler flow wire to measure changes in blood flow volume and vascular resistance of the profunda arterial bed. We assessed the variability over 6 months in measuring microvascular endothelium-dependent dilation to acetylcholine and endothelium-independent dilation to adenosine in 20 subjects who were part of a larger study of Gulf War Illness without obstructive peripheral artery disease. Vasomotor function was assessed by Infusions of control (dextrose), acetylcholine (10-6M), adenosine (50μg), and nitroglycerin (25μg/ml). 400 IVUS and 240 flow velocity images were measured a mean 6 (SD = 2) months apart blind to measurement and infusion stage. The mean (SD) baseline profunda flow was 227 (172) ml/min and vascular resistance 4.6 x 104 (2.4 x 104) dynes-s/cm5. The intraclass correlation coefficients for 6-month variability for vascular function were excellent (range 0.827–0.995). Bland-Altman analyses showed mean differences of less than 2% for microvascular endothelium-dependent function (flow volume and resistance) and less than 1% for macrovascular endothelium-dependent function with acceptable limits of agreement. In 49 subjects assessing concurrent validity of the technique against atherosclerosis risk factors, we observed greater impairment in microvascular endothelium-dependent function per year of age (flow volume = -1.4% (p = 0.018), vascular resistance = 1.5% (p = 0.015)) and current smoking (flow volume = -36.7% (p = .006), vascular resistance = 50.0% (p<0.001)). This novel method of assessing microvascular vasomotor function had acceptable measurement reproducibility and validity.

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<![CDATA[Latanoprost could exacerbate the progression of presbyopia]]> https://www.researchpad.co/article/5c5ca29cd5eed0c48441e76d

Purpose

Prostaglandin analogues (PG) reduce intra-ocular pressure by enhancing uveoscleral flow at the ciliary body, which controls accommodation via the ciliary muscle. We investigated the effect of PG on accommodation and presbyopia progression in glaucoma patients.

Methods

We conducted a clinic-based, retrospective, cross-sectional study. Inclusion criteria were bilateral phakic patients aged 40–69 years with best corrected visual acuity better than 20/30. Exclusion criteria were any disease affecting vision other than glaucoma and history of ocular surgery. Subjects with no prescription or vision-affecting disease served as controls (n = 260). The glaucoma patients were prescribed eye drops containing 0.005% latanoprost for more than six months (n = 23). We measured the binocular near add power at a distance of 30 cm in both groups and compared the results using Kaplan-Meier analysis.

Results

The mean age (± SD) of the control subjects was 51.5 ± 5.2 years and 39% were male. Similarly, the glaucoma patients had a mean age of 51.0 ± 7.2 years and 39% were male. There were no significant differences in age, gender, intra-ocular pressure, spherical equivalent, astigmatism, or anisometropia between groups. Survival analysis indicated that the glaucoma patients in this study reached the endpoint (near add power of +3.00 D) significantly earlier than control patients (P = 0.0001; generalized Wilcoxon test).

Conclusions

Exacerbation of presbyopia progression in glaucoma patients is a potential side effect of latanoprost eyedrops.

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<![CDATA[Nandrolone decanoate administration does not attenuate muscle atrophy during a short period of disuse]]> https://www.researchpad.co/article/5c58d610d5eed0c484031507

Background

A few days of bed rest or immobilization following injury, disease, or surgery can lead to considerable loss of skeletal muscle mass and strength. It has been speculated that such short, successive periods of muscle disuse may be largely responsible for the age-related loss of muscle mass throughout the lifespan.

Objective

To assess whether a single intramuscular injection of nandrolone decanoate prior to immobilization can attenuate the loss of muscle mass and strength in vivo in humans.

Design, setting and participants

Thirty healthy (22 ± 1 years) men were subjected to 7 days of one-legged knee immobilization by means of a full leg cast with (NAD, n = 15) or without (CON, n = 15) prior intramuscular nandrolone decanoate injection (200 mg).

Measures

Before and immediately after immobilization, quadriceps muscle cross-sectional area (CSA) (by means of single-slice computed tomography (CT) scans of the upper leg) and one-legged knee extension strength (one-repetition maximum [1-RM]) were assessed for both legs. Furthermore, muscle biopsies from the immobilized leg were taken before and after immobilization to assess type I and type II muscle fiber cross-sectional area.

Results

Quadriceps muscle CSA decreased during immobilization in both CON and NAD (-6 ± 1% and -6 ± 1%, respectively; main effect of time P<0.01), with no differences between the groups (time × treatment interaction, P = 0.59). Leg muscle strength declined following immobilization (-6 ± 2% in CON and -7 ± 3% in NAD; main effect of time, P<0.05), with no differences between groups (time × treatment interaction, P = 0.55).

Conclusions

This is the first study to report that nandrolone decanoate administration does not preserve skeletal muscle mass and strength during a short period of leg immobilization in vivo in humans.

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<![CDATA[Lifelong aerobic exercise protects against inflammaging and cancer]]> https://www.researchpad.co/article/5c57e679d5eed0c484ef3350

Biological aging is associated with progressive damage accumulation, loss of organ reserves, and systemic inflammation ('inflammaging'), which predispose for a wide spectrum of chronic diseases, including several types of cancer. In contrast, aerobic exercise training (AET) reduces inflammation, lowers all-cause mortality, and enhances both health and lifespan. In this study, we examined the benefits of early-onset, lifelong AET on predictors of health, inflammation, and cancer incidence in a naturally aging mouse model (C57BL/J6). Lifelong, voluntary wheel-running (O-AET; 26-month-old) prevented age-related declines in aerobic fitness and motor coordination vs. age-matched, sedentary controls (O-SED). AET also provided partial protection against sarcopenia, dynapenia, testicular atrophy, and overall organ pathology, hence augmenting the ‘physiologic reserve’ of lifelong runners. Systemic inflammation, as evidenced by a chronic elevation in 17 of 18 pro- and anti-inflammatory cytokines and chemokines (P < 0.05 O-SED vs. 2-month-old Y-CON), was potently mitigated by lifelong AET (P < 0.05 O-AET vs. O-SED), including master regulators of the cytokine cascade and cancer progression (IL-1β, TNF-α, and IL-6). In addition, circulating SPARC, previously known to be upregulated in metabolic disease, was elevated in old, sedentary mice, but was normalized to young control levels in lifelong runners. Remarkably, malignant tumours were also completely absent in the O-AET group, whereas they were present in the brain (pituitary), liver, spleen, and intestines of sedentary mice. Collectively, our results indicate that early-onset, lifelong running dampens inflammaging, protects against multiple cancer types, and extends healthspan of naturally-aged mice.

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