Muscle strength, quantity and quality and muscle fat quantity and their association with oxidative stress in patients with facioscapulohumeral muscular dystrophy: Effect of antioxidant supplementation.

The purpose of this study was to identify causes of quadriceps muscle weakness in facioscapulohumeral muscular dystrophy (FSHD). To this aim, we evaluated quadriceps muscle and fat volumes by magnetic resonance imaging and their relationships with muscle strength and oxidative stress markers in adult patients with FSHD (n = 32) and healthy controls (n = 7), and the effect of antioxidant supplementation in 20 of the 32 patients with FSHD (n = 10 supplementation and n = 10 placebo) (NCT01596803). Compared with healthy controls, the dominant quadriceps strength and quality (muscle strength per unit of muscle volume) were decreased in patients with FSHD. In addition, fat volume was increased, without changes in total muscle volume. Moreover, in patients with FSHD, the lower strength of the non-dominant quadriceps was associated with lower muscle quality compared with the dominant muscle. Antioxidant supplementation significantly changed muscle and fat volumes in the non-dominant quadriceps, and muscle quality in the dominant quadriceps. This was associated with improved muscle strength (both quadriceps) and antioxidant response. These findings suggest that quadriceps muscle strength decline may not be simply explained by atrophy and may be influenced also by the muscle intrinsic characteristics. As FSHD is associated with increased oxidative stress, supplementation might reduce oxidative stress and increase antioxidant defenses, promoting changes in muscle function.

Relationship between quadriceps femoris echotexture biomarkers and muscle strength and physical function in older adults with heart failure with preserved ejection fraction.

BACKGROUND: Muscle wasting is pronounced in patients with heart failure with preserved ejection fraction (HFpEF). The quadriceps femoris echotexture biomarkers assessed by ultrasound (US) have not been studied in these patients. OBJECTIVE: To describe echotexture biomarkers assessed by the US and to assess their relationship with sex, age, body mass index (BMI), self-reported outcomes, muscle strength and physical function in older adults with HFpEF. METHODS: A cross-sectional study was conducted. Patients 70 years and older with HFpEF were included. The sex, age, BMI, and self-reported outcomes were collected. The US assessed muscle and subcutaneous fat tissue contrast, correlation, energy, homogeneity, and entropy at rest and maximal voluntary isometrical contraction (MVIC). The six-minute walk test (6MWT), the short physical performance battery (SPPB), the timed up and go test (TUG), the usual pace gait speed test (UGS), and the fast pace gait speed test (FGS) were used to assess physical function. The five-repetitions sit-to-stand test (5-STS) was performed to assess muscle strength. Bivariant Pearson correlations and subsequent multivariate linear regression analyses were conducted. RESULTS: Seventy-two older adults with HFpEF [81.06 years, 29.13 BMI, and 55.60% females] were recruited. In women, relaxed and MVIC muscle energy and entropy explained 35.40% of the TUG variance; relaxed muscle entropy and MVIC muscle energy shared 24.00% of the UGS variance; relaxed and MVIC muscle entropy, MVIC muscle contrast and MVIC muscle energy explained 32.60% of the FGS variance, adjusted all the models by age and BMI. CONCLUSIONS: Echotexture biomarkers are related to women's muscle strength and physical function, especially muscle energy, contrast, and entropy. Echotexture biomarkers assessed by the US could facilitate the management of older adults with HFpEF, monitor its progression and assess the effectiveness of treatments on the musculoskeletal structure. TRIAL REGISTRATION: NCT03909919. April 10, 2019. Retrospectively registered.

Leg strength and incidence of heart failure in patients with acute coronary syndrome.

AIMS: The risk of developing heart failure (HF) after acute coronary syndrome (ACS) remains high. It is unclear whether skeletal muscle strength, in addition to existing risk factors, is a predictor for developing HF after ACS. We aimed to clarify the relationship between quadriceps isometric strength (QIS), a skeletal muscle strength indicator, and the risk of developing HF in patients with ACS. METHODS AND RESULTS: We included 1053 patients with ACS without a prior HF or complications of HF during hospitalization. The median (interquartile range) age was 67 (57-74) years. The patients were classified into two groups-high and low QIS-using the sex-specific median QIS. The endpoint was HF admissions. During a mean follow-up period of 4.4 ± 3.7 years, 75 (7.1%) HF admissions were observed. After multivariate adjustment, a high QIS was associated with a lower risk of HF [hazard ratio: 0.52, 95% confidence interval (CI): 0.32-0.87]. Hazard ratio (95% CI) per 5% body weight increment increase of QIS for HF incidents was 0.87 (0.80-0.95). Even when competing risks of death were taken into account, the results did not change. The inclusion of QIS was associated with increases in net reclassification improvement (0.26; 95% CI: 0.002-0.52) and an integrated discrimination index (0.01; 95% CI: 0.004-0.02) for HF. CONCLUSION: The present study showed that a higher level of QIS was strongly associated with a lower risk of developing HF after ACS. These findings suggest that skeletal muscle strength could be one of the factors contributing to the risk of developing HF after ACS.

The risk of developing heart failure (HF) after acute coronary syndrome (ACS) remains high. Basic attributes, coronary risk factors, and cardiac and renal function have been reported as risk factors for developing HF after ACS. However, the association between skeletal muscle strength and the development of HF after ACS is unclear. We included 1053 patients with ACS without a prior HF or complications of HF during hospitalization and used quadriceps isometric strength (QIS) as a measure of skeletal muscle strength. We found that higher QIS was associated with a lower risk of developing HF after ACS. The results of our study suggest the benefit of assessing skeletal muscle strength in addition to basic attributes, coronary risk factors, and cardiac and renal function to assess the risk of developing HF after ACS.

Comparison of posture and muscle stiffness between adolescent boys with haemophilia and age-matched healthy peers: An observational comparative study.

BACKGROUND: Haemophilic arthropathy is likely to influence posture and muscle stiffness in adolescent male haemophilia patients (HP). OBJECTIVE: This study aimed to investigate the possible change in upright standing posture and stiffness of the superficial postural muscles in HP. METHODS: Twenty-two HP aged between 12 and 19 years and twenty-two healthy peers were included in the study. The photogrammetry was used to assess the upright standing posture from sagittal and frontal planes. Also, stiffness of the superficial postural muscles was evaluated using the myotonometry. RESULTS: A significant difference was found in the craniovertebral, lumbar lordosis, knee flexion-valgus, and ankle plantar flexion angles between the groups (p< 0.05). Craniovertebral, knee flexion, and knee valgus angles were lower; whereas lumbar lordosis and ankle plantar flexion angles were higher in HP compared to the healthy peers. Stiffness of the rectus femoris muscle was lower in HP (p< 0.001). CONCLUSION: This study revealed that the ankle, knee, lumbar, and craniovertebral segments' posture angles were changed and the stiffness of the rectus femoris muscle decreased in HP. Postural alterations and reduced rectus femoris stiffness should be considered in management of the musculoskeletal complications of haemophilia.

Neural drive and motor unit characteristics after anterior cruciate ligament reconstruction: implications for quadriceps weakness.

Purpose: The purpose of this investigation was to compare the quality of neural drive and recruited quadriceps motor units' (MU) action potential amplitude (MUAPAMP) and discharge rate (mean firing rate (MFR)) relative to recruitment threshold (RT) between individuals with anterior cruciate ligament reconstruction (ACLR) and controls. Methods: Fourteen individuals with ACLR and 13 matched controls performed trapezoidal knee extensor contractions at 30%, 50%, 70%, and 100% of their maximal voluntary isometric contraction (MVIC). Decomposition electromyography (dEMG) and torque were recorded concurrently. The Hoffmann reflex (H-reflex) and central activation ratio (CAR) were acquired bilaterally to detail the proportion of MU pool available and volitionally activated. We examined MUAPAMP-RT and MFR-RT relationships with linear regression and extracted the regression line slope, y-intercept, and RT range for each contraction. Linear mixed effect modelling used to analyze the effect of group and limb on regression line slope and RT range. Results: Individuals with ACLR demonstrated lower MVIC torque in the involved limb compared to uninvolved limb. There were no differences in H-reflex or CAR between groups or limbs. The ACLR involved limb demonstrated smaller mass-normalized RT range and slower MU firing rates at high contraction intensities (70% and 100% MVIC) compared to uninvolved and control limbs. The ACLR involved limb also demonstrated larger MU action potentials in the VM compared to the contralateral limb. These differences were largely attenuated with relative RT normalization. Conclusions: These results suggest that persistent strength deficits following ACLR may be attributable to a diminished quadriceps motor neuron pool and inability to upregulate the firing rate of recruited MUs.

Eccentric contractions during downhill running induce Osgood‒Schlatter disease in the tibial tuberosity in rats: a focus on histological structures.

Osgood-Schlatter disease (OSD), a condition that affects adolescents, causes inflammation, pain, and prominence at the tibial tuberosity. The causes of OSD are not well understood, but eccentric contractions in the quadriceps have been suggested as a possible factor. To investigate this, a study was conducted in which 24 rats were divided into two groups: the downhill treadmill running (DR) group and the control (CO) group. The DR group underwent a preliminary running program for 1 week, followed by a main running program for 3 weeks. The results showed that the deep region of the tibial tuberosity in the DR group was larger than that in the CO group, and inflammatory cytokines involved in gene expression were upregulated in the DR group. The anterior articular cartilage and deep region in the DR group were also immunoreactive to substance P. Additionally, high-activity chondrocytes of small size were observed in the non-calcified matrix. Thus, the DR group exhibited symptoms similar to OSD, including inflammation, pain, and prominence. These findings suggest that eccentric contractions in the quadriceps may play a role in the development of OSD. Further research is needed to better understand the pathophysiology of this condition and develop effective treatment options.

Análisis biomecánico de la continuación prepatelar del cuádriceps / Biomechanical assessment of the prepatellar quadriceps continuation

OBJETIVO Determinar la resistencia máxima a la tracción (RMT) de la continuación prepatelar del cuádriceps (CPC).MATERIALES Y MÉTODOS Se realizó un estudio en cadáveres humanos. Fueron incluidos diez especímenes, en los cuales se utilizaron los tercios proximal y medial de la cortical anterior de la patela para evaluar las propiedades mecánicas de la CPC. En cada espécimen, se estudió un área de sección transversal de 0,2 cm2 (A1) y 1 cm2 (A2). Se aplicó una carga gradual para determinar la RMT.RESULTADOS La mediana de la RMT en el A1 fue de 232,56 N (rango: 141,23 N a 295,33 N) y en el A2 fue de 335,30 N (rango: 216,45 N a 371,40 N). El incremento en la TMR fue significativo entre las 2 áreas (p = 0,006).CONCLUSIÓN El ignificado clínico de este estudio es que la CPC es un tejido fuerte que puede servir de anclaje seguro para reconstrucciones alrededor de la patela. Un área relativamente pequeña tolera al menos 140 N y, a medida que crece el área, también aumenta la RMT.

OBJETIVE To determine the ultimate tensile strength (UTS) of the prepatellar quadriceps continuation (PQC). MATERIALS AND METHODS A human cadaveric study was performed. Ten fresh-frozen specimens were used. The proximal and medial thirds of the anterior cortex of the patella were used to assess the mechanical properties of the PQC. In each specimen, transverse section areas measuring 0.2 cm2 (A1) and 1 cm2 (A2) were studied. A gradual load was applied to determine the UTS. RESULTS The median UTS of A1 was of 232.56 N (range: 141.23 N to 295.33 N), and that of A2 was of 335.30 N (range: 216.45 N to 371.40 N). The increment in UTS was significant between the 2 areas (p » 0.006). CONCLUSION The clinical significance of the present study lies in the fact that it shows that the PQC is a strong tissue that can be a safe anchor for reconstruction around the patella. A relatively small area supports at least 140 N, and, as the area grows, the UTS increases as well.

Relationship between muscle mass and fraction of intramuscular adipose tissue of the quadriceps in older inpatients.

BACKGROUND: In 2021, the International Society of Physical and Rehabilitation Medicine (ISPRM) special interest group on sarcopenia included the quadriceps thickness assessed with ultrasound image as an indicator of muscle mass in the diagnosis criteria of sarcopenia. If quadriceps echo intensity of older inpatients is to be a strong predictor of quadriceps thickness, muscle quality of the quadriceps may be estimated by the muscle mass when diagnosing sarcopenia using the criteria of ISPRM. OBJECTIVE: This study aimed to examine the association between muscle mass and fraction of intramuscular adipose tissue of the quadriceps in older inpatients. METHODS: This cross-sectional study included 399 inpatients aged ≥ 65 years. Primary outcomes were muscle mass and fraction of intramuscular adipose tissue of the quadriceps. Images were acquired using a B-mode ultrasound. Muscle mass and fraction of intramuscular adipose tissue of the quadriceps were assessed based on the muscle thickness and echo intensity, respectively. A multiple regression analysis (forced entry method) was performed to confirm whether quadriceps echo intensity was related to quadriceps thickness even after adjusting for other factors. RESULTS: In the multiple regression analyses for both male and female models, quadriceps echo intensity (male: ß = - 0.537, p < 0.001; female: ß = - 0.438, p < 0.001), Geriatric Nutritional Risk Index (male: ß = 0.236, p < 0.001; female: ß = 0.213, p < 0.001), and subcutaneous fat thickness of the thigh (male: ß = 0.197, p < 0.001; female: ß = 0.248, p < 0.001) were independently and significantly associated with quadriceps thickness. CONCLUSIONS: Our results show that there is a negative and significant association between muscle mass and fraction of intramuscular adipose tissue in older inpatients. Muscle quality of the quadriceps in older inpatients may be estimated to some extent by the muscle mass.

Quadriceps physiological response during the 1-min sit-to-stand test in people with severe COPD and healthy controls.

We compared quadriceps oxygenation and surface electromyography (sEMG) responses during the 1-min sit-to-stand (1STS) in 14 people with severe COPD and 12 controls, in whom cardiorespiratory response, near-infrared spectroscopy signals (oxy [Hb-Mb], deoxy [Hb-Mb], total [Hb-Mb], and SmO2) and sEMG signals of the quadriceps were recorded. Time duration of each sit-to-stand cycle and the total work performed during the 1STS were measured. The quadriceps oxygenation parameters were normalized by reporting their values according to the total work during 1STS. The rate of sit-to-stand maneuvers decelerated in people with COPD leading to smaller total work compared with controls. The pattern of quadriceps oxygenation response during 1STS was similar between groups. However, in COPD, the recovery after 1STS was characterized by larger overshoots in oxy [Hb-Mb], total [Hb-Mb], and SmO2. When corrected for the cumulative total work, the increase in muscle O2 extraction (deoxy [Hb-Mb]) during the first 30 s of recovery was greater in people with COPD compared to controls. Quadriceps sEMG changes suggestive of a fatiguing contraction pattern was observed only in people with COPD. All together, these results highlighted physiological misadaptation of people with severe COPD to the 1STS.

The impact of skeletal muscle disuse on distinct echo intensity bands: A retrospective analysis.

Echo intensity (EI) is a novel tool for assessing muscle quality. EI has traditionally been reported as the mean of the pixel histogram, with 0 and 255 arbitrary units (A.U.) representing excellent and poor muscle quality, respectively. Recent work conducted in youth and younger and older adults suggested that analyzing specific EI bands, rather than the mean, may provide unique insights into the effectiveness of exercise and rehabilitation interventions. As our previous work showed deterioration of muscle quality after knee joint immobilization, we sought to investigate whether the increase in EI following disuse was limited to specific EI bands. Thirteen females (age = 21 yrs) underwent two weeks of left knee immobilization and ambulated via crutches. B-mode ultrasonography was utilized to obtain images of the immobilized vastus lateralis. The percentage of the total number of pixels within bands of 0-50, 51-100, 101-150, 151-200, and 201-255 A.U. was examined before and after immobilization. We also sought to determine if further subdividing the histogram into 25 A.U. bands (i.e., 0-25, 26-50, etc.) would be a more sensitive methodological approach. Immobilization resulted in a decrease in the percentage of pixels within the 0-50 A.U. band (-3.11 ± 3.98%), but an increase in the 101-150 A.U. (2.94 ± 2.64%) and 151-200 A.U. (0.93 ± 1.42%) bands. Analyses of variance on the change scores indicated that these differences were large and significant (%EI0-50 vs. %EI101-150: p < .001, d = 1.243); %EI0-50 vs. %EI151-200: p = .043, d = 0.831). The effect size for the %EI51-100 versus %EI101-150 comparison was medium/large (d = 0.762), but not statistically significant (p = .085). Further analysis of the 25 A.U. bands indicated that the percentage of pixels within the 25-50 A.U. band decreased (-2.97 ± 3.64%), whereas the 101-125 (1.62 ± 1.47%) and 126-150 A.U. (1.18 ± 1.07%) bands increased. Comparison of the 50 A.U. and 25 A.U. band methods found that 25 A.U. bands offer little additional insight. Though studies are needed to ascertain the factors that may influence specific bands, changes in EI during muscle disuse are not homogeneous across the pixel histogram. We encourage investigators to think critically about the robustness of data obtained from EI histograms, rather than simply reporting the EImean value, in muscle quality research.

Rate of force development in the quadriceps of individuals with severe knee osteoarthritis: A preliminary cross-sectional study.

Knee osteoarthritis (KOA) is a leading cause of knee pain and disability due to irreversible cartilage degeneration. Previous studies have not identified modifiable risk factors for KOA. In this preliminary cross-sectional study, we aimed to test the following hypotheses: individuals with severe KOA would have a significantly lower quadriceps rate of force development (RFD) than individuals with early KOA, and the decrease in quadriceps RFD would be greater than the decrease in maximum quadriceps strength in individuals with severe KOA. The maximum isometric strength of the quadriceps was assessed in individuals with mild (Kellgren and Lawrence [K&L] grade 1-2) and severe KOA (K&L grade 3-4) using a handheld dynamometer. The RFD was analyzed at 200 ms from torque onset and normalized to the body mass and maximum voluntary isometric contraction torque. To test whether the quadriceps RFD was lowered and whether the lower in the quadriceps RFD was greater than the lower in maximum quadriceps strength in individuals with severe knee OA, the Mann-Whitney U-test and analysis of covariance were performed, respectively. The effect size (ES) based on Hedges' g with a 95% confidence interval (CI) was calculated for the quadriceps RFD and maximum quadriceps strength. Sixty-six participants were analyzed. Individuals with severe KOA displayed significantly lower quadriceps RFD (p = 0.009), the lower being greater than the lower in maximum quadriceps strength (between-group difference, ES: 0.88, -1.07 vs. 0.06, -0.22). Our results suggest that a decreased quadriceps RFD is a modifiable risk factor for progressive KOA. Our finding could help in the early detection and prevention of severe KOA.

Association of Quadriceps Strength Symmetry and Surgical Status With Clinical Osteoarthritis Five Years After Anterior Cruciate Ligament Rupture.

OBJECTIVE: The objective of this study was to examine the association of quadriceps strength symmetry and surgical status (anterior cruciate ligament [ACL] reconstruction or nonoperative management) with early clinical knee osteoarthritis (OA) 5 years after ACL injury or reconstruction. METHODS: In total, 204 of 300 athletes were analyzed 5 years after ACL injury or reconstruction. Quadriceps strength was measured and reported as a limb symmetry index. We identified participants with early clinical knee OA using the criteria that 2 of 4 Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales score ≤85%. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression and adjusted for age, sex, meniscal injury, and body mass index to examine the associations of quadriceps strength and surgical status with clinical knee OA. RESULTS: In all, 21% of participants met the KOOS criteria for clinical knee OA. For every 1% increase in quadriceps limb symmetry index, there was a 4% lower odds of clinical OA (adjusted OR [ORadj ] 0.96 [95% CI 0.93-0.99]) at 5 years. Surgical status was not associated with clinical knee OA (ORadj 0.58 [95% CI 0.23-1.50]). CONCLUSION: More symmetric quadriceps strength, but not surgical status, 5 years after ACL injury or reconstruction was associated with lower odds of clinical knee OA.

Magnetic twitch assessment of diaphragm and quadriceps weakness in critically ill mechanically ventilated patients.

Critically ill mechanically ventilated (MV) patients develop significant muscle weakness, which has major clinical consequences. There remains uncertainty, however, regarding the severity of leg weakness, the precise relationship between muscle strength and thickness, and the risk factors for weakness in MV patients. We therefore measured both diaphragm (PdiTw) and quadriceps (QuadTw) strength in MV patients using magnetic stimulation and compared strength to muscle thickness. Both PdiTw and QuadTw were profoundly reduced for MV patients, with PdiTw 19 % of normal and QuadTw 6% of normal values. There was a poor correlation between strength and thickness for both muscles, with thickness often remaining in the normal range when strength was severely reduced. Regression analysis revealed reductions in PdiTw correlated with presence of infection (p = 0.006) and age (p = 0.007). QuadTw best correlated with duration of MV (p = 0.036). Limb muscles are profoundly weak in critically ill patients, with a severity that mirrors the level of weakness observed in the diaphragm.

Effects of an acute exercise bout in hypoxia on extracellular vesicle release in healthy and prediabetic subjects.

The purpose of this study is to investigate exosome-like vesicle (ELV) plasma concentrations and markers of multivesicular body (MVB) biogenesis in skeletal muscle in response to acute exercise. Seventeen healthy [body mass index (BMI): 23.5 ± 0.5 kg·m-2] and 15 prediabetic (BMI: 27.3 ± 1.2 kg·m-2) men were randomly assigned to two groups performing an acute cycling bout in normoxia or hypoxia ([Formula: see text] 14.0%). Venous blood samples were taken before (T0), during (T30), and after (T60) exercise, and biopsies from m. vastus lateralis were collected before and after exercise. Plasma ELVs were isolated by size exclusion chromatography, counted by nanoparticle tracking analysis (NTA), and characterized according to international standards, followed by expression analyses of canonical ELV markers in skeletal muscle. In the healthy normoxic group, the total number of particles in the plasma increased during exercise from T0 to T30 (+313%) followed by a decrease from T30 to T60 (-53%). In the same group, an increase in TSG101, CD81, and HSP60 protein expression was measured after exercise in plasma ELVs; however, in the prediabetic group, the total number of particles in the plasma was not affected by exercise. The mRNA content of TSG101, ALIX, and CD9 was upregulated in skeletal muscle after exercise in normoxia, whereas CD9 and CD81 were downregulated in hypoxia. ELV plasma abundance increased in response to acute aerobic exercise in healthy subjects in normoxia, but not in prediabetic subjects, nor in hypoxia. Skeletal muscle analyses suggested that this tissue did not likely play a major role of the exercise-induced increase in circulating ELVs.

Skeletal Muscle Phenotype in Patients Undergoing Long-Term Hemodialysis Awaiting Kidney Transplantation.

BACKGROUND AND OBJECTIVES: Age and comorbidity-related sarcopenia represent a main cause of muscle dysfunction in patients on long-term hemodialysis. However, recent findings suggest muscle abnormalities that are not associated with sarcopenia. The aim of this study was to isolate functional and cellular muscle abnormalities independently of other major confounding factors, including malnutrition, age, comorbidity, or sedentary lifestyle, which are common in patients on maintenance hemodialysis. To overcome these confounding factors, alterations in skeletal muscle were analyzed in highly selected patients on long-term hemodialysis undergoing kidney transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 22 patients on long-term hemodialysis scheduled for kidney transplantation with few comorbidities, but with a long-term uremic milieu exposure, and 22 age, sex, and physical activity level frequency-matched control participants were recruited. We compared biochemical, functional, and molecular characteristics of the skeletal muscle using maximal voluntary force and endurance of the quadriceps, 6-minute walking test, and muscle biopsy of vastus lateralis. For statistical analysis, mean comparison and multiple regression tests were used. RESULTS: In patients on long-term hemodialysis, muscle endurance was lower, whereas maximal voluntary force was not significantly different. We observed a transition from type I (oxidative) to type II (glycolytic) muscle fibers, and an alteration of mitochondrial structure (swelling) without changes in DNA content, genome replication (peroxisome proliferator activator receptor γ coactivator-1α and mitochondrial transcription factor A), regulation of fusion (mitofusin and optic atrophy 1), or fission (dynamin-related protein 1). Notably, there were autophagosome structures containing glycogen along with mitochondrial debris, with a higher expression of light chain 3 (LC3) protein, indicating phagophore formation. This was associated with a greater conversion of LC3-I to LC3-II and the expression of Gabaralp1 and Bnip3l genes involved in mitophagy. CONCLUSIONS: In this highly selected long-term hemodialysis population, a low oxidative phenotype could be defined by a poor endurance, a fiber-type switch, and an alteration of mitochondria structure, without evidence of sarcopenia. This phenotype could be related to uremia through the activation of autophagy/mitophagy. CLINICAL TRIAL REGISTRATION NUMBERS: NCT02794142 and NCT02040363.

Effect of photobiomodulation combined with physical therapy on functional performance in children with myelomeningocele: A protocol randomized clinical blind study.

INTRODUCTION: Myelomeningocele is a severe type of spina bifida, resulting from improper closure of the neural tube. This condition drastically affects the structures of the spinal cord resulting in deficiencies. The combination of these deficiencies results in an overall decrease in mobility and functional participation amongst this population. Physiotherapy plays an essential role in rehabilitating people with MMC. The current literature shows that resources such as photobiomodulation (PBM) may support the rehabilitation of neurological conditions. The aim of the proposed study is to evaluate the effects of photobiomodulation (PBM) combined with physical therapy on functional performance in children with low lumbosacral myelomeningocele. MATERIALS AND METHODS: This is a protocol randomized clinical blind study, that will include 30 individuals of both sexes, aged between 5 to 8 years, diagnosed with low and sacral lumbar myelomeningocele and capable of performing the sit-to-stand task. The participants will be randomly assigned into two treatment groups: PBM + physiotherapeutic exercises and sham PBM + physiotherapeutic exercises. Irradiation will be carried out with light emitting diode (LED) at a wavelength of 850 nm, energy of 25 J per point, 50 seconds per point and a power of 200 mW. The same device will be used in the placebo group but will not emit light. Muscle activity will be assessed using a portable electromyograph (BTS Engineering) and the sit-to-stand task will be performed as a measure of functioning. Electrodes will be positioned on the lateral gastrocnemius, tibialis anterior and rectus femoris muscles. The Pediatric Evaluation of Disability Inventory will be used to assess functional independence. Quality of life will be assessed using the Child Health Questionnaire-Parent Form 50. Changes in participation will be assessed using the Participation and Environment Measure for Children and Youth. The data will be analyzed with the aid of GraphPad PRISM. DISCUSSION: The results of this study can contribute to a better understanding of the effectiveness of PBM on functioning and quality of life in children with myelomeningocele. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04425330.

Heterogeneity of human adaptations to bed rest and hypoxia: a retrospective analysis within the skeletal muscle oxidative function.

This retrospective study was designed to analyze the interindividual variability in the responses of different variables characterizing the skeletal muscle oxidative function to normoxic (N-BR) and hypoxic (H-BR) bed rests and to a hypoxic ambulatory confinement (H-AMB) of 10 and 21 days. We also assessed whether and how the addition of hypoxia to bed rest might influence the heterogeneity of the responses. In vivo measurements of O2 uptake and muscle fractional O2 extraction were carried out during an incremental one-leg knee-extension exercise. Mitochondrial respiration was assessed in permeabilized muscle fibers. A total of 17 subjects were included in this analysis. This analysis revealed a similar variability among subjects in the alterations induced by N-BR and H-BR both in peak O2 uptake (SD: 4.1% and 3.3% after 10 days; 4.5% and 8.1% after 21 days, respectively) and peak muscle fractional O2 extraction (SD: 5.9% and 7.3% after 10 days; 6.5% and 7.3% after 21 days), independently from the duration of the exposure. The individual changes measured in these variables were significantly related (r = 0.66, P = 0.004 after N-BR; r = 0.61, P = 0.009 after H-BR). Mitochondrial respiration showed a large variability of response after both N-BR (SD: 25.0% and 15.7% after 10 and 21 days) and H-BR (SD: 13.0% and 19.8% after 10 and 21 days); no correlation was found between N-BR and H-BR changes. When added to bed rest, hypoxia altered the individual adaptations within the mitochondria but not those intrinsic to the muscle oxidative function in vivo, both after the short- and medium-term exposures.

Skeletal muscle bioenergetic health and function in people living with HIV: association with glucose tolerance and alcohol use.

At-risk alcohol use is prevalent and increases dysglycemia among people living with human immunodeficiency virus (PLWH). Skeletal muscle (SKM) bioenergetic dysregulation is implicated in dysglycemia and type 2 diabetes. The objective of this study was to determine the relationship between at-risk alcohol, glucose tolerance, and SKM bioenergetic function in PLWH. Thirty-five PLWH (11 females, 24 males, age: 53 ± 9 yr, body mass index: 29.0 ± 6.6 kg/m2) with elevated fasting glucose enrolled in the ALIVE-Ex study provided medical history and alcohol use information [Alcohol Use Disorders Identification Test (AUDIT)], then underwent an oral glucose tolerance test (OGTT) and SKM biopsy. Bioenergetic health and function and mitochondrial volume were measured in isolated myoblasts. Mitochondrial gene expression was measured in SKM. Linear regression adjusting for age, sex, and smoking was performed to examine the relationship between glucose tolerance (2-h glucose post-OGTT), AUDIT, and their interaction with each outcome measure. Negative indicators of bioenergetic health were significantly (P < 0.05) greater with higher 2-h glucose (proton leak) and AUDIT (proton leak, nonmitochondrial oxygen consumption, and bioenergetic health index). Mitochondrial volume was increased with the interaction of higher 2-h glucose and AUDIT. Mitochondrial gene expression decreased with higher 2-h glucose (TFAM, PGC1B, PPARG, MFN1), AUDIT (MFN1, DRP1, MFF), and their interaction (PPARG, PPARD, MFF). Decreased expression of mitochondrial genes were coupled with increased mitochondrial volume and decreased bioenergetic health in SKM of PLWH with higher AUDIT and 2-h glucose. We hypothesize these mechanisms reflect poorer mitochondrial health and may precede overt SKM bioenergetic dysregulation observed in type 2 diabetes.

Alterations in skeletal muscle repair in young adults with type 1 diabetes mellitus.

Though preclinical models of type 1 diabetes (T1D) exhibit impaired muscle regeneration, this has yet to be investigated in humans with T1D. Here, we investigated the impact of damaging exercise (eccentric quadriceps contractions) in 18 physically active young adults with and without T1D. Pre- and postexercise (48 h and 96 h), the participants provided blood samples, vastus lateralis biopsies, and performed maximal voluntary quadriceps contractions (MVCs). Skeletal muscle sarcolemmal integrity, extracellular matrix (ECM) content, and satellite cell (SC) content/proliferation were assessed by immunofluorescence. Transmission electron microscopy was used to quantify ultrastructural damage. MVC was comparable between T1D and controls before exercise. Postexercise, MVC was decreased in both groups, but subjects with T1D exhibited moderately lower strength recovery at both 48 h and 96 h. Serum creatine kinase, an indicator of muscle damage, was moderately higher in participants with T1D at rest and exhibited a small elevation 96 h postexercise. Participants with T1D showed lower SC content at all timepoints and demonstrated a moderate delay in SC proliferation after exercise. A greater number of myofibers exhibited sarcolemmal damage (disrupted dystrophin) and increased ECM (laminin) content in participants with T1D despite no differences between groups in ultrastructural damage as assessed by electron microscopy. Finally, transcriptomic analyses revealed dysregulated gene networks involving RNA translation and mitochondrial respiration, providing potential explanations for previous observations of mitochondrial dysfunction in similar cohorts with T1D. Our findings indicate that skeletal muscle in young adults with moderately controlled T1D is altered after damaging exercise, suggesting that longer recovery times following intense exercise may be necessary.

Ultrasound assessment of the rectus femoris in patients with chronic obstructive pulmonary disease predicts poor exercise tolerance: an exploratory study.

BACKGROUND: Reduced exercise tolerance is an important clinical feature of chronic obstructive pulmonary disease (COPD) and is associated with poor prognosis. The 6-min walk test (6MWT) is widely used to assess exercise capacity; however, it is not commonly administered in primary medical institutions because it requires a suitable site and professional training. Ultrasound has great potential for evaluating skeletal muscle dimensions in COPD. However, whether skeletal muscle ultrasound can predict impaired exercise tolerance is unclear. METHODS: The study included 154 stable patients with COPD, who were randomly divided into a development set and a validation set. The thickness (RFthick) and cross-sectional area (RFcsa) of the rectus femoris were measured using ultrasound. Standardized RFthick (STD- RFthick) and Standardized RFcsa (STD-RFcsa) were obtained via standardization of RFthick and RFcsa by patients' height. RESULTS: Strong correlations were observed between the 6MWD and RFthick (r = 0.84, p < 0.001) and between the 6MWD and RFcsa (r = 0.81, p < 0.001). In the development set, the optimal cut-off values for men and women for predicting poor exercise tolerance were < 3.098 cm/m and < 3.319 cm/m for STD-RFthick and < 4.052 cm2/m and < 4.366 cm2/m for STD-RFcsa, respectively. In the validation set, the area under the curve (AUC) values for the prediction of a 6MWD < 350 by STD-RFthick and STD-RFcsa were 0.881 and 0.903, respectively. Finally, the predictive efficacy of STD-RFthick (AUC: 0.922), STD-RFcsa (AUC: 0.904), and the derived nomogram model (AUC: 0.98) for exercise tolerance was superior to that of the sit-to-stand test and traditional clinical features. CONCLUSIONS: Rectus femoris ultrasound has potential clinical application to predict impaired exercise tolerance in patients with COPD.