Acute and Chronic Changes in Muscle Androgen Receptor Markers Are Not Associated with Muscle Hypertrophy in Women and Men.

PURPOSE: Androgen receptor (AR) expression and signaling has been regarded as a mechanism for regulating muscle hypertrophy. However, little is known about the associations between acute and chronic changes in skeletal muscle total AR, cytoplasmic AR (cAR), nuclear AR (nAR) and AR DNA-binding (AR-DNA) induced by resistance training (RT) and hypertrophy outcomes in women and men. This study aimed to investigate the acute and chronic effects of RT on skeletal muscle total AR, cAR, nAR contents and AR-DNA in women and men. Additionally, we investigated whether these acute and chronic changes in these markers were associated with muscle hypertrophy in both sexes. METHODS: Nineteen women and 19 men underwent 10 weeks of RT. Muscle biopsies were performed at baseline, 24 h after the first RT session and 96-120 h after the last session. AR, cAR and nAR were analyzed using Western blotting, and AR-DNA using an ELISA-oligonucleotide assay. Fiber cross-sectional area (fCSA) was analyzed through immunohistochemistry and muscle cross-sectional area (mCSA) by ultrasound. RESULTS: At baseline, men demonstrated greater nAR than women. Baseline cAR was significantly associated with type II fCSA hypertrophy in men. Acutely, both sexes decreased AR and cAR, whereas men demonstrated greater decreases in nAR. After 10 weeks of RT, AR and nAR remained unchanged, men demonstrated greater cAR compared to women, and both sexes decreased AR-DNA activity. Acute and chronic changes in AR markers did not correlate with muscle hypertrophy (type I/II fCSA and mCSA) in women or men. CONCLUSIONS: Baseline cAR content may influence hypertrophy in men, while neither RT-induced acute nor chronic changes in AR, cAR, nAR, and AR-DNA are associated with muscle hypertrophy in women or men.

Skeletal muscle myosin heavy chain protein fragmentation as a potential marker of protein degradation in response to resistance training and disuse atrophy.

We sought to examine how resistance exercise (RE), cycling exercise, and disuse atrophy affect myosin heavy chain (MyHC) protein fragmentation in humans. In the first study (1boutRE), younger adult men (n=8; 5±2 years of RE experience) performed a lower body RE bout with vastus lateralis (VL) biopsies obtained immediately before, 3-, and 6-hours post-exercise. In the second study (10weekRT), VL biopsies were obtained in untrained younger adults (n=36, 18 men and 18 women) before and 24 hours (24h) after their first/naïve RE bout. These participants also engaged in 10 weeks (24 sessions) of resistance training and donated VL biopsies before and 24h after their last RE bout. VL biopsies were also examined from a third acute cycling study (n=7) and a fourth study involving two weeks of leg immobilization (n=20, 15 men and 5 women) to determine how MyHC fragmentation was affected. In the 1boutRE study, the fragmentation of all MyHC isoforms (MyHCTotal) increased 3 hours post-RE (~ +200%, p=0.018) and returned to pre-exercise levels by 6 hours post-RE. Immunoprecipitation of MyHCTotal revealed ubiquitination levels remained unaffected at the 3- and 6-hour post-RE time points. Interestingly, a greater increase in magnitude for MyHC type IIa versus I isoform fragmentation occurred 3-hours post-RE (8.6±6.3-fold versus 2.1±0.7-fold, p=0.018). In all 10weekRT participants, the first/naïve and last RE bouts increased MyHCTotal fragmentation 24h post-RE (+65% and +36%, respectively; p<0.001); however, the last RE bout response was attenuated compared to the first bout (p=0.045). The first/naïve bout response was significantly elevated in females only (p<0.001), albeit females also demonstrated a last bout attenuation response (p=0.002). Although an acute cycling bout did not alter MyHCTotal fragmentation, ~8% VL atrophy with two weeks of leg immobilization led to robust MyHCTotal fragmentation (+108%, p<0.001), and no sex-based differences were observed. In summary, RE and disuse atrophy increase MyHC protein fragmentation. A dampened response with 10 weeks of resistance training, and more refined responses in well-trained men, suggest this is an adaptive process. Given the null polyubiquitination IP findings, more research is needed to determine how MyHC fragments are processed. Moreover, further research is needed to determine how aging and disease-associated muscle atrophy affect these outcomes, and whether MyHC fragmentation is a viable surrogate for muscle protein turnover rates.

Resistance training-induced changes in muscle proteolysis and extracellular matrix remodeling biomarkers in the untrained and trained states.

PURPOSE: Resistance training (RT) induces muscle growth at varying rates across RT phases, and evidence suggests that the muscle-molecular responses to training bouts become refined or attenuated in the trained state. This study examined how proteolysis-related biomarkers and extracellular matrix (ECM) remodeling factors respond to a bout of RT in the untrained (UT) and trained (T) state. METHODS: Participants (19 women and 19 men) underwent 10 weeks of RT. Biopsies of vastus lateralis were collected before and after (24 h) the first (UT) and last (T) sessions. Vastus lateralis cross-sectional area (CSA) was assessed before and after the experimental period. RESULTS: There were increases in muscle and type II fiber CSAs. In both the UT and T states, calpain activity was upregulated and calpain-1/-2 protein expression was downregulated from Pre to 24 h. Calpain-2 was higher in the T state. Proteasome activity and 20S proteasome protein expression were upregulated from Pre to 24 h in both the UT and T. However, proteasome activity levels were lower in the T state. The expression of poly-ubiquitinated proteins was unchanged. MMP activity was downregulated, and MMP-9 protein expression was elevated from Pre to 24 h in UT and T. Although MMP-14 protein expression was acutely unchanged, this marker was lower in T state. TIMP-1 protein levels were reduced Pre to 24 h in UT and T, while TIMP-2 protein levels were unchanged. CONCLUSION: Our results are the first to show that RT does not attenuate the acute-induced response of proteolysis and ECM remodeling-related biomarkers.

Application of Artificial Intelligence to Automate the Reconstruction of Muscle Cross-Sectional Area Obtained by Ultrasound.

PURPOSE: Manual reconstruction (MR) of the vastus lateralis (VL) muscle cross sectional area (CSA) from sequential ultrasound (US) images is accessible, reproducible and has concurrent validity with magnetic resonance imaging. However, this technique requires numerous controls and procedures during image acquisition and reconstruction, making it laborious and time-consuming. The aim of this study was to determine the concurrent validity of VL CSA assessments between MR and computer vision-based automatic reconstruction (AR) of CSA from sequential images of the VL obtained by US. METHODS: The images from each sequence were manually rotated to align the fascia between images and thus visualize the VL CSA. For the AR, an artificial neural network model was utilized to segment areas of interest in the image, such as skin, fascia, deep aponeurosis, and femur. This segmentation was crucial to impose necessary constraints for the main assembly phase. At this stage, an image registration application, combined with differential evolution, was employed to achieve appropriate adjustments between the images. Next, the VL CSA obtained from the MR (n = 488) and AR (n = 488) techniques were used to determine their concurrent validity. RESULTS: Our findings demonstrated a low coefficient of variation (CV) (1.51%) for AR compared to MR. The Bland-Altman plot showed low bias and close limits of agreement (+1.18 cm2, -1.19 cm2), containing more than 95% of the data points. CONCLUSIONS: The AR technique is valid compared to MR when measuring VL CSA in a heterogeneous sample.

Effects of Resistance Training Overload Progression Protocols on Strength and Muscle Mass.

The aim of this study was to compare the effects of progressive overload in resistance training on muscle strength and cross-sectional area (CSA) by specifically comparing the impact of increasing load (LOADprog) versus an increase in repetitions (REPSprog). We used a within-subject experimental design in which 39 previously untrained young persons (20 men and 19 women) had their legs randomized to LOADprog and REPSprog. Outcomes were assessed before and after 10 weeks of training. Muscle strength was assessed using the one repetition maximum (1RM) test on the leg extension exercise, and the CSA of the vastus lateralis was assessed by ultrasonography. Both protocols increased 1RM values from pre (LOADprog: 52.90±16.32 kg; REPSprog: 51.67±15.84 kg) to post (LOADprog: 69.05±18.55 kg, REPSprog: 66.82±17.95 kg), with no difference between them (P+>+0.05). Similarly, both protocols also increased in CSA values from pre (LOADprog: 21.34±4.71 cm²; REPSprog: 21.08±4.62 cm²) to post (LOADprog: 23.53±5.41 cm², REPSprog: 23.39±5.19 cm²), with no difference between them (P+>+0.05). In conclusion, our findings indicate that the progression of overload through load or repetitions can be used to promote gains in strength and muscle hypertrophy in young men and women in the early stages of training.

Low-Load Resistance Training Performed to Muscle Failure or Near Muscle Failure Does Not Promote Additional Gains on Muscle Strength, Hypertrophy, and Functional Performance of Older Adults.

ABSTRACT: Bergamasco, JGA, Gomes da Silva, D, Bittencourt, DF, Martins de Oliveira, R, Júnior, JCB, Caruso, FC, Godoi, D, Borghi-Silva, A, and Libardi, CA. Low-load resistance training performed to muscle failure or near muscle failure does not promote additional gains on muscle strength, hypertrophy, and functional performance of older adults. J Strength Cond Res 36(5): 1209-1215, 2022-The aim of the present study was to compare the effects of low-load resistance training (RT) protocols performed to failure (FAI), to voluntary interruption (VOL), and with a fixed low repetitions (FIX) on muscle strength, hypertrophy, and functional performance in older adults. Forty-one subjects (60-77 years) were randomized into one of the RT protocols (FAI, VOL, or FIX) and completed 12 weeks of RT at 40% of 1 repetition maximum (1RM), twice a week. The assessments included 1RM test, muscle cross-sectional area (CSA), rate of torque development (RTD), and functional performance (chair stand [CS], habitual gait speed [HGS], maximal gait speed [MGS], and timed up-and-go [TUG]). All protocols significantly increased 1RM values from Pre (FAI: 318.3 ± 116.3 kg; VOL: 342.9 ± 93.7 kg; FIX: 328.0 ± 107.2 kg) to Post (FAI: 393.0 ± 143.1 kg, 23.5%; VOL: 423.0 ± 114.5 kg, 23.3%; FIX: 397.8 ± 94.6 kg, 21.3%; p < 0.0001 for all groups). Regarding CS, all protocols showed significant improvements from Pre (FAI: 11.5 ± 2.4 seconds; VOL: 12.1 ± 2.5 seconds; FIX: 11.3 ± 1.1 seconds) to Post (FAI: 10.5 ± 1.1 seconds, -8.5%, p = 0.001; VOL: 10.3 ± 1.5 seconds, -15.1%, p = 0.001; FIX: 11.0 ± 1.1, -3.2%, p = 0.001). Habitual gait speed values increased significantly from Pre (FAI: 1.3 ± 0.2 m·s-1; VOL: 1.3 ± 0.1 m·s-1; FIX: 1.3 ± 0.1 m·s-1) to Post (FAI: 1.4 ± 0.2 m·s-1, 2.5%, p = 0.03; VOL: 1.4 ± 0.2 m·s-1, 5.2%, p = 0.036; FIX: 1.4 ± 0.1 m·s-1, 5.7%, p = 0.03). No significant differences between protocols were found (p > 0.05). In addition, there were no significant changes in CSA, RTD, MGS, and TUG for any protocols (p > 0.05). In conclusion, low-load RT performed without muscle failure promotes significant improvements in muscle strength and some parameters of functional performance in older adults.

Effects of Blood Flow Restriction Combined With Resistance Training or Neuromuscular Electrostimulation on Muscle Cross-Sectional Area.

CONTEXT: Low-load resistance training (LL) and neuromuscular electrostimulation (NES), both combined with blood flow restriction (BFR), emerge as effective strategies to maintain or increase muscle mass. It is well established that LL-BFR promotes similar increases in muscle cross-sectional area (CSA) and lower rating of perceived exertion (RPE) and pain compared with traditional resistance training protocols. On the other hand, only 2 studies with conflicting results have investigated the effects of NES-BFR on CSA, RPE, and pain. In addition, no study directly compared LL-BFR and NES-BFR. OBJECTIVE: The aim of the study was to compare the effects of LL-BFR and NES-BFR on vastus lateralis CSA, RPE, and pain. Individual response for muscle hypertrophy was also compared between protocols. DESIGN: Intrasubject longitudinal study. SETTING: University research laboratory. INTERVENTION: Fifteen healthy young males (age = 23 [5] y; weight = 77.6 [11.3] kg; height = 1.76 [0.08] m). MAIN OUTCOME MEASURES: Vastus lateralis CSA was measured through ultrasound at baseline (pre) and after 20 training sessions (post). The RPE and pain responses were obtained through modified 10-point scales, handled during all training sessions. RESULTS: Both protocols demonstrated significant increases in muscle CSA (P < .0001). However, the LL-BFR demonstrated significantly greater CSA changes compared with NES-BFR (LL-BFR = 11.2%, NES-BFR = 4.6%; P < .0001). Comparing individual increases in CSA, 12 subjects (85.7% of the sample) presented greater muscle hypertrophy for LL-BFR than for the NES-BFR protocol. In addition, LL-BFR produced significantly lower RPE and pain responses (P < .0001). CONCLUSIONS: The LL-BFR produced significantly greater increases in CSA with significant less RPE and pain than NES-BFR. In addition, LL-BFR resulted in greater individual muscle hypertrophy responses for most subjects compared with NES-BFR.

Resistance Training With Partial Blood Flow Restriction in a 99-Year-Old Individual: A Case Report.

In aging populations for which the use of high loads is contraindicated, low load resistance training associated with blood flow restriction (RT-BFR) is an alternative strategy to induce muscle mass gains. This study investigates the effects of RT-BFR on muscle mass, muscle function, and quality of life of a 99-year-old patient with knee osteoarthritis and advanced muscle mass deterioration. Training protocol consisted of 24 sessions of a unilateral free-weight knee extension exercise associated with partial blood flow restriction through a manometer cuff set at 50% of complete vascular occlusion pressure. We evaluated: cross-sectional area (CSA) and thickness (MT) of the vastus lateralis muscle by ultrasound; function through the Timed Up and Go (TUG) test; and quality of life (QoL) by the WHOQOL-bref, WHOQOL-OLD and WOMAC questionnaires. All tests were performed prior to the training period (Pre) and after the 12th (Mid) and 24th (Post) sessions. Changes were considered significant if higher than 2 times the measurement's coefficient of variation (CV). After 24 sessions, there was an increase of 12% in CSA and 8% in MT. Questionnaires scores and TUG values worsened from Pre to Mid and returned in Post. We consider RT-BFR a viable and effective strategy to promote muscle mass gains in nonagenarians and delay the decline in functionality and QoL associated with aging.

Suspension training vs. traditional resistance training: effects on muscle mass, strength and functional performance in older adults.

PURPOSE: We compared the effects of suspension training (ST) with traditional resistance training (TRT) on muscle mass, strength and functional performance in older adults. METHODS: Forty-two untrained older adults were randomized in TRT, ST (both performed 3 sets of whole body exercises to muscle failure) or control group (CON). Muscle thickness (MT) of biceps brachii (MTBB) and vastus lateralis (MTVL), maximal dynamic strength test (1RM) for biceps curl (1RMBC) and leg extension exercises (1RMLE), and functional performance tests (chair stand [CS], timed up and go [TUG] and maximal gait speed [MGS]) were performed before and after 12 weeks of training. RESULTS: MTBB increased significantly and similarly for all training groups (TRT 23.35%; ST 21.56%). MTVL increased significantly and similarly for all training groups (TRT 13.03%; ST 14.07%). 1RMBC increased significantly and similarly for all training groups (TRT 16.06%; ST 14.33%). 1RMLE increased significantly and similarly for all training groups (TRT 14.89%; ST 18.06%). MGS increased significantly and similarly for all groups (TRT 6.26%; ST 5.99%; CON 2.87%). CS decreased significantly and similarly for all training groups (TRT - 20.80%; ST - 15.73%). TUG decreased significantly and similarly for all training groups (TRT - 8.66%; ST - 9.16%). CONCLUSION: Suspension training (ST) promotes similar muscle mass, strength and functional performance improvements compared to TRT in older adults.

Neuroendocrine pancreatic tumor causing chronic diarrhea in young adult, a case report.

Secretory tumors of vasoactive intestinal polypeptides (VIPomas) are rare neuroendocrine pancreatic neoplasms usually associated with secretory diarrhea. Most cases present themselves with diarrhea, weight loss, and hypokalemia. Although VIPoma patients share easily distinguishable symptoms, early diagnosis remains a challenge. Therefore, tumors are usually found in large proportions and with later staging. The presenting case portrays a unique situation where the tumor found was still in a small size, is worth reporting it to the current literature. The diagnosis was made through laboratory evaluation and imaging studies. The primary treatment consists of exeresis surgery, but cytoreductive surgery also can provide several benefits. This way is necessary to pay attention to diagnoses also in the ways of treatment.

Late cholestatic syndrome due to previous perforating trauma: Case report.

INTRODUCTION: The presence of a foreign body obstructing the bile duct may appear through a typical picture of cholangitis, usually caused by the presence of gallstones. PRESENTATION OF CASE: Male patient, 31 years old, involved an in accident with gunshot in 2006, injured in the abdominal region. Evolved to a picture of intense pain in the right hypochondrium, mainly after fat meals, without irradiation 12 years after being injured. Presented jaundice episode associated to fecal acholia, choluria, pruritus and sporadic fever. It was diagnosed cholangitis due to the foreign body like a bullet, located in the hepatic duct after tomography performed for investigation. The conduction of the case is described next. DISCUSSION: Cholestatic syndrome caused by gun bullet in a prior event to the symptoms is a rare event in the literature. Total, there are 8 case reports of bullets found in bile ducts with distinct evolution time among themselves. The first exam will not necessarily identify the bullet, but it simplifies the visualization of the bile ducts dilation, characterizing obstruction. CONCLUSION: The presence of a foreign body in the bile ducts is well reported in literature, and it is directly dependent on previous history. We should always avoid using cholangioresonance in dubious cases. To keep the ERCP as initial treatment is recommended due to the advances on the procedure quality, but in more severe cases or lack of resources, the surgical exploration is still indicated.

The Association Between Muscle Deoxygenation and Muscle Hypertrophy to Blood Flow Restricted Training Performed at High and Low Loads.

The metabolic stress induced by blood flow restriction (BFR) during resistance training (RT) might maximize muscle growth. However, it is currently unknown whether metabolic stress are associated with muscle hypertrophy after RT protocols with high- or low load. Therefore, the aim of the study was to compare the effect of high load RT (HL-RT), high load BFR (HL-BFR), and low load BFR (LL-BFR) on deoxyhemoglobin concentration [HHb] (proxy marker of metabolic stress), muscle cross-sectional area (CSA), activation, strength, architecture and edema before (T1), after 5 (T2), and 10 weeks (T3) of training with these protocols. Additionally, we analyzed the occurrence of association between muscle deoxygenation and muscle hypertrophy. Thirty young men were selected and each of participants' legs was allocated to one of the three experimental protocols in a randomized and balanced way according to quartiles of the baseline CSA and leg extension 1-RM values of the dominant leg. The dynamic maximum strength was measured by 1-RM test and vastus lateralis (VL) muscle cross-sectional area CSA echo intensity (CSAecho) and pennation angle (PA) were performed through ultrasound images. The measurement of muscle activation by surface electromyography (EMG) and [HHb] through near-infrared spectroscopy (NIRS) of VL were performed during the training session with relative load obtained after the 1-RM, before (T1), after 5 (T2), and 10 weeks (T3) training. The training total volume (TTV) was greater for HL-RT and HL-BFR compared to LL-BFR. There was no difference in 1-RM, CSA, CSAecho, CSAecho/CSA, and PA increases between protocols. Regarding the magnitude of the EMG, the HL-RT and HL-BFR groups showed higher values than and LL-BFR. On the other hand, [HHb] was higher for HL-BFR and LL-BFR. In conclusion, our results suggest that the addition of BFR to exercise contributes to neuromuscular adaptations only when RT is performed with low-load. Furthermore, we found a significant association between the changes in [HHb] (i.e., metabolic stress) and increases in muscle CSA from T2 to T3 only for the LL-BFR, when muscle edema was attenuated.

Train High Eat Low for Osteoarthritis study (THE LO study): protocol for a randomized controlled trial.

INTRODUCTION: Osteoarthritis (OA) is one of the most prevalent chronic conditions among older adults, with the medial tibio-femoral joint being most frequently affected. The knee adduction moment is recognized as a surrogate measure of the medial tibio-femoral compartment joint load and therefore represents a valid intervention target. This article provides the rationale and methodology for THE LO study (Train High, Eat Low for Osteoarthritis), which is a randomized controlled trial that is investigating the effects of a unique, targeted lifestyle intervention in overweight/obese adults with symptomatic medial knee OA. RESEARCH QUESTION: Compared to a control group given only lifestyle advice, do the effects of the following interventions result in significant reductions in the knee adduction moment: (1) gait retraining; and (2) combined intervention (which involves a combination of three interventions: (a) gait retraining, (b) high-intensity progressive resistance training, and (c) high-protein/low-glycaemic-index energy-restricted diet)? It is hypothesized that the combined intervention group will be superior to the isolated interventions of the high-protein/low-glycaemic-index diet group and the progressive resistance training group. Finally, it is hypothesized that the combined intervention will result in a greater range of improvements in secondary outcomes, including: muscle strength, functional status, body composition, metabolic profile, and psychological wellbeing, compared to any of the isolated interventions or control group. DESIGN: Single-blinded, randomized controlled trial adhering to the CONSORT guidelines on conduct and reporting of non-pharmacological clinical trials. PARTICIPANTS: One hundred and twenty-five community-dwelling people are being recruited. Inclusion criteria include: medial knee OA, low physical activity levels, no current resistance training, body mass index ≥ 25kg/m(2) and age ≥ 40 years. INTERVENTION AND CONTROL: The participants are stratified by sex and body mass index, and randomized into one of five groups: (1) gait retraining; (2) progressive resistance training; (3) high-protein/low-glycaemic-index energy-restricted diet (25 to 30% of energy from protein, 45% of energy from carbohydrates, < 30% of energy from fat, and glycaemic index diet value < 50); (4) a combination of these three active interventions; or (5) a lifestyle-advice control group. All participants receive weekly telephone checks for health status, adverse events and optimisation of compliance. MEASUREMENTS: Outcomes are measured at baseline, 6 and 12 months. The primary outcome is the peak knee adduction moment during the early stance phase of gait. The secondary outcome measures are both structural (radiological), with longitudinal reduction in medial minimal joint space width at 12 months, and clinical, including: change in body mass index; joint pain, stiffness and function; body composition; muscle strength; physical performance/mobility; nutritional intake; habitual physical activity and sedentary behaviour; sleep quality; psychological wellbeing and quality of life. DISCUSSION: THE LO study will provide the first direct comparison of the long-term benefits of gait retraining, progressive resistance training and a high-protein/low-glycaemic-index energy-restricted diet, separately and in combination, on joint load, radiographic progression, symptoms, and associated co-morbidities in overweight/obese adults with OA of the knee.