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Background Chronic obstructive pulmonary disease (COPD) patients exhibit skeletal muscle atrophy, denervation, and reduced mitochondrial oxidative capacity. Whilst chronic tobacco smoke exposure is implicated in COPD muscle impairment, the mechanisms involved are ambiguous. The aryl hydrocarbon receptor (AHR) is a ligand‐activated transcription factor that activates detoxifying pathways with numerous exogenous ligands, including tobacco smoke. Whereas transient AHR activation is adaptive, chronic activation can be toxic. On this basis, we tested the hypothesis that chronic smoke‐induced AHR activation causes adverse muscle impact. Methods We used clinical patient muscle samples, and in vitro (C2C12 myotubes) and in vivo models (mouse), to perform gene expression, mitochondrial function, muscle and neuromuscular junction morphology, and genetic manipulations (adeno‐associated virus‐mediated gene transfer). Results Sixteen weeks of tobacco smoke exposure in mice caused muscle atrophy, neuromuscular junction degeneration, and reduced oxidative capacity. Similarly, smoke exposure reprogrammed the muscle transcriptome, with down‐regulation of mitochondrial and neuromuscular junction genes. In mouse and human patient specimens, smoke exposure increased muscle AHR signalling. Mechanistically, experiments in cultured myotubes demonstrated that smoke condensate activated the AHR, caused mitochondrial impairments, and induced an AHR‐dependent myotube atrophy. Finally, to isolate the role of AHR activity, expression of a constitutively active AHR mutant without smoke exposure caused atrophy and mitochondrial impairments in cultured myotubes, and muscle atrophy and neuromuscular junction degeneration in mice. Conclusions These results establish that chronic AHR activity, as occurs in smokers, phenocopies the atrophy, mitochondrial impairment, and neuromuscular junction degeneration caused by chronic tobacco smoke exposure.

Elevated mitochondrial reactive oxygen species (mROS) and an increase in caspase-3 activity are established mechanisms that lead to skeletal muscle atrophy via the upregulation of protein degradation pathways. However, the mechanisms upstream of an increase in mROS and caspase-3 activity in conditions of muscle atrophy have not been identified. Based upon knowledge that an event known as mitochondrial permeability transition (MPT) causes an increase in mROS emission and the activation of caspase-3 via mitochondrial release of cytochrome c, as well as the circumstantial evidence for MPT in some muscle atrophy conditions, we tested MPT as a mechanism of atrophy. Briefly, treating cultured single mouse flexor digitorum brevis (FDB) fibers from adult mice with a chemical inducer of MPT (Bz423) for 24 h caused an increase in mROS and caspase-3 activity that was accompanied by a reduction in muscle fiber diameter that was able to be prevented by inhibitors of MPT, mROS, or caspase-3 (p < 0.05). Similarly, a four-day single fiber culture as a model of disuse caused atrophy that could be prevented by inhibitors of MPT, mROS, or activated caspase-3. As such, our results identify MPT as a novel mechanism of skeletal muscle atrophy that operates through mROS emission and caspase-3 activation.

In advanced age, there is an accelerated decline in skeletal muscle mass that appears to be secondary to repeated cycles of denervation-reinnervation and eventually, failed reinnervation. However, whether variation in reinnervation capacity explains why some muscles are less vulnerable to age-related atrophy has not been addressed. In this study we examined changes in neuromuscular junction (NMJ) morphology, fiber cross-sectional area (CSA) and fiber type, accumulation of severely atrophied myofibers, and expression of a marker of denervation in four muscles that exhibit differences in the degree of age-related atrophy and which span the extremes of fiber type composition in 8 mo old (8 M) and 34 mo old (34 M) male Fischer 344 Brown Norway F1 hybrid rats. Aging muscle atrophy was most pronounced in the fast twitch gastrocnemius (Gas; 25%) and similar between extensor digitorum longus (EDL) and slow-twitch soleus (Sol) muscle (14-15%), whereas the slow-twitch adductor longus (AL) increased in mass by 21% between 8 M and 34 M (P 0.05 for all). Only the Sol exhibited significant alterations in fiber type with aging, and there was a decrease in fiber CSA in the Gas, EDL, and Sol (P 0.05) with aging that was not seen in the AL. Muscles that atrophied had an increased fraction of severely atrophic myofibers (P 0.05), but this was not observed in the AL. The Gas and EDL both demonstrated a similar degree of age-related remodeling of pre- and post-synaptic NMJ components. On the other hand, pre- and post-synaptic morphology underwent greater changes with aging in the AL, and many of these same morphological variables were already greater in the Sol vs AL at 8 M, suggesting the Sol had already undergone substantial remodeling and may be nearing its adaptive limits. Consistent with this idea, analysis of NMJ morphology in Sol from 3 M rats exhibited similar values as 8 M AL, and the Sol demonstrated greater expression of the denervation marker neural cell adhesion molecule (NCAM) compared to the AL at 34 M. Collectively, our results are consistent with NMJ remodeling capacity being finite with aging and that maintained remodeling potential confers atrophy protection in aging skeletal muscle by reducing the degree of persistent denervation.

Chronic kidney disease (CKD) causes progressive skeletal myopathy involving atrophy, weakness, and fatigue. Mitochondria have been thought to contribute to skeletal myopathy; however, the molecular mechanisms underlying muscle metabolism changes in CKD are unknown. We employed a comprehensive mitochondrial phenotyping platform to elucidate the mechanisms of skeletal muscle mitochondrial impairment in mice with adenine-induced CKD. CKD mice displayed significant reductions in mitochondrial oxidative phosphorylation (OXPHOS), which was strongly correlated with glomerular filtration rate, suggesting a link between kidney function and muscle mitochondrial health. Biochemical assays uncovered that OXPHOS dysfunction was driven by reduced activity of matrix dehydrogenases. Untargeted metabolomics analyses in skeletal muscle revealed a distinct metabolite profile in CKD muscle including accumulation of uremic toxins that strongly associated with the degree of mitochondrial impairment. Additional muscle phenotyping found CKD mice experienced muscle atrophy and increased muscle protein degradation, but only male CKD mice had lower maximal contractile force. CKD mice had morphological changes indicative of destabilization in the neuromuscular junction. This study provides the first comprehensive evaluation of mitochondrial health in murine CKD muscle to our knowledge and uncovers several unknown uremic metabolites that strongly associate with the degree of mitochondrial impairment.

Practicing clinicians must use moral reasoning to solve ethical problems and combat moral distress. Development of moral reasoning in occupational therapy (OT) and physical therapy (PT) students has been significantly under researched. The purpose of this study was to analyze the differences in moral reasoning between first year and second year OT and PT students and between students and OT and PT practitioners. Investigators utilized a cross-sectional study design with a convenience sample of University of Indianapolis OT and PT students and a combination of convenience and snowball sampling to recruit licensed OT and PT practitioners. One hundred and fifty-four participants completed the Defining Issues Test - 2 (DIT-2; Rest et al., 1999) survey. Comparisons of N2 scores using t-tests found no differences between groups in moral reasoning schema (one’s preferred way of approaching moral issues, divided into stratified developmental levels). However, Pearson’s Chi-Square analysis for a comparison of all students to all practitioners for moral reasoning patterns (one’s ability to discriminate between types of moral reasoning schemas when presented with a complex moral dilemma) was significant between students (transitional) and practitioners (consolidated), with the greatest difference between second-year students and practitioners. Continual expansion of ethics content, including interjecting clinical experiences into the classroom, within OT and PT graduate programs may promote moral reasoning pattern development with carryover into practice. Clinical experiences provide real-world opportunities necessary to progress students from transitional to consolidated thinking patterns. To improve ethics education, authors recommend active learning strategies and ethics mentorship throughout clinical experiences.

OBJECTIVES: Yes-Associated Protein (YAP) is implicated as a regulator of the post-exercise skeletal muscle response through mechanical transduction. We recently observed that resistance exercise (RE) increased both total (t) and phosphorylated (p) muscle YAP content, which correlated with extracellular signal-regulated kinase 1/2 (Erk1/2). Other anabolic signaling pathways (i.e., mTORC1) are known to be potentiated by the combined stimuli of RE and protein ingestion during post-exercise recovery. However, the impact of protein ingestion on t- and p-muscle YAP content during recovery from RE is unknown. Therefore, we aimed to determine the nutrient sensitivity of YAP in both an acute and chronic exercise setting in aging skeletal muscle. METHODS: Acute study: 13 untrained older women (59.8 ± 0.5 y) were randomized to perform an acute bout of unilateral RE (3 sets × 12 repetitions at 65% of one repetition maximum) followed by the ingestion of whey protein (0.3 g/kg lean body mass) or water. Muscle biopsies of both the rested and exercised legs were collected before and during the postprandial period. Chronic study: 20 untrained middle-aged men and women (47.5 ± 0.3 y) performed 3 weeks of whole body RE (3 d/wk) with moderate or high protein intake set at 1.2 g/kg/d or 1.6 g/kg/d, respectively. Muscle biopsies were taken weekly in the rested state. Total and phosphorylated YAP(Ser127) and Erk1/2(Thr202/Tyr204) were examined by western blotting. RESULTS: Acute study: Protein ingestion decreased t- and p-YAP compared to the water condition in the non-exercised leg (main effect: P 0.05). There was a decrease in t-Erk1/2 irrespective of condition (P = 0.04). There was no change in p/t ratio of Erk1/2 throughout training. There was a significant correlation between t-Erk1/2 and t-YAP (r = 0.741 and P

During a traditional set configuration of resistance exercise (TRD), characterized by a continuous completion of repetitions, a decrease in power output tends to occur throughout a set of repetitions. Inclusion of intraset rest, otherwise known as a cluster set configuration (CLU), counteracts this power decline. However, the effect of a CLU configuration on postexercise myofibrillar protein synthesis rates (MPS) and anabolic signaling has not been investigated. PURPOSE We aimed to determine if any mechanistic differences exist between TRD and CLU signaling events associated with muscle anabolism. METHODS In randomized crossover trials, eight resistance-trained participants (23 ± 1 yr, 81 ± 4.7 kg, body fat: 18% ± 1.9%; 1 repetition maximum [1RM], 150 ± 9.1 kg) performed an acute bout of CLU (4 sets × (2 × 5) repetitions, 30-s intraset rest, 90-s interset rest) and TRD (4 sets × 10 repetitions, 120-s interset rest) barbell back squats at approximately 70% 1RM with total volume load equated during primed continuous L-[ring-C6]phenylalanine infusions. Blood and muscle biopsy samples were collected at rest and after exercise at 0, 2, and 5 h. RESULTS There was no difference in postexercise MPS between the CLU and TRD condition (P > 0.05) and no changes in phosphorylation of mTORC1 downstream targets (p70S6K and 4EBP1). Total and phosphorylated yes-associated protein on Ser127 transiently increased (P < 0.01) immediately after exercise (t = 0) in CLU (~2.1-fold) and TRD condition (~2.2-fold). CONCLUSIONS Our results show that CLU is a viable anabolic option by preserving power output with similar MPS stimulation when compared with the TRD condition in trained young adults.

Physical therapy intervention is often sought to treat cervical spine conditions and a comprehensive physical therapy examination has been associated with more favourable outcomes. The cervical relocation test (CRT) is one method used to assess joint position sense (PS) integrity of the cervical spine. Previous research has found significant differences in the CRT between symptomatic and asymptomatic subjects. Impaired kinaesthetic awareness in the cervical spine may be associated with degenerative joint disease, chronicity of the complaint and increased susceptibility to re-injury.The purpose of this study was to determine the intertester and intratester reliability of cervical relocation using the cervical range of motion instrument (CROM) and an affixed laser (AL) device among subjects with and without a history of neck pain. In addition, it was hypothesised that those individuals with a history of neck pain would have greater difficulty on the CRT.A total of 50 asymptomatic subjects (n = 50) were assigned to two researchers. The CRT was performed for each tester by the subject rotating the cervical spine for three trials to the right and left for the CROM and AL.The results indicate a significant intertester reliability of the CROM (interclass correlation coefficient (ICC) = 0.717[0.502-0.839]; 0.773[0.595-0.873]) for the subjects in this sample.This study demonstrated that the CROM is a reliable device for measuring cervical relocation between different testers. Future research should investigate if the CRT is predictive of prognosis in patients with cervical pathology.

OBJECTIVES: Over 35% of adults have elevated abdominal obesity. This is concerning because abdominal obesity increases risk for type 2 diabetes. Therefore, dietary interventions with the potential to prevent abdominal obesity and its metabolic consequences have gained increasing importance. Habitual intake of the Hass avocado (Persea Americana) has been cross-sectionally linked to lower abdominal obesity; however, the effects of regular avocado consumption for abdominal adiposity and glycemic measures are unknown. Accordingly, we conducted a single-blind, randomized, controlled trial examining the effects of daily avocado consumption on abdominal adiposity and oral glucose tolerance (OGTT). METHODS: 111 adults (65 females) between 25 and 45y with overweight or obesity (BMI >= 25 kg/m(2)) were randomized to an intervention group (N = 54) that received a daily meal with one fresh avocado or a control group (N = 57) that received an isocaloric meal without avocado for 3 months. DXA was used to assess abdominal fat distribution changes, calculated as the ratio of visceral adipose tissue to subcutaneous abdominal tissue (VS Ratio) and an OGTT was conducted following an overnight fast. RESULTS: A group by time effect (P = 0.04) was observed whereby the intervention group exhibited a reduction in the VS Ratio (0.02; 95% CI, 0.0003 to 0.04) whereas there was no change in the control group (0.003; 95% CI, −0.02 to 0.01). Changes in the VS ratio were driven by a reduction in visceral adipose tissue among intervention participants (28.3 g; 95% CI, 3.4 to 53.3). Avocado consumption did not affect the Matsuda Insulin Sensitivity Index (P = 0.28), Glucose AUC (P = 0.37), or Insulin AUC (P = 0.09). However, there was a group by time effect (P = 0.005) whereby the control group exhibited an increase in insulin concentration at 120 m (21.9 µU/ml; 95% CI, 3.3 to 40.5) whereas there was no change in the intervention group (6.1 µU/ml; 95% CI, −4.4 to 16.5). CONCLUSIONS: Inclusion of one fresh avocado per day over 3 months had abdominal adiposity lowering effects. However, the effects for oral glucose tolerance were limited to insulin secretion 2 h postprandial. Our results demonstrate that avocados have beneficial effects on fat distribution while maintaining insulin sensitivity over time among adults with overweight and obesity. FUNDING SOURCES: This work was supported by funds provided by the Hass Avocado Board. Partial support was also provided by the Department of Kinesiology and Community Health at the University of Illinois and the USDA National Institute of Food and Agriculture, Hatch project 1009249.

Zinc deficiency continues to be a major concern of international nutrition, yet there are still few sensitive and reliable biomarkers for identifying moderate zinc deficiency or monitoring changes ...