The Impact of Medicare on the Distribution of Public Health Care Expenditures in Oklahoma

The purpose of the study is to determine what effect medicare has had on the distribution of public health care expenditures in the state of Oklahoma. The study tests that there is a significant correlation between medical vendor payments and indigency in Oklahoma or in other words that pre-medicare public health care dollars in Oklahoma were distributed to indigents

Effect of individual environmental heat stress variables on training and recovery in professional team sport

Context: Exercise in hot environments increases body temperature and thermoregulatory strain. However, little is known regarding the magnitude of effect that ambient temperature (Ta), relative humidity (RH), and solar radiation individually have on team-sport athletes. Purpose: To determine the effect of these individual heat-stress variables on team-sport training performance and recovery. Methods: Professional Australian Rules Football players (N = 45) undertook 8-wk preseason training producing a total of 579 outdoor field-based observations with Ta, RH, and solar radiation recorded at every training session. External load (distance covered, in m/min; percentage high-speed running [%HSR] >14.4 km/h) was collected via a global positioning system. Internal load (ratings of perceived exertion and heart rate) and recovery (subjective ratings of well-being and heart-rate variability [root mean square of the successive differences]) were monitored throughout the training period. Mixed-effects linear models analyzed relationships between variables using standardized regression coefficients. Results: Increased solar-radiation exposure was associated with reduced distance covered (−19.7 m/min, P 85% HRmax (3.9%, P a was associated with increased distance covered (19.7 m/min, P < .001) and %HSR (3.5%, P = .005). Conclusions: The authors show the importance of considering the individual factors contributing to thermal load in isolation for team-sport athletes and that solar radiation and RH reduce work capacity during team-sport training and have the potential to slow recovery between sessions.</p

Protein coingestion with alcohol following strenuous exercise attenuates alcohol-induced intramyocellular apoptosis and inhibition of autophagy

Alcohol ingestion decreases postexercise rates of muscle protein synthesis, but the mechanism(s) (e.g., increased protein breakdown) underlying this observation is unknown. Autophagy is an intracellular “recycling” system required for homeostatic substrate and organelle turnover; its dysregulation may provoke apoptosis and lead to muscle atrophy. We investigated the acute effects of alcohol ingestion on autophagic cell signaling responses to a bout of concurrent (combined resistance- and endurance-based) exercise. In a randomized crossover design, eight physically active males completed three experimental trials of concurrent exercise with either postexercise ingestion of alcohol and carbohydrate (12 ± 2 standard drinks; ALC-CHO), energy-matched alcohol and protein (ALC-PRO), or protein (PRO) only. Muscle biopsies were taken at rest and 2 and 8 h postexercise. Select autophagy-related gene (Atg) proteins decreased compared with rest with ALC-CHO (P < 0.05) but not ALC-PRO. There were parallel increases (P < 0.05) in p62 and PINK1 commensurate with a reduction in BNIP3 content, indicating a diminished capacity for mitochondria-specific autophagy (mitophagy) when alcohol and carbohydrate were coingested. DNA fragmentation increased in both alcohol conditions (P < 0.05); however, nuclear AIF accumulation preceded this apoptotic response with ALC-CHO only (P < 0.05). In contrast, increases in the nuclear content of p53, TFEB, and PGC-1α in ALC-PRO were accompanied by markers of mitochondrial biogenesis at the transcriptional (Tfam, SCO2, and NRF-1) and translational (COX-IV, ATPAF1, and VDAC1) level (P < 0.05). We conclude that alcohol ingestion following exercise triggers apoptosis, whereas the anabolic properties of protein coingestion may stimulate mitochondrial biogenesis to protect cellular homeostasis

The muscle proteome reflects changes in mitochondrial function, cellular stress and proteolysis after 14 days of unilateral lower limb immobilization in active young men

Skeletal muscle unloading due to joint immobilization induces muscle atrophy, which has primarily been attributed to reductions in protein synthesis in humans. However, no study has evaluated the skeletal muscle proteome response to limb immobilization using SWATH proteomic methods. This study characterized the shifts in individual muscle protein abundance and corresponding gene sets after 3 and 14 d of unilateral lower limb immobilization in otherwise healthy young men. Eighteen male participants (25.4 ±5.5 y, 81.2 ±11.6 kg) underwent 14 d of unilateral knee-brace immobilization with dietary provision and following four-weeks of training to standardise acute training history. Participant phenotype was characterized before and after 14 days of immobilization, and muscle biopsies were obtained from the vastus lateralis at baseline (pre-immobilization) and at 3 and 14 d of immobilization for analysis by SWATH-MS and subsequent gene-set enrichment analysis (GSEA). Immobilization reduced vastus group cross sectional area (-9.6 ±4.6%, P <0.0001), immobilized leg lean mass (-3.3 ±3.9%, P = 0.002), unilateral 3-repetition maximum leg press (-15.6 ±9.2%, P <0.0001), and maximal oxygen uptake (-2.9 ±5.2%, P = 0.044). SWATH analyses consistently identified 2281 proteins. Compared to baseline, two and 99 proteins were differentially expressed (FDR <0.05) after 3 and 14 d of immobilization, respectively. After 14 d of immobilization, 322 biological processes were different to baseline (FDR <0.05, P <0.001). Most (77%) biological processes were positively enriched and characterized by cellular stress, targeted proteolysis, and protein-DNA complex modifications. In contrast, mitochondrial organization and energy metabolism were negatively enriched processes. This study is the first to use data independent proteomics and GSEA to show that unilateral lower limb immobilization evokes mitochondrial dysfunction, cellular stress, and proteolysis. Through GSEA and network mapping, we identify 27 hub proteins as potential protein/gene candidates for further exploration

PO-140 Physiological and Molecular Adaptations to Concurrent Training in Combination with High Protein Availability

Objective Attenuated muscle strength, hypertrophy and power adaptations with combined resistance and endurance (‘concurrent’) training may result from blunted cell signalling. Protein intake potentiates anabolic signalling pathways to facilitate adaptation. We hypothesized that 12 wk concurrent training with a high protein diet would elicit similar adaptations to a) strength, hypertrophy and power compared to resistance training alone, and b) aerobic capacity compared to endurance training. Methods Thirty-two recreationally active males (age 25±5y; BMI 24±3kg•m-2; mean±SD) performed 12 wk of either resistance (RES; n=10) or endurance (END; n=10) training (3x•w-1), or concurrent training (CET; n=12; 6x•w-1) with a high-protein (2g•kg-1•d-1) diet. Strength (1RM), aerobic capacity (VO2peak) and anaerobic power (Wingate) were assessed PRE and POST. Vastus lateralis biopsies (immunoblotting) and thickness (ultrasound) were assessed PRE, after week 4 (WK4) and 8 (WK8), and POST. Changes were analyzed by two-way ANOVA with repeated measures. Results Muscle thickness increased PRE to POST by 18% in CET, 14% in RES and 10% in END (P&lt;0.001) and was greater in CET and RES compared to END (P&lt;0.05). Leg press 1RM increased PRE to POST by 24% in CET and 33% in RES (P&lt;0.01) but was not different between CET and RES. VO2peak (L•min-1) increased PRE to POST by 7% in CET and 12% in END (P&lt;0.05) but was not different between CET and END. Wingate peak power (N•kg-1) increased PRE to POST by 10% in RES (P&lt;0.01) and was greater compared to CET and END (P&lt;0.05). Total mTORC1 increased PRE to POST in CET (P&lt;0.001) and was greater in CET compared to RES and END (P&lt;0.01) and RES compared to END (P&lt;0.05). Conclusions Despite a high protein intake, concurrent training selectively attenuates developments to anaerobic power compared to resistance training. High protein availability may be effective for curtailing interferences to strength and hypertrophy with concurrent training

Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle

Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3176). We show that: (1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, (2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns toward a younger profile, and (3) muscle disuse "ages" the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted toward a younger state after exercise training interventions, while the transcriptome shifted toward an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism, and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity

Meta-analysis of genome-wide DNA methylation and integrative omics of age in human skeletal muscle

International audienceBackground: Knowledge of age-related DNA methylation changes in skeletal muscle is limited, yet this tissue is severely affected by ageing in humans.Methods: We conducted a large-scale epigenome-wide association study meta-analysis of age in human skeletal muscle from 10 studies (total n = 908 muscle methylomes from men and women aged 18-89 years old). We explored the genomic context of age-related DNA methylation changes in chromatin states, CpG islands, and transcription factor binding sites and performed gene set enrichment analysis. We then integrated the DNA methylation data with known transcriptomic and proteomic age-related changes in skeletal muscle. Finally, we updated our recently developed muscle epigenetic clock (https://bioconductor.org/packages/release/bioc/html/MEAT.html).Results: We identified 6710 differentially methylated regions at a stringent false discovery rate <0.005, spanning 6367 unique genes, many of which related to skeletal muscle structure and development. We found a strong increase in DNA methylation at Polycomb target genes and bivalent chromatin domains and a concomitant decrease in DNA methylation at enhancers. Most differentially methylated genes were not altered at the mRNA or protein level, but they were nonetheless strongly enriched for genes showing age-related differential mRNA and protein expression. After adding a substantial number of samples from five datasets (+371), the updated version of the muscle clock (MEAT 2.0, total n = 1053 samples) performed similarly to the original version of the muscle clock (median of 4.4 vs. 4.6 years in age prediction error), suggesting that the original version of the muscle clock was very accurate.Conclusions: We provide here the most comprehensive picture of DNA methylation ageing in human skeletal muscle and reveal widespread alterations of genes involved in skeletal muscle structure, development, and differentiation. We have made our results available as an open-access, user-friendly, web-based tool called MetaMeth (https://sarah-voisin.shinyapps.io/MetaMeth/)