ANDROGEN AND GLUCOCORTICOID RECEPTOR PHOSPHORYLATION FOLLOWING AN ACUTE RESISTANCE EXERCISE BOUT IN TRAINED AND UNTRAINED MEN

INTRODUCTION: Optimizing the concentration of hormones through variation of load, repetitions, and rest periods is suggested for building muscle mass in current resistance exercise prescription guidelines. Physiological actions of testosterone and cortisol occur when bound to their respective intracellular receptor. Muscle growth is initiated when testosterone binds to its androgen receptor (AR); conversely, muscle breakdown is initiated when cortisol binds to its glucocorticoid receptor (GR) in muscle cells. The secretion of both testosterone and cortisol increase following a single bout of resistance exercise (RE). While both in vitro and in vivo models indicate the significant contribution to muscle growth, the importance of the acute hormonal response in humans has been justified and refuted. However, there is recent evidence showing phosphorylation and regulation of ARs and GRs can occur in the absence of testosterone and cortisol. The equivocal results of prior studies on hormonal responses and muscle adaptation could be clarified by understanding how AR and GR are regulated. PURPOSE: The purpose of this study is to examine the differences in the androgen and glucocorticoid receptor phosphorylation between resistance trained and untrained men following an acute bout of moderate intensity resistance training. It will also look at the biopsy time point post resistance exercise for AR and GR phosphorylation following resistance training. METHODS: Ten resistance trained (RT) and ten untrained (UT) healthy, college aged (18-30) men volunteered for this study. One UT subject was unable to complete the protocol resulting in an N of 9. Subjects performed 1RM tests for back squat and leg extension 4-7 days prior to the RE protocol. There were no differences in the protocol between RT and UT groups. Subjects arrived at the lab at least 6 hours fasted and euhydrated between 10:00am-2:00pm to control for diurnal variations of hormones. Prior to training, baseline blood and muscle biopsy were collected for baseline levels. After a warm-up, subjects performed 6 sets of 10 repetitions at 75% of their 1RM with 1.5 minutes rest following each set followed by 4 set of 10 repetitions at 75% of their 1RM for leg extension with 1.5 minutes rest after each set. After completing the leg extension exercise, blood samples were collected at 5 min, 15 min, and 45 min post exercise, and biopsies were taken at 10 min, 30 min, 60 min, and 180 min post exercise. Hormonal data were analyzed using parametric methods. 2 x 4 (group x time) RMANOVAs were used to determine potential differences in testosterone and cortisol between groups (group) at PRE, 5P, 15P and 45P (time). Total receptor data were not normally distributed, thus total receptor data were analyzed using Mann-Whitney U test, Friedman test, and Wilcoxon signed-rank test. Performance data were analyzed using RMANOVAs and independent t tests. RESULTS: 1RM was significantly different between groups (p 0.05), although there were RPE significant differences across sets. There were significant differences for mean force (N) between RT and UT groups for all sets, and the RT group began to significantly decrease by set 6. There was a significant difference in work (J) between groups for sets 1 and 2, with the RT group significantly decreasing by sets 5 and 6. In both the RT and UT groups testosterone significantly increased from PRE values at 5min and 15min post exercise (p .05); however, there were differences between time points within the UT group (p = .016). In the UT group, total AR expression significantly decreased at 30P (-19.33%∆, z = -2.192, p = .027) and 60P (-10.89%∆, z = -2.192, p = .027) post exercise, but returned to baseline values by 180P (3%∆, z = -.178, p .05). There were significant decreases at 10P in p-AR Ser213 in both the RT (-28.73%∆, z = -2.293, p = .020) and UT (-32.25%∆, z = -2.073, p = .039) groups. There were no differences between or within groups (p .05) for p-AR Ser81, p-AR Ser515, or p-AR Ser650. For Total GR content, there were no differences between time points within the RT or UT groups (p .05). Total GR content was significantly greater in the RT group compared to the UT group at 10P (Mann-Whitney U = 19, z = -2.123, p = .035). For p-GR Ser134 the RT group was significantly higher than the UT group at PRE (Mann-Whitney U = 15, z = 2.449, p = .014), but the UT group was significantly higher than the RT group at 30P (Mann-Whitney U = 9, z = -2.939, p = .003). Within the RT group for p-GR Ser134 there were decreases compared to PRE at 10P (-33.13%∆, z = -2.395, p = .017), 30P (-32.89%∆, z = -2.803, p = .005), and 60P (-22.71%∆, z = -2.803, p = .005), but returned to baseline by 180P (-6.63%∆, z = -1.274, p = .203); conversely, in the UT group, increases were shown compared to PRE values at 30P (85.84%∆, z = -2.666, p = .008), 60P (111.24%∆, z = -2.666, p = .008), and 180P (68.30%∆, z = -2.666, p = .008). There were significant decreases in p-GR Ser211 from PRE to 60P (-30.76%∆, z = -2.701, p = .007) and 180P (-30.33%∆, z = -2.599, p = .009) in the RT group and from PRE to 180P (-42.98%∆, z = -2.666, p = .008) in the UT group. In p-GR Ser226, the UT group had a higher expression at 10P (Mann-Whitney U = 21, z = -1.960, p = .050) and 180P (Mann-Whitney U = 20, z = -2.041, p = .041) compared to the RT group. There were significant increases from PRE in both the RT group at 10P (311.5%∆, z = -2.803, p = .005), 30P (33.97%∆, z = -2.803, p = .005), 60P (387.42%∆, z = -2.803, p = .005), and 180P (240.16%∆, z = -2.803, p = .005) as well as the UT group at 10P (615.52%∆, z = -2.666, p = .008), 30P (568.66%∆, z = -2.666, p = .008), 60P (441.12%∆, z = -2.666, p = .008), and 180P (395.26%∆, z = -2.666, p = .008). CONCLUSION: When analyzing androgen and glucocorticoid receptors, training status needs to be accounted for as there are training status dependent differences. Although the importance of the acute hormonal response on muscle hypertrophy is still controversial, it appears to have some effect at the receptor level in preserving content and in phosphorylation of various receptor sites that cannot be ignored. The RT group was able to maintain their total AR content up to 180 min post RE; whereas, the UT group saw decreases at 30 min and 60 min post exercise. In addition, the ligand dependent GR Ser211 site did not show a phosphorylation decrease in the UT group, who had a prolonged elevation in cortisol compared to the RT group, until 180 min post RE, whereas the RT group decreased at 60 min post RE. Also, at the ligand dependent and independent GR Ser134 site we saw almost opposite effects in training group where the RT group decreased phosphorylation at 10P, 30P, and 60P, but the UT group saw and increase in phosphorylation at 30P, 60P, and 180P. Phosphorylation of GR Ser226 increased at all post time points in both groups, but was higher in the UT group at 10P and 180P. AR Ser213 decreased in both groups at 10P, and no differences were seen at AR Ser81, Ser515, or Ser650 sites in our moderate intensity protocol. Further research could elucidate the hormone-receptor and receptor phosphorylation responses to RE by looking at a variety of training protocols, later muscle collection time points, MAPK responses, chronic training, and responses in a fed state

Chronic training status affects muscle excitation of the vastus lateralis during repeated contractions

This study examined electromyographic amplitude (EMGRMS)-force relationships during repeated submaximal knee extensor muscle actions among chronic aerobically-(AT), resistance-trained (RT), and sedentary (SED) individuals. Fifteen adults (5/group) attempted 20 isometric trapezoidal muscle actions at 50% of maximal strength. Surface electromyography (EMG) was recorded from vastus lateralis (VL) during the muscle actions. For the first and last successfully completed contractions, linear regression models were fit to the log-transformed EMGRMS-force relationships during the linearly increasing and decreasing segments, and the b terms (slope) and a terms (antilog of y-intercept) were calculated. EMGRMS was averaged during steady force. Only the AT completed all 20 muscle actions. During the first contraction, the b terms for RT (1.301 ​± ​0.197) were greater than AT (0.910 ​± ​0.123; p ​= ​0.008) and SED (0.912 ​± ​0.162; p ​= ​0.008) during the linearly increasing segment, and in comparison to the linearly decreasing segment (1.018 ​± ​0.139; p ​= ​0.014), respectively. For the last contraction, the b terms for RT were greater than AT during the linearly increasing (RT ​= ​1.373 ​± ​0.353; AT ​= ​0.883 ​± ​0.129; p ​= ​0.018) and decreasing (RT ​= ​1.526 ​± ​0.328; AT ​= ​0.970 ​± ​0.223; p ​= ​0.010) segments. In addition, the b terms for SED increased from the linearly increasing (0.968 ​± ​0.144) to decreasing segment (1.268 ​± ​0.126; p ​= ​0.015). There were no training, segment, or contraction differences for the a terms. EMGRMS during steady force increased from the first- ([64.08 ​± ​51.68] ​μV) to last-contraction ([86.73 ​± ​49.55] ​μV; p ​= ​0.001) collapsed across training statuses. The b terms differentiated the rate of change for EMGRMS with increments in force among training groups, indicating greater muscle excitation to the motoneuron pool was necessary for the RT than AT during the linearly increasing and decreasing segments of a repetitive task

The Relationship between resistance exercise induced testosterone and cortisol responses and steroid receptor phosphorylation

The precise contribution of hormones to resistance training adaptations remains unclear. Recently, resistance exercise (RE) has been shown to change phosphorylation of androgen (pAR) & glucocorticoid receptors (pGR). Examining the relationships between the hormonal responses & steroid receptor phosphorylation may elucidate the role of acute hormonal responses to training adaptations. PURPOSE: The purpose of this study was to examine relationships between exercise-induced hormonal responses and pGR & pAR. METHODS: Resistance trained (RT) (n = 10; age = 21.3±1.7yrs, ht = 175.8±6.8cm, bodymass = 84.5±13.5kg) & untrained (UT) (n = 9; age = 20.8±3.1yrs, ht = 178.7±8.9cm, bodymass = 81.0±14.0kg) men completed an acute RE session of 6 sets of 10 reps, & 4 sets of 10 reps at 75% 1RM of barbell back squats, & knee extension, respectively. Muscle biopsies were obtained at rest, 10+, 30+, 60+, & 180+ minutes post-exercise & analyzed for total AR, pAR at ser81, ser213, ser515, ser650, total GR, and pGR at ser134, ser211, ser226. Testosterone & cortisol samples were obtained before, & up to 45 minutes post-exercise. Pearson correlations were performed to determine relationships between endocrine responses (area-under-curve [AUC]) & changes in total & phosphorylated AR & GR. Significance was determined at p≤0.05. RESULTS: The change in total AR at 180+ was correlated with cortisol (Pooled: r = -0.668, p = 0.002) & was strongest in RT subjects (RT: r = -0.767, p = 0.010). Cortisol was correlated with pARser81 at 60+ (r = 0.601, p = 0.006) & 180+ (r = 0.537, p = 0.018). Cortisol was correlated with the change in pARser650 at 180+ (r = 0.724, p = 0.018) in RT subjects. In UT the changes in pGRser134 & pGRser226 were correlated at 10+ (r = 0.987, p = 0.001) & 30+ (r = 0.943, p = 0.001). CONCLUSION: Cortisol responses were related to AR content, & changes in phosphorylation at sites regulating AR ligand sensitivity, & AR localization. There was a training status-specific relationship in UT subjects between pGR sites that regulate receptor localization, & GR sensitivity to cellular stress. Individualized cortisol responses are strongly related to AR activity and may explain the discrepancy in studies that solely investigated anabolic hormones & training adaptations, since these relationships also appear to be specific to different training statuses

Early childhood lung function is a stronger predictor of adolescent lung function in cystic fibrosis than early Pseudomonas aeruginosa infection

Pseudomonas aeruginosa has been suggested as a major determinant of poor pulmonary outcomes in cystic fibrosis (CF), although other factors play a role. Our objective was to investigate the association of early childhood Pseudomonas infection on differences in lung function in adolescence with CF

Closing the Gap in High-Risk Pregnancy Care Using Machine Learning and Human-AI Collaboration

Health insurers often use algorithms to identify members who would benefit from care and condition management programs, which provide personalized, high-touch clinical support. Timely, accurate, and seamless integration between algorithmic identification and clinical intervention depends on effective collaboration between the system designers and nurse care managers. We focus on a high-risk pregnancy (HRP) program designed to reduce the likelihood of adverse prenatal, perinatal, and postnatal events and describe how we overcome three challenges of HRP programs as articulated by nurse care managers; (1) early detection of pregnancy, (2) accurate identification of impactable high-risk members, and (3) provision of explainable indicators to supplement predictions. We propose a novel algorithm for pregnancy identification that identifies pregnancies 57 days earlier than previous code-based models in a retrospective study. We then build a model to predict impactable pregnancy complications that achieves an AUROC of 0.760. Models for pregnancy identification and complications are then integrated into a proposed user interface. In a set of user studies, we collected quantitative and qualitative feedback from nurses on the utility of the predictions combined with clinical information driving the predictions on triaging members for the HRP program

The selfie and the transformation of the public–private distinction

The selfie is a contemporary form of self-portraiture, representing a photographic image of the human face. The selfie is created for the purpose of reproduction and to communicate images visually with others from a distance. The proliferation of web 2.0 technologies and mobile smart phones enables users to generate and disseminate images at an unprecedented scale. Coupled with the increasing popularity of social media platforms, these technologies allow the selfie to be distributed to a wide audience in close to real time. Drawing upon Erving Goffman’s approach to the study of face-to-face social interaction, this article presents a discussion of the production and consumption of the selfie. We draw upon Goffman’s dramaturgical approach, to explore how the ‘presentation of self’ occurs in the context of a selfie. Next, we consider how the selfie as a form of visual communication holds critical implications for mediated life online as individuals go about doing privacy. We conclude by reflecting on the role of the selfie and its impact on the boundaries between public and private domains in contemporary social life

Genome-wide association study identifies common variants associated with circulating vitamin E levels

In genome-wide association studies (GWAS) of common genetic variants associated with circulating alpha- and gamma-tocopherol concentrations in two adult cohorts comprising 5006 men of European descent, we observed three loci associated with alpha-tocopherol levels, two novel single-nucleotide polymorphisms (SNPs), rs2108622 on 19pter-p13.11 (P= 1.7 × 10−8) and rs11057830 on 12q24.31 (P= 2.0 × 10−8) and confirmed a previously reported locus marked by rs964184 on 11q23.3 (P= 2.7 × 10−10). The three SNPs have been reported to be associated with lipid metabolism and/or regulation. We replicated these findings in a combined meta-analysis with two independent samples, P= 7.8 × 10−12 (rs964184 on 11q23.3 near BUD13, ZNF259 and APOA1/C3/A4/A5), P= 1.4 × 10−10 (rs2108622 on 19pter-p13.11 near CYP4F2) and P= 8.2 × 10−9 (rs11057830 on 12q24.31 near SCARB1). Combined, these SNPs explain 1.7% of the residual variance in log alpha-tocopherol levels. In one of the two male GWAS cohorts (n= 992), no SNPs were significantly associated with gamma-tocopherol concentrations after including data from the replication sample for 71 independent SNPs with P< 1 × 10−4 identified

Psychiatric diagnoses and punishment for misconduct: the effects of PTSD in combat-deployed Marines

<p>Abstract</p> <p>Background</p> <p>Research on Vietnam veterans suggests an association between psychological problems, including posttraumatic stress disorder (PTSD), and misconduct; however, this has rarely been studied in veterans of Operation Iraqi Freedom or Operation Enduring Freedom. The objective of this study was to investigate whether psychological problems were associated with three types of misconduct outcomes (demotions, drug-related discharges, and punitive discharges.)</p> <p>Methods</p> <p>A population-based study was conducted on all U.S. Marines who entered the military between October 1, 2001, and September 30, 2006, and deployed outside of the United States before the end of the study period, September 30, 2007. Demographic, psychiatric, deployment, and personnel information was collected from military records. Cox proportional hazards regression analysis was conducted to investigate associations between the independent variables and the three types of misconduct in war-deployed (n = 77 998) and non-war-deployed (n = 13 944) Marines.</p> <p>Results</p> <p>Marines in both the war-deployed and non-war-deployed cohorts with a non-PTSD psychiatric diagnosis had an elevated risk for all three misconduct outcomes (hazard ratios ranged from 3.93 to 5.65). PTSD was a significant predictor of drug-related discharges in both the war-deployed and non-war-deployed cohorts. In the war-deployed cohort only, a specific diagnosis of PTSD was associated with an increased risk for both demotions (hazard ratio, 8.60; 95% confidence interval, 6.95 to 10.64) and punitive discharges (HR, 11.06; 95% CI, 8.06 to 15.16).</p> <p>Conclusions</p> <p>These results provide evidence of an association between PTSD and behavior problems in Marines deployed to war. Moreover, because misconduct can lead to disqualification for some Veterans Administration benefits, personnel with the most serious manifestations of PTSD may face additional barriers to care.</p

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure