Influence of Acute Turkesterone Dosing on Resting Metabolic Rate and Substrate Utilization in Recreationally-active Males

Turkesterone is a relatively novel phytoecdysteroid compound that has become increasingly popular amongst recreationally active adults seeking to improve body composition. Although many of the these hypothetical benefits arose from prior rodent data demonstrating enhanced substrate utilization, no data presently exist amongst humans in this regard. PURPOSE: to determine the effect of multiple turkesterone doses on both resting metabolic rate (RMR) and substrate utilization in a healthy human population. METHODS: Eleven recreationally active males (23.3±2.2y) visited the laboratory on three occasions separated by at least seven days and were randomized in single-blind, placebo-controlled, and counter-balanced crossover fashion to either 2000mg cellulose placebo (PLA), 1000mg turkesterone + 1000mg placebo, (1000T) or 2000mg (2000T) turkesterone. RMR and respiratory exchange ratio were assessed using a metabolic cart for 20 minutes prior to supplement provision (i.e. baseline [PRE)), as well as 60-minutes (POST60M), 120-minutes (POST120M), and 180-minutes (POST180M) post-acute supplementation timepoints at each visit. RMR, as well as both carbohydrate (CHO) and Fat (FAT) oxidation were analyzed using a two-way (condition [PLA, 1000T, 2000T] x time [PRE, POST60M, POST120M, POST180M) ANOVA with repeated measures at a significance level of pRESULTS: Analyses failed to reveal any significant condition, time, nor interaction effects for RMR, nor CHO or FAT oxidation (p\u3e0.05). Nonetheless, both 1000T (2.7%, 5.6%, and 7.8%) and 2000T (0.7%, 4.2%, and 3.6%) increased mean RMR above baseline at POST60M, POST120M, and POST180M timepoints, respectively. Conversely, PLA decreased mean RMR by 0.9% and 0.7% at POST60M and POST120M, respectively. Incidentally, the 1000T condition displayed increased mean FAT oxidation by 1.85, 5.34, and 7.96% at the POST60M, POST120M, and POST180M timepoints, respectively, and when compared to the consistent decreases observed with both PLA and 2000T. CONCLUSION: Although these data fail to display a significant turkesterone-mediated enhancement in the investigated metabolic parameters, there were interesting mean differences that should be further explored to determine any longitudinal and/or exercise-dependent permissive impacts on RMR and substrate utilization

Influence of Acute Turkesterone Dosing on Serum Insulin-like Growth Factor 1 (IGF-1) and Subjective Digestibility Scores in Recreationally-active Males

Turkesterone is a relatively novel phytoecdysteroid compound that has become increasingly popular amongst recreationally active demographics. Despite prior in vitro data suggesting that this compound may support enhanced body composition via both insulin-like growth factor 1 (IGF-1)-mediated protein synthesis, no human evidence exists in this regard nor how well its digestibility is tolerated. PURPOSE: To determine the effect of multiple turkesterone doses on serum IGF-1 and to report any gastrointestinal (GI) distress symptoms in a healthy human sample. METHODS: Eleven recreationally active males (23.3±2.2y) visited the laboratory on three occasions separated by at least seven days and were randomized in single-blind, placebo-controlled, and counter-balanced crossover fashion to either 2000mg cellulose placebo (PLA), 1000mg turkesterone + 1000mg placebo, (1000T) or 2000mg (2000T) turkesterone. Venous blood was sampled to determine serum IGF-1 concentrations and a GI distress questionnaire was (nausea, vomiting, heartburn symptoms, etc.) administered both at baseline (PRE), as well as 3-hours (POST3H) and 24-hours (POST24H) post-acute supplementation at each visit. Serum IGF-1 was analyzed using a two-way (condition [PLA, 1000T, 2000T] x time [PRE, POST3H, POST24H]) ANOVA with repeated measures at a significance level of pRESULTS: Analyses failed to reveal any significant condition (p=.180; ηp2=0.228), time (p=0.227; ηp2=.390), nor interaction effects (p=0.547; ηp2=0.211) for serum IGF-1. Moreover, no participants reported any GI distress symptoms across any condition and/or time permutation. CONCLUSION: Although the current study did not find any significant IGF-1-associated serum alterations to multiple acute turkesterone doses in the times assessed, there were fortunately no adverse GI symptoms experienced by the participants across any dose throughout the investigation. Nevertheless, these data support turkesterone supplementation is well tolerated and thus future research should build upon our analysis by employing a longitudinal supplementation regimen alongside an exercise intervention to elucidate the potential long-term and anabolism-permissive impacts of this compound on the presently-explored and additional associated parameters

The Impacts of Wrist Wrap Type and Sex on Bench Press Muscular Strength and Power

While wrist wraps have become increasingly prevalent in both competitive and recreational demographics, their posited ability to augment bench press performance by enhanced wrist stability still remains unclear. PURPOSE: To determine the effect of varying wrap styles on bench-specific muscular strength and associated power, as well as quantitative and subjective differences between sexes. METHODS: Eighteen resistance trained males and females (9M/9F; 24±4y; 176±33cm; 80±15kg) visited the laboratory on three separate occasions in randomized, crossover, and counterbalanced design to sport either a flexible wrist wrap (FW), stiff wrap (SW), or a no wrap control (NW) condition. All participants underwent a bench press one-repetition maximum (1RM) test and linear position transducer-derived peak power and velocity assessments. Furthermore, subjective stability (SS) and discomfort (SD) were determined promptly following 1RM attempts. Bench press performance and sex-collapsed subjective variables were analyzed using a two-way (condition x sex) mixed model ANOVA with repeated measures and a nonparametric Friedman’s ANOVA, respectively. Both analyses were performed at a p\u3c.05 significance level. RESULTS: Analyses failed to detect any main condition or interaction effects for bench press 1RM, however, a statistically significant main sex effect was observed (p\u3c.001; ηp2=.597) favoring males relative to females (p\u3c.001; 114±22kg vs 68±16kg). Both peak power and velocity failed to reveal any significant main condition or sex effects, nor any interactions. Nonparametric assessments further revealed significant wrist wrap condition effects for both SS (p\u3c.001; Kendall’s W=.628) and SD (p\u3c.001; Kendall’s W=.935), whereby NW was statistically more comfortable (p\u3c.001) than either wrap condition, without any difference between DW and SW (p\u3e.05). CONCLUSION: Although wrist wraps did not significantly alter bench press-specific strength and power, participants nonetheless perceived wrist wraps as subjectively more stable irrespective of increased discomfort. ACKNOWLEDGEMENTS: The authors of this abstract would like to thank Peter Spence and SBD Apparel for generously donating the wrist wraps utilized in the present investigation

Parental predictors of children's executive functioning from ages 6 to 10.

According to prominent models of child development, parental factors may contribute to individual differences in children's executive functioning (EF). Here, we examine the relative importance of parents' socio-economic status, mental health, and parenting as predictors of EF development, drawing on a large (n = 1,070) community sample of Norwegian children who received biennial EF assessments from 6 to 10 years of age. We measure EF by means of the Behavior Rating Inventory of Executive Function. We assess parenting through observer ratings of parent-child interactions and parental mental health via the Beck Anxiety Inventory, Beck Depression Inventory, and Hopkins Symptom Checklist. When we adjust for all time-invariant unmeasured confounders, higher parental education predicts superior EF development, whereas harsh parenting forecasts poorer EF development. However, parenting does not mediate the effect of parental education. These results indicate that harsh parenting should be targeted in interventions aimed at improving EF. Statement of contribution What is already known on this subject? Parental factors seem to affect child development of executive functions (EF). Specifically, parental socio-economic status, mental health, and their parenting seem to influence the developmental course of child EF. What does this study add? To what degree the parental influence on EF development is likely to be driven by time-invariant factors, for example, genetics. The relative influence of positive and negative parenting on EF development

The Prevalence of Wrist Wrap Use in Actively Competing Powerlifters

Wrist wraps are often ergogenically employed by competitive powerlifters to improve bench press performance, but several product-specific variations may impact any potential benefits. Moreover, the prevalence of athletic wrist wrap use is hitherto undescribed. PURPOSE: to characterize the pervasiveness of wrist wrap use amongst competitive powerlifters with regards to style (flexible [F] or stiff [S]), length, and tightness amongst competitive powerlifters. METHODS: Powerlifters (n = 70; 27±6y) who competed in the last two years were randomly recruited at sanctioned meets across the USA. After providing consent and following a 5-minute seated rest, participant wrist wrap use descriptive data (wrap style [F or S], wrap length, and events used) were collected. Additionally, wrap tightness was assessed via pulse oximeter-detected oxygen saturation (SpO2). Post-meet bench press one repetition maximum (1RM) was also recorded from the Openpowerlifting.com open database. Wrist wrap use prevalence data (wrap style [F or S], wrap length, and events used) were assessed across Central, West Coast, and East Coast regions via separate Pearson’s Chi-squared tests. Furthermore, the relationships between both region-collapsed wrapped SpO2 and bench press 1RM were assessed using Pearson’s product-moment correlations and all statistical analyses were set at a significance level of pRESULTS: Analyses failed to detect any significant regional differences in wrap style, length, or events used (p\u3e0.05). Furthermore, there was a weak, negative correlation between wrapped SpO2 and bench press 1RM (r = -0.393, p = 0.086). CONCLUSIONS: Although we failed to detect any significant relationships between performance and wrap tightness, actively competing powerlifters nonetheless prominently utilize wraps similarly across the US regions assessed. Therefore, the potential for wrist wraps to augment bench press performance warrants further elucidation in a controlled, standardized investigation

Temporal Patterns in Perchlorate, Thiocyanate, and Iodide Excretion in Human Milk

BACKGROUND: Perchlorate and thiocyanate interfere with iodide uptake at the sodium–iodide symporter and are potential disruptors of thyroid hormone synthesis. Perchlorate is a common contaminant of water, food, and human milk. Although it is known that iodide undergoes significant diurnal variations in serum and urinary excretion, less is known about diurnal variations of milk iodide levels. OBJECTIVES: Variability in perchlorate and thiocyanate excretion in human milk has not been examined. Our objective was to determine variability of perchlorate, thiocyanate, and iodide in serially collected samples of human milk. METHODS: Ten lactating women were asked to collect six milk samples on each of 3 days. As an alternative, subjects were asked to collect as many milk samples as comfortably possible over 3 days. Samples were analyzed for perchlorate, iodide, and thiocyanate by ion chromatography coupled with mass spectrometry. RESULTS: Individual perchlorate, iodide, and thiocyanate levels varied significantly over time; there was also considerable variation among individuals. The iodide range, mean ± SD, and median for all samples (n = 108) were 3.1–334 μg/L, 87.9 ± 80.9 μg/L, and 55.2 μg/L, respectively. The range, mean ± SD, and median of perchlorate in all samples (n = 147) were 0.5–39.5 μg/L, 5.8 ± 6.2 μg/L, and 4.0 μg/L. The range, mean ± SD, and median of thiocyanate in all samples (n = 117) were 0.4 –228.3 μg/L, 35.6 ± 57.9 μg/L, and 5.6 μg/L. The data are not symmetrically distributed; the mean is higher than the median in all cases. CONCLUSIONS: Iodine intake may be inadequate in a significant fraction of this study population. Perchlorate and thiocyanate appear to be common in human milk. The role of these chemicals in reducing breast milk iodide is in need of further investigation

The Effect of Fish Oil Supplementation on Resistance Training-induced Adaptations

Background: Resistance exercise training (RET) is a common and well-established method to induce hypertrophy and improvement in strength. Interestingly, fish oil supplementation (FOS) may aug-ment RET-induced adaptations. However, few studies have been conducted on young, healthy adults. Methods: A randomized, placebo-controlled design was used to determine the effect of FOS, a concentrated source of eicosapen-taenoic acid (EPA) and docosahexaenoic acid (DHA), compared to placebo (PL) on RET-induced adaptations following a 10-week RET program (3 days·week−1). Body composition was measured by dual- energy x-ray absorptiometry (LBM, fat mass [FM], percent body fat [%BF]) and strength was measured by 1-repetition maximum bar-bell back squat (1RMSQT) and bench press (1RMBP) at PRE (week 0) and POST (10 weeks). Supplement compliance was assessed via self-report and bottle collection every two weeks and via fatty acid dried blood spot collection at PRE and POST. An a priori α- level of 0.05 was used to determine statistical significance and Cohen’s d was used to quantify effect sizes (ES). Results: Twenty-one of 28 male and female participants (FOS, n = 10 [4 withdrawals]; PL, n = 11 [3 withdrawals]) completed the 10- week progressive RET program and PRE/POST measurements. After 10-weeks, blood EPA+DHA substantially increased in the FOS group (+109.7%, p\u3c .001) and did not change in the PL group (+1.3%, p = .938). Similar between-group changes in LBM (FOS: +3.4%, PL: +2.4%, p = .457), FM (FOS: −5.2%, PL: 0.0%, p = .092), and %BF (FOS: −5.9%, PL: −2.5%, p = .136) were observed, although, the between- group ES was considered large for FM (d = 0.84). Absolute and relative (kg·kg [body mass]−1) 1RMBP was significantly higher in the FOS group compared to PL (FOS: +17.7% vs. PL: +9.7%, p = .047; FOS: +17.6% vs. PL: +7.3%, p = .011; respectively), whereas absolute 1RMSQT was similar between conditions (FOS: +28.8% vs. PL: +20.5%, p = .191). Relative 1RMSQT was higher in the FOS group (FOS: +29.3% vs. PL: +17.9%, p = .045). Conclusions: When combined with RET, FOS improves absolute and relative 1RM upper-body and relative 1RM lower-body strength to a greater extent than that observed in the PL group of young, recreationally trained adults

Massively parallel reporter assays of melanoma risk variants identify MX2 as a gene promoting melanoma

Genome-wide association studies (GWAS) have identified ~20 melanoma susceptibility loci, most of which are not functionally characterized. Here we report an approach integrating massively-parallel reporter assays (MPRA) with cell-type-specific epigenome and expression quantitative trait loci (eQTL) to identify susceptibility genes/variants from multiple GWAS loci. From 832 high-LD variants, we identify 39 candidate functional variants from 14 loci displaying allelic transcriptional activity, a subset of which corroborates four colocalizing melanocyte cis-eQTL genes. Among these, we further characterize the locus encompassing the HIV-1 restriction gene, MX2 (Chr21q22.3), and validate a functional intronic variant, rs398206. rs398206 mediates the binding of the transcription factor, YY1, to increase MX2 levels, consistent with the cis-eQTL of MX2 in primary human melanocytes. Melanocyte-specific expression of human MX2 in a zebrafish model demonstrates accelerated melanoma formation in a BRAFV600E background. Our integrative approach streamlines GWAS follow-up studies and highlights a pleiotropic function of MX2 in melanoma susceptibility

Imperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG

Beclin 1 is a core component of the Class III Phosphatidylinositol 3-Kinase VPS34 complex. The coiled coil domain of Beclin 1 serves as an interaction platform for assembly of distinct Atg14L- and UVRAG-containing complexes to modulate VPS34 activity. Here we report the crystal structure of the coiled coil domain that forms an antiparallel dimer and is rendered metastable by a series of 'imperfect' a-d' pairings at its coiled coil interface. Atg14L and UVRAG promote the transition of metastable homodimeric Beclin 1 to heterodimeric Beclin1-Atg14L/UVRAG assembly. Beclin 1 mutants with their 'imperfect' a-d' pairings modified to enhance self-interaction, show distinctively altered interactions with Atg14L or UVRAG. These results suggest that specific utilization of the dimer interface and modulation of the homodimer–heterodimer transition by Beclin 1-interacting partners may underlie the molecular mechanism that controls the formation of various Beclin1–VPS34 subcomplexes to exert their effect on an array of VPS34-related activities, including autophagy

Nedd4-dependent lysine-11-linked polyubiquitination of the tumour suppressor Beclin 1

Beclin 1, a subunit of the class III phosphatidylinositol 3-kinase complex, is a tumour suppressor with a central role in endocytic trafficking, cytokinesis and the cross-regulation between autophagy and apoptosis. Interestingly, not only reduced expression but also overexpression of Beclin 1 is correlated with cancer development and metastasis. Thus it seems necessary for the cell to balance the protein levels of Beclin 1. In the present study we describe a regulatory link between Beclin 1 and the ubiquitin ligase Nedd4 (neural-precursor-cell-expressed developmentally down-regulated 4). We establish Nedd4 as a novel binding partner of Beclin 1 and demonstrate that Nedd4 polyubiquitinates Beclin 1 with Lys11- and Lys63-linked chains. Importantly, Nedd4 expression controls the stability of Beclin 1, and depletion of the Beclin 1-interacting protein VPS34 causes Nedd4-mediated proteasomal degradation of Beclin 1 via Lys11-linked polyubiquitin chains. Beclin 1 is thus the first tumour suppressor reported to be controlled by Lys11-linked polyubiquitination