The influence of different concentrations of flavanol chocolate bars under acute supplement conditions on exercise and performance

The purpose of this study was to assess the effects and acute dosage of different flavanol concentrations in a dark chocolate bar on physiological parameters during steady state (SS) and incremental exercise. In a double-blind, randomised, crossover study, 15 healthy participants with a mean ± SD age of 30 ± 7 years; stature 176.8 ± 8.6 cm and body mass 80.3 ± 8.4 kg supplemented with high flavanol (HF) (1060 mg), moderate flavanol (MF) (746 mg), low flavanol (LF) (406 mg), or a control (CON) (88 mg) chocolate bar (~ 34 g), 2 h prior to 40 min of SS cycling (80% gas-exchange threshold) followed by an incremental test to volitional fatigue. During the SS cycle oxygen consumption ([Formula: see text]), respiratory exchange ratio (RER) and heart rate (HR) were continuously monitored. Plasma samples were collected prior to commencing exercise to determine nitrate (NO ) and nitrite (NO ) levels under each condition. There was no observed effect between flavanol concentrations on [Formula: see text], RER, and HR during SS cycling (P > 0.05). [Formula: see text], peak power, HR peak, and RER peak also did not significantly differ between conditions (P > 0.05). There was a small trend for higher plasma NO levels following higher flavanol concentration; however, this did not reach statistical significance (P > 0.05). Acute supplementation with cocoa of differing flavanol concentrations does not appear to have any effect on exercise and performance. It is plausible that longer flavanol supplementation periods might have greater accumulative effects and thus may potentially elicit a larger effect

Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium

BACKGROUND Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC. METHODS Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals). RESULTS Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation. CONCLUSION This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts

Genetic determinants of daytime napping and effects on cardiometabolic health

This is the final version. Available from Nature Research via the DOI in this record. Summary GWAS statistics are publicly available at The Sleep Disorder Knowledge Portal webpage: http://sleepdisordergenetics.org/.Daytime napping is a common, heritable behavior, but its genetic basis and causal relationship with cardiometabolic health remain unclear. Here, we perform a genome-wide association study of self-reported daytime napping in the UK Biobank (n = 452,633) and identify 123 loci of which 61 replicate in the 23andMe research cohort (n = 541,333). Findings include missense variants in established drug targets for sleep disorders (HCRTR1, HCRTR2), genes with roles in arousal (TRPC6, PNOC), and genes suggesting an obesity-hypersomnolence pathway (PNOC, PATJ). Association signals are concordant with accelerometer-measured daytime inactivity duration and 33 loci colocalize with loci for other sleep phenotypes. Cluster analysis identifies three distinct clusters of nap-promoting mechanisms with heterogeneous associations with cardiometabolic outcomes. Mendelian randomization shows potential causal links between more frequent daytime napping and higher blood pressure and waist circumference.National Institute of HealthNational Institute of HealthNational Institute of HealthNational Institute of HealthNational Institute of HealthMGH Research Scholar Fund, Academy of FinlandMedical Research CouncilSpanish Government of Investigation, Development and InnovationSeneca FoundationNIDDKInstrumentarium Science FoundationYrjö Jahnsson Foundatio

Head and neck rhabdomyosarcoma with TFCP2

Aims Primary intraosseous rhabdomyosarcoma (RMS) is a rare entity defined by EWSR1/FUS-TFCP2 or, less commonly, MEIS1-NCOA2 fusions. The lesions often show a hybrid spindle and epithelioid phenotype, frequently coexpress myogenic markers, ALK, and cytokeratin, and show a striking propensity for the pelvic and craniofacial bones. The aim of this study was to investigate the clinicopathological and molecular features of 11 head and neck RMSs (HNRMSs) characterised by the genetic alterations described in intraosseous RMS. Methods and results The molecular abnormalities were analysed with fluorescence in-situ hybridisation and/or targeted RNA/DNA sequencing. Seven cases had FUS-TFCP2 fusions, four had EWSR1-TFCP2 fusions, and none had MEIS1-NCOA2 fusions. All except one case were intraosseous, affecting the mandible (n = 4), maxilla (n = 3), and skull (n = 3). One case occurred in the superficial soft tissue of the neck. The median age was 29 years (range, 16-74 years), with an equal sex distribution. All tumours showed mixed epithelioid and spindle morphology. Immunohistochemical coexpression of desmin, myogenin, MyoD1, ALK, and cytokeratin was seen in most cases. An intragenic ALK deletion was seen in 43% of cases. Regional and distant spread were seen in three and four patients, respectively. Two patients died of their disease. Conclusions We herein present the largest series of HNRMSs with TFCP2 fusions to date. The findings show a strong predilection for the skeleton in young adults, although we also report an extraosseous case. The tumours are characterised by a distinctive spindle and epithelioid phenotype and a peculiar immunoprofile, with coexpression of myogenic markers, epithelial markers, and ALK. They are associated with a poor prognosis, including regional or distant spread and disease-related death