Severe and protracted cholestasis in 44 young men taking bodybuilding supplements: assessment of genetic, clinical and chemical risk factors.

BACKGROUND: Bodybuilding supplements can cause a profound cholestatic syndrome. AIM: To describe the drug-Induced liver injury network's experience with liver injury due to bodybuilding supplements. METHODS: Liver injury pattern, severity and outcomes, potential genetic associations, and exposure to anabolic steroids by product analysis were analysed in prospectively enrolled subjects with bodybuilding supplement-induced liver injury with causality scores of probable or higher. RESULTS: Forty-four males (mean age 33 years) developed liver injury with a median latency of 73 days. Forty-one per cent presented with hepatocellular pattern of liver injury as defined by the R > 5 ([Fold elevation of ALT] ÷ [Fold elevation of Alk Phos] (mean, range = 6.4, 0.5-31.4, n = 42) despite all presenting with clinical features of cholestatic liver injury (100% with jaundice and 84% with pruritus). Liver biopsy (59% of subjects) demonstrated a mild hepatitis and profound cholestasis in most without bile duct injury, loss or fibrosis. Seventy-one per cent were hospitalised, and none died or required liver transplantation. In some, chemical analysis revealed anabolic steroid controlled substances not listed on the label. No enrichment of genetic variants associated with cholestatic syndromes was found, although mutations in ABCB11 (present in up to 20%) were significantly different than in ethnically matched controls. CONCLUSIONS: Patients with bodybuilding supplements liver injury uniformly presented with cholestatic injury, which slowly resolved. The ingested products often contained anabolic steroids not identified on the label, and no enrichment in genetic variants was found, indicating a need for additional studies.

Factors affecting pitch discrimination performance in a cohort of extensively phenotyped healthy volunteers.

Despite efforts to characterize the different aspects of musical abilities in humans, many elements of this complex area remain unknown. Musical abilities are known to be associated with factors like intelligence, training, and sex, but a comprehensive evaluation of the simultaneous impact of multiple factors has not yet been performed. Here, we assessed 918 healthy volunteers for pitch discrimination abilities-their ability to tell two tones close in pitch apart. We identified the minimal threshold that the participants could detect, and we found that better performance was associated with higher intelligence, East Asian ancestry, male sex, younger age, formal music training-especially before age 6-and English as the native language. All these factors remained significant when controlling for the others, with general intelligence, musical training, and male sex having the biggest impacts. We also performed a small GWAS and gene-based collapsing analysis, identifying no significant associations. Future genetic studies of musical abilities should involve large sample sizes and an unbiased genome-wide approach, with the factors highlighted here included as important covariates.

The fractionated orthology of Bs2 and Rx/Gpa2 supports shared synteny of disease resistance in the Solanaceae.

Comparative genomics provides a powerful tool for the identification of genes that encode traits shared between crop plants and model organisms. Pathogen resistance conferred by plant R genes of the nucleotide-binding-leucine-rich-repeat (NB-LRR) class is one such trait with great agricultural importance that occupies a critical position in understanding fundamental processes of pathogen detection and coevolution. The proposed rapid rearrangement of R genes in genome evolution would make comparative approaches tenuous. Here, we test the hypothesis that orthology is predictive of R-gene genomic location in the Solanaceae using the pepper R gene Bs2. Homologs of Bs2 were compared in terms of sequence and gene and protein architecture. Comparative mapping demonstrated that Bs2 shared macrosynteny with R genes that best fit criteria determined to be its orthologs. Analysis of the genomic sequence encompassing solanaceous R genes revealed the magnitude of transposon insertions and local duplications that resulted in the expansion of the Bs2 intron to 27 kb and the frequently detected duplications of the 5'-end of R genes. However, these duplications did not impact protein expression or function in transient assays. Taken together, our results support a conservation of synteny for NB-LRR genes and further show that their distribution in the genome has been consistent with global rearrangements.