Ramsey Gustafson (winterslave9)

We start with summary statistics in the form of SNP effect sizes from a large GWAS cohort. We then remove the correlation structure across summary statistics arising due to linkage disequilibrium and apply a piecewise linear interpolation on conditional mean effects. In both simulated and real datasets, this new non-parametric shrinkage (NPS) method can reliably allow for linkage disequilibrium in summary statistics of 5 million dense genome-wide markers and consistently improves prediction accuracy. We show that NPS improves the identification of groups at high risk for breast cancer, type 2 diabetes, inflammatory bowel disease, and coronary heart disease, all of which have available early intervention or prevention treatments.The burden of several common diseases including obesity, diabetes, hypertension, asthma, and depression is increasing in most world populations. However, the mechanisms underlying the numerous epidemiological and genetic correlations among these disorders remain largely unknown. We investigated whether common polymorphic inversions underlie the shared genetic influence of these disorders. We performed an inversion association analysis including 21 inversions and 25 obesity-related traits on a total of 408,898 Europeans and validated the results in 67,299 independent individuals. Seven inversions were associated with multiple diseases while inversions at 8p23.1, 16p11.2, and 11q13.2 were strongly associated with the co-occurrence of obesity with other common diseases. Transcriptome analysis across numerous tissues revealed strong candidate genes for obesity-related traits. Analyses in human pancreatic islets indicated the potential mechanism of inversions in the susceptibility of diabetes by disrupting the cis-regulatory effect of SNPs from their target genes. Our data underscore the role of inversions as major genetic contributors to the joint susceptibility to common complex diseases.Three new oxygenated xanthones, fuscaxanthones L-N (1-3), and 14 known xanthones 4-17, together with the other known metabolites 18-20 were isolated from the stem barks of Garcinia fusca Pierre. Their chemical structures were determined based on NMR and MS spectroscopic data analysis, as well as single X-ray crystallography. The geranylated compounds, cowanin (13), cowagarcinone E (15), norcowanin (16) and cowanol (17) exhibited potent inhibitions against acetylcholinesterase (AChE) (IC50 0.33-1.09 μM) and butyrylcholinesterase (BChE) (IC50 0.048-1.84 μM), which were more active than the reference drug, galanthamine. Compound 15 was highly potent BChE inhibitor (IC50 0.048 μM) and was 76-fold more potent than the drug. Structure-activity relationship studies indicated that the C-2 prenyl and C-8 geranyl substituents in the tetraoxygenated scaffold are important for high activity. 7-Ketocholesterol Molecular docking studies revealed that the leads 13 and 15-17 showed similar binding orientations on both enzymes and very well-fitted at the double binding active sites of PAS and CAS with strong hydrophobic interactions from both isoprenyl side chains.Introduction The aim of this prospective, randomized, double-blind, clinical trial was to evaluate the effect of a preoperative, single, oral dose of diclofenac potassium (DFK) on postoperative pain and rescue-analgesic intake in patients with symptomatic irreversible pulpitis (SIP) in mandibular molars treated in one visit. Methods Seventy emergency patients with moderate-to-severe preoperative pain randomly received either 50mg DFK or placebo tablets (PLC) one hour before starting endodontic treatment (n=35). Patients recorded their pain level 6, 12, 24 and 48h after treatment on a 170-mm Heft-Parker visual analogue scale. The incidence of rescue-analgesic intake was, also, recorded. Outcome data were statistically analyzed using Mann Whitney U, Friedman's test, Wilcoxon's sign rank and Chi2 (χ2) tests. Binary logistic regression assessed predisposing factors' association w