Hypervitaminosis A is prevalent in children with CKD and contributes to hypercalcemia.

Vitamin A accumulates in renal failure, but the prevalence of hypervitaminosis A in children with predialysis chronic kidney disease (CKD) is not known. Hypervitaminosis A has been associated with hypercalcemia. In this study we compared dietary vitamin A intake with serum retinoid levels and their associations with hypercalcemia

Factors affecting facial selectivity in the hydroboration of steroidal Δ5-Alkenes

A comparison between the α- and β-facial selectivity observed in the hydroboration of some androst-5-enes and B-norandrost-5-enes does not parallel the difference between the calculated force field energies for α- and β-cyclobutane models suggesting that the facial selectivity is not determined by the four-centre transition state but by the relative ease of formation of the initial π-complex between the alkene and the borane

Sex Differences in Atrial Fibrillation Risk: The VITAL Rhythm Study.

Importance Women have a lower incidence of atrial fibrillation (AF) compared with men in several studies, but it is unclear whether this sex difference is independent of sex differences in prevalent cardiovascular disease (CVD), body size, and other risk factors. Objective To examine sex differences in AF incidence and whether AF risk factors differ by sex in a contemporary cohort of men and women without prevalent CVD. Design, Setting, and Participants This was a prospective cohort analysis within the Vitamin D and Omega-3 Trial (VITAL) Rhythm Study, a randomized trial that examined the effect of vitamin D and ω-3 fatty acid supplementation on incident AF among men 50 years or older and women 55 years or older without a prior history of prevalent AF, CVD, or cancer at baseline. Data were analyzed from September 29, 2020, to June 29, 2021. Exposures Sex, height, weight, body mass index (BMI), body surface area (BSA), and other AF risk factors at study enrollment. Main Outcomes and Measures Incident AF confirmed by medical record review. Results A total of 25 119 individuals (mean [SD] age, 67.0 [7.1] years; 12 757 women [51%]) were included in this study. Over a median (IQR) follow-up of 5.3 (5.1-5.7) years, 900 confirmed incident AF events occurred among 12 362 men (495 events, 4.0%) and 12 757 women (405 events, 3.2%). After adjustment for age and treatment assignment, women were at lower risk for incident AF than men (hazard ratio [HR], 0.68; 95% CI, 0.59-0.77; P < .001). The inverse association between female sex and AF persisted after adjustment for race and ethnicity, smoking, alcohol intake, hypertension, diabetes (type 1, type 2, gestational), thyroid disease, exercise, and BMI (HR, 0.73; 95% CI, 0.63-0.85; P <.001). However, female sex was positively associated with AF when height (HR, 1.39; 95% CI, 1.14-1.72; P = .001), height and weight (HR 1.49, 95% CI, 1.21-1.82; P <.001), or BSA (HR, 1.25; 95% CI, 1.06-1.49; P = .009) were substituted for BMI in the multivariate model. In stratified models, risk factor associations with incident AF were similar for women and men. Conclusions and Relevance In this cohort study, findings suggest that after controlling for height and/or body size, women without CVD at baseline were at higher risk for AF than men, suggesting that sex differences in body size account for much of the protective association between female sex and AF. These data underscore the importance of AF prevention in women

HER-3 Expression and MEK Activation in Non-small Cell Lung Cancer

Abstract BackgroundHER-3 has a role in pathogenesis and development of resistance to targeted therapies in non-small cell lung cancer (NSCLC). MethodsWe analysed tumour samples from 45 patients with adenocarcinoma of the lung. HER-3 and HER-2 expression was identified using immunohistochemistry as well as bioinformatic interrogation of The Cancer Genome Atlas (TGCA). ResultsHER-3 was highly expressed in 42.2% of cases and observed more frequently than HER-2 overexpression. ERBB3 copy number alone did not account for HER-3 overexpression. Bioinformatic analysis of TCGA demonstrated that MEK activity score (a score of downstream pathway activity and surrogate of functional HER-3 signalling) did not correlate with HER-3 ligands. EGFR pathway signalling was predominant with a significantly positive correlation of EGFR and AREG expression with MEK activity score. In the ERBB3 expressed group, ERBB3 RNA expression levels were significantly correlated with MEK activity score. ERBB3 expression level remained highly positively correlated with MEK activity after adjusting for EGFR expression. ConclusionHER-3 expression is common and it is not associated with gene amplification nor is it ligand dependent. HER-3 is an alternative pathway to EGFR activating MEK. HER-3 is a potential therapeutic target in NSCLC by virtue of frequent overexpression and functional downstream signalling