Publications

Body weight is a quantitative trait with significant heritability in humans. To identify potential genetic contributors to this phenotype, we resequenced the coding exons and splice junctions of 58 genes in 379 obese and 378 lean individuals. Our 96-Mb survey included 21 genes associated with monogenic forms of obesity in humans or mice, as well as 37 genes that function in body weight-related pathways. We found that the monogenic obesity-associated gene group was enriched for rare nonsynonymous variants unique to the obese population compared with the lean population. In addition, computational analysis predicted a greater fraction of deleterious variants within the obese cohort. Together, these data suggest that multiple rare alleles contribute to obesity in the population and provide a medical sequencing-based approach to detect them.

BACKGROUND

Prior investigation has shown that intravenous beta-blockers decrease T-wave alternans (TWA) positivity in patients undergoing electrophysiology study (EPS). The present study examined whether oral beta-blocker use within 24 hours of TWA influences yield and predictive value of TWA and EPS.

METHODS

We prospectively evaluated 387 patients (312 [81%] men, mean age 67 +/- 11 years) with coronary artery disease, left ventricular ejection fraction < or = 40%, and nonsustained ventricular tachycardia who underwent EPS and were followed for a mean of 2.8 +/- 1.4 years. T-Wave alternans was performed using an atrial pacing protocol and interpreted using standard criteria. Beta-blocker status was determined based on oral beta-blocker use in the 24 hours preceding the test: beta-blocker (-) (n = 62), beta-blocker (+) (n = 325). Follow-up for ventricular tachycardia, ventricular fibrillation, and death was obtained from chart review, device interrogation, and the Social Security Death Index. Estimated sensitivity and specificity of TWA and EPS stratified by beta-blocker use were calculated based on event-free 2-year survival.

RESULTS

There was no difference in EPS (31 [50%] inducible off beta-blockers vs 166 [51%] on beta-blockers [P = .89]) or TWA (26 [42%] positive, 17 [27%] indeterminate off beta-blockers vs 136 [42%] positive, 81 [25%] indeterminate on beta-blockers [P = .89]). Beta-blocker use within 24 hours of testing did not affect the predictive value of TWA or EPS for overall or 2-year event-free survival.

CONCLUSIONS

Oral beta-blocker therapy appears to have no effect on yield or predictive value of EPS or TWA in patients with coronary artery disease, diminished left ventricular function, and a history of nonsustained ventricular tachycardia.

Currently, schistosomes infect approximately 40 million women of child-bearing age, yet little is known about schistosome-associated morbidity in pregnant women and their offspring. Animal models indicate a deleterious effect of schistosome infection on maternal, fetal and neonatal outcomes. Case reports have documented maternal infection in association with poor birth outcomes, and two observational studies indicate that maternal schistosome infection might be associated with decreased birth weight. Rigorously identifying and quantifying the impact of schistosome infection on pregnancy outcomes with well-designed observational and treatment studies are crucial for improving birth outcomes in schistosome-endemic areas. In addition, studies that address the safety of praziquantel during pregnancy could lead to further adoption of the recent informal recommendation by the World Health Organization to treat schistosome-infected pregnant and lactating women.