Contemporary Controversies in Digoxin Use in Systolic Heart Failure

Digoxin remains one of the oldest therapies for heart failure; however, its safety and efficacy have been controversial since its initial use. Questions that remain include the clinical efficacy of digoxin when added to contemporary medical therapy, when and if it should be added, and how to minimize adverse effects. In this review, we will summarize recent data on the use of digoxin in systolic heart failure and address some of the controversies regarding the role of digoxin in the modern era of heart failure treatment.     

Functional studies and rare variant screening of SLC1A1/EAAC1 in males with obsessive-compulsive disorder

Several studies have found that the neuronal glutamate transporter gene SLC1A1/EAAC1 is associated with obsessive-compulsive disorder (OCD), with a stronger association in males. Previous studies have primarily focused on common single-nucleotide polymorphisms, rather than rare functional variants that are likely to have larger effects. We screened 184 males with OCD for rare variation in SLC1A1 exons; however, no new coding variation was found. When combined with previous screens, only one SLC1A1 amino acid variant has been detected among the 841 individuals screened, which is less than for other neurotransmitter transporter genes (P=0.0001). We characterized the function of the one SLC1A1 missense variant reported previously in OCD, Thr164Ala, and found that the Ala164 allele leads to decreased Vmax and Km (P<0.0001) in transfected human embryonic kidney cells. Further work will be necessary to understand the impact of this rare SLC1A1/EAAC1 Ala164 variant on neuronal function and circuitry relevant to OCD.