Reduced Ssy1-Ptr3-Ssy5 (SPS) signaling extends replicative life span by enhancing NAD+ homeostasis in Saccharomyces cerevisiae.

Attenuated nutrient signaling extends the life span in yeast and higher eukaryotes; however, the mechanisms are not completely understood. Here we identify the Ssy1-Ptr3-Ssy5 (SPS) amino acid sensing pathway as a novel longevity factor. A null mutation of SSY5 (ssy5Δ) increases replicative life span (RLS) by ∼50%. Our results demonstrate that several NAD(+) homeostasis factors play key roles in this life span extension. First, expression of the putative malate-pyruvate NADH shuttle increases in ssy5Δ cells, and deleting components of this shuttle, MAE1 and OAC1, largely abolishes RLS extension. Next, we show that Stp1, a transcription factor of the SPS pathway, directly binds to the promoter of MAE1 and OAC1 to regulate their expression. Additionally, deletion of SSY5 increases nicotinamide riboside (NR) levels and phosphate-responsive (PHO) signaling activity, suggesting that ssy5Δ increases NR salvaging. This increase contributes to NAD(+) homeostasis, partially ameliorating the NAD(+) deficiency and rescuing the short life span of the npt1Δ mutant. Moreover, we observed that vacuolar phosphatase, Pho8, is partially required for ssy5Δ-mediated NR increase and RLS extension. Together, our studies present evidence that supports SPS signaling is a novel NAD(+) homeostasis factor and ssy5Δ-mediated life span extension is likely due to concomitantly increased mitochondrial and vacuolar function. Our findings may contribute to understanding the molecular basis of NAD(+) metabolism, cellular life span, and diseases associated with NAD(+) deficiency and aging.

Intracoronary brachytherapy for the treatment of recurrent drug-eluting stent in-stent restenosis: A systematic review and meta-analysis.

BACKGROUND: We performed a meta-analysis on observational studies since randomized control trials are not available. We studied intracoronary brachytherapy (ICBT) and recurrent drug eluting stent in-stent restenosis (DES-ISR) to evaluate the procedural success, target lesion revascularization (TLR), incidence of myocardial infarction (MI) and all-cause mortality at 2 years follow-up. AIM: To perform meta-analysis for patients undergoing ICBT for recurrent DES-ISR. METHODS: We performed a systematic search of the PubMed/MEDLINE, Cochrane and DARE databases to identify relevant articles. Studies were excluded if intra-coronary brachytherapy was used as a treatment modality for initial ISR and studies with bare metal stents. We used a random-effect model with DerSimonian & Laird method to calculate summary estimates. Heterogeneity was assessed using I 2 statistics. RESULTS: A total of 6 observational studies were included in the final analysis. Procedural angiographic success following intra-coronary brachytherapy was 99.8%. Incidence of MI at 1-year was 2% and 4.1% at 2-years, respectively. The incidence of TLR 14.1% at 1-year and 22.7% at 2-years, respectively. All-cause mortality at 1- and 2-year follow-up was 3% and 7.5%, respectively. CONCLUSION: Given the observational nature of the studies included in the analysis, heterogeneity was significantly higher for outcomes. While there are no randomized controlled trials or definitive guidelines available for recurrent ISR associated with DES, this analysis suggests that brachytherapy might be the alternative approach for recurrent DES-ISR. Randomized controlled trials are required to confirm results from this study.

Comparison of Management and Outcomes of Acute Heart Failure Hospitalization in Medicaid Beneficiaries Versus Privately Insured Individuals.

Medicaid expansion in terms of its eligibility and federal funding has led to improved healthcare access in previously uninsured individuals. However, proposed lower Medicaid rates have unintentionally led to lower utilization of substantial life-saving therapies and poor outcomes compared with private insurance. We examined heart failure (HF) management, in-hospital mortality, and resource utilization in Medicaid and privately insured individuals hospitalized with HF. The authors screened the National Inpatient Sample from January 2012 to September 2015 for HF hospitalizations with Medicaid or private insurance as the primary payer. The authors identified a total of 226,265 and 292,070 patients with HF hospitalizations with Medicaid and private insurance, respectively. In propensity-matched cohort of 155,790 hospitalizations in each group, Medicaid beneficiaries with HF hospitalization had lower rates of intra-aortic balloon pump/left ventricular assist device/extracorporeal membrane oxygenation utilization (0.6 vs 0.9%; odds ratio [OR] 0.64; 95% confidence interval [CI] 0.59 to 0.69), heart transplantation (0.15 vs 0.44%; OR 0.35; 95% CI 0.30 to 0.40), implantable cardioverter-defibrillator/cardiac resynchronization therapy/permanent pacemaker (3.3 vs 3.9%; OR 0.84; 95% CI 0.81 to 0.87), and had higher rates of in-hospital mortality (1.9 vs 1.7%; OR 1.12; 95% CI 1.07 to 1.19) compared with privately insured individuals (p <0.001 for both). In conclusion, Medicaid recipients with HF hospitalizations had a lower rate of device utilization, heart transplantation, and a higher rate of in-hospital mortality compared with the privately insured sector. Further studies are needed to explore and understand the variation in the outcomes of HF hospitalizations stratified by insurance status.