Nonalcoholic fatty liver disease (NAFLD), the accumulation of lipid within hepatocytes, is increasing in prevalence. Increasing fructose consumption correlates with this increased prevalence, and rodent studies directly support fructose leading to NAFLD. The mechanisms of NAFLD and in particular fructose-induced lipid accumulation remain unclear, although there is evidence for a role for endoplasmic reticulum (ER) stress and oxidative stress. We have evidence that NAFLD models demonstrate activation of the target of rapamycin complex 1 (Torc1) pathway. We set out to assess the contribution of ER stress, oxidative stress, and Torc1 up-regulation in the development of steatohepatitis in fructose-treated larval zebrafish. Zebrafish were treated with fructose or glucose as a calorie-matched control. We also treated larvae with rapamycin, tunicamycin (ER stress), or valinomycin (oxidative stress). Fish were stained with oil red O to assess hepatic lipid accumulation, and we also performed quantitative polymerase chain reaction (qPCR)and western blot analysis. We performed immunostaining on samples from patients with NAFLD and nonalcoholic steatohepatitis (NASH). Treatment with fructose induced hepatic lipid accumulation, mitochondrial abnormalities, and ER defects. In addition, fructose-treated fish showed activation of inflammatory and lipogenic genes. Treatment with tunicamycin or valinomycin also induced hepatic lipid accumulation. Expression microarray studies of zebrafish NAFLD models showed an elevation of genes downstream of Torc1 signaling. Rapamycin treatment of fructose-treated fish prevented development of hepatic steatosis, as did treatment of tunicamycin-or valinomycin-treated fish. Examination of liver samples from patients with hepatic steatosis demonstrated activation of Torc1 signaling. Conclusion: Fructose treatment of larval zebrafish induces hepatic lipid accumulation, inflammation, and oxidative stress. Our results indicate that Torc1 activation is required for hepatic lipid accumulation across models of NAFLD, and in patients. (HEPATOLOGY 2014;60:1581-1592

A bracing device for stabilizing cardiac catheters inside the heart was developed to provide surgical-level dexterity to minimally invasive catheter-based procedures for cardiac valve disease. The brace was designed to have a folding structure, which lies flat along a catheter during navigation through vasculature and then unfolds into a rigid bracing configuration after deployment across the interatrial septum. The brace was designed to be easily deployable, provide bracing support for a transseptal catheter, and also be compliant enough to be delivered to the heart via tortuous vasculature. This aims to improve dexterity in catheter-based mitral valve repair and enable other complex surgical procedures to be done with minimally invasive instruments.

An Integrated Wet Weather Management approach seeks to achieve the overarching goal of surface water quality protection though coordinated planning, prioritization and implementation of wet weather management initiatives across programmatic and regulatory boundaries. The result is a holistic program designed to efficiently and effectively meet the requirements and goals of multiple regulatory programs, avoid duplicative efforts and derive the maximum water quality benefit feasible. This paper introduces an approach for Integrated Wet Weather Management planning and provides a case study of the approach as is currently being implemented by the City of Wilmington, Delaware. A concurrent comparative analysis of standard regulatory requirements highlights areas of overlap between combined sewer overflow (CSO) and municipal separate storm sewer (MS4) programs and facilitates the integrated approach. A prioritization strategy guides implementation planningand the program is vetted internally and externally to gain acceptance and support.