The morphological and functional differentiation of neuronal dendrites is controlled through transcriptional programs and cell-cell signaling. Synaptic activity is thought to play an important role in the maturation of dendritic arbors, but the signaling pathways that couple neuronal activity and morphological changes in dendrites are not well understood. We explored the function of ␣1-chimaerin, a neuronal diacylglycerol-binding protein with a Rho GTPaseactivating protein domain that inactivates Rac1. We find that stimulation of phospholipase C␤-coupled cell surface receptors recruits ␣1-chimaerin to the plasma membrane of cultured hippocampal neurons. We further show that ␣1-chimaerin protein levels are controlled by synaptic activity and that increased ␣1-chimaerin expression results in the pruning of dendritic spines and branches. This pruning activity requires both the diacylglycerolbinding and Rac GTPase-activating protein activity of ␣1-chimaerin. Suppression of ␣1-chimaerin expression resulted in increased process growth from the dendritic shaft and from spine heads. Our data suggest that ␣1-chimaerin is an activity-regulated Rho GTPase regulator that is activated by phospholipase C␤-coupled cell surface receptors and contributes to pruning of dendritic arbors.spine ͉ neuronal activity ͉ phospholipase C ͉ pruning

Angiosarcoma is an aggressive mesenchymal sarcoma of endothelial cell origin with high mortality. Its occurrence in the small intestine is exceedingly low. In addition to the rarity of small intestine angiosarcoma, the nonspecific early clinical symptoms obscure the suspicion of such tumors and thereby delay the diagnosis. In a hope to improve the knowledge of this rare but fatal neoplasm, we report one case of angiosarcoma of duodenum and jejunum in a 73-year-old man. Furthermore, we summarize and analyze the common clinical features, tumor markers, treatment, and survival of previous reported cases of this malignancy. Small bowel angiosarcoma occurs more often in men than women (1.6:1). The median age at diagnosis is 68.5 years. The overall median survival time is 150 days; the median survival time in female (300 days) is longer than that of male patients (120 days). Von Willebrand factor (vWF), CD31, CD34, vimentin, and Ulex europaeus agglutinin 1 appear to be the most useful markers for the diagnosis. The majority of the patients underwent surgical resection alone or surgery with subsequent chemotherapy. The patients treated with surgery plus chemotherapy survive longer than those underwent surgical resection only (median 420 days, n = 7 vs. 96.5 days, n = 26, respectively; P = 0.0275). Further studies of more cases are needed for a better understanding of this rare entity, as well as the development of effective strategies for prevention, early diagnosis, and treatment.

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. The spread of obesity worldwide in pandemic proportions has led to a rapid rise of NAFLD in developed and developing countries alike. There are no approved pharmacological agents to treat steatohepatitis or advanced fibrosis but obeticholic acid recently has shown some promise in phase III trial. Currently, NAFLD is the number one etiology for simultaneous liver and kidney transplantation in the USA, second most common indication for liver transplantation (LT) and projected to become number one very soon. LT for NAFLD poses unique challenges, as these patients are generally older, obese and more likely to have a number of metabolic risk factors. Bariatric surgery is an option and can be considered if a structured weight loss program does not achieve the sustained weight loss goal. Comprehensive cardiovascular risk assessment and aggressive management of comorbid conditions are crucial in the LT evaluation process to improve post-transplant survival. Recurrent nonalcoholic steatohepatitis after LT is not uncommon, and thus warrants primary and secondary prevention strategies through a multidisciplinary approach. Prevalence of NAFLD in a donor population is a unique and growing concern that limits the access to quality liver grafts.

The exclusion of large endoscopic varices by CT, using standardized criteria, may obviate the need or frequency of EGD screening in select patient populations. Alternatively, CT findings highly suggestive of esophageal varices in cirrhotic patients may warrant further investigation and/or treatment. Further studies are needed to validate these findings.

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