HIF‐1α triggers long‐lasting glutamate excitotoxicity via system xc− in cerebral ischaemia–reperfusion

Hypoxia‐inducible factor 1α (HIF ‐1α) controls many genes involved in physiological and pathological processes. However, its roles in glutamatergic transmission and excitotoxicity are unclear. Here, we proposed that HIF ‐1α might contribute to glutamate‐mediated excitotoxicity during cerebral ischaemia–reperfusion (CIR ) and investigated its molecular mechanism. We showed that an HIF ‐1α conditional knockout mouse displayed an inhibition in CIR ‐induced elevation of extracellular glutamate and N ‐methyl‐d ‐aspartate receptor (NMDAR ) activation. By gene screening for glutamate transporters in cortical cells, we found that HIF ‐1α mainly regulates the cystine–glutamate transporter (system x_c^?) subunit xCT by directly binding to its promoter; xCT and its function are up‐regulated in the ischaemic brains of rodents and humans, and the effects lasted for several days. Genetic deletion of xCT in cortical cells of mice inhibits either oxygen glucose deprivation/reoxygenation (OGDR ) or CIR ‐mediated glutamate excitotoxicity in vitro and in vivo . Pharmaceutical inhibition of system x_c^? by a clinically approved anti‐cancer drug, sorafenib, improves infarct volume and functional outcome in rodents with CIR and its therapeutic window is at least 3 days. Taken together, these findings reveal that HIF ‐1α plays a role in CIR ‐induced glutamate excitotoxicity via the long‐lasting activation of system x_c^?‐dependent glutamate outflow and suggest that system x_c^? is a promising therapeutic target with an extended therapeutic window in stroke. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Event-Related Household Discussions Following the Boston Marathon Bombing and Associated Posttraumatic Stress Among Area Youth

Despite research documenting the scope of disaster-related posttraumatic stress (PTS) in youth, less is known about how family processes immediately postdisaster might associate with child outcomes. The 2013 Boston Marathon bombing affords a unique opportunity to assess links between immediate family discussions about community trauma and child mental health outcomes. The present study examined associations between attack-related household discussions and child PTS among Boston-area youth ages 4 to 19 following the Marathon bombing (N = 460). Caregivers completed surveys 2 to 6 months postattack about immediate household discussions about the events, child exposure to potentially traumatic attack-related experiences, and child PTS. During the Marathon bombing and manhunt, there was considerable heterogeneity in household discussions across area families, and several discussion items were differentially predictive of variability in children’s PTS. Specifically, after controlling for children’s direct exposure to the potentially traumatic attack/manhunt events, children showed lower PTS when it was their caregivers who informed them about the attack and manhunt, and when their caregivers expressed confidence in their safety and discussed their own feelings about the manhunt with their child. Children showed higher PTS when their caregivers did not discuss the events in front of them, asked others to avoid discussing the events in front of them, and expressed concern at the time that their child might not be safe. Child age and traumatic attack/manhunt exposure moderated several links between household discussions and child PTS. Findings underscore the importance of family communication and caregiver modeling during times of community threat and uncertainty.     

Type I Choledochal Cyst Complicated With Acute Hemorrhagic Pancreatitis: A Case Report

Choledochal cysts rarely present with acute pancreatitis. We report a patient with type I choledochal cyst(s) who had concomitant acute frank hemorrhagic pancreatitis.A 14-year-old male noted with a history of recurrent abdominal pain, fever and jaundice. Ultrasonography (US) of abdomen at the Emergency Department depicted distended gall bladder with wall thickening. Apparently dilated intrahepatic ducts (IHDs) and fusiform dilatation of the common bile duct (CBD), and mild dilatation of the pancreatic duct were also noted, suggesting a type I choledochal cyst( ). Computed tomography (CT) demonstrated calcifications in the uncinate process of the pancreas in addition to the similar findings on US. He subsequently underwent choledochal cyst excision with a Roux-en-Y hepaticojejunostomy. After surgical treatment, he has been doing well for 3 years.     

Left Ulnar Artery Pseudoaneurysm and Left Hand Swelling Simulated by Elephantiasis in a Patient with Neurofibromatosis Type 1

Elephantiasis is a condition featured by gross enlargement of body parts to massive proportions. Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder. Vascular anomaly is one among the complications of NF1. We report a case of NF1 who had a left hand vascular pseudoaneurysm with left hand swelling mimicking elephantiasis. The characteristics of sonography make it an excellent imaging modality to investigate this sort of superficial vascular lesion.