p53 is a tumor suppressor gene with well-characterized roles in cell cycle regulation, apoptosis and the maintenance of genome stability. Recent evidence suggests that p53 may also contribute to the regulation of migration and invasion. Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that is overexpressed in the majority of human epithelial carcinomas, including breast and colorectal carcinomas. We demonstrate by chromatin immunoprecipitation assays that p53 interacts with a candidate p53 binding site within the EpCAM gene. p53-mediated transcriptional repression of EpCAM was confirmed in gain-of-function, and loss-of-function experimental systems. Induction of wildtype p53 was associated with a significant dose-dependent decrease in EpCAM expression; conversely, specific ablation of p53 was associated with a significant increase in EpCAM expression. At the functional level, specific ablation of p53 expression is associated with increased breast cancer invasion, and this effect is abrogated by concomitant specific ablation of EpCAM expression. Taken together, these biochemical and functional data are the first demonstration that (1) wildtype p53 protein binds to a response element within the EpCAM gene and negatively regulates EpCAM expression, and (2) transcriptional repression of EpCAM contributes to p53 control of breast cancer invasion.

Patients revived with naloxone after heroin overdose may be safely released without transport to the hospital if they have normal mentation and vital signs. In the absence of co-intoxicants and further opioid use there is very low risk of death from rebound opioid toxicity. For those patients treated in the ED for opioid overdose, an observation period of one hour is sufficient if they ambulate as usual, have normal vital signs and a Glasgow Coma Scale of 15. Patients suffering opioid toxicity can be administered naloxone safely by first responders and trained lay people. Programs that train these individuals are likely safe and beneficial, however further research is necessary.

Background: Over 5 million central venous catheters (CVCs) are placed annually. Pneumothorax and catheter malpositioning are common adverse events (AE) that requires attention. This study aims to evaluate local practices of mechanical complication frequency, type, and subsequent intervention(s) related to mechanical AE with an emphasis on catheter malpositioning. Methods: This is a retrospective review of CVC placements in a tertiary hospital setting from 1/2013 to 12/2013. Pneumothorax and CVC positioning were evaluated on post-insertion chest x-ray (CXR). Malposition was defined as unintended placement of the catheter in a vessel other than the intended superior vena cava on CXR. Catheter reposition was defined as radiographic evidence of a new catheter with removal of the old catheter less than 24hrs after initial placement. Data points analyzed included pneumothorax and thoracostomy rate, CVC malposition frequency, catheter reposition rate, catheter duration, and incidence of complications such as catheter associated venous thrombosis. Result: Among 2045 eligible CVC insertions, pneumothoraces occurred in 14 (0.7%; 95%CI 0.38, 1.17) and malpositions were identified in 275 (13.4%; 95% CI 12.3, 15.3). The proportion of pneumothoraces that required tube thoracostomy was 57%. The proportion of CVCs with malposition that were removed or replaced within 24h was 32.7%. "Malpositioned" catheters that were left in place by the clinical team (n = 185) had an average catheter duration of 8.2 days (95% CI 7.2, 9.3) versus 7.2 days (95% CI 6.17, 8.23) for catheters that were replaced after initial malposition (p = 0.14, t test). The incidence of venous thrombosis in repositioned “malpositioned” catheters was 7.8% versus 4.9% for “malpositioned” catheters that were left in place. Conclusions: Clinically significant catheter malposition and pneumothorax after CVC insertion are low. In this study, replaced and non-replaced “malpositioned” catheters had similar catheter duration and rates of complications, challenging the current dogma of CVC malposition practice.

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