Reticuloendotheliosis virus strain T induces miR-155, which targets JARID2 and promotes cell survival.

The oncogenic microRNA miR-155 is upregulated by several oncogenic viruses. The precursor of miR-155, termed bic, was first observed to cooperate with myc in chicken B-cell lymphomas induced by avian leukosis proviral integrations. We identified another oncogenic retrovirus, reticuloendotheliosis virus strain T (REV-T), that upregulates miR-155 in chicken embryo fibroblasts. We also observed very high levels of miR-155 in REV-T-induced B-cell lymphomas. To study the role of miR-155 in these tumors, we identified JARID2/Jumonji, a cell cycle regulator and part of a histone methyltransferase complex, as a target of miR-155. The overexpression of miR-155 decreased levels of endogenous JARID2 mRNA. We confirmed that miR-155 directly targets both human and chicken JARID2 by assaying the repression of reporters containing the JARID2 3'-untranslated regions. Further, the overexpression of a sponge complementary to miR-155 in a tumor cell line increased endogenous JARID2 mRNA levels. The overexpression of JARID2 in chicken fibroblasts led to decreased cell numbers and an increase in apoptotic cells. The overexpression of miR-155 rescued cells undergoing cytopathic effect caused by infection with subgroup B avian retroviruses. Therefore, we propose that miR-155 has a prosurvival function that is mediated through the downregulation of targets including JARID2.

Prevention of central venous catheter-related bloodstream infections: is it time to add simulation training to the prevention bundle?

STUDY OBJECTIVE: To study the impact of adding simulation-based education to the pre-intervention mandatory hospital efforts aimed at decreasing central venous catheter-related blood stream infections (CRBSI) in intensive care units (ICU). DESIGN: Pre- and post-intervention retrospective observational investigation. SETTING: 24-bed ICU and a 562-bed university-affiliated, urban teaching hospital. PATIENTS: ICU patients July 2004-June 2008 were studied for the development of central venous catheter related blood stream infections (CRBSI). MEASUREMENTS: ICU patients from July 2004-June 2008 were studied for the development of central venous catheter-related blood stream infections (CRBSI). PRE-INTERVENTION: mandatory staff and physician education began in 2004 to reduce CRBSI. The CRBSI-prevention program included online and didactic courses, and a pre- and post-test. Elements in the pre-intervention efforts included hand hygiene, full barrier precautions, use of Chlorhexidine skin preparation, and mask, gown, gloves, and hat protection for operators. A catheter-insertion cart containing all supplies and checklist were was a mandatory element of this program; a nurse was empowered to stop the procedure for non-performance of checklist items. INTERVENTION: As of July 1, 2006, a mandatory simulation-based program for all intern, resident, and fellow physicians was added to teach central venous catheter (CVC) insertion. MEASUREMENTS: Data collected pre- and post-intervention were CRBSI incidence, number of ICU catheter days, mortality, laboratory pathogen results, and costs. MAIN RESULTS: The pre-intervention CRBSI incidence of 6.47/1,000 catheter days was reduced significantly to 2.44/1,000 catheter days post-intervention (58%; P < 0.05), resulting in a $539,902 savings (USD; 47%), and was attributed to shorter ICU and hospital lengths of stay. CONCLUSIONS: Following simulation-based CVC program implementation, CRBSI incidence and costs were significantly reduced for two years post-intervention.

Spatial memory using active allothetic place avoidance in adult rats after isoflurane anesthesia: a potential model for postoperative cognitive dysfunction.

BACKGROUND: We described a paradigm of active allothetic place avoidance (AAPA) as a measure of spatial memory in adult rats. We hypothesized that, pending successful AAPA training, treatment with isoflurane would trigger spatial memory deficits. METHODS: Fifteen of 20 adult rats were successfully trained and randomly allocated to control and isoflurane treatment groups. An additional 7 animals were used to demonstrate hemodynamic stability during general anesthesia. After training, experimental animals received a 2-hour isoflurane anesthetic. General endotracheal anesthesia was maintained at an isoflurane concentration of 1.8% to 2%. After intervention, retention of training was tested on postanesthesia days 1, 3, and 7. RESULTS: Animals treated with isoflurane displayed selected spatial memory changes up to postanesthesia day 7. There were 2 findings of decreased active avoidance behavior in rats receiving isoflurane: a significant (P=0.029) reduction in maximum path of avoidance in the isoflurane-treated rats compared with controls, and a significant (P=0.038) increase in total path length in the controls. No other measured AAPA parameters achieved statistical significance. CONCLUSIONS: Control animals demonstrated increased active avoidance behavior in the AAPA task compared with isoflurane-treated animals. Animals exposed to 2-hour isoflurane general anesthetic had a reduction in the maximum path of avoidance measure up to 7 days postanesthesia, whereas gross spatial parameters such as number of entrances into the shock zone were not significantly different between groups. The AAPA model may prove useful in ascertaining the learning and memory deficits of postoperative cognitive dysfunction.