Simulation of risk of tuberculosis infection in healthcare workers in hospitals of an intermediate incidence country

We simulated the frequency of tuberculosis infection in healthcare workers in order to classify the risk of TB transmission for nine hospitals in Medellín, Colombia. We used a risk assessment approach to estimate the average number of infections in three risk groups of a cohort of 1082 workers exposed to potentially infectious patients over 10- and 20-day periods. The risk level of the hospitals was classified according to TB prevalence: two of the hospitals were ranked as being of very high priority, six as high priority and one as low priority. Consistent results were obtained when the simulation was validated in two hospitals by studying 408 healthcare workers using interferon gamma release assays and tuberculin skin testing. The latent infection prevalence using laboratory tests was 41% [95% confidence interval (CI) 34·3–47·7] and 44% (95% CI 36·4–51·0) in those hospitals, and in the simulation, it was 40·7% (95% CI 32·3–49·0) and 36% (95% CI 27·9–44·0), respectively. Simulation of risk may be useful as a tool to classify local and regional hospitals according to their risk of nosocomial TB transmission, and to facilitate the design of hospital infection control plans

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Mechanisms of Acute Alcohol Intoxication-Induced Modulation of Cyclic Mobilization of [Ca 2+

Background: We have demonstrated that acute alcohol intoxication (AAI) increases the magnitude of Ca(2+) transients in pumping lymphatic vessels. We tested the contribution of extracellular Ca(2+) via L-type Ca(2+) channels and intracellular Ca(2+) release from the sarcoplasmic reticulum (SR) to the AAI-induced increase in Ca(2+) transients. Methods and Results: AAI was produced by intragastric administration of 30% alcohol to conscious, unrestrained rats; isovolumic administration of water served as the control. Mesenteric lymphatic vessels were isolated, cannulated, and loaded with Fura-2 AM to measure changes in intracellular Ca(2+). Measurements were made at intraluminal pressures of 2, 6, and 10 cm H(2)O. L-type Ca(2+) channels were blocked with nifedipine; IP-3 receptors were inhibited with xestospongin C; and SR Ca(2+) release and Ca(2+) pool (Ca(2+) free APSS) were achieved using caffeine. Nifedipine reduced lymphatic Ca(2+) transient magnitude in both AAI and control groups at all pressures tested, but reduced lymphatic contraction frequency only in the control group. Xestospongin C did not significantly change any of the Ca(2+) parameters in either group; however, fractional shortening increased in the controls at low transmural pressure. RyR (ryanodine receptor) activation with caffeine resulted in a single contraction with a greater Ca(2+) transient in lymphatics from AAI than those from controls. SR Ca(2+) pool was also greater in lymphatics isolated from AAI- than from control animals. Conclusions: These data suggest that 1) L-type Ca(2+) channels contribute to the AAI-induced increase in lymphatic Ca(2+) transient, 2) blockage of IP-3 receptors could increase calcium sensitivity, and 3) AAI increases Ca(2+) storage in the SR in lymphatic vessels

Huntingtine est requise pour l'orientation du fuseau mitotique et la neurogenèse chez les mammifères

SummaryHuntingtin is the protein mutated in Huntington's disease, a devastating neurodegenerative disorder. We demonstrate here that huntingtin is essential to control mitosis. Huntingtin is localized at spindle poles during mitosis. RNAi-mediated silencing of huntingtin in cells disrupts spindle orientation by mislocalizing the p150Glued subunit of dynactin, dynein, and the large nuclear mitotic apparatus NuMA protein. This leads to increased apoptosis following mitosis of adherent cells in vitro. In vivo inactivation of huntingtin by RNAi or by ablation of the Hdh gene affects spindle orientation and cell fate of cortical progenitors of the ventricular zone in mouse embryos. This function is conserved in Drosophila, the specific disruption of Drosophila huntingtin in neuroblast precursors leading to spindle misorientation. Moreover, Drosophila huntingtin restores spindle misorientation in mammalian cells. These findings reveal an unexpected role for huntingtin in dividing cells, with potential important implications in health and disease