Five-minute exposure to caspofungin results in prolonged postantifungal effects and eliminates the paradoxical growth of Candida albicans

We studied the impact of brief caspofungin exposures on postantifungal effects (PAFEs) and paradoxical effects for five Candida albicans isolates. In time-kill studies, caspofungin at 4× and 16× the MIC resulted in significant killing of all isolates. Caspofungin at 8 μg/ml resulted in lower levels of killing, and paradoxical effects were evident with 4 isolates. Caspofungin exposures of 5 to 60 min caused prolonged, concentration-dependent killing that approached or exceeded the results seen with time-kill experiments and eliminated paradoxical growth.     

Aggression and violence – a problem in Irish Accident and Emergency departments?

Health care employees are more likely than other workers to be victims of violence or aggression. Results from one Australian study suggest that 30% of respondents experienced aggression on a daily or near daily basis. In an Irish context, a total of 22% of all reported injuries in the health and social sector related to injuries inflicted by another person. However, both in Ireland and internationally, there has been an inadequate categorization of the types of incident to which staff are exposed. This contributes to definitional difficulties as well as problems in comparing research findings and using such findings to make work environments safe. The current study aimed to identify the types of violent or aggressive incidents that staff in Irish Accident and Emergency departments were exposed to within a month long period. A cross-sectional study was undertaken with all nurses (N = 80) working in Accident and Emergency departments in two sites nationally as part of a larger study of aggression and violence in health services looking at both Mental Health Services and Accident and Emergency departments. Data were collected using the Scale of Aggressive and Violent Experiences - questionnaire adapted from the Perception of Prevalence of Aggression Scale. The questionnaire captured data on personal and professional demographics as well as experiences of aggressive or violent incidents respondents may have encountered 'in their work situation'. There was a response rate of 46% (n = 37). Data were analysed utilizing spss-11. The relevant data were subjected to a series of one-way anovas and chi-square analysis. The findings suggest that nursing staff in Accident and Emergency departments experienced high levels of verbal aggression. Additionally, they encountered violence or aggression that is vicariously experienced more than forms that were overtly directed towards staff. It is a matter of concern that less than one-third of staff in this study reported that they had training in the management of aggression and violence. The implications will be discussed in relation to both policy and practice.     

Discovery and characterization of inhibitors of human palmitoyl acyltransferases

The covalent attachment of palmitate to specific proteins by the action of palmitoyl acyltransferases (PAT) plays critical roles in the biological activities of several oncoproteins. Two PAT activities are expressed by human cells: type 1 PATs that modify the farnesyl-dependent palmitoylation motif found in H- and N-Ras, and type 2 PATs that modify the myristoyl-dependent palmitoylation motif found in the Src family of tyrosine kinases. We have previously shown that the type 1 PAT HIP14 causes cellular transformation. In the current study, we show that mRNA encoding HIP14 is up-regulated in a number of types of human tumors. To assess the potential of HIP14 and other PATs as targets for new anticancer drugs, we developed three cell-based assays suitable for high-throughput screening to identify inhibitors of these enzymes. Using these screens, five chemotypes, with activity toward either type 1 or type 2 PAT activity, were identified. The activity of the hits were confirmed using assays that quantify the in vitro inhibition of PAT activity, as well as a cell-based assay that determines the abilities of the compounds to prevent the localization of palmitoylated green fluorescent proteins to the plasma membrane. Representative compounds from each chemotype showed broad antiproliferative activity toward a panel of human tumor cell lines and inhibited the growth of tumors in vivo. Together, these data show that PATs, and HIP14 in particular, are interesting new targets for anticancer compounds, and that small molecules with such activity can be identified by high-throughput screening.     

Is there a best approach for extracorporeal life support cannulation: a review of the extracorporeal life support organization

Background

Neurologic complications are common, and amongst the most devastating complications in pediatric patients undergoing extracorporeal life support (ECLS). Carotid artery cannulation (CAN) has been associated with an increase in these complications, thereby shaping practices to avoid this approach in most pediatric patients in which other cannulation approaches are viable.

Why saying what you mean matters: An analysis of trauma team communication

Background

We hypothesized that team communication with unmatched grammatical form and communicative intent (mixed mode communication) would correlate with worse trauma teamwork.

A Systematic Review and Framework for the Use of Hormone Therapy with Salvage Radiation Therapy for Recurrent Prostate Cancer

Context

Salvage radiotherapy (SRT) is a standard of care for men who recur postprostatectomy, and recent randomized trials have assessed the benefit and toxicity of adding hormone therapy (HT) to SRT with differing results.