Neutrophils from p40phox-/- mice exhibit severe defects in NADPH oxidase regulation and oxidant-dependent bacterial killing.

The generation of reactive oxygen species (ROS) by the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex plays a critical role in the antimicrobial functions of the phagocytic cells of the immune system. The catalytic core of this oxidase consists of a complex between gp91(phox), p22(phox), p47(phox), p67(phox), p40(phox), and rac-2. Mutations in each of the phox components, except p40(phox), have been described in cases of chronic granulomatous disease (CGD), defining their essential role in oxidase function. We sought to establish the role of p40(phox) by investigating the NADPH oxidase responses of neutrophils isolated from p40(phox-/-) mice. In the absence of p40(phox), the expression of p67(phox) is reduced by approximately 55% and oxidase responses to tumor necrosis factor alpha/fibrinogen, immunoglobulin G latex beads, Staphylococcus aureus, formyl-methionyl-leucyl-phenylalanine, and zymosan were reduced by approximately 97, 85, 84, 75, and 30%, respectively. The defect in ROS production by p40(phox-/-) neutrophils in response to S. aureus translated into a severe, CGD-like defect in the killing of this organism both in vitro and in vivo, defining p40(phox) as an essential component in bacterial killing.

The development of an evaluation framework for injury surveillance systems.

BACKGROUND: Access to good quality information from injury surveillance is essential to develop and monitor injury prevention activities. To determine if information obtained from surveillance is of high quality, the limitations and strengths of a surveillance system are often examined. Guidelines have been developed to assist in evaluating certain types of surveillance systems. However, to date, no standard guidelines have been developed to specifically evaluate an injury surveillance system. The aim of this research is to develop a framework to guide the evaluation of injury surveillance systems. METHODS: The development of an Evaluation Framework for Injury Surveillance Systems (EFISS) involved a four stage process. First, a literature review was conducted to identify an initial set of characteristics that were recognised as important and/or had been recommended to be assessed in an evaluation of a surveillance system. Second, this set of characteristics was assessed using SMART criteria. Third, those surviving were presented to an expert panel using a two round modified-Delphi study to gain an alternative perspective on characteristic definitions, practicality of assessment, and characteristic importance. Finally, a rating system was created for the EFISS characteristics. RESULTS: The resulting EFISS consisted of 18 characteristics that assess three areas of an injury surveillance system - five characteristics assess data quality, nine characteristics assess the system's operation, and four characteristics assess the practical capability of an injury surveillance system. A rating system assesses the performance of each characteristic. CONCLUSION: The development of the EFISS builds upon existing evaluation guidelines for surveillance systems and provides a framework tailored to evaluate an injury surveillance system. Ultimately, information obtained through an evaluation of an injury data collection using the EFISS would be useful for agencies to recommend how a collection could be improved to increase its usefulness for injury surveillance and in the long-term injury prevention.