In the failing heart, NADPH oxidase and uncoupled NO synthase utilize cytosolic NADPH to form superoxide. NADPH is supplied principally by the pentose phosphate pathway, whose rate-limiting enzyme is glucose 6-phosphate dehydrogenase (G6PD). Therefore, we hypothesized that cardiac G6PD activation drives part of the excessive superoxide production implicated in the pathogenesis of heart failure. Pacing-induced heart failure was performed in eight chronically instrumented dogs. Seven normal dogs served as control. End-stage failure occurred after 28 +/- 1 days of pacing, when left ventricular end-diastolic pressure reached 25 mm Hg. In left ventricular tissue homogenates, spontaneous superoxide generation measured by lucigenin (5 microM) chemiluminescence was markedly increased in heart failure (1338 +/- 419 vs. 419 +/- 102 AU/mg protein, P < 0.05), as were NADPH levels (15.4 +/- 1.5 vs. 7.5 +/- 1.5 micromol/gww, P < 0.05). Superoxide production was further stimulated by the addition of NADPH. The NADPH oxidase inhibitor gp91(ds-tat) (50 microM) and the NO synthase inhibitor L-NAME (1 mM) both significantly lowered superoxide generation in failing heart homogenates by 80% and 76%, respectively. G6PD was upregulated and its activity higher in heart failure compared to control (0.61 +/- 0.10 vs. 0.24 +/- 0.03 nmol/min/mg protein, P < 0.05), while superoxide production decreased to normal levels in the presence of the G6PD inhibitor 6-aminonicotinamide. We conclude that the activation of myocardial G6PD is a novel mechanism that enhances NADPH availability and fuels superoxide-generating enzymes in heart failure.

In response to U.S. Public Health Service projects promoting attention to disparities in the outcomes of mental health treatments, in July 2001, the American Psychological Association, the National Institute of Mental Health, and the Fordham University Center for Ethics Education convened a group of national leaders in bioethics, multicultural research, and ethnic minority mental health to produce a living document to guide ethical decision making for mental health research involving ethnic minority children and youths. This report summarizes the key recommendations distilled from these discussions.

Introduction The value of simulation in medical education and procedural skills training is well recognized. Despite this, many mannequin-based trainers are limited by the inability of the trainee to view the internal anatomical structures. This study evaluates the usability and feasibility of a 1st person point of view (POV) augmented reality (AR) trainer on needle insertion as a component of central venous catheter (CVC) placement. Methods Forty subjects, including medical students and anesthesiology residents and faculty participated. AR glasses were provided through which the relevant internal anatomical landmarks were projected. Following a practice period, participants were asked to place the needle in the mannequin without the benefit of the AR projected internal anatomy. The ability of the trainees to correctly place the needle was documented. Participants also completed a short survey describing their perceptions of the AR technology. Results Participants reported that the AR technology was realistic (77.5%) and that the ability to view the internal anatomy was helpful (92.5%). Furthermore, 85% and 82.1%, respectively, believed that the AR technology promoted learning and should be incorporated into medical training. The ability to successfully place the needle was similar between experienced and non-experienced participants, however, less experienced participants were more likely to inadvertently puncture the carotid artery. Conclusions Results of this pilot study demonstrated the usability and feasibility of AR technology as a potentially important adjunct to simulated medical skills training. Further development and evaluation of this innovative technology under a variety of simulated medical training settings would be an important next step.

Because of the importance of including ethical considerations in planning efforts for pandemic influenza, in February 2005 the Centers for Disease Control and Prevention requested that the Ethics Subcommittee of the Advisory Committee to the Director develop guidance that would serve as a foundation for decision making in preparing for and responding to pandemic influenza. Specifically, the ethics subcommittee was asked to make recommendations regarding ethical considerations relevant to decision making about vaccine and antiviral drug distribution prioritization and development of interventions that would limit individual freedom and create social distancing. The ethics subcommittee identified a number of general ethical considerations including identification of clear goals for pandemic planning, responsibility to maximize preparedness, transparency and public engagement, sound science, commitment to the global community, balancing individual liberty and community interests, diversity in ethical decision making, and commitment to justice. These general ethical considerations are applied to the issues of vaccine and antiviral drug distribution and use of community mitigation interventions.

Overall the AR module was better received compared with the control group with regards to realism, identifying landmarks, visualization of internal organs, ease of use, usefulness, and promoting learning and understanding.