The Veterans Affairs Learners' Perceptions Survey: the foundation for educational quality improvement.

PURPOSE: The U.S. Department of Veterans Affairs (VA) supports 8,700 resident positions nationally to enhance quality of care for veterans and to educate physicians. This study sought to establish a yearly quality indicator to identify and follow strengths and opportunities for improvement in VA clinical training programs. METHOD: In March 2001, the VA Learners' Perceptions Survey, a validated 57-item questionnaire, was mailed to 3,338 residents registered at 130 VA facilities. They were asked to rate their overall satisfaction with the VA clinical training experience and their satisfaction in four domains: faculty/preceptor, learning, working, and physical environments using a five-point Likert scale. Questionnaires were received from 1,775 residents (53.2%). A full analysis was conducted using 1,436 of these questionnaires, whose respondents were categorized in four training programs: medicine (n = 706), surgery (n = 291), subspecialty (n = 266), and psychiatry (n = 173). RESULTS: On a scale of 0 to 100, residents gave their clinical training experience an average score of 79. Eighty-four percent would have recommended VA training to peers, and 81% would have chosen VA training again. Overall, 87% were satisfied with their faculty/preceptors, 78% with the learning environment, and 67% with the working and physical environments. The survey was sensitive to differences in satisfaction among the trainee groups, with residents in internal medicine (IM) the least satisfied. CONCLUSION: The VA Learners' Perceptions Survey is the first validated survey to address comprehensive satisfaction issues in clinical training. The survey highlights strengths and opportunities for improvement in VA clinical training and is the first step toward improving education.     

In vitro evidence for both the nucleus and cytoplasm as subcellular sites of pathogenesis in Huntington's disease

A unifying feature of the CAG expansion diseases is the formation of intracellular aggregates composed of the mutant polyglutamine-expanded protein. Despite the presence of aggregates in affected patients, the precise relationship between aggregates and disease pathogenesis is unresolved. Results from in vivo and in vitro studies of mutant huntingtin have lead to the hypothesis that nuclear localization of aggregates is critical for the pathology of Huntington's disease (HD). We tested this hypothesis using a 293T cell culture model system that compared the frequency and toxicity of cytoplasmic and nuclear huntingtin aggregates. We first assessed the mode of nuclear transport of N-terminal fragments of huntingtin, and show that the predicted endogenous NLS is not functional, providing data in support of passive nuclear transport. This result suggests that proteolysis is a necessary step for nuclear entry of huntingtin. Additionally, insertion of nuclear import or export sequences into huntingtin fragments containing 548 or 151 amino acids was used to reverse the normal localization of these proteins. Changing the subcellular localization of the fragments did not influence their total aggregate frequency. There were also no significant differences in toxicity associated with the presence of nuclear compared with cytoplasmic aggregates. The findings of nuclear and cytoplasmic aggregates in affected brains, together with these in vitro data, support the nucleus and cytosol as subcellular sites for pathogenesis in HD.      

Parental smoking impairs vaccine responses in children with atopic genotypes

BACKGROUND: Gene-environment interactions play central roles in controlling postnatal maturation of immune function, but their effects on infant vaccine responses are unknown. Genetic variants associated with atopy and the environmental factor of exposure to parental smoking (PS) of tobacco independently alter immune responses. OBJECTIVE: We sought to investigate the hypothesis that genetic variants associated with atopy and their interaction with PS influence infant vaccine responsiveness. METHODS: In 200 infants with parental atopic history, relationships were sought between polymorphisms in the IL-4, IL-4 receptor alpha (IL-4Ralpha), and IL-13 genes; PS; and immune responses to diphtheria/tetanus vaccination. RESULTS: Analyses stratified by PS unmasked negative associations between atopic alleles of these genes and vaccine outcomes. The most consistent involved the IL-4Ralpha 551 QR/QQ genotypes, which were associated with reduced IgG levels (P = .02) and T-cell responses (IFN-gamma, P = .002; IL-10, P = .01; 1L-13, P = .01; IL-5, P = .06) to tetanus toxoid and parallel reductions in polyclonal T-cell responses and innate immune responses in PS-exposed infants. CONCLUSION: PS potentiates suppressive effects of variants in immune response genes in children. These effects are not observed in the absence of this exposure. Ultimately, this finding might have implications for infant vaccination in countries with high smoking rates. It might also have broader implications in relation to environmental toxicology because it demonstrates specific mechanisms through which the developing immune system might be differentially sensitive to low-level toxicant exposures. CLINICAL IMPLICATIONS: PS interacts with genes associated with atopy to impair vaccine responses. These interactions might have vaccine design and public health implications.     

Nocturnal Blood Pressure Non-Dipping,Posttraumatic Stress Disorder,and Sleep Quality in Women

Women with posttraumatic stress disorder (PTSD) have poor sleep quality and increased risk of cardiovascular disease (CVD). Non-dipping of nocturnal blood pressure may be an explanatory factor for the relationship between sleep and CVD found in previous research. The current study was designed to determine if non-dipping nocturnal blood pressure was associated with trauma exposure, PTSD diagnosis, PTSD symptoms, and sleep quality in a sample of women. Participants completed 24 hours of ABPM and self-report questionnaires. Non-dipping was defined as less than 10% reduction in blood pressure during sleep. The frequency of non-dippers did not differ by diagnostic status (d = .15). However, non-dippers endorsed more traumatic event categories (d = .53), more PTSD hyperarousal symptoms (d = .53), poorer overall sleep quality (d = .59), more frequent use of sleep medication (d = .62), greater sleep-related daytime dysfunction (d = .58), and longer sleep onset latencies (d = .55) than dippers. Increased attention to nocturnal blood pressure variation may be needed to improve blood pressure control in trauma-exposed women.     

Osteopontin augments CD3-mediated interferon-gamma and CD40 ligand expression by T cells, which results in IL-12 production from peripheral blood mononuclear cells

Osteopontin is an RGD-containing bone matrix protein with cytokine-like functions that is associated with early stages of Th1-mediated diseases. Although the function of osteopontin in these responses is unknown, it is expressed by activated T cells and macrophages and can costimulate T cell proliferation. Studies have demonstrated that early IL-12 and IFN-gamma expression is required to induce a protective response to many intracellular pathogens. Herein, we demonstrate that osteopontin stimulation augments the ability of anti-CD3 monoclonal antibody to induce CD40 ligand (CD40L) and IFN-gamma expression on human T cells, resulting in CD40L- and IFN-gamma-dependent IL-12 production in vitro. These findings suggest a functional role for osteopontin in early Th1 responses, namely regulation of T cell-dependent IL-12 production. Further, osteopontin up-regulation of CD40L provides mechanistic support for the association of osteopontin with polyclonal B cell proliferation and humoral autoimmune disease.     

Thrombolysis with systemically administered t-PA in a new venous thrombosis model

Early thrombosis of either the arterial or venous supply of a free flap or island pedicle flap results in total flap necrosis. Until very recently, the only option for flap salvage was surgical intervention and, often, revision of the vascular pedicle. Current advances in the pharmacologic treatment of coronary artery and deep leg vein thrombosis have kindled interest in the field of reconstructive surgery for pharmacologic treatment of thromboses that compromise flaps. In the past, there has been research on the local and systemic administration of thrombolytic agents for lysis of experimentally induced thrombi in various animal models. A new venous inversion graft thrombosis model is presented here, which possesses many advantages over previously employed research models. This study demonstrates thrombolysis with systemically administered tissue plasminogen activator (t-PA) in this model.