Internal medicine and general surgery residents' attitudes about the ACGME duty hours regulations: a multicenter study.

PURPOSE: To assess internal medicine and general surgery residents' attitudes about the effects of the Accreditation Council for Graduate Medical Education duty hours regulations on medical errors, quality of patient care, and residency experiences. METHOD: In 2005, the authors surveyed 200 residents who trained both before and after duty hours reform at six residency programs (three internal medicine, three general surgery) at five academic medical centers in the United States. Residents' attitudes about the effects of the duty hours regulations on the quality of patient care, residency education, and quality of life were measured using a survey instrument containing 19 Likert scale questions on a scale of 1 to 5. Survey responses were compared using the Student's t-test. RESULTS: The response rate was 80% (159 residents). Residents reported that whereas fatigue-related errors decreased slightly, errors related to reduced continuity of care significantly increased. Additionally, duty hours regulations somewhat decreased opportunities for formal education, bedside learning, and procedures, but there was no consensus that graduates would be less well trained after duty hours reform. Residents, particularly surgical trainees, reported improvements in quality of life and reduced burnout. CONCLUSIONS: Residents in medicine and surgery had similar opinions about the effects of duty hours reform, including improved quality of life. However, resident opinions suggest that reduced fatigue-related errors have been offset by errors related to decreased continuity of care and that the quality of the educational experience may have declined. Quantifying the degree to which regulating duty hours affected errors related to discontinuity of care should be a focus of future research.     

Cell lines that support replication of a novel herpes simplex virus 1 UL31 deletion mutant can properly target UL34 protein to the nuclear rim in the absence of UL31

Previous results indicated that the herpes simplex virus 1 (HSV-1) U(L)31 gene is necessary and sufficient for localization of the U(L)34 protein exclusively to the nuclear membrane of infected Hep2 cells. In the current studies, a bacterial artificial chromosome containing the entire HSV-1 strain F genome was used to construct a recombinant viral genome in which a gene encoding kanamycin resistance was inserted in place of 262 codons of the 306 codon U(L)31 open reading frame. The deletion virus produced virus titers approximately 10- to 50-fold lower in rabbit skin cells, more than 2000-fold lower in Vero cells, and more than 1500-fold lower in CV1 cells, compared to a virus bearing a restored U(L)31 gene. The replication of the U(L)31 deletion virus was restored on U(L)31-complementing cell lines derived either from rabbit skin cells or CV1 cells. Confocal microscopy indicated that the majority of U(L)34 protein localized aberrantly in the cytoplasm and nucleoplasm of Vero cells and CV1 cells, whereas U(L)34 protein localized at the nuclear membrane in rabbit skin cells, and U(L)31 complementing CV1 cells infected with the U(L)31 deletion virus. We conclude that rabbit skin cells encode a function that allows proper localization of U(L)34 protein to the nuclear membrane. We speculate that this function partially complements that of U(L)31 and may explain why U(L)31 is less critical for replication in rabbit skin cells as opposed to Vero and CV1 cells.     

Virus overrides the propensity of human CD40L-activated plasmacytoid dendritic cells to produce Th2 mediators through synergistic induction of IFN-{gamma} and Th1 chemokine production

Depending on the activation status, plasmacytoid dendritic cells (PDC) and myeloid DC have the ability to induce CD4 T cell development toward T helper cell type 1 (Th1) or Th2 pathways. Thus, we tested whether different activation signals could also have an impact on the profile of chemokines produced by human PDC. Signals that induce human PDC to promote a type 1 response (i.e., viruses) and a type 2 response [i.e., CD40 ligand (CD40L)] also induced PDC isolated from tonsils to secrete chemokines preferentially attracting Th1 cells [such as interferon-gamma (IFN-gamma)-inducible protein (IP)-10/CXC chemokine ligand 10 (CXCL10) and macrophage inflammatory protein-1beta/CC chemokine ligand 4 (CCL4)] or Th2 cells (such as thymus and activation-regulated chemokine/CCL17 and monocyte-derived chemokine/CCL22), respectively. Activated natural killer cells were preferentially recruited by supernatants of virus-activated PDC, and supernatants of CD40L-activated PDC attracted memory CD4(+) T cells, particularly the CD4(+)CD45RO(+)CD25(+) T cells described for their regulatory activities. It is striking that CD40L and virus synergized to trigger the production of IFN-gamma by PDC, which induces another Th1-attracting chemokine monokine-induced by IFN-gamma/CXCL9 and cooperates with endogenous type I IFN for IP-10/CXCL10 production. In conclusion, our studies reveal that PDC participate in the selective recruitment of effector cells of innate and adaptive immune responses and that virus converts the CD40L-induced Th2 chemokine patterns of PDC into a potent Th1 mediator profile through an autocrine loop of IFN-gamma.     

Interleukin-4 receptor alpha chain and STAT6 signaling inhibit gamma interferon but not Th2 cytokine expression within schistosome granulomas

Compared to wild-type (WT) mice, schistosome granulomas in Stat6 knockout (KO) mice lacked eosinophils and had Th1 features. Interleukin-4 (IL-4) acts through Stat6 in assisting Th2 cell development. The importance of Stat6 for Th2-cell development within schistosome granulomas had not been explored. Therefore we studied gamma interferon (IFN-gamma), IL-4, and IL-5 production in granulomas from Stat6 KO and WT mice. Dispersed granuloma cells from Stat6 KO and WT mice made similar amounts of IL-4 and IL-5. Only Stat6 KO granuloma cells released IFN-gamma. Granuloma T cells contained most of the IL-4, IL-5, and IFN-gamma mRNA and secreted these cytokines. In Stat6 KO mice, 16.6% of the granuloma cells were CD4(+). Of these, 10.7% stained for IFN-gamma and/or IL-4 by intracytoplasmic flow analysis. Few CD4(-) T cells stained positively. The IL-4-producing T cells did not stain for DX5 or with labeled alpha-GalCer CD1d tetramer, suggesting an absence of NK T cells. Thus, conventional Th cells in Stat6 KO granulomas produce IFN-gamma and Th2 cytokines. Stat6 limits IFN-gamma production but is unnecessary for Th2-cell development or localization within the granuloma.     

Evaluation of dry and wet transported intravaginal swabs in detection of Chlamydia trachomatis and Neisseria gonorrhoeae infections in female soldiers by PCR

Screening women for sexually transmitted diseases (STD) in nonclinic settings is highly desirable because many infections are asymptomatic. This is especially true for military women, for whom logistical, social, and other job-related obstacles present barriers to accessing medical care. We assessed the accuracy of intravaginal swabs transported by mail in a wet versus a dry state for PCR (Amplicor CT/NG test) detection of chlamydia and gonorrhea infections in a cross-sectional study of 793 active-duty military women attending an STD clinic. PCR tests of vaginal swabs (wet and dry) were compared to local clinical methods used on cervical swabs. Standard wet vaginal swab PCR testing detected more chlamydia (11.6%) than cervical enzyme immunoassay (9.3%). For detection of chlamydia using wet swabs, the sensitivity and specificity compared with adjudicated true positives were 94.6% (87 of 92) and 99.3% (696 of 701), respectively. Comparing dry swabs to true-positives for chlamydia, the sensitivity was 91.3% (84 of 92) and the specificity was 99.3% (696 of 701). Standard wet vaginal swab PCR detected more gonorrhea (3.3%) than routine cervical culture (2.1%). The sensitivity and specificity of PCR testing of wet swabs compared to true-positives (infected patients) were 96.3% (26 of 27) and 98.2% (752 of 766) for gonorrhea, respectively. For gonorrhea, the sensitivity and specificity of dry swabs compared to true-positives (infected patients) were 88.9% (24 of 27) and 98.3% (753 of 766), respectively. PCR testing of wet and dry transported intravaginal swabs to detect chlamydia and gonorrhea infections was an accurate diagnostic method for military women.     

Brain regions and their dynamics in prospective memory retrieval: a MEG study.

We measured brain activity using magnetoencephalography in five participants during ongoing tasks that included prospective memory, retrospective memory, and oddball trials. Sources were identified in the hippocampal formation and posterior parietal and frontal lobes. Posterior parietal cortex activation had an earlier onset in the prospective memory condition than retrospective memory or oddball conditions, a higher level of theta activity in the retrospective condition, and higher levels of upper alpha in the prospective and oddball conditions. Activation of the hippocampal formation had a longer duration in the retrospective memory and prospective memory conditions than the oddball condition, but prominent alpha and theta band activity was present in all three conditions. We interpret the early (87 ms) onset of activity in parietal cortex as evidence for an initial noticing of appropriate conditions for a PM response. Hippocampal activity may reflect a subsequent memory search for the intended action.     

Autosomal dominant inheritance of Klein–Waardenburg syndrome

We report on 2 sibs with the Klein–Waardenburg syndrome; they had dystopia canthorum, blepharophimosis, and bilateral flexion contractures of the fingers. The children's father and paternal aunt are also affected. This report confirms that the Klein–Waardenburg syndrome is an autosomal dominant syndrome.     

Assessing the Impact of Salt Reduction Initiatives on the Chronic Disease Burden of Singapore

Globally, many countries are facing an increasing burden of chronic disease due to ageing populations, of which cardiovascular disease forms a large proportion. Excess dietary sodium contributes to cardiovascular disease risk and requires intervention at a population level. This study aimed to quantify the impact of several salt reduction initiatives on population health over a 30-year horizon using GeoDEMOS, a population model from Singapore. Four interventions were modelled in four demographic groups in 2020 for a total of 16 intervention scenarios. The effect of 0.5, 2.0, and 4.0 g/day reductions in daily salt consumption, along with adherence to the World Health Organization guidelines of a maximum of 5.0 g of salt each day, was modelled in the entire population, including the overweight and obese, the elderly, and diabetics. In each scenario, the number of averted incident cases of acute myocardial infarction and stroke, along with the disability-adjusted life years up to 2050, was monitored. We found 4.0 g/day reductions in salt consumption were the most effective when implemented across the entire population, resulting in 24,000 averted incident cases of cardiovascular disease and 215,000 disability-adjusted life years over 30 years. This is a large figure when compared with the 29,200 projected annual incident cases of cardiovascular disease in 2050. When targeted at specific high-risk demographic groups, the largest effects were observed in the overweight and obese, with the same intervention yielding 10,500 averted incident cases of cardiovascular disease and 91,500 disability-adjusted life years. Quantifying the benefits of salt reduction initiatives revealed a significant impact when administered across the entire population or the overweight and obese. Health promotion efforts directed toward sustainably reducing salt consumption will help to lower the chronic disease burden on the healthcare system in years to come.