Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus Disease Outcomes

We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus–infected patients. We studied the relationship between KIR–human leukocyte antigen (HLA) combinations and the clinical outcomes of patients with Ebola virus disease (EVD). We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The activating 2DS4–003 and inhibitory 2DL5 genes were significantly more common among persons who died of EVD; 2DL2 was more common among survivors. We used logistic regression analysis and Bayesian modeling to identify 2DL2, 2DL5, 2DS4–003, HLA-B-Bw4-Thr, and HLA-B-Bw4-Ile as probably having a significant relationship with disease outcome. Our findings highlight the importance of innate immune response against Ebola virus and show the association between KIRs and the clinical outcome of EVD.     

Early and Direct Rehab Transfer Leads to Significant Cost Savings and Decreased Hospital Length of Stay for Total Joint Arthroplasty in a Veteran Population

BackgroundTotal joint arthroplasty is the most common elective orthopedic procedure in the Veterans Affairs hospital system. In 2019, physical medicine and rehabilitation began screening patients before surgery to select candidates for direct transfer to acute rehab after surgery. The primary outcome of this study was to demonstrate that the accelerated program was successful in decreasing inpatient costs and length of stay (LOS). The secondary outcome was to show that there was no increase in complication, reoperation, and readmission rates.MethodsA retrospective review of total joint arthroplasty patients was conducted with three cohorts: 1) control (n = 193), 2) transfer to rehab orders on postop day #1 (n = 178), and 3) direct transfers to rehab (n = 173). To assess for demographic disparities between cohorts, multiple analysis of variance tests followed by a Bonferroni P-value correction were used. Differences between test groups regarding primary outcomes were assessed with analysis of variance tests followed by pairwise t-tests with Bonferroni P-value corrections.ResultsThere were no significant differences between the cohort demographics or comorbidities. The mean total LOS decreased from 7.0 days in the first cohort, to 6.9 in the second, and 6.0 in the third (P = .00034). The mean decrease in cost per patient was $14,006 between cohorts 1 and 3, equating to over $5.6 million in savings annually. There was no significant change in preintervention and postintervention short-term complications (P = .295).ConclusionsSignificant cost savings and decrease in total LOS was observed. In the current health care climate focused on value-based care, a similar intervention could be applied nationwide to improve Veterans Affair services.     

Contraceptive use at first sexual intercourse among adolescent and young adult women with disabilities: The role of formal sex education

ObjectivesThis study examines receipt of formal sex education as a potential mechanism that may explain the observed associations between disability status and contraceptive use among young women with disabilities.Study designUsing the 2011?2017 National Survey of Family Growth, we analyzed data from 2861 women aged 18 to 24 years, who experienced voluntary first sexual intercourse with a male partner. Women whose first intercourse was involuntary (7% of all women reporting sexual intercourse) were excluded from the analytic sample. Mediation analysis was used to estimate the indirect effect of receipt of formal sex education before first sexual intercourse on the association between disability status and contraceptive use at first intercourse.ResultsCompared to nondisabled women, women with cognitive disabilities were less likely to report receipt of instruction in each of 6 discrete formal sex education topics and received instruction on a fewer number of topics overall (B = ?0.286, 95% CI = ?0.426 to ?0.147), prior to first voluntary intercourse. In turn, the greater number of topics received predicted an increased likelihood of contraceptive use at first voluntary intercourse among these women (B = 0.188, 95% CI = 0.055?0.321). No significant association between noncognitive disabilities and receipt of formal sex education or contraceptive use at first intercourse was observed.ConclusionsGiven the positive association between formal sex education and contraceptive use among young adult women with and without disabilities, ongoing efforts to increase access to formal sex education are needed. Special attention is needed for those women with cognitive disabilities.     

Chemically-induced histone modification as a predictor of carcinogenicity

The interaction between carcinogens and DNA is believed to initiate neoplastic transformation, but evidence suggests that epigenetic mechanisms may also be of importance. Because the histone proteins have important roles in chromatin structure and cellular function, they provide a reasonably well understood epigenetically-based system for the detection of carcinogens. In this study, human foreskin fibroblastic cells were exposed to one of several mutagens and/or carcinogens for 3, 12, or 24 h to determine if induced histone modification may be a means of predicting chemical carcinogenicity.Butyric acid (5 mM), known to result in acetylation of histones H3 and H4, and 12-O-tetradecanoylphorbol-13-acetate (3 M), known to result in phosphorylated histone H1, were tested initially. Electrophoresis of the histone fractions was capable of resolving multiple forms of histones H1, H3, and H4.Propane sultone (0.1 mM) induced a broadening of the H2A and H2B bands after a 24 h exposure and carbon tetrachloride (1 mM) induced the formation of new histone forms in the H1 fraction after 24 h and in the H3 fraction after 3 h. Experimental variability limited the statistically significant modifications to carbon tetrachloride and propane sultone, two known carcinogens, where new forms of modified histone were detected. Therefore, the histone modification assay, with further experimentation, may be an alternate method of detecting carcinogens, especially when conventional genotoxic tests prove unreliable.     

Health reform planning models. The case of veterans hospitals

As part of the national effort to reform healthcare, the Department of Veterans Affairs is undergoing a major reassessment of its healthcare mission. As Veterans Affairs prepares to meet the challenges of the twenty-first century, one underlying issue of critical importance is which planning assumptions will be selected and employed. Will historical patterns of veterans' use be interpreted as indicators of the market demand for Veterans Affairs healthcare services, or will estimates of disease prevalence among veterans be used as indicators of future healthcare need? If Veterans Affairs is to continue as a critical component of the nation's healthcare delivery system, its selection of a planning basis will have major implications for tomorrow's healthcare system.     

Endothelial lipopigment as an indicator of α-tocopherol deficiency in two equine neurodegenerative diseases

Two spontaneous neurodegenerative diseases of the horse, equine motor neuron disease (EMND) and equine degenerative myeloencephalopathy (EDM), have been associated with -tocopherol deficiency, and both were characterized by prominent accumulations of endothelial lipopigment in the small vessels of the spinal cord. These endothelial pigment deposits appear to be reversible. In EMND horses pasture-supplemented for 9 months or more after the progression of weakness and wasting had arrested, there was very little endothelial lipopigment. The origin and the potential effects of these endothelial lipopigment accumulations are discussed.