Infection and Activation of B Cells by Theiler's Murine Encephalomyelitis Virus (TMEV) Leads to Autoantibody Production in an Infectious Model of Multiple Sclerosis.

Theiler's murine encephalomyelitis virus (TMEV) induces immune-mediated inflammatory demyelinating disease in susceptible mice that is similar to human multiple sclerosis (MS). In light of anti-CD20 therapies for MS, the susceptibility of B cells to TMEV infection is particularly important. In our study, direct viral exposure to macrophages and lymphocytes resulted in viral replication and cellular stimulation in the order of DCs, macrophages, B cells, and T cells. Notably, B cells produced viral proteins and expressed elevated levels of CD69, an activation marker. Similarly, the expression of major histocompatibility complex class II and costimulatory molecules in B cells was upregulated. Moreover, TMEV-infected B cells showed elevated levels of antigen-presenting function and antibody production. TMEV infection appeared to polyclonally activate B cells to produce autoantibodies and further T cell stimulation. Thus, the viral infection might potentially affect the outcome of autoimmune diseases, and/or the development of other chronic infections, including the protection and/or pathogenesis of TMEV-induced demyelinating disease.

Trends in smoking cessation counseling: experience from American Heart Association-get with the guidelines.

BACKGROUND: Successful smoking cessation in stroke and coronary artery disease (CAD) patients is important, as smoking contributes to significant morbidity and mortality. The American Heart Association developed Get With The Guidelines (GWTG) to improve compliance with national guideline recommendations for cardiovascular care. Using data from GWTG, we examined trends associated with the smoking-cessation counseling (SCC) performance measure. HYPOTHESIS: Implementation of a systematic quality improvement program will increase compliance with the SCC performance measure. METHODS: We evaluated compliance with SCC in current or recent smokers identified from 224 671 CAD admissions between 2002 and 2008 in the GWTG-CAD database, and from 405 681 stroke admissions between 2002 and 2007 in the GWTG-Stroke database. Additionally, we examined adherence to other performance and quality measures related to CAD and stroke care. RESULTS: Overall, 55 904 GWTG-CAD and 58 865 GWTG-Stroke admissions were used for the analysis. Rates of SCC improved in each successive year during the study, from 67.6% to 97.4% (P < 0.001) in GWTG-CAD and from 40.1% to 90.7% (P < 0.001) in GWTG-Stroke. Compliance with SCC was up to 34.7% lower (P < 0.0001) in GWTG-Stroke compared with GWTG-CAD, but this difference decreased to 6.7% (P < 0.0001) by the end of the study period. Compliance with many other performance and quality measures was significantly lower among patients not receiving SCC. CONCLUSIONS: Get With The Guidelines has improved compliance with the SCC performance measure among patients with CAD and stroke. Although the initial disparity in rates of SCC between CAD and stroke patients gradually improved, the difference remained significant.

Sex and ethnic differences in 47 candidate proteomic markers of cardiovascular disease: the Mayo Clinic proteomic markers of arteriosclerosis study.

BACKGROUND: Cardiovascular disease (CVD) susceptibility differs between men and women and varies with ethnicity. This variability is not entirely explained by conventional CVD risk factors. We examined differences in circulating levels of 47 novel protein markers of CVD in 2561 men and women of African-American (AA) and non-Hispanic White (NHW) ethnicity, enrolled at geographically distinct sites. METHODOLOGY/PRINCIPAL FINDINGS: Participants (1,324 AAs, mean age 63.5 y, 71% women; 1,237 NHWs, mean age 58.9 y, 57% women) belonged to sibships ascertained on the basis of hypertension. Solid-phase immunoassays and immunoturbidometric, clot-based, chromogenic, and electrophoretic assays were used to measure the 47 protein markers in plasma or serum. Marker levels were log transformed and outliers were adjusted to within 4 SD. To identify markers independently associated with sex or ethnicity, we employed multivariable regression analyses that adjusted for conventional risk factors, prior history of CVD, medication use and lifestyle factors (physical activity, alcohol consumption and education). Generalized estimating equations were used to correct for intrafamilial correlations. After adjustment for the above covariates, female sex was associated with higher levels of 29 markers and lower levels of 6 markers. Female sex was independently associated with higher levels of several inflammatory markers as well as lipoproteins, adipokines, natriuretic peptides, vasoconstrictor peptides and markers of calcification and thrombosis. AA ethnicity was associated with higher levels of 19 markers and lower levels of 6 markers, including higher levels of several inflammatory makers, higher leptin and lower adiponectin levels, lower levels of vasodilator-natriuretic peptides, higher levels of vasoconstrictor-antidiuretic peptides and markers of calcification and thrombosis. CONCLUSIONS/SIGNIFICANCE: Plasma levels of several novel protein markers of CVD differ significantly in the context of sex and ethnicity. These results have implications for individualized CVD risk assessment.

Primary coronary intervention in acute myocardial infarction.

Percutaneous coronary intervention (PCI) with stent implantation has become the standard of care for acute myocardial infarction <12 hours from symptom onset. This has led to decreased morbidity and mortality both short and long term compared to thrombolytic therapy. Stent implantation has been demonstrated to be superior to balloon PCI for mechanical reperfusion of acute myocardial infarction. Intravenous antiplatelet glycoprotein IIb/IIIa inhibitors may have a role in improving TIMI flow prior to PCI and decreasing morbidity and mortality. The role of thrombolytics vs. IIb/IIIa inhibitors in "facilitated reperfusion" is unclear at this time and further research is needed to define the indication of adjunctive pharmacology.