Improved Survival in Heart Failure Associated with Aspirin Alone or in Combination with ACE Inhibition: An Observational Study

Background: The appropriate role of aspirin in heart failure is controversial. Retrospective analyses have suggested the use of aspirin may attenuate the benefit seen with angiotensin converting enzyme inhibitor (ACEI) therapy. This study investigates the relationship between aspirin use and survival in the UNC Heart Failure Database. This cohort has substantially greater representation of women (32%), African-Americans (44%), and patients with heart failure of a non-ischemic etiology (68%) than previously examined populations. Methods: Data from 872 patients with symptomatic heart failure (HF) and systolic dysfunction were reviewed. These patients were enrolled in the UNC Heart Failure Database from 1984 through 1999, and were followed for a mean of 3.7 years. Data on vital status, available in 96% of patients, revealed 392 deaths. The Cox proportional-hazards regression method was used to determine the relationship of baseline characteristics to all-cause mortality. Results: Multivariate, adjusted survival analysis indicated aspirin use at baseline was associated with a significant reduction in all-cause mortality, with a hazard ratio (HR) for aspirin use of 0.71 (95% CI 0.55-0.92). In patients taking ACEI at baseline, the HR for aspirin use was 0.76 (0.57-1.01) compared to a HR of 0.61 (0.31-1.19) for those not taking ACEI. In patients with ischemic heart disease (IHD) as their primary HF etiology, the HR for aspirin use was 0.65 (0.46-0.94) compared to a HR of0.93 (0.64-1.34) for those with a primary HF etiology other than IHD. Conclusion: Aspirin use at baseline in patients with symptomatic heart failure was independently associated with reduced all-cause mortality.Master of Public Healt

Expression of Dkk 1 in Endometrial Endometrioid Carcinoma & Its Correlation with Wnt / β-catenin Signaling Pathway

Objective: Endometrial cancer is the most common form of cancer affecting female reproductive organs. Most common histologic type endometrioid carcinoma constitutes 75 to 80% of all cases. Studies on Dkk1 expression profiles and its inhibitory role in Wnt signaling pathway in genesis and development of endometrial carcinoma are very few. This study aims to investigate Dkk1 expression in endometrial carcinoma and its correlation with Wnt/β-catenin pathway. Methods: A total of 160 formalin fixed paraffin embedded samples including 50 cases each of endometrial atypical hyperplasia and endometrioid endometrial carcinoma along with 30 cases each of proliferative and secretory endometrium were included in this study. We investigated expression pattern of Dkk1, E-cadherin, β-catenin and c-myc in endometrial atypical hyperplasia and carcinoma as well as compared with that of proliferative and secretory endometrium. Immunohistochemistry and analysis were performed from July, 2018 to June, 2020. Results: We showed decreasing pattern of immunopositivity for Dkk1, E-cadherin and β-catenin from proliferative/secretory endometrium to endometrial atypical hyperplasia and endometrioid carcinoma. Increasing c-myc immunopositivity was noted from proliferative/secretory endometrium to endometrial atypical hyperplasia and endometrioid carcinoma. Moreover, decreasing Dkk1 immunopositivity was well correlated with both E-cadherin, β-catenin and c-myc immunopositivity. Conclusion: Decreasing Dkk1 positivity from benign endometrium to endometrioid carcinoma suggests a negative regulatory function of Dkk1 in endometrioid carcinoma. Dkk1 is downregulated in Wnt signaling pathway in endometrioid endometrial carcinoma. Thus, Dkk1 can show promise as a biomarker for screening endometrioid carcinoma. Future researches can study the reactivation of the Dkk1 gene that could be a valuable strategy for antagonizing Wnt signaling pathway. Keywords: Endometrioid carcinoma, Dkk1, Wnt/β-catenin pathway, β-catenin, E-cadheri

Associations Among Androgens, Estrogens, and Natriuretic Peptides in Young Women Observations From the Dallas Heart Study

ObjectivesWe sought to determine if natriuretic peptides are associated with estrogen and androgen status in a population study of young women without known cardiac disease.BackgroundCirculating concentrations of plasma B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are higher in women than in men, and they may be influenced by estrogens and androgens.MethodsCardiac magnetic resonance imaging, dual energy X-ray absorbtiometry, and measurements of BNP, NT-proBNP, follicle-stimulating hormone (FSH), total testosterone, and sex hormone-binding globulin (SHBG), were performed in 682 women (ages 35 to 49 years) participating in the Dallas Heart Study.ResultsIn multivariable analyses adjusting for age, race/ethnicity, body mass index (BMI), serum creatinine, left ventricular mass and left ventricular ejection fraction <55%, menopausal status, and FSH were not associated with BNP and NT-proBNP. In contrast, higher SHBG was associated with higher BNP and NT-proBNP, while the free androgen index and calculated free testosterone were inversely associated with BNP and NT-proBNP (p < 0.0001 for each). Addition of SHBG or any measure of free testosterone to the multivariable models modified the effect of BMI and lean mass, such that measures of body composition were no longer significantly associated with BNP or NT-proBNP.ConclusionsAmong young women, measures of free testosterone were independently and inversely associated with BNP and NT-proBNP. These results suggest that circulating free testosterone, not estradiol, mediates gender differences in natriuretic peptides. In addition, the association between higher BMI and lean body mass with natriuretic peptides may be mediated by testosterone

Race and Gender Differences in C-Reactive Protein Levels

ObjectivesThis study sought to determine whether there are race and gender differences in the distribution of C-reactive protein (CRP) levels.BackgroundFew data are available comparing CRP distributions in different race and gender groups. Recent clinical practice recommendations for CRP testing for cardiovascular risk assessment suggest a uniform threshold to define high relative risk (>3 mg/l).MethodsWe measured CRP in 2,749 white and black subjects ages 30 to 65 participating in the Dallas Heart Study, a multiethnic, population-based, probability sample, and compared levels of CRP between different race and gender groups.ResultsBlack subjects had higher CRP levels than white subjects (median, 3.0 vs. 2.3 mg/l; p < 0.001) and women had higher CRP levels than men (median, 3.3 vs. 1.8 mg/l; p < 0.001). The sample-weight adjusted proportion of subjects with CRP levels >3 mg/l was 31%, 40%, 51%, and 58% in white men, black men, white women, and black women, respectively (p < 0.05 for each group vs. white men). After adjustment for traditional cardiovascular risk factors, estrogen and statin use, and body mass index, a CRP level >3 mg/l remained more common in white women (odds ratio [OR] 1.6; 95% confidence interval [CI] 1.1 to 2.5) and black women (OR 1.7; 95% CI 1.2 to 2.6) but not in black men (OR, 1.3; 95% CI, 0.8 to 1.9) when compared with white men.ConclusionsSignificant race and gender differences exist in the population distribution of CRP. Further research is needed to determine whether race and gender differences in CRP levels contribute to differences in cardiovascular outcomes, and whether thresholds for cardiovascular risk assessment should be adjusted for different race and gender groups

Phylogenomics Reveals Ancient Gene Tree Discordance in the Amphibian Tree of Life

Molecular phylogenies have yielded strong support for many parts of the amphibian Tree of Life, but poor support for the resolution of deeper nodes, including relationships among families and orders. To clarify these relationships, we provide a phylogenomic perspective on amphibian relationships by developing a taxon-specific Anchored Hybrid Enrichment protocol targeting hundreds of conserved exons which are effective across the class. After obtaining data from 220 loci for 286 species (representing 94% of the families and 44% of the genera), we estimate a phylogeny for extant amphibians and identify gene tree–species tree conflict across the deepest branches of the amphibian phylogeny. We perform locus-by-locus genealogical interrogation of alternative topological hypotheses for amphibian monophyly, focusing on interordinal relationships. We find that phylogenetic signal deep in the amphibian phylogeny varies greatly across loci in a manner that is consistent with incomplete lineage sorting in the ancestral lineage of extant amphibians. Our results overwhelmingly support amphibian monophyly and a sister relationship between frogs and salamanders, consistent with the Batrachia hypothesis. Species tree analyses converge on a small set of topological hypotheses for the relationships among extant amphibian families. These results clarify several contentious portions of the amphibian Tree of Life, which in conjunction with a set of vetted fossil calibrations, support a surprisingly younger timescale for crown and ordinal amphibian diversification than previously reported. More broadly, our study provides insight into the sources, magnitudes, and heterogeneity of support across loci in phylogenomic data sets

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum