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Bidstrup posted an update 7 months, 1 week ago
Lower dehydroepiandrosterone-sulfate (DHEA-S) levels have been inconsistently associated with coronary heart disease (CHD) and mortality. Data are limited for heart failure (HF) and association between DHEA-S change and events.
Assess associations between low DHEA-S/DHEA-S change and incident HF hospitalization, CHD, and mortality in older adults.
DHEA-S was measured in stored plasma from visits 4 (1996-1998) and 5 (2011-2013) of the Atherosclerosis Risk in Communities study. Follow-up for incident events 18 years for DHEA-S level; 5.5 years for DHEA-S change.
General community.
Individuals without prevalent cardiovascular disease (n = 8143, mean age 63 years).
Associations between DHEA-S and incident HF hospitalization, CHD, or mortality; associations between 15-year change in DHEA-S (n = 3706) and cardiovascular events.
DHEA-S below the 15th sex-specific percentile of the study population (men 55.4 µg/dL; women 27.4 µg/dL) was associated with increased HF hospitalization (men hazard ratio [HR] 1.30, 95% confidence interval [CI], 1.07-1.58; women HR 1.42, 95% CI, 1.13-1.79); DHEA-S below the 25th sex-specific percentile (men 70.0 µg/dL; women 37.1 µg/dL) was associated with increased death (men HR 1.12, 95% CI, 1.01-1.25; women HR 1.19, 95% CI, 1.03-1.37). In men, but not women, greater percentage decrease in DHEA-S was associated with increased HF hospitalization (HR 1.94, 95% CI, 1.11-3.39). Low DHEA-S and change in DHEA-S were not associated with incident CHD.
Low DHEA-S is associated with increased risk for HF and mortality but not CHD. Further investigation is warranted to evaluate mechanisms underlying these associations.
Low DHEA-S is associated with increased risk for HF and mortality but not CHD. Further investigation is warranted to evaluate mechanisms underlying these associations.Gamma-glutamyl carboxylase (GGCX) is an integral membrane protein that catalyzes posttranslational carboxylation of a number of vitamin K-dependent (VKD) proteins involved in a wide variety of physiological processes, including blood coagulation, vascular calcification, and bone metabolism. Naturally occurring GGCX mutations are associated with multiple distinct clinical phenotypes. However, the genotype-phenotype correlation of GGCX remains elusive. Here, we systematically examined the effect of all naturally occurring GGCX mutations on the carboxylation of three structure-function distinct VKD proteins in a cellular environment. find more GGCX mutations were transiently introduced into GGCX-deficient human embryonic kidney 293 cells stably expressing chimeric coagulation factor, matrix Gla protein (MGP), or osteocalcin as VKD reporter-proteins, then the carboxylation efficiency of these reporter-proteins were evaluated. Our results show that GGCX mutations differentially affect the carboxylation of these reporter-proteins and the efficiency of using vitamin K as a cofactor. Carboxylation of these reporter-proteins by a C-terminal truncation mutation (R704X) implies that GGCX’s C-terminus plays a critical role in the binding of osteocalcin, but not in the binding of coagulation factors and MGP. This has been confirmed by probing the protein-protein interaction between GGCX and its protein substrates in live cells using bimolecular fluorescence complementation and chemical cross-linking assays. Additionally, using a minigene splicing assay, we demonstrated that several GGCX missense mutations affect GGCX’s pre-mRNA splicing rather than altering the corresponding amino acid residues. Results from this study interpreted the correlation of GGCX’s genotype and its clinical phenotypes, and clarified why vitamin K administration rectified bleeding disorders but not non-bleeding disorders.
This study assessed historical and current gender, racial, and ethnic diversity trends within US pathology graduate medical education (GME) and the pathologist workforce.
Data from online, publicly available sources were assessed for significant differences in racial, ethnic, and sex distribution in pathology trainees, as well as pathologists in practice or on faculty, separately compared with the US population and then each other using binomial tests.
Since 1995, female pathology resident representation has been increasing at a rate of 0.45% per year (95% confidence interval [CI], 0.29-0.61; P < .01), with pathology now having significantly more females (49.8%) compared to the total GME pool (45.4%; P < .0001). In contrast, there was no significant trend in the rate of change per year in black or American Indian, Alaskan Native, Native Hawaiian, and Pacific Islander (AI/AN/NH/PI) resident representation (P = .04 and .02). Since 1995, underrepresented minority (URM) faculty representation has increased by 0.03% per year (95% CI, 0.024-0.036; P < .01), with 7.6% URM faculty in 2018 (5.2% Hispanic, 2.2% black, 0.2% AI/AN/NH/PI).
This assessment of pathology trainee and physician workforce diversity highlights significant improvements in achieving trainee gender parity. However, there are persistent disparities in URM representation, with significant underrepresentation of URM pathologists compared with residents.
This assessment of pathology trainee and physician workforce diversity highlights significant improvements in achieving trainee gender parity. However, there are persistent disparities in URM representation, with significant underrepresentation of URM pathologists compared with residents.
Evidence of U.S. adult flavored e-cigarette use prevalence stratified by age, smoking status, and purpose for vaping (i.e., quitting smoking, to use when/where smoking is not allowed) can inform policies that reduce the tobacco-related cancer burden.
Current flavored e-cigarette use (use >1 non-tobacco flavors) prevalence estimates were compared across subpopulation groups using two-sided statistical significance tests in the July 2018 Current Population Survey Tobacco Use Supplement, a nationally representative cross-sectional adult survey (n = 46,759).
Current flavored e-cigarette use was reported by 1.6% (95% CI = 1.47% to 1.69%) of all respondents. Among current vapers, the percentage that used flavored e-cigarettes was higher in adults aged 18-24 (89.6%), 25-34 (86.7%), or 35-44 (76.0%) than adults aged ≥45 years (60.4%, Ps < .001); higher in never (89.8%) than current (72.9%), long-term former (73.9%), or recent former (80.4%) smokers (Ps ≤ .009); higher in smokers that reportedly did (78.9%) vs.