Ratios of plasma and salivary testosterone throughout puberty: Production versus bioavailability

Because diffusion of testosterone (T) into the salivary gland is thought to be largely limited to the free, biolog

Relations between Preschool Attention Span-Persistence and Age 25 Educational Outcomes

This study examined relations between children’s attention span-persistence in preschool and later school achievement and college completion. Children were drawn from the Colorado Adoption Project using adopted and non-adopted children (N = 430). Results of structural equation modeling indicated that children’s age 4 attention span-persistence significantly predicted math and reading achievement at age 21 after controlling for achievement levels at age 7, adopted status, child vocabulary skills, gender, and maternal education level. Relations between attention span-persistence and later achievement were not fully mediated by age 7 achievement levels. Logistic regressions also revealed that age 4 attention span-persistence skills significantly predicted the odds of completing college by age 25. The majority of this relationship was direct and was not significantly mediated by math or reading skills at age 7 or age 21. Specifically, children who were rated one standard deviation higher on attention span-persistence at age 4 had 48.7% greater odds of completing college by age 25. Discussion focuses on the importance of children’s early attention span-persistence for later school achievement and educational attainment.Keywords: self-regulation, academic achievement, educational attainment, attention span-persistenc

The 2016 Model of The Clinical Practice of Emergency Medicine

Emergency medicine (EM) has a scientifically derived and commonly accepted description of the domain of its clinical practice. That document, “The Model of the Clinical Practice of Emergency Medicine” (EM Model), was developed through the collaboration of six organizations: the American Board of Emergency Medicine (ABEM), the administrative organization for the project, the American College of Emergency Physicians (ACEP), the Council of Emergency Medicine Residency Directors (CORD), the Emergency Medicine Residents\u27 Association (EMRA), the Residency Review Committee for Emergency Medicine (RRC-EM), and the Society for Academic Emergency Medicine (SAEM). Development of the EM Model was based on an extensive practice analysis of the specialty. The practice analysis relied on both empiric data gathered from actual emergency department visits and several expert panels (1). The resulting product was first published in 2001, and has successfully served as the common source document for all EM organizations (2,3). One of its strengths is incorporating the reality that EM is a specialty driven by symptoms not diagnoses, requiring simultaneous therapeutic and diagnostic interventions

A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells

The host cell serine protease TMPRSS2 is an attractive therapeutic target for COVID-19 drug discovery. This protease activates the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of other coronaviruses and is essential for viral spread in the lung. Utilizing rational structure-based drug design (SBDD) coupled to substrate specificity screening of TMPRSS2, we have discovered covalent small-molecule ketobenzothiazole (kbt) TMPRSS2 inhibitors which are structurally distinct from and have significantly improved activity over the existing known inhibitors Camostat and Nafamostat. Lead compound MM3122 (4) has an I

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Population Frequencies of the Triallelic 5HTTLPR in Six Ethnicially Diverse Samples from North America, Southeast Asia, and Africa

Genetic differences between populations are a potentially an important contributor to health disparities around the globe. As differences in gene frequencies influence study design, it is important to have a thorough understanding of the natural variation of the genetic variant(s) of interest. Along these lines, we characterized the variation of the 5HTTLPR and rs25531 polymorphisms in six samples from North America, Southeast Asia, and Africa (Cameroon) that differ in their racial and ethnic composition. Allele and genotype frequencies were determined for 24,066 participants. Results indicated higher frequencies of the rs25531 G-allele among Black and African populations as compared with White, Hispanic and Asian populations. Further, we observed a greater number of ‘extra-long’ (‘XL’) 5HTTLPR alleles than have previously been reported. Extra-long alleles occurred almost entirely among Asian, Black and Non-White Hispanic populations as compared with White and Native American populations where they were completely absent. Lastly, when considered jointly, we observed between sample differences in the genotype frequencies within racial and ethnic populations. Taken together, these data underscore the importance of characterizing the L-G allele to avoid misclassification of participants by genotype and for further studies of the impact XL alleles may have on the transcriptional efficiency of SLC6A4

Genome-wide Linkage Scan to Identify Loci for Age at First Cigarette in Dutch Sibling Pairs

Most smokers begin smoking during adolescence and early age of smoking initiation is related to more frequent current smoking, daily smoking and more dependent smoking (Everret et al., 1999; Lando et al.