Use of the Location-Based Social Networking Application GRINDR as a Recruitment Tool in Rectal Microbicide Development Research

Mobile phone social networking applications such as GRINDR are potential tools for recruitment of men who have sex with men (MSM) for HIV prevention research. Demographics and sexual risk behaviors of men recruited through GRINDR and through traditional media were compared. GRINDR participants were younger (mean age 31 vs. 42, p?<?0.0001), more White identified (44 vs. 30?%, p?<?0.01), and had more sex partners in the previous 14 days (1.88 vs. 1.10, p?<?0.05) than other recruits. Email responses were less successful for enrollment than phone calls (5 vs. 50?%). This approach resulted in successful recruitment of younger and more educated, White identified MSM.     

Molecular basis of telomere syndrome caused by CTC1 mutations

Mutations in CTC1 lead to the telomere syndromes Coats Plus and dyskeratosis congenita (DC), but the molecular mechanisms involved remain unknown. CTC1 forms with STN1 and TEN1 a trimeric complex termed CST, which binds ssDNA, promotes telomere DNA synthesis, and inhibits telomerase-mediated telomere elongation. Here we identify CTC1 disease mutations that disrupt CST complex formation, the physical interaction with DNA polymerase α-primase (polα-primase), telomeric ssDNA binding in vitro, accumulation in the nucleus, and/or telomere association in vivo. While having diverse molecular defects, CTC1 mutations commonly lead to the accumulation of internal single-stranded gaps of telomeric DNA, suggesting telomere DNA replication defects as a primary cause of the disease. Strikingly, mutations in CTC1 may also unleash telomerase repression and telomere length control. Hence, the telomere defect initiated by CTC1 mutations is distinct from the telomerase insufficiencies seen in classical forms of telomere syndromes, which cause short telomeres due to reduced maintenance of distal telomeric ends by telomerase. Our analysis provides molecular evidence that CST collaborates with DNA polα-primase to promote faithful telomere DNA replication.     

Optimization of the High-Shear Wet Granulation Wetting Process Using Fuzzy Logic Modeling

A fuzzy model has been developed for the optimization of high-shear wet granulation wetting on a plant scale depending on the characteristics of pharmaceutical active substance particles. The model optimized on the basis of experimental data involves a set of rules obtained from expert knowledge and full-scale process data. The skewness coefficient of particle size distribution and the tapped density of the granulated mixture were chosen as the model input variables. The output of the fuzzy ruled system is the optimal quantity of wetting liquid. In comparison to manufacturing practice, a very strong sensitivity of the optimal quantity of the added wetting liquid to the size and shape of the active substance particles has been identified by fuzzy modeling.     

The Astounding Breadth of Health Disparity: Phenome-Wide Effects of Race on Disease Risk

ObjectiveWe conducted a phenotype-wide association study (PheWAS) to compare diagnoses among Blacks with those of Whites in one health center in Tennessee using data from 1,883,369 patients.MethodsWe used our deidentified EHR, the Synthetic Derivative, to assess risk of diagnoses associated with Black as compared with White race using Firth logistic regression with covariates including age, sex, and density of clinical encounters.ResultsThere were anchoring associations in both directions, including the highest increased risk for Blacks of having sickle cell anemia, and strongest decreased risk of basal cell carcinoma. Results included established areas of disparity and many novel associations.ConclusionsPheWAS is a viable tool for calculating risk associated with any biomarker. The current analysis provide a new approach to generating hypotheses and understanding the breadth of health disparities. Future analyses will further explore causality, risk factors, and potential confounders not accounted for here.