Examining County-Level Associations between Federally Qualified Health Centers and Sexually Transmitted Infections: A Political Ecology of Health Framework.

Federally Qualified Health Centers (FQHCs) are the largest providers of healthcare for sexually transmitted infections (STIs) in medically underserved communities in the United States (US). Through the Affordable Care Act (ACA), FQHCs have grown in number, but the impact of this growth on STIs is poorly understood. This ecological study seeks to quantify the association between FQHCs and STI prevalence in all US counties. Variables were described utilizing medians and interquartile ranges, and distributions were compared using Kruskal-Wallis tests. Median rates of chlamydia in counties with high, low, and no FQHCs were 370.3, 422.6, and 242.1 cases per 100,000 population, respectively. Gonorrhea rates were 101.9, 119.7, and 49.9 cases per 100,000 population, respectively. Multivariable linear regression models, adjusted for structural and place-based characteristics (i.e., Medicaid expansion, social vulnerability, metropolitan status, and region), were used to examine county-level associations between FQHCs and STIs. Compared to counties with no FQHCs, counties with a high number of FQHCs had chlamydia rates that were an average of 68.6 per 100,000 population higher (ß = 68.6, 95% CI: 45.0, 92.3) and gonorrhea rates that were an average of 25.2 per 100,000 population higher (ß = 25.2, 95% CI: 13.2, 37.2). When controlled for salient factors associated with STI risks, greater FQHC availability was associated with greater diagnosis and treatment of STIs. These findings provide empirical support for the utility of a political ecology of health framework and the critical role of FQHCs in confronting the STI epidemic in the US.

CHRFAM7A: A human specific fusion gene, accounts for the translational gap for cholinergic strategies in Alzheimer's disease.

BACKGROUND: Cholinergic neuronal loss is one of the hallmarks of AD related neurodegeneration; however, preclinical promise of α7 nAChR drugs failed to translate into humans. CHRFAM7A, a uniquely human fusion gene, is a negative regulator of α7 nAChR and was unaccounted for in preclinical models. METHODS: Molecular methods: Function of CHRFAM7A alleles was studied in vitro in two disease relevant phenotypic readouts: electrophysiology and Aß uptake. Genome edited human induced pluripotent stem cells (iPSC) were used as a model system with the human context. Double blind pharmacogenetic study: We performed double-blind pharmacogenetic analysis on the effect of AChEI therapy based on CHRFAM7A carrier status in two paradigms: response to drug initiation and DMT effect. Mini Mental Status Examination (MMSE) was used as outcome measure. Change in MMSE score from baseline was compared by 2-tailed T-test. Longitudinal analysis of clinical outcome (MMSE) was performed using a fitted general linear model, based on an assumed autoregressive covariance structure. Model independent variables included age, sex, and medication regimen at the time of the first utilized outcome measure (AChEI alone or AChEI plus memantine), APOE4 carrier status (0, 1 or 2 alleles as categorical variables) and CHRFAM7A genotype. FINDINGS: The direct and inverted alleles have distinct phenotypes. Functional CHRFAM7A allele classifies the population as 25% non-carriers and 75% carriers. Induced pluripotent stem cell (iPSC) models α7 nAChR mediated Aß neurotoxicity. Pharmacological readout translates into both first exposure (p = 0.037) and disease modifying effect (p = 0.0048) in two double blind pharmacogenetic studies. INTERPRETATION: CHRFAM7A accounts for the translational gap in cholinergic strategies in AD. Clinical trials not accounting for this uniquely human genetic factor may have rejected drug candidates that would benefit 25% of AD. Reanalyses of the completed trials using this pharmacogenetic paradigm may identify effective therapy.