Pittsboro, North Carolina, Chatham County : an action-oriented community diagnosis including secondary data analysis and qualitative data collection

PURPOSE OF COMMUNITY DIAGNOSIS The Chatham Coalition for Adolescent Health and five graduate students from the Department of Health Behavior and Health Education at the UNC School of Public Health collaborated to conduct this community diagnosis of Pittsboro’s adolescents. The purpose of this community diagnosis was to learn about the health and quality of life concerns of residents of Pittsboro, both adult and adolescent, and the resources and strengths that exist in the town for dealing with these concerns. The community diagnosis process used primary and secondary data to discover and analyze both the concerns and strengths of Pittsboro and its adolescents. INTRODUCTION TO OUR COMMUNITY Pittsboro is a small, semi-rural, Southern town that has been in existence for over 200 years. It is the Chatham County seat, located 35 miles west of Raleigh and 17 miles south of Chapel Hill. The town was founded in 1787 and until recently, the population increased very little. The “quaint” downtown is Mecca for antiques lovers, and features over ten antiques stores. In addition, there are several old-fashioned country stores, and a local farmers market situated in the town fairgrounds. However, while antique shopping and tourism entice many to come to Pittsboro, the cornerstone of the community is the people who live, work, and are educated there. Within the larger community of Pittsboro, we focused on adolescents. These teens, ages 11-18, either live or work in the town of Pittsboro or attend school in the Pittsboro District. While many of the adolescents do not actually live in the town of Pittsboro proper, those who work or go to school in the district are just as much influenced by the resources and activities in Pittsboro as are those who live there. This is particularly the case with after-school activities and the county health, educational, and recreational resources that are within reasonable distance of the schools and places of employment. Because we were working in Pittsboro with the Chatham County Coalition for Adolescent Health, it was not difficult to identify teens as our target population. The challenge came in determining which adolescents to include: only those who live within the city limits or residents as well as those who go to school or work in town. Through communications with our preceptor and the service providers we interviewed, it became clear that including the teens who come into Pittsboro daily, for school or work, along with teen residents was necessary since they all have access to the various county departments and other resources in the town and convene at local places such as convenience stores and restaurants. While adolescents are an integral part of Pittsboro, they are a group that tends not to have a collective voice. In addition, it became apparent from the interviews that we conducted that there are several issues facing the entire Pittsboro population that have both direct and indirect effects on the adolescent community. In particular, the growing number of businesses turning teens away, the lack of funding for a city-run recreational center, and the community’s lack of awareness about the existing Teen Center have precluded the ability of teens to convene in a single setting or come together around organized activities. According to one service provider, the consequence is that teens have lost their sense of community and are increasingly prevented from gaining it back. Hence, while we have defined Pittsboro as our community and teens as our focus within that community, the teens may not, in fact, sense that they belong to it. Our intent through this community diagnosis is to help Pittsboro recognize the strengths and needs of its teens and take ownership over the issues relevant to them in order to help the adolescents find their own voice and role within the larger community.Master of Public Healt

CYP19A1 mediates severe SARS-CoV-2 disease outcome in males

Stanelle-Bertram S, Beck S, Mounogou NK, et al. CYP19A1 mediates severe SARS-CoV-2 disease outcome in males. Cell Reports Medicine . 2023: 101152.Male sex represents one of the major risk factors for severe COVID-19 outcome. However, underlying mechanisms that mediate sex-dependent disease outcome are as yet unknown. Here, we identify the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (also known as aromatase) as a host factor that contributes to worsened disease outcome in SARS-CoV-2-infected males. We analyzed exome sequencing data obtained from a human COVID-19 cohort (n= 2,866) using a machine-learning approach and identify a CYP19A1-activity-increasing mutation to be associated with the development of severe disease in men but not women. We further analyzed human autopsy-derived lungs (n= 86) and detect increased pulmonary CYP19A1 expression at the time point of death in men compared with women. In the golden hamster model, we show that SARS-CoV-2 infection causes increased CYP19A1 expression in the lung that is associated with dysregulated plasma sex hormone levels and reduced long-term pulmonary function in males but not females. Treatment of SARS-CoV-2-infected hamsters with a clinically approved CYP19A1 inhibitor (letrozole) improves impaired lung function and supports recovery of imbalanced sex hormones specifically in males. Our study identifies CYP19A1 as a contributor to sex-specific SARS-CoV-2 disease outcome in males. Furthermore, inhibition of CYP19A1 by the clinically approved drug letrozole may furnish a new therapeutic strategy for individualized patient management and treatment. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case–control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10^−7) and PKP4 (P=8.67 × 10^−7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, P_FDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (r_g=0.28 [P=2.99 × 10^−3]), SCZ (r_g=0.34 [P=4.37 × 10^−5]) and MDD (r_g=0.57 [P=1.04 × 10^−3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies