High Crime Neighborhoods as a Driver for Toxic Stress Leading to Asthma

BACKGROUND: Social determinants of health and allostatic load theory suggest social environment can drive asthma diagnoses via the mechanism of toxic stress, the prolonged activation of stress response systems. While research has linked neighborhood crime to asthma, multivariate causal modeling has not been used to test toxic stress as the mechanism that links the two. The current study investigates neighborhood crime as a driver of pediatric asthma diagnoses via toxic stress. METHODS: A retrospective geospatial analysis of health and crime data was conducted. Health data was collected from the OU-Tulsa General Pediatric Clinic’s Electronic Medical Record while crime data was collected from the Tulsa Police Department. All variables were mapped geospatially using census tract as the unit of analysis. Structural equation modeling was used to test the causal model. Neighborhood crime indicators included homicide, rape, and narcotic-related offenses. Diagnoses of conduct, attention deficit, and other anxiety disorders were used in the analysis as toxic stress indicators. Asthma diagnoses were the outcome variable. To further test the model, data from 2016 was used as a calibration sample while data from 2017 was used as a validation sample. RESULTS: A full mediation model of high crime neighborhoods (n = 134) as a driver of toxic stress resulting in increased asthma diagnoses fit the 2016 data well (Χ2 = 15.6, p =.27; df = 13; RMSEA = .04 [90% CI: .00, .10]; CFI: .99; SRMR = .04). The results indicated the model accounted for 78% (R2 = .78) of the variance in asthma diagnoses. The model also provided a good fit to the 2017 data (X2= 23.6, p<.001; df= 13; RMSEA = .08 [90% CI: .02, .13]; CFI: .96; SRMR=.06). CONCLUSION: The results of the current study have important practice and research implications. While clinicians and researchers have become increasingly aware of the impact of social determinants of health, there has been little focus on improving clinical practices. Physicians interested in alleviated the burden of toxic stress and asthma should explore ways to reduce neighborhood crime at the policy level while also being aware of each of their patients’ unique circumstances in relation to where they live.N

CD133-positive dermal papilla-derived Wnt ligands regulate postnatal hair growth

Active Wnt/β-catenin signaling in the dermal papilla (DP) is required for postnatal hair cycling. In addition, maintenance of the hair-inducing ability of DP cells in vitro requires external addition of Wnt molecules. However, whether DP cells are a critical source of Wnt ligands and induce both autocrine and paracrine signaling cascades to promote adult hair follicle growth and regeneration remains elusive. To address this question, we generated an animal model that allows inducible ablation of Wntless (Wls), a transmembrane Wnt exporter protein, in CD133-positive (CD133+) DP cells. CD133+ cells have been shown to be a specific subpopulation of cells in the DP, which possesses the hair-inducing capability. Here, we show that ablation of Wls expression in CD133+ DP cells results in a shortened period of postnatal hair growth. Mutant hair follicles were unable to enter full anagen (hair growth stage) and progressed toward a rapid regression. Notably, reduced size of the DP and decreased expression of anagen DP marker, versican, were observed in hair follicles when CD133+ DP cells lost Wls expression. Further analysis showed that Wls-deficient CD133+ DP cells led to reduced proliferation and differentiation in matrix keratinocytes and melanocytes that are needed for the generation of the hair follicle structure and a pigmented hair shaft. These findings clearly demonstrate that Wnt ligands produced by CD133+ DP cells play an important role in postnatal hair growth by maintaining the inductivity of DP cells and mediating the signaling cross-talk between the mesenchyme and the epithelial compartment