Spatial Analysis of Greenspace and Mental Health in North Carolina: Consideration of Rural and Urban Communities.

Greenspace positively impacts mental health. Previous research has focused on the greenspace-mental health relationship in urban areas. Yet, little work has looked at rural areas despite rural communities reporting similar rates of poor mental health outcomes and higher rates of suicide mortality compared with urban areas. This ecological research study examined the following research questions: (1) Do public and/or private greenspaces affect the spatial distribution of mental health outcomes in North Carolina? (2) Does this relationship change with rurality? Emergency department data for 6 mental health conditions and suicide mortality data from 2009 to 2018 were included in this analysis. Spatial error and ordinary least squares regressions were used to examine the influence of public and private greenspace quantity on mental health in rural and urban communities. Results suggest greenspace benefits mental health in rural and urban communities. The strength of this relationship varies with urbanity and between public and private greenspaces, suggesting a more complex causal relationship. Given the high case counts and often lower density of mental health care facilities in rural areas, focusing attention on low-cost mental health interventions, such as greenspace, is important when considering rural mental health care.

Racial and ethnic disparities in pregnancy complications and the protective role of greenspace: A retrospective birth cohort study.

Greenspace may positively impact pregnancy health for racially and economically minoritized populations; few studies have examined local availability and accessibility of green/park space in reducing maternal morbidity. The objective of this retrospective birth cohort study was to examine the association between residential exposure to greenspace and adverse pregnancy health outcomes in a Southern US state characterized by high poverty and racial disparities in maternal health (2013-2017). National data from the Protected Area database - United States (PAD-US) and ParkServe estimated three publicly available and accessible residential greenspace measures-a more direct proxy than using remotely-sensed greenness indicators (e.g., normalized difference vegetation index (NDVI))-(a) percent area of greenspace (M1), (b) area of available greenspace per person (M2), (c) total population within a 10-minute walk (M3). Generalized Estimating Equations with logistic regression were used to examine the association between individual greenspace metrics and South Carolina hospital deliveries (n = 238,922 deliveries) for women with correlated maternal health outcomes for gestational hypertension (GHTN), gestational diabetes (GD), severe maternal morbidity (SMM), preeclampsia (PRE), mental disorders (MD), depressive disorders (DD), and preterm birth (PTB). Lowest compared to highest tertiles of all three metrics were associated with increased risk for MD, DD, and a monotonic increase in GD, particularly for black women. Women with the lowest access to M2 and M3 were more at risk for PRE, PTB, and MD. We observed that women in low-income, majority-black communities in the lowest versus highest tertile of M2 were more likely to experience a DD, MD, SMM, or PTB compared to primarily high-income majority-white communities. Available and accessible green/park space may present as an effective nature-based intervention to reduce maternal complications, particularly for gestational diabetes and other pregnancy health risks for which there are currently few known evidence-based primary prevention strategies.

Inter-species interactions alter antibiotic efficacy in bacterial communities.

The efficacy of antibiotic treatments targeting polymicrobial communities is not well predicted by conventional in vitro susceptibility testing based on determining minimum inhibitory concentration (MIC) in monocultures. One reason for this is that inter-species interactions can alter the community members' susceptibility to antibiotics. Here we quantify, and identify mechanisms for, community-modulated changes of efficacy for clinically relevant antibiotics against the pathogen Pseudomonas aeruginosa in model cystic fibrosis (CF) lung communities derived from clinical samples. We demonstrate that multi-drug resistant Stenotrophomonas maltophilia can provide high levels of antibiotic protection to otherwise sensitive P. aeruginosa. Exposure protection to imipenem was provided by chromosomally encoded metallo-ß-lactamase that detoxified the environment; protection was dependent upon S. maltophilia cell density and was provided by S. maltophilia strains isolated from CF sputum, increasing the MIC of P. aeruginosa by up to 16-fold. In contrast, the presence of S. maltophilia provided no protection against meropenem, another routinely used carbapenem. Mathematical ordinary differential equation modelling shows that the level of exposure protection provided against different carbapenems can be explained by differences in antibiotic efficacy and inactivation rate. Together, these findings reveal that exploitation of pre-occurring antimicrobial resistance, and inter-specific competition, can have large impacts on pathogen antibiotic susceptibility, highlighting the importance of microbial ecology for designing successful antibiotic treatments for multispecies communities.

Physiologically based pharmacokinetic modeling of dibromoacetic acid in F344 rats.

A novel physiologically based pharmacokinetic (PBPK) model structure, which includes submodels for the common metabolites (glyoxylate (GXA) and oxalate (OXA)) that may be involved in the toxicity or carcinogenicity of dibromoacetic acid (DBA), has been developed. Particular attention is paid to the representation of hepatic metabolism, which is the primary elimination mechanism. DBA-induced suicide inhibition is modeled by irreversible covalent binding of the intermediate metabolite alpha-halocarboxymethylglutathione (alphaH1) to the glutathione-S-transferase zeta (GSTzeta) enzyme. We also present data illustrating the presence of a secondary non-GSTzeta metabolic pathway for DBA, but not dichloroacetic acid (DCA), that produces GXA. The model is calibrated with plasma and urine concentration data from DBA exposures in female F344 rats through intravenous (IV), oral gavage, and drinking water routes. Sensitivity analysis is performed to confirm identifiability of estimated parameters. Finally, model validation is performed with data sets not used during calibration. Given the structural similarity of dihaloacetates (DHAs), we hypothesize that the PBPK model presented here has the capacity to describe the kinetics of any member or mixture of members of this class in any species with the alteration of chemical-and species-specific parameters.

Reduced ischemia/reperfusion injury via glutathione-initiated nitric oxide-releasing dendrimers.

We report the therapeutic potential of S-nitroso-N-acetylpenicillamine-derivatized generation-4 polyamidoamine dendrimers (G4-SNAP) for reducing ischemia/reperfusion (I/R) injury in an isolated, perfused rat heart. The use of this dendrimer scaffold to deliver the nitrosothiol therapeutic did not inhibit NO donor activity as the required dose of G4-SNAP to minimize I/R injury (31nM corresponding to 2microM SNAP) was consistent with the optimum concentration of small molecule SNAP alone. An exploration of G4-SNAP NO release kinetics in the presence of physiologically relevant concentrations of glutathione (GSH) indicated enhanced NO release (t[NO]=1.28microM NO/mg) at 500microM GSH. Reperfusion experiments conducted with 500microM GSH further lowered the optimal therapeutic G4-SNAP dose to 230pM (i.e., 15nM SNAP). The unique combination of G4-SNAP dendrimer and glutathione trigger represents a novel strategy with possible clinical relevance toward salvaging ischemic tissue.

Short-term effects of specific humidity and temperature on COVID-19 morbidity in select US cities.

Little is known about the environmental conditions that drive the spatiotemporal patterns of SARS-CoV-2. Preliminary research suggests an association with meteorological parameters. However, the relationship with temperature and humidity is not yet apparent for COVID-19 cases in US cities first impacted. The objective of this study is to evaluate the association between COVID-19 cases and meteorological parameters in select US cities. A case-crossover design with a distributed lag nonlinear model was used to evaluate the contribution of ambient temperature and specific humidity on COVID-19 cases in select US cities. The case-crossover examines each COVID case as its own control at different time periods (before and after transmission occurred). We modeled the effect of temperature and humidity on COVID-19 transmission using a lag period of 7 days. A subset of 8 cities were evaluated for the relationship with meteorological parameters and 5 cities were evaluated in detail. Short-term exposure to humidity was positively associated with COVID-19 transmission in 4 cities. The associations were small with 3 out of 4 cities exhibiting higher COVID19 transmission with specific humidity that ranged from 6 to 9 g/kg. Our results suggest that weather should be considered in infectious disease modeling efforts. Future work is needed over a longer time period and across different locations to clearly establish the weather-COVID19 relationship.

Am I safe here?: improving patients' perceptions of safety in hospitals.

Little is known about the current status of hospitalized patients' perceptions of safety or what affects them. This study analyzes safety ratings data of more than 600,000 patients. After describing how patients rate their safety in US acute care hospitals, we delineate the greatest opportunities for improving patient experiences of safety in hospitals. In addition, we offer practical strategies for planning improvements in safety-related elements of care from the patient's perspective.