Multi-tissue transcriptomic and serum metabolomic assessment reveals systemic implications of acute ozone-induced stress response in male Wistar Kyoto rats.

Air pollutant exposures have been linked to systemic disease; however, the underlying mechanisms between responses of the target tissue and systemic effects are poorly understood. A prototypic inducer of stress, ozone causes respiratory and systemic multiorgan effects through activation of a neuroendocrine stress response. The goal of this study was to assess transcriptomic signatures of multiple tissues and serum metabolomics to understand how neuroendocrine and adrenal-derived stress hormones contribute to multiorgan health outcomes. Male Wistar Kyoto rats (12-13 weeks old) were exposed to filtered air or 0.8 ppm ozone for 4-hours, and blood/tissues were collected immediately post-exposure. Each tissue had distinct expression profiles at baseline. Ozone changed 1,640 genes in lung, 274 in hypothalamus, 2,516 in adrenals, 1,333 in liver, 1,242 in adipose, and 5,102 in muscle (adjusted p-value < 0.1, absolute fold-change > 50%). Serum metabolomic analysis identified 863 metabolites, of which 447 were significantly altered in ozone-exposed rats (adjusted p-value < 0.1, absolute fold change > 20%). A total of 6 genes were differentially expressed in all 6 tissues. Glucocorticoid signaling, hypoxia, and GPCR signaling were commonly changed, but ozone induced tissue-specific changes in oxidative stress, immune processes, and metabolic pathways. Genes upregulated by TNF-mediated NFkB signaling were differentially expressed in all ozone-exposed tissues, but those defining inflammatory response were tissue-specific. Upstream predictor analysis identified common mediators of effects including glucocorticoids, although the specific genes responsible for these predictors varied by tissue. Metabolomic analysis showed major changes in lipids, amino acids, and metabolites linked to the gut microbiome, concordant with transcriptional changes identified through pathway analysis within liver, muscle, and adipose tissues. The distribution of receptors and transcriptional mechanisms underlying the ozone-induced stress response are tissue-specific and involve induction of unique gene networks and metabolic phenotypes, but the shared initiating triggers converge into shared pathway-level responses. This multi-tissue transcriptomic analysis, combined with circulating metabolomic assessment, allows characterization of the systemic inhaled pollutant-induced stress response.

Assessing Adherence to Statin Prescription Guidelines at a Student-Run Free Clinic: A Retrospective Review.

OBJECTIVE:  The goals of this quality improvement project are to assess the BRIDGE Student-Run Free Clinic's adherence to the 2019 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline on the Primary Prevention of Cardiovascular Disease and to compare our rate of statin prescription to the national average and to uninsured groups. METHODS: A quality improvement project of 205 patients qualified by initial inclusion criteria at a student-run free healthcare clinic. Socio-demographic information, clinical measures associated with cardiovascular risk, and documentation regarding statin prescription at the follow-up visit after a patient's first lipid panel were abstracted from medical records. Descriptive statistics were calculated on the sample (proportions, means), and the proportion of patients eligible for statin treatment was determined. RESULTS: Of 58 patients eligible by guidelines to receive statins, 29 received a statin (50%) at their follow-up visit. Patients with clinical atherosclerotic cardiovascular disease (ASCVD) were more likely to receive statin therapy (83.3%) compared to other groups. Patients who were prescribed a statin were older, had higher total cholesterol, higher low-density lipoprotein (LDL), higher systolic blood pressure, and had higher ASCVD risk. Patients receiving statins were also more likely to be male or have a history of either hypertension, diabetes, or clinical ASCVD. CONCLUSION: Patients with established ASCVD had high rates of statin prescription. Following the first lipid panel, clinicians prescribed statins to approximately 50% of eligible patients. Although this proportion is below the national average for insured patients, it is higher than the national average for uninsured patients and represents a relatively high proportion of eligible patients within the examined time frame.