Concordance between Self-Reported Visual Difficulty and Objective Visual Impairment: The National Health and Aging Trends Study.

PURPOSE: To examine the performance of self-reported visual difficulty (VD) in predicting objective visual impairment (VI) in older adults and explore factors that influence discordance. DESIGN: Cross-sectional analysis of the National Health and Aging Trends Study (2022). METHODS: Participants reporting blindness or difficulties with distance or near vision were characterized as having VD. Presenting binocular distance visual acuity (VA), near VA, and contrast sensitivity (CS) were assessed. Objective VI was defined as having VI in distance VA (worse than 20/40), near VA (worse than 20/40), or CS (worse than 1.55 logCS). Receiver operating characteristic analysis was used to compare performance of VD in predicting VI. To investigate factors that influence discordance, we limited our sample to adults with VI and used a multivariable logistic regression model to identify factors associated with not reporting VD. Similar analyses were performed to explore factors associated with reporting VD in adults without VI. MAIN OUTCOME MEASURES: Discordance factors. RESULTS: Four thousand nine hundred ninety-nine adults were included in the 2022 cohort. Visual difficulty achieved an area under the curve (AUC) of 56.0 (95% confidence interval [CI], 55.2-56.9) in predicting VI, with a sensitivity of 15.8 (95% CI, 14.2-17.5) and specificity of 96.3 (95% CI, 95.5-96.9). Characteristics associated with not reporting VD in adults with VI included female gender (odds ratio [OR], 0.64 [95% CI, 0.42-0.99]), Hispanic ethnicity (OR, 0.49 [95% CI, 0.31-0.78), higher income (≥75 000, OR, 1.99 [95% CI, 1.14-3.45]), ≥4 comorbidities (OR, 0.46 [95% CI, 0.29-0.72]), and depressive symptoms (OR, 0.49 [95% CI, 0.25-0.93]). Factors associated with self-reporting VD in the absence of VI included Hispanic ethnicity (OR, 2.11 [95% CI, 1.15-3.86]), higher income (≥$75 000, OR, 0.27 [95% CI, 0.12-0.63]), and anxiety symptoms (OR, 3.05 [95% CI, 1.56-5.97]). CONCLUSIONS: Self-reported VD is a distinct measure assessing disability and has limited ability in predicting objective VI. Caution is advised when using self-reported VD as a surrogate measure for objective VI in epidemiological studies, although it may still be an effective way to capture risk of current or future disability. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Cymoxanil disrupts RNA synthesis through inhibiting the activity of dihydrofolate reductase.

The agricultural fungicide cymoxanil (CMX) is commonly used in the treatment of plant pathogens, such as Phytophthora infestans. Although the use of CMX is widespread throughout the agricultural industry and internationally, the exact mechanism of action behind this fungicide remains unclear. Therefore, we sought to elucidate the biocidal mechanism underlying CMX. This was accomplished by first performing a large-scale chemical-genomic screen comprising the 4000 haploid non-essential gene deletion array of the yeast Saccharomyces cerevisiae. We found that gene families related to de novo purine biosynthesis and ribonucleoside synthesis were enriched in the presence of CMX. These results were confirmed through additional spot-test and colony counting assays. We next examined whether CMX affects RNA biosynthesis. Using qRT-PCR and expression assays, we found that CMX appears to target RNA biosynthesis possibly through the yeast dihydrofolate reductase (DHFR) enzyme Dfr1. To determine whether DHFR is a target of CMX, we performed an in-silico molecular docking assay between CMX and yeast, human, and P. infestans DHFR. The results suggest that CMX directly interacts with the active site of all tested forms of DHFR using conserved residues. Using an in vitro DHFR activity assay we observed that CMX inhibits DHFR activity in a dose-dependent relationship.

The skin is no barrier to mixtures: Air pollutant mixtures and reported psoriasis or eczema in the Personalized Environment and Genes Study (PEGS).

BACKGROUND: Autoimmune (AI) diseases appear to be a product of genetic predisposition and environmental triggers. Disruption of the skin barrier causes exacerbation of psoriasis/eczema. Oxidative stress is a mechanistic pathway for pathogenesis of the disease and is also a primary mechanism for the detrimental effects of air pollution. METHODS: We evaluated the association between autoimmune skin diseases (psoriasis or eczema) and air pollutant mixtures in 9060 subjects from the Personalized Environment and Genes Study (PEGS) cohort. Pollutant exposure data on six criteria air pollutants are publicly available from the Center for Air, Climate, and Energy Solutions and the Atmospheric Composition Analysis Group. For increased spatial resolution, we included spatially cumulative exposure to volatile organic compounds from sites in the United States Environmental Protection Agency Toxic Release Inventory and the density of major roads within a 5 km radius of a participant's address from the United States Geological Survey. We applied logistic regression with quantile g-computation, adjusting for age, sex, diagnosis with an autoimmune disease in family or self, and smoking history to evaluate the relationship between self-reported diagnosis of an AI skin condition and air pollution mixtures. RESULTS: Only one air pollution variable, sulfate, was significant individually (OR = 1.06, p = 3.99E-2); however, the conditional odds ratio for the combined mixture components of PM2.5 (black carbon, sulfate, sea salt, and soil), CO, SO2, benzene, toluene, and ethylbenzene is 1.10 (p-value = 5.4E-3). SIGNIFICANCE: While the etiology of autoimmune skin disorders is not clear, this study provides evidence that air pollutants are associated with an increased prevalence of these disorders. The results provide further evidence of potential health impacts of air pollution exposures on life-altering diseases. SIGNIFICANCE AND IMPACT STATEMENT: The impact of air pollution on non-pulmonary and cardiovascular diseases is understudied and under-reported. We find that air pollution significantly increased the odds of psoriasis or eczema in our cohort and the magnitude is comparable to the risk associated with smoking exposure. Autoimmune diseases like psoriasis and eczema are likely impacted by air pollution, particularly complex mixtures and our study underscores the importance of quantifying air pollution-associated risks in autoimmune disease.

Discovery and identification of genes involved in DNA damage repair in yeast.

DNA repair defects are common in tumour cells and can lead to misrepair of double-strand breaks (DSBs), posing a significant challenge to cellular integrity. The overall mechanisms of DSB have been known for decades. However, the list of the genes that affect the efficiency of DSB repair continues to grow. Additional factors that play a role in DSB repair pathways have yet to be identified. In this study, we present a computational approach to identify novel gene functions that are involved in DNA damage repair in Saccharomyces cerevisiae. Among the primary candidates, GAL7, YMR130W, and YHI9 were selected for further analysis since they had not previously been identified as being active in DNA repair pathways. Originally, GAL7 was linked to galactose metabolism. YHI9 and YMR130W encode proteins of unknown functions. Laboratory testing of deletion strains gal7Δ, ymr130wΔ, and yhi9Δ implicated all 3 genes in Homologous Recombination (HR) and/or Non-Homologous End Joining (NHEJ) repair pathways, and enhanced sensitivity to DNA damage-inducing drugs suggested involvement in the broader DNA damage repair machinery. A subsequent genetic interaction analysis revealed interconnections of these three genes, most strikingly through SIR2, SIR3 and SIR4 that are involved in chromatin regulation and DNA damage repair network.