Features Associated with Visible Lamina Cribrosa Pores in Individuals of African Ancestry with Glaucoma: Primary Open-Angle African Ancestry Glaucoma Genetics (POAAGG) Study.

There are scarce data regarding the rate of the occurrence of primary open-angle glaucoma (POAG) and visible lamina cribrosa pores (LCPs) in the eyes of individuals with African ancestry; the potential impact of these features on disease burden remains unknown. We recruited subjects with POAG to the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Through regression models, we evaluated the association between the presence of LCPs and various phenotypic features. In a multivariable analysis of 1187 glaucomatous eyes, LCPs were found to be more likely to be present in eyes with cup-to-disc ratios (CDR) of ≥0.9 (adjusted risk ratio (aRR) 1.11, 95%CI: 1.04-1.19, p = 0.005), eyes with cylindrical-shaped (aRR 1.22, 95%CI: 1.11-1.33) and bean pot (aRR 1.24, 95%CI: 1.13-1.36) cups versus conical cups (p < 0.0001), moderate cup depth (aRR 1.24, 95%CI: 1.06-1.46) and deep cups (aRR 1.27, 95%CI: 1.07-1.50) compared to shallow cups (p = 0.01), and the nasalization of central retinal vessels (aRR 1.33, 95%CI: 1.23-1.44), p < 0.0001). Eyes with LCPs were more likely to have a higher degree of African ancestry (q0), determined by means of SNP analysis (aRR 0.96, 95%CI: 0.93-0.99, p = 0.005 for per 0.1 increase in q0). Our large cohort of POAG cases of people with African ancestry showed that LCPs may be an important risk factor in identifying severe disease, potentially warranting closer monitoring by physicians.

The Impact of Social Determinants of Health on Eye Care Utilization in a National Sample of People with Diabetes.

PURPOSE: To evaluate the association of social determinants of health (SDoH) with eye care utilization among people with diabetes mellitus using the 2013-2017 National Health Interview Survey (NHIS). DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Participants ≥ 18 years of age with self-reported diabetes. METHODS: The SDoH in the following domains were used: (1) economic stability; (2) neighborhood, physical environment, and social cohesion; (3) community and social context; (4) food environment; (5) education; and (6) health care system. An aggregate SDoH score was calculated and divided into quartiles, with Q4 representing those with the highest adverse SDoH burden. Survey-weighted multivariable logistic regression models evaluated the association of SDoH quartile with eye care utilization in the preceding 12 months. A linear trend test was conducted. Domain-specific mean SDoH scores were calculated, and the performance of domain-specific models was compared using area under the curve (AUC). MAIN OUTCOME MEASURE: Eye care utilization in the preceding 12 months. RESULTS: Of 20 807 adults with diabetes, 43% had not used eye care. Greater adverse SDoH burden was associated with decrements in odds of eye care utilization (P < 0.001 for trend). Participants in the highest quartile of adverse SDoH burden (Q4) had a 58% lower odds (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.37-0.47) of eye care utilization than those in Q1. The domain-specific model using economic stability had the highest performing AUC (0.63; 95% CI, 0.62-0.64). CONCLUSIONS: Among a national sample of people with diabetes, adverse SDoH were associated with decreased eye care utilization. Evaluating and intervening upon the effects of adverse SDoH may be a means by which to improve eye care utilization and prevent vision loss. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Idiosyncratic Fitness Costs of Ampicillin-Resistant Mutants Derived from a Long-Term Experiment with Escherichia coli.

Antibiotic resistance is a growing concern that has prompted a renewed focus on drug discovery, stewardship, and evolutionary studies of the patterns and processes that underlie this phenomenon. A resistant strain's competitive fitness relative to its sensitive counterparts in the absence of drug can impact its spread and persistence in both clinical and community settings. In a prior study, we examined the fitness of tetracycline-resistant clones that evolved from five different Escherichia coli genotypes, which had diverged during a long-term evolution experiment. In this study, we build on that work to examine whether ampicillin-resistant mutants are also less fit in the absence of the drug than their sensitive parents, and whether the cost of resistance is constant or variable among independently derived lines. Like the tetracycline-resistant lines, the ampicillin-resistant mutants were often less fit than their sensitive parents, with significant variation in the fitness costs among the mutants. This variation was not associated with the level of resistance conferred by the mutations, nor did it vary across the different parental backgrounds. In our earlier study, some of the variation in fitness costs associated with tetracycline resistance was explained by the effects of different mutations affecting the same cellular pathway and even the same gene. In contrast, the variance among the ampicillin-resistant mutants was associated with different sets of target genes. About half of the resistant clones suffered large fitness deficits, and their mutations impacted major outer-membrane proteins or subunits of RNA polymerases. The other mutants experienced little or no fitness costs and with, one exception, they had mutations affecting other genes and functions. Our findings underscore the importance of comparative studies on the evolution of antibiotic resistance, and they highlight the nuanced processes that shape these phenotypes.

Idiosyncratic variation in the fitness costs of tetracycline-resistance mutations in Escherichia coli.

A bacterium's fitness relative to its competitors, both in the presence and absence of antibiotics, plays a key role in its ecological success and clinical impact. In this study, we examine whether tetracycline-resistant mutants are less fit in the absence of the drug than their sensitive parents, and whether the fitness cost of resistance is constant or variable across independently derived lines. Tetracycline-resistant lines suffered, on average, a reduction in fitness of almost 8%. There was substantial among-line variation in the fitness cost. This variation was not associated with the level of resistance conferred by the mutations, nor did it vary significantly across several genetic backgrounds. The two resistant lines with the most extreme fitness costs involved functionally unrelated mutations on different genetic backgrounds. However, there was also significant variation in the fitness costs for mutations affecting the same pathway and even different alleles of the same gene. Our findings demonstrate that the fitness costs of antibiotic resistance do not always correlate with the phenotypic level of resistance or the underlying genetic changes. Instead, these costs reflect the idiosyncratic effects of particular resistance mutations and the genetic backgrounds in which they occur.