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Browsing by Author "James, Rebecca"
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Item Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa(Springer Nature, 2021-06-01) Ganzen, Logan; Ko, Mee Jung; Zhang, Mengrui; Xie, Rui; Chen, Yongkai; Zhang, Liyun; James, Rebecca; Mumm, Jeff; van Rijn, Richard M.; Zhong, Wenxuan; Pang, Chi Pui; Zhang, Mingzhi; Tsujikawa, Motokazu; Leung, Yuk Fai; Biochemistry and Molecular Biology, School of MedicineRetinitis Pigmentosa (RP) is a mostly incurable inherited retinal degeneration affecting approximately 1 in 4000 individuals globally. The goal of this work was to identify drugs that can help patients suffering from the disease. To accomplish this, we screened drugs on a zebrafish autosomal dominant RP model. This model expresses a truncated human rhodopsin transgene (Q344X) causing significant rod degeneration by 7 days post-fertilization (dpf). Consequently, the larvae displayed a deficit in visual motor response (VMR) under scotopic condition. The diminished VMR was leveraged to screen an ENZO SCREEN-WELL REDOX library since oxidative stress is postulated to play a role in RP progression. Our screening identified a beta-blocker, carvedilol, that ameliorated the deficient VMR of the RP larvae and increased their rod number. Carvedilol may directly on rods as it affected the adrenergic pathway in the photoreceptor-like human Y79 cell line. Since carvedilol is an FDA-approved drug, our findings suggest that carvedilol can potentially be repurposed to treat autosomal dominant RP patients.Item The role of trauma and positive youth development in polysubstance use among rural middle school students: a latent class analysis(BMC, 2022-12-14) Zervos, Andrew P.; Hensel, Devon J.; James, Rebecca; Hunt, Abby; Ott, Mary A.; Pediatrics, School of MedicineBackground: Rural youth often begin developing polysubstance use and other risk behaviors during middle school. However, little polysubstance use research focuses on rural middle school youth. Our research uses Latent Class Analysis to understand existing patterns of rural middle school polysubstance use and risk and protective factors associated with polysubstance use. Methods: We used survey data from a rural middle school pregnancy prevention program (N = 2,708). The survey included measures of demographics, lifetime substance use, trauma (adverse childhood experiences and bullying victimization) and aspects of youth development (parent communication on drugs and alcohol, parent connectedness and school connectedness). We used latent class analysis to produce participant polysubstance use profiles and multinomial regression to examine associations between polysubstance use, demographics, trauma and aspects of youth development. Results: We categorized our participants into four latent classes. Our analysis classified 2.2% of participants as Regular Polysubstance users, 6.9% as Polysubstance experimenters, 19% as Vape + Alcohol experimenters and 71.9% as Non-Users. More adverse childhood experiences were associated with greater risk of polysubstance use and experimentation. Bullying was positively associated with greater risk of vape and alcohol experimentation. Higher reported parental and school connectedness were associated with lower risk of high frequency polysubstance use. Higher reported school connection was also associated with lower risk of polysubstance experimentation. Conclusion: Rural substance use prevention programs should begin during middle school, as polysubstance use development is common among rural middle schoolers. These programs should be trauma informed and focus on connectedness as a modifiable factor to reduce risk of polysubstance use development.