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Item Effect of Vitamin C Supplementation for Pregnant Smokers on Offspring Airway Function and Wheeze at Age 5 Years: Follow-up of a Randomized Clinical Trial(American Medical Association, 2023) McEvoy, Cindy T.; Shorey-Kendrick, Lyndsey E.; Milner, Kristin; Harris, Julia; Vuylsteke, Brittany; Cunningham, Michelle; Tiller, Christina; Stewart, Jaclene; Schilling, Diane; Brownsberger, Julie; Titus, Hope; MacDonald, Kelvin D.; Gonzales, David; Vu, Annette; Park, Byung S.; Spindel, Eliot R.; Morris, Cynthia D.; Tepper, Robert S.; Pediatrics, School of MedicineImportance: Vitamin C supplementation (500 mg/d) for pregnant smokers has been reported to increase offspring airway function as measured by forced expiratory flow (FEF) through age 12 months; however, its effects on airway function at age 5 years remain to be assessed. Objective: To assess whether vitamin C supplementation in pregnant smokers is associated with increased and/or improved airway function in their offspring at age 5 years and whether vitamin C decreases the occurrence of wheeze. Design, setting, and participants: This study followed up the Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) double-blind, placebo-controlled randomized clinical trial conducted at 3 centers in the US (in Oregon, Washington, and Indiana) between 2012 and 2016. Investigators and participants remain unaware of the treatment assignments. Forced expiratory flow measurements at age 5 years were completed from 2018 to 2021. Interventions: Pregnant smokers were randomized to vitamin C (500 mg/d) or placebo treatment. Main outcomes and measures: The primary outcome was the prespecified measurement of FEF between 25% and 75% expired volume (FEF25-75) by spirometry at age 5 years. Secondary outcomes included FEF measurements at 50% and 75% of expiration (FEF50 and FEF75), forced expiratory volume in 1 second (FEV1), and occurrence of wheeze. Results: Of the 251 pregnant smokers included in this study, 125 (49.8%) were randomized to vitamin C and 126 (50.2%) were randomized to placebo. Of 213 children from the VCSIP trial who were reconsented into this follow-up study, 192 (90.1%) had successful FEF measurements at age 5 years; 212 (99.5%) were included in the analysis of wheeze. Analysis of covariance demonstrated that offspring of pregnant smokers allocated to vitamin C compared with placebo had 17.2% significantly higher mean (SE) measurements of FEF25-75 at age 5 years (1.45 [0.04] vs 1.24 [0.04] L/s; adjusted mean difference, 0.21 [95% CI, 0.13-0.30]; P < .001). Mean (SE) measurements were also significantly increased by 14.1% for FEF50 (1.59 [0.04] vs 1.39 [0.04] L/s; adjusted mean difference, 0.20 [95% CI, 0.11-0.30]; P < .001), 25.9% for FEF75 (0.79 [0.02] vs 0.63 [0.02] L/s; 0.16 [95% CI, 0.11-0.22]; P < .001), and 4.4% for FEV1 (1.13 [0.02] vs 1.09 [0.02] L; 0.05 [95% CI, 0.01-0.09]; P = .02). In addition, offspring of pregnant smokers randomized to vitamin C had significantly decreased wheeze (28.3% vs 47.2%; estimated odds ratio, 0.41 [95% CI, 0.23-0.74]; P = .003). Conclusions and relevance: In this follow-up study of offspring of pregnant smokers randomized to vitamin C vs placebo, vitamin C supplementation during pregnancy resulted in significantly increased airway function of offspring at age 5 years and significantly decreased the occurrence of wheeze. These findings suggest that vitamin C supplementation for pregnant smokers may decrease the effects of smoking in pregnancy on childhood airway function and respiratory health.Item Evidence-Based Utility of Adjunct Antioxidant Supplementation for the Prevention and Treatment of Dermatologic Diseases: A Comprehensive Systematic Review(MDPI, 2023-07-27) Tran, Jasmine Thuy; Diaz, Michael Joseph; Rodriguez, Daphnee; Kleinberg, Giona; Aflatooni, Shaliz; Palreddy, Siri; Abdi, Parsa; Taneja, Kamil; Batchu, Sai; Forouzandeh, Mahtab; Medicine, School of MedicineSkin conditions are a significant cause of fatal and nonfatal disease burdens globally, ranging from mild irritations to debilitating diseases. Oxidative stress, which is an imbalance between reactive oxygen species and the cells' ability to repair damage, is implicated in various skin diseases. Antioxidants have been studied for their potential benefits in dermatologic health, but the evidence is limited and conflicting. Herein, we conducted a systematic review of controlled trials, meta-analyses, and Cochrane review articles to evaluate the current evidence on the utility of antioxidant supplementation for adjunct prevention and treatment of skin disease and to provide a comprehensive assessment of their role in promoting dermatologic health. The Cochrane Library, PubMed, EMBASE, and Epistemonikos databases were queried. Eligibility criteria included (1) primary focus on nanoparticle utility for skin cancer; (2) includes measurable outcomes data with robust comparators; (3) includes a number of human subjects or cell-line types, where applicable; (4) English language; and (5) archived as full-text journal articles. A total of 55 articles met the eligibility criteria for the present review. Qualitative analysis revealed that topical and oral antioxidant supplementation has demonstrated preliminary efficacy in reducing sunburns, depigmentation, and photoaging. Dietary exogenous antioxidants (namely vitamins A, C, and E) have shown chemopreventive effects against skin cancer. Antioxidant supplementation has also shown efficacy in treating non-cancer dermatoses, including rosacea, psoriasis, atopic dermatitis, and acne vulgaris. While further studies are needed to validate these findings on a larger scale, antioxidant supplementation holds promise for improving skin health and preventing skin diseases.Item Heavy metals and neurodevelopment of children in low and middle-income countries: A systematic review(PLOS, 2022-03-31) Heng, Yi Yan; Asad, Iqra; Coleman, Bailey; Menard, Laura; Benki-Nugent, Sarah; Were, Faridah Hussein; Karr, Catherine J.; McHenry, Megan S.; Pediatrics, School of MedicineBackground: The presence of harmful environmental exposures, which disproportionately affects low-and-middle income countries (LMICs), contributes to >25% of deaths and diseases worldwide and detrimentally affects child neurodevelopment. Few resources succinctly summarize the existing literature on this topic. Our objective is to systematically review and characterize the evidence regarding the relationship between heavy metals and neurodevelopment of children in LMICs. Methods: We conducted a medical librarian-curated search on multiple online databases to identify articles that included individuals <18 years living in a LMIC, quantitatively measured exposure to a heavy metal (either prenatal or postnatal), and used a standardized measurement of neurodevelopment (i.e. cognitive, language, motor, and behavior). Reviews, editorials, or case studies were excluded. Results were analyzed qualitatively, and quality was assessed. Results: Of the 18,043 screened articles, 298 full-text articles were reviewed, and 100 articles met inclusion criteria. The included studies represented data from 19 LMICs, only one of which was classified as a low-income country. Ninety-four percent of postnatal lead and all postnatal manganese studies showed a negative association with metal exposure and neurodevelopment, which were the strongest relationships among the metals studied. Postnatal exposure of mercury was associated with poor neurodevelopment in only half of studies. Limited data on postnatal arsenic and cadmium suggests an association with worse neurodevelopment. Findings were mixed for prenatal arsenic and lead, although some evidence supports that the neurotoxicity of lead was amplified in the presence of manganese. Conclusions and potential impact: We found that lead and manganese appear to consistently have a detrimental effect on the neurodevelopment of children, and more evidence is needed for mercury, arsenic, and cadmium. Better characterization of these effects can motivate and inform prioritization of much needed international policies and programs to reduce heavy metal exposures for young children within LMICs.Item A translational bioinformatic approach in identifying and validating an interaction between Vitamin A and CYP19A1(Springer (Biomed Central Ltd.), 2015) Philips, Santosh; Zhou, Jing; Li, Zhigao; Skaar, Todd C.; Li, Lang; Department of Medicine, IU School of MedicineINTRODUCTION: One major challenge in personalized medicine research is to identify the environmental factors that can alter drug response, and to investigate their molecular mechanisms. These environmental factors include co-medications, food, and nutrition or dietary supplements. The increasing use of dietary supplements and their potential interactions with cytochrome P450 (CYP450) enzymes is a highly significant personalized medicine research domain, because most of the drugs on the market are metabolized through CYP450 enzymes. METHODS: Initial bioinformatics analysis revealed a number of regulators of CYP450 enzymes from a human liver bank gene expression quantitative loci data set. Then, a compound-gene network was constructed from the curated literature data. This network consisted of compounds that interact with either CYPs and/or their regulators that influence either their gene expression or activity. We further evaluated this finding in three different cell lines: JEG3, HeLa, and LNCaP cells. RESULTS: From a total of 868 interactions we were able to identify an interesting interaction between retinoic acid (i.e. Vitamin A) and the aromatase gene (i.e. CYP19A1). Our experimental results showed that retinoic acid at physiological concentration significantly influenced CYP19A1 gene expressions. CONCLUSIONS: These results suggest that the presence of retinoic acid may alter the efficacy of agents used to suppress aromatase expression.