Correlates of antioxidant nutrients and oxidative DNA damage differ by race in a cross-sectional study of healthy African American and white adults

Although antioxidant nutrients and oxidative DNA damage have been associated with carcinogenesis, few studies have investigated the factors that influence antioxidant intake and oxidative DNA damage in racially diverse populations. Demographic, behavioral, and diet-related psychosocial correlates of plasma antioxidant (carotenoids, vitamin C, and vitamin E) concentrations and oxidative DNA damage were examined using data from a cross-sectional study of 147 generally healthy, non-smoking African American and White adults in North Carolina, age 20 to 45 years. All participants completed self-administered demographic, diet, and health questionnaires and provided semi-fasting (≥ 6 hours) blood samples. Multivariate regression analyses were computed separately for each race to determine associations between the potential correlates with plasma antioxidant concentrations and oxidative DNA damage, separately. Our findings suggest appreciable differences by race. Only a few factors (age, supplement use, and several psychosocial factors) were associated with antioxidant concentrations in African Americans, whereas these and additional factors, including physical activity, waist circumference, and passive smoke exposure, were associated with antioxidant concentrations in Whites. For oxidative DNA damage, passive smoke exposure was significantly associated with oxidative DNA damage in African Americans, and age and alcohol were significant in Whites. In addition, the regression models generally explained more of the variance in plasma antioxidant concentrations and oxidative DNA damage in Whites than in African Americans. Considering the salient correlates differed by race, this work has important implications for the design and implementation of future research studies investigating antioxidant nutrients and/or oxidative stress, especially those in racially diverse populations

VALIDATION OF AN ANTIOXIDANT NUTRIENT QUESTIONIARE IN WHITES AND AFRICAN AMERICANS

High antioxidant intakes are inversely related to risk for many diseases. However, there is no comprehensive instrument that captures consumption of antioxidant nutrients from both foods and dietary supplements. This report examines the validity of a newly developed questionnaire assessing self-reported dietary and supplemental intakes of antioxidant nutrients (carotenoids, vitamin C, and vitamin E). Between March and December 2005, participants (n=164), 20–45 years, completed the new 92-item antioxidant nutrient questionnaire, a demographic/health questionnaire, four 24-hour dietary recalls, a dietary supplement inventory, and provided semi-fasting blood samples that were analyzed for plasma antioxidant levels. Data analyses included descriptive statistics, correlation coefficients, and linear regression. The mean age of participants was 31.9 years, 51% were African American, and 52% were female. Median antioxidant intakes from the questionnaire and mean of the four recalls were generally comparable. Adjusted Pearson’s correlations of questionnaire- and recall-derived intakes ranged from r=0.06–0.56; correlations for the questionnaire and biomarkers ranged from r=0.10–0.33. Agreement rates for classification of intakes from the questionnaire and recalls into the same/adjacent quartiles were 65–89%; misclassification to the opposite quartile was rare (0–12%). For most nutrients, there were linear trends of increasing plasma concentrations with higher questionnaire-derived intakes (p<0.01). Correlations of supplement use between the questionnaire and a supplement inventory were r=0.33–0.84. The new antioxidant nutrient questionnaire demonstrated good validity for collecting self-reported antioxidant nutrient intakes from foods and supplements in both whites and African Americans. The study also underscores the importance of examining the performance characteristics of dietary assessment instruments separately in different population subgroups

Associations of psychosocial factors with fruit and vegetable intake among African-Americans

OBJECTIVE: To examine associations of various psychosocial factors with fruit and vegetable intake in African-American adults. METHODS: A cross-sectional survey of a population-based sample of 658 African-Americans, aged 18-70 years, in North Carolina. Information was collected on diet-related psychosocial (predisposing, reinforcing and enabling) factors based on the PRECEDE (Predisposing, Reinforcing, and Enabling Constructs in Educational Diagnosis and Evaluation) planning framework; demographic, lifestyle and behavioural characteristics, and fruit and vegetable intake. RESULTS: The mean participant age was 43.9 years (standard deviation 11.6), 57% were female and 76% were overweight/obese. Participants expressed healthy beliefs regarding many of, but not all, the psychosocial factors. For example, although half of the respondents believed it is important to eat a diet high in fruits/vegetables, only 26% knew that >or=5 daily servings are recommended. The strongest associations of the psychosocial factors with fruit/vegetable intake were for predisposing factors (e.g. belief in the importance of a high fruit/vegetable diet and knowledge of fruit/vegetable recommendations) and one reinforcing factor (social support), with differences between the healthiest and least healthy responses of 0.5-1.0 servings per day. There was evidence of effect modification by gender in associations between psychosocial factors and fruit/vegetable consumption (e.g. self-efficacy was only significant in women), with higher intakes and generally healthier responses to the psychosocial variables in women than men. CONCLUSIONS: Interventions to increase fruit/vegetable intake in African-Americans may be more effective if they focus primarily on predisposing factors, such as knowledge, self-efficacy and attitudes, but not to the exclusion of reinforcing and enabling factors. The psychosocial factors that are targeted may also need to be somewhat different for African-American men and women

Qualitative Study to Explore Prospect Theory and Message Framing and Diet and Cancer Prevention-Related Issues Among African American Adolescents

To develop and test cancer prevention messages based on Prospect theory on motivation to improve dietary intake in African American adolescents, and to explore other salient factors that may inform dietary intervention design and implementation in this population

Analysis of 8-oxo-7,8-dihydro-2′-deoxyguanosine by ultra high pressure liquid chromatography–heat assisted electrospray ionization–tandem mass spectrometry

Increased amounts of reactive oxygen species (ROS), generally termed oxidative stress, are frequently hypothesized to be causally associated with many diseases. Analyses of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) in DNA and urine are widely used biomarkers for oxidative stress. Over the years it became clear that analysis of 8-oxo-dG in DNA is challenging due to artifactual formation during sample work up. The present study demonstrates that 8-oxo-dG can be measured reliably and accurately when appropriate precautions are taken. First, the presence of an antioxidant, metal chelator, or free radical trapping agent during sample preparation improves reproducibility. Second, sample enrichment by HPLC fraction collection was used to optimize sensitivity. Third, heat assisted electrospray ionization (HESI) eliminated potential interferences and improved assay performance and sensitivity. Subsequently, the UPLC–HESI–MS/MS method was applied to show the biphasic dose response of 8-oxo-dG in H2O2-treated HeLa cells. Application of this method to human lymphocyte DNA (n = 156) gave a mean±SD endogenous amount of 1.57±0.88 adducts per 106 dG, a value that is in agreement with the suggested amount previously estimated by European Standard Committee on Oxidative DNA Damage (ESCODD) and others. These results suggest that the present method is well suited for application to molecular toxicology and epidemiology studies investigating the role of oxidative stress

Comparison of three oxidative stress biomarkers in a sample of healthy adults Oxidative stress biomarkers in healthy adults J. L. Watters et al.

Oxidative stress is a potentially important etiologic factor for many chronic diseases, including cardiovascular disease, neurodegenerative disease, and cancer, yet studies often find inconsistent results. The associations between three of the most widely-used biomarkers of oxidative stress, i.e., F2-isoprostanes for lipid peroxidation and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) and the comet assay with FPG for oxidative DNA damage, were compared in a sample of 135 healthy African American and White adults. Modest associations were observed between F2-isoprostanes and the comet assay (r=0.22, p=0.01), but there were no significant correlations between 8-oxo-dG and the comet assay (r=−0.09) or F2-IsoP (r=−0.04). These results are informative for researchers seeking to compare results pertaining to oxidative stress across studies and/or assessment methods in healthy disease-free populations. The development and use of oxidative stress biomarkers is a promising field; however, additional validation studies are necessary to establish accuracy and comparability across oxidative stress biomarkers

Psychosocial correlates of dietary fat intake in African-American adults: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Current dietary guidelines recommend that dietary fat should comprise 20–35% percent of total energy intake, with less than 10% of energy from saturated fat. However, many Americans exceed these goals and data suggest that African Americans tend to consume a higher percentage of energy from dietary fat than Whites. Because diets low in dietary fat, particularly saturated fat, are associated with lower risk for many chronic illnesses, it is important to identify strategies to reduce high fat intakes. This study examined associations of psychosocial factors with dietary fat intake in African American adults 18 to 70 years.</p> <p>Methods</p> <p>Data are self-reported from a cross-sectional survey of African Americans (n = 658) using an 11-page questionnaire, collected from June to October 2003. Associations of psychosocial (predisposing, reinforcing, and enabling) factors based on the PRECEDE framework, dietary fat-related behaviors, and participant characteristics (e.g., age, sex, education, BMI) with total and saturated fat consumption are described using linear regression and analysis of variance.</p> <p>Results</p> <p>The mean age of participants was 43.9 years, 57% were female, 37% were college graduates, and 76% were overweight/obese. Respondents with lower fat intakes were female, older, had high education and very good/excellent perceived health. Among the psychosocial factors, the strongest (inverse) associations with fat intake were with two predisposing factors: <it>belief in the importance of a low-fat diet </it>(both genders) and <it>high self-efficacy </it>(women only). Fat intake was also significantly lower among participants who could <it>count on those close for encouragement to eat healthy foods </it>(a reinforcing factor) and among men who <it>needed more information about preparing healthy foods </it>(an enabling factor).</p> <p>Conclusion</p> <p>Dietary interventions to decrease fat intake in African American adults may benefit from incorporating predisposing factors, such as personal beliefs and self-efficacy, in their design and implementation.</p

Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma

Funder: Galderma; doi: http://dx.doi.org/10.13039/501100009754Funder: NIHR-BRC Cambridge core grantFunder: National Institute for Health Research; doi: http://dx.doi.org/10.13039/501100000272Funder: NHS EnglandAbstract: T-cell non-Hodgkin’s lymphomas develop following transformation of tissue resident T-cells. We performed a meta-analysis of whole exome sequencing data from 403 patients with eight subtypes of T-cell non-Hodgkin’s lymphoma to identify mutational signatures and associated recurrent gene mutations. Signature 1, indicative of age-related deamination, was prevalent across all T-cell lymphomas, reflecting the derivation of these malignancies from memory T-cells. Adult T-cell leukemia-lymphoma was specifically associated with signature 17, which was found to correlate with the IRF4 K59R mutation that is exclusive to Adult T-cell leukemia-lymphoma. Signature 7, implicating UV exposure was uniquely identified in cutaneous T-cell lymphoma (CTCL), contributing 52% of the mutational burden in mycosis fungoides and 23% in Sezary syndrome. Importantly this UV signature was observed in CD4 + T-cells isolated from the blood of Sezary syndrome patients suggesting extensive re-circulation of these T-cells through skin and blood. Analysis of non-Hodgkin’s T-cell lymphoma cases submitted to the national 100,000 WGS project confirmed that signature 7 was only identified in CTCL strongly implicating UV radiation in the pathogenesis of cutaneous T-cell lymphoma

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570