15 research outputs found

    Income and Markers of Immunological Cellular Aging

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    Socioeconomic disadvantage may contribute to poor health through immune-related biological mechanisms. We examined the associations between socioeconomic status, as measured by annual household income, and T-cell markers of aging, including the ratios of CD4 and CD8 effector cells to naïve cells (E:N ratio) and the CD4:CD8 T-cell ratio. We hypothesized that participants with a lower income would have higher E:N ratios and lower CD4:CD8 ratios compared to participants with a higher income, and that these associations would be partially mediated by elevated cytomegalovirus (CMV) IgG antibody levels, a virus implicated in aging and clonal expansion of T-cells

    PTSD is associated with an increase in aged T cell phenotypes in adults living in Detroit

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    Psychosocial stress is thought to play a key role in the acceleration of immunological aging. This study investigated the relationship between lifetime and past-year history of post-traumatic stress disorder (PTSD) and the distribution of T cell phenotypes thought to be characteristic of immunological aging

    Income and Markers of Immunological Cellular Aging

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    OBJECTIVE: Socioeconomic disadvantage may contribute to poor health through immune-related biological mechanisms. We examined the associations between socioeconomic status, as measured by annual household income, and T-cell markers of aging, including the ratios of CD4 and CD8 effector cells to naïve cells (E:N ratio) and the CD4:CD8 T-cell ratio. We hypothesized that participants with a lower income would have higher E:N ratios and lower CD4:CD8 ratios compared to participants with a higher income, and that these associations would be partially mediated by elevated cytomegalovirus (CMV) IgG antibody levels, a virus implicated in aging and clonal expansion of T-cells. METHODS: Data were from 79 individuals who participated in the population-based Detroit Neighborhood Health Study. We used linear regression to quantify the association between a $10,000 decrease in income and each ratio outcome. RESULTS: Adjusting for age, sex, race, smoking, medication use, and lifetime history of mental health conditions, lower income was associated with a 0.41 (95% CI: 0.09, 0.72) log-unit increase in the CD4 E:N ratio and a 0.20 (95% CI: 0.02, 0.39) log-unit increase in the CD8 E:N ratio. CMV IgG antibody level partially mediated these associations. CONCLUSIONS: Our study suggests that low socioeconomic status is associated with immunological aging as measured by the E:N ratio and that impaired immune control of CMV may partially mediate these associations

    Soluble urokinase plasminogen activator receptor and cardiotoxicity in doxorubicin-treated breast cancer patients: a prospective exploratory study

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    Abstract Background Soluble urokinase plasminogen activator receptor is an inflammatory biomarker that may prognosticate cardiovascular outcomes. We sought to determine the associations between soluble urokinase plasminogen activator receptor and established markers of cardiotoxicity in breast cancer patients receiving doxorubicin. Methods We conducted a prospective cohort study of women with newly diagnosed breast cancer receiving standard-dose doxorubicin (240 mg/m2) at Rush University Medical Center and Rush Oak Park Hospital (Chicago, IL) between January 2017 and May 2019. Left ventricular ejection fraction, global longitudinal strain, and cardiac biomarkers (N-terminal prohormone B-type natriuretic peptide, troponin-I, and high-sensitivity C-reactive protein) were measured at baseline and at intervals up to 12-month follow-up after end of treatment. The associations between soluble urokinase plasminogen activator receptor and these endpoints were evaluated using multivariable mixed effects linear regression. Results Our study included 37 women (mean age 47.0 ± 9.3 years, 60% white) with a median baseline soluble urokinase plasminogen activator receptor level of 2.83 ng/dL. No participant developed cardiomyopathy based on serial echocardiography by one-year follow-up. The median percent change in left ventricular strain was -4.3% at 6-month follow-up and absolute changes in cardiac biomarkers were clinically insignificant. There were no significant associations between soluble urokinase plasminogen activator receptor and these markers of cardiotoxicity (all p > 0.05). Conclusions In this breast cancer cohort, doxorubicin treatment was associated with a very low risk for cardiotoxicity. Across this narrow range of clinical endpoints, soluble urokinase plasminogen activator receptor was not associated with markers of subclinical cardiotoxicity. Further studies are needed to clarify the prognostic utility of soluble urokinase plasminogen activator receptor in doxorubicin-associated cardiomyopathy and should include a larger cohort of leukemia and lymphoma patients who receive higher doses of doxorubicin

    Implementing machine learning methods with complex survey data: Lessons learned on the impacts of accounting sampling weights in gradient boosting.

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    Despite the prominent use of complex survey data and the growing popularity of machine learning methods in epidemiologic research, few machine learning software implementations offer options for handling complex samples. A major challenge impeding the broader incorporation of machine learning into epidemiologic research is incomplete guidance for analyzing complex survey data, including the importance of sampling weights for valid prediction in target populations. Using data from 15, 820 participants in the 1988-1994 National Health and Nutrition Examination Survey cohort, we determined whether ignoring weights in gradient boosting models of all-cause mortality affected prediction, as measured by the F1 score and corresponding 95% confidence intervals. In simulations, we additionally assessed the impact of sample size, weight variability, predictor strength, and model dimensionality. In the National Health and Nutrition Examination Survey data, unweighted model performance was inflated compared to the weighted model (F1 score 81.9% [95% confidence interval: 81.2%, 82.7%] vs 77.4% [95% confidence interval: 76.1%, 78.6%]). However, the error was mitigated if the F1 score was subsequently recalculated with observed outcomes from the weighted dataset (F1: 77.0%; 95% confidence interval: 75.7%, 78.4%). In simulations, this finding held in the largest sample size (N = 10,000) under all analytic conditions assessed. For sample sizes <5,000, sampling weights had little impact in simulations that more closely resembled a simple random sample (low weight variability) or in models with strong predictors, but findings were inconsistent under other analytic scenarios. Failing to account for sampling weights in gradient boosting models may limit generalizability for data from complex surveys, dependent on sample size and other analytic properties. In the absence of software for configuring weighted algorithms, post-hoc re-calculations of unweighted model performance using weighted observed outcomes may more accurately reflect model prediction in target populations than ignoring weights entirely

    Pathogen burden and leukocyte telomere length in the United States

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    Abstract Background Prior studies in humans have suggested that telomere shortening may be accelerated by infection, but research on multiple pathogens and use of large population-based study samples has been limited. We estimated cross-sectional associations between seropositivity to five persistent pathogens (Herpes Simplex Virus Type-1 (HSV-1), Herpes Simplex Virus Type-2 (HSV-2), cytomegalovirus (CMV), Helicobacter pylori (H.pylori), and Hepatitis B) as well as total pathogen burden and leukocyte telomere length. Data were derived from the National Health and Nutrition Examination Survey (1999–2000) for individuals 20–49 years of age, N = 1708. We analyzed the influence of each pathogen separately, a pathogen count score and a latent class model of pathogen burden on log telomere length using linear regression models, adjusted for covariates. Results Individuals in a latent pathogen burden class characterized by high probabilities of infection with HSV-1, CMV, and H. pylori, had significantly decreased log telomere length (− 0.30 [95% CI: − 0.36, − 0.24]) compared to those in a latent class characterized by low probabilities of all five infections. There were limited significant associations using other pathogen measures. Conclusions These results suggest that infection with specific combinations of pathogens may be one mechanism contributing to accelerated cellular senescence with possible origins early in the life course.http://deepblue.lib.umich.edu/bitstream/2027.42/173879/1/12979_2020_Article_206.pd
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