Medical Misadventures as Errors and Mistakes and Motor Vehicular Accidents in the Disproportionate Burden of Childhood Mortality among Blacks/African Americans in the United States: CDC Dataset, 1968-2015.

PURPOSE: Racial disparities in infant mortality in the United States persist after adjustment for known confounders of race and mortality association, as well as heterogeneity assessment. Epidemiologic and clinical data continue to show the survival disadvantages of Black/AA children: when Black/AAs are compared to whites, they are three times as likely to die from all-cause mortality. The persistent inability to remove the variance in race-mortality association is partly due to unobserved, unmeasured, and residual confounding, as well as implicit biases in public health and clinical medicine in health equity transformation. This current epidemiologic-perspective explanatory model study aimed to examine the possible explanation of racial differences in U.S. infant mortality using medical misadventures as errors and mistakes, and infants' involvement in motor vehicular traffic accidents. MATERIALS AND METHOD: Using CDC WONDER ecologic data from 1968 to 2015, we assessed the infant mortality-rate ratio and percent change associated with medical misadventures as well as motor vehicular accidents or trauma. The rate ratio and percent change were estimated using stratification analysis and trend homogeneity, respectively. RESULTS: There was a Black-white racial difference in medical misadventures during the study period. Relative to the years 1968-1978 (rate ratio [RR], 1.43), there was a steady increase in the mortality-rate ratio in 1979-1998 (52%, RR = 1.52), and mortality was more than two times as likely in 1999-2015 (RR = 2.37). However, with respect to motor vehicular accident/trauma mortality, the mortality ratio, although lower among Blacks in 1968-1978 (RR, 0.92), increased in 1979-1998 by 27% (RR = 1.27) but decreased in 1999-2015 (RR, 1.17), though there was still an excess of 17% mortality among Black/AAs. The percent change for medical misadventures indicated an increasing trend from 9.3% in 1998 to 52% in 2015. However, motor vehicular-related mortality indicated a positive trend in 1998 (38.5%) but a negative trend in 2015 (-8.4%). CONCLUSIONS: There were substantial race differentials or variances in infant mortality associated with medical misadventures compared to traffic accidents, and Black/AA children relative to whites experienced a survival disadvantage. These comparative findings are suggestive of medical misadventures and motor vehicular trauma as potential explanations for some of the persistent Black-white disparities in overall infant mortality in the U.S. From these findings, we recommend a national effort to address these issues, thus narrowing the observed disparities in the U.S. infant mortality burden among Black/AAs.

Implication of Spiritual Network Support System in Epigenomic Modulation and Health Trajectory.

With challenges in understanding the multifactorial etiologies of disease and individual treatment effect heterogeneities over the past four decades, much has been acquired on how physical, chemical and social environments affect human health, predisposing certain subpopulations to adverse health outcomes, especially the socio-environmentally disadvantaged (SED). Current translational data on gene and adverse environment interaction have revealed how adverse gene-environment interaction, termed aberrant epigenomic modulation, translates into impaired gene expression via messenger ribonucleic acid (mRNA) dysregulation, reflecting abnormal protein synthesis and hence dysfunctional cellular differentiation and maturation. The environmental influence on gene expression observed in most literature includes physical, chemical, physicochemical and recently social environment. However, data are limited on spiritual or religious environment network support systems, which reflect human psychosocial conditions and gene interaction. With this limited information, we aimed to examine the available data on spiritual activities characterized by prayers and meditation for a possible explanation of the nexus between the spiritual network support system (SNSS) as a component of psychosocial conditions, implicated in social signal transduction, and the gene expression correlate. With the intent to incorporate SNSS in human psychosocial conditions, we assessed the available data on bereavement, loss of spouse, loneliness, social isolation, low socio-economic status (SES), chronic stress, low social status, social adversity (SA) and early life stress (ELS), as surrogates for spiritual support network connectome. Adverse human psychosocial conditions have the tendency for impaired gene expression through an up-regulated conserved transcriptional response to adversity (CTRA) gene expression via social signal transduction, involving the sympathetic nervous system (SNS), beta-adrenergic receptors, the hypothalamus-pituitary-adrenal (HPA) axis and the glucocorticoid response. This review specifically explored CTRA gene expression and the nuclear receptor subfamily 3 group C member 1 (NR3C1) gene, a glucocorticoid receptor gene, in response to stress and the impaired negative feedback, given allostatic overload as a result of prolonged and sustained stress and social isolation as well as the implied social interaction associated with religiosity. While more remains to be investigated on psychosocial and immune cell response and gene expression, current data on human models do implicate appropriate gene expression via the CTRA and NR3C1 gene in the SNSS as observed in meditation, yoga and thai-chi, implicated in malignant neoplasm remission. However, prospective epigenomic studies in this context are required in the disease causal pathway, prognosis and survival, as well as cautious optimism in the application of these findings in clinical and public health settings, due to unmeasured and potential confoundings implicated in these correlations.

Aberrant Epigenomic Modulation of Glucocorticoid Receptor Gene (NR3C1) in Early Life Stress and Major Depressive Disorder Correlation: Systematic Review and Quantitative Evidence Synthesis.

Early life stress (ELS) induced by psychological trauma, child maltreatment, maternal separation, and domestic violence predisposes to psycho-behavioral pathologies during adulthood, namely major depressive disorder (MDD), anxiety, and bipolar affective disorder. While environmental data are available in illustrating this association, data remain to be established on the epigenomic underpinning of the nexus between ELS and MDD predisposition. Specifically, despite the observed aberrant epigenomic modulation of the NR3C1, a glucocorticoid receptor gene, in early social adversity and social threats in animal and human models, reliable scientific data for intervention mapping in reducing social adversity and improving human health is required. We sought to synthesize the findings of studies evaluating (a) epigenomic modulations, mainly DNA methylation resulting in MDD following ELS, (b) epigenomic modifications associated with ELS, and (c) epigenomic alterations associated with MDD. A systematic review and quantitative evidence synthesis (QES) were utilized with the random effect meta-analytic procedure. The search strategy involved both the PubMed and hand search of relevant references. Of the 1534 studies identified through electronic search, 592 studies were screened, 11 met the eligibility criteria for inclusion in the QES, and 5 examined ELS and MDD; 4 studies assessed epigenomic modulation and ELS, while 2 studies examined epigenomic modulations and MDD. The dense DNA methylation of the 1F exon of the NR3C1, implying the hypermethylated region of the glucocorticoid receptor gene, was observed in the nexus between ELS and MDD, common effect size (CES) = 14.96, 95%CI, 10.06-19.85. With respect to epigenomic modulation associated with child ELS, hypermethylation was observed, CES = 23.2%, 95%CI, 8.00-38.48. In addition, marginal epigenomic alteration was indicated in MDD, where hypermethylation was associated with increased risk of MDD, CES = 2.12%, 95%CI, -0.63-4.86. Substantial evidence supports the implication of NR3C1 and environmental interaction, mainly DNA methylation, in the predisposition to MDD following ELS. This QES further supports aberrant epigenomic modulation identified in ELS as well as major depressive episodes involving dysfunctional glucocorticoid-mediated negative feedback as a result of allostatic overload. These findings recommend prospective investigation of social adversity and its predisposition to the MDD epidemic via aberrant epigenomic modulation. Such data will facilitate early intervention mapping in reducing MDD in the United States population.