Search Results (5)

Objective: Renal cell carcinoma (RCC) is a rare but severe and aggressive pediatric malignancy. While incidence is uncommon, survival is relatively low with respect to acute lymphocytic leukemia (ALL), AML, lymphoma, ependymoma, glioblastoma, and Wilms Tumor. The pediatric renal cell carcinoma (pRCC) incidence, cumulative incidence (period prevalence), and mortality vary by health disparities’ indicators, namely sex, race, ethnicity, age at tumor diagnosis, and social determinants of health (SDHs) as well as Epigenomic Determinants of Health (EDHs). However, studies are unavailable on some pRCC risk determinants, such as area of residence and socio-economic status (SES). The current study aimed at assessing the temporal trends, cumulative incidence, household median income, urbanity, mortality, and pRCC survival differentials. Materials and Methods: A retrospective cohort design was utilized to examine the event-free survival of children (0–19) with RCC using the Surveillance Epidemiology and End Result Data, 1973–2015. While the time-dependent variable, namely survival months, was utilized, we assessed the predictors of pRCC survival, mainly sex, age at diagnosis, education, insurance status, income, and tumor grade, as prognostic factors. In examining the joint effect of area of residence and race, as an exposure function with time in survival, we utilized the Cox proportional hazard model, while the annual percent change was assessed using a generalized linear model, implying a weighted average. Results: Between 1973 and 2015, there were 174 cases of pRCC, of whom 49 experienced mortality (28.2%). The pRCC cumulative incidence tends to increase with advancing age. A significant survival differential was observed between black/AA children with RCC and their white counterparts. Compared with white children, black/AA children were almost three times as likely to die, hazard ratio (HR) = 2.90, 95% CI = 1.56–5.31, p = 0.001. A survival differential was observed in sex, with males presenting with a 21% increased likelihood of dying, HR = 1.21; 95% CI, 0.69–2.11. In the metropolitan area, the risk of dying was almost three times as likely among black/AA children compared to their white counterparts, HR = 2.78; 95% CI, 1.45–5.43, while in the urban area, the risk of dying was almost four times as likely among black/AA children compared to their white counterparts, HR = 4.18; 95% CI, 0.84–20.80. After controlling for age, sex, education, and insurance, the risk of dying increased amongst black/AA children in metropolitan areas, adjusted HR (aHR) = 3.37, 99% CI = 1.35–8.44. In the urban area, after adjustment for age, sex, and insurance, there was an increased risk of dying for black/AA children, compared with their white counterparts with pRCC, aHR = 8.87, 99% CI = 2.77–28.10. Conclusion: pRCC indicates an increased trend in males and age at diagnosis between 10 and 14, as well as a survival disadvantage among black/AA children, compared with their white counterparts. Additionally, urbanity significantly influences the racial differences in survival. These data are suggestive of the conjoined effect of environment and race in pRCC survival, indicative of further assessment of gene–environment interaction (epigenomics) in incidence, mortality, and survival in pRCC. Full article

Cardiac diseases form the lion’s share of the global disease burden, owing to the paradigm shift to non-infectious diseases from infectious ones. The prevalence of CVDs has nearly doubled, increasing from 271 million in 1990 to 523 million in 2019. Additionally, the global trend for the years lived with disability has doubled, increasing from 17.7 million to 34.4 million over the same period. The advent of precision medicine in cardiology has ignited new possibilities for individually personalized, integrative, and patient-centric approaches to disease prevention and treatment, incorporating the standard clinical data with advanced “omics”. These data help with the phenotypically adjudicated individualization of treatment. The major objective of this review was to compile the evolving clinically relevant tools of precision medicine that can help with the evidence-based precise individualized management of cardiac diseases with the highest DALY. The field of cardiology is evolving to provide targeted therapy, which is crafted as per the “omics”, involving genomics, transcriptomics, epigenomics, proteomics, metabolomics, and microbiomics, for deep phenotyping. Research for individualizing therapy in heart diseases with the highest DALY has helped identify novel genes, biomarkers, proteins, and technologies to aid early diagnosis and treatment. Precision medicine has helped in targeted management, allowing early diagnosis, timely precise intervention, and exposure to minimal side effects. Despite these great impacts, overcoming the barriers to implementing precision medicine requires addressing the economic, cultural, technical, and socio-political issues. Precision medicine is proposed to be the future of cardiovascular medicine and holds the potential for a more efficient and personalized approach to the management of cardiovascular diseases, contrary to the standardized blanket approach. Full article

IgA Nephropathy (IgAN) is a primary glomerulonephritis problem worldwide that develops mainly in the 2nd and 3rd decade of life and reaches end-stage kidney disease after 20 years from the biopsy-proven diagnosis, implying a great socio-economic burden. IgAN may occur in a sporadic or familial form. Studies on familial IgAN have shown that 66% of asymptomatic relatives carry immunological defects such as high IgA serum levels, abnormal spontaneous in vitro production of IgA from peripheral blood mononuclear cells (PBMCs), high serum levels of aberrantly glycosylated IgA1, and an altered PBMC cytokine production profile. Recent findings led us to focus our attention on a new perspective to study the pathogenesis of this disease, and new studies showed the involvement of factors driven by environment, lifestyle or diet that could affect the disease. In this review, we describe the results of studies carried out in IgAN patients derived from genomic and epigenomic studies. Moreover, we discuss the role of the microbiome in the disease. Finally, we suggest a new vision to consider IgA Nephropathy as a disease that is not disconnected from the environment in which we live but influenced, in addition to the genetic background, also by other environmental and behavioral factors that could be useful for developing precision nephrology and personalized therapy. Full article

Physical, chemical, and social environments adversely affect the molecular process and results in cell signal transduction and the subsequent transcription factor dysregulation, leading to impaired gene expression and abnormal protein synthesis. Stressful environments such as social adversity, isolation, sustained social threats, physical inactivity, and highly methylated diets predispose individuals to molecular level alterations such as aberrant epigenomic modulations that affect homeostasis and hemodynamics. With cardiovascular disease as the leading cause of mortality in the US and blacks/African Americans being disproportionately affected by hypertension (HTN) which contributes substantially to these deaths, reflecting the excess mortality and survival disadvantage of this sub-population relative to whites, understanding the molecular events, including epigenomic and socio-epigenomic modulations, is relevant to narrowing the black-white mortality risk differences. We aimed to synthesize epigenomic findings in HTN namely (a) angiotensin-converting enzyme 2 (ACE II) gene, (b) Toll-like receptor 2 (TLR2) gene, (c) interferon γ (IFN-γ) gene, and (d) Capping Actin Protein, Gelosin-Like (CAPG) gene, adducin 1(ADD1) gene, (e) Tissue inhibitor of metalloproteinase 3 (TIMP3), (f) mesoderm specific transcript (MEST) loci, (g) sodium channel epithelial 1 alpha subunit 2 (SCNN1B), (h) glucokinase (CKG) gene (i) angiotensin II receptor, type1 (AGTR1), and DNA methylation (mDNA). A systematic review and quantitative evidence synthesis (QES) was conducted using Google Scholar and PubMed with relevant search terms. Data were extracted from studies on: (a) Epigenomic modulations in HTN based on ACE II (b) TLR2, (c) IFN-γ gene, (d) CAPG, ADD1, TIMP3, MEST loci, and mDNA. The random-effect meta-analysis method was used for a pooled estimate of the common effect size, while z statistic and I^2 were used for the homogeneity of the common effect size and between studies on heterogeneity respectively. Of the 642 studies identified, five examined hypermethylation while seven studies assessed hypomethylation in association with HTN. The hypermethylation of ACE II, SCNN1B, CKG, IFN-γ gene, and miR-510 promoter were associated with hypertension, the common effect size (CES) = 6.0%, 95% CI, −0.002–11.26. In addition, the hypomethylation of TLR2, IFN-γ gene, ADD1, AGTR1, and GCK correlated with hypertension, the CES = 2.3%, 95% CI, −2.51–7.07. The aberrant epigenomic modulation of ACE II, TLR2, IFN-γ, AGTR1, and GCK correlated with essential HTN. Transforming the environments resulting from these epigenomic lesions will facilitate early intervention mapping in reducing HTN in the US population, especially among socially disadvantaged individuals, particularly racial/ethnic minorities. Full article

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. Full article