Apolipoprotein E and Protection Against Hepatitis E Viral Infection in American Non-Hispanic Blacks

Hepatitis E viral (HEV) infection imposes a heavy health burden worldwide and is common in the United States. Previous investigations of risks addressed environmental and host behavioral/ lifestyle factors, but host genetic factors have not been examined. We assessed strength of associations between antibody to HEV (anti-HEV) immunoglobulin G seropositivity indicating past or recent HEV infection and human genetic variants among three major racial/ ethnic populations in the United States, involving 2434 non-Hispanic whites, 1919 non- Hispanic blacks, and 1919 Mexican Americans from the Third National Health and Nutrition Examination Survey, 1991-1994. We studied 497 single-nucleotide polymorphisms across 190 genes (particularly those associated with lipid metabolism). The genomic control method was used to adjust for potential population stratification. Non-Hispanic blacks had the lowest seroprevalence of anti-HEV immunoglobulin G (15.3%, 95% confidence interval [CI] 12.3%-19.0%) compared with non-Hispanic whites (22.3%, 95% CI 19.1%-25.7%) and Mexican Americans (21.8%, 95% CI 19.0%-25.3%; P \u3c 0.01). Non-Hispanic blacks were the only population that showed association between anti-HEV seropositivity and functional Ɛ3 and Ɛ4 alleles of the apolipoprotein E (APOE) gene, encoding the apolipoprotein E protein thatmediates lipoprotein metabolism. Seropositivity was significantly lower in participants carrying APOE Ɛ4 (odds ratio50.5, 95% CI 0.4-0.7; P50.00004) and Ɛ3 (odds ratio50.6, 95% CI 0.4-0.8; P50.001) compared to those carrying APOE Ɛ2. No significant associations were observed between other single-nucleotide polymorphisms and anti-HEV seropositivity in non-Hispanic blacks or between any single-nucleotide polymorphisms and anti-HEV seropositivity in non-Hispanic whites or Mexican Americans. Conclusion: Both APOE Ɛ3 and Ɛ4 are significantly associated with protection against HEV infection in non- Hispanic blacks; additional studies are needed to understand the basis of protection so that preventive services can be targeted to at-risk persons

Apolipoprotein E and Protection Against Hepatitis E Viral Infection in American Non-Hispanic Blacks

Hepatitis E viral (HEV) infection imposes a heavy health burden worldwide and is common in the United States. Previous investigations of risks addressed environmental and host behavioral/ lifestyle factors, but host genetic factors have not been examined. We assessed strength of associations between antibody to HEV (anti-HEV) immunoglobulin G seropositivity indicating past or recent HEV infection and human genetic variants among three major racial/ ethnic populations in the United States, involving 2434 non-Hispanic whites, 1919 non- Hispanic blacks, and 1919 Mexican Americans from the Third National Health and Nutrition Examination Survey, 1991-1994. We studied 497 single-nucleotide polymorphisms across 190 genes (particularly those associated with lipid metabolism). The genomic control method was used to adjust for potential population stratification. Non-Hispanic blacks had the lowest seroprevalence of anti-HEV immunoglobulin G (15.3%, 95% confidence interval [CI] 12.3%-19.0%) compared with non-Hispanic whites (22.3%, 95% CI 19.1%-25.7%) and Mexican Americans (21.8%, 95% CI 19.0%-25.3%; P \u3c 0.01). Non-Hispanic blacks were the only population that showed association between anti-HEV seropositivity and functional Ɛ3 and Ɛ4 alleles of the apolipoprotein E (APOE) gene, encoding the apolipoprotein E protein thatmediates lipoprotein metabolism. Seropositivity was significantly lower in participants carrying APOE Ɛ4 (odds ratio50.5, 95% CI 0.4-0.7; P50.00004) and Ɛ3 (odds ratio50.6, 95% CI 0.4-0.8; P50.001) compared to those carrying APOE Ɛ2. No significant associations were observed between other single-nucleotide polymorphisms and anti-HEV seropositivity in non-Hispanic blacks or between any single-nucleotide polymorphisms and anti-HEV seropositivity in non-Hispanic whites or Mexican Americans. Conclusion: Both APOE Ɛ3 and Ɛ4 are significantly associated with protection against HEV infection in non- Hispanic blacks; additional studies are needed to understand the basis of protection so that preventive services can be targeted to at-risk persons

Influence of Familial Risk on Diabetes Risk–Reducing Behaviors Among U.S. Adults Without Diabetes

OBJECTIVE: To test the association of family history of diabetes with the adoption of diabetes risk–reducing behaviors and whether this association is strengthened by physician advice or commonly known factors associated with diabetes risk. RESEARCH DESIGN AND METHODS: We used cross-sectional data from the 2005–2008 National Health and Nutrition Examination Survey (NHANES) to examine the effects of family history of diabetes on the adoption of selected risk-reducing behaviors in 8,598 adults (aged ≥20 years) without diabetes. We used multiple logistic regression to model three risk reduction behaviors (controlling or losing weight, increasing physical activity, and reducing the amount of dietary fat or calories) with family history of diabetes. RESULTS: Overall, 36.2% of U.S. adults without diabetes had a family history of diabetes. Among them, ~39.8% reported receiving advice from a physician during the past year regarding any of the three selected behaviors compared with 29.2% of participants with no family history (P < 0.01). In univariate analysis, adults with a family history of diabetes were more likely to perform these risk-reducing behaviors compared with adults without a family history. Physician advice was strongly associated with each of the behavioral changes (P < 0.01), and this did not differ by family history of diabetes. CONCLUSIONS: Familial risk for diabetes and physician advice both independently influence the adoption of diabetes risk–reducing behaviors. However, fewer than half of participants with familial risk reported receiving physician advice for adopting these behaviors

Molecular events associated with epithelial to mesenchymal transition of nasopharyngeal carcinoma cells in the absence of Epstein-Barr virus genome

Epithelial-mesenchymal transition (EMT) is an important process in tumor metastasis. The EMT-related events associated with metastasis of NPC in the absence of EBV have not been elucidated. We established an EBV-negative NPC cell line from a bone marrow biopsy of an NPC patient. Using a Matrigel system we isolated an invasive and non-invasive sublines, designated NPC-BM29 and NPC-BM00. NPC-BM29 acquired an invasive-like phenotype characterized by EMT, marked by down-regulation of E-cadherin and β-catenin with concomitant increased expression of Ets1. NPC-BM29 cells expressed ≥ 10-fold higher of MMP-9 than NPC-BM00 cells. NPC-BM29 cells grew better in 2% serum than NPC-BM00 cells, with a population doubling-time of 26.8 h and 30.7 h, respectively. A marked reduction in colony-formation ability of NPC-BM00 cells compared to NPC-BM29 was observed. Wound-healing assay revealed that NPC-BM29 cells displayed higher motility than NPC-BM00 and the motility was further enhanced by cell treatment with TPA, a PKC activator. Cell surface markers and tumor-associated molecules, AE3, MAK6 and sialyl-Tn, were up-regulated in NPC-BM29 cells, whereas the expression of HLA-DR and CD54 was significantly increased in NPC-BM00 cells. NPC-BM29 consistently released higher levels of IL-8 and IL-10 than NPC-BM00, with low levels of IL-1α expression in both cell lines. Higher level of VEGF production was detected in NPC-BM00 than NPC-BM29 cells. These data show that EBV is not required for exhibiting multiple metastatic phenotypes associated with EMT. More studies that target right molecules/signalings associated with the EMT may offer new therapeutic intervention options for NPC invasion and metastasis

Race-Ethnic Differences in the Association of Genetic Loci with HbA1c levels and Mortality in U.S. Adults: The Third National Health and Nutrition Examination Survey (NHANES III)

Background: Hemoglobin A1c (HbA1c) levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs) in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1) HbA1c-associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2) association of SNPs with HbA1c and 3) association of SNPs with mortality. Methods We studied 3,041 non-diabetic individuals in the NHANES (National Health and Nutrition Examination Survey) III. We stratified the analysis by race/ethnicity (NHW: non-Hispanic white; NHB: non-Hispanic black; MA: Mexican American) to calculate RAF, calculated a genotype score by adding risk SNPs, and tested associations with SNPs and the genotype score using an additive genetic model, with type 1 error = 0.05. Results: RAFs varied widely and at six loci race-ethnic differences in RAF were significant (p < 0.0002), with NHB usually the most divergent. For instance, at ATP11A, the SNP RAF was 54% in NHB, 18% in MA and 14% in NHW (p < .0001). The mean genotype score differed by race-ethnicity (NHW: 10.4, NHB: 11.0, MA: 10.7, p < .0001), and was associated with increase in HbA1c in NHW (β = 0.012 HbA1c increase per risk allele, p = 0.04) and MA (β = 0.021, p = 0.005) but not NHB (β = 0.007, p = 0.39). The genotype score was not associated with mortality in any group (NHW: OR (per risk allele increase in mortality) = 1.07, p = 0.09; NHB: OR = 1.04, p = 0.39; MA: OR = 1.03, p = 0.71). Conclusion: At many HbA1c loci in NHANES III there is substantial RAF race-ethnic heterogeneity. The combined impact of common HbA1c-associated variants on HbA1c levels varied by race-ethnicity, but did not influence mortality

An Overview of Regional Experiments on Biomass Burning Aerosols and Related Pollutants in Southeast Asia: From BASE-ASIA and the Dongsha Experiment to 7-SEAS

By modulating the Earth-atmosphere energy, hydrological and biogeochemical cycles, and affecting regional-to-global weather and climate, biomass burning is recognized as one of the major factors affecting the global carbon cycle. However, few comprehensive and wide-ranging experiments have been conducted to characterize biomass-burning pollutants in Southeast Asia (SEA) or assess their regional impact on meteorology, the hydrological cycle, the radiative budget, or climate change. Recently, BASEASIA (Biomass-burning Aerosols in South-East Asia: Smoke Impact Assessment) and the 7-SEAS (7- South-East Asian Studies) Dongsha Experiment were conducted during the spring seasons of 2006 and 2010 in northern SEA, respectively, to characterize the chemical, physical, and radiative properties of biomass-burning emissions near the source regions, and assess their effects. This paper provides an overview of results from these two campaigns and related studies collected in this special issue, entitled Observation, modeling and impact studies of biomass burning and pollution in the SE Asian Environment. This volume includes 28 papers, which provide a synopsis of the experiments, regional weatherclimate, chemical characterization of biomass-burning aerosols and related pollutants in source and sink regions, the spatial distribution of air toxics (atmospheric mercury and dioxins) in source and remote areas, a characterization of aerosol physical, optical, and radiative properties, as well as modeling and impact studies. These studies, taken together, provide the first relatively complete dataset of aerosol chemistry and physical observations conducted in the sourcesink region in the northern SEA, with particular emphasis on the marine boundary layer and lower free troposphere (LFT). The data, analysis and modeling included in these papers advance our present knowledge of source characterization of biomass-burning pollutants near the source regions as well as the physical and chemical processes along transport pathways. In addition, we raise key questions to be addressed by a coming deployment during springtime 2013 in northern SEA, named 7-SEASBASELInE (Biomass-burning Aerosols Stratocumulus Environment: Lifecycles and Interactions Experiment). This campaign will include a synergistic approach for further exploring many key atmospheric processes (e.g., complex aerosol-cloud interactions) and impacts of biomass burning on the surface-atmosphere energy budgets during the lifecycles of biomass burning emissions

Endemic, Notifiable Bioterrorism-Related Diseases, United States, 1992–1999

Little information is available in the United States regarding the incidence and distribution of diseases caused by critical microbiologic agents with the potential for use in acts of terrorism. We describe disease-specific, demographic, geographic, and seasonal distribution of selected bioterrorism-related conditions (anthrax, botulism, brucellosis, cholera, plague, tularemia, and viral encephalitides) reported to the National Notifiable Diseases Surveillance System in 1992–1999. Tularemia and brucellosis were the most frequently reported diseases. Anthrax, plague, western equine encephalitis, and eastern equine encephalitis were rare. Higher incidence rates for cholera and plague were noted in the western United States and for tularemia in the central United States. Overall, the incidence of conditions caused by these critical agents in the United States is low. Individual case reports should be considered sentinel events. For potential bioterrorism-related conditions that are endemic and have low incidence, the use of nontraditional surveillance methods and complementary data sources may enhance our ability to rapidly detect changes in disease incidence