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2.  Analysis of social epidemiology research on infectious diseases: historical patterns and future opportunities 
Background
Despite the many triumphs of biomedical research over infectious diseases, human pathogens continue to impact profoundly populations deprived of social resources. Correspondingly, health researchers have advocated a social determinants approach to the study and prevention of infectious diseases. However, it is unknown whether this call has resulted in an increase in the number of studies examining social determinants of infectious outcomes.
Methods
Research on social determinants of infectious diseases was systematically quantified by assessing temporal trends in the published literature using MEDLINE, PsycINFO and ISI Web of Science.
Results
Results of the literature review spanning 1966–2005 show that socially related citations increased an annual average of 180.3 for neuropsychiatric conditions, 81.9 for chronic conditions, 44.7 for sexually transmitted diseases and 18.9 for non‐sexually transmitted infectious diseases (p<0.0001). Of the 279 publications found to employ the term “social epidemiology”, 15 (5.4%) investigated infectious outcomes.
Conclusions
The results of the literature review suggest a paucity of social research on infectious diseases. There is a need for increased dialogue and collaboration between infectious disease epidemiologists and social epidemiologists.
doi:10.1136/jech.2006.057216
PMCID: PMC2465670  PMID: 18000122
3.  Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women 
Psychoneuroendocrinology  2013;38(12):10.1016/j.psyneuen.2013.08.014.
Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder with a particularly high burden for women. Emerging evidence suggests PTSD may be more heritable among women and evidence from animal models and human correlational studies suggest connections between sex-linked biology and PTSD vulnerability, which may extend to the disorder’s genetic architecture. We conducted a genome-wide association study (GWAS) of PTSD in a primarily African American sample of women from the Detroit Neighborhood Health Study (DNHS) and tested for replication in an independent cohort of primarily European American women from the Nurses Health Study II (NHSII).
We genotyped 413 DNHS women - 94 PTSD cases and 319 controls exposed to at least one traumatic event - on the Illumina HumanOmniExpress BeadChip for > 700,000 markers and tested 578 PTSD cases and 1963 controls from NHSII for replication. We performed a network-based analysis integrating data from GWAS-derived independent regions of association and the Reactome database of functional interactions.
We found genome-wide significant association for one marker mapping to a novel RNA gene, lincRNA AC068718.1, for which we found suggestive evidence of replication in NHSII. Our network-based analysis indicates that our top GWAS results were enriched for pathways related to telomere maintenance and immune function. Our findings implicate a novel RNA gene, lincRNA AC068718.1, as risk factor for PTSD in women and add to emerging evidence that non-coding RNA genes may play a crucial role in shaping the landscape of gene regulation with putative pathological effects that lead to phenotypic differences.
doi:10.1016/j.psyneuen.2013.08.014
PMCID: PMC3844079  PMID: 24080187
PTSD; GWAS; lincRNA; telomere maintenance; immune system
6.  PTSD and Obesity in the Detroit Neighborhood Health Study 
General hospital psychiatry  2013;35(6):10.1016/j.genhosppsych.2013.07.015.
Objective
Posttraumatic stress disorder (PTSD) has been associated with adverse health consequences, including overweight, obesity, and cardiovascular disease. African Americans, particularly women, have among the highest rates of overweight and obesity in the U.S. compared to other racial groups. High rates of violence exposure in urban African Americans may lead to the development of PTSD and increase risk for overweight and obesity. The current study investigated the comorbidity of lifetime PTSD and overweight/obesity in a population-based African American, urban sample.
Method
Data were from 463 African American male and female participants of the Detroit Neighborhood Health Study. Multivariable logistic regression models estimated the impact of lifetime PTSD on risk for overweight and obesity.
Results
The prevalence of obesity was significantly higher among women (60.9%) than men (33.1%; p<0.001). In sex-stratified models, after controlling for demographic variables, PTSD was associated obesity (OR=4.4, 95% CI: 1.3, 14.3) only among women.
Conclusions
PTSD was associated with obesity, after controlling for confounding variables, among African American women. Results underscore the contribution of PTSD to obesity among African American women and the importance of addressing the physical health correlates of women with PTSD.
doi:10.1016/j.genhosppsych.2013.07.015
PMCID: PMC3823753  PMID: 24035634
PTSD; obesity; urban; African American
7.  Helicobacter pylori Infection Is Associated With an Increased Rate of Diabetes 
Diabetes Care  2012;35(3):520-525.
OBJECTIVE
Chronic infections could be contributing to the socioeconomic gradient in chronic diseases. Although chronic infections have been associated with increased levels of inflammatory cytokines and cardiovascular disease, there is limited evidence on how infections affect risk of diabetes.
RESEARCH DESIGN AND METHODS
We examined the association between serological evidence of chronic viral and bacterial infections and incident diabetes in a prospective cohort of Latino elderly. We analyzed data on 782 individuals aged >60 years and diabetes-free in 1998–1999, whose blood was tested for antibodies to herpes simplex virus 1, varicella virus, cytomegalovirus, Helicobacter pylori, and Toxoplasma gondii and who were followed until June 2008. We used Cox proportional hazards regression to estimate the relative incidence rate of diabetes by serostatus, with adjustment for age, sex, education, cardiovascular disease, smoking, and cholesterol levels.
RESULTS
Individuals seropositive for herpes simplex virus 1, varicella virus, cytomegalovirus, and T. gondii did not show an increased rate of diabetes, whereas those who were seropositive for H. pylori at enrollment were 2.7 times more likely at any given time to develop diabetes than seronegative individuals (hazard ratio 2.69 [95% CI 1.10–6.60]). Controlling for insulin resistance, C-reactive protein and interleukin-6 did not attenuate the effect of H. pylori infection.
CONCLUSIONS
We demonstrated for the first time that H. pylori infection leads to an increased rate of incident diabetes in a prospective cohort study. Our findings implicate a potential role for antibiotic and gastrointestinal treatment in preventing diabetes.
doi:10.2337/dc11-1043
PMCID: PMC3322696  PMID: 22279028
8.  Secular Trends in Helicobacter pylori Seroprevalence in Adults in the United States: Evidence for Sustained Race/Ethnic Disparities 
American Journal of Epidemiology  2011;175(1):54-59.
Helicobacter pylori seroprevalence levels in US adults participating in the continuous National Health and Nutrition Examination Survey (1999–2000) increased with age in all racial/ethnic groups, with significantly higher age-standardized levels in Mexican Americans (64.0%, 95% confidence interval (CI): 58.8, 69.2) and non-Hispanic blacks (52.0%, 95% CI: 48.3, 55.7) compared with non-Hispanic whites (21.2%, 95% CI: 19.1, 23.2). Although seroprevalence levels remained similar to those found in National Health and Nutrition Examination Surveys from 1988 to 1991 among non-Hispanic blacks and Mexican Americans, they were significantly lower in non-Hispanic whites, especially at older ages. The factors driving the decline in H. pylori seroprevalence appear to be acting preferentially on the non-Hispanic white population.
doi:10.1093/aje/kwr288
PMCID: PMC3244610  PMID: 22085628
cohort effect; ethnic groups; health status disparities; Helicobacter pylori; nutrition surveys; seroepidemiologic studies
9.  Time and dose-dependent risk of pneumococcal pneumonia following influenza: a model for within-host interaction between influenza and Streptococcus pneumoniae 
A significant fraction of seasonal and in particular pandemic influenza deaths are attributed to secondary bacterial infections. In animal models, influenza virus predisposes hosts to severe infection with both Streptococcus pneumoniae and Staphylococcus aureus. Despite its importance, the mechanistic nature of the interaction between influenza and pneumococci, its dependence on the timing and sequence of infections as well as the clinical and epidemiological consequences remain unclear. We explore an immune-mediated model of the viral–bacterial interaction that quantifies the timing and the intensity of the interaction. Taking advantage of the wealth of knowledge gained from animal models, and the quantitative understanding of the kinetics of pathogen-specific immunological dynamics, we formulate a mathematical model for immune-mediated interaction between influenza virus and S. pneumoniae in the lungs. We use the model to examine the pathogenic effect of inoculum size and timing of pneumococcal invasion relative to influenza infection, as well as the efficacy of antivirals in preventing severe pneumococcal disease. We find that our model is able to capture the key features of the interaction observed in animal experiments. The model predicts that introduction of pneumococcal bacteria during a 4–6 day window following influenza infection results in invasive pneumonia at significantly lower inoculum size than in hosts not infected with influenza. Furthermore, we find that antiviral treatment administered later than 4 days after influenza infection was not able to prevent invasive pneumococcal disease. This work provides a quantitative framework to study interactions between influenza and pneumococci and has the potential to accurately quantify the interactions. Such quantitative understanding can form a basis for effective clinical care, public health policies and pandemic preparedness.
doi:10.1098/rsif.2013.0233
PMCID: PMC3730679  PMID: 23825111
influenza–pneumococcal interaction; within-host model; influenza; pneumococcus; mathematical model
10.  Population Levels of Psychological Stress, Herpesvirus Reactivation and HIV 
AIDS and behavior  2008;14(2):308-317.
Nearly 40,000 Americans are newly infected with Human Immunodeficiency Virus (HIV) each year. Recently, studies have demonstrated associations between group-level characteristics and the prevalence and incidence of HIV/Acquired Immune Deficiency Syndrome (AIDS) and other sexually transmitted diseases. Two mechanisms previously posited to explain these associations are neighborhood effects on risk behaviors and social or institutional policies. In this paper, we hypothesize that adversity at the population level, such as neighborhood poverty, also influences HIV risk through stress-mediated aberrations in immunological susceptibility by reviewing existing data examining each of these pathways. In particular, we review the evidence showing that: (1) Neighborhood ecologic stressors influence neighborhood-and individual-levels of mental health, psychosocial stress, and HIV/AIDS risk, (2) Individual-level psychosocial stressors influence progression from HIV to AIDS through stress-related hormonal changes, and (3) Individual-level psychosocial stressors influence HIV acquisition via stress-related reactivation of latent herpesviruses, specifically EBV and HSV-2. Our review indicates that further studies are needed to examine the joint pathways linking neighborhood-level sources of psychosocial stress, stress-related reactivation of HSV-2 and EBV, and increased acquisition rates of HIV. We suggest using a multi-level framework for targeting HIV prevention efforts that address not only behavioral risk factors, but structural, political, and institutional factors associated with neighborhood disadvantage, levels of psychosocial stress, and prevention or treatment of HSV-2 and EBV.
doi:10.1007/s10461-008-9358-4
PMCID: PMC4156100  PMID: 18264753
HIV; Neighborhood; Psychosocial stress; HSV-2; EBV
11.  Neighborhood Socioeconomic Context and Cognitive Decline Among Older Mexican Americans: Results From the Sacramento Area Latino Study on Aging 
American Journal of Epidemiology  2011;174(4):423-431.
In 1 previous study, it was shown that neighborhood socioeconomic disadvantage is associated with cognitive decline among Latinos. No studies have explored whether and to what extent individual-level socioeconomic factors account for the relation between neighborhood disadvantage and cognitive decline. The purpose of the present study was to assess the influence of neighborhood socioeconomic position (SEP) on cognitive decline and examine how individual-level SEP factors (educational level, annual income, and occupation) influenced neighborhood associations over the course of 10 years. Participants (n = 1,789) were community-dwelling older Mexican Americans from the Sacramento Area Latino Study on Aging. Neighborhood SEP was derived by linking the participant's individual data to the 2000 decennial census. The authors assessed cognitive function with the Modified Mini-Mental State Examination. Analyses used 3-level hierarchical linear mixed models of time within individuals within neighborhoods. After adjustment for individual-level sociodemographic characteristics, higher neighborhood SEP was significantly associated with cognitive function (β = −0.033; P < 0.05) and rates of decline (β = −0.0009; P < 0.10). After adjustment for individual educational level, neighborhood SEP remained associated with baseline cognition but not with rates of decline. Differences in individual educational levels explained most of the intra- and interneighborhood variance. These results suggest that the effect of neighborhood SEP on cognitive decline among Latinos is primarily accounted for by education.
doi:10.1093/aje/kwr095
PMCID: PMC3159426  PMID: 21715645
aging; cognition; education; Mexican Americans; residence characteristics
12.  Secular trends in the association between nativity/length of US residence with body mass index and waist circumference among Mexican-Americans, 1988–2008 
Objectives
We investigated whether associations between nativity/length of US residence and body mass index (BMI) and waist circumference (WC) varied over the past two decades.
Methods
Mexican-Americans aged 20–64 years from the National Health and Nutrition Survey (NHANES) III (1988–1994), and NHANES (1999–2008). Sex-stratified multivariable linear regression models further adjusted for age, education, and NHANES period.
Results
We found no evidence of secular variation in the nativity/length of US residence gradient for men or women. Foreign-born Mexican-Americans, irrespective of residence length, had lower mean BMI and WC than their US-born counterparts. However among women, education modified secular trends in nativity differentials: notably, in less-educated women, nativity gradients widened over time due to alarming increases in BMI among the US-born and little increase in the foreign-born.
Conclusions
Associations between nativity/length of US residence and BMI/WC did not vary over this 20-year period, but we noted important modifications by education in women. Understanding these trends is important for identifying vulnerable subpopulations among Mexican-Americans and for the development of effective health promotion strategies in this fast-growing segment of the population.
doi:10.1007/s00038-012-0414-5
PMCID: PMC3570586  PMID: 23052250
Obesity; Trends; Mexican; Immigrants; Socioeconomic status
13.  The influence of knowledge, perceptions, and beliefs, on hand hygiene practices in nursing homes 
There are few studies that have assessed factors influencing infection control practices among health care workers (HCW) in nursing homes. We conducted a cross-sectional survey of HCWs (N = 392) in 4 nursing homes to assess whether knowledge, beliefs, and perceptions influence reported hand hygiene habits. Positive perceptions and beliefs regarding effectiveness of infection control in nursing homes were associated with reported appropriate glove use and fingernail characteristics, respectively, among HCWs. Further research on hand hygiene interventions, including targeted educational in-services should be conducted in the nursing home setting.
doi:10.1016/j.ajic.2008.04.258
PMCID: PMC3319389  PMID: 18945512
14.  Socioeconomic Position and Inflammatory and Immune Biomarkers of Cardiovascular Disease: Applications to the Panel Study of Income Dynamics 
Biodemography and Social Biology  2009;55(2):178-205.
Biomarkers are an important aspect of research linking psychosocial stress and health. This paper aims to characterize the biological pathways that may mediate the relationship between socioeconomic position (SEP) and cardiovascular disease (CVD) and address opportunities for further research within the Panel Study for Income Dynamics (PSID), with a focus on psychosocial stressors related to SEP. We review the literature on CVD biomarkers, including adhesion and proinflammatory molecules (IL-6, other cytokines, C-reactive proteins, fibrinogen, etc.) and microbial pathogens. The impact of socioeconomic determinants and related psychosocial stressors on CVD biomarkers mediated by behavioral and central nervous system pathways are described. We also address measurement and feasibility issues including: specimen collection methods, processing and storage procedures, laboratory error, and within-person variability. In conclusion, we suggest that PSID consider adding important assessments of specific CVD biomarkers and mediating behavioral measures, health, and medications that will ultimately address many of the gaps in the literature regarding the relationship between socioeconomic position and cardiovascular health.
doi:10.1080/19485560903382304
PMCID: PMC3319671  PMID: 20183904
15.  ADCYAP1R1 GENOTYPE, POSTTRAUMATIC STRESS DISORDER, AND DEPRESSION AMONG WOMEN EXPOSED TO CHILDHOOD MALTREATMENT 
Depression and anxiety  2012;30(3):251-258.
Background
A growing literature indicates that genetic variation, in combination with adverse early life experiences, shapes risk for later mental illness. Recent work also suggests that molecular variation at the ADCYAP1R1 locus is associated with posttraumatic stress disorder (PTSD) in women. We sought to test whether childhood maltreatment (CM) interacts with ADCYAP1R1 geno-type to predict PTSD in women.
Methods
Data were obtained from 495 adult female participants from the Detroit Neighborhood Health Study. Genotyping of rs2267735, an ADCYAP1R1 variant, was conducted via TaqMan assay. PTSD, depression, and CM exposure were assessed via structured interviews. Main and interacting effects of ADCYAP1R1 and CM levels on past month PTSD and post-traumatic stress (PTS) severity were examined using logistic regression and a general linear model, respectively. As a secondary analysis, we also assessed main and interacting effects of ADCYAP1R1 and CM variation on risk of past-month depression diagnosis and symptom severity.
Results
No significant main effects were observed for ADCYAP1R1 genotype on either PTSD/PTS severity. In contrast, a significant ADCYAP1R1 × CM interaction was observed for both past month PTSD and PTS severity, with carriers of the “C” allele showing enhanced risk for these outcomes among women exposed to CM. No significant main or interaction effects were observed for past month depression/depression severity.
Conclusions
Genetic variation at the ADCYAP1R1 locus interacts with CM to shape risk of later PTSD, but not depression, among women. The molecular mechanisms contributing to this interaction require further investigation.
doi:10.1002/da.22037
PMCID: PMC4081452  PMID: 23280952
PTSD; depression; childhood maltreatment; candidate gene; replication; gene-environment interaction
16.  Persistent Infection, Inflammation, and Functional Impairment in Older Latinos 
Background
The objective of this study was to examine whether cytomegalovirus (CMV), herpes simplex virus type-1 (HSV-1), and C-reactive protein (CRP) are associated with functional impairment in older Latinos.
Methods
A cross-sectional analysis of a cohort study conducted with a community dwelling elderly population. The sample was a subset (N = 1507/1789) of participants in the Sacramento Area Latino Study on Aging (SALSA) ages 60–101 with available serum samples and functional impairment measures. Baseline serum samples were assayed for levels of immunoglobulin G antibodies to CMV and HSV-1 and for levels of CRP. Several measures were used to assess functional impairment, including activities of daily living (ADL), instrumental activities of daily living (IADL), and walking pace.
Results
CMV and CRP showed statistically significant graded associations with ADL functional impairment, even after controlling for age and gender. The relationship between CMV and ADL was slightly attenuated, and the confidence interval contained the null value when adjusted for total number of health conditions, body mass index, and household income. Only high levels of CRP were significantly related to ADL and IADL impairment even after adjusting for all other covariates.
Conclusion
Inflammation is clearly linked to physical functioning among aging Latinos. This study also suggests a role for CMV infection in relation to ADL impairment. Further research examining the influence of infection, immune response, and inflammation on longitudinal trajectories of physical functioning is warranted.
PMCID: PMC3178457  PMID: 18559636
Cytomegalovirus (CMV); CRP; Latinos; Physical function; Community
17.  Cytomegalovirus Antibody Levels, Inflammation, and Mortality Among Elderly Latinos Over 9 Years of Follow-up 
American Journal of Epidemiology  2010;172(4):363-371.
This study examined the relation between immune response to cytomegalovirus (CMV) and all-cause and cardiovascular disease (CVD) mortality, and possible mediating mechanisms. Data were derived from the Sacramento Area Latino Study on Aging, a population-based study of older Latinos (aged 60–101 years) in California followed in 1998–2008. CMV immunoglobulin G (IgG), tumor necrosis factor, and interleukin-6 were assayed from baseline blood draws. Data on all-cause and CVD mortality were abstracted from death certificates. Analyses included 1,468 of 1,789 participants. For individuals with CMV IgG antibody titers in the highest quartile compared with lower quartiles, fully adjusted models showed that all-cause mortality was 1.43 times (95% confidence interval: 1.14, 1.79) higher over 9 years. In fully adjusted models, the hazard of CVD mortality was also elevated (hazard ratio = 1.35, 95% confidence interval: 1.01, 1.80). A composite measure of tumor necrosis factor and interleukin-6 mediated a substantial proportion of the association between CMV and all-cause (18.9%, P < 0.001) and CVD (29.0%, P = 0.02) mortality. This study is the first known to show that high CMV IgG antibody levels are significantly related to mortality and that the relation is largely mediated by interleukin-6 and tumor necrosis factor. Further studies investigating methods for reducing IgG antibody response to CMV are warranted.
doi:10.1093/aje/kwq177
PMCID: PMC2950794  PMID: 20660122
cardiovascular diseases; cytomegalovirus; immune system; infection; inflammation
18.  Disparities among 2009 Pandemic Influenza A (H1N1) Hospital Admissions: A Mixed Methods Analysis – Illinois, April–December 2009 
PLoS ONE  2014;9(4):e84380.
During late April 2009, the first cases of 2009 pandemic influenza A (H1N1) (pH1N1) in Illinois were reported. On-going, sustained local transmission resulted in an estimated 500,000 infected persons. We conducted a mixed method analysis using both quantitative (surveillance) and qualitative (interview) data; surveillance data was used to analyze demographic distribution of hospitalized cases and follow-up interview data was used to assess health seeking behavior. Invitations to participate in a telephone interview were sent to 120 randomly selected Illinois residents that were hospitalized during April–December 2009. During April–December 2009, 2,824 pH1N1 hospitalizations occurred in Illinois hospitals; median age (interquartile range) at admission was 24 (range: 6–49) years. Hospitalization rates/100,000 persons for blacks and Hispanics, regardless of age or sex were 2–3 times greater than for whites (blacks, 36/100,000 (95% Confidence Interval ([95% CI], 33–39)); Hispanics, 35/100,000 [95%CI,32–37] (; whites, 13/100,000[95%CI, 12–14); p<0.001). Mortality rates were higher for blacks (0.9/100,000; p<0.09) and Hispanics (1/100,000; p<0.04) when compared with the mortality rates for whites (0.6/100,000). Of 33 interview respondents, 31 (94%) stated that they had heard of pH1N1 before being hospitalized, and 24 (73%) did not believed they were at risk for pH1N1. On average, respondents reported experiencing symptoms for 2 days (range: 1–7) before seeking medical care. When asked how to prevent pH1N1 infection in the future, the most common responses were getting vaccinated and practicing hand hygiene. Blacks and Hispanics in Illinois experienced disproportionate pH1N1 hospitalization and mortality rates. Public health education and outreach efforts in preparation for future influenza pandemics should include prevention messaging focused on perception of risk, and ensure community wide access to prevention messages and practices.
doi:10.1371/journal.pone.0084380
PMCID: PMC4002432  PMID: 24776852
19.  Socioeconomic and Psychosocial Gradients in Cardiovascular Pathogen Burden and Immune Response: The Multi-Ethnic Study of Atherosclerosis 
Brain, behavior, and immunity  2008;23(5):663-671.
Background
The biologic mechanisms linking socioeconomic position and psychosocial factors to cardiovascular disease (CVD) are not well understood. Immune response to persistent pathogens may be one of these mechanisms.
Methods
We analyzed cross-sectional data from the Multi-Ethnic Study of Atherosclerosis (N=999) composed of adults age 45–84. Log-binomial regression and ordinal logistic regression models were used to examine associations of socioeconomic factors and psychosocial factors with pathogen burden and immune response among those infected. Pathogen burden was assessed based on seroprevalence of Helicobacter pylori, cytomegalovirus, herpes simplex virus-1, and Chlamydia pneumoniae and antibody levels were used to characterize high immune response to all four pathogens.
Results
Low education was a strong and significant independent predictor of higher pathogen burden after adjustment for covariates (adjusted odds ratio (OR) 95% confidence interval (CI) 1.37, 1.19–1.57). Among subjects seropositive for all four pathogens, low education and a higher level of chronic psychosocial stress showed a positive association with higher antibody response, although associations were no longer significant in models with all covariates included (OR = 1.64, 95%CI 0.82–3.31 for lowest vs. highest educational category and OR= 1.29, 95%CI 0.96–1.73 for a one level increase in chronic stress).
Conclusion
Pathogen burden and heightened immune response may represent a biological pathway by which low socioeconomic position and chronic stress are related to increased rates of cardiovascular disease.
doi:10.1016/j.bbi.2008.12.006
PMCID: PMC2694852  PMID: 19150399
Infection; inflammation; epidemiology; cardiovascular diseases
20.  Cytomegalovirus is associated with reduced telomerase activity in the Whitehall II cohort 
Experimental gerontology  2013;48(4):385-390.
Telomere length and telomerase activity have received increased attention as markers of cellular aging, but the determinants of inter-individual variation in these markers are incompletely understood. Cytomegalovirus (CMV) infection may be particularly important for telomere and telomerase dynamics due to its dramatic impact on peripheral blood lymphocyte composition, i.e., increasing the number and proportions of highly differentiated T cells that are characterized by shorter telomere length (TL) and lowered telomerase activity (TA). However, the possible relationship between CMV infection and leukocyte TL and TA has not been well-examined in vivo. This study examined the associations of CMV seropositivity and CMV IgG antibodies with leukocyte (TL) and (TA) in a sample of 434 healthy individuals (ages 53–76) from the Whitehall II cohort. Positive CMV serostatus was significantly associated with lower TA among women, and higher CMV IgG antibody levels were associated with lower TA in the overall sample. However, neither CMV seropositivity nor CMV IgG antibody levels (reflecting subclinical reactivation) among the seropositive were significantly associated with TL. These associations were robust to adjustment for age, employment grade, BMI, and smoking status. The results demonstrate that CMV seropositivity and subclinical reactivation predict lower TA. Future longitudinal studies should test whether the association of CMV with lower TA contributes to accelerated telomere shortening over time.
doi:10.1016/j.exger.2013.01.016
PMCID: PMC3626117  PMID: 23403382
telomeres; telomerase; cytomegalovirus; infections; Whitehall II
21.  The Association between Influenza Treatment and Hospitalization-Associated Outcomes among Korean Children with Laboratory-Confirmed Influenza 
Journal of Korean Medical Science  2014;29(4):485-493.
There are limited data evaluating the relationship between influenza treatment and hospitalization duration. Our purpose assessed the association between different treatments and hospital stay among Korean pediatric influenza patients. Total 770 children ≤ 15 yr-of-age hospitalized with community-acquired laboratory-confirmed influenza at three large urban tertiary care hospitals were identified through a retrospective medical chart review. Demographic, clinical, and cost data were extracted and a multivariable linear regression model was used to assess the associations between influenza treatment types and hospital stay. Overall, there were 81% of the patients hospitalized with laboratory-confirmed influenza who received antibiotic monotherapy whereas only 4% of the patients received oseltamivir monotherapy. The mean treatment-related charges for hospitalizations treated with antibiotics, alone or with oseltamivir, were significantly higher than those treated with oseltamivir-only (P < 0.001). Influenza patients treated with antibiotics-only and antibiotics/oseltamivir combination therapy showed 44.9% and 28.2%, respectively, longer duration of hospitalization compared to those treated with oseltamivir-only. Patients treated with antibiotics, alone or combined with oseltamivir, were associated with longer hospitalization and significantly higher medical charges, compared to patients treated with oseltamivir alone. In Korea, there is a need for more judicious use of antibiotics, appropriate use of influenza rapid testing.
Graphical Abstract
doi:10.3346/jkms.2014.29.4.485
PMCID: PMC3991790  PMID: 24753694
Influenza, Human; Hospitalizations; Oseltamivir; Therapeutics; Child
22.  Socioeconomic and Race/Ethnic Patterns in Persistent Infection Burden Among U.S. Adults 
Background
The pathophysiological mechanisms that underlie health disparities by socioeconomic status and race/ethnicity are poorly understood. Promising new research suggests that the burden of persistent infection may influence adult disease risk and mortality. This article examines how multiple persistent infections cluster within individuals and how this clustering varies by socioeconomic position and race/ethnicity in U.S. adults.
Methods
We analyze data from the National Health and Nutrition Examination Survey III (N = 19,275) for adults aged 17–90 years. The clustering of infections within individuals is studied using tetrachoric correlations. Multiple indicator multiple cause models are used to analyze the infection burden construct as measured by seropositivity to Helicobacter pylori, cytomegalovirus, herpes simplex virus-1, and hepatitis B, focusing on the burden's distribution by socioeconomic position and race/ethnicity. The results are corroborated using ordered logistic regression for a commonly used count index of individual infections.
Results
Seroprevalence of individual persistent infections is positively correlated, suggesting common factors related to exposure or susceptibility. Education, income, and race/ethnicity are strong and significant independent predictors of infection burden in U.S. adults in all models.
Conclusion
The disproportionate burden of persistent infections among disadvantaged groups across all ages may be one biologic pathway by which low socioeconomic position is related to increased rates of morbidity and mortality in the United States.
doi:10.1093/gerona/gln012
PMCID: PMC2655034  PMID: 19196638
Socioeconomic; Race; Ethnic; United states; Adults; Infection; Biomarkers
23.  PhenX RISING: real world implementation and sharing of PhenX measures 
BMC Medical Genomics  2014;7:16.
Background
The purpose of this manuscript is to describe the PhenX RISING network and the site experiences in the implementation of PhenX measures into ongoing population-based genomic studies.
Methods
Eighty PhenX measures were implemented across the seven PhenX RISING groups, thirty-three of which were used at more than two sites, allowing for cross-site collaboration. Each site used between four and 37 individual measures and five of the sites are validating the PhenX measures through comparison with other study measures. Self-administered and computer-based administration modes are being evaluated at several sites which required changes to the original PhenX Toolkit protocols. A network-wide data use agreement was developed to facilitate data sharing and collaboration.
Results
PhenX Toolkit measures have been collected for more than 17,000 participants across the PhenX RISING network. The process of implementation provided information that was used to improve the PhenX Toolkit. The Toolkit was revised to allow researchers to select self- or interviewer administration when creating the data collection worksheets and ranges of specimens necessary to run biological assays has been added to the Toolkit.
Conclusions
The PhenX RISING network has demonstrated that the PhenX Toolkit measures can be implemented successfully in ongoing genomic studies. The next step will be to conduct gene/environment studies.
doi:10.1186/1755-8794-7-16
PMCID: PMC3994539  PMID: 24650325
PhenX; Phenotype; Epidemiology; Risk factors; Harmonization
24.  Impact of Technical Sources of Variation on the Hand Microbiome Dynamics of Healthcare Workers 
PLoS ONE  2014;9(2):e88999.
We assessed the dynamics of hand microbial community structure of 34 healthcare workers from a single surgical intensive care unit over a short (3 week) time period, whilst taking into account the technical sources of variability introduced by specimen collection, DNA extraction, and sequencing. Sample collection took place at 3 different time points. Only the sampling collection method appeared to have a significant impact on the observed hand microbial community structure among the healthcare workers. Analysis of samples collected using glove-juice showed a slightly more similar microbial composition within individual hand samples over time than between the hands of different individuals over time. This was not true for samples collected using a swab, where samples from a single individual were no more similar to each other over time than those among other individuals over time, suggesting they were essentially independent. DNA extraction techniques (lysozyme only versus enzyme cocktail) and sequencing (replicate set 1 versus 2) using Ion Torrent Personal Genome Machine, were not influential to the microbial community structures. Glove-juice sample collection may likely be the method of choice in hand hygiene studies in the healthcare setting.
doi:10.1371/journal.pone.0088999
PMCID: PMC3925205  PMID: 24551205
25.  Epigenetic Signatures May Explain the Relationship Between Socioeconomic Position and Risk of Mental Illness: Preliminary Findings from an Urban Community Based Sample 
Low socioeconomic position (SEP) has previously been linked to a number of negative health indicators, including poor mental health. The biologic mechanisms linking SEP and mental health remain poorly understood. Recent work suggests that social exposures influence DNA methylation in a manner salient to mental health. We conducted a pilot investigation to assess whether SEP, measured as educational attainment, modifies the association between genomic methylation profiles and traumatic stress in a trauma-exposed sample. Results show that methylation × SEP interactions occur preferentially in genes pertaining to nervous system function, suggesting a plausible biologic pathway by which SEP may enhance sensitivity to stress, and, in turn, risk of post-traumatic stress disorder.
doi:10.1080/19485565.2013.774627
PMCID: PMC3754421  PMID: 23701537

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