What Were the Information Voids? A Qualitative Analysis of Questions Asked by Dear Pandemic Readers between August 2020-August 2021.

In the current infodemic, how individuals receive information (channel), who it is coming from (source), and how it is framed can have an important effect on COVID-19 related mitigation behaviors. In light of these challenges presented by the infodemic, Dear Pandemic (DP) was created to directly address persistent questions related to COVID-19 and other health topics in the online environment. This is a qualitative analysis of 3806 questions that were submitted by DP readers to a question box on the Dear Pandemic website between August 30, 2020 and August 29, 2021. Analyses resulted in four themes: the need for clarification of other sources; lack of trust in information; recognition of possible misinformation; and questions on personal decision-making. Each theme reflects an unmet informational need of Dear Pandemic readers, which may be reflective of the broader informational gaps in our science communication efforts.This study highlights the role of an ad hoc risk communication platform in the current environment and uses questions submitted to the Dear Pandemic question box to identify informational needs of DP readers over the course of the COVID-19 pandemic. These findings may help clarify how organizations addressing health misinformation in the digital space can contribute to timely, responsive science communication and improve future communication efforts.

Latent Class Models of Early-life Trauma and Incident Breast Cancer.

BACKGROUND: Psychosocial trauma has been hypothesized to influence breast cancer risk, but little is known about how co-occurring traumas-particularly during early life-may impact incidence. We examine the relationship between multiple measures of early-life trauma and incident breast cancer. METHODS: The Sister Study is a prospective cohort study of US women (n = 50,884; enrollment 2003-2009; ages 35-74). Of 45,961 eligible participants, 3,070 developed invasive breast cancer or ductal carcinoma in situ through 2017. We assessed trauma before age 18 using previously studied measures (cumulative score, individual trauma type, and substantive domain) and a six-class latent variable to evaluate co-occurring traumas. We accounted for missing data using multiple imputation and estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional-hazards models. RESULTS: Approximately 49% of participants reported early-life trauma. Using the latent class variable approach, breast cancer hazard was higher among participants who had sexual trauma or household dysfunction (HR = 1.1; CI = 0.93, 1.3) or moderate (HR = 1.2; CI = 0.99, 1.4) but not high trauma (HR = 0.66; CI = 0.44, 0.99) compared to low trauma. Breast cancer HRs associated with sexual early-life trauma or household dysfunction were elevated for pre- and postmenopausal breast cancer and by estrogen receptor status. We found no effect modification by race-ethnicity. Estimated effects were attenuated with report of constant childhood social support. CONCLUSIONS: Breast cancer incidence varied by latent patterns of co-occurring early-life trauma. Models capturing childhood social support and trauma patterning, rather than cumulative or discrete indicators, may be more meaningful in breast cancer risk assessment.

Association Between Immune Response to Cytomegalovirus and Cognition in the Health and Retirement Study.

Chronic infections and the subsequent immune response have recently been shown to be risk factors for cognitive decline and Alzheimer disease and related dementias (ADRD). While some studies have shown an association between cytomegalovirus (CMV), a chronic and highly prevalent infection, and cognition and/or ADRD, these studies have been limited by nonrepresentative and small samples. Using 2016 data on 5,617 adults aged 65 years or more from the Health and Retirement Study, we investigated the cross-sectional associations of both CMV serostatus and immunoglobulin G (IgG) antibody response with cognitive function using linear regression models adjusting for age, sex, race/ethnicity, and educational attainment. We further investigated potential effect-measure modification by educational attainment. Overall, both CMV seropositivity and higher IgG antibody response were associated with lower cognitive function, though the relationship was not statistically significant in adjusted models. Among participants with less than a high school diploma, CMV seropositivity and being in the first tertile of IgG response, relative to seronegative persons, were associated with lower scores on the Telephone Interview for Cognitive Status (-0.56 points (95% confidence interval: -1.63, 0.52) and -0.89 points (95% confidence interval: -2.07, 0.29), respectively), and the relationship was attenuated among those with higher education. Our results suggest that CMV may be a risk factor for cognitive impairment, particularly among persons with fewer educational resources.

Objective and subjective childhood socioeconomic disadvantage and incident depression in adulthood: a longitudinal analysis in the Sister Study.

Understanding of the role of objective versus subjective childhood socioeconomic disadvantage (SD) in depression onset in adulthood among women, independent of later life SD, and across birth cohorts, is limited. We examined the association between objective (i.e., household education level) and subjective (i.e., rank of family income and report of not enough food to eat) SD during childhood and diagnosis of clinical depression after age 30 among 47,055 women in the Sister Study. We used Cox proportional hazard models adjusting for women's race/ethnicity, childhood household composition, mother's age at her birth adulthood educational attainment, and calendar year of birth. Analyses were repeated stratified by 10-year birth group. A total of 8036 (17.1%) women were diagnosed with clinical depression over a mean follow-up of 24.0 (± 9.9) years. Those reporting being poor (versus well-off) or not having enough food to eat in childhood had a 1.28 (95% confidence interval (CI) 1.13, 1.44) and 1.30 (95% CI 1.21, 1.41) times higher rate of depression diagnosis, respectively, with consistent associations observed across birth year groups. An inverse association between low household education level and incident depression was observed at baseline (i.e., age 30) becoming positive over time in the total sample but only among women born between 1935-1954 in analyses stratified by 10-year birth group. Our findings suggest that subjective SD in childhood is a largely consistent predictor of depression onset among women in adulthood whereas the effects of household education level in childhood may vary across women born into different birth cohorts, and for some, across the lifecourse.

Dear Pandemic: Nurses as key partners in fighting the COVID-19 infodemic.

The COVID-19 pandemic and subsequent proliferation of misinformation have created parallel public health crises. Social media offers a novel platform to amplify evidence-based communication to broader audiences. This paper describes the application of science communication engagement on social media platforms by an interdisciplinary team of female scientists in a campaign called Dear Pandemic. Nurses are trusted professionals trained in therapeutic communication and are central to this effort. The Dear Pandemic campaign now has more than 97,000 followers with international and multilingual impact. Public health strategies to combat misinformation and guide individual behavior via social media show promise, and require further investment to support this novel dissemination of science communication.

Pathogen burden and leukocyte telomere length in the United States.

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.

Testing allostatic load factor structures among adolescents: A structural equation modeling approach.

OBJECTIVES: Allostatic load (AL) represents cumulative biological "wear and tear" that results from chronic stress exposure over time, ultimately increasing risk for chronic disease. A consensus is lacking regarding the best operationalization of AL, particularly for younger, less studied populations. The purpose of this study was to test multiple hypothesized factor structures for AL to determine the best measurement approach for adolescents. METHODS: We analyzed biologic data for 1900 adolescents aged 12-18 from four waves (2003-2010) of the National Health and Nutrition Examination Survey. AL indicator variables included cardiovascular (systolic BP, creatinine), metabolic (HDL, LDL, triglycerides, insulin, fasting glucose, HA1C, body mass index [BMI], waist circumference), and immune (albumin, CRP, WBC, EBV) biomarkers. Structural equation modeling was used to test the fit of five hypothesized AL factor structures. RESULTS: The data best supported a unidimensional factor structure, where the AL construct directly influenced each of the indicator variables. All but two of the indicators (HDL and albumin) had positive factor loadings, thus, as AL increases the values for those indicators also increase. The best indicators for AL were those measuring metabolic dysregulation, with BMI and waist circumference having the highest factor loadings (0.95 and 0.982, respectively). CONCLUSIONS: BMI and waist circumference may be some of the earliest clinical signs of elevated AL that manifest among adolescents. Future research should aim to include neuroendocrine biomarkers in their AL measures to have a more robust estimation of AL in younger populations.

Differences in the association between persistent pathogens and mood disorders among young- to middle-aged women and men in the U.S.

BACKGROUND: A growing literature supports the role of immune system alterations in the etiology of mood regulation, yet there is little population-based evidence regarding the association between persistent pathogens, inflammation and mood disorders among younger women and men in the U.S. METHODS: We used data from the National Health and Nutrition Examination Survey III on individuals 15-39 years of age assessed for major depression, dysthymia, and/or bipolar disorder I and tested for cytomegalovirus (N=6825), herpes simplex virus (HSV)-1 (N=5618) and/or Helicobacter pylori (H. pylori) (N=3167) seropositivity as well as C-reactive protein (CRP) level (N=6788). CMV immunoglobulin G (IgG) antibody level was also available for a subset of women (N=3358). We utilized logistic regression to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between pathogens, CRP levels and each mood disorder overall and among women and men, separately. RESULTS: H. pylori seropositivity was associated with increased odds of dysthymia (OR 2.37, 95% confidence interval (CI): 1.07, 5.24) among women, but decreased odds among men (OR 0.51, 95% CI: 0.28, 0.92). CMV seropositivity was also associated with lower odds of depression (OR 0.54, 95% CI: 0.32, 0.91) among men, while elevated CMV IgG level was marginally associated with increased odds of mood disorders among women. Associations were not mediated by CRP level. CONCLUSIONS: Our findings suggest that persistent pathogens such as CMV and H. pylori may differentially influence mood disorders among women and men, warranting further investigation into biological and/or sociocultural explanations for the contrasting associations observed.

Income and Markers of Immunological Cellular Aging.

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 with 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: After adjustment for age, sex, race, smoking, medication use, and lifetime history of mental health conditions, lower income was associated with a 0.41 (95% confidence interval = 0.09-0.72) log-unit increase in the CD4 E/N ratio and a 0.20 (95% confidence interval = 0.02-0.39) log-unit increase in the CD8 E/N ratio. CMV immunoglobulin G 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.

Toxoplasma gondii and anxiety disorders in a community-based sample.

A growing body of literature suggests that exposure to the neurotropic parasite Toxoplasma gondii (T. gondii) is associated with increased risk of mental disorders, particularly schizophrenia. However, a potential association between T. gondii exposure and anxiety disorders has not been rigorously explored. Here, we examine the association of T. gondii infection with both anxiety and mood disorders. Participants (n=484) were drawn from the Detroit Neighborhood Health Study, a population-representative sample of Detroit residents. Logistic regression was used to examine the associations between T. gondii exposure (defined by seropositivity and IgG antibody levels) and three mental disorders: generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD) and depression. We found that T. gondii seropositivity was associated with a 2 times greater odds of GAD (odds ratio (OR), 2.25; 95% confidence interval (CI), 1.11-4.53) after adjusting for age, gender, race, income, marital status, and medication. Individuals in the highest antibody level category had more than 3 times higher odds of GAD (OR, 3.35; 95% CI, 1.41-7.97). Neither T. gondii seropositivity nor IgG antibody levels was significantly associated with PTSD or depression. Our findings indicate that T. gondii infection is strongly and significantly associated with GAD. While prospective confirmation is needed, T. gondii infection may play a role in the development of GAD.

Persistent viral pathogens and cognitive impairment across the life course in the third national health and nutrition examination survey.

BACKGROUND: Herpesviruses have been linked to cognitive impairment in older individuals but little is known about the association in the general US population. METHODS: We determined whether cytomegalovirus (CMV) and herpes simplex virus 1 (HSV-1) seropositivity were associated with cognitive impairment among children (aged 6-16 years) and adults aged 20-59 or ≥60 years, using data from the National Health and Nutrition Examination Survey (NHANES) III. Linear and logistic regression models were used to examine the associations between pathogen seropositivity and cognitive impairment. RESULTS: Among children, HSV-1 seropositivity was associated with lower reading and spatial reasoning test scores (ß, -0.69; 95% confidence interval [CI], -1.18 to -.21 and ß, -0.82; 95% CI, -1.29 to -.36, respectively). Among middle-aged adults, HSV-1 and CMV seropositivity were associated with impaired coding speed (odds ratio [OR], 1.54; 95% CI, 1.13-2.11, and OR, 1.41; 95% CI, 1.09-1.82, respectively). CMV seropositivity was also associated with impaired learning and recall (OR, 1.43; 95% CI, 1.14-1.80). Among older adults, HSV-1 seropositivity was associated with immediate memory impairment (OR, 3.26; 95% CI, 1.68-6.32). CONCLUSIONS: Future studies examining the biological pathways by which herpesviruses influence cognitive impairment across the life course are warranted.

Asthma as a Risk Factor for Hospitalization in Children and Youth With COVID-19: A Retrospective Cohort Study.

BACKGROUND: Studies examining the association between asthma and hospitalization among children and youth with coronavirus disease 2019 (COVID-19) have yielded mixed results. Both asthma and COVID-19 hospitalization are characterized by racial, ethnic and socioeconomic disparities which also pattern geographically, yet no studies to date have adjusted for neighborhood context in the assessment of this association. METHODS: Mixed effects logistic regression was used to estimate the association between asthma and hospitalization due to COVID-19 in a sample of 28,997 children and youth diagnosed with COVID-19 in Milwaukee County, Wisconsin, from March 1, 2020, to May 31, 2022. Models adjusted for individual-level sociodemographic factors (age, gender, race, ethnicity and city/suburb residence) and season of diagnosis were examined as moderators. Random intercepts by census tract accounted for geographic variation in neighborhood factors and census tract-level measures of education, health and environment, and social and economic factors were assessed via childhood opportunity indices. RESULTS: Asthma history was statistically significantly associated with hospitalization due to COVID-19 among children and youth. Hospitalization rates varied statistically significantly by census tract, and results were unchanged after accounting for childhood opportunity indices and census tract. Season of diagnosis was not found to moderate the effect of asthma history on COVID-19 hospitalization. CONCLUSION: Our study suggests that asthma history is a risk factor for hospitalization in the context of COVID-19 infection among children and youth, warranting observation and follow-up of children with asthma as well as continued measures to prevent COVID-19 in this population.

Association between prenatal socioeconomic disadvantage, adverse birth outcomes, and inflammatory response at birth.

Prenatal socioeconomic disadvantage is associated with inflammation in mid- to late-life, yet whether a pro-inflammatory phenotype is present at birth and the role of adverse birth outcomes in this pathway remains unclear. We utilized data on prenatal socioeconomic disadvantage at the individual- (i.e., mother's and father's education level, insurance type, marital status, and Women, Infants, and Children benefit receipt) and census-tract level as well as preterm (< 37 weeks gestation) and small-for-gestational-age (SGA) (i.e., < 10th percentile of sex-specific birth weight for gestational age) birth status, and assessed inflammatory markers (i.e., C-reactive protein, serum amyloid p, haptoglobin, and α-2 macroglobulin) in archived neonatal bloodspots from a Michigan population-based cohort of 1000 neonates. Continuous latent variables measuring individual- and combined individual- and neighborhood-level prenatal socioeconomic disadvantage were constructed and latent profile analysis was used to create a categorical inflammatory response variable (high versus low) based on continuous inflammatory marker levels. Structural equation models were used to estimate the total and direct effect of prenatal socioeconomic disadvantage on the inflammatory response at birth as well as indirect effect via preterm or SGA birth (among term neonates only), adjusting for mother's age, race/ethnicity, body mass index, smoking status, comorbidities, and antibiotic use/infection as well as grandmother's education level. There was a statistically significant total effect of both individual- and combined individual- and neighborhood-level prenatal socioeconomic disadvantage on high inflammatory response among all neonates as well as among term neonates only, and a positive but not statistically significant direct effect in both groups. The indirect effects via preterm and SGA birth were both negative, but not statistically significant. Our findings suggest prenatal socioeconomic disadvantage contributes to elevated neonatal inflammatory response, but via pathways outside of these adverse birth outcomes.

Vaccination Against Pneumonia May Provide Genotype-Specific Protection Against Alzheimer's Disease.

Vaccine repurposing that considers individual genotype may aid personalized prevention of Alzheimer's disease (AD). In this retrospective cohort study, we used Cardiovascular Health Study data to estimate associations of pneumococcal polysaccharide vaccine and flu shots received between ages 65-75 with AD onset at age 75 or older, taking into account rs6859 polymorphism in NECTIN2 gene (AD risk factor). Pneumococcal vaccine, and total count of vaccinations against pneumonia and flu, were associated with lower odds of AD in carriers of rs6859 A allele, but not in non-carriers. We conclude that pneumococcal polysaccharide vaccine is a promising candidate for genotype-tailored AD prevention.

Dear Pandemic: A topic modeling analysis of COVID-19 information needs among readers of an online science communication campaign.

BACKGROUND: The COVID-19 pandemic was accompanied by an "infodemic"-an overwhelming excess of accurate, inaccurate, and uncertain information. The social media-based science communication campaign Dear Pandemic was established to address the COVID-19 infodemic, in part by soliciting submissions from readers to an online question box. Our study characterized the information needs of Dear Pandemic's readers by identifying themes and longitudinal trends among question box submissions. METHODS: We conducted a retrospective analysis of questions submitted from August 24, 2020, to August 24, 2021. We used Latent Dirichlet Allocation topic modeling to identify 25 topics among the submissions, then used thematic analysis to interpret the topics based on their top words and submissions. We used t-Distributed Stochastic Neighbor Embedding to visualize the relationship between topics, and we used generalized additive models to describe trends in topic prevalence over time. RESULTS: We analyzed 3839 submissions, 90% from United States-based readers. We classified the 25 topics into 6 overarching themes: 'Scientific and Medical Basis of COVID-19,' 'COVID-19 Vaccine,' 'COVID-19 Mitigation Strategies,' 'Society and Institutions,' 'Family and Personal Relationships,' and 'Navigating the COVID-19 Infodemic.' Trends in topics about viral variants, vaccination, COVID-19 mitigation strategies, and children aligned with the news cycle and reflected the anticipation of future events. Over time, vaccine-related submissions became increasingly related to those surrounding social interaction. CONCLUSIONS: Question box submissions represented distinct themes that varied in prominence over time. Dear Pandemic's readers sought information that would not only clarify novel scientific concepts, but would also be timely and practical to their personal lives. Our question box format and topic modeling approach offers science communicators a robust methodology for tracking, understanding, and responding to the information needs of online audiences.

Prenatal Socioeconomic Disadvantage and Epigenetic Alterations at Birth Among Children Born to White British and Pakistani Mothers in the Born in Bradford Study.

Prenatal socioeconomic disadvantage (SD) has been linked to DNA methylation (DNAm) in adulthood, but whether such epigenetic alterations are present at birth remains unclear. We carried out an epigenome-wide analysis of the association between several measures of individual- and area-level prenatal SD and DNAm assessed in neonatal cord blood via the Infinium EpicBeadChip among offspring born to mothers of White British (N = 455) and Pakistani (N = 493) origin in the Born in Bradford Study. Models were adjusted for mother's age, ethnicity, and education level as well as cell-type fractions and then for maternal health behaviours and neonate characteristics, and last, stratified by mother's ethnicity. P-values were corrected for multiple testing and a permutation-based approach was used to account for small cell sizes. Among all children, housing tenure (owning versus renting) as well as father's occupation (manual versus non-manual) were each associated with DNAm of one CpG site and index of multiple deprivation (IMD) was associated with DNAm of 11 CpG sites. Among children born to White British mothers, father's occupation (student or unemployed versus non-manual) was associated with DNAm of 1 CpG site and IMD with DNAm of 3 CpG sites. Among children born to Pakistani mothers, IMD was associated with DNAm of 1 CpG site. Associations were largely unchanged after further adjustment for maternal health behaviours or neonate characteristics and remained statistically significant. Our findings suggest that individual- and area-level prenatal SD may shape alterations to the neonatal epigenome, but associations vary across ethnic groups.

Lessons Learned From Dear Pandemic, a Social Media-Based Science Communication Project Targeting the COVID-19 Infodemic.

The World Health Organization has identified excessive COVID-19 pandemic-related information as a public health crisis, calling it an "infodemic." Social media allows misinformation to spread quickly and outcompete scientifically grounded information delivered via other methods. Dear Pandemic is an innovative, multidisciplinary, social media-based science communication project whose mission is to educate and empower individuals to successfully navigate the overwhelming amount of information circulating during the pandemic. This mission has 2 primary objectives: (1) to disseminate trustworthy, comprehensive, and timely scientific content about the pandemic to lay audiences via social media and (2) to promote media literacy and information-hygiene practices, equipping readers to better manage the COVID-19 infodemic within their own networks. The volunteer team of scientists publishes 8-16 posts per week on pandemic-relevant topics. Nearly 2 years after it launched in March 2020, the project has a combined monthly reach of more than 4 million unique views across 4 social media channels, an email newsletter, and a website. We describe the project's guiding principles, lessons learned, challenges, and opportunities. Dear Pandemic has emerged as an example of a promising new paradigm for public health communication and intervention. The contributors deliver content in ways that are personal, practical, actionable, responsive, and native to social media platforms. The project's guiding principles are a model for public health communication targeting future infodemics and can bridge the chasm between the scientific community and the practical daily decision-making needs of the general public.

Early life trauma and adult leucocyte telomere length.

BACKGROUND: Telomere length, a biomarker of cell division and cellular aging, has been associated with multiple chronic disease endpoints. Experienced trauma over the life course may contribute to telomere shortening via mechanisms of stress embodiment. However, it is unclear how patterns of co-occurring trauma during sensitive periods (e.g., early life) throughout the life course may influence telomere shortening. We examine the relationship between co-occurring early life trauma on adult telomere length and the extent to which adulthood trauma, socioeconomic position, and health and lifestyle factors may mediate this relationship. METHODS: We use data from a sample of participants in the Sister Study (N = 740, analytic sample: n = 602), a prospective cohort of U.S. self-identified females aged 35-74 years at enrollment (2003-2009) for whom leukocyte telomere length was measured in baseline blood samples. Participants reported their experience of 20 different types of trauma, from which we identified patterns of co-occurring early life trauma (before age 18) using latent class analysis. We estimated the direct and indirect effects of early life trauma on leukocyte telomere length using structural equation modeling, allowing for mediating adult pathways. RESULTS: Approximately 47 % of participants reported early life trauma. High early life trauma was associated with shorter telomere length compared to low early life trauma (ß = -0.11; 95 % CI: -0.22, -0.004) after adjusting for age and childhood socioeconomic position. The inverse association between early life trauma and adult leukocyte telomere length was largely attributable to the direct effect of early life trauma on telomere length (ß = -0.12; 95 %CI: -0.23, -0.01). Mediating indirect pathways via adult trauma, socioeconomic position, and health metrics did not substantively contribute the overall association. CONCLUSIONS: These findings highlight the role of patterns of co-occurring early life trauma on shortened telomere length independent of adult pathways.

Cytomegalovirus infection is associated with an increase in aortic stiffness in older men which may be mediated in part by CD4 memory T-cells.

Human Cytomegalovirus (CMV) infection is associated with atherosclerosis, higher cardiovascular disease (CVD) risk, and an increase in memory T-cells (Tmem). T-cells have also been implicated in CVD, independently of CMV infection. To better understand the CMV-associated CVD risk, we examined the association between CMV (IgG) serostatus and central aortic (carotid-to-femoral) pulse wave velocity (cfPWV), an early, independent predictor of CVD. We also investigated if such an association might be reflected by the distribution of Tmem and/or other T-cell subsets. Methods: Healthy older volunteers (60-93 years) underwent routine clinical and laboratory evaluation, including assessment of cfPWV in eligible participants. Flow-cytometry was used to assess proportions of memory T-cells, CD28null T-cells, and CMV-specific T-cells. The following associations were examined; CMV serostatus/cfPWV, CMV serostatus/proportion of Tmem, proportion of Tmem/cfPWV, CD28null T-cells/cfPWV, and CMV-specific T-cells/cfPWV. Linear regression models were used to adjust for age, sex, socioeconomic status, smoking, waist-to-hip ratio, cholesterol, and blood pressure as required. Results: Statistically significant positive associations were found (P-values for the fully adjusted models are given); CMV serostatus/cfPWV in men (P ≤ 0.01) but not in women, CMV serostatus/proportions of CD4 Tmem in men (P ≤ 0.05) but not in women; proportions of CD4 Tmem/cfPWV among CMV seropositive (CMV+) people (P ≤ 0.05) but not CMV seronegative (CMV-) people. Conclusion: CMV infection increases the CVD risk of older men by increasing cfPWV. This may be mediated in part by increased proportions of CD4 Tmem, higher numbers of which are found in CMV+ older people and more so among men than women. Given the high prevalence of CMV worldwide, our findings point to a significant global health issue. Novel strategies to mitigate the increased CVD risk associated with CMV may be required.

Population levels of psychological stress, herpesvirus reactivation and HIV.

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.