Twenty-Five-Year Changes in Office and Ambulatory Blood Pressure: Results From the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: Blood pressure (BP) measured in the office setting increases from early through later adulthood. However, it is unknown to what extent out-of-office BP derived via ambulatory BP monitoring (ABPM) increases over time, and which participant characteristics and risk factors might contribute to these increases. METHODS: We assessed 25-year change in office- and ABPM-derived BP across sex, race, diabetes mellitus (DM), and body mass index (BMI) subgroups in the Coronary Artery Risk Development in Young Adults study using multivariable-adjusted linear mixed effects models. RESULTS: We included 288 participants who underwent ABPM at the Year 5 Exam (mean [SD] age, 25.1 [3.7]; 45.8% men) and 455 participants who underwent ABPM at the Year 30 Exam (mean [SD] age, 49.5 [3.7]; 42.0% men). Office, daytime, and nighttime systolic BP (SBP) increased 12.8 (95% confidence interval [CI], 7.6-17.9), 14.7 (95% CI, 9.7-19.8), and 16.6 (95% CI, 11.4-21.8) mm Hg, respectively, over 25 years. Office SBP increased 6.5 (95% CI, 2.3-10.6) mm Hg more among black compared with white participants. Daytime SBP increased 6.3 (95% CI, 0.2-12.4) mm Hg more among participants with a BMI ≥25 vs. <25 kg/m2. Nighttime SBP increased 4.7 (95% CI, 0.5-8.9) mm Hg more among black compared with white participants, and 17.3 (95% CI, 7.2-27.4) mm Hg more among participants with vs. without DM. CONCLUSIONS: Office- and ABPM-derived BP increased more from early through middle adulthood among black adults and participants with DM and BMI ≥25 kg/m2.

Barriers to Mental Health Treatment in the Saudi National Mental Health Survey.

Objectives: To examine barriers to initiation and continuation of treatment among individuals with common mental disorders in the Saudi National Mental Health Survey (SNMHS). Methods: The SNMHS is a community-based epidemiological survey in a nationally representative household sample of respondents aged 15-65 in the Kingdom of Saudi Arabia. The World Health Organization Composite International Diagnostic Interview (CIDI) 3.0 was used. Predictors of barriers to treatment were analyzed with multivariable logistic regression. Results: Among participants with a 12-month DSM-IV/CIDI disorder (n = 711), 86.1% reported no service use. Of those (n = 597), 50.7% did not think they needed any help (categorized as "low perceived need") and 49.3% did perceive need. Of those who perceived need (n = 309), the majority (98.9%) reported attitudinal barriers to initiation. In contrast, 10.3% of those with a perceived need reported structural barriers. Respondents who were previously married or indicated below-average income were more likely to believe they needed help. Conclusions: Among people with a diagnosed mental disorder, low perceived need and attitudinal barriers are the primary barriers to mental health treatment in the KSA. The results suggest that addressing poor mental health literacy may be essential factor in reducing the unmet need for mental health treatment in the KSA.

Reservation-Urban Comparison of Suicidal Ideation/Planning and Attempts in American Indian Youth.

BACKGROUND: Our aim was to identify sex- and location-specific risk factors for suicide ideation/planning and attempts among American Indian youth. METHODS: Biennial data for 6417 American Indian high school students attending reservation and urban schools were extracted from the Montana volunteer sample Youth Risk Behavior Survey data for pooled years 2003 to 2011. Logistic regression was used to identify sex- and school location-specific risk behaviors and psychosocial factors for past 12-month ideation/planning and past 12-month attempts. RESULTS: Contrary to our hypothesis, the prevalence of ideation/planning and attempts did not significantly differ between reservation/urban location; however, risk factors associated with suicidality did. Sadness/hopelessness was associated with both outcomes for all groups. However, violent victimization was associated with both outcomes only among girls. Lack of school safety was associated with attempts but not ideation/planning among all students. There were distinct differences in risk factors associated with both outcomes among boys. CONCLUSIONS: The results indicate differences and similarities in risk behaviors and psychosocial factors associated with suicidality by sex and reservation/urban setting. Implications include screening potentially at-risk students for depression, violent victimization, substance use, and school safety and use of the findings by tribal and school programs in designing prevention and intervention programs.

Rubella immunity and serum perfluoroalkyl substances: Sex and analytic strategy.

BACKGROUND: Perfluoroalkyl substances (PFASs) have been associated with decreased immunity to childhood tetanus and diphtheria immunizations. If these vaccinations are vulnerable to influence from PFASs, questions arise about associations with other common inoculations. OBJECTIVE: To examine whether serum PFASs were associated with reduced immunity to rubella immunization, and whether interactions with sex or ethnicity warranted analytic stratification. Usually, toxicology analyses are calculated controlling for race and sex. However, sex differences in immune function have been reported and a reduction of immunity to rubella in women could pose risks such miscarriage. METHODS: We analyzed a nationally representative sample of individuals ≥ 12 years from the National Health and Nutrition Examination Survey (NHANES) for years 1999-2000 and 2003-2004 for whom PFAS measures were available. Our analytic strategy was to start with separate analyses for youth and adults controlling for several covariates including ethnicity and sex, as well as the interaction of these terms with PFASs. If there was a main effect of PFASs and an interaction term, we would stratify analyses of effect size. The outcome variable was Rubella IgG titers by quartile of perfluoroalkyl substances. RESULTS: After exclusion for missing data, the analyzed sample contained 581 adult women, 621 adult men, and 1012 youth. There was no significant effect of PFASs on immunity in youths but a significant effect of both PFOA and PFOS in adults, as well as a significant interaction of PFOA x sex and a borderline significant interaction of PFOS x sex. When effect size analyses were stratified by sex, a significant association between rubella titres and PFOA was found in men but not women and PFOS was not significant in either sex. CONCLUSIONS: These results support our earlier studies showing sex specific responses to PFASs and indicate the importance of thinking carefully about analytic strategies in population based toxicology research.

Sleep quality and the cortisol awakening response (CAR) among law enforcement officers: The moderating role of leisure time physical activity.

OBJECTIVE: The goal of this study was to investigate the role of leisure time physical activity (LTPA) on the association between sleep quality and the cortisol awakening response (CAR) in people with an occupation that exposes them to high levels of stress. METHODS: Participants were 275 police officers (age = 42 years ± 8.3, 27% women) enrolled in the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) study (conducted between 2004 and 2009). Officers provided four salivary cortisol samples (on awakening and 15, 30, and 45 min after awakening). Hours of leisure time physical activity were assessed using the Seven-Day Physical Activity Recall questionnaire. Sleep quality (good/poor) was evaluated using the Pittsburgh Sleep Quality Index (PSQI) scale. Analysis of covariance and repeated measures models were used to examine the association of sleep quality to the two aspects of CAR: cortisol levels (total area under the curve (AUCG), mean, and peak cortisol) and cortisol profiles (the overall pattern in cortisol level during the 45 min period following awakening, the increase in cortisol from baseline to average of post awakening values (mean increase), and area under the curve with respect to increase (AUCI)). Analyses were stratified by participant level of reported LTPA (sufficiently vs. insufficiently active, defined as ≥ 150 vs. < 150 min/week of moderate intensity activity, respectively). Since cortisol activity is known to be influenced by gender, we conducted additional analyses also stratified by gender. RESULTS: Overall, results demonstrated that LTPA significantly moderated the association of sleep quality with CAR. Among participants who were sufficiently active, CAR did not differ by sleep quality. However, in those who were insufficiently active during their leisure time, poor sleep quality was associated with a significantly reduced level of total awakening cortisol secretion (AUCG (a.u.) = 777.4 ±â€¯56 vs. 606.5 ±â€¯45, p = 0.02; mean cortisol (nmol/l) = 16.7 ±â€¯1.2 vs. 13.3 ±â€¯0.9, p = 0.03; peak cortisol (nmol/l) = 24.0 ±â€¯1.8 vs. 18.9 ±â€¯1.5, p = 0.03 for good vs. poor sleep quality, respectively). The normal rise in cortisol after awakening was also significantly lower in inactive officers with poor sleep quality than in those with good sleep quality (mean increase (nmol/l) = 6.7 ±â€¯1.5 vs. 2.3 ±â€¯1.2, p = 0.03; AUCI (a.u.) = 249.3 ±â€¯55 vs. 83.3 ±â€¯44, p = 0.02 for those with good vs. poor sleep quality, respectively). While findings for male officers were consistent with the overall results, CAR did not differ by sleep quality in female officers regardless of LTPA level. CONCLUSION: Findings of this study suggest that poor sleep quality is associated with diminished awakening cortisol levels and dysregulated cortisol patterns over time, but only among officers who were inactive or insufficiently active during their leisure time. In contrast, sleep quality was not associated with any measures of CAR in officers who reported sufficient activity, suggesting a potential protective effect of LTPA. In analyses stratified by gender, findings for male officers were similar to those in the pooled sample, although we found no evidence for a modifying effect of LTPA in women. Future longitudinal studies in a larger population are needed to confirm these findings and further elucidate the relationships between LTPA, sleep quality, and cortisol response.

A comparison of risk factors associated with suicide ideation/attempts in American Indian and White youth in Montana.

We examined racial/ethnic and gender-specific associations between suicide ideation/attempts and risky behaviors, sadness/hopelessness, and victimization in Montana American Indian and White youth using 1999-2011 Youth Risk Behavior Survey data. Logistic regression was used to calculate odds ratios and 95% confidence intervals in stratified racial/ethnic-gender groups. The primary results of this study show that although the American Indian youth had more statistically significant suicidal thoughts and attempts than the White youth, they had fewer statistically significant predictors compared to the White youth. Sadness/hopelessness was the strongest, and the only statistically significant, predictor of suicide ideation/attempts common across all four groups. The unhealthy weight control cluster was a significant predictor for the White youth and the American Indian/Alaska Native girls; the alcohol/tobacco/marijuana cluster was a significant predictor for the American Indian boys only. Results show important differences across the groups and indicate directions for future research targeting prevention and intervention.

Identifying multiple risks of low birth weight using person-centered modeling.

OBJECTIVES: Low birth weight outcomes result from multiple potential risks. The present study used latent class analysis to identify subgroups of women with multiple co-occurring risks and to examine the relationship of these risk classes to low birth weight outcome. METHODS: Data were analyzed on all live singleton births in 2010 and 2011 in West Virginia (N = 28,820). Ten risks were examined including marital status, stress, mother's age, parity status, reported smoking and drug use during pregnancy, delayed prenatal care, Medicaid coverage, uninsurance, and low education. RESULTS: Six latent classes were identified that ranged from a low-risk referent group to higher risk classes characterized by unique constellations of risk factors. Compared with the low-risk referent, all of the remaining five latent classes were significantly associated with increased odds of low birth weight. However, one class was at especially high risk; this class was characterized by unmarried women in the Medicaid program who reported drug use, smoking, stress, and late prenatal care (odds ratio, 4.78; 95% confidence interval, 4.07-5.61). CONCLUSIONS: The person-centered approach identified subgroups of women with unique risk profiles. The results suggest that eliminating a single risk would not resolve the low birth weight problem. Smoking, for example, co-occurs with higher stress and higher levels of drug use among a Medicaid population. It may be beneficial to develop and test tailored interventions to groups with specific co-occurring risks to reduce low birth weight outcomes. Programs targeted to women in the Medicaid program who also engage in substance use and experience stress are especially indicated.

Emotion assessment using the NIH Toolbox.

One of the goals of the NIH Toolbox for Assessment of Neurological and Behavioral Function was to identify or develop brief measures of emotion for use in prospective epidemiologic and clinical research. Emotional health has significant links to physical health and exerts a powerful effect on perceptions of life quality. Based on an extensive literature review and expert input, the Emotion team identified 4 central subdomains: Negative Affect, Psychological Well-Being, Stress and Self-Efficacy, and Social Relationships. A subsequent psychometric review identified several existing self-report and proxy measures of these subdomains with measurement characteristics that met the NIH Toolbox criteria. In cases where adequate measures did not exist, robust item banks were developed to assess concepts of interest. A population-weighted sample was recruited by an online survey panel to provide initial item calibration and measure validation data. Participants aged 8 to 85 years completed self-report measures whereas parents/guardians responded for children aged 3 to 12 years. Data were analyzed using a combination of classic test theory and item response theory methods, yielding efficient measures of emotional health concepts. An overview of the development of the NIH Toolbox Emotion battery is presented along with preliminary results. Norming activities led to further refinement of the battery, thus enhancing the robustness of emotional health measurement for researchers using the NIH Toolbox.

Implications of systemic dysfunction for the etiology of malignancy.

The current approach to treatment in oncology is to replace the generally cytotoxic chemotherapies with pharmaceutical treatment which inactivates specific molecular targets associated with cancer development and progression. The goal is to limit cellular damage to pathways perceived to be directly responsible for the malignancy. Its underlying assumptions are twofold: (1) that individual pathways are the cause of malignancy; and (2) that the treatment objective should be destruction-either of the tumor or the dysfunctional pathway. However, the extent to which data actually support these assumptions has not been directly addressed. Accumulating evidence suggests that systemic dysfunction precedes the disruption of specific genetic/molecular pathways in most adult cancers and that targeted treatments such as kinase inhibitors may successfully treat one pathway while generating unintended changes to other, non-targeted pathways. This article discusses (1) the systemic basis of malignancy; (2) better profiling of pre-cancerous biomarkers associated with elevated risk so that preventive lifestyle modifications can be instituted early to revert high-risk epigenetic changes before tumors develop; (3) a treatment emphasis in early stage tumors that would target the restoration of systemic balance by strengthening the body's innate defense mechanisms; and (4) establishing better quantitative models of systems to capture adequate complexity for predictability at all stages of tumor progression.

Circulating maternal perfluoroalkyl substances during pregnancy in the C8 Health Study.

Perfluoroalkyl substances are manmade chemicals used in many consumer products and have become ubiquitous in the environment. Animal studies and a limited number of human studies have demonstrated developmental effects in offspring exposed to perfluoroalkyl substances in utero, but the implications of timing of in utero exposure have not been systematically investigated. The present study investigated variation in perfluorocarbon levels of 9952 women of childbearing age who had been exposed to perfluorooctanoic acid (PFOA) in drinking water contaminated by industrial waste. An analysis of variance with contrast was performed to compare the levels of PFOA and perfluorooctanesulfonic acid (PFOS) in pregnant and nonpregnant women overall and during each trimester of pregnancy. We found that pregnant women had lower circulating PFOA and PFOS concentrations in peripheral blood than nonpregnant women and that PFOA levels were consistently lower throughout all trimesters for pregnancy, suggesting transfer to the fetus at an early stage of gestation. These results are discussed in the context of the endocrine-disrupting properties of perfluoroalkyl substances that have been characterized in animal and human studies. Our conclusion is that further, systematic study of the potential implications of intrauterine perfluorocarbon exposure during critical periods of fetal development is urgently needed.

Assessment of self-reported negative affect in the NIH Toolbox.

We report on the selection of self-report measures for inclusion in the NIH Toolbox that are suitable for assessing the full range of negative affect including sadness, fear, and anger. The Toolbox is intended to serve as a "core battery" of assessment tools for cognition, sensation, motor function, and emotional health that will help to overcome the lack of consistency in measures used across epidemiological, observational, and intervention studies. A secondary goal of the NIH Toolbox is the identification of measures that are flexible, efficient, and precise, an agenda best fulfilled by the use of item banks calibrated with models from item response theory (IRT) and suitable for adaptive testing. Results from a sample of 1763 respondents supported use of the adult and pediatric item banks for emotional distress from the Patient-Reported Outcomes Measurement Information System (PROMIS(®)) as a starting point for capturing the full range of negative affect in healthy individuals. Content coverage for the adult Toolbox was also enhanced by the development of a scale for somatic arousal using items from the Mood and Anxiety Symptom Questionnaire (MASQ) and scales for hostility and physical aggression using items from the Buss-Perry Aggression Questionnaire (BPAQ).

Depressive symptom clusters and 5-year incidence of coronary artery calcification: the coronary artery risk development in young adults study.

BACKGROUND: Because depression is a multidimensional construct and few studies have compared the relative importance of its facets in predicting cardiovascular risk, we evaluated the utility of depressive symptom clusters in predicting the 5-year incidence of coronary artery calcification (CAC). METHODS AND RESULTS: Participants were 2171 middle-aged adults (58% female; 43% black) from the Coronary Artery Risk Development in Young Adults (CARDIA) study who were free of cardiovascular disease. Depressive symptom clusters (z scores) were measured by questionnaires in 2000 to 2001, and CAC was measured by electron beam computed tomography in 2000 to 2001 and 2005 to 2006. There were 243 cases (11%) of incident CAC, defined as the absence of CAC at baseline and the presence of CAC at follow-up. Total depressive symptoms (odds ratio, 1.16; 95% confidence interval, 1.02-1.33; P=0.03) and the depressed affect cluster (odds ratio, 1.17; 95% confidence interval, 1.03-1.33; P=0.02) predicted incident CAC; however, the somatic, interpersonal distress, low positive affect, and pessimism clusters did not. The depressed affect-incident CAC relationship was independent of age, sex, race, education, and antidepressant use; was similar across sex and racial groups; and was partially accounted for by tobacco use and mean arterial pressure. CONCLUSIONS: In contrast to recent results indicating that the somatic cluster is the most predictive of cardiovascular outcomes, we found that the prospective association between depressive symptoms and incident CAC was driven by the depressed affect cluster. Our findings raise the possibility that there may not be 1 facet of depression that is the most cardiotoxic across all contexts.

Association between depressive symptoms and metabolic syndrome in police officers: results from two cross-sectional studies.

Policing is one of the most dangerous and stressful occupations and such stress can have deleterious effects on health. The purpose of this study was to examine the association between depressive symptoms and metabolic syndrome (MetSyn) in male and female police officers from two study populations, Buffalo, NY and Spokane, WA. Depressive symptoms were measured using the Center for Epidemiologic Studies-Depression (CES-D) scale. MetSyn was defined using the 2005 AHA/NHBLI guidelines. Analysis of covariance was used to describe differences in number of MetSyn components across depressive symptom categories. The number of MetSyn components increased significantly across categories of CES-D for Spokane men only (p-trend = 0.003). For each 5-unit increase in CES-D score, odds increased by 47.6% for having hypertriglyceridemia, by 51.8% for having hypertension, and by 56.7% for having glucose intolerance. Exploring this association is important since both are predictors of future chronic health problems and the results could be helpful in developing future gender-specific prevention and intervention efforts among police officers.

Perfluorocarbon exposure, gender and thyroid function in the C8 Health Project.

Perfluorocarbons from common household products such as food containers, stain- resistant protection for clothing, furniture and carpets, paints, and fire-fighting foams are found in soil, water, plants, animal and human serum worldwide. Previous research has shown a significant association between these chemicals and thyroid disease in women. The present data from the C8 Health Project assessed thyroid function in a cross-sectional analysis of 52,296 adults with a year or more of exposure to perfluorooctanoate (PFOA) from drinking water. Outcomes were: thyroxine, T3 uptake, and thyroid stimulating hormone (TSH). Analyses were stratified by gender and age group (< 20 - < 50 years and > 50). Both PFOA and perfluorooctane sulfonate (PFOS) were associated with significant elevations in serum thyroxine and a significant reduction in T3 uptake in all participants. There were also significant gender/PFOS interactions for T3( )uptake and thyroxine, as well as gender/PFOA interactions for T3 uptake. Results provide evidence for disruption of thyroid function related to these common chemicals and possible mechanisms are discussed.

Metabolic syndrome and carotid intima media thickness in urban police officers.

OBJECTIVE: To examine the association between metabolic syndrome (MetSyn) and carotid intima media thickness (IMT) separately in male and female police officers. METHODS: MetSyn was defined using 2005 guidelines. B-mode ultrasound was used to measure mean and maximum (12 and 36 segments) carotid artery thickness. Analysis of covariance was used to compare mean IMT values across individuals categorized by number of MetSyn components. Adjustments were made for age, smoking status, and low-density lipoprotein cholesterol. RESULTS: Among 106 women, the adjusted mean common and maximum36 carotid IMT were significantly and positively associated with number of MetSyn components. No associations were found in men (n = 304). Adjusted carotid IMT values were inversely associated with low high-density lipoprotein cholesterol and directly with hypertension in women. CONCLUSIONS: Number of MetSyn components was significantly associated with carotid IMT in female but not in male officers.

Implications of early menopause in women exposed to perfluorocarbons.

CONTEXT: Perfluorocarbons (PFC) are man-made chemicals used in numerous household products. They have a long half-life in humans and complex animal toxicity, and accumulating evidence points toward associations with multiple human health endpoints. OBJECTIVE: Our objective was to investigate whether PFC are associated with endocrine disruption in women. DESIGN: Cross-sectional analyses were made between quintiles of serum PFC, serum estradiol, and menopause onset. SETTING: The C8 Health Project, with cohort of 69,030 adults and children, was conducted due to PFC contamination of drinking water from six water districts in two states. PARTICIPANTS: Participants included 25,957 women aged 18-65 yr. MAIN OUTCOME MEASURES: Serum estradiol levels and onset of menopause were assessed. The survey was the result of a class action suit, and survey designers (an independent corporation) had no a priori hypotheses. All hypotheses have been formulated by other investigators after data collection. RESULTS: After excluding women who reported hysterectomy and adjusting for age within the group, smoking, alcohol consumption, body mass index, and exercise, the odds of having experienced menopause were significantly higher in the highest quintile relative to the lowest quintile of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in the perimenopausal [PFOS odds = 1.4, confidence interval (CI) = 1.1-1.8; PFOA odds =1.4, CI = 1.1-1.8] and menopausal age groups (PFOS odds = 2.1, CI=1.6-2.8; PFOA odds = 1.7, CI = 1.3-2.3). After appropriate exclusions and adjustment for covariates, there was a significant inverse association between PFOS and estradiol in perimenopausal (ß = -3.65; P < 0.0001) and menopausal age groups (ß = -0.83; P = 0.007) but not between PFOA and estradiol. CONCLUSIONS: These data suggest that PFC are associated with endocrine disruption in women and that further research on mechanisms is warranted.

Associations between police officer stress and the metabolic syndrome.

The purpose of this study was to examine the association of police officer stress with metabolic syndrome (MetSyn) and its individual components. Participants included 288 men and 102 women from the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) Study. Police stress was measured using the Spielberger police stress survey. MetSyn was defined using 2005 guidelines. Results were stratified by gender ANCOVA was used to describe differences in number of MetSyn components across police stress categories after adjusting for age and smoking status. Logistic regression was used to calculate odds ratios for having each MetSyn component by increased police stress levels. The multivariate-adjusted number of MetSyn components increased significantly in women across tertiles of the three perceived stress subscales, and administrative and organizational pressure and lack of support indices for the previous month. No association was found among male officers. Abdominal obesity and reduced high density lipoprotein cholesterol (HDL-C) were consistently associated with police stress in women. Police stress, particularly organizational pressure and lack of support, was associated with MetSyn among female but not male police officers. Given the stress of policing and the adverse cardiovascular disease (CVD) risk factors prevalent among police officers, exploring the association between specific types of police stress and subclinical CVD is important.

AGT M235T genotype/anxiety interaction and gender in the HyperGEN study.

BACKGROUND: Both anxiety and elevated heart rate (HR) have been implicated in the development of hypertension. The HyperGen cohort, consisting of siblings with severe and mild hypertension, an age-matched random sample of persons from the same base populations, and unmedicated adult offspring of the hypertensive siblings (N = 1,002 men and 987 women), was analyzed for an association of the angiotenisinogen AGTM235T genotype (TT, MT, MM) with an endophenotype, heart rate (HR) in high and low anxious groups. METHODOLOGY: The interaction of AGTM genotype with anxiety, which has been independently associated with hypertension, was investigated adjusting for age, hypertension status, smoking, alcohol consumption, beta blocker medication, body mass index, physical activity and hours of television viewing (sedentary life style). PRINCIPAL FINDINGS: Although there was no main effect of genotype on HR in men or women, high anxious men with the TT genotype had high HR, whereas high anxious men with the MM genotype had low HR. In women, HR was inversely associated with anxiety but there was no interaction with genotype. CONCLUSION/SIGNIFICANCE: The results suggest that high anxiety in men with the TT genotype may increase risk for hypertension whereas the MM genotype may be protective in high anxious men. This type of gene x environment interaction may be one reason why genome wide association studies sometimes fail to replicate. The locus may be important only in combination with certain environmental factors.

Perfluorooctanoic acid, perfluorooctanesulfonate, and serum lipids in children and adolescents: results from the C8 Health Project.

BACKGROUND: Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) are man-made compounds with widespread presence in human sera. In previous occupational and adult studies, PFOA and PFOS were positively associated with serum lipid levels. OBJECTIVE: To interrogate associations between PFOA and PFOS and serum lipids in children and adolescents. DESIGN: Cross-sectional community-based study. SETTING: Mid-Ohio River Valley. PARTICIPANTS: A total of 12 476 children and adolescents included in the C8 Health Project, which resulted from the pretrial settlement of a class action lawsuit pursuant to PFOA contamination of the drinking water supply. MAIN OUTCOME MEASURES: Serum lipids (total, high-density lipoprotein [HDL-C], and low-density lipoprotein [LDL-C] cholesterol and fasting triglycerides). RESULTS: Mean (SD) serum PFOA and PFOS concentrations were 69.2 (111.9) ng/mL and 22.7 (12.6) ng/mL, respectively. In linear regression after adjustment for covariables, PFOA was significantly associated with increased total cholesterol and LDL-C, and PFOS was significantly associated with increased total cholesterol, HDL-C, and LDL-C. Using general linear model analysis of covariance, between the first and fifth quintiles of PFOA there was a 4.6-mg/dL and a 3.8-mg/dL increase in the adjusted mean levels of total cholesterol and LDL-C levels, respectively, and an 8.5-mg/dL and a 5.8-mg/dL increase in the adjusted mean levels of total cholesterol and LDL-C, respectively, between the first and fifth quintiles of PFOS. Increases were 10 mg/dL for some age- and sex-group strata. Observed effects were nonlinear, with larger increases in total cholesterol and LDL-C levels occurring at the lowest range, particularly of PFOA. CONCLUSION: Although the epidemiologic and cross-sectional natures of this study limit causal inferences, the consistently observed associations between increasing PFOA and PFOS and elevated total cholesterol and LDL-C levels warrant further study.

From 'omics' to complex disease: a systems biology approach to gene-environment interactions in cancer.

BACKGROUND: Cancer is a complex disease that involves a sequence of gene-environment interactions in a progressive process that cannot occur without dysfunction in multiple systems, including DNA repair, apoptotic and immune functions. Epigenetic mechanisms, responding to numerous internal and external cues in a dynamic ongoing exchange, play a key role in mediating environmental influences on gene expression and tumor development. HYPOTHESIS: The hypothesis put forth in this paper addresses the limited success of treatment outcomes in clinical oncology. It states that improvement in treatment efficacy requires a new paradigm that focuses on reversing systemic dysfunction and tailoring treatments to specific stages in the process. It requires moving from a reductionist framework of seeking to destroy aberrant cells and pathways to a transdisciplinary systems biology approach aimed at reversing multiple levels of dysfunction. CONCLUSION: Because there are many biological pathways and multiple epigenetic influences working simultaneously in the expression of cancer phenotypes, studying individual components in isolation does not allow an adequate understanding of phenotypic expression. A systems biology approach using new modeling techniques and nonlinear mathematics is needed to investigate gene-environment interactions and improve treatment efficacy. A broader array of study designs will also be required, including prospective molecular epidemiology, immune competent animal models and in vitro/in vivo translational research that more accurately reflects the complex process of tumor initiation and progression.