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The ETS transcription factor Elf-4 is an important regulator of hematopoietic stem cell (HSC) and T cell homeostasis. To gain insights into the transcriptional circuitry within which Elf-4 operates, we used comparative sequence analysis coupled with chromatin immunoprecipitation (ChIP) with microarray technology (ChIP-chip) assays for specific chromatin marks to identify three promoters and two enhancers active in hematopoietic and endothelial cell lines. Comprehensive functional validation of each of these regulatory regions in transgenic mouse embryos identified a tissue-specific enhancer (-10E) that displayed activity in fetal liver, dorsal aorta, vitelline vessels, yolk sac, and heart. Integration of a ChIP-sequencing (ChIP-Seq) data set for 10 key stem cell transcription factors showed Pu.1, Fli-1, and Erg were bound to the -10E element, and mutation of three highly conserved ETS sites within the enhancer abolished its activity. Finally, the transcriptional repressor Gfi1b was found to bind to and repress one of the Elf-4 promoters (-30P), and we show that this repression of Elf-4 is important for the maturation of primary fetal liver erythroid cells. Taken together, our results provide a comprehensive overview of the transcriptional control of Elf-4 within the hematopoietic system and, thus, integrate Elf-4 into the wider transcriptional regulatory networks that govern hematopoietic development.

In animal models, inflammatory processes have been shown to have an important role in the development of kidney disease. In humans, however, the independent relation between markers of inflammation and the risk of chronic kidney disease (CKD) is not known. To clarify this, we examined the relationship of several inflammatory biomarker levels (high-sensitivity C-reactive protein, tumor necrosis factor-α receptor 2, white blood cell count, and interleukin-6) with the risk of developing CKD in a population-based cohort of up to 4926 patients with 15 years of follow-up. In cross-sectional analyses, we found that all these inflammation markers were positively associated with the outcome of interest, prevalent CKD. However, in longitudinal analyses examining the risk of developing incident CKD among those who were CKD-free at baseline, only tumor necrosis factor-α receptor 2, white blood cell count, and interleukin-6 levels (hazard ratios comparing highest with the lowest tertile of 2.10, 1.90, and 1.45, respectively), and not C-reactive protein (hazard ratio 1.09), were positively associated with incident CKD. Thus, elevations of most markers of inflammation predict the risk of developing CKD. Each marker should be independently verified.

Background: Atherosclerosis may be associated with cognitive function; however the studies are few, especially among midlife adults., Methods: Participants in the beaver dam offspring study who had cognitive test data and gradable carotid artery ultrasound scans were included (n=2794, mean age: 49 years). Atherosclerosis was measured by carotid intima-media thickness (IMT) and the presence of plaque. Cognitive function was measured by the trail making test (TMT), grooved pegboard test (GPT) and mini-mental state examination (MMSE). Generalized cognitive function was defined by a summary score calculated from the TMT and GPT. Linear regression was used to evaluate the associations between carotid atherosclerosis and cognitive function tests., Results: Larger IMT was associated with lower GPT, MMSE and the summary score adjusting for multiple factors, the coefficients were: 13.8s (p<0.0001), -0.6 (p=0.007), and 0.47 (p=0.01), respectively for 1mm increase in IMT. Plaque scores were significantly associated with TMT-B, GPT, MMSE, and the summary score adjusting for age, sex and education. The associations remained statistically significant after further adjustments except for the association with TMT-B, which was attenuated and no longer significant., Conclusions: Our results show the significant associations between markers of carotid atherosclerosis and cognitive function in a cohort of persons aged 21-84 years. Longitudinal studies are needed to further examine these associations., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess the prevalence of tinnitus along with factors potentially associated with having tinnitus., Design: Data were from the Beaver Dam Offspring Study, an epidemiological cohort study of aging., Study Sample: After a personal interview and audiometric examination, participants (n = 3267, ages 21-84 years) were classified as having tinnitus if in the past year they reported having tinnitus of at least moderate severity or that caused difficulty in falling asleep., Results: The prevalence of tinnitus was 10.6%. In a multivariable logistic regression model adjusting for age and sex, the following factors were associated with having tinnitus: hearing impairment (Odds Ratio (OR) = 3.20), currently having a loud job (OR = 1.90), history of head injury (OR = 1.84), depressive symptoms (OR = 1.82), history of ear infection (men, OR = 1.75), history of target shooting (OR = 1.56), arthritis (OR = 1.46), and use of NSAID medications (OR = 1.33). For women, ever drinking alcohol in the past year was associated with a decreased risk of having tinnitus (OR = 0.56)., Conclusions: These results suggest that tinnitus is a common symptom in this cohort and may be associated with some modifiable risk factors.

Background: Recent cross-sectional studies have reported an association between retinal vessel caliber and chronic kidney disease (CKD), but the direction of the association between these 2 processes is not clear. In a prospective study with multiple measurements of retinal vessel diameters and serum creatinine, we examined whether baseline retinal vessel diameter is associated with future risk of decreased kidney function, or vice versa., Study Design: Population-based cohort study., Setting & Participants: 3,199 Wisconsin adults aged 43-84 years who were followed up prospectively for 15 years., Predictor: Baseline retinal arteriolar and venular diameters for analysis 1 and baseline estimated glomerular filtration rate (eGFR) categories for analysis 2., Outcomes & Measurements: For analysis 1, incident CKD, defined as eGFR <60 mL/min/1.73 m(2) accompanied by a 25% decrease in eGFR, during follow-up. For analysis 2, incident retinal arteriolar narrowing, defined as a central retinal arteriolar equivalent measurement <144.0 μm, and incident retinal venular dilation, defined as a central retinal venular equivalent measurement >243.8 μm., Results: Baseline retinal arteriolar and venular diameters were not associated with 15-year risk of incident CKD. After adjustment for age, sex, diabetes, hypertension, and other confounders, the multivariable HR of incident CKD comparing the narrowest with the widest quartile was 1.15 (95% CI, 0.74-1.80) for retinal arteriolar diameter and 1.05 (95% CI, 0.67-1.67) for retinal venular diameter. Similarly, there was no significant association between eGFR and 15-year risk of incident retinal arteriolar narrowing or retinal venular widening. Compared with eGFR >90 mL/min/1.73 m(2) (referent), the multivariable HR for those with eGFR <45 mL/min/1.73 m(2) was 1.66 (95% CI, 0.93-2.96) for incident retinal arteriolar narrowing and 0.60 (95% CI, 0.17-1.85) for retinal venular widening., Limitations: Lack of data for albuminuria and loss to follow-up., Conclusions: Retinal vessel diameters and CKD may run together through shared mechanisms, but are not causally related., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Research on children's responses to wartime trauma has mostly addressed Post-Traumatic Stress Disorder (PTSD). However, PTSD is only one aspect of a complex set of responses. This study proposes to expand knowledge of well-being in children exposed to political violence through widening the conceptualization of well-being beyond PTSD, morbidity, and mortality by measuring health-related quality of life (HRQOL) and its facets, physical health, and psychosocial health., Methods: In 2007, we used a cross-sectional random sample of kindergartens to examine factors associated with HRQOL, as measured by the PedsQL 4.0, in 350 preschoolers in the Gaza Strip, Palestine, where political violence and deprivation are widespread., Results: About 65% of the mothers reported severely impaired psychosocial and emotional functioning in their children. Preschoolers had lower HRQOL than the US reference sample and samples of children in other low income countries with large effect size. HRQOL was comparable to those of US children with several chronic diseases. Factors associated with lower HRQOL were older child age, male gender, and more exposures to traumatic events. Factors associated with HRQOL subscales were for lower psychosocial health: older child age, history of food, water, and electricity deprivation during incursion, and witnessing assassination of people by rockets. For lower physical health: older child age, history of food, water, and electricity deprivation during incursion, and having heard of a killing of a friend by soldiers., Conclusions: HRQOL, including psychosocial health and emotional functioning is often severely impaired among preschoolers in the Gaza Strip. Exposure to both violent and non-violent negative events was associated with HRQOL in preschoolers.

Objective: This study investigated the long-term effects of socioeconomic status (SES) on atherosclerosis., Methods: Data from the Epidemiology of Hearing Loss Study and the Beaver Dam Eye Study (Beaver Dam, WI, 1998-2000), were used to examine adult SES (education, household income, and longest-held job) and childhood SES (household density and parental home ownership at age 13) associations with carotid intima-media thickness (IMT) and carotid plaque in a cohort of 2042 men and women aged 53 to 94 years., Results: For education, income, and occupation (women), those in the lowest SES group had statistically larger age-sex-adjusted IMT than those in the highest SES group (<12 vs. >12 years education: 0.92 vs. 0.86 mm respectively, P<0.0001), (<$10,000 vs. >$45,000: 0.97 vs. 0.87 mm, P<0.0001), (operator/fabricator/labor vs. manager/professional: 0.89 vs. 0.82 mm, P<0.001). Associations were similar using carotid plaque as the outcome. Participants with low levels of both adult and childhood SES measures had age-sex-adjusted IMT greater than those with persistently high levels of SES (0.93 vs. 0.84 mm, P<0.0001)., Conclusions: Measures of SES at two points in the life-span were associated with subclinical atherosclerosis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The control of differential gene expression is central to all metazoan biology. Haematopoiesis represents one of the best understood developmental systems where multipotent blood stem cells give rise to a range of phenotypically distinct mature cell types, all characterised by their own distinctive gene expression profiles. Small combinations of lineage-determining transcription factors drive the development of specific mature lineages from multipotent precursors. Given their powerful regulatory nature, it is imperative that the expression of these lineage-determining transcription factors is under tight control, a fact underlined by the observation that their misexpression commonly leads to the development of leukaemia. Here we review recent studies on the transcriptional control of key haematopoietic transcription factors, which demonstrate that gene loci contain multiple modular regulatory regions within which specific regulatory codes can be identified, that some modular elements cooperate to mediate appropriate tissue-specific expression, and that long-range approaches will be necessary to capture all relevant regulatory elements. We also explore how changes in technology will impact on this area of research in the future.

Aims: This study of participants in a US drug treatment court describes the relationship between the imposition of short-term jail sanctions and substance abuse treatment dropout, and examines offender characteristics moderating or modifying the impact of jail sanctions on treatment dropout., Methods: Data were derived from administrative information collected by the Dane County Wisconsin Drug Treatment Court from 1996-2004 on all 573 participants achieving a final disposition of treatment completion or failure during those program years. Iterative Cox proportional hazards models of time to treatment failure were created; jail sanctions during drug court participation were framed as time-dependent covariates. A theoretical framework and specific statistical criteria guided construction of a final parsimonious model of time to treatment drop-out., Findings: Treatment failure was associated with unemployment [hazard ratio (HR) in unemployed versus employed = 1.41, P-value 0.0079], lower educational attainment (HR in high school non-graduate versus graduate = 1.41, P = 0.02) and application of the first jail sanction (HR 2.71, P < 0.001). The association between treatment failure and a first sanction was considerably stronger for sanctions administered earlier in participation (HR for sanction 1 at <30 days 11.34, P-value 0.0002). Conclusions  An initial jail sanction for non-adherence may be more likely to foster treatment compliance in less refractory individuals (i.e. those not already acclimated or socialized to incarceration or other corrections interventions). More stringent supervisory conditions and individualized services may be required to reintegrate such offenders and promote longer-term public safety., (© 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.)

Background: Evidence-based public health requires the existence of reliable information systems for priority setting and evaluation of interventions. Existing data systems in the United States are either too crude (e.g., vital statistics), rely on administrative data (e.g., Medicare) or, because of their national scope (e.g., NHANES), lack the discriminatory power to assess specific needs and to evaluate community health activities at the state and local level. This manuscript describes the rationale and methods of the Survey of the Health of Wisconsin (SHOW), a novel infrastructure for population health research., Methods/design: The program consists of a series of independent annual surveys gathering health-related data on representative samples of state residents and communities. Two-stage cluster sampling is used to select households and recruit approximately 800-1,000 adult participants (21-74 years old) each year. Recruitment and initial interviews are done at the household; additional interviews and physical exams are conducted at permanent or mobile examination centers. Individual survey data include physical, mental, and oral health history, health literacy, demographics, behavioral, lifestyle, occupational, and household characteristics as well as health care access and utilization. The physical exam includes blood pressure, anthropometry, bioimpedance, spirometry, urine collection and blood draws. Serum, plasma, and buffy coats (for DNA extraction) are stored in a biorepository for future studies. Every household is geocoded for linkage with existing contextual data including community level measures of the social and physical environment; local neighborhood characteristics are also recorded using an audit tool. Participants are re-contacted bi-annually by phone for health history updates., Discussion: SHOW generates data to assess health disparities across state communities as well as trends on prevalence of health outcomes and determinants. SHOW also serves as a platform for ancillary epidemiologic studies and for studies to evaluate the effect of community-specific interventions. It addresses key gaps in our current data resources and increases capacity for etiologic, applied and translational population health research. It is hoped that this program will serve as a model to better support evidence-based public health, facilitate intervention evaluation research, and ultimately help improve health throughout the state and nation.

Ets transcription factors play important roles during the development and maintenance of the haematopoietic system. One such factor, Elf-1 (E74-like factor 1) controls the expression of multiple essential haematopoietic regulators including Scl/Tal1, Lmo2 and PU.1. However, to integrate Elf-1 into the wider regulatory hierarchies controlling haematopoietic development and differentiation, regulatory elements as well as upstream regulators of Elf-1 need to be identified. Here, we have used locus-wide comparative genomic analysis coupled with chromatin immunoprecipitation (ChIP-chip) assays which resulted in the identification of five distinct regulatory regions directing expression of Elf-1. Further, ChIP-chip assays followed by functional validation demonstrated that the key haematopoietic transcription factor PU.1 is a major upstream regulator of Elf-1. Finally, overexpression studies in a well-characterized erythroid differentiation assay from primary murine fetal liver cells demonstrated that Elf-1 downregulation is necessary for terminal erythroid differentiation. Given the known activation of PU.1 by Elf-1 and our newly identified reciprocal activation of Elf-1 by PU.1, identification of an inhibitory role for Elf-1 has significant implications for our understanding of how PU.1 controls myeloid-erythroid differentiation. Our findings therefore not only represent the first report of Elf-1 regulation but also enhance our understanding of the wider regulatory networks that control haematopoiesis.

Runx1 is a developmentally regulated transcription factor that is essential for haemopoiesis. Runx1 can bind as a monomer to the core consensus sequence TGTGG, but binds more efficiently as a hetero-dimer together with the non-DNA binding protein CBFβ as a complex termed core binding factor (CBF). Here, we demonstrated that CBF can also assemble as a dimeric complex on two overlapping Runx1 sites within the palindromic sequence TGTGGCTGCCCACA in the human granulocyte macrophage colony-stimulating factor enhancer. Furthermore, we demonstrated that binding of Runx1 to the enhancer is rigidly controlled at the level of chromatin accessibility, and is dependent upon prior induction of NFAT and AP-1, which disrupt a positioned nucleosome in this region. We employed in vivo footprinting to demonstrate that, upon activation of the enhancer, both sites are efficiently occupied. In vitro binding assays confirmed that two CBF complexes can bind this site simultaneously, and transfection assays demonstrated that both sites contribute significantly to enhancer function. Computer modelling based on the Runx1/CBFβ/DNA crystal structure further revealed that two molecules of CBF could potentially bind to this class of palindromic sequence as a dimeric complex in a conformation whereby both Runx1 and CBFβ within the two CBF complexes are closely aligned.

Background: Depression and obesity are both important public health problems. However, it is not clear whether obesity contributes to depression. Our study aims to evaluate the association between obesity and possible depression., Methods: During the Beaver Dam Offspring Study examination, participants' body weight and height were measured with a Detecto 758C digital scale with height bar, and depression symptoms were measured with the Center for Epidemiological Studies-Depression (CES-D) Scale. Other relevant information, such as demographic factors, lifestyle factors, comorbidities, and use of antidepressants, was also collected during the examination. There were 2,641 participants included in the analyses., Results: Obesity was associated with possible depression measured by CES-D Scale (OR=1.6, 95% CI: 1.3-2.0) after controlling for age and gender. The association remained similar after further adjustments. Obesity was significantly associated with all four domains measured by CES-D Scale after controlling for age and sex, with the largest effect on "Somatic Complaints" domain (beta .15, 95% CI: 0.0836-0.223). The association with "Interpersonal Difficulties" was not significant after further adjustments., Conclusions: Obesity was associated with a higher risk of possible depression and had different influences on specific domains of depression symptoms measured by CES-D Scale. These findings suggest the need for longitudinal studies on the effects of obesity on specific depression symptoms., ((c) 2010 Wiley-Liss, Inc.)

Objectives: To determine the prevalence of age-related macular degeneration (AMD) and to examine how retinal drusen, retinal pigmentary abnormalities, and early AMD are related to age, sex, and other risk factors., Participants: A total of 2810 people aged 21 to 84 years participating in the Beaver Dam Offspring Study., Methods: The presence and severity of various characteristics of drusen and other lesions typical of AMD were determined by grading digital color fundus images using the Wisconsin Age-Related Maculopathy Grading System., Results: Early AMD was present in 3.4% of the cohort and varied from 2.4% in those aged 21 to 34 years to 9.8% in those aged 65 years or older. In a multivariable model (expressed as odds ratio; 95% confidence interval), age (per 5 years of age, 1.22; 1.09-1.36), being male (1.65; 1.01-2.69), more pack-years of cigarettes smoked (1-10 vs 0, 1.31; 0.75-2.29; >or=11 vs 0, 1.67; 1.03-2.73), higher serum high-density lipoprotein cholesterol level (per 5 mg/dL, 0.91; 0.83-0.998), and hearing impairment (2.28; 1.41-3.71) were associated with early AMD. There were no associations of blood pressure level, body mass index, physical activity level, history of heavy drinking, white blood cell count, hematocrit level, platelet count, serum total cholesterol level, or carotid intimal-medial thickness with early AMD., Conclusions: These data indicate that early AMD is infrequent before age 55 years but increases with age thereafter. Early AMD is related to modifiable risk factors, eg, smoking and serum high-density lipoprotein cholesterol level.

Background: Silencing of transgenes in mice is a common phenomenon typically associated with short multi-copy transgenes. We have investigated the regulation of the highly inducible human granulocyte-macrophage colony-stimulating-factor gene (Csf2) in transgenic mice., Results: In the absence of any previous history of transcriptional activation, this transgene was expressed in T lineage cells at the correct inducible level in all lines of mice tested. In contrast, the transgene was silenced in a specific subset of lines in T cells that had encountered a previous episode of activation. Transgene silencing appeared to be both transcription-dependent and mediated by epigenetic mechanisms. Silencing was accompanied by loss of DNase I hypersensitive sites and inability to recruit RNA polymerase II upon stimulation. This pattern of silencing was reflected by increased methylation and decreased acetylation of histone H3 K9 in the transgene. We found that silenced lines were specifically associated with a single pair of tail-to-tail inverted repeated copies of the transgene embedded within a multi-copy array., Conclusions: Our study suggests that epigenetic transgene silencing can result from convergent transcription of inverted repeats which can lead to silencing of an entire multi-copy transgene array. This mechanism may account for a significant proportion of the reported cases of transgene inactivation in mice.

Objective: To compare refraction measured before and after pharmacologic cycloplegia., Methods: This study used preliminary data from the Beaver Dam Offspring Study, which includes adult children of participants in the population-based Epidemiology of Hearing Loss Study of older adults living in Beaver Dam, Wisconsin. Data were available for 5018 eyes of 2529 participants. Refraction was defined by the spherical equivalent (SE), using autorefractor readings. Differences were calculated as the SE after drops were administered minus the SE before drops were administered. Myopia was defined as SE of -1 diopter (D) or less; emmetropia, as SE more than -1 D and less than 1 D; and hyperopia, as SE of 1 D or more., Results: The mean age was 48 years (range, 22-84 years). The mean difference in SE between measurements before and after cycloplegia was 0.29 D (95% confidence interval, 0.28-0.31). The difference decreased with age and varied by refractive status for participants younger than 50 years, with the largest differences observed among young persons with hyperopic refractive errors. Across all age groups, agreement on classifications of refraction was high (84%-92%)., Conclusions: Overall, clinically inconsequential differences were observed between SEs before and after pharmacologic cycloplegia, suggesting that cycloplegia may not be necessary in epidemiological studies of refraction in adults.

This paper puts forward the design, construction and testing of a new automatic system for angular-response measurement and calibration in radiometric instruments. Its main characteristics include precision, speed, resolution, noise immunity, easy programming and operation. The developed system calculates the cosine error of the radiometer under test by means of a virtual instrument, from the measures it takes and through a mathematical procedure, thus allowing correcting the radiometer with the aim of preventing cosine error in its measurements.

Background: Some studies suggest that high levels of blood and hair mercury (Hg) increase the risk of atherothrombotic diseases, an effect that may be explained by oxidative damage to the vascular endothelium., Objectives: We tested whether high Hg levels impair the vasodilating function of the vascular endothelium or increase blood pressure., Methods: We measured the association between high blood and hair Hg and brachial artery flow mediated vasodilation (FMD%), middle cerebral artery reactivity to CO2 (MCAR%) and hypertensive status in 101 participants in the Wisconsin Sleep Cohort Study (mean age of 59.4 years; 52.5% male). Whole blood total Hg and hair total Hg were tested using inductively coupled plasma mass spectrometry and cold vapor atomic fluorescence spectrometry, respectively., Results: Geometric mean blood and hair Hg were 1.16 microg/L and 270.1 ng/g. Blood and hair Hg were not significantly associated with FMD% and MCAR%. However, after adjustment for other risk factors, people in the upper quartile of blood Hg were 1.9 times (P=0.23) more likely to be hypertensive and those in the upper quartile of hair Hg were more than 4 times more likely (P=0.02)., Conclusion: High hair and blood Hg levels do not seem to influence vascular reactivity, but may increase the risk of hypertension.

Background: Sleep disordered breathing (SDB) has been associated with cardiovascular disease, hypertension, and insulin resistance. This article examines the association between SDB and the prevalence of metabolic syndrome (MS) in a community-based sample., Methods: A subset of participants in the Wisconsin Sleep Cohort Study (N=546) participated in an ancillary study to measure vascular and metabolic function. SDB was characterized using the apnea-hypopnea index (AHI) obtained in the polysomnography study closest to the collection of the metabolic measures. MS was defined using the National Cholesterol Education Program definition, and the homeostasis model assessment method (HOMA) was used to characterize insulin resistance., Results: SDB was significantly correlated with insulin resistance (Spearman r correlation between AHI and HOMA=0.30, P<0.0001). Compared with those without SDB (AHI <5), the age-sex-adjusted odds ratios of MS associated with mild (AHA 5-14.9) and moderate/severe SDB (AHI > or = 15 or CPAP) were 4.0 (95% CI 2.6, 6.3) and 5.3 (95% CI 3.2, 8.8), respectively. Additional adjustment for markers of sympathetic or neuroendocrine activation (urinary norepinephrine, cortisol, heart rate variability) did not materially alter these estimates. These associations were weaker but remained statistically significant after adjusting for body mass index., Conclusion: SDB might be considered an integral component of MS.

Context: Untreated sleep apnea is a prevalent but treatable condition of breathing pauses during sleep. With approximately 15% of the US population affected, understanding of the total health burden is necessary to guide policy, population initiatives, and clinical practice to reduce the prevalence of this condition., Objective: To outline the history and need for a population approach to understanding sleep apnea and provide a review of the first longitudinal population study of this disorder., Data Source: The results of cross-sectional and longitudinal data from 1500 participants in the Wisconsin Sleep Cohort, initiated 2 decades ago, illustrate the population burden of sleep apnea., Results: The prevalence of sleep apnea is increasing with trends of increased obesity. Prospective findings from 4- to 15-year follow-up data indicate untreated sleep apnea predicts increased blood pressure, hypertension, stroke, depression, and mortality., Conclusions: The high prevalence of untreated sleep apnea and links to serious morbidity and mortality underscore the population burden of this condition and the need for greater clinical recognition and strategies to reduce prevalence.

Olfactory function may be important for environmental and nutritional safety and enjoyment. Population-based epidemiological studies of olfaction are needed to understand the magnitude of the health burden, identify modifiable risk factors, and develop and test prevention and treatment strategies for olfactory impairment. However, measuring olfaction in large studies is challenging, requiring repeatable, efficient methods that can measure change over time. Two large cohort studies, the Epidemiology of Hearing Loss Study (EHLS) and the Beaver Dam Offspring Study (BOSS), included olfactory testing. In both studies, the San Diego Odor Identification Test (SDOIT) was used to measure olfaction. Subjects were asked to identify eight common household odors (such as coffee and chocolate). Olfactory impairment was defined as correctly identifying fewer than six out of eight odorants after two trials. The EHLS participants were age 53-95 years at the time of the first measurement (1998-2000), and participants in the BOSS were age 21-84 years. The prevalence of olfactory impairment in the EHLS was 25% overall, more common in men than women, and increased with age. Five years later olfaction was measured a second time and the majority (84%) of the EHLS participants were classified the same. Among those with impairment at the base line nearly one-third (31%) improved to unimpaired. This heterogeneity in olfactory impairment has unique implications for data analyses and predicting outcomes and associations. Preliminary data from the BOSS suggest the prevalence of olfactory impairment may be lower in younger generations. All these factors point to a continuing need for epidemiological studies of olfaction.

Taste or gustatory function may play an important role in determining diet and nutritional status and therefore indirectly impact health. Yet there have been few attempts to study the spectrum of taste function and dysfunction in human populations. Epidemiologic studies are needed to understand the impact of taste function and dysfunction on public health, to identify modifiable risk factors, and to develop and test strategies to prevent clinically significant dysfunction. However, measuring taste function in epidemiologic studies is challenging and requires repeatable, efficient methods that can measure change over time. Insights gained from translating laboratory-based methods to a population-based study, the Beaver Dam Offspring Study (BOSS) will be shared. In this study, a generalized labeled magnitude scale (gLMS) method was used to measure taste intensity of filter paper disks saturated with salt, sucrose, citric acid, quinine, or 6-n-propylthiouracil, and a gLMS measure of taste preferences was administered. In addition, a portable, inexpensive camera system to capture digital images of fungiform papillae and a masked grading system to measure the density of fungiform papillae were developed. Adult children of participants in the population-based Epidemiology of Hearing Loss Study in Beaver Dam, Wisconsin, are eligible for this ongoing study. The parents were residents of Beaver Dam and 43-84 years of age in 1987-1988; offspring ranged in age from 21-84 years in 2005-2008. Methods will be described in detail and preliminary results about the distributions of taste function in the BOSS cohort will be presented.

The human interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating-factor (GM-CSF, or CSF2) gene cluster arose by duplication of an ancestral gene. Although just 10 kb apart and responsive to the same signals, the IL-3 and GM-CSF genes are nevertheless regulated independently by separate, tissue-specific enhancers. To understand the differential regulation of the IL-3 and GM-CSF genes we have investigated a cluster of three ubiquitous DNase I-hypersensitive sites (DHSs) located between the two genes. We found that each site contains a conserved CTCF consensus sequence, binds CTCF, and recruits the cohesin subunit Rad21 in vivo. The positioning of these sites relative to the IL-3 and GM-CSF genes and their respective enhancers is conserved between human and mouse, suggesting a functional role in the organization of the locus. We found that these sites effectively block functional interactions between the GM-CSF enhancer and either the IL-3 or the GM-CSF promoter in reporter gene assays. These data argue that the regulation of the IL-3 and the GM-CSF promoters depends on the positions of their enhancers relative to the conserved CTCF/cohesin-binding sites. We suggest that one important role of these sites is to enable the independent regulation of the IL-3 and GM-CSF genes.

Background: Sleep-disordered breathing (SDB) is a treatable but markedly under-diagnosed condition of frequent breathing pauses during sleep. SDB is linked to incident cardiovascular disease, stroke, and other morbidity. However, the risk of mortality with untreated SDB, determined by polysomnography screening, in the general population has not been established., Methods: An 18-year mortality follow-up was conducted on the population-based Wisconsin Sleep Cohort sample (n = 1522), assessed at baseline for SDB with polysomnography, the clinical diagnostic standard. SDB was described by the number of apnea and hypopnea episodes/hour of sleep; cutpoints at 5, 15 and 30 identified mild, moderate, and severe SDB, respectively. Cox proportional hazards regression was used to estimate all-cause and cardiovascular mortality risks, adjusted for potential confounding factors, associated with SDB severity levels., Results: All-cause mortality risk, adjusted for age, sex, BMI, and other factors was significantly increased with SDB severity. The adjusted hazard ratio (HR, 95% CI) for all-cause mortality with severe versus no SDB was 3.0 (1.4,6.3). After excluding persons who had used CPAP treatment (n = 126), the adjusted HR (95% CI) for all-cause mortality with severe versus no SDB was 3.8 (1.6,9.0); the adjusted HR (95% CI) for cardiovascular mortality was 5.2 (1.4,19.2). Results were unchanged after accounting for daytime sleepiness., Conclusions: Our findings of a significant, high mortality risk with untreated SDB, independent of age, sex, and BMI underscore the need for heightened clinical recognition and treatment of SDB, indicated by frequent episodes of apnea and hypopnea, irrespective of symptoms of sleepiness.

Objectives: To examine the extent to which subjective and objective sleep quality are related to age independent of chronic health conditions., Design: Cross-sectional study., Setting: The Sleep Heart Health Study (SHHS) is a multicenter study designed to determine the cardiovascular consequences and the natural history of sleep disordered breathing., Participants: Five thousand four hundred seven community-dwelling adults who participated in the SHHS (mean age 63, range 45-99; 52% women)., Measurements: Unattended home polysomnography (PSG) and sleep questionnaires., Results: Older age was associated with shorter sleep time, diminished sleep efficiency, and more arousals in men and women. In men, age was independently associated with more Stage 1 and Stage 2 sleep and less slow-wave (Stage 3 to 4) and rapid eye movement sleep. In women, older age was less strongly associated according to linear trend with sleep stage. Conversely, poor subjective sleep quality was not associated with older age in men, but older women had more trouble falling asleep, and there was a trend toward older women having more problems with waking up during the night and waking up too early. Associations between self-report and directly measured sleep time and sleep latency were low to moderate across age groups (correlation coefficient=0.06-0.32)., Conclusion: Older age was more strongly associated with poorer sleep according to PSG in men than women, yet the subjective report of poor sleep with older age was stronger in women. The higher prevalence of chronic health conditions, including sleep apnea, in older adults did not explain changes of sleep parameters with aging and age-sex differences in these relationships.

Objective: We examined the association between increasing serum GGT levels and PAD in the US general population., Methods: Cross-sectional study among 3941 National Health and Nutrition Examination Survey 1999-2002 participants aged >or=40 years. Main outcome-of-interest was PAD defined as ankle-brachial index <0.9 (n=219)., Results: Overall, serum GGT levels were positively associated with PAD among men but not women (p-interaction=0.0421). Among men, the multivariable odds ratio (OR) [95% confidence intervals (CI)] comparing the highest quartile of serum GGT (>35U/L) to the lowest quartile (<16U/L) was 4.25 (1.65-10.94); p-trend=0.0008. Also the observed positive association between GGT quartiles and PAD among men was predominantly present among non-Hispanic whites and current nondrinkers (multivariable OR [95% CI] comparing the highest quartile of serum GGT to the lowest quartile was 10.59 [2.31-48.55]; p-trend=0.0104). In contrast among women, the multivariable OR (95% CI) comparing the highest quartile of serum GGT to the lowest quartile was 0.76 (0.41-1.41); p-trend=0.8308., Conclusions: There was a positive association between serum GGT level and PAD among men, particularly non-Hispanic white and nondrinker men, but not among women. Future prospective studies are required to clarify the temporal nature of this relationship and to confirm the observed gender-specific nature of this association.

Background: Higher serum uric acid levels have been implicated in the development and progression of atherosclerotic cardiovascular disease. However, it is not clear whether serum uric acid levels are related to subclinical measures of cardiovascular disease, including peripheral arterial disease (PAD). We examined the association between increasing serum uric acid levels and PAD in the US general population., Methods: A cross-sectional study was conducted among 3987 National Health and Nutrition Examination Survey 1999-2002 participants aged > or =40 years, without clinical history of cardiovascular disease. Main outcome-of-interest was PAD defined as ankle-brachial index <0.9 (n=229)., Results: Higher serum uric acid levels were positively associated with PAD, independent of smoking, body mass index (BMI), hypertension, diabetes, serum total cholesterol, serum creatinine, and other confounders. Multivariable odds ratio (OR) [95 percent confidence intervals (CI)] comparing serum uric acid levels > or =75th percentile (> or =380.8 micromol/L) to uric acid levels <50th percentile (<315.6 micromol/L) was 1.62 (1.08-2.44), p-trend=0.015. This association persisted in separate analysis among men and women. Further, the results were consistent in subgroup analyses by categories of age, current smoking, BMI, and diabetes mellitus., Conclusions: Higher serum uric acid levels are associated with PAD in the US general population. These results suggest that PAD may be an important indicator of the reported association between higher serum uric acid levels and clinical cardiovascular disease. Future prospective studies are required to clarify the temporal nature of this relationship.

Objectives: We explored whether higher levels of acculturation were associated with higher rates of cigarette smoking among pregnant Hispanic women residing in the United States., Methods: We evaluated data from the Latina Gestational Diabetes Mellitus Study, a prospective study of 1231 Hispanic prenatal care patients conducted from 2000 to 2004 in Massachusetts. Self-reported data on acculturation, cigarette smoking, and covariates were collected by bilingual interviewers using a questionnaire. We conducted logistic regression multivariate analyses to examine the impact of acculturation level on the odds of smoking., Results: Overall, 21% of women reported smoking during pregnancy. Acculturation was associated with elevated smoking rates in pregnant Hispanic women. US-born Hispanic women who preferred English had more than twice the odds of smoking compared with Puerto Rican or foreign-born Hispanic women who preferred Spanish (odds ratio [OR]=2.76, 95% confidence interval [CI] 1.36, 5.63)., Conclusions: Our findings suggest that higher-acculturated Hispanic women living in the United States are more likely to smoke cigarettes during pregnancy than are less-acculturated Hispanic women. These results will inform interventions aimed at reducing cigarette smoking during pregnancy among US Hispanic women.

Background: Evidence regarding the safety profile of drugs may vary depending on study sponsorship. We aimed to evaluate differences between studies funded by the pharmaceutical manufacturer of the drug (PF) and those with no pharmaceutical funding (NoPF) regarding the finding and interpretation of adverse effects of inhaled corticosteroids., Methods: We assessed the safety reporting of inhaled corticosteroids in 275 PF and 229 NoPF studies identified by a MEDLINE search using prespecified criteria., Results: Overall, the finding of statistically significant differences for adverse effects was significantly less frequent in PF (34.5%) than in NoPF (65.1%) studies (prevalence ratio, 0.53; 95% confidence interval, 0.44-0.64). This association became nonsignificant (prevalence ratio, 0.94; 95% confidence interval, 0.77-1.15) after controlling for design features (such as dose or use of parallel groups) that tended to be associated with less frequent finding of adverse effects and were more common in PF studies. Among studies finding a statistically significant increase in adverse effects associated with the study drug, the authors of PF articles concluded that the drug was "safe" more frequently than the authors of NoPF studies (prevalence ratio, 3.68; 95% confidence interval, 2.14-6.33)., Conclusions: The type of funding may have determinant effects on the design of studies and on the interpretation of findings: funding by the industry is associated with design features less likely to lead to finding statistically significant adverse effects and with a more favorable clinical interpretation of such findings. Disclosure of conflicts of interest should be strengthened for a more balanced opinion on the safety of drugs.

Background: Inflammatory processes are implicated in the development and progression of atherosclerotic cardiovascular disease (CVD). C-reactive protein (CRP), a specific marker of inflammation, has been found to be related to CVD and subclinical atherosclerosis, including peripheral arterial disease (PAD). However, it is not entirely clear whether CRP levels are related to subclinical CVD independent of traditional risk factors, including diabetes and hypertension. We examined the association between CRP levels and PAD among US adults free of CVD, diabetes, and hypertension., Methods: Cross-sectional study was performed among 1611 National Health and Nutrition Examination Survey 1999-2002 participants aged > or = 40 years and without CVD, diabetes, or hypertension. Main outcome of interest was PAD defined as ankle-brachial index < 0.9., Results: Higher CRP levels were positively associated with PAD, independent of smoking, waist circumference, body mass index, blood pressure, glycosylated hemoglobin, serum total cholesterol, and other confounders. Multivariable odds ratio (95% CI) comparing quartile 4 of CRP (> 0.54 mg/dL) to quartile 1 (< 0.09 mg/dL) was 6.38 (1.77-22.96); P trend = .005. This association persisted in separate analysis in men and women. Furthermore, the results were consistent in subgroup analyses by categories of age, education, smoking, and body mass index. In nonparametric models, the positive association between CRP and PAD seemed to be present across the full range of CRP without any apparent threshold., Conclusions: Higher CRP levels are associated with PAD among US adults free of CVD, diabetes, and hypertension. These results suggest that inflammatory mechanisms related to atherosclerosis may be operative even among clinically healthy adults.

This paper examines the association between trait anger and subclinical carotid artery atherosclerosis among 14,098 Black or White men and women, aged 48-67 years, in the Atherosclerosis Risk in Communities Study cohort, 1990-1992. Trait anger was assessed using the 10-item Spielberger Trait Anger Scale. Carotid atherosclerosis was determined by an averaged measure of the wall intimal-medial thickness (IMT) of the carotid bifurcation and of the internal and common carotids, measured by high-resolution B-mode ultrasound. In the full study cohort, trait anger and carotid IMT were significantly and positively associated (p = 0.04). In race-gender stratified analysis, the association was strongest and independent only in Black men, among whom a significant trait anger-carotid IMT relation was observed for both the overall trait anger measure (p = 0.004) and the anger reaction dimension (p = 0.001). In Black men, carotid IMT levels increased across categories of overall trait anger and anger reaction, resulting in clinically significant differences (67 microm (95% confidence interval: 23, 110) and 82 microm (95% confidence interval: 40, 125), respectively) from low to high anger. Sociodemographic, lifestyle, anthropometric, and biologic cardiovascular disease risk factors appear to mediate the relation in Black women, White men, and White women. In conclusion, these findings document disparate race-gender patterns in the association of trait anger with subclinical carotid artery atherosclerosis.

Background: Peripheral arterial disease (PAD), defined by a low ankle-brachial index (ABI), is associated with an increased risk of cardiovascular events, but the risk of coronary heart disease (CHD) over the range of the ABI is not well characterized, nor described for African Americans., Methods: The ABI was measured in 12186 white and African American men and women in the Atherosclerosis Risk in Communities Study in 1987-89. Fatal and non-fatal CHD events were ascertained through annual telephone contacts, surveys of hospital discharge lists and death certificate data, and clinical examinations, including electrocardiograms, every 3 years. Participants were followed for a median of 13.1 years. Age- and field-center-adjusted hazard ratios (HRs) were estimated using Cox regression models., Results: Over a median 13.1 years follow-up, 964 fatal or non-fatal CHD events accrued. In whites, the age- and field-center-adjusted CHD hazard ratio (HR, 95% CI) for PAD (ABI<0.90) was 2.81 (1.77-4.45) for men and 2.05 (1.20-3.53) for women. In African Americans, the HR for men was 4.86 (2.76-8.47) and for women was 2.34 (1.26-4.35). The CHD risk increased exponentially with decreasing ABI as a continuous function, and continued to decline at ABI values > 1.0, in all race-gender subgroups. The association between the ABI and CHD relative risk was similar for men and women in both race groups. A 0.10 lower ABI increased the CHD hazard by 25% (95% CI 17-34%) in white men, by 20% (8-33%) in white women, by 34% (19-50%) in African American men, and by 32% (17-50%) in African American women., Conclusion: African American members of the ARIC cohort had higher prevalences of PAD and greater risk of CHD associated with ABI-defined PAD than did white participants. Unlike in other cohorts, in ARIC the CHD risk failed to increase at high (>1.3) ABI values. We conclude that at this time high ABI values should not be routinely considered a marker for increased CVD risk in the general population. Further research is needed on the value of the ABI at specific cutpoints for risk stratification in the context of traditional risk factors.

Current recommendations, largely based on studies in type 2 diabetes, suggest lower target blood pressures (BPs) for individuals with diabetes than for the general population. However, the effect of lower BP on renal outcomes in type 1 diabetes is uncertain. In a population-based cohort of type 1 diabetes adults (mean age: 33.1 years) based in Wisconsin, of which the distribution of baseline BP was in the low-normal range, we examined the relationship between decreasing categories of systolic and diastolic BP and the 16-year incidence of proteinuria (n=232 of 604) and estimated glomerular filtration rate of <60 mL/min/1.73 m(2) (n=158 of 547). Decreasing BP categories had lower relative risk (RR) of developing incident proteinuria (RR comparing decreasing quartiles of systolic BP: 1.00, 0.76, 0.58, 0.73; P for trend=0.03; RR comparing decreasing quartiles of diastolic BP: 1.00, 0.81, 0.66, 0.42; P for trend <0.0001) and incident estimated glomerular filtration rate <60 mL/min/1.73 m(2) (RR comparing decreasing quartiles of systolic BP: 1.00, 0.83, 0.61, 0.65; P for trend=0.03; RR comparing decreasing quartiles of diastolic BP: 1.00, 0.84, 0.82, 0.43; P for trend=0.001). These associations were independent of glycemic control and several putative confounding factors. Subjects with either systolic BP <120 mm Hg or diastolic BP <70 mm Hg had significantly lower RR (95% confidence interval) of incident proteinuria (0.63 [0.48 to 0.82]) and incident estimated glomerular filtration rate <60 mL/min/1.73 m(2) (0.60 [0.43 to 0.82]); corresponding population-attributable risks for these outcomes were 26.7% and 29.5%, respectively. Our study suggests that lower BP levels, even below the accepted normal range, are protective against kidney disease in adults with type 1 diabetes. Interventional trials are desirable to clarify the clinical significance of this association.

The topography of platinum electrodes produced by electrodeposition (19 to 200 mC cm-2) on highly oriented pyrolytic graphite (HOPG) under different potential modulations was investigated by atomic force microscopy, scanning tunneling microscopy, and H-atom electrosorption voltammetry. To modulate electrodeposition, (i) triangular potential cycling at 0.1 V s-1, (ii) a linear cathodic potential at 0.1 V s-1 and anodic potential step cycling, and (iii) square wave potential cycling at 5000 Hz were utilized. AFM and STM imaging showed that at lower platinum loading the HOPG surface was partially covered by a 3D sublayer of platinum. Electrodes produced by procedure (i) were made of faceted platinum aggregates of about 200 nm and nanoclusters in the range of 5-20 nm; those that resulted from procedure (ii) consisted of anisotropic aggregates of nanoclusters arranged as quasi-parallel domains. These electrodes from (i) and (ii) behaved as fractal objects. The electrodes resulting from procedure (iii) exhibited a flat surface that behaved as a Euclidean object. For all WEs, as the platinum loading was increased the HOPG surface was fully covered by a thin 3D layer of platinum aggregates produced by electrodeposition and coalescence phenomena. Large platinum loading led to electrodes with fractal geometry. Statistical parameters (root-mean-square height, skewedness, kurtosis, anisotropy, Abbot curve, number of protrusions and valleys, and fractal dimension) were obtained from the analysis of AFM and STM imaging data. Platinum electrodeposition coupled to either H-adatom formation for procedures (i) and (ii) or phonon dispersion for (iii) was involved in the surface atom rearrangements related to electrofaceting. The H-adatom electrosorption voltammetry data were used to evaluate the real electrode surface area via the voltammetric charge and to advance a tentative explanation of the contribution of the different crystallographic facets to the global electrochemical process dominated by weak H-Pt adsorption interactions.

Increasing experimental evidence, including recently developed animal models support a causal role for uric acid in the development of hypertension. However, it is not clear whether serum uric acid levels are independently associated with the long-term incidence of hypertension. We examined the association between serum uric acid levels and 10-year incidence of hypertension in a population-based cohort study based in Beaver Dam city and township, Wisconsin, US. We studied 2520 hypertension-free individuals (56.3% women, age: 43-84 years, 98% Caucasian) at the baseline examination (1988-1990). The main outcome of interest was hypertension (systolic blood pressure (BP) of 140 mm Hg or higher, diastolic BP 90 mm Hg or higher, or combination of self-reported high BP diagnosis and use of antihypertensive medications) incidence over 10 years among baseline normotensive individuals. Nine hundred and fifty-six individuals developed hypertension over a 10-year follow-up period. The relative risk (RR) (95% confidence intervals (CI)) of incident hypertension increased in a dose-dependent manner (P-trend < 0.05 in all models) with increasing uric acid quartiles. Multivariable RR (95% CI) comparing the highest quartile of serum uric acid (> or =390 micromol/l) to the lowest quartile (< or =260 micromol/l) was 1.65 (1.41-1.93). This association persisted in subgroup analyses by categories of smoking, alcohol intake, body mass index, baseline blood pressure and estimated glomerular filtration rate (GFR). In conclusion, increasing quartiles of serum uric acid was associated with 10-year incidence of hypertension independent of smoking, alcohol intake and baseline kidney function suggesting an independent positive association between serum uric acid levels and hypertension development among community-dwelling older adults.

Serum uric acid has been positively associated with incident hypertension, but previous studies have had limited ability to explore this relationship across sex and ethnic strata. We sought to evaluate this association in a biethnic cohort of middle-aged men and women. Participants in the Atherosclerosis Risk in Communities (ARIC) study who were free of hypertension at baseline (N=9104) were evaluated for hypertension at 3-year intervals over 4 examinations. Adjusted Cox proportional hazards models evaluated risk of incident hypertension or progression of blood category for each SD higher baseline serum uric acid. At baseline, the mean age was 53.3 years (range: 45 to 64 years), with a mean (SD) systolic blood pressure of 113.8 (12.2) mm Hg, mean diastolic blood pressure of 70.2 (8.6) mm Hg, and mean serum uric acid of 5.7 (1.4). Higher serum uric acid was associated with greater risk of hypertension in the overall cohort (hazard ratio for each SD of higher uric acid [95% CI]: 1.10 [1.04 to 1.15]) and in subgroup analyses (black men: 1.32 [1.14 to 1.54]; black women: 1.16 [1.03 to 1.31]; white men: 1.01 [0.94 to 1.09]; white women: 1.04 [0.96 to 1.11]), after adjustment for age, baseline blood pressure, body mass index, renal function, diabetes, and smoking. The pattern was similar when modeling blood pressure progression (overall: 1.10 [1.05 to 1.14]; black men: 1.26 [1.11 to 1.42]; black women: 1.18 [1.06 to 1.31]; white men: 1.05 [0.99 to 1.11]; white women: 1.05 [1.00 to 1.12]). In conclusion, serum uric acid was positively associated with incident hypertension over 9 years of follow-up, and this relationship was stronger in blacks than in whites. More research is warranted concerning the physiological and clinical consequences of hyperuricemia, especially in blacks.

Recent studies have linked hepatitis C virus (HCV) infection with carotid atherosclerosis. We investigated the association between HCV seropositivity and acute myocardial infarction using a well-established cohort of young men in the US military and found no evidence to support this association.

Aims: Since serum uric acid (UA) is strongly associated with cardiovascular risk factors, it has been debated whether serum UA is a stroke risk factor or whether UA may be simply "marking" subjects with other, causal risk factors. We therefore investigated the relation between UA and ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) Study., Methods and Results: Of 15,792 ARIC participants, 13,413 who were free of recognized stroke or coronary heart disease (CHD) at baseline and had a baseline UA measurement were included in the analysis. We followed the participants for ischemic stroke incidence (N=381) over 12.6 years. Although serum UA was independently and positively related to ischemic stroke incidence when we adjusted for age, sex, race, and education, the positive relation was weakened when additionally adjusted for possible confounding variables. The positive multivariate-adjusted association between serum UA and ischemic stroke was observed among subjects not using diuretics (adjusted relative hazard in the highest quartile versus the lowest: relative hazard (RH)=1.49; 95% confidence interval (CI): 1.00-2.23) (P for trend: 0.02), but not among diuretic users (P for interaction: 0.08)., Conclusion: Our findings suggest that UA is an independent predictor of ischemic stroke among subjects not using diuretics, but that elevated UA itself may not cause ischemic stroke.

Objective: Trait anger has been shown to predict coronary heart disease; however, there are no prior studies evaluating anger as a risk factor for type 2 diabetes. The objective of this study was to determine if anger proneness predicted type 2 diabetes using prospective analyses., Methods: We analyzed data on trait anger, assessed by questionnaire, in a longitudinal, bi-racial cohort study of 11,615 initially non-diabetic adults aged 48-67, who were subsequently followed for 6 years for the development of type 2 diabetes., Results: There was no relation between overall trait anger and the subsequent risk of diabetes; however, individuals in the highest tertile of trait anger temperament scores had a 34% increased risk of developing diabetes compared to those in the lowest tertile (Relative hazard [RH] = 1.34; 95% confidence interval: 1.10, 1.62), following adjustment for age, race, gender, and education. The relation between anger temperament and diabetes remained significant following adjustment for behavioral factors (smoking, physical activity, and caloric intake) (RH = 1.31; 95% CI: 1.08, 1.60) but was non-significant after additional adjustment for waist-to-hip ratio and body-mass index (RH = 1.18; 95% CI: 0.97, 1.44)., Conclusions: While we found no relation between overall trait anger and incident diabetes, persons who had higher anger temperament subscale scores had a slightly increased risk of type 2 diabetes, which was largely explained by adiposity. Anger temperament may deserve further attention as a potential risk factor for type 2 diabetes.

Objective: To examine the association of socioeconomic factors with progression of carotid intimal-medial thickness (IMT) in middle-aged adults. Cross-sectional associations of IMT with socioeconomic status (SES) have been demonstrated in middle-aged cohorts. It is unclear whether these factors are associated with progression of IMT., Methods and Results: We examined IMT progression over 9 years among a middle-aged cohort of 12,085 black and white subjects free of cardiovascular disease recruited from 4 US sites participating in the Atherosclerosis Risk in Communities (ARIC) study. Baseline IMT was inversely related to SES among whites and blacks. Repeated measures regression models of IMT progression showed moderate inverse relationships of IMT progression with income in whites so that the difference in 5-year IMT progression rates between the highest and lowest categories was -11.5 microm (CI, -17.4 to -5.6). In contrast, among blacks, this gradient is reversed, with an 11.1 microm (CI, -0.1 to 22.3) difference in 5-year progression between highest and lowest income category. Generally, similar patterns were observed for other socioeconomic indicators. Patterns were not accounted for by baseline cardiovascular risk factors., Conclusions: SES is inversely related to IMT progression in middle-aged whites but positively related to IMT progression among middle-aged blacks. These differences do not appear to be attributable to selective attrition or higher IMT among blacks at baseline.

Background: Lower extremity arterial disease (LEAD) is one of the most common manifestations of atherosclerosis. Its epidemiologic characteristics have not been well described, particularly in African Americans. Our purpose was to estimate the prevalence of LEAD and its associations with cardiovascular risk factors in a biracial population of men and women aged 45 to 64 years., Methods: We examined 15,173 African-American and white men and women who participated in the baseline examination (1987-1989) of the Atherosclerosis Risk in Communities (ARIC) Study. LEAD was defined by a resting ankle-brachial index (ABI), the ratio of ankle systolic blood pressure to brachial systolic pressure, of < or = 0.90. Cross-sectional analyses were used to determine the association of LEAD with cardiovascular risk factors., Results: The age-adjusted prevalence of ABI < or = 0.90 was 3.1% in African-American men, 4.4% in African-American women, 2.3% in white men, and 3.2% in white women. Cigarette smoking was the single most important risk factor for prevalent LEAD. The odds ratio estimate for LEAD in ever smokers versus never smokers was 6.6 (95% confidence interval [CI]=2.0-21.5) in African-American men, 2.3 (95% CI=1.5-3.5) in African-American women, 10.4 (95% CI=3.8-28.3) in white men, and 1.9 (95% CI=1.4-2.6) in white women, after adjustment for age, LDL cholesterol, hypertension, and diabetes. Prevalent LEAD was also associated with hypertension, diabetes, and higher concentrations of total cholesterol, triglycerides, LDL-cholesterol, and fibrinogen, and lower concentrations of HDL cholesterol, but the associations were not always significant across race/ethnic and gender groups. The associations of LEAD with plasma lipids were generally stronger in African Americans than whites., Conclusions: The prevalence of LEAD appears to be higher in African Americans than whites. Elevations in traditional cardiovascular risk factors are associated with a higher prevalence of LEAD across race/ethnic and gender groups.

Background: The relationship of weight changes to the incidence, progression, and remission of sleep-disordered breathing (SDB) is not well defined. This study aims to determine the relationship between change in weight and progression or remission of SDB by polysomnography., Methods: We performed a longitudinal cohort study of the cardiovascular consequences of sleep apnea in diverse US communities. Sleep apnea and polysomnographic indicators of SDB were assessed 5 years apart., Results: A total of 2968 men and women (mean age, 62 years) participated in the study. Men were more likely to have an increase in Respiratory Disturbance Index (RDI) with a given increase in weight than were women, and this was not explained by differences in starting weight, waist circumference, age, or ethnicity. In a linear regression analysis, both men and women had a greater increase in RDI with weight gain than a decrease in RDI with weight loss. In a categorical analysis of larger degrees of change, this sex difference was also evident. Associations were similar in diverse ethnic groups. However, SDB progressed over time, even in those with stable weight., Conclusion: Modest changes in weight were related to an increase or decrease in SDB, and this association was stronger in men than in women.

The objective of our study was to analyze the perceived (belief) or adopted (behavior) measures to reduce cancer risk in a Spanish population. We used cross-sectional data from the Cornella Health Interview Survey Follow-up Study (CHIS.FU). We analyzed 1,438 subjects who in 2002 answered questions about risk perceptions on cancer and related behavior (668 males and 770 females). The benefits of avoiding cigarette smoking (95.8%), sunlight exposure (94.9%) and alcohol (81.0%) were widely recognized. On the other hand, electromagnetic fields (92.1%), food coloring and other food additives (78.4%) or pesticides (69.4%), whose role in cancer occurrence, if any, remain unproven, were clearly considered as cancer risk factors in this population. Compared to men, women more frequently reported healthy behaviors, and the role of exogenous factors (i.e., environmental risk factors) were widely popular. There was a socioeconomic gradient on cancer risk perception with respect to several lifestyle or dietary factors. Individuals with higher educational level scored lower in several risk factors than those with primary or less than primary school education. Smokers reported adopting fewer healthy behaviors than former or never smokers. How people perceive health issues and risk or make choices about their own behavior does not always follow a predictable or rational pattern., (Copyright (c) 2005 Wiley-Liss, Inc.)

The kinetics and mechanism of the oxidation of Glycine (Gly), Alanine (Ala), Tyrosine (Tyr), Tryptophan (Trp) and some di-(Gly-Gly, Ala-Ala, Gly-Ala, Gly-Trp, Trp-Gly, Gly-Tyr, Tyr-Gly), tri-(Gly-Gly-Gly, Ala-Gly-Gly) and tetrapeptides (Gly-Gly-Gly-Gly) mediated by sulfate (SO(4) (-)) and hydrogen phosphate (HPO(4) (-)) radicals was studied, employing the flash-photolysis technique. The substrates were found to react with sulfate radicals (SO(4) (-), produced by photolysis of the S(2)O(8)(2-)) faster than with hydrogen phosphate radicals (HPO(4) (-), generated by photolysis of P(2)O(8)(4-) at pH = 7.1). The reactions of the zwitterions of the aliphatic amino acids and peptides with SO(4) (-) radicals take place by electron transfer from the carboxylate moiety to the inorganic radical, whereas those of the HPO(4) (-) proceed by H-abstraction from the alpha carbon atom. The phenoxyl radical of Tyr-Gly and Gly-Tyr are formed as intermediate species of the oxidation of these peptides by the inorganic radicals. The radical cations of Gly-Trp and Trp-Gly (at pH = 4.2) and their corresponding deprotonated forms (at pH = 7) were detected as intermediates species of the oxidation of these peptides with SO(4) (-) and HPO(4) (-). Reaction mechanisms which account for the observed intermediates are proposed.

Objective: To examine cross sectional and longitudinal associations of socioeconomic position and neighborhood environments with BMI in a middle-aged and bi-ethnic cohort., Research Methods and Procedures: Analyses were based on 13,167 subjects (45 to 64 years) who participated in the Atherosclerosis Risk in Communities Study, a population-based study. Census block groups were used as proxies for neighborhoods and were characterized using a summary socioeconomic score. BMI was measured at baseline and at three follow-up visits over a 9-year period., Results: Individual and neighborhood socioeconomic characteristics were independently and inversely associated with BMI at baseline in women [mean difference in kilograms per meter squared per unit increase in socioeconomic category (SE) for white and black women respectively; -1.56 (0.14), -1.59 (0.19) for education; -1.07 (0.10), -1.18 (0.18) for income; and -1.04 (0.09), -0.77 (0.18) for neighborhood characteristics]. Results for men were not as consistent. Baseline BMI was negatively associated with income in white men but was positively associated with education, income, and neighborhood characteristics in black men. BMI increased over time regardless of gender or race and in most age groups. In whites, there were no consistently patterned differences in longitudinal trends in BMI by individual or neighborhood socioeconomic characteristics. However, in blacks, there was some evidence of greater increases in the higher socioeconomic status groups., Discussion: Socioeconomic factors are inversely associated with BMI in middle-aged women, possibly reflecting socially patterned exposures occurring in childhood and adolescence. However, recent increases over time in BMI are either not clearly patterned by socioeconomic factors or are greater in the higher socioeconomic status groups.

Background: Experimental sleep restriction causes impaired glucose tolerance (IGT); however, little is known about the metabolic effects of habitual sleep restriction. We assessed the cross-sectional relation of usual sleep time to diabetes mellitus (DM) and IGT among participants in the Sleep Heart Health Study, a community-based prospective study of the cardiovascular consequences of sleep-disordered breathing., Methods: Participants were 722 men and 764 women, aged 53 to 93 years. Usual sleep time was obtained by standardized questionnaire. Diabetes mellitus was defined as a serum glucose level of 126 mg/dL or more (> or =7.0 mmol/L) fasting or 200 mg/dL or more (> or =11.1 mmol/L) 2 hours following standard oral glucose challenge or medication use for DM. Impaired glucose tolerance was defined as a 2-hour postchallenge glucose level of 140 mg/dL or more (> or =7.8 mmol/L) and less than 200 mg/dL. The relation of sleep time to DM and IGT was examined using categorical logistic regression with adjustment for age, sex, race, body habitus, and apnea-hypopnea index., Results: The median sleep time was 7 hours per night, with 27.1% of subjects sleeping 6 hours or less per night. Compared with those sleeping 7 to 8 hours per night, subjects sleeping 5 hours or less and 6 hours per night had adjusted odds ratios for DM of 2.51 (95% confidence interval, 1.57-4.02) and 1.66 (95% confidence interval, 1.15-2.39), respectively. Adjusted odds ratios for IGT were 1.33 (95% confidence interval, 0.83-2.15) and 1.58 (95% confidence interval, 1.15-2.18), respectively. Subjects sleeping 9 hours or more per night also had increased odds ratios for DM and IGT. These associations persisted when subjects with insomnia symptoms were excluded., Conclusions: A sleep duration of 6 hours or less or 9 hours or more is associated with increased prevalence of DM and IGT. Because this effect was present in subjects without insomnia, voluntary sleep restriction may contribute to the large public health burden of DM.

Study Objectives: Population-based studies have demonstrated associations between sleep-disordered breathing (SDB), hypertension, and cardiovascular disease; few large-scale studies have examined associations of SDB with objective measures of cerebrovascular disease. This study tested the significance of associations of SDB with evidence of brain injury or ischemia determined by cerebral magnetic resonance imaging (MRI) studies., Design: Cross-sectional and longitudinal analyses in a nested sample of Cardiovascular Health Study participants in the Sleep Heart Health Study., Participants: The 843 individuals (mean age 77, SD 4.3 years, 58% women) who had MRI studies as part of the Cardiovascular Health Study before and after polysomnography obtained as part of the Sleep Heart Health Study., Measurements: A 12-channel polysomnogram was used to derive indexes of sleep-disordered breathing. Repeated MRI measurements provided indexes of infarct (presence and size) and white matter disease. Logistic regression analyses were used to model MRI changes of infarct-like lesions and white matter disease as a function of age, baseline white matter grade, and indexes of central and obstructive sleep-disordered breathing., Results: Individuals who showed progression in white matter disease compared to those who did not were significantly more likely to show a Cheyne-Stokes respiration pattern and to have an increased number of central but not obstructive apneas., Conclusions: An association between change in white matter grade and measures of central sleep apnea was demonstrated that was consistent with a causal pathway in which central sleep apnea contributes to the progression of white matter disease; alternatively, central sleep apnea may be a marker of subclinical cerebrovascular or cardiovascular disease.

Background: Several investigators have found that Chlamydia pneumoniae and cytomegalovirus infections may be risk factors for coronary heart disease. However, the data remain controversial. To address this hypothesis, data and specimens were collected from a well-established prospective cohort of active-duty personnel from the US military., Methods: A nested case-control study was conducted with 300 case patients and 300 matched control subjects. Case patients were men (age, 30-50 years) with a medically documented, first-time hospitalization for acute myocardial infarction (MI) and from whom a serum specimen had been drawn >or=1 year before the time of the acute MI. Population-based control subjects were chosen from the same cohort and were individually matched by age, race, and time of specimen collection. Evidence of past infections with C. pneumoniae and cytomegalovirus were measured by microimmunofluorescence assay and enzyme-linked immunosorbent assay, respectively., Results: Significant risk was associated with high titer (>or=1 : 64) to C. pneumoniae immunoglobulin A (IgA) (adjusted relative risk [RR(adj)], 1.67; 95% confidence interval [CI], 1.04-2.70). This increased risk was greatest when specimens were collected 1-5 years before the event (RR(adj), 2.11; 95% CI, 1.06-4.21). High titer (>or=1 : 256) to C. pneumoniae immunoglobulin G (IgG) was also associated with an elevated risk (RR(adj), 1.74; 95% CI, 0.90-3.34) after full adjustment for cardiovascular risk factors, whereas no independent risk for acute MI was associated with cytomegalovirus IgG seropositivity., Conclusions: This study demonstrates a significant association between high titers to C. pneumoniae IgG and IgA and acute MI in a cohort of young men and suggests that recent or chronic active infections could be associated with an increased risk for MI.