Is the cholesterol-perfluoroalkyl substance association confounded by dietary fiber intake?: a Bayesian analysis of NHANES data with adjustment for measurement error in fiber intake.

BACKGROUND: Serum concentrations of total cholesterol and related lipid measures have been associated with serum concentrations of per- and polyfluoroalkyl substances (PFAS) in humans, even among those with only background-level exposure to PFAS. Fiber is known to decrease serum cholesterol and a recent report based on National Health and Nutrition Examination Survey (NHANES) showed that PFAS and fiber are inversely associated. We hypothesized that confounding by dietary fiber may account for some of the association between cholesterol and PFAS. METHODS: We implemented a Bayesian correction for measurement error in estimated intake of dietary fiber to evaluate whether fiber confounds the cholesterol-PFAS association. The NHANES measure of diet, two 24-h recalls, allowed calculation of an estimate of the "true" long-term fiber intake for each subject. We fit models to the NHANES data on serum cholesterol and serum concentration of perfluorooctanoic acid (PFOA) and two other PFAS for 7,242 participants in NHANES. RESULTS: The Bayesian model, after adjustment for soluble fiber intake, suggested a decrease in the size of the coefficient for PFOA by 6.4% compared with the fiber-unadjusted model. CONCLUSIONS: The results indicated that the association of serum cholesterol with PFAS was not substantially confounded by fiber intake.

Underground salt and potash workers exposed to nitrogen oxides and diesel exhaust: assessment of specific effect biomarkers.

PURPOSE: Occupational exposure limits (OEL) for nitrogen oxides (NO, NO2) and diesel exhaust (EC-DPM) were reassessed by the German authorities in 2016/2017. We performed a clinical cross-sectional study among salt and potash underground workers exposed to these substances at relatively high levels to examine possible indicators of acute effects on workers' health. METHODS: We measured post- versus pre-shift differences in cardiovascular, inflammatory, immune, and respiratory effect biomarkers and assessed their associations with personal exposures measured during the same shift. We also compared post- versus pre-shift differences in biomarker levels between exposure groups defined based on work site and job type. RESULTS: None of the above-ground workers exceeded the OEL for NO2 and only 5% exceeded the OEL for EC-DPM exposure. Among underground workers, 33% of miners and 7% underground maintenance workers exceeded the OEL for NO2; the OEL for EC-DPM was exceeded by 56% of miners and 17% of maintenance workers. Some effect biomarkers (thrombocytes, neutrophils, MPO, TNF-α, IgE, FeNO) showed statistically significant differences between pre- versus post-shift measurements; however, there were no consistent associations between pre- and post-shift differences and exposure group or personal exposure measurements during the shift. CONCLUSIONS: We did not find evidence of associations between workplace exposure to NO, NO2 or EC-DPM and clinically relevant indicators of acute cardiovascular, inflammatory and immune, or respiratory effects among salt and potash underground workers in Germany.

Estimating the Population Health Impact of Recently Introduced Modified Risk Tobacco Products: A Comparison of Different Approaches.

INTRODUCTION: Various approaches have been used to estimate the population health impact of introducing a Modified Risk Tobacco Product (MRTP). AIMS AND METHODS: We aimed to compare and contrast aspects of models considering effects on mortality that were known to experts attending a meeting on models in 2018. RESULTS: Thirteen models are described, some focussing on e-cigarettes, others more general. Most models are cohort-based, comparing results with or without MRTP introduction. They typically start with a population with known smoking habits and then use transition probabilities either to update smoking habits in the "null scenario" or joint smoking and MRTP habits in an "alternative scenario". The models vary in the tobacco groups and transition probabilities considered. Based on aspects of the tobacco history developed, the models compare mortality risks, and sometimes life-years lost and health costs, between scenarios. Estimating effects on population health depends on frequency of use of the MRTP and smoking, and the extent to which the products expose users to harmful constituents. Strengths and weaknesses of the approaches are summarized. CONCLUSIONS: Despite methodological differences, most modellers have assumed the increase in risk of mortality from MRTP use, relative to that from cigarette smoking, to be very low and have concluded that MRTP introduction is likely to have a beneficial impact. Further model development, supplemented by preliminary results from well-designed epidemiological studies, should enable more precise prediction of the anticipated effects of MRTP introduction. IMPLICATIONS: There is a need to estimate the population health impact of introducing modified risk nicotine-containing products for smokers unwilling or unable to quit. This paper reviews a variety of modeling methodologies proposed to do this, and discusses the implications of the different approaches. It should assist modelers in refining and improving their models, and help toward providing authorities with more reliable estimates.

C-reactive protein from dried blood spots: Application to household air pollution field studies.

Household air pollution (HAP) is estimated to be an important risk factor for cardiovascular disease, but little clinical evidence exists and collecting biomarkers of disease risk is difficult in low-resource settings. Among 54 Nicaraguan women with woodburning cookstoves, we evaluated cross-sectional associations between 48-hour measures of HAP (eg, fine particulate matter, PM2.5 ) and C-reactive protein (CRP) via dried blood spots; secondary analyses included seven additional biomarkers of systemic injury and inflammation. We conducted sub-studies to calculate the intraclass correlation coefficient (ICC) in biomarkers collected over four consecutive days in Nicaragua and to assess the validity of measuring biomarkers in dried blood by calculating the correlation with paired venous-drawn samples in Colorado. Measures of HAP were associated with CRP (eg, a 25% increase in indoor PM2.5 was associated with a 7.4% increase in CRP [95% confidence interval: 0.7, 14.5]). Most of the variability in CRP concentrations over the 4-day period was between-person (ICC: 0.88), and CRP concentrations were highly correlated between paired dried blood and venous-drawn serum (Spearman ρ = .96). Results for secondary biomarkers were primarily consistent with null associations, and the sub-study ICCs and correlations were lower. Assessing CRP via dried blood spots provides a feasible approach to elucidate the association between HAP and cardiovascular disease risk.

Exposure to household air pollution from biomass cookstoves and self-reported symptoms among women in rural Honduras.

Household air pollution from combustion of solid fuels is an important risk factor for morbidity and mortality, causing an estimated 2.6 million premature deaths globally in 2016. Self-reported health symptoms are a meaningful measure of quality of life, however, few studies have evaluated symptoms and quantitative measures of exposure to household air pollution. We assessed the cross-sectional association of self-reported symptoms and exposures to household air pollution among women in rural Honduras using stove type (traditional [n = 76]; cleaner-burning Justa [n = 74]) and 24-hour average personal and kitchen fine particulate matter (PM2.5) concentrations. The odds of prevalent symptoms were higher among women using traditional stoves vs Justa stoves (e.g. headache: odds ratio = 2.23; 95% confidence interval = 1.13-4.39). Associations between symptoms and measured PM2.5 were generally consistent with the null. These results add to the evidence suggesting reduced exposures and better health-related quality of life among women using cleaner-burning biomass stoves.

Household air pollution from biomass-burning cookstoves and metabolic syndrome, blood lipid concentrations, and waist circumference in Honduran women: A cross-sectional study.

BACKGROUND: Household air pollution from cooking with solid fuels affects nearly 3 billion people worldwide and is responsible for an estimated 2.5 million premature deaths and 77 million disability-adjusted life years annually. Investigating the effect of household air pollution on indicators of cardiometabolic disease, such as metabolic syndrome, can help clarify the pathways between this widespread exposure and cardiovascular diseases, which are increasing in low- and middle-income countries. METHODS: Our cross-sectional study of 150 women in rural Honduras (76 with traditional stoves and 74 with cleaner-burning Justa stoves) explored the effect of household air pollution exposure on cardiovascular disease risk factors. Household air pollution was measured by stove type and 24-h average kitchen and personal fine particulate matter [PM2.5] mass and black carbon concentrations. Health endpoints included non-fasting total cholesterol, high-density lipoprotein, calculated low-density lipoprotein, triglycerides, waist circumference to indicate abdominal obesity, and presence of metabolic syndrome (defined by current modified international guidelines: waist circumference ≥ 80 cm plus any two of the following: triglycerides > 200 mg/dL, HDL < 50 mg/dL, systolic blood pressure ≥ 130 mmHg, diastolic blood pressure ≥ 85 mmHg, or glycated hemoglobin > 5.6%). RESULTS: Forty percent of women met the criteria for metabolic syndrome. The prevalence ratio [PR] for metabolic syndrome (versus normal) per interquartile range increase in kitchen PM2.5 and kitchen black carbon was 1.16 (95% confidence interval [CI]: 1.01-1.34) per 312 µg/m3 increase in PM2.5, and 1.07 (95% CI: 1.03-1.12) per 73 µg/m3 increase in black carbon. There is suggestive evidence of a stronger effect in women ≥ 40 years of age compared to women < 40 (p-value for interaction = 0.12 for personal PM2.5). There was no evidence of associations between all other exposure metrics and health endpoints. CONCLUSIONS: The prevalence of metabolic syndrome among our study population was high compared to global estimates. We observed a suggestive effect between metabolic syndrome and exposure to household air pollution. These results for metabolic syndrome may be driven by specific syndrome components, such as blood pressure. Longitudinal research with repeated health and exposure measures is needed to better understand the link between household air pollution and indicators of cardiometabolic disease risk.

Exposure to household air pollution from biomass cookstoves and blood pressure among women in rural Honduras: A cross-sectional study.

Growing evidence links household air pollution exposure from biomass cookstoves with elevated blood pressure. We assessed cross-sectional associations of 24-hour mean concentrations of personal and kitchen fine particulate matter (PM2.5 ), black carbon (BC), and stove type with blood pressure, adjusting for confounders, among 147 women using traditional or cleaner-burning Justa stoves in Honduras. We investigated effect modification by age and body mass index. Traditional stove users had mean (standard deviation) personal and kitchen 24-hour PM2.5 concentrations of 126 µg/m3 (77) and 360 µg/m3 (374), while Justa stove users' exposures were 66 µg/m3 (38) and 137 µg/m3 (194), respectively. BC concentrations were similarly lower among Justa stove users. Adjusted mean systolic blood pressure was 2.5 mm Hg higher (95% CI, 0.7-4.3) per unit increase in natural log-transformed kitchen PM2.5 concentration; results were stronger among women of 40 years or older (5.2 mm Hg increase, 95% CI, 2.3-8.1). Adjusted odds of borderline high and high blood pressure (categorized) were also elevated (odds ratio = 1.5, 95% CI, 1.0-2.3). Some results included null values and are suggestive. Results suggest that reduced household air pollution, even when concentrations exceed air quality guidelines, may help lower cardiovascular disease risk, particularly among older subgroups.

Assessing the Likelihood and Magnitude of a Population Health Benefit Following the Market Introduction of a Modified-Risk Tobacco Product: Enhancements to the Dynamic Population Modeler, DPM(+1).

Researchers and those responsible for evaluating and implementing policies intended to reduce population harm must assess the potential for both intended and unintended consequences associated with those policies. Such assessments should be based on the combined dimensions of magnitude, and thus likelihood, of shifts in exposure patterns needed to produce a population benefit or harm, and magnitude of the expected population benefit or harm. In response to this assessment need, we provide a conceptual description of the dynamic population modeler, DPM(+1), as well as illustrative analyses that estimate the effects on all-cause mortality, life expectancy, and quality of life-adjusted life expectancy if exposure patterns in the population shift from a higher risk product (e.g., cigarettes) to a lower, or modified, risk tobacco product (MRTP) in specified ways. Estimates from these analyses indicate that, within a single birth cohort, switching completely from cigarette smoking to MRTP use is more likely to lead to a population-level survival benefit than initiating tobacco use with an MRTP instead of cigarettes. This is because tobacco initiation rarely occurs beyond young adulthood, whereas continuing smokers exist in all subsequent age categories, leading to a greater cumulative effect. In addition, complete switching to MRTP use among a small proportion of smokers in each age category offsets the survival deficit caused by unintended shifts in exposure patterns, such as MRTP initiation among never tobacco users followed by transitioning to cigarette smoking and/or cigarette smokers switching to MRTP use instead of quitting.

Interactions Between Diet and Exposure to Secondhand Smoke on Glycated Hemoglobin Levels Among US Children: Results From NHANES 2007-2012.

INTRODUCTION: Antioxidant-rich diets may lessen the adverse metabolic responses triggered by exposure to secondhand smoke (SHS), but no studies have investigated these potential interactions. OBJECTIVE: To examine the interaction between diet and exposure to SHS on glycated hemoglobin (HbA1c) levels among 2551 children, ages 12-19 years, who participated in the 2007-2012 National Health and Nutrition Examination Survey (NHANES). METHODS: Exposure to SHS was assessed by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), cotinine, and self-report. Weighted linear regression models evaluated the cross-sectional association between exposure to SHS and HbA1c levels. Additive interaction was assessed by introducing product terms (with SHS) of individual nutrients (dietary fiber, eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], vitamin C, and vitamin E) to separate models. RESULTS: Over half of the children had NNAL or cotinine levels above the limit of detection (56% and 71%, respectively). The median HbA1c level was 5.2% (95% confidence interval: 5.17%, 5.23%). The interaction results suggest that the effects of exposure to SHS and certain dietary nutrients (EPA, DHA, vitamin C) on HbA1c levels may not be independent. For example, although there was only a slight difference in adjusted mean HbA1c levels across NNAL categories among children with high EPA intakes, the adjusted mean HbA1c level was 0.09% higher for high NNAL as compared to low NNAL among children with low EPA intakes. CONCLUSIONS: Further research is needed to inform public health strategies for limiting increases in HbA1c levels among children. Messages may need to focus both on reducing exposure to SHS and improving diets to obtain the maximum benefit. IMPLICATIONS: Our results suggest that the effects of exposure to SHS and diet on HbA1c levels may not be independent. For example, although there was little effect of exposure to SHS on HbA1c levels among children with high EPA intakes, high exposure to SHS was associated with an increase in HbA1c levels among children with low EPA intakes. Further research is necessary; however, based on these joint effects, strategies for limiting increases in HbA1c levels that focus both on reducing exposure to SHS and improving diets may achieve the largest public health benefits.

REPEATABILITY AND RELIABILITY OF GLOMERULAR FILTRATION RATE DETERMINATION VIA GAMMA CAMERA UPTAKE OF TC-99M-DTPA IN CATS WITH CHRONIC KIDNEY DISEASE.

Measurement of glomerular filtration rate (GFR) via gamma camera uptake of 99mTc-diethylenetriaminepentaacetic acid is a standard method for quantifying renal function. Aims of this retrospective, observer agreement study were to determine intra- and interobserver variation in GFR values for cats with chronic kidney disease and to determine whether renal insufficiency classification changed between observers. Guideline cut-points were established for the difference in repeated GFRs to differentiate changes caused by therapeutic effect vs. inherent variation. Included cats had a diagnosis of chronic kidney disease and had undergone GFR examinations between the years of 2010 and 2013. Twenty-nine GFR studies were sampled. Each study was read twice, 6 months apart, by two veterinary radiologists and one radiology resident. Modified Bland-Altman plots were used to investigate differences between readings 1 and 2 by observer and between pairs of observers by reading. Reliability of clinical classification was assessed through comparisons between readings and observers. Measurements were not systematically different between readings for the experienced observers but were higher in reading 1 than reading 2 for the inexperienced observer. Measurements were not systematically different between the experienced observers in reading 1 or between any two observers in reading 2. Reliability for GFR measurements was high among experienced observers; variations in GFR measurements rarely led to differences in clinical classification. Results suggested that, for experienced observers, changes in GFR values following treatment in cats with chronic kidney disease between -0.4 and 0.4 mL/min/kg may be due to inherent variability rather than treatment effect.

Associations between thoracic radiographic changes and severity of pulmonary arterial hypertension diagnosed in 60 dogs via Doppler echocardiography: A retrospective study.

Doppler echocardiography is a noninvasive method for estimating and grading pulmonary arterial hypertension. No current literature associates significance of radiographic findings with severity of pulmonary arterial hypertension. We hypothesized that the number and conspicuity of radiographic findings suggestive of pulmonary arterial hypertension would be greater based on the severity of pulmonary arterial hypertension. Dogs with pulmonary arterial hypertension and normal control dogs were included in this retrospective, case control study. Three radiologists blinded to echocardiographic results scored thoracic radiographs for right ventricular and main pulmonary artery enlargement and pulmonary lobar artery enlargement, tortuosity, and blunting by multiple methods. Presence or absence of each finding was scored in an additive fashion and averaged for each grade of pulmonary arterial hypertension severity. Seventy-one dogs (60 dogs with pulmonary arterial hypertension and 11 control dogs) of which some had multiple studies were included: 20 mild, 21 moderate, 25 severe, and 11 absent pulmonary arterial hypertension. The following radiographic findings were significantly associated with increasing pulmonary arterial hypertension severity: right ventricular enlargement by "reverse D" and "3/5-2/5 cardiac ratio" methods, main pulmonary artery enlargement, and caudal lobar artery enlargement by the "3rd rib" method. Mean scores for severe pulmonary arterial hypertension and normal dogs were significantly different (P-value < 0.0001). Mean scores between different pulmonary arterial hypertension grades increased with severity but were not statistically significant. Individually and in combination, radiographic findings performed poorly in differentiating severity of pulmonary arterial hypertension. Findings indicated that thoracic radiographs should be utilized in conjunction with Doppler echocardiography in a complete diagnostic work-up for dogs with suspected pulmonary arterial hypertension.

Can Incorrect Analysis of Time-Dependent Exposure Explain Associations between PM2.5 Exposure and Risk of Dementia?

Background: Epidemiological studies have reported positive associations between long-term exposure to particulate matter of 2.5 microns or less in diameter (PM2.5) and risk of Alzheimer's disease and other clinical dementia. Many of these studies have analyzed data using Cox Proportional Hazards (PH) regression, which estimates a hazard ratio (HR) for the treatment (in this case, exposure) effect on the time-to-event outcome while adjusting for influential covariates. PM2.5 levels vary over time. As air quality standards for PM2.5 have become more stringent over time, average outdoor PM2.5 levels have decreased substantially. Objective: Investigate whether a Cox PH analysis that does not properly account for exposure that varies over time could produce a biased HR of similar magnitude to the HRs reported in recent epidemiological studies of PM2.5 and dementia risk. Methods: Simulation analysis. Results: We found that the biased HR can affect statistical analyses that consider exposure levels at event times only, especially if PM2.5 levels decreased consistently over time. Furthermore, the direction of such bias is away from the null and of a magnitude that is consistent with the reported estimates of dementia risk in several epidemiological studies of PM2.5 exposure (HR≈1.2 to 2.0). Conclusions: This bias can be avoided by correctly assigning exposure to study subjects throughout the entire follow-up period. We recommend that investigators provide a detailed description of how time-dependent exposure variables were accounted for in their Cox PH analyses when they report their results.

Formaldehyde exposure and leukemia: critical review and reevaluation of the results from a study that is the focus for evidence of biological plausibility.

A recent study (Zhang et al., 2010) has provided results attributed to aneuploidy in circulating stem cells that has been characterized as providing potential support for proposed mechanisms for formaldehyde to impact bone marrow. A critical review of the study, as well as a reanalysis of the underlying data, was performed and the results of this reanalysis suggested factors other than formaldehyde exposure may have contributed to the effects reported. In addition, although the authors stated in their paper that "all scorable metaphase spreads on each slide were analyzed, and a minimum of 150 cells per subject was scored," this protocol was not followed. In fact, the protocol to evaluate the presence of monosomy 7 or trisomy 8 was followed for three or less samples in exposed workers and six or less samples in non-exposed workers. In addition, the assays used (CFU-GM) do not actually measure the proposed events in primitive cells involved in the development of acute myeloid leukemia. Evaluation of these data indicates that the aneuploidy measured could not have arisen in vivo, but rather arose during in vitro culture. The results of our critical review and reanalysis of the data, in combination with recent toxicological and mechanistic studies, do not support a mechanism for a causal association between formaldehyde exposure and myeloid or lymphoid malignancies.

A dynamic population model for estimating all-cause mortality due to lifetime exposure history.

We developed a comprehensive, flexible dynamic model that estimates all-cause mortality for a hypothetical cohort. All model input is user-specified. In the base case, members of the cohort may be exposed to a high risk product as they age. The counterfactual scenario includes exposure to both a high risk and a lower risk product. The model sorts the population into age and exposure categories, and applies the appropriate mortality rates to each category. The model tracks individual exposure histories, and estimates, at the end of each modeled age category, the number of survivors in the two exposure scenarios (base case and counterfactual), and the difference between them. Markov Chain Monte Carlo techniques are used to estimate the variability of the results. Model output was compared against US and Swedish life tables using population-specific tobacco exposure transition probabilities derived from the literature, and it produced similar survival estimates.

Ultrasonographic findings of feline cholangitis.

Cholangitis is a common inflammatory disorder of the biliary system in cats. There are two major forms based on the predominate type of inflammatory cell infiltrates: lymphocytic or neutrophilic. Ultrasound is a common imaging modality used in these patients. This retrospective study evaluated the ultrasound examinations of 26 cats with a histologic diagnosis of cholangitis. Most cats with cholangitis had sonographically normal liver size, echogenicity, and normal biliary systems. Statistically significant sonographic changes for cats with cholangitis included hyperechoic liver parenchyma, hyperechoic gallbladder contents, and increased pancreatic size. No statistically significant changes were noted to distinguish lymphocytic and neutrophilic forms of cholangitis. Cats with the sonographic features of diffuse liver hyperechogenicity, gallbladder contents and enlarged pancreas may suggest cholangitis.

Cross-sectional Study of Workers Employed at a Copper Smelter-Effects of Long-term Exposures to Copper on Lung Function and Chronic Inflammation.

OBJECTIVE: The aim of the study was to assess the effect of exposure to copper-containing dust on lung function and inflammatory endpoints among workers of a German copper plant, effects rarely studied before. METHODS: One hundred four copper-exposed smelter workers and 70 referent workers from the precious metal and lead facilities were included, with different metal exposures in both groups due to the different process materials. Body plethysmography, exhaled nitric oxide (FeNO) measurements, and blood sampling were conducted in all workers. Smoking status and the use of respiratory protective equipment were considered. In a subgroup of 40 nonsmoking volunteers (28 copper-exposed and 12 referents), sputum biomarkers were assessed. RESULTS: Median lung function values of both copper-exposed and the referent groups were within reference ranges of "healthy" individuals, and statistical differences between the groups were mostly not evident. Similarly, differences in blood and sputum biomarkers were too small to be biologically relevant. CONCLUSION: The results suggest the absence of the detectable effects of copper-containing dust exposure on lung function or chronic inflammation within the investigated cohort.

Household air pollution from wood-burning cookstoves and C-reactive protein among women in rural Honduras.

Household air pollution from solid fuel combustion was estimated to cause 2.31 million deaths worldwide in 2019; cardiovascular disease is a substantial contributor to the global burden. We evaluated the cross-sectional association between household air pollution (24-h gravimetric kitchen and personal particulate matter (PM2.5) and black carbon (BC)) and C-reactive protein (CRP) measured in dried blood spots among 107 women in rural Honduras using wood-burning traditional or Justa (an engineered combustion chamber) stoves. A suite of 6 additional markers of systemic injury and inflammation were considered in secondary analyses. We adjusted for potential confounders and assessed effect modification of several cardiovascular-disease risk factors. The median (25th, 75th percentiles) 24-h-average personal PM2.5 concentration was 115 µg/m3 (65,154 µg/m3) for traditional stove users and 52 µg/m3 (39, 81 µg/m3) for Justa stove users; kitchen PM2.5 and BC had similar patterns. Higher concentrations of PM2.5 and BC were associated with higher levels of CRP (e.g., a 25% increase in personal PM2.5 was associated with a 10.5% increase in CRP [95% CI: 1.2-20.6]). In secondary analyses, results were generally consistent with a null association. Evidence for effect modification between pollutant measures and four different cardiovascular risk factors (e.g., high blood pressure) was inconsistent. These results support the growing evidence linking household air pollution and cardiovascular disease.

Early detection of neuropathophysiology using diffusion-weighted magnetic resonance imaging in asymptomatic cats with feline immunodeficiency viral infection.

HIV infection results in a highly prevalent syndrome of cognitive and motor disorders designated as HIV-associated dementia (HAD). Neurologic dysfunction resembling HAD has been documented in cats infected with strain PPR of the feline immunodeficiency virus (FIV), whereas another highly pathogenic strain (C36) has not been known to cause neurologic signs. Animals experimentally infected with equivalent doses of FIV-C36 or FIV-PPR, and uninfected controls were evaluated by magnetic resonance diffusion-weighted imaging (DW-MRI) and spectroscopy (MRS) at 17.5-18 weeks post-infection, as part of a study of viral clade pathogenesis in FIV-infected cats. The goals of the MR imaging portion of the project were to determine whether this methodology was capable of detecting early neuropathophysiology in the absence of outward manifestation of neurological signs and to compare the MR imaging results for the two viral strains expected to have differing degrees of neurologic effects. We hypothesized that there would be increased diffusion, evidenced by the apparent diffusion coefficient as measured by DW-MRI, and altered metabolite ratios measured by MRS, in the brains of FIV-PPR-infected cats relative to C36-infected cats and uninfected controls. Increased apparent diffusion coefficients were seen in the white matter, gray matter, and basal ganglia of both the PPR and C36-infected (asymptomatic) cats. Thalamic MRS metabolite ratios did not differ between groups. The equivalently increased diffusion by DW-MRI suggests similar indirect neurotoxicity mechanisms for the two viral genotypes. DW-MRI is a sensitive tool to detect neuropathophysiological changes in vivo that could be useful during longitudinal studies of FIV.

Menstrual cycle characteristics and reproductive hormone levels in women exposed to atrazine in drinking water.

Atrazine is the most commonly used herbicide in the U.S. and a wide-spread groundwater contaminant. Epidemiologic and laboratory evidence exists that atrazine disrupts reproductive health and hormone secretion. We examined the relationship between exposure to atrazine in drinking water and menstrual cycle function including reproductive hormone levels. Women 18-40 years old residing in agricultural communities where atrazine is used extensively (Illinois) and sparingly (Vermont) answered a questionnaire (n=102), maintained menstrual cycle diaries (n=67), and provided daily urine samples for analyses of luteinizing hormone (LH), and estradiol and progesterone metabolites (n=35). Markers of exposures included state of residence, atrazine and chlorotriazine concentrations in tap water, municipal water and urine, and estimated dose from water consumption. Women who lived in Illinois were more likely to report menstrual cycle length irregularity (odds ratio (OR)=4.69; 95% confidence interval (CI): 1.58-13.95) and more than 6 weeks between periods (OR=6.16; 95% CI: 1.29-29.38) than those who lived in Vermont. Consumption of >2 cups of unfiltered Illinois water daily was associated with increased risk of irregular periods (OR=5.73; 95% CI: 1.58-20.77). Estimated "dose" of atrazine and chlorotriazine from tap water was inversely related to mean mid-luteal estradiol metabolite. Atrazine "dose" from municipal concentrations was directly related to follicular phase length and inversely related to mean mid-luteal progesterone metabolite levels. We present preliminary evidence that atrazine exposure, at levels below the US EPA MCL, is associated with increased menstrual cycle irregularity, longer follicular phases, and decreased levels of menstrual cycle endocrine biomarkers of infertile ovulatory cycles.