Risk factors for endometrial cancer in Black women.

PURPOSE: The incidence of endometrial cancer (EC) has been increasing faster among Black women than among other racial/ethnic groups in the United States. Although the mortality rate is nearly twice as high among Black than White women, there is a paucity of literature on risk factors for EC among Black women, particularly regarding menopausal hormone use and severe obesity. METHODS: We pooled questionnaire data on 811 EC cases and 3,124 controls from eight studies with data on self-identified Black women (4 case-control and 4 cohort studies). We analyzed cohort studies as nested case-control studies with up to 4 controls selected per case. We used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We observed a positive association between BMI and EC incidence (Ptrend < 0.0001) The OR comparing BMI ≥ 40 vs. < 25 kg/m2 was 3.92 (95% CI 2.91, 5.27). Abdominal obesity among those with BMI < 30 kg/m2 was not appreciably associated with EC risk (OR 1.21, 95% CI 0.74, 1.99). Associations of reproductive history with EC were similar to those observed in studies of White women. Long-term use of estrogen-only menopausal hormones was associated with an increased risk of EC (≥ 5 years vs. never use: OR 2.08, 95% CI: 1.06, 4.06). CONCLUSIONS: Our results suggest that the associations of established risk factors with EC are similar between Black and White women. Other explanations, such as differences in the prevalence of known risk factors or previously unidentified risk factors likely underlie the recent increases in EC incidence among Black women.

Quality and Completeness of Myocardial Infarction Recording in Clinical Practice Research Datalink Aurum.

BACKGROUND: Validation studies of the Clinical Practice Research Datalink (CPRD) Aurum database in the UK are critical for making decisions about its suitability and validity for research purposes. OBJECTIVE: To examine data source agreement of myocardial infarction (MI) diagnoses recorded in CPRD Aurum compared with linked Hospital Episode Statistics (HES) data. This comparison provides information on CPRD Aurum data correctness (accuracy, validity) and completeness (presence, missingness). METHODS: Patients with MI diagnoses recorded in either data source were selected from a random sample of 50,000 patients in CPRD Aurum with HES linkage (1997-2017). Correctness was defined as the proportion of MI cases in CPRD Aurum with a concordant MI diagnosis recorded in HES or with strong supporting evidence in either data source. Completeness was defined as the proportion of patients with primary HES-coded MIs with strong supporting evidence that were also present in CPRD Aurum. RESULTS: There were 1260 patients with MI recorded in the CPRD Aurum sample. The overall correctness of the recorded MI diagnoses was 94%: 986 patients (78%) had concordant diagnoses in HES within 90 days; 123 (10%) were concordant with HES, but with an inconclusive date and another 71 (6%) had strong supporting evidence for being a true MI case. There were 1125 patients with MI recorded in HES primary diagnosis fields with strong supporting evidence in either data source. Of these, 880 (78%) were present in CPRD Aurum, with completeness somewhat higher in more recent years. CONCLUSION: MI diagnoses recorded in CPRD Aurum were highly likely to be correct, supporting its use in clinical research studies. Completeness was lower, indicating the need for data linkage for some studies.

Abuse in Childhood and Risk for Sleep Disruption in Adulthood in the Black Women's Health Study.

OBJECTIVE: To investigate the association of early life abuse with sleep disruption risk in adulthood among U.S. Black women. METHODS: We analyzed data from the Black Women's Health Study, a prospective cohort study. In 2005, 29,998 women completed a self-administered questionnaire on early-life experiences of abuse (child and teen) and exposure to danger at any life stage. Participants reported on their sleep quality (snoring and diagnosed sleep apnea) in 2001, whether their "sleep was restless" in 2005, and their average sleep duration in 2009. We used log-binomial regression models to derive risk ratios (RRs) and 95% confidence intervals (CIs) for the association of child/teen abuse and danger at any life stage with snoring, diagnosis of sleep apnea, restless sleep, and short sleep duration. RESULTS: Nearly 50% of participants reported one or more measure of sleep disruption in adulthood. Higher severity of physical abuse was associated with increased risk of sleep disruption and higher severity of sexual abuse was associated with increased risk for most sleep disruptions. The RR comparing child/teen physical and sexual abuse relative to no abuse was highest for diagnosed sleep apnea (2.03, 95% CI: 1.70, 2.41). Feeling in danger at any life stage (child, teen, adult, past year) was generally associated with greater increases in risk of sleep disruption among women with a history of early life abuse than among women without such a history. CONCLUSIONS: Our findings suggest that abuse as a child and/or teen is related to disrupted sleep in adulthood.

Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium.

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.

Night Shift Work and Fecundability in Late Reproductive-Aged African American Women.

Background: We estimated the association between night shift work and fecundability among African American women. Methods: Black Women's Health Study participants (n = 560) aged 30-45 years reported their history of night shift work in 2005. Time to pregnancy for all pregnancies resulting in a livebirth was reported in 2011. We estimated the fecundability ratio (FR) and 95% confidence interval (CI) using proportional probabilities regression, accounting for multiple observations of individual women using generalized estimating equations. Results: We observed 4,417 months of pregnancy attempt time resulting in 390 births. After adjustment for covariates, women who reported ever working night shifts had 20% lower fecundability compared with those who never reported night shift work (FR = 0.80, 95% CI: 0.59-1.04). The FR for women reporting night shift work with a frequency of ≥1 time per month and a duration of ≥2 years was 0.65 (95% CI: 0.47-0.94) relative to women reporting no shift work. We observed a decrease in fecundability associated with ever working night shifts (FR = 0.74, 95% CI: 0.56-0.96) among women aged ≥35 years, but not among younger women (FR = 1.33, 95% CI: 0.78-2.28). Conclusion: A history of working night shifts was associated with reduced fecundability among older reproductive-aged African American women attempting pregnancy.

CPRD Aurum database: Assessment of data quality and completeness of three important comorbidities.

PURPOSE: The Clinical Practice Research Datalink (CPRD) now provides a new medical record database, CPRD Aurum. This is the second of several studies being undertaken to assess the quality of CPRD Aurum data for research. METHODS: We included patients aged 20+, with at least one lab test result of any type from a random sample of 50 000 patients in CPRD Aurum. We assessed whether diagnosis codes for type 2 diabetes, hyperlipidemia, and iron deficiency or unspecified anemia were accompanied by supporting codes including lab results and treatments (correctness) and whether lab results, treatments, or other codes indicate a missing diagnosis record (completeness). RESULTS: Among 37 502 patients in CPRD Aurum, correctness of type 2 diabetes, hyperlipidemia, and anemia diagnoses was high (99%, 93%, and 97%, respectively). Completeness was only high for type 2 diabetes (94%-98%); completeness for hypercholesterolemia and anemia diagnoses was modest even when the presence of treatments and lab results indicated the conditions were likely present (51%-59% and 58%-70%, respectively). CONCLUSIONS: Our findings indicate that for studies of type 2 diabetes, hyperlipidemia, and iron deficiency or unspecified anemia, the diagnosis code is likely to be correct where present. However, a significant proportion of cases of hyperlipidemia or anemia will be missed if only diagnosis codes are used to select patients with these conditions. Researchers should consider using treatments, supporting codes, and, when available, lab data to supplement diagnosis codes and enhance case capture when including these conditions in studies using CPRD Aurum.

Association of Variability in Body Mass Index and Metabolic Health With Cardiometabolic Disease Risk.

Background Metabolic syndrome is associated with high risk of cardiovascular disease, although risk may differ according to the specific conditions present and variability in those conditions. Methods and Results We defined obesity (body mass index [BMI] ≥30 kg/m2) and metabolic health (<2 nonobesity National Cholesterol Education Program Adult Treatment Panel III conditions) among 3632 Framingham Heart Study offspring cohort participants (mean age, 50.8 years; 53.8% women) who were followed up from 1987 to 2014. We defined participants whose variance independent of the mean for a metabolic syndrome-associated measure was in the top quintile as being "variable" for that measure. Variable metabolic health was defined as ≥2 variable nonobesity metabolic syndrome components. We investigated the interaction between obesity and metabolic health in their associations with cardiometabolic disease and cardiovascular disease using Cox proportional hazards regression. In addition, we estimated the associations of BMI variability and variable metabolic health with study outcomes within categories of obesity and metabolic health status, respectively. We observed 567 incident obesity (41 439 person-years), 771 incident metabolically unhealthy state (25 765 person-years), 272 incident diabetes mellitus (56 233 person-years), 503 incident hypertension (12 957 person-years), 589 cardiovascular disease (60 300 person-years), and 195 chronic kidney disease (47 370 person-years) events on follow-up. Obesity and being metabolically unhealthy were independently and positively associated with all outcomes. BMI variability, compared with stable BMI, was associated with 163%, 67%, 58%, and 74% higher risks of having obesity, becoming metabolically unhealthy, having diabetes mellitus, and having hypertension, respectively, among nonobese participants. Variable metabolic health, compared with stable metabolic health, was associated with a 28% higher risk of cardiovascular disease, among metabolically healthy participants. Conclusions We did not observe evidence for a positive interaction between obesity and metabolic health status with regard to study outcomes. BMI and metabolic health variability are associated with adverse health outcomes.

Natural History of Obesity Subphenotypes: Dynamic Changes Over Two Decades and Prognosis in the Framingham Heart Study.

Context: The natural histories of obesity subphenotypes are incompletely delineated. Objectives: To investigate dynamic changes in obesity subphenotypes and associations with outcomes. Design, Setting, Participants, and Measurements: Framingham Offspring Cohort participants (n = 4291) who attended the examination cycles 2 (1979 to 1983) to 7 (1998 to 2001), which included 26,508 participant observations. Obesity subphenotypes [metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUNO), and metabolically unhealthy obese (MUO)] were ascertained based on metabolic health (<2 Adult Treatment Panel III criteria). The outcomes were subclinical cardiovascular disease (CVD), incident diseases [diabetes, hypertension, chronic kidney disease (CKD), CVD], and all-cause mortality. Results: At baseline, 4% and 31% of participants exhibited the MHO and MUNO subphenotypes, respectively. Four-year probability of MHO participants becoming MUO was 43% in women and 46% in men. Compared with MHNO, MHO participants had 1.28-fold (95% CI, 0.85 to 1.93) and 1.92-fold (95% CI, 1.38 to 2.68) higher odds of subclinical CVD and coronary artery calcification, respectively; corresponding values for MUNO were 1.95 (1.54 to 2.47) and 1.92 (1.38 to 2.68). During follow-up (median of 14 years), 231 participants developed diabetes, 784 hypertension, 423 CKD, 639 CVD, and 1296 died. Compared with MHNO, MHO conferred higher risks of diabetes [hazard ratio (HR), 4.69; 95% CI, 2.21 to 9.96] and hypertension (HR, 2.21; 95% CI, 1.66 to 2.94). Compared with MUO, MHO conferred lower risks of diabetes (0.21; 0.12 to 0.39), CVD (0.64; 0.43 to 0.95), and CKD (0.44; 0.27 to 0.73), but similar hypertension, cardiovascular mortality, and overall mortality risks. Conclusion: Over time, most MHO participants developed metabolic abnormalities and clinical disease. The MHO subphenotype is a harbinger of future risk.

Contribution of the neighborhood environment to cross-sectional variation in long-term CVD risk scores in the Framingham Heart Study.

Few studies of the health impact of the built environment have examined downstream outcomes, such as cardiovascular disease. We analyzed the neighborhood-level proportional variance in the 10- and 30-year Framingham risk scores (FRS) in the Framingham Heart Study. Our analysis included 3,103 Offspring- and Generation 3 cohort participants 20-74 years old, inhabiting private residences in Massachusetts geocoded to neighborhoods (defined as 2000 US Census block groups) containing the residences of ≥5 participants. The outcome variables were log-transformed to mitigate the effects of the non-normal distributions. In order to remove the possible effects of neighborhood clustering by age and sex, we analyzed residuals of the transformed FRS regressed upon age and sex. Neighborhood-level intraclass correlations (ICCs) and 95% confidence intervals (CIs) of age- and sex-independent, log-transformed FRS were estimated using multilevel linear regression. Individual- and neighborhood-level variables were then added to models to evaluate their influence on ICCs. Analyses were repeated stratified by sex. Among 2,888 participants living in 187 neighborhoods, 1.73% (95% CI: 0.62, 4.72%) of the variance in 10-year FRS was explained at the neighborhood level. The neighborhood ICC was 2.70% (95% CI: 0.93, 7.56) among women but 0.23% (95% CI: 0.00, 99.47%) among men. In the analysis of the neighborhood-level variances in 30-year FRS among 2,317 participants residing in 164 neighborhoods, the ICCs were 3.31% (95% CI: 1.66, 6.47%), 6.47% (95% CI: 3.22, 12.58), and 0.74% (95% CI: 0.01, 33.31), among all participants, women, and men, respectively. In our homogenous middle-class white population in Massachusetts, residential neighborhoods explained a small proportion of the variance in CVD risk.

Exogenous Hormone Use and Endometrial Cancer in U.S. Black Women.

Background: Although endometrial cancer risk differs among white and black women, few data on its associations with exogenous hormone use in the latter group are available. Studies have reported lower endometrial cancer risk among users of oral contraceptives (OCs), but higher risk among users of estrogen-only female menopausal hormones (FMHs). Evidence for the risk among estrogen plus progestin FMHs users is equivocal.Methods: We followed 47,555 Black Women's Health Study participants with an intact uterus from 1995 through 2013. Data on exogenous hormone use, covariates, and endometrial cancer were obtained biennially. Self-reported incident cases of endometrial cancer were confirmed by medical records or cancer registries whenever possible. We estimated incidence rate ratios (IRRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression.Results: We observed 300 endometrial cancer cases during 689,546 person-years of follow-up. Compared with never use, ≥10 years' duration of OC use was associated with lower risk (multivariable IRR = 0.45, 95% CI, 0.27-0.74), but risk was higher among current users of estrogen-only (IRR = 3.78, 95% CI, 1.69-8.43) and estrogen plus progestin FMH (IRR = 1.55, 95% CI, 0.78-3.11). Risk was not increased among former users of estrogen-only (IRR = 0.87, 95% CI, 0.44-1.72) or estrogen plus progestin FMH (IRR = 0.63, 95% CI, 0.36-1.09).Conclusions: Current use of estrogen-only and estrogen plus progestin FMH was associated with increased risk of endometrial cancer. Risk appeared lower among former users of estrogen plus progestin FMH. Long-term OC use was associated with reduced risk.Impact: Our results are generally consistent with those among white women. Cancer Epidemiol Biomarkers Prev; 27(5); 558-65. ©2018 AACR.

Breastfeeding and Endometrial Cancer Risk: An Analysis From the Epidemiology of Endometrial Cancer Consortium.

OBJECTIVE: To investigate the association between breastfeeding and endometrial cancer risk using pooled data from 17 studies participating in the Epidemiology of Endometrial Cancer Consortium. METHODS: We conducted a meta-analysis with individual-level data from three cohort and 14 case-control studies. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the association between breastfeeding and risk of endometrial cancer using multivariable logistic regression and pooled using random-effects meta-analysis. We investigated between-study heterogeneity with I  and Q statistics and metaregression. RESULTS: After excluding nulliparous women, the analyses included 8,981 women with endometrial cancer and 17,241 women in a control group. Ever breastfeeding was associated with an 11% reduction in risk of endometrial cancer (pooled OR 0.89, 95% CI 0.81-0.98). Longer average duration of breastfeeding per child was associated with lower risk of endometrial cancer, although there appeared to be some leveling of this effect beyond 6-9 months. The association with ever breastfeeding was not explained by greater parity and did not vary notably by body mass index or histologic subtype (grouped as endometrioid and mucinous compared with serous and clear cell). CONCLUSION: Our findings suggest that reducing endometrial cancer risk can be added to the list of maternal benefits associated with breastfeeding. Ongoing promotion, support, and facilitation of this safe and beneficial behavior might therefore contribute to the prevention of this increasingly common cancer.

Reproductive factors and incidence of endometrial cancer in U.S. black women.

PURPOSE: Previous studies have shown that reproductive history is a strong determinant of endometrial cancer risk among white women. Less is known about how reproductive history affects endometrial cancer risk among black women, whose incidence and mortality differ from white women. We investigated the associations of age at menarche, parity, timing of births, and menopausal age with endometrial cancer in the Black Women's Health Study, a prospective cohort study. METHODS: Every 2 years from 1995 to 2013, 47,555 participants with intact uteri at baseline in 1995 completed questionnaires on reproductive and medical history, and lifestyle factors. Self-reported cases of endometrial cancer were confirmed by medical record, cancer registry, or death certificate when available. Cox proportional hazards regression was used to estimate multivariable incidence rate ratios (IRR) and 95% confidence intervals (CI). RESULTS: During 689,501 person-years of follow-up, we identified 300 incident cases of endometrial cancer. The strongest associations with endometrial cancer were found for early age at menarche (<11 vs. 12-13 years: IRR 1.82, 95% CI 1.31, 2.52), and later age at first birth (≥30 vs. <20 years: IRR 0.26, 95% CI 0.13, 0.50). Parous women were less likely than nulliparous women to develop endometrial cancer (IRR 0.77, 95% CI 0.57, 1.05), but there was little evidence of a dose-response relationship for number of births. CONCLUSION: Associations between reproductive factors and endometrial cancer among black women were generally consistent with those in studies of white women.

History of uterine leiomyoma and risk of endometrial cancer in black women.

BACKGROUND: Previous studies have found an association between uterine leiomyomata (UL) and uterine malignancies. This relation has not been studied in black women, who are disproportionately affected by UL. METHODS: We investigated prospectively the association between self-reported physician-diagnosed UL and endometrial cancer in the Black Women's Health Study. During 1995-2013, 47,267 participants with intact uteri completed biennial health questionnaires. Reports of endometrial cancer were confirmed by pathology data from medical records and cancer registries. Cox regression was used to derive incidence rate ratios (IRR) and 95% confidence intervals (CI). RESULTS: There were 300 incident endometrial cancer cases during 689,546 person-years of follow-up. In multivariable models, UL history was associated with a 42% greater incidence of endometrial cancer compared with no such history (95% CI 1.12-1.80). IRRs for cancer diagnosed 0-2, 3-9, and ≥10 years after UL diagnosis were 3.20 (95% CI 2.06-4.98), 0.95 (95% CI 0.60-1.52), and 1.35 (95% CI 1.03-1.77), respectively. Stronger overall associations between UL history and endometrial cancer were observed for later stages at cancer diagnosis (IRR = 2.25, 95% CI 1.09-4.63) and type II/III cancers (IRR = 3.13, 95% CI 1.64-5.99). CONCLUSIONS: In this large cohort of black women, a history of UL was positively associated with endometrial cancer, particularly type II/III tumors. The strongest association was observed for cancer diagnosed within 2 years of UL diagnosis, a finding that might be explained by greater surveillance of women with UL or misdiagnosis of cancer as UL. However, an association was also observed for cancer reported ≥10 years after UL diagnosis.

Body Size, Metabolic Factors, and Risk of Endometrial Cancer in Black Women.

Total and abdominal obesity, as well as metabolic factors such as type 2 diabetes, have been associated with a higher risk of endometrial cancer in white women. It remains unclear to what extent these factors influence the risk of endometrial cancer in black women. We followed 47,557 participants from the Black Women's Health Study for incident endometrial cancer from 1995 through 2013 (n = 274). We used Cox regression models to estimate incidence rate ratios and 95% confidence intervals while accounting for potential confounders. Incidence rate ratios for body mass indices (weight (kg)/height (m)(2)) of 25.0-29.9, 30.0-34.9, 35.0-39.9, and ≥40.0 versus those <25.0 were 1.00 (95% confidence interval (CI): 0.67, 1.48), 1.49 (95% CI: 0.97, 2.30), 2.16 (95% CI: 1.34, 3.49), and 3.60 (95% CI: 2.24, 5.78), respectively (Ptrend <0.0001). A high weight-to-height ratio was also associated with a higher risk (for the highest quartile vs. the lowest, incidence rate ratio = 2.83, 95% CI: 1.77, 4.53), as was type 2 diabetes mellitus (incidence rate ratio = 1.52, 95% CI: 1.04, 2.21). Positive associations with measures of central adiposity (waist circumference, waist-to-hip ratio, and waist-to-height ratio) and hypertension were attenuated after we controlled for body mass index. Total adiposity was an independent risk factor for endometrial cancer among black women and appeared to explain most of the associations seen with other adiposity measures and metabolic factors.

Associations of Dietary Long-Chain ω-3 Polyunsaturated Fatty Acids and Fish Consumption With Endometrial Cancer Risk in the Black Women's Health Study.

Dietary long-chain (LC) ω-3 polyunsaturated fatty acids (PUFAs), which derive primarily from intakes of fatty fish, are thought to inhibit inflammation and de novo estrogen synthesis. This study prospectively examined the associations of dietary LC ω-3 PUFAs and fish with endometrial cancer risk in 47,602 African-American women living in the United States, aged 21-69 years at baseline in 1995, and followed them until 2013 (n = 282 cases). Multivariable-adjusted Cox regression models estimated hazard ratios and 95% confidence intervals for associations of LC ω-3 PUFA (quintiled) and fish (quartiled) intake with endometrial cancer risk, overall and by body mass index (BMI; weight (kg)/height (m)(2)). The hazard ratio for quintile 5 of total dietary LC ω-3 PUFAs versus quintile 1 was 0.79 (95% confidence interval (CI): 0.51, 1.24); there was no linear trend. Hazard ratios for the association were smaller among normal-weight women (BMI <25: hazard ratio (HR) = 0.53, 95% CI: 0.18, 1.58) than among overweight/obese women (BMI ≥ 25: HR = 0.88, 95% CI: 0.54, 1.43), but these differences were not statistically significant. Fish intake was also not associated with risk (quartile 4 vs. quartile 1: HR = 0.86, 95% CI: 0.56, 1.31). Again hazard ratios were smaller among normal-weight women (HR = 0.65) than among overweight/obese women (HR = 0.94). While compatible with no association, the hazard ratios observed among leaner African-American women are similar to those from recent prospective studies conducted in predominantly white populations.

Occupational exposures and chronic kidney disease: Possible associations with endotoxin and ultrafine particles.

BACKGROUND: Chronic kidney disease (CKD) carries a high public health burden yet there is limited research on occupational factors, which are examined in this retrospective case-control study. METHODS: Newly diagnosed cases of CKD (n = 547) and controls (n = 508) from North Carolina provided detailed work histories in telephone interviews. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: There was heterogeneity in the association of CKD and agricultural work, with crop production associated with increased risk and work with livestock associated with decreased risk. Work with cutting/cooling/lubricating oils was associated with a reduced risk. CKD risk was increased for working in dusty conditions. CONCLUSIONS: CKD risk was reduced in subjects with occupational exposures previously reported to involve endotoxin exposure. Further, exposure to dusty conditions was consistently associated with increased risk of glomerulonephritis across industry, suggesting that research on CKD and ultrafine particulates is needed.

Association between inflammatory biomarkers and bone mineral density in a community-based cohort of men and women.

OBJECTIVE: Based upon evidence in animal and in vitro studies, we tested the hypothesis that higher serum concentrations of the cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) and the inflammatory marker C-reactive protein (CRP) would be inversely associated with bone mineral density (BMD) in a community-based cohort of men and women, with the strongest associations among postmenopausal women not receiving menopause hormonal therapy (MHT). METHODS: We ascertained fasting serum concentrations of IL-6, TNFα, and CRP and measured BMD at the femoral neck, trochanter, total femur, and spine (L2-L4) using dual x-ray absorptiometry in 2,915 members of the Framingham Offspring Study (1996-2001). We used multivariable linear regression to estimate the difference (ß) in BMD at each bone site associated with a 1-unit increase in log-transformed serum concentrations of IL-6, TNFα, and CRP separately for men (n = 1,293), premenopausal women (n = 231), postmenopausal women receiving MHT (n = 498), and postmenopausal women not receiving MHT (n = 893). RESULTS: Inflammatory biomarkers were not associated with BMD in men. Among premenopausal women, there were statistically significant, modest inverse associations between IL-6 and trochanter BMD (ß = -0.030, P < 0.01) and between CRP and femoral neck (ß = -0.015, P = 0.05) and trochanter BMD (ß = -0.014, P = 0.04). TNFα was positively associated with spine BMD (ß = 0.043, P = 0.01). In postmenopausal women receiving MHT, CRP was positively associated with femoral neck BMD (ß = 0.011, P = 0.04). There were no associations among postmenopausal women not receiving MHT. CONCLUSION: The lack of consistency in our results suggests that elevated circulating concentrations of inflammatory biomarkers may not be a risk factor for low BMD.

A novel method of imaging calcium urolithiasis using fluorescence.

PURPOSE: In the surgical management of urolithiasis the goal of treatment is not only to remove calculi, but also prevent future stone formation by rendering the patient stone-free/fragment-free. Achieving this goal is often difficult with endoscopic procedures due to the inability to visualize small calculi well even with x-ray or ultrasound. We evaluated fluorescence probes as a novel method of identifying calculi in the urinary tract. MATERIALS AND METHODS: In vitro calcium stones were incubated with each of the Osteosense 680 and Osteosense 750 calcium binding fluorescence probes, and imaged with a near infrared fluorescence imaging system. Using a mouse model calculi were placed in the renal pelvis and the probes were injected intravenously. Imaging was performed at various times after injection. RESULTS: In vitro the Osteosense 680 probe demonstrated high binding affinity for calcium oxalate-struvite, calcium phosphate-struvite and ammonium urate-calcium oxalate-calcium phosphate stones, and lower binding affinity for the calcium phosphate stone. In contrast, the Osteosense 750 probe demonstrated high binding affinity for calcium oxalate-struvite and calcium phosphate-struvite stones, and lower binding affinity for calcium phosphate and ammonium urate-calcium oxalate-calcium phosphate stones. In vivo intravenous administration of the probes was successful in labeling all calcium stone types tested. CONCLUSIONS: Fluorescence imaging provides a new method for identifying calculi in the urinary tract. The improved visualization of these stones/fragments would make endoscopic procedures less difficult, decrease the risk of complications and increase the chance of rendering the patient stone-free/fragment-free.

Effects of ethanol on photoreceptors and visual function in developing zebrafish.

PURPOSE: Children born to mothers who have consumed alcohol during pregnancy have an array of retinal abnormalities and visual dysfunctions. In the past, rodent systems have been used to study the teratogenic effects of ethanol on vertebrate embryonic development. The exact developmental windows in which ethanol causes specific developmental defects have been difficult to determine because rodents and other mammals develop in utero. In this study, we characterized how ethanol affects the function and development of the visual system in an ex utero embryonic system, the zebrafish. METHODS: Zebrafish embryos were raised in fish water containing various concentrations of ethanol from 2 to 5 days after fertilization. The effects of ethanol on retinal morphology were assessed by histologic and immunohistochemical analyses and those on retinal function were analyzed by optokinetic response (OKR) and electroretinography (ERG). RESULTS: Zebrafish embryos exposed to moderate and high levels of ethanol during early embryonic development had morphological abnormalities of the eye characterized by hypoplasia of the optic nerve and inhibition of photoreceptor outer segment growth. Ethanol treatment also caused an increased visual threshold as measured by the OKR. Analysis with the ERG indicated that there was a severe reduction of both the a- and b-waves, suggesting that ethanol affects the function of the photoreceptors. Indeed, low levels of ethanol that did not cause obvious morphologic changes in either the body or retina did affect both the OKR visual threshold and the a- and b-wave amplitudes. CONCLUSIONS: Ethanol affects photoreceptor function at low concentrations that do not disturb retinal morphology. Higher levels of ethanol inhibit photoreceptor development and cause hypoplasia of the optic nerve.