Covariation between serum cotinine and blood lead levels among US pediatric populations: Trends from 1999 to 2018.

BACKGROUND: Tobacco smoke, including both active and passive smoke, can be an important source of lead exposure. However, the relationship between passive tobacco smoke exposure (PTSE) and blood lead levels (BLL), especially in vulnerable populations, needs to be further explored. The present study was to assess the covariation between serum cotinine, a measure of PTSE, and BLL in a pediatric population during 1999-2018. METHODS: Data on 21,817 children, aged 3-19 years, was extracted from the biennial nationally representative surveys. The trends of the prevalence of lead exposure (BLL ≥ 3.5 µg/dL) and PTSE (cotinine ≥ 1 ng/mL but < 10 ng/mL) were determined, and the covariation between BLL and cotinine was assessed. The population attributable fraction (PAF) of PTSE to the BLL was proxied using the partial R2 of the hierarchical linear regression. The association between PTSE and lead exposure was estimated using multivariate logistic regression. RESULTS: A parallel decreasing trend in the prevalence of lead exposure and PTSE was observed. Similarly, the means of both BLL and cotinine declined simultaneously. Overall, the PAF from PTSE towards blood lead was 7 %, doubling the PAF from race/ethnicity and family income combined. Stratified by race/ethnicity, PAF from PTSE was 8 % in Blacks and Whites and 4 % for Hispanics. The odds ratio of PTSE with lead exposure was 2.45 (95 % CI, 1.75, 3.44), 2.00 (1.21, 3.33), and 1.16 (0.64, 2.13) for Black, White, and Hispanic children, respectively. Cotinine mean remained two times higher in Blacks than non-Black children at the end of the study period. CONCLUSION: Serum cotinine and BLL may have a significant association in children that persists even as both have been steadily declining in recent years. The contribution from PTSE to blood lead variations could be greater than that from socioeconomic factors. Further reducing lead exposure might be achieved by eliminating PTSE, particularly for the Black pediatric population.

The Diverging Trend in Exposure to Environmental Tobacco Smoke Among US Children.

OBJECTIVE: Environmental tobacco smoke exposure (ETSE) was race/ethnicity-specific, but how the race/ethnicity-specific ETSE has changed over time, diverging or converging, remains unclear. We examined ETSE trends by race/ethnicity in US children aged 3-11 years. METHODS: We analyzed the data of 9678 children who participated in the biennial National Health and Nutrition Examination Surveys, 1999-2018. ETSE was defined as serum cotinine ≥ 0.05 ng/ml, with ≥ 1 ng/ml as heavy exposure. For trend description, adjusted biennial prevalence ratios (abiPR: the ratio associated with a 2-year increase in time) were estimated by race/ethnicity. The prevalence ratios between races/ethnicities were used to quantify ethnoracial differences in different survey periods. Analyses were performed in 2021. RESULTS: The overall ETSE prevalence was cut by almost half, from 61.59% (95% confidence interval = 56.55%, 66.62%) in the 1999-2004 survey to 37.61% (33.90%, 41.31%) in 2013-2018, exceeding the national 2020 health target (47.0%). However, the decrease occurred unequally between races/ethnicities. Heavy ETSE declined significantly in white [abiPR = 0.80 (0.74, 0.86)] and Hispanic children [0.83 (0.74, 0.93)], but insignificantly in black children [0.97 (0.92, 1.03)]. Consequently, the adjusted prevalence ratio between black children and white children increased from 0.82 (0.47, 1.44) in 1999-2004 to 2.73 (1.51, 4.92) in 2013-2018 for heavy ETSE. Hispanic children remained at the lowest risk throughout the study period. CONCLUSION: Overall ETSE prevalence was cut by half between 1999 and 2018. However, due to uneven declines, the gaps between black children and others have expanded in heavy ETSE. Special vigilance is needed in preventive medicine practice with black children.

Exposure to p-dichlorobenzene and prevalent endocrine-related reproductive cancers among US women.

P-dichlorobenzene (p-DCB) is a pest repellent and air deodorant that is commonly found in the household and public buildings. Exposure to p-DCB has been suggested to have potential metabolic and endocrine effects. Little is known about its association with endocrine-related female cancers. In this cross-sectional study, a nationally representative subsample of 4459 women, aged 20 years or older, in the 2003-2016 National Health and Nutrition Examination Survey was analyzed for the association between p-DCB exposure, measured as urinary concentrations of 2,5-dichlorophenol (2,5-DCP), the primary metabolite of p-DCB, and prevalent endocrine-related female cancers (defined as breast, ovarian, and uterine cancers) using multivariate logistic regression models, adjusting for potential confounders. Of the study participants, 202 women (weighted prevalence, 4.20%) reported being diagnosed with any of these endocrine-related reproductive cancers. Women with reproductive cancers showed a statistically significant increase in urinary 2,5-DCP concentrations (weighted geometric mean, 7.97 vs. 5.84 µg/g creatinine; p < 0.0001), compared to women without these cancers. After adjusting for potential confounders, we found that women in the moderate (1.94- < 28.10 µg/g creatinine) and high level (≥ 28.10 µg/g creatinine) of 2,5-DCP had significantly increased odds of endocrine-related reproductive cancers (odds ratio of 1.66 (95% CI: 1.02, 2.71) and 1.89 (1.08, 3.29), respectively), as compared with those in the low exposure group (< 1.94 µg/g creatinine). This study demonstrates a potential relation between p-DCB exposure and prevalent endocrine-related reproductive cancers in US women. Prospective and mechanistic studies would further explore these interactions and elucidate the pathogenesis of endocrine-related female cancers potentially associated with p-DCB exposure.

Exposure to endocrine-disrupting metals and serum estrogen levels among US women.

Multiple factors could affect estrogen levels in the body; however, the impact of exposure to endocrine-disrupting chemicals on estrogen levels in humans remains inconclusive. This cross-sectional study was to assess the association between blood levels of endocrine-disrupting metals (including cadmium, lead, and mercury) and serum estradiol levels in 1618 women (aged ≥ 20 years) who participated in the 2013-2016 National Health and Nutrition Examination Survey. Using multiple general linear models, we estimated percent changes of estradiol levels in association with blood metal concentrations. Age-specific analysis was further conducted. The median level of blood cadmium, lead, and mercury was 0.31 µg/L (range: 0.07-7.23), 0.76 µg/dL (0.11-12.80), and 0.73 µg/L (0.20-36.90), respectively, and the median estradiol level was 31.10 pg/mL (range: 2.12-523.00) among women aged 20-80 years. After adjusting for potential confounders, a 10 % increase in blood cadmium and lead levels was associated with 1.43 % (95 % CI: 0.50, 2.37) increased levels and 1.45 % (- 2.17, - 0.11) decreased levels of estrogen, respectively, in the total study population. When stratified by age, the positive association with cadmium was only seen in women aged 20-49 years [1.47 % (0.39, 2.56) increased estradiol] and the inverse association with lead was seen among women aged 50-80 years [3.40 % (- 4.78, - 2.00) decreased estradiol]. Mercury was not significantly associated with estrogen levels. Our study demonstrates a potential relationship between exposure to endocrine-disrupting cadmium and lead and serum estrogen levels in US women. Age-specific associations were observed. Prospective and mechanistic studies are warranted to further explore these interactions and the associated reproductive toxicities.

Urinary Concentrations of Endocrine-Disrupting Metals and Prevalent Breast Cancer in US Women.

The toxic metals cadmium, lead, and mercury are endocrine-disrupting agents that could produce estrogenic effects involving breast carcinogenesis. In this study, we further explored the relationship between exposure to these metals and prevalent breast cancer among female participants, aged 20 years or older, in the 2007-2016 National Health and Nutrition Examination Survey (NHANES). Exposure was determined by measuring urinary concentrations of metals using inductively coupled plasma mass spectrometry. Urine creatinine-corrected concentrations of metals were calculated for each study participant. Multivariate logistic regression models were constructed to examine the association between urinary metals and prevalent breast cancer, adjusting for potential confounders. Of the 3352 study participants, 106 had been diagnosed with breast cancer (weighted prevalence, 3.13%). The results show that women with breast cancer had significantly higher urinary concentrations of lead and cadmium (both p < 0.0001) than those without breast cancer. After adjusting for all the covariates included in the study, however, only urinary lead was shown to be significantly associated with increased prevalence of breast cancer, with an odds ratio of 2.95 (95% CI: 1.13, 7.70) in the highest quartile of urinary lead concentrations (≥ 0.71 µg/g creatinine) as compared with the lowest quartile. No statistically significant associations were observed between urine cadmium or mercury levels and breast cancer. This study demonstrates a potential association between lead exposure and prevalent breast cancer among US women. Prospective and mechanistic studies are warranted to further investigate this interaction and explore the role of lead in breast carcinogenesis.

Crossover Trends in Current Cigarette Smoking Between Racial and Ethnic Groups of US Adolescents Aged 12-19 Years Old, 1999-2018.

OBJECTIVE: To examine the racial difference and trends in cigarette smoking among adolescents from 1999 to 2018. METHODS: We analyzed the data of 10,760 adolescents aged 12-19 who participated in the National Health and Nutrition Examination Surveys (NHANES), 1999-2018. Current tobacco smoking (CTS) was defined as participants with serum cotinine ≥10 ng/mL. Adjusted biennial prevalence ratios (abiPR: the ratio associated with a two-year increase in time) were estimated. RESULTS: Diverging trends in CTS prevalence were revealed in adolescents. The steepest decrease occurred in Hispanics aged 12-17, with 15% declining every two calendar years [abiPR = 0.85(0.77, 0.94)]. The sharpest increase occurred with Blacks aged 18-19 years [abiPR = 1.06(0.99, 1.14)]. A crossover of prevalence trend between Blacks and Whites occurred in adolescents aged 18-19 years old due to the diverging trends. The average CTS prevalence was significantly higher in Whites than in Blacks in the early [(1999-2008, 13.65% (11.85%, 15.46%) vs. 8.80% (7.55%, 10.04%)], but Blacks had a higher average in recent years [(2009-2018, 8.32% (6.53%, 10.12%) vs. 7.77% (5.86%, 9.68%)]. For adolescents aged 18-19 years, the survey cycles or calendar years linearly explained 71% of the variations in the prevalence for Hispanics, 60% for Whites, but only 1% for Blacks. CONCLUSIONS: A crossover in the trend of current tobacco smoking occurred between 1999 and 2018 due to an increase in prevalence among Black adolescents and a significant decrease in prevalence among other racial groups.

Ambient air emissions of endocrine-disrupting metals and the incidence of hormone receptor- and HER2-dependent female breast cancer in USA.

Limited evidence exists on the relationship between exposure to endocrine-disrupting metals in ambient air and hormone receptor- and HER2-dependent breast cancer. This study investigates the association between ambient air emissions of endocrine-disrupting metals and the incidence of female breast cancer of different receptor status. County-level data from the US national datasets were analyzed for the association between emissions of various metals including arsenic, cadmium, chromium VI, lead, and mercury, and the annual age-adjusted incidence of hormone receptor-dependent breast cancer for 1990-2016 and HER2-dependent breast cancer for 2010-2016 using adjusted linear regression models. Lead emissions showed the strongest association among the metals examined with the incidence of different receptor status breast cancers, including ER-positive, ER-negative, PR-negative, HER2-negative, and Triple-negative breast cancers, with the adjusted ß ranging from 917.26 for ER-negative to 3182.37 for HER2-negative breast cancer. Arsenic and mercury showed significant associations with the incidence of ER-positive, ER-negative, PR-positive, and PR-negative breast cancers. However, cadmium emissions were only significantly associated with ER-negative breast cancer. Moreover, chromium was not associated with any subtypes of breast cancer. Among all of the metals, only lead and mercury emissions showed significant associations with HER2-negative and Triple-negative breast cancer incidence. The results from this study suggest that increased exposure to endocrine-disrupting metals, especially lead, in ambient air could be associated with an increased incidence of female breast cancers with various receptor status in the US. Prospective studies are warranted to further explore this relationship.

Pet ownership and risk of dying from cancer: observation from a nationally representative cohort.

We longitudinally examined the relationship between pet ownership and risk of dying from cancer in a nationally representative cohort of 13,725 adults in the Third National Health and Nutrition Examination Survey, 1988-1994. The vital status was followed through 31 December 2010. Women who owned pets (any type) presented one-year shorter survival time (15.88 years) than non-pet owner (16.83 years). A larger difference of survival time was particularly seen in bird owners (13.01 years) compared to non-bird owners (16.82 years). After adjusting for potential confounders, hazard ratio (HR) of dying from cancer associated with any type of pets was 1.08 (95% CI = 0.77-1.50) for men and 1.40 (1.01-1.93) for women. The association in women was presumably driven by owning birds [HR 2.41 (1.34-4.31)] or cats [HR 1.48 (0.97-2.24)]. Keeping birds and cats in the household was associated with an increased risk of dying from cancer, especially in women.

Blood levels of endocrine-disrupting metals and prevalent breast cancer among US women.

A growing body of evidence has pointed to a role of environmental chemical exposures in breast cancer etiology. This study was to examine the association between exposure to the endocrine-disrupting metals, including cadmium (Cd), lead (Pb), and mercury (Hg), and breast cancer in US women. A nationally representative subsample of 9260 women aged ≥ 20 years in the 2003-2012 National Health and Nutrition Examination Survey was analyzed for the association of blood levels of these metals with prevalent breast cancer using multivariate logistic regression models. Of the study participants, 284 women (weighted prevalence, 2.8%) were self-reported being diagnosed with breast cancer during 2003-2012. Breast cancer women showed significantly elevated blood levels of Cd and Pb, but not Hg. After adjusting for potential confounders, we found that women in all of the higher quartiles of blood lead levels (BLLs) had significantly increased odds ratio of prevalent breast cancer compared with those in the lowest quartile. However, a significant association with prevalent breast cancer was not seen with blood levels of either Cd or Hg. Our study demonstrates a potential relationship between lead exposure, measured as BLLs, and female breast cancer. Additional epidemiologic and mechanistic studies would further explore these interactions and elucidate the potential role of lead exposure in breast cancer etiology.

Endocrine-disrupting metals in ambient air and female breast cancer incidence in US.

Metals could act as endocrine disruptors that mimic the actions of hormones, such as estrogens, and contribute to the development and progression of breast cancer. In this study, we examined the association between ambient air emissions of several endocrine-disrupting metals and the incidence of female breast cancer in the United States by analyzing county-level data from national datasets. Linear regression analysis was conducted to evaluate the association in unadjusted and adjusted models. Of the metals analyzed, air emissions of arsenic, cadmium, lead, and mercury, but not chromium VI, were significantly associated with the incidence of all breast cancers, after adjusting for potential confounders. Emissions of arsenic, lead, and mercury were found to be significantly associated with the incidence of estrogen receptor (ER)-positive breast cancer. Among these metals, air emissions of lead showed the strongest association with breast cancer incidence with the ß of 3756.66 (95% CI: 1660.29, 5853.03) for all breast cancers and 2433.85 (440.59, 4427.10) for ER-positive breast cancer. Our results demonstrate that exposure to endocrine-disrupting metals in ambient air may be associated with an increased incidence of breast cancer in the United States. Further studies are needed to explore these interactions and to elucidate mechanisms of action.

Pet ownership and the risk of dying from lung cancer, findings from an 18 year follow-up of a US national cohort.

PURPOSE: In contrast to the popularity of pets, research on the health effects of living with pets, particularly, on the risk of cancer, is minimal and inconclusive. We longitudinally examined relationships between pet ownership and the risk of dying from lung cancer. METHODS: We analyzed nationally representative data of 13,725 adults aged ≥ 19 who answered the question about pet ownership in the Third National Health and Nutrition Examination Survey, 1988-1994, as the baseline survey. Vital status was followed through December 31st, 2010. RESULTS: About 43% of the study population owned pets, with 20.4% having cats and 4.6% having birds. A total of 213 lung cancer deaths were recorded by the end of 183,094 unweighted person-years of follow-up with a lung-cancer specific death rate of 1.00 per 1000 person-years. After adjustment for cigarette smoking, alcohol drinking, physical activity, body mass index, history of atopic conditions, and serum cotinine, owning a pet (any) was associated with a doubled mortality rate among women for lung cancer [hazard ratio (HR)= 2.31 (1.41-3.79)] over non-owners. This association was largely attributed to having a cat or a bird. The HR was 2.85 (1.62-5.01) for cats, and 2.67 (0.68-10.5) for birds. The HR for dogs was 1.01 (0.57-1.77). No significant patterns of association were observed among men either for any pets or for a subtype of pet. CONCLUSIONS: Living with a pet, especially, a cat or a bird, was significantly associated with elevated hazard of dying from lung cancer among women. The detrimental effect that pets conferred was not explained by confounding from cigarette smoking or atopic conditions.

Exposure to ambient PM2.5 during pregnancy and preterm birth in metropolitan areas of the state of Georgia.

A number of studies has pointed to air pollution as an additional factor that could be associated with preterm birth. We assessed in this study the association between exposure to PM2.5 in ambient air during pregnancy and preterm birth in metropolitan areas of the state of Georgia, where the rate of preterm birth has been among the highest in the nation over the years. Birth data were obtained from the National Center for Health Statistics natality dataset. The study population consisted of 53,094 singleton live births between January 1 and December 31, 2004 in nine metropolitan counties of Georgia. Preterm birth was defined as birth, which occurs before 37 weeks of gestation. County-level daily air quality index (AQI) data obtained from the US Environmental Protection Agency (EPA) was used to estimate individual exposure levels of PM2.5 for each study participant based on the county of residence for the duration of the pregnancy. A multivariate logistic regression analysis was conducted to assess the association, adjusting for potential confounders. Of the infants whose mothers resided in the nine metropolitan counties of Georgia, 4543 (8.6%) were born preterm. A higher rate of preterm birth (9.8%) was observed in infants whose mothers were exposed to ambient PM2.5 with AQI values > 50 than the ones with AQI ≤ 50 (EPA standard for good air quality conditions). Mothers with exposure to PM2.5 at average AQI values greater than 50 during the entire pregnancy were at increased risk of preterm birth (odds ratio 1.15; 95% CI 1.07, 1.25), after adjusting for sex of infant, mother's age, race/ethnicity, education, marital status, prenatal care, cigarette smoking, alcohol consumption, and season of conception. The study provides more evidence on the role of PM2.5 in preterm birth. Reducing exposure to ambient particulate matter, especially in urban areas, for pregnant women would be necessary to improve the health of infants.

Ambient air emissions of polycyclic aromatic hydrocarbons and female breast cancer incidence in US.

To examine ambient air pollutants, specifically polycyclic aromatic hydrocarbons (PAHs), as a factor in the geographic variation of breast cancer incidence seen in the US, we conducted an ecological study involving counties throughout the US to examine breast cancer incidence in relation to PAH emissions in ambient air. Age-adjusted incidence rates of female breast cancer from the surveillance, epidemiology, and end results (SEER) program of the US National Cancer Institute were collected and analyzed using SEER*Stat 8.3.2. PAH emissions data were obtained from the Environmental Protection Agency. Linear regression analysis was performed using SPSS 23 software for Windows to analyze the association between PAH emissions and breast cancer incidence, adjusting for potential confounders. Age-adjusted incidence rates of female breast cancer were found being significantly higher in more industrialized metropolitan SEER regions over the years of 1973-2013 as compared to less industrialized regions. After adjusting for sex, race, education, socioeconomic status, obesity, and smoking prevalence, PAH emission density was found to be significantly associated with female breast cancer incidence, with the adjusted ß of 0.424 (95% CI 0.278, 0.570; p < 0.0001) for emissions from all sources and of 0.552 (95% CI 0.278, 0.826; p < 0.0001) for emissions from traffic source. This study suggests that PAH exposure from ambient air could play a role in the increased breast cancer risk among women living in urban areas of the US. Further research could provide insight into breast cancer etiology and prevention.

Risk factors of periodontal disease in maintenance hemodialysis patients.

To explore the characteristics and relevant risk factors of periodontal disease (PD) among hemodialysis patients.Uremic patients on maintenance hemodialysis from November 2015 to March 2016 were retrospectively reviewed. Patients were divided into a PD group and a non-PD group. Demographic and laboratory data were collected and analyzed.In all, 136 uremic patients (79 males and 57 females, aged 50.8 ±â€Š15.3 years) on maintenance hemodialysis were included in this study. The incidence of PD increased with age. Hemodialysis patients most likely developed PD if they were male, smokers, or diabetic (P = .009, <.001, and <.001, respectively). Patients brushing their teeth twice daily had significantly less chance of developing PD as compared with those only brushing once daily (P < .001). Hemodialysis patients in the PD group had significantly higher levels of total cholesterol, high-sensitivity C-reactive protein, fasting blood glucose, and peripheral white blood cell counts, compared with the non-PD group (all P < .001). Logistic regression analysis revealed that diabetes, total cholesterol, high-sensitivity C-reactive protein, and peripheral white blood cell count were independent risk factors for developing PD, whereas teeth brushing twice daily and serum calcium were favorable factors for maintenance hemodialysis patients against PD.Identification of risk factors provides a theoretical basis for prevention and improvement of PD among maintenance hemodialysis patients.

Geographic variations in female breast cancer incidence in relation to ambient air emissions of polycyclic aromatic hydrocarbons.

A significant geographic variation of breast cancer incidence exists, with incidence rates being much higher in industrialized regions. The objective of the current study was to assess the role of environmental factors such as exposure to ambient air pollution, specifically carcinogenic polycyclic aromatic hydrocarbons (PAHs) that may be playing in the geographic variations in breast cancer incidence. Female breast cancer incidence and ambient air emissions of PAHs were examined in the northeastern and southeastern regions of the USA by analyzing data from the Surveillance, Epidemiology, and End Results (SEER) Program and the State Cancer Profiles of the National Cancer Institute and from the Environmental Protection Agency. Linear regression analysis was conducted to evaluate the association between PAH emissions and breast cancer incidence in unadjusted and adjusted models. Significantly higher age-adjusted incidence rates of female breast cancer were seen in northeastern SEER regions, when compared to southeastern regions, during the years of 2000-2012. After adjusting for potential confounders, emission densities of total PAHs and four carcinogenic individual PAHs (benzo[a]pyrene, dibenz[a,h]anthracene, naphthalene, and benzo[b]fluoranthene) showed a significantly positive association with annual incidence rates of breast cancer, with a ß of 0.85 (p = 0.004), 58.37 (p = 0.010), 628.56 (p = 0.002), 0.44 (p = 0.041), and 77.68 (p = 0.002), respectively, among the northeastern and southeastern states. This study suggests a potential relationship between ambient air emissions of carcinogenic PAHs and geographic variations of female breast cancer incidence in the northeastern and southeastern US. Further investigations are needed to explore these interactions and elucidate the role of PAHs in regional variations of breast cancer incidence.

Early markers of kidney dysfunction and cognitive impairment among older adults.

BACKGROUND: Age-related decline in kidney function can be an important risk factor for cognitive impairment in older adults. In this study, we examined several kidney function measures for the association with cognitive function in older adults in hope to identify early and sensitive markers that can be used for the detection or screening for cognitive impairment. METHODS: A total of 1982 older participants (aged ≥60years) in the 1999-2002 National Health and Nutrition Examination Survey was analyzed for the association between kidney function and cognitive impairment using multivariate logistic regression and general linear models. Cognitive functioning was assessed during the household interview using a version of the Digit Symbol Substitution Test of the Wechsler Adult Intelligence Scale III. In our study, participants with a score of <31, the 25th percentiles of the distribution, or who were unable to complete the sample exercise due to cognitive limitations were classified as having cognitive impairment. RESULTS: Of 1982 older adults, 503 were having cognitive impairment (weighted prevalence, 15.38%). Among the kidney function measures that we examined, the levels of serum cystatin C and urinary albumin were found being significantly associated with cognitive impairment after adjusting for age, sex, race/ethnicity, poverty status, education, physical activity, BMI, cigarette smoking, and alcohol consumption. Cognitive functioning scores were significantly decreasing with increasing levels of kidney dysfunction markers. CONCLUSION: Serum cystatin C and urinary albumin that are early markers of chronic kidney disease might serve as early and effective markers for cognitive decline in older adults. Mechanisms underlying the observed association need to be further characterized.

Differences in pathological characteristics and laboratory indicators in adult and pediatric patients with Henoch-Schönlein purpura nephritis.

We aimed to investigate the differences in renal histopathological changes and laboratory parameters between adult and pediatric patients with Henoch-Schönlein purpura nephritis (HSPN), and to analyze the correlation between laboratory parameters and renal histopathological grading. A total of 139 patients diagnosed with HSPN between September 2010 and December 2014 at the First Hospital of Jilin University, China, were retrospectively reviewed. The clinical and pathological characteristics were examined and compared between the adult and the pediatric patients. A majority of adult (75.0%) and pediatric (66.2%) patients were categorized as pathological grade III HSPN. Adults having crescent lesions, interstitial fibrosis and renal artery involvement significantly outnumbered child counterparts (all P<0.05). Pathological grading showed a positive correlation with 24-h urine protein (r=0.307, P=0.009), microalbuminuria (r=0.266, P=0.000) and serum globulin (r=0.307, P=0.014), and a negative correlation with serum albumin (r=0.249, P=0.037) in pediatric patients with HSPN. Among adult patients with HSPN, histopathological grading showed a positive correlation with 24-h urine protein (r=0.294, P=0.015), microalbuminuria (r=0.352, P=0.006), α1-microglobulin (r=0.311, P=0.019) and immunoglobulin G (r=0.301, P=0.023) in urine, and serum creatinine (r=0.292, P=0.018). Further, a negative correlation between serum albumin and pathological grading was also observed (r=0.291, P=0.018). In conclusion, the severity of renal pathological lesions in HSPN patients is well reflected by the levels of proteinuria. Adult patients have more severe renal histopathological changes than pediatric patients.

PAHs and PM2.5 emissions and female breast cancer incidence in metro Atlanta and rural Georgia.

Environmental chemical exposure could be an important etiologic factor for geographic differences in breast cancer incidence. In this study, we examined emissions of polycyclic aromatic hydrocarbons (PAHs) and PM2.5 in relation to breast cancer incidence in metro Atlanta and rural Georgia by analyzing data from the Surveillance, Epidemiology, and End Results Program and the Environmental Protection Agency. The results showed that metro Atlanta had a significantly higher age-adjusted annual incidence rate of female breast cancer than rural Georgia (132.6 vs. 113.7 per 100,000) for 1992-2011. Emissions of both PAHs [adjusted ß = 0.568 (95 % CI: 0.209, 0.927); p = 0.004] and PM2.5 [adjusted ß = 2.964 (95 % CI: 0.468, 5.459); p = 0.023] were significantly associated with breast cancer incidence in metro Atlanta area. This study suggests that ambient air pollution, especially PAHs and PM2.5, could have a significant impact on the increased incidence of female breast cancer in urban areas.

Genistein Induces Cytochrome P450 1B1 Gene Expression and Cell Proliferation in Human Breast Cancer MCF-7 Cells.

Cytochrome P450 1B1 (CYP1B1) plays an important role in breast cancer development and progression by bioactivating endogenous estrogens and environmental carcinogens. In this study, we examined the effect of the soy isoflavone genistein on CYP1B1 gene expression, reactive oxygen species (ROS) production, and cell proliferation in human breast cancer MCF-7 cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) analysis showed a dose-dependent induction of CYP1B1 gene expression in the cells treated with 5 and 25 µM of genistein. Genistein at 5 µM exhibited a synergistic effect on the CYP1B1 mRNA level induced by the environmental carcinogen 7,12-dimethylbenz[a]anthracene. We also found that genistein at 5 µM increased cellular levels of ROS and stimulated cell proliferation starting from the second day of culture. This study suggests that physiological concentrations of genistein stimulate ROS production and breast cancer cell proliferation through the induction of CYP1B1 gene expression. More extensive studies are warranted to further characterize the role of genistein and the CYP1B1 enzyme in human breast carcinogenesis.

Fluoride decreased osteoclastic bone resorption through the inhibition of NFATc1 gene expression.

Over the past two decades, fluoride effects on osteoclasts have been evaluated; however, its molecular mechanisms remain unclear. In this study, we investigated the effect of fluoride on osteoclast formation, function, and regulation using osteoclasts formed from mice bone marrow macrophages treated with the receptor activator of NF-κB ligand and macrophage colony-stimulating factor. Our data showed that fluoride levels ≤ 8 mg/L had no effect on osteoclast formation; however, it significantly reduced osteoclast resorption at 0.5 mg/L. Fluoride activity on bone resorption occurred through the inhibition of nuclear factor of active T cells (NFAT) c1 expression. Furthermore, the expression of its downstream genes, including the dendritic cell-specific transmembrane protein, c-Src, the d2 isoform of vacuolar (H+) ATPase v0 domain, matrix metalloproteinase 9, and cathepsin K were decreased, leading to impaired osteoclast acidification, reduced secretion of proteolytic enzymes, and decreased bone resorption. In summary, our results suggested that fluoride has different roles in osteoclast formation and function. Fluoride ≤ 8 mg/L did not impact osteoclast formation; however, it significantly decreased the resorption activity of newly formed osteoclasts. The molecular mechanism of fluoride action may involve inhibition of NFATc1 and its downstream genes.