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Photooxidation of volatile organic compounds (VOCs) produces condensable oxidized organics (COOs) to yield secondary organic aerosol (SOA), but the fundamental chemical mechanism for gas-to-particle conversion remains uncertain. Here we elucidate the production of COOs and their roles in SOA and brown carbon (BrC) formation from m-xylene oxidation by simultaneously monitoring the evolution of gas-phase products and aerosol properties in an environmental chamber. Four COO types with the distinct functionalities of dicarbonyls, carboxylic acids, polyhydroxy aromatics/quinones, and nitrophenols are identified from early-generation oxidation, with the yields of 25 %, 37 %, 5 %, and 3 %, respectively. SOA formation occurs via several heterogeneous processes, including interfacial interaction, ionic dissociation/acid–base reaction, and oligomerization, with the yields of (20 ± 4) % and (32 ± 7) % at 10 % and 70 % relative humidity (RH), respectively. Chemical speciation shows the dominant presence of oligomers, nitrogen-containing organics, and carboxylates at high RH and carboxylates at low RH. The identified BrC includes N-heterocycles/N-heterochains and nitrophenols, as evident from reduced single scattering albedo. The measured uptake coefficient (γ) for COOs is dependent on the functionality, ranging from 3.7 × 10−4 to 1.3 × 10−2. A functionality-based kinetic framework is developed to predict SOA production from the observed concentrations and uptake coefficients for COOs, which reproduces the measurement from m-xylene oxidation. Our results reveal that photochemical oxidation of m-xylene represents a major source for SOA and BrC formation under urban environments, because of its large abundance, high reactivity with OH, and high yields for COOs.

Objectives: We aimed to evaluate the association of testosterone deficiency with inflammation and how long-term testosterone therapy affects inflammation biomarkers over time. Methods: We conducted a 2-component study. First, we conducted a cross-sectional study using the recently released 2015-2016 National Health and Nutrition Examination Survey (NHANES) data to examine the association between testosterone deficiency and inflammation biomarkers including high sensitivity C-reactive protein (hsCRP), liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the US general population. Then we conducted a longitudinal study to investigate the longitudinal effect of testosterone therapy on inflammation biomarkers and the risk of cardiovascular events, using data from 776 hypogonadal men based on a registry study in Germany with up to 11 years’ follow-up. Results: The adjusted odds ratios (ORs) describing the associations between testosterone deficiency and hsCRP ≥ 3mg/L, ALT > 40U/L, and AST > 40U/L were 1.81 ( P-value < 0.001), 1.46 ( P-value = 0.009), and 0.99 ( P-value = 0.971), respectively. In the control group, CRP, ALT, and AST levels increased by 0.003 (95%CI: −0.001, 0.007) mg/L, 0.157 U/L (95%CI: 0.145, 0.170), and 0.147 (95%CI: 0.136, 0.159) U/L per month, while in the treatment group, CRP, ALT, and AST levels decreased by 0.05 (95%CI: −0.055, −0.046) mg/L, 0.142 U/L (95%CI: −0.154, −0.130), and 0.148 (95%CI: −0.158, −0.137) U/L per month. Conclusion: Testosterone deficiency was associated with an increased level of inflammation; long-term testosterone therapy alleviated inflammation among hypogonadal men, which may contribute to the reduced cardiovascular risk. Future large trials are warranted to confirm our observational study findings.

Background Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health effects in children. Valid exposure assessment methods with accurate spatial and temporal resolution across pregnancy is a critical need for advancing environmental health studies. Objective The objective of this study was to quantify maternal PAH exposure in pregnant women residing in McAllen, Texas where the prematurity rate and childhood asthma prevalence rates are high. A secondary objective was to compare PAH levels in silicone wristbands deployed as passive samplers with concentrations measured using standardized active air-sampling techniques. Methods Participants carried a backpack that contained air-sampling equipment (i.e., filter and XAD sorbent) and a silicone wristband (i.e., passive sampler) for three nonconsecutive 24-h periods. Filters, XAD tubes, and wristbands were analyzed for PAHs. Results The median level of exposure for the sum of 16 PAHs measured via active sampling over 24 h was 5.54 ng/m3 (filters) and 43.82 ng/m3 (XADs). The median level measured in wristbands (WB) was 586.82 ng/band. Concentrations of the PAH compounds varied across sampling matrix type. Phenanthrene and fluorene were consistently measured for all participants and in all matrix types. Eight additional volatile PAHs were measured in XADs and WBs; the median level of exposure for the sum of these eight PAHs was 342.98 ng/m3 (XADs) and 632.27 ng/band. The silicone wristbands (WB) and XAD sorbents bound 1-methynaphthalyne, 2-methylnaphthalene, biphenyl following similar patterns of detection. Significance Since prior studies indicate linkages between PAH exposure and adverse health outcomes in children at the PAH levels detected in our study, further investigation on the associated health effects is needed. Data reflect the ability of silicone wristbands to bind smaller molecular weight, semivolatile PAHs similar to XAD resin. Application of wristbands as passive samplers may be useful in studies evaluating semivolatile PAHs.

Low baseline testosterone level has been associated with the development of risk factors for cardiovascular disease such as insulin resistance and obesity. In addition to the absolute testosterone level, remarkable changes in testosterone level may have an acute effect on cardiovascular disease development and progression, which has been rarely investigated. In this study, we used a clinical dataset of 376 hypogonadal men whose testosterone levels were measured every six months for up to 11 years from a registry study in Germany, and conducted survival analyses to investigate the effect of testosterone changes since the last visit (time-varying) on the risk of cardiovascular events. Given the potential discrepancies in comorbidity conditions among patients with prior cardiovascular events and those without, all the analyses were stratified by patients' prior cardiovascular event status. We found the effects were not different among patients with prior cardiovascular events and those without. Regardless of patients' prior cardiovascular event status, patients with larger testosterone declines (≥3.12 nmol/L, 90

Particulate matter (PM) causes adverse developmental outcomes following prenatal exposure, but the underlying biological mechanisms remain uncertain. Here we elucidate the effects of diesel exhaust ultrafine particle (UFP) exposure during pregnancy on placental and fetal development. Time-mated C57Bl/6n mice were gestationally exposed to UFPs at a low dose (LD, 100 µg/m3) or high dose (HD, 500 µg/m3) for 6 h daily. Phenotypic effects on fetuses and placental morphology at gestational day (GD) of 18.5 were evaluated, and RNA sequencing was characterized for transcriptomic changes in placental tissue from male and female offspring. A significant decrease in average placental weights and crown to rump lengths was observed in female offspring in the LD exposure group. Gestational UFP exposure altered placental morphology in a dose- and sex-specific manner. Average female decidua areas were significantly greater in the LD and HD groups. Maternal lacunae mean areas were increased in the female LD group, whereas fetal blood vessel mean areas were significantly greater in the male LD and HD groups. RNA sequencing indicated several disturbed cellular functions related to lipid metabolism, which were most pronounced in the LD group and especially in female placental tissue. Our findings demonstrate the vulnerability of offspring exposed to UFPs during pregnancy, highlighting sex-specific effects and emphasizing the importance of mitigating PM exposure to prevent adverse health outcomes.

Unprecedented inland precipitation and catastrophic flooding associated with Hurricane Harvey potentially redistributed contaminants from industrial sites and transportation infrastructure to recreational areas that make up networks of green infrastructure, creeks, and waterways used for flood control throughout the Greater Houston Area. Sediment samples were collected in parks located near the Buffalo Bayou watershed 1 week after Hurricane Harvey made landfall and again 7 weeks later. Total concentrations of the U.S. Environmental Protection Agency's (EPA's) 16 priority polycyclic aromatic hydrocarbons (PAHs) were measured in each sample at both time points. Diagnostic ratios were calculated to improve understanding of potential sources of PAHs after flooding. Diagnostic ratios suggest vehicular traffic to be a potential source for PAHs in parks. Although the concentrations of PAHs in all samples were below EPA actionable levels, given that no background values were available for comparison, it is difficult to quantify the impact flooding from Hurricane Harvey had on PAH concentrations in Houston parks. However, given the high frequency of flooding in Houston, and the concentration of industrial facilities and transportation infrastructure adjacent to recreation areas, these data demonstrate that PAHs were still present after unprecedented flooding. This study may also serve as a baseline for future efforts to understand the environmental health impacts of disasters.

Exploration of animal models leads to discoveries that can reveal candidate biomarkers for translation to human populations. Herein, a model of hepatocarcinogenesis and protection was used in which rats treated with aflatoxin (AFB1 ) daily for 28 days (200 µg/kg BW) developed tumors compared with rats completely protected from tumors by concurrent administration of the chemoprotective agent, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im). Differential expression of miRNAs in tumors (AFB1 ) and nontumor (AFB1 + CDDO-Im) bearing livers and their levels in sera over the life-course of the animals was determined. miRNA transcriptome analysis identified 17 miRNAs significantly upregulated at greater than five-fold in the tumors. The ten most dysregulated miRNAs judged by fold-change and biological significance were selected for further study, including liver-specific miR-122-5p. Validation of sequencing results by real-time PCR confirmed the upregulation of the majority of these miRNAs in tumors, including miR-182, as well as miR-224-5p as the most dysregulated of these miRNAs (over 400-fold). The longitudinal analysis of levels of miR-182 in sera demonstrated significant and persistent increases (5.13-fold; 95% CI: 4.59-5.70). The increase in miR-182 was detected months before any clinical symptoms were present in the animals. By the terminal time point of the study, in addition to elevated levels of serum miR-182, serum miR-122-5p was also found to be increased (>1.5-fold) in animals that developed hepatocarcinomas. Thus, using the data from an unbiased discovery approach of the tissue findings, serum miR-182 was found to track across the complex, multistage process of hepatocarcinogenesis opening an opportunity for translation to human populations.

Significance Particulate matter exposure causes infant respiratory morbidity and mortality, but the role of ultrafine particles (UFPs) with an aerodynamic diameter of less than 0.1 μm in asthma and respiratory tract infections is unclear. Limited mechanistic information is available concerning UFP influence on the etiology of childhood asthma or susceptibility to respiratory infections. Here we exposed two strains of mice (sensitive to oxidative stress or allergen exposure) to UFPs throughout gestation at concentrations relevant to human exposures. Our results reveal a window of pulmonary immunosuppression in offspring following in utero UFP exposure. A dampened host immune response during early development underlies increased childhood susceptibility to respiratory infections, highlighting the necessity to develop strategies to protect the fetus during this vulnerable period., Early life exposure to fine particulate matter (PM) in air is associated with infant respiratory disease and childhood asthma, but limited epidemiological data exist concerning the impacts of ultrafine particles (UFPs) on the etiology of childhood respiratory disease. Specifically, the role of UFPs in amplifying Th2- and/or Th17-driven inflammation (asthma promotion) or suppressing effector T cells (increased susceptibility to respiratory infection) remains unclear. Using a mouse model of in utero UFP exposure, we determined early immunological responses to house dust mite (HDM) allergen in offspring challenged from 0 to 4 wk of age. Two mice strains were exposed throughout gestation: C57BL/6 (sensitive to oxidative stress) and BALB/C (sensitive to allergen exposure). Offspring exposed to UFPs in utero exhibited reduced inflammatory response to HDM. Compared with filtered air (FA)-exposed/HDM-challenged mice, UFP-exposed offspring had lower white blood cell counts in bronchoalveolar lavage fluid and less pronounced peribronchiolar inflammation in both strains, albeit more apparent in C57BL/6 mice. In the C57BL/6 strain, offspring exposed in utero to FA and challenged with HDM exhibited a robust response in inflammatory cytokines IL-13 and Il-17. In contrast, this response was lost in offspring exposed in utero to UFPs. Circulating IL-10 was significantly up-regulated in C57BL/6 offspring exposed to UFPs, suggesting increased regulatory T cell expression and suppressed Th2/Th17 response. Our results reveal that in utero UFP exposure at a level close to the WHO recommended PM guideline suppresses an early immune response to HDM allergen, likely predisposing neonates to respiratory infection and altering long-term pulmonary health.

People and animals can be unintentionally exposed to complex mixtures of hazardous chemicals that can threaten the safety of food and water supplies following natural and man-made disasters and emergencies. Our research has focused on the development of broad-acting adsorbents that will tightly bind environmental contaminants in the gastrointestinal tract and decrease their bioavailability to humans and animals during these events. In this study, benzo[a]pyrene (BaP) and aldicarb were used as representative chemicals due to their high toxicity and extensive distribution in the environment. Both chemicals have been commonly detected in water and sediments in the US, and their distribution and concentrations can be enhanced during disasters. To address this problem, we have amended and functionalized montmorillonite clays with the nutrients, L-carnitine and choline to enhance their attraction for lipophilic toxins, such as BaP and aldicarb. Based on equilibrium isothermal analyses, we have demonstrated a significantly increased binding capacity (Qmax) and affinity (Kd) for BaP and aldicarb compared to the parent clay. Adsorption isotherms also showed that talc bound strongly to BaP with the highest Qmax, which was twice that of activated carbon. Additionally, cultures of adult hydra with a metabolism activation package were used as an in vivo toxicity indicator to confirm the ability of test adsorbents to protect against toxicity at low inclusion levels. We anticipate that the optimal adsorbents developed can be delivered in food and flavored water, or administered by sachet or capsule during emergencies and disasters to decrease human and animals exposures to environmental toxins.

With increasing urbanisation, industrialisation and economic growth worldwide, air pollution has emerged as one of the greatest global public health epidemics in the 21st century. The impacts of air pollution on human health are enormous. Globally, nine in ten people breathe air containing high levels of pollutants, and one in nine of the deaths are caused by exposure to air pollution, reaching an annual premature mortality of over seven million.1 Air pollutants comprise a complex mixture of gases and particulate matter (PM), which are directly emitted from natural and anthropogenic sources or are formed in air via a multitude of chemical processes.2 In particular, fine PM (diameter smaller than 2.5 µm or PM2.5) has been unequivocally linked to various adverse human health effects, ranging from aggravated allergies to the development of chronic diseases, to premature death.3 Exposure of vulnerable individuals to air pollution is especially worrisome, such as pregnant women and children.4 5 The morbidity and mortality associated with air pollution for children are relevant to both prenatal and postnatal exposures. For example, epidemiological and animal model studies have revealed that maternal exposure to fine PM results in adverse birth outcomes and postnatal health conditions.5 Specifically, animal model experiments employing ultrafine particles (diameter smaller than 0.1 µm or UFP) have shown that prenatal exposure predisposes offspring to long-term metabolic syndrome and pulmonary immunosuppression, with profound implications for respiratory infection risks.6 7 In this issue, Fang …

It is now clear that parental histories of drug use, toxicant exposure, and social stress all have a significant influence on the health and development of the next generation. However, the ability of epigenetic parental life memories to interact with subsequent gestational exposures and cumulatively modify the developmental trajectory of the offspring remains an unexplored perspective in toxicology. Studies from our laboratory have identified male-specific postnatal growth restriction in a mouse model of chronic, preconception paternal alcohol exposure. The goal of the current study was to determine if paternal alcohol use, before conception, could modify the susceptibility of the offspring to a completely separate exposure encountered by the mother during pregnancy. In independent experiments, we previously identified altered developmental programming and increased markers of severe asthma induced by gestational exposure to particulate air pollution. In this study, male mice were exposed to either the control or alcohol preconception treatments, then mated to naive females, which we subsequently exposed to an ultrafine mixture of particulate matter via inhalation. Individually, neither preconception paternal drinking nor gestational exposures to particulate air pollution impacted the postnatal growth of female offspring. However, when both exposures were combined, females displayed a 30% reduction in weight gain. Unexpectedly, this exposure paradigm resulted in a dramatic postnatal increase in litter loss due to maternal cannibalism, which prevented additional measures of offspring health. These preliminary studies provide evidence of a complex interplay between preconception life history and intrauterine environmental factors in the control of postnatal growth.

Low birth weight is an important risk factor for many co-morbidities both in early life as well as in adulthood. Numerous studies report associations between prenatal exposure to particulate matter (PM) air pollution and low birth weight. Previous systematic reviews and meta-analyses report varying effect sizes and significant heterogeneity between studies, but did not systematically evaluate the quality of individual studies or the overall body of evidence. We conducted a new systematic review to determine how prenatal exposure to PM(2.5), PM(10), and coarse PM (PM(2.5–10)) by trimester and across pregnancy affects infant birth weight. Using the Navigation Guide methodology, we developed and applied a systematic review protocol [CRD42017058805] that included a comprehensive search of the epidemiological literature, risk of bias (ROB) determination, meta-analysis, and evidence evaluation, all using pre-established criteria. In total, 53 studies met our inclusion criteria, which included evaluation of birth weight as a continuous variable. For PM(2.5) and PM(10), we restricted meta-analyses to studies determined overall as “low” or “probably low” ROB; none of the studies evaluating coarse PM were rated as “low” or “probably low” risk of bias, so all studies were used. For PM(2.5), we observed that for every 10 μg/m(3) increase in exposure to PM(2.5) in the 2(nd) or 3(rd) trimester, respectively, there was an associated 5.69g decrease (I(2): 68%, 95% CI: −10.58, −0.79) or 10.67g decrease in birth weight (I(2): 84%, 95% CI: −20.91, −0.43). Over the entire pregnancy, for every 10 μg/m(3) increase in PM(2.5) exposure, there was an associated 27.55g decrease in birth weight (I(2): 94%, 95% CI: −48.45, −6.65). However, the quality of evidence for PM(2.5) was rated as “low” due to imprecision and/or unexplained heterogeneity among different studies. For PM(10), we observed that for every 10 μg/m(3) increase in exposure in the 3(rd) trimester or the entire pregnancy, there was a 6.57g decrease (I(2): 0%, 95% CI: −10.66, −2.48) or 8.65g decrease in birth weight (I(2): 84%, 95% CI: −16.83, −0.48), respectively. The quality of evidence for PM(10) was rated as “moderate,” as heterogeneity was either absent or could be explained. The quality of evidence for coarse PM was rated as very low/low (for risk of bias and imprecision). Overall, while evidence for PM(2.5) and course PM was inadequate primarily due to heterogeneity and risk of bias, respectively, our results support the existence of an inverse association between prenatal PM(10) exposure and low birth weight.

Background: Reducing hospital readmission after acute myocardial infarction (AMI) has the potential to both improve quality and reduce costs. As such, readmission after AMI has been a target of financial penalties through Medicare. However, substantial concern exists about potential adverse effects and efficacious readmission-reduction strategies are not well validated. Methods and Results: We started an AMI readmissions reduction program in November 2017. Between July 2016 and February 2019, hospital billing data were queried to detect all inpatient hospitalizations at the Massachusetts General Hospital for AMI. Thirty-day readmission was identified through hospital billing data, and mortality was extracted from our electronic health record. The data set was merged with claims data for patients in accountable care organizations to detect readmission at other hospitals. We performed segmented linear regression, adjusting for secular trend and case mix, to assess the independent association of our program on both outcome variables. After inclusion and exclusion criteria were applied, the study population included 2020 patients. The overall 30-day readmission rate was higher before the intervention than after the intervention (15.5% versus 10.7%, P =0.002). The overall 30-day mortality rate was similar in both time periods (1.8% versus 1.4%, P =0.457). The program was associated with initial reduction in 30-day readmission (−9.8%, P =0.0002) and 30-day mortality (−2.6%, P =0.041). The program did not change trend in 30-day readmission (+0.19% readmissions/mo, P =0.554) and trend in 30-day mortality (−0.21% deaths/mo, P =0.119). Conclusions: An AMI readmissions reduction program that increases outpatient and emergency department (ED) access to cardiology care is associated with reduced 30-day readmission and 30-day mortality. Similar statistical techniques can be used to conduct a rigorous, mechanistic program evaluation of other quality improvement initiatives.

In this study, we characterized personal exposure to fine particulate matter (PM2.5), black carbon (BC), and nicotine in pregnant women in Hidalgo County, where the hospitalization rates of childhood asthma are the highest in the state of Texas. The measurements were conducted over three non-consecutive sampling days for 17 participants in their third trimester. Measurements were partitioned into four microenvironments, i.e., Residential, Vehicular, Commercial, and Other, on the basis of GPS coordinates and temperature and humidity measurements. The daily average PM2.5 mass concentration was 24.2 (standard deviation = 22.0) μg/m3, with the highest daily mass concentration reaching 126.0 μg/m3. The daily average BC concentration was 1.44 (SD = 0.82) μg/m3, ranging from 0.5 to 5.4 μg/m3. Hair nicotine concentrations were all near the detection level (i.e., 49.2 pg/mg), indicating that the participants were not routinely exposed to tobacco smoke. The Residential microenvironment contributed dominantly to the mass concentration since the participants chiefly remained at home and cooking activities contributed significantly to the total PM2.5. When compared to an ambient monitoring station, the person-specific PM2.5 was frequently more than double the ambient measurement (10.4 μg/m3 overall), revealing that even in regions where ambient concentrations are below national standards, individuals may be still be exposed to elevated PM2.5 mass concentrations.

Aflatoxin B1 (AFB1) is a potent human and animal hepatocarcinogen. To investigate the effects of aflatoxin on miRNA expression during the initiation phase of carcinogenesis, next-generation sequencing was used to analyze liver tissues from F344 rats exposed to 200 µg/kg per day AFB1 for 4 weeks. A panel of miRNAs was identified that was upregulated with AFB1 treatment compared to controls: rno-miR-434-3p, rno-miR-411-5p, rno-miR-221-3p, rno-miR-127-3p, rno-miR-205, rno-miR-429, rno-miR-34a-5p, rno-miR-181c-3p, rno-miR-200b-3p, and rno-miR-541-5p. Analysis of rat livers exposed to AFB1 plus the chemopreventive triterpenoid CDDO-Im revealed a striking abrogation of this upregulation. These changes were validated by real-time PCR. We also explored the temporal variation in expression of the candidate miRNAs during the 4-week dosing period. Most of the candidate miRNAs were upregulated at week 1 and increased for the duration of AFB1 dosing over the 4-week period. Treatment with CDDO-Im ameliorated these effects at all time points. All candidate miRNAs were detectable in serum from aflatoxin treated animals; however, there was no significant difference in expression for 7 of the 11 miRNAs examined. Exposure to AFB1 upregulated miR-122-5p (5 fold), 34a-5p (13 fold), and 181c-3p (170 fold) compared with controls. The findings from this study give insight into epigenetic changes induced by aflatoxin taking place during the initial step of carcinogenesis. This article is protected by copyright. All rights reserved

The World Health Organization estimates that about 4 million people die every year due to air pollution exposure including deaths from ischemic heart disease and stroke, respiratory diseases, and lung cancer. Transportation sector emissions are one of the major sources of air pollutants. In recent years, research on the health effects of traffic-related air pollution has expanded beyond respiratory, cancer, and cardiovascular diseases to include a growing literature on pregnancy, birth outcomes and development, neurotoxicity and various neurological diseases and disorders. This chapter describes the range of health effects that have been associated with traffic-related air pollution. Several special topics including cumulative risk assessment and environmental justice considerations related to traffic-related air pollution exposures are also presented.

Exposure to fine particulate matter (PM) during pregnancy is associated with high risks of birth defects/fatality and adverse long-term postnatal health. However, limited mechanistic data are available to assess the detailed impacts of prenatal PM exposure. Here we evaluate fine PM exposure during pregnancy on prenatal/postnatal organogenesis in offspring and in predisposing metabolic syndrome for adult life. Between days 0 and 18 of gestation, two groups of adult female rats (n = 10 for each) were placed in a dual-exposure chamber device, one with clean ambient air (∼3 µg·m(−3)) and the other with ambient air in the presence of 100 to 200 µg·m(−3) of ultrafine aerosols of ammonium sulfate. At birth (postnatal day 0, PND0), four males and four females were selected randomly from each litter to be nursed by dams, whereas tissues were collected from the remaining pups. At PND21, tissues were collected from two males and two females, whereas the remaining pups were fed either a high- or low-fat diet until PND105, when tissues were obtained for biochemical and physiological analyses. Maternal exposure to fine PM increased stillbirths; reduced gestation length and birth weight; increased concentrations of glucose and free fatty acids in plasma; enhanced lipid accumulation in the liver; and decreased endothelium-dependent relaxation of aorta. This lead to altered organogenesis and predisposed progeny to long-term metabolic defects in an age-, organ-, and sex-specific manner. Our results highlight the necessity to develop therapeutic strategies to remedy adverse health effects of maternal PM exposure on conceptus/postnatal growth and development.

Background Ambient fine particulate matter (PM2.5) air pollution has been associated with increased airway inflammation, but the roles of various PM2.5 constituents remain to be determined. Objectives To investigate the acute effects of PM2.5 constituents on fractional exhaled nitric oxide (FeNO), a well-established biomarker of respiratory inflammation. Methods A longitudinal panel study was performed among 32 healthy young adults in Shanghai, China from January 12th to February 6th, 2015. FeNO was repeatedly measured, 6–8 times per subject. Real-time mass concentration of ambient PM2.5 and chemical constituents were obtained from a nearby monitoring station. Linear mixed-effect models were applied to evaluate the association between FeNO and PM2.5 constituents, with the adjustment of age, gender, body mass index, temperature, relative humidity and day of week. The robustness of constituents’ effects was also evaluated. Results A total of 234 effective measurements of FeNO were obtained with a geometric mean of 13.1 ppb. The PM2.5-FeNO associations were strongest at lags of 0–6 h and diminished at lags longer than 12 h. An interquartile range increase in PM2.5 constituents (NH4+, NO3−, K+, SO42− and elemental carbon) at lags of 0–6 h were significantly associated with increments in FeNO by 12.3%, 11.3%, 11.1%, 9.6% and 10.7%, respectively. After controlling for PM2.5 total mass and the colinearity, only elemental carbon remained significant. Conclusion Several chemical constituents of PM2.5 may impact FeNO following acute exposure. Elemental carbon in particular may be the primary component responsible for increased airway inflammation.

Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG) in the aquatic environment have become an emerging contaminant issue, which has implications for human and ecological health. This review begins with an introduction to the occurrence of ARB and ARG in different environmental systems such as natural environments and drinking water resources. For example, ARG or ARB with resistance to ciprofloxacin, sulfamethoxazole, trimethoprim, quinolone, vancomycin, or tetracycline (e.g., tet(A), tet(B), tet(C), tet(G), tet(O), tet(M), tet(W), sul I, and sul II) have been detected in the environment. The development of resistance may be intrinsic, may be acquired through spontaneous mutations (de novo), or may occur due to horizontal gene transfer from donor bacteria, phages, or free DNA to recipient bacteria. An overview is also provided of the current knowledge regarding inactivation of ARB and ARG, and the mechanism of the effects of different disinfection processes in water and wastewater (chlorination, UV irradiation, Fenton reaction, ozonation, and photocatalytic oxidation). The effects of constructed wetlands and nanotechnology on ARB and ARG are also summarized.

Ozone Exposure, Glucose Homeostasis and Insulin Resistance in the USABackground: Epidemiological studies have suggested the associations between ambient air pollution levels and metabolic syndrome ...

In this study, we assessed trends of serum cotinine levels over time among US children ages 3-11 years and compared the risk of asthma in groups exposed to passive tobacco smoke. We utilized National Health and Nutrition Examination Survey (NHANES) data collected from 2003 to 2014 (n = 8064). Serum cotinine level, household smoker status, asthma status, and sociodemographic information were extracted for multiple regression analyses. The adjusted biannual change in log (cotinine) in comparison to earlier NHANES survey cycles was - 0.196 (p 0.001) overall, - 0.055 (p = 0.089) among children with household smoker(s), and - 0.129 (p 0.001) among children without. The proportion of children living with household smokers decreased from 24.9% in the 2003-2004 cycle to 11.4% in the 2013-2014 cycle. The adjusted odds ratios (ORs) for asthma were 1.34 (95% confidence interval (CI): 1.00-1.80; 2nd tertile vs 1st tertile) and 1.69 (95%CI: 1.25-2.29; 3rd tertile vs1st tertile), respectively. Highly exposed asthmatic children, in the 3rd cotinine tertile (0.13 ng/mL), were primarily Non-Hispanic Black (61.0%) and whose family incomes were below poverty guidelines. Overall results reveal passive smoke exposure level among children ages 3-11 in the US decreased over the study period. Nevertheless, higher exposure to passive smoke is still associated with higher odds of childhood asthma. Targeted smoking cessation interventions in clinical practices are needed to reduce tobacco smoke exposure and related asthma risk in children, particularly in low-income and minority groups.

Background Asthma is the most common chronic disease in children and has been linked to high levels of ambient air pollution and certain hazardous air pollutants (HAPs). Outdoor pollutants such as benzene, released by car emissions, and organic chemicals found in diesel exhaust, as well as particles and irritant gases, including nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3), contribute to an increased prevalence of respiratory diseases such as asthma. Objectives The objectives of this study were to: 1) conduct a screening survey to identify high risk for asthma among school-age children in Hidalgo County, and, 2) study the potential health impact of school-related exposure to HAPs pertaining to asthma risk. Methods We carried out a quantitative cross-sectional study combining a school-based asthma screening survey across 198 schools in Hidalgo County, Texas, with information on school neighborhood environments, including census tract-level information on hazardous air pollutants (HAPs) and socioeconomic status (SES) in the respective school neighborhoods. HAPs levels were assessed based on the EPA 2011 National-Scale Air Toxics Assessment (NATA) while SES information was assessed using data from the 2010–2014 American Community Survey. Results 2930 students completed the asthma screening survey and results showed an overall asthma prevalence of 9.4%, slightly higher than the national and state prevalence. Participants in the 14–18 years old age group showed a much higher asthma prevalence of 16.7%. When assessing school-neighborhood characteristics, our results revealed no significant differences in asthma prevalence across census tracts with different SES levels. For HAPs, in the single-pollutant model, chlorine levels showed a significant linear trend for prevalence of asthma (p=0.03) while hydrochloric acid had a marginally significant linear trend (p=0.08). The association with chlorine remained significant in the multi-pollutant model. Conclusions Asthma prevalence among school-age children in Hidalgo County, Texas, is 9.4%, which is slightly higher than the state rate, especially among young adults, ages 14–18 years who had an asthma rate of 16.7%. Results support an association between exposures to school-neighborhood HAPs and risk for pediatric asthma, especially as related to chlorine. No significant effects of school-level SES on asthma risk were observed.

Mice are resistant to aflatoxin hepatotoxicity, primarily due to high expression of glutathione S-transferases (GSTs), and in particular the GSTA3 subunit. Nuclear factor erythroid 2 related factor 2 (Nrf2) signaling, which controls a broad-based cytoprotective response, was activated either genetically or pharmacologically in an attempt to rescue GSTA3 knockout mice from aflatoxin genotoxicity. Genetic activation of Nrf2 signaling was attained in a GSTA3: hepatocyte-specific Keap1 double knockout (DKO) mouse whereas pharmacologic activation of Nrf2 was achieved through pretreatment of mice with the triterpenoid 1-[2-cyano-3-,12-dioxoleana-1,9(11)-dien-28-oyl] imidazole (CDDO-Im) prior to aflatoxin B1 exposure. Following oral treatment with aflatoxin, urine was collected from mice for 24 h and hepatic and urinary aflatoxin metabolites then quantified using isotope dilution-mass spectrometry. Although Nrf2 was successfully activated genetically and pharmacologically, neither means affected the response of GSTA3 knockout mice to chemical insult with aflatoxin. Hepatic aflatoxin B1-N(7)-guanine levels were elevated 120-fold in GSTA3 knockout mice compared with wild-type and levels were not attenuated by the interventions. This lack of effect was mirrored in the urinary excretion of aflatoxin B1-N(7)-guanine. By contrast, urinary excretion of aflatoxin B1-N-acetylcysteine was200-fold higher in wild-type mice compared with the single GSTA3 knockout or DKO mouse. The inability to rescue GSTA3 knockout mice from aflatoxin genotoxicity through the Nrf2 transcriptional program indicates that Gsta3 is unilaterally responsible for the detoxication of aflatoxin in mice.

Background The US-Mexico border region has several major ports of entry, which serve as the gateway for large volumes of binational passenger and freight movement. Due to congestion and high wait times, vehicles are found to idle or “creep-idle” at border crossing locations, and these vehicles have been identified as a significant contributor to emissions in border areas. There are also concerns about the exposure of different groups of people - occupational exposures of truck drivers and workers in the border crossing facilities, commuters who cross the border, and residents who live and work near the border crossings. The El Paso region in Texas (across the border from Ciudad Juarez in Mexico) is home to some of the busiest border crossings in the US. The region is also in violation of federal ambient air quality standards. This study characterized the emissions impact of border crossings in El Paso to identify population groups, areas and neighborhoods potentially affected by emissions from the border crossing. Methods A literature review was conducted on assessment of health impacts of traffic-related air pollution, with a focus on impacts at border crossings and similar near-road environments. This was followed by a qualitative assessment of the ports of entry in the El Paso region (some of which carry larger truck volumes and others that serve commuter traffic including pedestrians), and their surrounding areas, and the affected population groups (occupational exposures and well as local communities). Finally, a geographic information systems (GIS)-based multi-criteria assessment was conducted to screen and prioritize areas in El Paso that can be viewed as being most affected by border crossing. The variables considered included proximity to the border crossing, proximity to truck routes, prevailing winds, etc. These were overlaid with population and demographic data, including consideration of sensitive populations to identify “hot-spots” that were most affected by border crossing emissions. Results This study provides insight into those affected by traffic-related air pollution generated by a border crossing, with a case study of the El Paso region. The results allow for the identification of neighborhoods or populations affected, who can be targeted for further exposure assessment studies including personal sampling studies, or for health interventions. Conclusions The study approach provides a systematic GIS-based approach for the screening of affected populations in a unique context (border crossings). The findings are relevant to address emissions exposure, health impacts, and environmental justice issues in border regions.

The use of dietary adsorbents to reduce arsenic (As) exposure is innovative. Ferrihydrite successfully sorbs arsenite and asenate over a wide range of pH conditions and the As-ferrihydrite complexes are stable in gastrointestinal (GIT) models. Our objectives were to (1) compare structural characteristics (using x-ray diffraction and Fourier-transform infrared [FTIR] spectroscopy) and As binding affinities of industrially produced ferrihydrite (IDF) and lab-synthesized ferrihydrite and (2) evaluate the efficacy of the material displaying the best sorption capability as an As enterosorbent in a short-term mammalian model. Lab-synthesized ferrihydrite displayed superior binding affinity for both arsenate and arsenite in vitro, which led to its use in the in vivo portion of the study. Young Sprague-Dawley male rats were fed either a control diet or a 0.5% w/w ferrihydrite feed. After 1 wk of acclimation, rats were given 0.5 ml of 500 mg/L arsenate or arsenite via gavage with or without ferrihydrite. Rats were then transferred to metabolism cages, and urine collected after 24 and 48 h was analyzed for total As. Rats were evaluated daily for signs of morbidity and mortality for up to 1 wk. Ferrihydrite reduced mean urinary As levels by 74.9% and 43.6% after 24 h and 49.1% and 39.5% after 48 h for arsenite- and arsenate-treated groups, respectively. Importantly, treatment groups receiving ferrihydrite displayed no signs of As-related toxicity. All As reductions were statistically significant except for arsenate treatments at 24 h. Data suggest that, as an enterosorbent, ferrihydrite reduces bioavailability after As exposures.

The global reference list of 100 core health indicators is a standard set of indicators published by the World Health Organization in 2015. We reviewed core health indicators in the public domain and in-country for Sierra Leone, the African continent and globally. Review objectives included assessing available sources, accessibility and feasibility of obtaining data and informing efforts to monitor program progress. Our search strategy was guided by feasibility considerations targeting mainly national household surveys in Sierra Leone and topic-specific and health statistics reports published annually by WHO. We also included national, regional and worldwide health indicator estimates published with open access in the literature and compared them with cumulative annual indicators from the weekly national epidemiological bulletin distributed by the Sierra Leone Ministry of Health and Sanitation. We obtained 70 indicators for Sierra Leone from Internet sources and 2 (maternal mortality and malaria incidence) from the national bulletin. Of the 70 indicators, 14 (20%) were modified versions of WHO indicators and provided uncertainty intervals. Maternal mortality showed considerable differences between 2 international sources for 2015 and the most recent national bulletin. We were able to obtain the majority of core indicators for Sierra Leone. Some indicators were similar but not identical, uncertainty intervals were limited and estimates differed for the same year between sources. Current efforts to improve health and mortality surveillance in Sierra Leone will improve availability and quality of reporting in the future. A centralized core indicator reporting website should be considered.

Aflatoxin B1 (AFB1) is a potent human and animal hepatocarcinogen. To investigate the effects of aflatoxin on miRNA expression during the initiation phase of carcinogenesis, next-generation sequencing was used to analyze liver tissues from F344 rats exposed to 200 μg/kg per day AFB1 for 4 weeks. A panel of miRNAs was identified that was upregulated with AFB1 treatment compared to controls: rno-miR-434-3p, rno-miR-411-5p, rno-miR-221-3p, rno-miR-127-3p, rno-miR-205, rno-miR-429, rno-miR-34a-5p, rno-miR-181c-3p, rno-miR-200b-3p, and rno-miR-541-5p. Analysis of rat livers exposed to AFB1 plus the chemopreventive triterpenoid CDDO-Im revealed a striking abrogation of this upregulation. These changes were validated by real-time PCR. We also explored the temporal variation in expression of the candidate miRNAs during the 4-week dosing period. Most of the candidate miRNAs were upregulated at week 1 and increased for the duration of AFB1 dosing over the 4-week period. Treatment with CDDO-Im ameliorated these effects at all time points. All candidate miRNAs were detectable in serum from aflatoxin treated animals; however, there was no significant difference in expression for 7 of the 11 miRNAs examined. Exposure to AFB1 upregulated miR-122-5p (5 fold), 34a-5p (13 fold), and 181c-3p (170 fold) compared with controls. The findings from this study give insight into epigenetic changes induced by aflatoxin taking place during the initial step of carcinogenesis.

p24 proteins comprise a family of type-I transmembrane proteins of ~24kD that are present in yeast and plants as well as metazoans ranging from Drosophila to humans. These proteins are most commonly localized to the endoplasmic reticulum (ER)-Golgi interface and are incorporated in anterograde and retrograde transport vesicles. Little is known about how disruption of p24 signaling affects individual tissue function or whole animals. Drosophila melanogaster express nine p24 genes, grouped into four subfamilies. Based upon our mRNA and protein expression data, Drosophila p24 family members are expressed in a variety of tissues. To identify functions for particular Drosophila p24 proteins, we used RNA interference (RNAi) to reduce p24 expression. Ubiquitous reduction of most p24 genes resulted in complete or partial lethality during development. We found that reducing p24 levels in adults caused defects in female fecundity (egg laying) and also reduced male fertility. We attributed reduced female fecundity to decreased neural p24 expression. These results provide the first genetic analysis of all p24 family members in a multicellular animal and indicate vital roles for Drosophila p24s in development and reproduction, implicating neural expression of p24s in the regulation of female behavior.

Fumonisin B1 (FB1) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF's carcinogenicity by acting as a cancer promoter. Calcium montmorillonite (i.e. NovaSil, NS) is a possible dietary intervention to help decrease chronic aflatoxin exposure where populations are at risk. Previous studies show that an oral dose of NS clay was able to reduce AF exposure in a Ghanaian population. In vitro analyses from our laboratory indicated that FB1 (like aflatoxin) could also be sorbed onto the surfaces of NS. Hence, our objectives were to evaluate the efficacy of NS clay to reduce urinary FB1 in a rodent model and then in a human population highly exposed to AF. In the rodent model, male Fisher rats were randomly assigned to either FB1 control, FB1 + 2% NS or absolute control group. FB1 alone or with clay was given as a single dose by gavage. For the human trial, participants received NS (1.5 or 3 g day−1) or placebo (1.5 g day−1) for 3 months. Urines from weeks 8 and 10 were collected from the ...

As social insect workers mature, outside-nest tasks associated with foraging and defense are typically performed at higher frequencies. Foraging in ants is often a pheromonally mediated collective action performed by mature workers; age-dependent differences in olfactory response thresholds may therefore proximately regulate task repertoire development. In the ant Pheidole dentata, foraging activity increases with chronological age in minor workers, and is chemically controlled. The onset of foraging in minor workers is accompanied by marked neuroanatomical and neurochemical changes, including synaptic remodeling in olfactory regions of the brain, proliferation of serotonergic neurons, and increased brain titers of monoamines, notably serotonin. We examined the linkage of serotonin and olfactory responsiveness by assaying trail-following performance in mature P. dentata minor workers with normal serotonin levels, or serotonin levels experimentally lowered by oral administration of the serotonin synthesis inhibitor α-methyltryptophan (AMTP). By assessing responsiveness to standardized pheromone trails, we demonstrate that trail-following behaviors are significantly reduced in serotonin-depleted workers. AMTP-treated individuals were less likely to initiate trail following, and oriented along pheromone trails for significantly shorter distances than untreated, similar-age workers. These results demonstrate for the first time that serotonin modulates olfactory processes and/or motor functions associated with cooperative foraging in ants.

Hepatocellular carcinoma (HCC) continues to be a major cause of cancer death globally, with aflatoxin B1 (AFB1) as a prevalent risk factor in low- and middle-income countries. MicroRNAs have been shown to be differentially expressed in HCC and may serve as predictive biomarkers. In this study, we analyzed tumor and non-tumor tissue from rats dosed with AFB1 (200 µg/kg BW) for 28 consecutive days that received vehicle only or AFB1 plus the chemopreventive agent CDDO-Im (30 µmol), and control animals (Johnson et al., CaPR, 2014). Total RNA was isolated from tumor or non-tumor tissue at the time of sacrifice and sequenced. MicroRNA transcriptomic analysis revealed 17 miRNAs significantly upregulated (> 5 fold) in tumors compared to non-tumor tissue. The top ten dysregulated miRNAs determined by fold change and biological significance were selected for further investigation: rno-miR- 205, 200b-3p, 182, 429, 31a-5p, 10b-5p, 141-3p, 132-3p, 802-5p. Validation of sequencing results by quantitative PCR (qPCR) confirmed the upregulation of the majority of candidate miRNAs in tumors and rno-miR-224-5p as the most dysregulated miRNA (over 400 fold). We also examined the levels of these candidates in terminal sera of the same animals by qPCR. Circulating miRs-224-5p, 182, and 122-5p were increased (> 1.5 fold) in animals diagnosed with HCC compared to untreated animals and those previously dosed with AFB1 plus CDDO-Im. Analysis of tracking of serum miR-182 by generalized estimating equations (GEE) revealed significantly increased levels (5 fold; CI: 2.17- 2.50) in animals that developed HCC. This sustained increase in serum miR-182 is seen months before any tumors or other symptoms are present, and highlights this miRNA as a potential predictive biomarker in AFB1-induced HCC. Supported by T32ES007141-31A1 and CA197222. Citation Format: Merricka C. Livingstone, Natalie M. Johnson, Bill D. Roebuck, Thomas W. Kensler, John D. Groopman. Dysregulated microRNAs in aflatoxin-induced hepatocellular carcinoma: Serum miR-182 as a potential predictive biomarker [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5401.

Arsenic (As) is a toxic trace element found in groundwater due to natural and industrial processes. Exposure has been linked to cancers of the bladder, lungs, skin, kidneys, nasal passages, liver, and the prostate. Arsenic in drinking water is a problem in many countries, notably Bangladesh and Taiwan. The purpose of this research was to utilize binding isotherms, a simulated gastrointestinal (GI) model, and the adult Hydra bioassay to evaluate ferrihydrite’s potential to bind As and serve as a potential enterosorbent for As found in drinking water. A variety of clay minerals and synthesized iron oxides including ferrihydrite were screened for their ability to bind As(III), as sodium arsenite, and As(V), as sodium arsenate. After ferrihydrite was demonstrated to be the most effective sorbent for both As species, adsorption isotherms were performed. All isotherm data were fit to the Langmuir equation to determine adsorption capacity (Qmax). Ferrihydrite bound 96% of As(III) and 97% of As(V) in the screening studies and had a Qmax of 1.288 mol/kg for As(III) and 0.744 mol/kg for As(V). Using a simulated GI model, ferrihydrite was found to effectively adsorb As(V) and As(III) in the stomach and intestine. Ferrihydrite (0.25% w/w) protected adult hydra at levels up to 200 times the minimal effective concentration (MEC) for As(III) and up to 2.5 times the MEC for As(V). These experiments confirm that ferrihydrite is a high capacity sorbent of As, and that it is effective at removing As in a simulated GI model. These results suggest that ferrihydrite could be used as a potential enterosorbent for As found in drinking water. Future work will focus on verifying ferrihydrite’s safety and efficacy in vivo.

To assess the potential interference of NovaSil (NS) clay with micronutrients in humans, vitamins A and E and minerals (15 nutrient and 15 non-nutrient minerals) were measured in serum samples from a 3-month intervention trial with NS. Participants (n = 177) were randomly divided into three groups that received 3.0 g NS day(-1) (high dose, HD), 1.5 g NS day(-1) (low dose, LD), or placebo (PL). Levels of vitamins A and E in serum were comparable among the three study groups at baseline, 1 month and 3 months of NS intervention. Gender-stratified non-parametric mixed-effect model analysis showed no significant effects of dose and dose-time interaction for levels of vitamins A and E. A significant time effect was detected; however, it was limited to an increase in vitamin E in the male participants over the course of the study. No significant differences were found in levels of the nutrient and non-nutrient minerals between the HD and PL groups at baseline and 3 months of NS intervention, except for strontium levels. Strontium was significantly increased (p0.001) in the HD group (male = 113.65 +/- 28.00 microg l(-1); female = 116.40 +/- 24.26 microg l(-1)) compared with the PL group (male = 83.55 +/- 39.90 microg l(-1); female = 90.47 +/- 25.68 microg l(-1)) following the 3-month intervention with NS. These results, combined with safety and efficacy data, confirm that NS clay is highly effective in reducing aflatoxin exposure and acts as a selective enterosorbent that does not affect the serum concentrations of important vitamins and nutrient minerals in humans.

The efficacy of NovaSil clay (NS) to reduce aflatoxin (AF) biomarkers of exposure was evaluated in 656 blood samples and 624 urine samples collected from study participants during a 3-month phase IIa clinical intervention trial in Ghana. NS was delivered before meals via capsules. Serum AFB (1)-albumin adduct was measured by radioimmunoassay and urinary AFM (1) metabolites were quantified by immunoaffinity-high-performance liquid chromatography (HPLC)-fluorescence methods. Levels of AFB (1) -albumin adduct in serum samples collected at baseline and at 1 month were similar (p = 0.2354 and p = 0.3645, respectively) among the placebo (PL), low dose (LD, 1.5 g NS day (-1)), and high dose (HD, 3.0 g NS day (-1)) groups. However, the levels of AFB (1)-albumin adduct at 3 months were significantly decreased in both the LD group (p < 0.0001) and the HD group (p < 0.0001) compared with levels in the PL group. Levels of AFM(1) in urine samples collected at baseline and at 1 month were not statistically different among the three study groups. However, a significant decrease (up to 58%) in the median level of AFM (1) in samples collected at 3 months was found in the HD group when compared with the median level in the PL group (p < 0.0391). In addition, significant effects were found for dose, time, and dose-time interaction with serum AFB(1)-albumin adduct and dose-time interaction with urinary AFM (1) metabolites. The results suggest that capsules containing NS clay can be used to reduce effectively the bioavailability of dietary AF based on a reduction of AF-specific biomarkers.

Innovative sorption strategies for the detoxification of aflatoxins have been developed. NovaSil clay (NS) has been shown to prevent aflatoxicosis in a variety of animals when included in their diet. Results have shown that NS clay binds aflatoxins with high affinity and high capacity in the gastrointestinal tract, resulting in a notable reduction in the bioavailability of these toxins without interfering with the utilization of vitamins and other micronutrients. This strategy is being evaluated as a potential remedy for acute aflatoxicosis, and as a sustainable human intervention for aflatoxins via the diet. Phase I and II clinical trials confirmed the apparent safety of NS for further study in humans. A recent study in Ghanaians at high risk for aflatoxicosis has indicated that NS (at a dose level of 0.25%) is effective in decreasing biomarkers of aflatoxin exposure and does not interfere with the levels of serum vitamins A and E, and iron and zinc. In summary, enterosorption strategies/therapies based on NS clay are promising for the management of aflatoxins and as a sustainable public health intervention. The NS clay remedy is novel, inexpensive and easily disseminated. Based on the present research, aflatoxin sequestering clays should be rigorously evaluated in vitro and in vivo, and should meet the following criteria: (1) favourable thermodynamic characteristics of mycotoxin sorption, (2) tolerable levels of priority metals, dioxins/furans and other hazardous contaminants, (3) safety and efficacy in multiple animal species, (4) safety and efficacy in long-term studies, and (5) negligible interactions with vitamins, iron and zinc and other micronutrients.

Pesticides have been used for many years to treat pests in agricultural fields; however, the toxicity of some chemicals has caused diverse neurocognitive effects in children even at very low doses. Scientists have noted a possible increased risk for attention disorders in children who were exposed to organophosphate pesticides while in the womb. Recently, there have been a number of studies investigating the impact of low-dose organophosphate exposure on children's neurodevelopment. Exposure to high levels of organophosphate pesticides can potentially increase the odds for attention-deficit/hyperactivity disorder in children. Numerous studies have demonstrated that in children the level of enzymes needed to metabolize pesticides are considerably lower than those in adults. In addition, recent studies suggest that some children may harbor genetic variations that increase their susceptibility to pesticide-related neurocognitive dysfunction. Despite the growing evidence regarding the impact of pesticides on neurocognitive development in children, there is a lack of research and clinical efforts regarding the development of diagnostic outcomes related to pesticide use, especially those that can be used in schools to identify pesticide-related decreases in a child’s academic and cognitive performance. No specific educational programs exist that address pesticide-related cognitive impairments as it relates to a student’s academic progress.

Early life exposure to air pollution is a pressing public health concern due to well-known respiratory effects and the increasing weight of evidence demonstrating the negative consequences on the developing brain. Air pollution is composed of aerosols and particles produced by vehicle emissions, energy production, and manufacturing and other combustion processes. Fine and ultrafine particles, which contain adsorbed metals and toxic compounds, have the ability to reach the brain to cause damage, as well as generate systemic oxidative stress. Collectively, this chapter highlights current epidemiological and mechanistic studies linking childhood air pollution exposure to adverse neurodevelopmental outcomes, including intellectual, academic, neuropsychological, and behavioral functioning changes. In summary, the accumulating evidence suggests a causative relationship and regulations for prevention should be considered.

A 3-month double-blind and placebo-controlled, phase IIa clinical trial was conducted in Ghana to investigate the safety, tolerance and aflatoxin-sorption efficacy of dietary NovaSil (NS). Volunteers (507 subjects) were clinically screened to evaluate their general health, pregnancy status and blood AFB(1)-albumin adduct levels. Of these subjects, 177 were randomly assigned to three groups: high-dose (HD), low-dose (LD) and placebo-control (PL) groups receiving 3.0, 1.5 and 0 g NS day(-1) in capsules. Trained study-monitors supervised NS capsule administration to participants and recorded side-effects daily. Physical examinations were performed monthly. Blood and urine samples were collected for laboratory analysis. Approximately 92% of the participants (162 of 177) completed the study and compliance rate was over 97%. Overall, 99.5% of person x time reported no side-effects throughout the study. Mild to moderate health events ( approximately 0.5% of person x time) were recorded in some participants. Symptoms included nausea, diarrhea, heartburn and dizziness. These side-effects were statistically similar among all three groups. No significant differences were shown in hematology, liver and kidney function or electrolytes in the three groups. These findings demonstrate that NS clay is apparently safe and practical for the protection of humans against aflatoxins in populations at high risk for aflatoxicosis.

The list of cancer markers of current interest has grown considerably, but none of the markers used in clinical work is a true tumor marker. These cancer biomarkers are based on the determination of tumor antigens. Here, we report a single method of autoantibody enzyme immunoassay (EIA) screens for a spectrum of serum tumor markers. A comparison of the autoantibody-based EIA to conventional antigen EIA kits, using receiver operating characteristic (ROC) plots, showed that the autoantibody EIA can significantly enhance the sensitivity and specificity of tumor markers. The detection of serum autoantibodies for a spectrum of serum tumor markers, as demonstrated here, suggests that most, if not all, serum cancer biomarkers produce autoantibodies. A unique autoantibody biomarker screening method, as presented here, might therefore facilitate achieving the accurate and early diagnosis of cancer.

In experimental animals and humans, aflatoxin B1 (AFB1) is a potent hepatic toxin and carcinogen. The synthetic oleanane triterpenoid 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), a powerful activator of Keap1-Nrf2 signaling, protects against AFB1-induced toxicity and preneoplastic lesion formation (GST-P–positive foci). This study assessed and mechanistically characterized the chemoprotective efficacy of CDDO-Im against AFB1-induced hepatocellular carcinoma (HCC). A lifetime cancer bioassay was undertaken in F344 rats dosed with AFB1 (200 μg/kg rat/day) for four weeks and receiving either vehicle or CDDO-Im (three times weekly), one week before and throughout the exposure period. Weekly, 24-hour urine samples were collected for analysis of AFB1 metabolites. In a subset of rats, livers were analyzed for GST-P foci. The comparative response of a toxicogenomic RNA expression signature for AFB1 was examined. CDDO-Im completely protected (0/20) against AFB1-induced liver cancer compared with a 96% incidence (22/23) observed in the AFB1 group. With CDDO-Im treatment, integrated level of urinary AFB1-N7-guanine was significantly reduced (66%) and aflatoxin-N-acetylcysteine, a detoxication product, was consistently elevated (300%) after the first AFB1 dose. In AFB1-treated rats, the hepatic burden of GST-P–positive foci increased substantially (0%–13.8%) over the four weeks, but was largely absent with CDDO-Im intervention. The toxicogenomic RNA expression signature characteristic of AFB1 was absent in the AFB1 + CDDO-Im–treated rats. The remarkable efficacy of CDDO-Im as an anticarcinogen is established even in the face of a significant aflatoxin adduct burden. Consequently, the absence of cancer requires a concept of a threshold for DNA damage for cancer development. Cancer Prev Res; 7(7); 658–65. ©2014 AACR.