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Background: The terrorist attacks on September 11, 2001, on the World Trade Center (WTC) led to intense fires and a massive dense cloud of toxic gases and suspended pulverized debris. In the subsequent years, following the attack and cleanup efforts, a cluster of chronic health conditions emerged among First Responders (FR) who were at Ground Zero for prolonged periods and were repeatedly exposed to high levels of WTC particulate matter (WTCPM). Among those are neurological complications which may increase the risk for the development of Alzheimer’s disease (AD) later in life. Objective: We hypothesize that WTCPM dust exposure affects the immune cross-talking between the periphery and central nervous systems that may induce brain permeability ultimately promoting AD-type phenotype. Methods: 5XFAD and wild-type mice were intranasally administered with WTCPM dust collected at Ground Zero within 72 h after the attacks. Y-maze assay and novel object recognition behavioral tests were performed for working memory deficits and learning and recognition memory, respectively. Transcriptomic analysis in the blood and hippocampus was performed and confirmed by RT qPCR. Results: Mice exposed to WTCPM dust exhibited a significant impairment in spatial and recognition short and long-term memory. Furthermore, the transcriptomic analysis in the hippocampal formation and blood revealed significant changes in genes related to immune-inflammatory responses, and blood-brain barrier disruption. Conclusion: These studies suggest a putative peripheral-brain immune inflammatory cross-talking that may potentiate cognitive decline, identifying for the first time key steps which may be therapeutically targetable in future studies in WTC FR.

Difference in gene expression between archived WTC and non WTC cases

Differentially expressed genes in rat prostates exposed to WTC dusts

Background Particle matter (PM) has been associated with increased morbidity and mortality rates across the world. This study was designed to test the hypotheses that pyrotechnic firework displays introduce significant amounts of toxic metals into the atmosphere and are hazardous to human health. Size-selective emissions from 10 different fireworks displays were collected during particle generation in a dynamic, stainless steel chamber and tested for toxicity in cells. A subset of 2 particle types were tested in vivo in mice. At doses that did not produce cytotoxicity in an LDH assay, in vitro reactive oxygen species (ROS) formation was measured in bronchial epithelial airway (BEAS-2B) and human pulmonary microvascular endothelial (HPMEC-ST1.6R) cell lines treated with size-fractionated particles from the emissions of fireworks. Results Significant increases in ROS, in both cell types, were dependent upon the type of firework but not particle size. The in vitro ROS activity was correlated with lung inflammation produced in groups of mice treated by oropharyngeal aspiration with 0, 50, or 100 μg fireworks PM10/mouse. Trace metal analyses of the PM10 samples showed significant differences in metal content among fireworks type. Interestingly, the PM10 sample for the fireworks type producing the greatest in vitro ROS response in BEAS-2B cells contained ~ 40,000 and ~ 12,000 ppm of lead and copper, respectively. This sample also produced the greatest inflammatory response (i.e., increased neutrophils in bronchoalveolar lavage fluid) in mice. Conclusions These findings demonstrate that pyrotechnic display particles can produce adverse effects in mammalian cells and lungs, thus suggesting that further research is needed to expand our understanding of the contribution of metal content to the adverse health effects of fireworks particles. This information will lead to the manufacture of safer fireworks.

Background: Studies have revealed the increased incidence of health disorders in First Responders (FR) who were at Ground Zero over the initial 72 hr after the World Trade Center (WTC) collapses. Previous studies in rats exposed to WTC dusts using exposure scenarios that mimicked FR mouthbreathing showed exposure led to altered expression of genes whose products could be involved in lung ailments. Nevertheless, it was uncertain if repeated exposures (as occurred in earliest days post-disaster) might have given rise to long-term changes in the lungs/other organs, in white blood cell (WBC) profiles, and/or systemic expression of select (mostly immune-related) proteins.Methods: To examine this, rats were exposed on 2 consecutive days (2 hr/d, intratracheal inhalation) to WTC dusts and then examined over a 1-yr period thereafter. At select times post-exposure, organ (lung, heart, liver, kidney, spleen) weights, WBC profiles, and blood levels of a variety of proteins were evaluated.Results: The study showed that over the 1-yr period, there were nominal effects on organ weights (absolute, index) as a result of the dust exposures. There were significant changes (relative to in naive rats) in WBC profiles, with exposed rats having increased monocyte-macrophage and decreased lymphocyte percentages. The study also found that dust exposure led to significant systemic increases in many proteins, including MCP-1, RANTES, MMP-9, RAGE, and Galectin-3.Conclusions: These results provide further support for our longstanding hypothesis that the WTC dusts could potentially have acted as direct inducers of many of the health effects that have been seen in the exposed FR.

Previous in vitro and in vivo World Trade Center particulate matter (WTC(PM)) exposure studies have provided evidence of exposure-driven oxidative/nitrative stress and inflammation on respiratory tract and aortic tissues. What remains to be fully understood are secondary organ impacts due to WTC(PM) exposure. This study was designed to test if WTC particle-induced nasal and neurologic tissue injury may result in unforeseen functional and behavioral outcomes. Namely, WTC(PM) exposure was found to incite neurologic injury and olfaction latency in intranasally (IN) exposed mice. Single high-dose and repeat low-dose nasal cavity insults from WTC(PM) dust resulted in significant olfaction delays and enduring olfaction deficits. Anxiety-dependent behaviors also occurred in mice experiencing olfaction loss including significant body weight loss, increased incidence and time spent in hind stretch postures, as well as increased stationary time and decreased exploratory time. Additionally, WTC(PM) exposure resulted in increased whole brain wet/dry ratios and wet whole brain to body mass ratios that were correlated with exposure and increased exposure dose (p

Consider the long-range models on $\mathbb{Z}^d$ of random walk, self-avoiding walk, percolation and the Ising model, whose translation-invariant 1-step distribution/coupling coefficient decays as $|x|^{-d-\alpha}$ for some $\alpha>0$. In the previous work (Ann. Probab., 43, 639--681, 2015), we have shown in a unified fashion for all $\alpha\ne2$ that, assuming a bound on the "derivative" of the $n$-step distribution (the compound-zeta distribution satisfies this assumed bound), the critical two-point function $G_{p_c}(x)$ decays as $|x|^{\alpha\wedge2-d}$ above the upper-critical dimension $d_c\equiv(\alpha\wedge2)m$, where $m=2$ for self-avoiding walk and the Ising model and $m=3$ for percolation. In this paper, we show in a much simpler way, without assuming a bound on the derivative of the $n$-step distribution, that $G_{p_c}(x)$ for the marginal case $\alpha=2$ decays as $|x|^{2-d}/\log|x|$ whenever $d\ge d_c$ (with a large spread-out parameter $L$). This solves the conjecture in the previous work, extended all the way down to $d=d_c$, and confirms a part of predictions in physics (Brezin, Parisi, Ricci-Tersenghi, J. Stat. Phys., 157, 855--868, 2014). The proof is based on the lace expansion and new convolution bounds on power functions with log corrections., Comment: 31 pages, 1 figure, 3 diagrams in equations

Recent studies have shown that some adverse pregnancy outcomes, especially intrauterine growth restriction (IUGR), are associated with gestational exposure to ambient fine particulate matter (PM

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic cigarette (e-cigarette) vaping has surpassed conventional cigarette smoking among adolescents and young adults in the United States and beyond. This review describes the experimental and clinical evidence of e-cigarette toxicity and deleterious health effects. Adverse health effects related to e-cigarette aerosols are influenced by several factors, including e-liquid components, physical device factors, chemical changes related to heating, and health of the e-cigarette user (e.g., asthmatic). Federal, state, and local regulations have attempted to govern e-cigarette flavors, manufacturing, distribution, and availability, particularly to underaged youths. However, the evolving e-cigarette landscape continues to impede timely toxicological studies and hinder progress made toward our understanding of the long-term health consequence of e-cigarettes.

In this review, we elucidate the central role played by fossil fuel combustion in the health-related effects that have been associated with inhalation of ambient fine particulate matter (PM2.5). We especially focus on individual properties and concentrations of metals commonly found in PM air pollution, as well as their sources and their adverse health effects, based on both epidemiologic and toxicological evidence. It is known that transition metals, such as Ni, V, Fe, and Cu, are highly capable of participating in redox reactions that produce oxidative stress. Therefore, particles that are enriched, per unit mass, in these metals, such as those from fossil fuel combustion, can have greater potential to produce health effects than other ambient particulate matter. Moreover, fossil fuel combustion particles also contain varying amounts of sulfur, and the acidic nature of the resulting sulfur compounds in particulate matter (e.g., as ammonium sulfate, ammonium bisulfate, or sulfuric acid) makes transition metals in particles more bioavailable, greatly enhancing the potential of fossil fuel combustion PM2.5 to cause oxidative stress and systemic health effects in the human body. In general, there is a need to further recognize particulate matter air pollution mass as a complex source-driven mixture, in order to more effectively quantify and regulate particle air pollution exposure health risks.

Background: Heatwave events are occurring more frequently, accompanied by a significant increase in the ambient concentration of fine particulate matter (PM2.5). Epidemiological studies have suggested that heat stress or PM2.5 exposure would impair glucose homeostasis and insulin sensitivity, but the combined effect and the exact mechanisms are not well understood.Methods: C57BL/6 mice were randomly divided into filtered air (FA), fine particulate matter (PM) group, filtered air combined with heat stress (FH) group, and fine particulate matter combined with heat stress (PH) group for a 4-week PM2.5 exposure, followed by a 2-week heat stress exposure, via a whole-body exposure system. Systemic glucose homeostasis, insulin sensitivity, and circulating inflammatory cytokines were examined. HSP72 expression and insulin signaling in the liver were measured.Results: Glucose tolerance and insulin sensitivity were impaired in response to heat stress, accompanied by lessened hepatic GLUT2 expression and inhibited insulin signaling pathway. No synergistic effects of heat stress and PM2.5 exposure on glucose homeostasis were observed, while heat-upregulated HSP72 expression was attenuated with accumulated TNF-α induced by further PM2.5 exposure.Conclusions: Heat stress combined with PM2.5 exposure induced TNF-α, which could inhibit heat-elevated hepatic HSP72 expression. Elevated circulating TNF-α impaired hepatic insulin signaling and GLUT2 expression. Then, glucose homeostasis was perturbed, and insulin action was impaired.

Significance Electronic-cigarette smoke (ECS) is designed to deliver nicotine, and its use is gaining popularity. Previously, we found that ECS induces DNA damage and inhibits DNA repair in the mouse lungs and bladder urothelium. Nicotine induces the same types of DNA adducts and has a similar effect on DNA repair inhibition in human cells. Nicotine also enhances human cells’ mutation and tumorigenic transformation susceptibility. Our current results show that ECS-exposed mice developed lung adenocarcinoma and bladder urothelial hyperplasia, indicating that ECS is a lung carcinogen and a potential bladder carcinogen in mice. While it is well established that tobacco smoke poses a huge threat to human health, the threat ECS poses to humans is not yet known and warrants in-depth investigation., Electronic-cigarettes (E-cigs) are marketed as a safe alternative to tobacco to deliver the stimulant nicotine, and their use is gaining in popularity, particularly among the younger population. We recently showed that mice exposed to short-term (12 wk) E-cig smoke (ECS) sustained extensive DNA damage in lungs, heart, and bladder mucosa and diminished DNA repair in lungs. Nicotine and its nitrosation product, nicotine-derived nitrosamine ketone, cause the same deleterious effects in human lung epithelial and bladder urothelial cells. These findings raise the possibility that ECS is a lung and bladder carcinogen in addition to nicotine. Given the fact that E-cig use has become popular in the past decade, epidemiological data on the relationship between ECS and human cancer may not be known for a decade to come. In this study, the carcinogenicity of ECS was tested in mice. We found that mice exposed to ECS for 54 wk developed lung adenocarcinomas (9 of 40 mice, 22.5%) and bladder urothelial hyperplasia (23 of 40 mice, 57.5%). These lesions were extremely rare in mice exposed to vehicle control or filtered air. Current observations that ECS induces lung adenocarcinomas and bladder urothelial hyperplasia, combined with our previous findings that ECS induces DNA damage in the lungs and bladder and inhibits DNA repair in lung tissues, implicate ECS as a lung and potential bladder carcinogen in mice. While it is well established that tobacco smoke poses a huge threat to human health, whether ECS poses any threat to humans is not yet known and warrants careful investigation.

An excess incidence of prostate cancer has been identified among World Trade Center (WTC) responders. In this study, we hypothesized that WTC dust, which contained carcinogens and tumor-promoting agents, could facilitate prostate cancer development by inducing DNA damage, promoting cell proliferation, and causing chronic inflammation. We compared expression of immunologic and inflammatory genes using a NanoString assay on archived prostate tumors from WTC Health Program (WTCHP) patients and non-WTC patients with prostate cancer. Furthermore, to assess immediate and delayed responses of prostate tissue to acute WTC dust exposure via intratracheal inhalation, we performed RNA-seq on the prostate of normal rats that were exposed to moderate to high doses of WTC dust. WTC prostate cancer cases showed significant upregulation of genes involved in DNA damage and G2–M arrest. Cell-type enrichment analysis showed that Th17 cells, a subset of proinflammatory Th cells, were specifically upregulated in WTC patients. In rats exposed to WTC dust, we observed upregulation of gene transcripts of cell types involved in both adaptive immune response (dendritic cells and B cells) and inflammatory response (Th17 cells) in the prostate. Unexpectedly, genes in the cholesterol biosynthesis pathway were also significantly upregulated 30 days after acute dust exposure. Our results suggest that respiratory exposure to WTC dust can induce inflammatory and immune responses in prostate tissue. Implications: WTC-related prostate cancer displayed a distinct gene expression pattern that could be the result of exposure to specific carcinogens. Our data warrant further epidemiologic and cellular mechanistic studies to better understand the consequences of WTC dust exposure. Visual Overview: http://mcr.aacrjournals.org/content/molcanres/17/8/1605/F1.large.jpg.

Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated.

Hookah smoking is becoming increasingly popular worldwide and recent epidemiological studies indicate that it is significantly associated with respiratory diseases, and could contain constituents more harmful than cigarette smoking. However, the gene expression alterations and mechanisms of disease development induced by the hookah constituents are still unclear. Here, we are the first to propose a new experimental design and use RNA sequencing to profile bronchial epithelial cells from different hookah smoking exposure conditions (GSE162386). For our hookah-smoking dataset, we developed an integrated genome-wide model, hierarchical-systems biology model (HiSBiM), to systematically investigate the effects of smoking hookah and to compare the biological pathways with public cigarette smoking datasets. Our results show that the infectious disease-related pathways were enriched in hookah smoking than in cigarette smoking, which could be due to polluted hookah devices or pathogen contaminated water filters. Furthermore, we investigate the subsystem and pathway differences in hookah smoking between charcoal and electronic heating ways. We observed that cardiovascular and atherosclerosis-related pathways were activated after exposure to charcoal combustion, which may relate to combustion components carbon monoxide and polyaromatic hydrocarbons. Overall, our results show that hookah smoking could involve a higher risk in several diseases than cigarette smoking and link the relations between hookah constituents to diseases. We believe that our HiSBiM is a useful integrated method for providing multiple-level valued insights for genome-wide analysis on various omics data sets.

[Figure: see text].

Emerging evidence has demonstrated that exposure to fine particulate matter (PM

Background & aims Emerging evidence supports ambient fine particulate matter (PM2.5) exposure is associated with insulin resistance (IR) and hepatic lipid accumulation. In this study, we aimed to evaluate the sex-dependent vulnerability in response to PM2.5 exposure and investigate the underlying mechanism by which PM2.5 modulates hepatic lipid metabolism. Methods Both male and female C57BL/6 mice were randomly assigned to ambient PM2.5 or filtered air for 24 weeks via a whole body exposure system. High-coverage quantitative lipidomics approaches and liquid chromatography-mass spectrometry techniques were performed to measure hepatic metabolites and hormones in plasma. Metabolic studies, histological analyses, as well as gene expression levels and molecular signal transduction analysis were applied to examine the effects and mechanisms by which PM2.5 exposure-induced metabolic disorder. Results Female mice were more susceptible than their male counterparts to ambient PM2.5 exposure-induced IR and hepatic lipid accumulation. The hepatic lipid profile was changed in response to ambient PM2.5 exposure. Levels of hepatic triacylglycerols (TAGs), free fatty acids (FFAs) and cholesterol were only increased in female mice from PM group compared to control group. Plasmalogens were dysregulated in the liver from PM2.5-exposed mice as well. In addition, exposure to PM2.5 led to enhanced hepatic ApoB and microsomal triglyceride transport protein expression in female mice. Finally, PM2.5 exposure inhibited hypothalamus-pituitary-adrenal (HPA) axis and decreased glucocorticoids levels, which may contribute to the vulnerability in PM2.5-induced metabolic dysfunction. Conclusions Ambient PM2.5 exposure inhibited HPA axis and demonstrated sex-associated differences in its effects on IR and disorder of hepatic lipid metabolism. These findings provide new mechanistic evidence of hormone regulation in air pollution-mediated metabolic abnormalities of lipids and more personalized care should be considered in terms of sex-specific risk factors.

Additional file 1: Supplemental Materials. Supplemental Figure 1. Body weight and fasting blood glucose before PM2.5 exposure in C57BL/6 mice. A, Absolute value of body weight. B, Absolute value of fasting blood glucose. C, Fold change of body weight relative to FA. D, Fold change of blood glucose relative to FA. n=8. Supplemental Figure 2. Effects of PM2.5 exposure on body weight and glucose homeostasis in C57BL/6 mice at the end of PM2.5 exposure. A, Fold change of body weight relative to FA. B, Fold change of fasting blood glucose relative to FA. C-D, Fold change of fasting insulin levels (C) and HOMA-IR (D). E, Fold change of AUC (area under curves) of ITT relative to FA. *P

Additional file 1: Supplemental Figure 1. The effect of 12 fireworks types on the fold increase (over media control) in ROS activity in HPMEC cells treated with 100 μg/ml (PM10). The columns and error bars represent the mean and SEM, respectively. * p

First responders (FR) exposed to the World Trade Center (WTC) Ground Zero air over the first week after the 9/11 disaster have an increased heart disease incidence compared to unexposed FR and the general population. To test if WTC dusts were causative agents, rats were exposed to WTC dusts (under isoflurane [ISO] anesthesia) 2 h/day on 2 consecutive days; controls received air/ISO or air only. Hearts were collected 1, 30, 240, and 360 d post-exposure, left ventricle total RNA was extracted, and transcription profiles were obtained. The data showed that differentially expressed genes (DEG) for WTC vs. ISO rats did not reach any significance with a false discovery rate (FDR) < 0.05 at days 1, 30, and 240, indicating that the dusts did not impart effects beyond any from ISO. However, at day 360, 14 DEG with a low FDR were identified, reflecting potential long-term effects from WTC dust alone, and the majority of these DEG have been implicated as having an impact on heart functions. Furthermore, the functional gene set enrichment analysis (GSEA) data at day 360 showed that WTC dust could potentially impact the myocardial energy metabolism via PPAR signaling and heart valve development. This is the first study showing that WTC dust could significantly affect some genes that are associated with the heart/CV system, in the long term. Even > 20 years after the 9/11 disaster, this has potentially important implications for those FR exposed repeatedly at Ground Zero over the first week after the buildings collapsed.

The allure of tobacco smoking is linked to the instant gratification provided by inhaled nicotine. Unfortunately, tobacco curing and burning generates many mutagens including more than 70 carcinogens. There are two types of mutagens and carcinogens in tobacco smoke (TS): direct DNA damaging carcinogens and procarcinogens, which require metabolic activation to become DNA damaging. Recent studies provide three new insights on TS-induced DNA damage. First, two major types of TS DNA damage are induced by direct carcinogen aldehydes, cyclic-1,N(2)-hydroxy-deoxyguanosine (γ- OH-PdG) and α-methyl-1,N(2)- γ -OH-PdG, rather than by the procarcinogens, polycyclic aromatic amines and aromatic amines. Second, TS reduces DNA repair proteins and activity levels. TS aldehydes also prevent procarcinogen activation. Based on these findings, we propose that aldehydes are major sources of TS induced DNA damage and a driving force for carcinogenesis. E-cigarettes (E-cigs) are designed to deliver nicotine in an aerosol state, without burning tobacco. E-cigarette aerosols (ECAs) contain nicotine, propylene glycol and vegetable glycerin. ECAs induce O(6)-methyl-deoxyguanosines (O(6)-medG) and cyclic γ-hydroxy-1,N(2)--propano-dG (γ -OH-PdG) in mouse lung, heart and bladder tissues and causes a reduction of DNA repair proteins and activity in lungs. Nicotine and nicotine-derived nitrosamine ketone (NNK) induce the same types of DNA adducts and cause DNA repair inhibition in human cells. After long-term exposure, ECAs induce lung adenocarcinoma and bladder urothelial hyperplasia in mice. We propose that E-cig nicotine can be nitrosated in mouse and human cells becoming nitrosamines, thereby causing two carcinogenic effects, induction of DNA damage and inhibition of DNA repair, and that ECA is carcinogenic in mice. Thus, this article reviews the newest literature on DNA adducts and DNA repair inhibition induced by nicotine and ECAs in mice and cultured human cells, and provides insights into ECA carcinogenicity in mice.

We consider a long-range Domany–Kinzel model proposed by Li and Zhang (1983), such that for every site ( i , j ) in a two-dimensional rectangular lattice there is a directed bond present from site ( i , j ) to ( i + 1 , j ) with probability one. There are also m + 1 directed bounds present from ( i , j ) to ( i − k + 1 , j + 1 ) , k = 0 , 1 , … , m with probability p k ∈ [ 0 , 1 ) , where m is a non-negative integer. Let τ m ( M , N ) be the probability that there is at least one connected-directed path of occupied edges from ( 0 , 0 ) to ( M , N ) . Defining the aspect ratio α = M ∕ N , we derive the correct critical value α m , c ∈ R such that as N → ∞ , τ m ( M , N ) converges to 1, 0 and 1 ∕ 2 for α > α m , c , α α m , c and α = α m , c , respectively, and we study the rate of convergence. Furthermore, we investigate the cases in the infinite m limit. Specifically, we discuss in details the case such that p n ∈ [ 0 , 1 ) with n ∈ Z + and p n ≈ n → ∞ p n − s for p ∈ ( 0 , 1 ) and s > 0 . We find that the behavior of lim m → ∞ τ m ( M , N ) for this case highly depends on the value of s and how fast one approaches to the critical aspect ratio. The present study corrects and extends the results given in Li and Zhang (1983).

Background The popularity of electronic cigarettes (E-cigarettes) has risen considerably. Several studies have suggested that nicotine may affect insulin resistance, however, the impact of E-cigarette exposure on insulin resistance, an early measure of cardiometabolic risk, is not known. Methods and results Using experimental animals and human data obtained from 3,989 participants of the United States National Health and Nutrition Examination Survey (NHANES), respectively, we assessed the association between E-cigarette and conventional cigarette exposures and insulin resistance, as modelled using the homeostatic model assessment of insulin resistance (HOMA-IR) and glucose tolerance tests (GTT). C57BL6/J mice (on standard chow diet) exposed to E-cigarette aerosol or mainstream cigarette smoke (MCS) for 12 weeks showed HOMA-IR and GTT levels comparable with filtered air-exposed controls. In the NHANES cohort, there was no significant association between defined tobacco product use categories (non-users; sole E-cigarette users; cigarette smokers and dual users) and insulin resistance. Compared with non-users of e-cigarettes/conventional cigarettes, sole E-cigarette users showed no significant difference in HOMA-IR or GTT levels following adjustment for age, sex, race, physical activity, alcohol use and BMI. Conclusion E-cigarettes do not appear to be linked with insulin resistance. Our findings may inform future studies assessing potential cardiometabolic harms associated with E-cigarette use.

Purpose: This study aimed to analyze and summarize the effects that waterpipe (WP) smoke has on the cardiopulmonary system through a systematic review and meta-analysis. Methods: We searched MEDLINE, Embase, Wiley Cochrane Library, Centre for Reviews and Dissemination, CINAHL Plus, and grey literature in March 2017. Our inclusion criteria for the studies were a comparison of WP smokers before and after waterpipe smoking (WPS) or to non-smokers. Results: Using a random effects meta-analysis, a WPS session was associated with an elevation in systolic blood pressure (SBP) by 6.45 mmHg (95% CI 3.87 to 9.04; p < 0.0001), diastolic blood pressure (DBP) by 3.71 mmHg (95% CI 2.34 to 5.08; p < 0.0001), mean arterial pressure by 5.54 mmHg (95% CI 3.33 to 7.76; p < 0.0001), heart rate by 7.03 bpm (95% CI 4.60 to 9.46; p < 0.0001), carboxyl hemoglobin (COHb) by 4.11% (95% CI 3.38 to 4.84; p < 0.0001), and expired carbon monoxide (CO) by 22.53 ppm (95% CI 15.99 to 29.08; p < 0.0001). Conclusion: WPS exposure is associated with significant acute increases in cardiopulmonary hemodynamic parameters, along with COHb and expired CO. These findings parallel the acute effects seen with cigarette smoking.

In this study, factor analysis and mass regression were used to identify four fine particulate matter sources and estimate their contributions to the ambient air pollution in Beijing. The identified sources were traffic re-suspended soil, mixed industrial sources, oil combustion, and secondary sulfate. The estimated source contributions were then introduced into two models as exposure variables to explore the relationships between cardiovascular responses in mice and PM exposures. We observed that PM2.5 has a small negative acute effect on heart rate, but the individual source factors showed much more significant effects. Traffic re-suspended soil had the most significant effect on heart rate, with a positive contribution on the day of exposure and a negative one on day lag 1. Acute heart rate variability outcomes were better explained by the total PM2.5 than by the source components. Chronic effects were observed as a decreased heart rate but an increased number of heart rate variability outcomes.

World Trade Center (WTC) responders were exposed to mixture of dust, smoke, chemicals and carcinogens. New York University (NYU) and Mount Sinai have recreated WTC exposure in rodents to observe the resulting systemic and local biological responses. These experiments aid in the interpretation of epidemiological observations and are useful for understanding the carcinogenesis process in the exposed human WTC cohort. Here we describe the implementation of a tissue bank system for the rodents experimentally exposed to WTC dust. NYU samples were experimentally exposed to WTC dust via intratracheal inhalation that mimicked conditions in the immediate aftermath of the disaster. Tissue from Mount Sinai was derived from genetically modified mice exposed to WTC dust via nasal instillation. All processed tissues include annotations of the experimental design, WTC dust concentration/dose, exposure route and duration, genetic background of the rodent, and method of tissue isolation/storage. A biobank of tissue from rodents exposed to WTC dust has been compiled representing an important resource for the scientific community. The biobank remains available as a scientific resource for future research through established mechanisms for samples request and utilization. Studies using the WTC tissue bank would benefit from confirming their findings in corresponding tissues from organs of animals experimentally exposed to WTC dust. Studies on rodent tissues will advance the understanding of the biology of the tumors developed by WTC responders and ultimately impact the modalities of treatment, and the probability of success and survival of WTC cancer patients.

Air pollution is a complex mixture of gaseous, volatile, and particulate matter (PM) containing inorganic and organic species. There is now abundant evidence in epidemiological and toxicological studies that air pollution contributes to the development and exacerbation of diseases of respiratory, cardiovascular, and other organs, and associated mortality. Studies showed that equal masses of PM could induce disparate health effects, suggesting that particle sizes and components may be at fault. The fine and ultrafine PM is considered to be particularly important because the small particles can be easily inhaled. Possible biological mechanisms of action leading to adverse effects include the production of inflammatory mediators in the lung causing systemic inflammation, interaction with neural receptors causing interference with the central nervous system regulation of cardiovascular function, and particle translocation via the bloodstream to other organs. This chapter reviews whether some components of the PM mixture are of a greater public health concern than others, and presents compelling evidence that trace elements are most strongly linked to the adverse effects. Air pollution has wide-ranging and harmful effects on human health and is a major issue for the global community. Further research should explore the effects of source-specific PM with more advanced approaches to exposure modeling, measurements, and statistics, which would lead to more effective legislation and interventions for greater benefits to public health.

This file contains the supplemental tables to the manuscript titled: chemokine receptor CXCR3 regulates pulmonary emphysema.

Background In Xuan Wei, China, the lung cancer mortality rate is rising significantly more than that of the nation overall. However, it remains unclear 1) if improved diagnosis can just partially explain this observation and how other local risk factors may be correlated with the lung cancer mortality rate and 2) how the lung cancer mortality rates differ within Xuan Wei and how these spatiotemporal patterns are linked with local risk factors. To increase etiological knowledge, this study evaluated the spatial and temporal distributions of the health effects (the lung cancer mortality rates) from 2011 to 2015. Methods Four steps of spatial analysis were applied, as follows: 1) hotspot analysis to determine the geographical patterns of lung cancer mortality, 2) spatially-weighted sum to identify areas with higher health risks, 3) bivariate statistical analysis to assess the overall correlation between coal mines and lung cancer mortality, and 4) geographically-weighted regression to test for correlations among different towns within Xuan Wei. Results Women had higher lung cancer mortality rates than those in men, with an increasing trend in both sexes over time. The incidence rates in Laibin Town were the highest in Xuan Wei every year. Over the 5-year study period, the lung cancer mortality was increasingly concentrated in Laibin, Shuanglong, and Longchang, where the smoky coal mines are most concentrated. The population-level health risks from the coal mine in Xuan Wei were mapped and divided into five types of risk areas (Type I – Type IV). Correlation analysis revealed that there was no significant correlation between lung cancer mortality as a whole and coal mine distribution during the 5-year study period. However, the geographically-weighted regression revealed a stronger correlation in medium (Type III) and second-lowest (Type IV) health risks. Conclusions Xuan Wei lung cancer mortality has increased continuously since the third national retrospective surveys on the causes of death by the Ministry of Health of the People’s Republic of China (2004–2005), especially for local women and residents over 35 years of age. Geographically, lung cancer in Xuan Wei showed unique spatiotemporal clustering. The local lung cancer mortality was significantly correlated with the smoky coal mine geographically. Some specific towns (Laibin, Shuanglong, and Longchang) within Xuan Wei manifested high correlations between lung cancer mortality and coal mines. The effects of coal mines on lung cancer mortality rates also spread geographically outward from these areas. Public health concern regarding lung cancer in Xuan Wei should prioritize higher-risk towns surrounded by smoking coal mines. Intervention strategies for particular toxic coal types require further studies on their chemical characteristics and mechanisms of carcinogenesis. Additional studies are also warranted to systematically examine the local environmental health risks related to coal industries and combustion air pollution and eventually to conduct early screening of lung cancer for local people who are more exposed to smoky coal in high-risk areas.