Faculty Bibliography

Since the advent of e-cigarettes (e-cigs) as alternatives to conventional cigarette smoking, there has been a dramatic increase in their use especially among adolescents and young adults. Vaping aerosols produced by e-cigs contain a variety of toxic and carcinogenic compounds, such as volatile organic compounds (VOCs), formaldehyde and acrolein, and metals including lead and nickel. General health effects of e-cig use range from respiratory health issues, hypertension and cardiovascular disease, as well as gastrointestinal problems and cognitive and nervous system decline. Unfortunately, there remains very limited information about e-cig use and its association with renal health, despite the fact that chronic kidney disease (CKD) affects about 37 million Americans. It has been reported that cigarette smoking causes the progression of CKD, and that nicotine, a constituent of both conventional cigarettes and e-cig devices, causes renal toxicity by promoting inflammation and injury through oxidative stress-mediated pathways. This contemporary review will discuss the results of current epidemiological and experimental toxicology literature (2016"“2022), as well as possible mechanisms of e-cig-induced renal injury.

Although there is rising global concern over the environmental, ecological, and human health risks associated with the discharge of leachates from e-waste dumpsites into the aquatic ecosystems, little is known in this research area. Thus, for this study, we first defined the chemistry of the test leachate, followed by assessment of the leachate on the development of a model aquatic organism (Fundulus heteroclitus) used extensively as a bioassay organism in pollution studies. Chemical analyses revealed that levels of phosphate (20.03 mg/L), cadmium (Cd) (0.4 mg/L), lead (Pb) (0.2 mg/L), and chromium (Cr) (0.4 mg/L) were higher than the 2009 US EPA and the 2009 National Environmental Standards and Regulations Enforcement Agency (NESREA) permissible limits. Polycyclic aromatic hydrocarbon (PAH) burdens were dominated mainly by the high molecular weight congeners, specifically the ∑4rings (73 µg/L). Total polychlorinated biphenyls (PCB) levels ranged from 0.00 to 0.40 µg/L with the ∑deca PCBs reaching the highest concentration. For the biological studies, F. heteroclitus embryos (48-h post-fertilization) were divided randomly into groups and exposed to one of six e-waste leachate concentrations (10, 1, 0.1, 0.01, 0.001, 0.0001%). Significant differences (p ≤ 0.05) between treated and control groups were observed in standard and total length, and head size. Further analysis using Duncan"™s post-hoc test of multiple comparison also revealed specific differences within and between specific treatment groups. We conclude that e-waste leachate arising from indiscriminate dumping into aquatic ecosystems in Nigeria contains mixtures of toxic constituents that can threaten ecosystem and public health.

Globally, ∼50 % of women smoke during pregnancy and the prevalence of vaping is increasing among women of reproductive age. However, the health effects of vaping during pregnancy are largely unknown. This study examined the effects of e-cig constituents alone and in combination (propylene glycol [PG], vegetable glycerin [VG], and nicotine) on human placental tissue viability (MTT assay) and immunoassayed levels of placenta-derived biomarkers, i.e., 8-isoprostane (8-IsoP), heme oxygenase-1 (HO-1), interleukin-6 (IL-6), β-estradiol (E₂), progesterone (P₄), allopregnanolone (AP), and brain-derived neurotrophic factor (BDNF). Placental explant cultures were exposed ex vivo for 24 h to media-containing either nicotine (0-5000 nM), PG/VG (0-8 % v/v at 50/50 ratio), or a combination of both. No effects on tissue viability were observed at PG/VG concentrations < 8 % (v/v), while viability significantly reduced at PG/VG concentrations ≥ 10 % (v/v); biomarker studies employed only non-cytotoxic doses. Exposure to PG/VG decreased levels of 8-IsoP, IL-6, and E_2, and treatment with 2 % or 8 % PG/VG significantly reduced HO-1 levels, compared to non-treated controls. Exposure to nicotine alone at 2,500 nM and 5,000 nM reduced MTT activity by 20 % (P = 0.04) and 70 % (P < 0.001), respectively, and significantly increased (P < 0.001) levels of HO-1 and BDNF, compared to controls. Treatment with nicotine alone and in combination with PG/VG reduced IL-6 and E₂ levels. Interestingly, nicotine-induced toxicity was attenuated by PG/VG addition to nicotine-treated groups. These studies demonstrate that e-cig constituents negatively impact the human placenta and alters production of critical placental biomarkers, suggesting that vaping is an unsafe alternative for pregnant women or their unborn fetus.

Electronic cigarettes (E-cigs), battery-powered devices containing vegetable glycerin and propylene glycol (PG/VG) as humectants, along with nicotine and flavors, are the most commonly used nicotine product amongst adolescents and young adults. Despite the lack of safety data, pregnant cigarette smokers are also turning to e-cigs as a 'safer' smoking alternative. This study hypothesized that like cigarette smoking, maternal vaping during pregnancy increases the risk of childhood obesity in the offspring. Thus, C57BL/6 mice were exposed both prenatally (3h/d; 5d/wk for ~3-wk) and postnatally from PND 4-21 to e-cig aerosols (50:50 PG/VG) with and without nicotine (16 mg/mL) and alterations in transcriptional and inflammatory activity in hypothalamic metabolic pathways associated with obesity were investigated. At 1-mo-of-age, offspring from filtered air (FA) control and both treatment groups were sacrificed, the hypothalami collected and expression of transporters associated with obesity (i.e., Glucose 1,2,3,4, PPARgamma, and Leptin) analyzed by Western blot. Results here demonstrated a significant increase in glucose transporter 1-4 expression in both the PG/VG alone and PG/VG plus nicotine treatment groups compared to control levels. In addition, gene expression of PPARgamma, LepRb, MC4R, SLC2A1 were significantly increased (p<0.01) in these same 1-moold offspring compared to matched FA controls. Alternatively, no significant changes in AMPK and POMC expression was observed between and amongst treatment groups. These findings suggest that like traditional cigarettes, early life exposure to vaping aerosols (with and without nicotine) predispose the young offspring to obesity later in life via e-cig-induced alterations in the neural-obesity pathways

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.

This study addresses healthcare providers' knowledge deficits in environmental health and genetics, and primarily focuses on student nurses and nurses serving marginalized, low-income communities frequently exposed to environmental toxicants. Our approach to improve public health is unique, combining hands-on modeling exercises with case-based lessons in addition to three targeted 40 min lectures on toxicology. These lectures included the team's community-based environmental health research among Indigenous peoples of the U.S. The hands-on approach employed DNA and protein molecular models designed to demonstrate normal and dysfunctional molecules, as well as genetic variants in world populations. The models provided learners with visuals and an experience of "learning by doing." Increased awareness of the effects of environmental toxicants is the first step toward improving health care for exposed communities. We measured knowledge gains by pre- and post-tests among student nurses and nurses serving Native Americans living both in urban and rural areas of the U.S. (n = 116). The modeling lessons illustrated genetic variants in liver proteins common in Native peoples and their resulting health vulnerabilities. Participants were engaged and enthusiastic; and pre- and post-test results reported substantial knowledge gains and a greater understanding of genetic susceptibility (p < 0.0001). Our study demonstrates the utility of this framework across diverse populations and remote communities.

Inhalation is a significant route of exposure to toxic chemicals for electronic waste (e-waste) workers, especially for those whose activities take place in the informal sector. However, there remains a dearth of research on the health effects produced by the hazardous dismantling of e-waste and associated outcomes and biological mechanisms that occur as a result of inhalation exposure. This contemporary review highlights a number of the toxicological and epidemiological studies published on this topic to bring to light the many knowledge gaps that require further research, including in vitro and ex vivo investigations to address the health outcomes and underlying mechanisms of inhaled e-waste-associated pulmonary disease.

Particulate air pollution (PM) is a mixture of heterogenous components from natural and anthropogenic sources and contributes to a variety of serious illnesses, including neurological and behavioral effects, as well as millions of premature deaths. Ultrafine (PM0.1) and fine-size ambient particles (PM2.5) can enter the circulatory system and cross the blood-brain barrier or enter through the optic nerve, and then upregulate inflammatory markers and increase reactive oxygen species (ROS) in the brain. Toxic and neurotoxic metals such as manganese (Mn), zinc (Zn), lead (Pb), copper (Cu), nickel (Ni), and barium (Ba) can adsorb to the PM surface and potentially contribute to the neurotoxic effects associated with PM exposure. Epidemiological studies have shown a negative relationship between exposure to PM-associated Mn and neurodevelopment amongst children, as well as impaired dexterity in the elderly. Inhaled PM-associated Cu has also been shown to impair motor performance and alter basal ganglia in schoolchildren. This paper provides a brief review of the epidemiological and toxicological studies published over the last five years concerning inhaled PM, PM-relevant metals, neurobiology, and mental health outcomes. Given the growing interest in mental health and the fact that 91% of the world"™s population is considered to be exposed to unhealthy air, more research on PM and PM-associated metals and neurological health is needed for future policy decisions and strategic interventions to prevent public harm.