Environmental Health Sciences Faculty Publication Series

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Roadside Exposure and Inflammation Biomarkers among a Cohort of Traffic Police in Kathmandu, Nepal
(2019-01-01) Shakya, Kabindra M.; Peltier, Richard E.; Zhang, Yimin; Pandey, Basu D.
Air pollution is a major environmental problem in the Kathmandu Valley. Specifically, roadside and traffic-related air pollution exposure levels were found at very high levels exceeding Nepal air quality standards for daily PM2.5. In an exposure study involving traffic police officers, we collected 78 blood samples in a highly polluted spring season (16 February 2014–4 April 2014) and 63 blood samples in the less polluted summer season (20 July 2014–22 August 2014). Fourteen biomarkers, i.e., C-reactive protein (CRP), serum amyloid A (SAA), intracellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), interferon gamma (IFN-γ), interleukins (IL1-β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13), and tumor necrosis factor (TNF-α) were analyzed in collected blood samples using proinflammatory panel 1 kits and vascular injury panel 2 kits. All the inflammatory biomarker levels were higher in the summer season than in the spring season, while particulate levels were higher in the spring season than in the summer season. We did not find significant association between 24-hour average PM2.5 or black carbon (BC) exposure levels with most of analyzed biomarkers for the traffic volunteers working and residing near busy roads in Kathmandu, Nepal, during 2014. Inflammation and vascular injury marker concentrations were generally higher in females, suggesting the important role of gender in inflammation biomarkers. Because of the small sample size of female subjects, further investigation with a larger sample size is required to confirm the role of gender in inflammation biomarkers.
A glance into how the cold war and governmental loyalty investigations came to affect a leading U.S. radiation geneticist: Lewis J. Stadler’s nightmare
(2017-01-01) Calabrese, Edward J.
This paper describes an episode in the life of the prominent plant radiation geneticist, Lewis J. Stadler (1897–1954) during which he became a target of the Federal Bureau of Investigation (FBI) concerning loyalty to the United States due to possible associations with the communist party. The research is based on considerable private correspondence of Dr. Stadler, the FBI interrogatory questions and Dr. Stadler’s answers and letters of support for Dr. Stadler by leading scientists such as, Hermann J. Muller.
Ambient PM2.5 and risk of emergency room visits for myocardial infarction: impact of regional PM2.5 oxidative potential: a case-crossover study
(2016-01-01) Weichenthal, Scott; Lavigne, Eric; Evans, Greg; Pollitt, Krystal; Burnett, Rick T.
Background Regional differences in the oxidative potential of fine particulate air pollution (PM2.5) may modify its impact on the risk of myocardial infarction. Methods A case-crossover study was conducted in 16 cities in Ontario, Canada to evaluate the impact of regional PM2.5 oxidative potential on the relationship between PM2.5and emergency room visits for myocardial infarction. Daily air pollution and meteorological data were collected between 2004 and 2011 from provincial monitoring sites and regional estimates of glutathione (OPGSH) and ascorbate-related (OPAA) oxidative potential were determined using an acellular assay based on a synthetic respiratory tract lining fluid. Exposure variables for the combined oxidant capacity of NO2 and O3 were also examined using their sum (Ox) and a weighted average (Ox wt) based on their redox potentials. Results In total, 30,101 cases of myocardial infarction were included in the analysis. For regions above the 90th percentile of OPGSH each 5 μg/m3 increase in same-day PM2.5 was associated with a 7.9 % (95 % CI: 4.1, 12) increased risk of myocardial infarction whereas a 4.1 % (95 % CI: 0.26, 8.0) increase was observed in regions above the 75th percentile and no association was observed below the 50th percentile (p-interaction = 0.026). A significant 3-way interaction was detected with the strongest associations between PM2.5 and myocardial infarction occurring in areas with high regional OPGSH and high Ox wt (p-interaction < 0.001). Conclusions Regional PM2.5 oxidative potential may modify the impact of PM2.5 on the risk of myocardial infarction. The combined oxidant capacity of NO2 and O3 may magnify this effect.
Developmental Exposure to 2,2′,4,4′-Tetrabromodiphenyl Ether Permanently Alters Blood-Liver Balance of Lipids in Male Mice
(2018-01-01) Khalil, Ahmed; Cevik, Sebnem Eren; Hung, Stephanie; Kolla, Sridurgadevi; Roy, Monika; Suvorov, Alexander
Polybrominated diphenyl ethers (PBDEs) were used as flame-retardant additives starting 1965 and were recently withdrawn from commerce in North America and Europe. Approximately 1/5 of the total U.S. population were born when environmental concentrations of PBDE plateaued at their maximum. Accumulating evidence suggests that developmental exposures to PBDE may result in long-lasting programming of liver metabolism. In this study, CD-1 mice were exposed prenatally or neonatally to 1 mg/kg body weight of 2,2′ ,4,4′ -tetrabromodiphenyl ether (BDE-47), and changes in liver histology, transcriptome, and liver-blood balance of triglycerides were analyzed in 10 months old male offspring. In both exposure groups, long-term reprogramming of lipid metabolism was observed, including increased liver triglycerides and decreased blood triglycerides, and altered expression of metabolic genes in the liver. Significant upregulation of lipid influx transporter Cd36 2.3- and 5.7-fold in pre- and neonatal exposure groups, respectively was identified as a potential mechanism of blood/liver imbalance of triglycerides. Analysis of our and previously published all-genome gene expression data identified changes in expression of ribosomal protein genes as a transcriptomic signature of PBDE exposure. Further comparison of our new data and published data demonstrate that low doses (0.2 mg/kg body weight) of PBDE induce long-lasting up-regulation of ribosomal genes, suppression of Cd36 in liver and increase circulating triglycerides in blood, while moderated doses (≥1 mg/kg body weight) produce opposite long-lasting effects. To conclude, this study shows that an environmentally relevant developmental exposures to BDE-47 permanently alter lipid uptake and accumulation in the liver, with low and moderate doses having opposite effect on liver transcriptomics and triglyceride balance. Similar effects of pre- and neonatal exposures point at hepatocyte maturation as a sensitive window of the liver metabolism programming. These results suggest that PBDE exposure may be an important factor increasing risks of cardio-vascular disease and non-alcoholic fatty liver disease via modulation of liver/blood balance of lipids. The translational relevance of these findings for human remain to be studied.
A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals
(2016-01-01) Vandenberg, Laura N.; Ågerstrand, Marlene; Beronius, Anna; Beausoleil, Claire; Bergman, Åke; Bero, Lisa A.; Bornehag, Carl-Gustaf; Boyer, C. Scott; Cooper, Glinda S.; Cotgreave, Ian; Gee, David; Grandjean, Philippe; Guyton, Kathryn Z.; Hass, Ulla; Heindel, Jerrold J.; Jobling, Susan; Kidd, Karen A.; Kortenkamp, Andreas; Macleod, Malcolm R.; Martin, Olwenn V.; Norinder, Ulf; Scheringer, Martin; Thayer, Kristina A.; Toppari, Jorma; Whaley, Paul; Woodruff, Tracey J.; Rudén, Christina
Background The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs. Methods We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity. Results Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs. Conclusions When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible.
Preconception Phthalate Exposure and Women’s Reproductive Health: Pregnancy, Pregnancy Loss, and Underlying Mechanisms
(2024-01-01) Nobles, Carrie J.
Background: Phthalates are endocrine-disrupting chemicals linked to adverse pregnancy outcomes. Despite the sensitivity of female reproductive processes to oxidation–reduction reaction stress and endocrine disruption, evidence for the impact of women’s phthalate exposure on the ability to establish and maintain pregnancy has been inconclusive. Objectives: We aimed to determine the relationship of preconception phthalate metabolite exposure with a) fecundability and pregnancy loss and b) markers of potential biological mechanisms, including reproductive hormones, inflammation, and oxidative stress. Methods: Data were collected from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, a preconception study following 1,228 women who were attempting pregnancy, for up to six menstrual cycles and throughout pregnancy if they became pregnant. Twenty phthalate metabolites were measured in a consecutive 3-d pooled urine sample at enrollment. Pregnancy was determined through urinary human chorionic gonadotropin (hCG) at the expected date of menses during each cycle and pregnancy loss as an observed loss following positive hCG. Highly sensitive C-reactive protein (hsCRP) and isoprostanes were measured at enrollment, and reproductive hormones were measured during the follicular phase, ovulation, and luteal phase. Discrete-time Cox proportional hazards models evaluated the relationship of phthalate metabolites with fecundability and weighted Poisson models with robust variance evaluated the risk of pregnancy loss. Results: An interquartile range (IQR) higher mono-(2-ethylhexyl) phthalate [fecundability odds ratio (FOR)=0.88; 95% confidence interval (CI): 0.78, 1.00], mono-butyl phthalate (FOR=0.82; 95% CI: 0.70, 0.96), and mono-benzyl phthalate (FOR=0.85; 95% CI: 0.74, 0.98) was associated with lower fecundability. No consistent associations were observed with pregnancy loss. Preconception phthalates were consistently associated with higher hsCRP and isoprostanes, as well as lower estradiol and higher follicle-stimulating hormone across the menstrual cycle.
Oxybenzone Alters Mammary Gland Morphology in Mice Exposed During Pregnancy and Lactation
(2018-01-01) LaPlante, Charlotte D.; Bansal, Ruby; Dunphy, Karen A.; Jerry, D. Joseph; Vandenberg, Laura N.
Hormones and endocrine-disrupting chemicals are generally thought to have permanent “organizational” effects when exposures occur during development but not adulthood. Yet, an increasing number of studies have shown that pregnant females are disrupted by endocrine-disrupting chemical exposures, with some effects that are permanent. Here, we examined the long-term effects of exposure to oxybenzone, an estrogenic chemical found in sunscreen and personal care products, on the morphology of the mammary gland in mice exposed during pregnancy and lactation. Female mice were exposed to vehicle or 30, 212, or 3000 µg oxybenzone/kg/d, from pregnancy day 0 until weaning. A nulliparous group, receiving vehicle treatment, was also evaluated. Mammary glands were collected 5 weeks after involution for whole-mount, histological, immunohistochemical, and molecular analyses. Exposure to 3000 µg oxybenzone/kg/d induced permanent changes to ductal density that was significantly different from both the nulliparous and vehicle groups. The two highest doses of oxybenzone similarly induced an intermediate phenotype for expression of progesterone receptor. A monotonic, dose-dependent increase in cell proliferation was also observed in the oxybenzone-treated females, becoming statistically significant at the highest dose. Finally, oxybenzone exposure induced an intermediate phenotype for Esr1 expression in all oxybenzone-treated groups. These data suggest that oxybenzone, at doses relevant to human exposures, produces long-lasting alterations to mammary gland morphology and function. Further studies are needed to determine if exposure to this chemical during pregnancy and lactation will interfere with the known protection that pregnancy provides against breast cancer.
Heterogeneous Contributions of Change in Population Distribution of Body Mass Index to Change in Obesity and Underweight
(2021-01-01)
From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
The challenges of defining hormesis in epidemiological studies: The case of radiation hormesis
(2023-01-01) Iavicoli, Ivo; Fontana, Luca; Guarino, Davide; Laudiero, Martina; Calabrese, Edward J.
In the current radiation protection system, preventive measures and occupational exposure limits for controlling occupational exposure to ionizing radiation are based on the linear no-threshold extrapolation model. However, currently an increasing body of evidence indicates that this paradigm predicts very poorly biological responses in the low-dose exposure region. In addition, several in vitro and in vivo studies demonstrated the presence of hormetic dose response curves correlated to ionizing radiation low exposure. In this regard, it is noteworthy that also the findings of different epidemiological studies, conducted in different categories of occupationally exposed workers (e.g., healthcare, nuclear industrial and aircrew workers), observed lower rates of mortality and/or morbidity from cancer and/or other diseases in exposed workers than in unexposed ones or in the general population, then suggesting the possible occurrence of hormesis. Nevertheless, these results should be considered with caution since the identification of hormetic response in epidemiological studies is rather challenging because of a number of major limitations. In this regard, some of the most remarkable shortcomings found in epidemiological studies performed in workers exposed to ionizing radiation are represented by lack or inadequate definition of exposure doses, use of surrogates of exposure, narrow dose ranges, lack of proper control groups and poor evaluation of confounding factors. Therefore, considering the valuable role and contribution that epidemiological studies might provide to the complex risk assessment and management process, there is a clear and urgent need to overcome the aforementioned limits in order to achieve an adequate, useful and more real-life risk assessment that should also include the key concept of hormesis. Thus, in the present conceptual article we also discuss and provide possible approaches to improve the capacity of epidemiological studies to identify/define the hormetic response and consequently improve the complex process of risk assessment of ionizing radiation at low exposure doses.
Modulating Glutathione Thiol Status Alters Pancreatic β-cell Morphogenesis in the Developing Zebrafish (Danio rerio) Embryo
(2021-01-01) Rastogi, Archit; Severance, Emily G.; Jacobs, Haydee M.; Conlin, Sarah M.; Islam, Sadia T.; Timme-Laragy, Alicia R.
Emerging evidence suggests that redox-active chemicals perturb pancreatic islet development. To better understand potential mechanisms for this, we used zebrafish (Danio rerio) embryos to investigate roles of glutathione (GSH; predominant cellular redox buffer) and the transcription factor Nrf2a (Nfe2l2a; zebrafish Nrf2 coortholog) in islet morphogenesis. We delineated critical windows of susceptibility to redox disruption of beta-cell morphogenesis, interrogating embryos at 24, 48 and 72 h post fertilization (hpf) and visualized Nrf2a expression in the pancreas using whole-mount immunohistochemistry at 96 hpf. Chemical GSH modulation at 48 hpf induced significant islet morphology changes at 96 hpf. Pro-oxidant exposures to tert-butylhydroperoxide (77.6 mu M; 10-min at 48 hpf) or tert-butylhydroquinone (1 mu M; 48-56 hpf) decreased beta-cell cluster area at 96 hpf. Conversely, exposures to antioxidant N-acetylcysteine (bolsters GSH pools; 100 mu M; 48-72 hpf) or sulforaphane (activates Nrf2a; 20 mu M; 48-72 hpf) significantly increased islet areas. Nrf2a was also stabilized in beta-cells: 10-min exposures to 77.6 mu M tert-butylhydroperoxide significantly increased Nrf2a protein compared to control islet cells that largely lack stabilized Nrf2a; 10-min exposures to higher (776 mu M) tert-butylhydroperoxide concentration stabilized Nrf2a throughout the pancreas. Using biotinylated-GSH to visualize in situ protein glutathionylation, islet cells displayed high protein glutathionylation, indicating oxidized GSH pools. The 10-min high (776 mu M) tert-butylhydroperoxide exposure (induced Nrf2a globally) decreased global protein glutathionylation at 96 hpf. Mutant fish expressing inactive Nrf2a were protected against tert-butylhydroperoxide-induced abnormal islet morphology. Our data indicate that disrupted redox homeostasis and Nrf2a stabilization during pancreatic beta-cell development impact morphogenesis, with implications for disease states at later life stages. Our work identifies a potential molecular target (Nrf2) that mediates abnormal beta-cell morphology in response to redox disruptions. Moreover, our findings imply that developmental exposure to exogenous stressors at distinct windows of susceptibility could diminish the reserve redox capacity of beta-cells, rendering them vulnerable to later-life stresses and disease.
Three Years of High Time-resolution Air Pollution Monitoring in the Complex Multi-source Harbor of New York and New Jersey
(2021-01-01) Hagler, Gayle; Birkett, Dan; Henry, Ronald C.; Peltier, Richard E.
In densely developed port areas with numerous emissions sources, relating measured air quality changes to emissions is challenging given the geographic density of sources without unique pollutant composition signatures. To better understand air quality during increasing emission controls at the Port of New York and New Jersey (Port), an air monitoring station was sited to minimize collinearity of sources along ordinal directions. The study area includes an international airport, interstate highway, port terminals and shipping lanes, and industrial sources, as well as typical urban emissions of a megacity. Because air flow travel time from sources to the monitor were usually much less than one hour, minute-by-minute, high-precision data were collected for three years (2013-2015) for sulfur dioxide (SO2), carbon monoxide (CO), oxides of nitrogen (NO, NO2), black carbon (BC), fine particulate matter (PM2.5), and meteorology (wind speed, wind direction, temperature, humidity). From summer 2014 to spring 2015, hourly metals data were also collected. A high degree of temporal variability was observed for pollutants associated with direct emissions, with highest hourly average coefficient of variation observed for NO (2.65), SO2 (1.45) and BC (1.21). Nonparametric trajectory analysis (NTA) was utilized to separate the source areas influencing the monitoring data and observe how they changed over time, with over 1.6 million trajectories computed in total. Comparing the last 5 quarters of the study to the first 5 quarters, concentrations at the monitoring site associated with three port-related geographic areas decreased by 34-41%, 11-17%, and 28-41% for SO2, NOx, and BC, respectively. Over the same period, indicators of shipping and cargo activity at the port remained relatively constant; therefore, a shift in emission factors is likely the cause of the change. This study demonstrates the value of high-time resolution, accurate monitoring data along with careful siting to understand source area influences.
The Science of Spin: Targeted Strategies to Manufacture Doubt With Detrimental Effects on Environmental and Public Health
(2021-01-01) Goldberg, Rebecca F.; Vandenberg, Laura N.
Background Numerous groups, such as the tobacco industry, have deliberately altered and misrepresented knowable facts and empirical evidence to promote an agenda, often for monetary benefit, with consequences for environmental and public health. Previous research has explored cases individually, but none have conducted an in-depth comparison between cases. The purpose of this study was to compile a comprehensive list of tactics used by disparate groups and provide a framework for identifying further instances of manufactured doubt. Methods We examined scholarly books, peer-reviewed articles, well-researched journalism pieces, and legal evidence related to five disparate industries and organizations selected for their destructive impacts on environmental and public health (tobacco, coal, and sugar industries, manufacturers of the pesticide Atrazine, and the Marshall Institute, an institute focused on climate change research, and other scientists from the era that associated with those in the Institute). These documents provided evidence for a list of tactics used to generate pro-industry spin and manufacture doubt about conferred harm. We then identified trends among sets of strategies that could explain their differential use or efficacy. Results We recognized 28 unique tactics used to manufacture doubt. Five of these tactics were used by all five organizations, suggesting that they are key features of manufactured doubt. The intended audience influences the strategy used to misinform, and logical fallacies contribute to their efficacy. Conclusions This list of tactics can be used by others to build a case that an industry or group is deliberately manipulating information associated with their actions or products. Improved scientific and rhetorical literacy could be used to render them less effective, depending on the audience targeted, and ultimately allow for the protection of both environmental health and public health more generally.
Spatial-Temporal Patterns of Ambient Fine Particulate Matter (PM 2.5) and Black Carbon (BC) Pollution in Accra
(2021-01-01) Alli, Abosede S.; Clark, Sierra N.; Hughes, Allison; Nimo, James; Bedford-Moses, Josephine; Baah, Solomon; Wang, Jiayuan; Vallarino, Jose; Agyemang, Ernest; Barratt, Benjamin
Sub-Saharan Africa (SSA) is rapidly urbanizing, and ambient air pollution has emerged as a major environmental health concern in growing cities. Yet, effective air quality management is hindered by limited data. We deployed robust, low-cost and low-power devices in a large-scale measurement campaign and characterized within-city variations in fine particulate matter (PM2.5) and black carbon (BC) pollution in Accra, Ghana. Between April 2019 and June 2020, we measured weekly gravimetric (filter-based) and minute-by-minute PM2.5 concentrations at 146 unique locations, comprising of 10 fixed (similar to 1 year) and 136 rotating (7 day) sites covering a range of land-use and source influences. Filters were weighed for mass, and light absorbance (10(-5)m(-1)) of the filters was used as proxy for BC concentration. Year-long data at four fixed sites that were monitored in a previous study (2006-2007) were compared to assess changes in PM2.5 concentrations. The mean annual PM2.5 across the fixed sites ranged from 26 mu g m(-3) at a peri-urban site to 43 mu g m(-3) at a commercial, business, and industrial (CBI) site. CBI areas had the highest PM2.5 levels (mean: 37 mu g m(-3)), followed by high-density residential neighborhoods (mean: 36 mu g m(-3)), while peri-urban areas recorded the lowest (mean: 26 mu g m(-3)). Both PM2.5 and BC levels were highest during the dry dusty Harmattan period (mean PM2.5: 89 mu g m(-3)) compared to non-Harmattan season (mean PM2.5: 23 mu g m(-3)). PM2.5 at all sites peaked at dawn and dusk, coinciding with morning and evening heavy traffic. We found about a 50% reduction (71 vs 37 mu g m(-3)) in mean annual PM2.5 concentrations when compared to measurements in 2006-2007 in Accra. Ambient PM2.5 concentrations in Accra may have plateaued at levels lower than those seen in large Asian megacities. However, levels are still 2- to 4-fold higher than the WHO guideline. Effective and equitable policies are needed to reduce pollution levels and protect public health.
Space-Time Characterization of Community Noise and Sound Sources in Accra, Ghana
(2021-01-01) Clark, Sierra N.; Alli, Abosede S.; Nathvani, Ricky; Hughes, Allison; Ezzati, Majid; Brauer, Michael; Toledano, Mireille B.; Baumgartner, Jill; Bennett, James E.; Nimo, James
Urban noise pollution is an emerging public health concern in growing cities in sub-Saharan Africa (SSA), but the sound environment in SSA cities is understudied. We leveraged a large-scale measurement campaign to characterize the spatial and temporal patterns of measured sound levels and sound sources in Accra, Ghana. We measured sound levels and recorded audio clips at 146 representative locations, involving 7-days (136 locations) and 1-year measurements between 2019 and 2020. We calculated metrics of noise levels and intermittency and analyzed audio recordings using a pre-trained neural network to identify sources. Commercial, business, and industrial areas and areas near major roads had the highest median daily sound levels (LAeq(24hr): 69 dBA and 72 dBA) and the lowest percentage of intermittent sound; the vice-versa was found for peri urban areas. Road-transport sounds dominated the overall sound environment but mixtures of other sound sources, including animals, human speech, and outdoor music, dominated in various locations and at different times. Environmental noise levels in Accra exceeded both international and national health-based guidelines. Detailed information on the acoustical environmental quality (including sound levels and types) in Accra may guide environmental policy formulation and evaluation to improve the health of urban residents.
Simple method for cutoff point identification in descriptive high-throughput biological studies
(2022-01-01) Suvorov, Alexander
Background Rapid development of high-throughput omics technologies generates an increasing interest in algorithms for cutoff point identification. Existing cutoff methods and tools identify cutoff points based on an association of continuous variables with another variable, such as phenotype, disease state, or treatment group. These approaches are not applicable for descriptive studies in which continuous variables are reported without known association with any biologically meaningful variables. Results The most common shape of the ranked distribution of continuous variables in high-throughput descriptive studies corresponds to a biphasic curve, where the first phase includes a big number of variables with values slowly growing with rank and the second phase includes a smaller number of variables rapidly growing with rank. This study describes an easy algorithm to identify the boundary between these phases to be used as a cutoff point. Discussion The major assumption of that approach is that a small number of variables with high values dominate the biological system and determine its major processes and functions. This approach was tested on three different datasets: human genes and their expression values in the human cerebral cortex, mammalian genes and their values of sensitivity to chemical exposures, and human proteins and their expression values in the human heart. In every case, the described cutoff identification method produced shortlists of variables (genes, proteins) highly relevant for dominant functions/pathways of the analyzed biological systems. Conclusions The described method for cutoff identification may be used to prioritize variables in descriptive omics studies for a focused functional analysis, in situations where other methods of dichotomization of data are inaccessible.
Transcriptomic Analysis of Gonadal Adispose Tissue in Male Mice Exposed Perinatally to 2,2',4,4'-Tetrabromodiphenyl Ether (BDE-47)
(2018-01-01) Abrha, Aser; Suvorov, Alexander
For the majority of lipophilic compounds, adipose tissue is traditionally considered as a storage depot and only rarely as a target organ. Meanwhile, abnormalities in adipose tissue physiology induced by chemical exposure may contribute to the current epidemic of obesity and metabolic diseases. Polybrominated diphenyl ethers (PBDEs) are a group of lipophilic flame retardants found in the majority of human samples in North America. Their ability to alter the physiology of adipose tissue is unknown. We exposed pregnant mice to 0.2 mg/kg body weight/day of BDE-47 perinatally. Transcriptomic changes in gonadal adipose tissue were analyzed in male offspring using the RNA-seq approach with subsequent bioinformatic analysis. The expression of genes of coagulation and complement cascade, de novo lipogenesis, and xenobiotic metabolism was altered in response to BDE-47 exposure. The affected molecular network included the following hubs: PPARα, HNF1A, and HNF4. These findings suggest that adipose tissue should be considered a target tissue for BDE-47, in addition to its role as a storage depot. This study also builds a background for a targeted search of sensitive phenotypic endpoints of BDE-47 exposure, including lipid profile parameters and coagulation factors in circulation. Additional studies are needed to investigate the role of PBDEs as an obesogen.
Chemical Exposures Affect Innate Immune Response to SARS-CoV-2
(2021-01-01) Arowolo, Olatunbosun; Pobezinsky, Leonid; Suvorov, Alexander
Severe outcomes of COVID-19 are associated with pathological response of the immune system to the SARS-CoV-2 infection. Emerging evidence suggests that an interaction may exist between COVID-19 pathogenesis and a broad range of xenobiotics, resulting in significant increases in death rates in highly exposed populations. Therefore, a better understanding of the molecular basis of the interaction between SARS-CoV-2 infection and chemical exposures may open opportunities for better preventive and therapeutic interventions. We attempted to gain mechanistic knowledge on the interaction between SARS-CoV-2 infection and chemical exposures using an in silico approach, where we identified genes and molecular pathways affected by both chemical exposures and SARS-CoV-2 in human immune cells (T-cells, B-cells, NK-cells, dendritic, and monocyte cells). Our findings demonstrate for the first time that overlapping molecular mechanisms affected by a broad range of chemical exposures and COVID-19 are linked to IFN type I/II signaling pathways and the process of antigen presentation. Based on our data, we also predict that exposures to various chemical compounds will predominantly impact the population of monocytes during the response against COVID-19.
Curcumin, Hormesis and the Nervous System
(2019-01-01) Scuto, Maria Concetta; Mancuso, Cesare; Tomasello, Barbara; Ontario, Maria Laura; Cavallaro, Andrea; Frasca, Francesco; Maiolino, Luigi; Salinaro, Angela Trovato; Calabrese, Edward J.; Calabrese, Vittorio
Curcumin is a polyphenol compound extracted from the rhizome of Curcuma longa Linn (family Zingiberaceae) commonly used as a spice to color and flavor food. Several preclinical studies have suggested beneficial roles for curcumin as an adjuvant therapy in free radical-based diseases, mainly neurodegenerative disorders. Indeed, curcumin belongs to the family of hormetins and the enhancement of the cell stress response, mainly the heme oxygenase-1 system, is actually considered the common denominator for this dual response. However, evidence-based medicine has clearly demonstrated the lack of any therapeutic effect of curcumin to contrast the onset or progression of neurodegeneration and related diseases. Finally, the curcumin safety profile imposes a careful analysis of the risk/benefit balance prior to proposing chronic supplementation with curcumin.
Hormesis and Ginseng: Ginseng Mixtures and Individual Constituents Commonly Display Hormesis Dose Responses, Especially for Neuroprotective Effects
(2020-01-01) Calabrese, Edward
This paper demonstrates that ginseng mixtures and individual ginseng chemical constituents commonly induce hormetic dose responses in numerous biological models for endpoints of biomedical and clinical relevance, typically providing a mechanistic framework. The principal focus of ginseng hormesis-related research has been directed toward enhancing neuroprotection against conditions such as Alzheimer’s and Parkinson’s Diseases, stroke damage, as well as enhancing spinal cord and peripheral neuronal damage repair and reducing pain. Ginseng was also shown to reduce symptoms of diabetes, prevent cardiovascular system damage, protect the kidney from toxicities due to immune suppressant drugs, and prevent corneal damage, amongst other examples. These findings complement similar hormetic-based chemoprotective reports for other widely used dietary-type supplements such as curcumin, ginkgo biloba, and green tea. These findings, which provide further support for the generality of the hormetic dose response in the biomedical literature, have potentially important public health and clinical implications.
Healthspan Enhancement by Olive Polyphenols in C. elegans Wild Type and Parkinson’s Models
(2020-01-01) Rosa, Gabriele Di; Brunetti, Givovanni; Scuto, Maria; Salinaro, Angela Trovato; Calabrese, Edward; Crea, Roberto; Schmitz-Linneweber, Christian; Calabrese, Vittorio; Saul, Nadine
Parkinson’s disease (PD) is the second most prevalent late-age onset neurodegenerative disorder, affecting 1% of the population after the age of about 60 years old and 4% of those over 80 years old, causing motor impairments and cognitive dysfunction. Increasing evidence indicates that Mediterranean diet (MD) exerts beneficial effects in maintaining health, especially during ageing and by the prevention of neurodegenerative disorders. In this regard, olive oil and its biophenolic constituents like hydroxytyrosol (HT) have received growing attention in the past years. Thus, in the current study we test the health-promoting effects of two hydroxytyrosol preparations, pure HT and Hidrox® (HD), which is hydroxytyrosol in its “natural” environment, in the established invertebrate model organism Caenorhabditis elegans. HD exposure led to much stronger beneficial locomotion effects in wild type worms compared to HT in the same concentration. Consistent to this finding, in OW13 worms, a PD-model characterized by α-synuclein expression in muscles, HD exhibited a significant higher effect on α-synuclein accumulation and swim performance than HT, an effect partly confirmed also in swim assays with the UA44 strain, which features α-synuclein expression in DA-neurons. Interestingly, beneficial effects of HD and HT treatment with similar strength were detected in the lifespan and autofluorescence of wild-type nematodes, in the neuronal health of UA44 worms as well as in the locomotion of rotenone-induced PD-model. Thus, the hypothesis that HD features higher healthspan-promoting abilities than HT was at least partly confirmed. Our study demonstrates that HD polyphenolic extract treatment has the potential to partly prevent or even treat ageing-related neurodegenerative diseases and ageing itself. Future investigations including mammalian models and human clinical trials are needed to uncover the full potential of these olive compounds.

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