Characterization of Atmospheric Particulate Matter in Mountaintop Mining and Non-mining Areas in West Virginia with Known Health Differences

Introduction: Mortality and morbidity rates in the Appalachian region are higher than in the national population. People who live in Appalachian areas where coal mining is prominent have increased health problems compared to people in non-mining areas of Appalachia. Health disparities remain higher in mining areas even after adjusting for lifestyle and demographic effects illustrating that additional factors, such as environmental influences, are associated with adverse health outcomes. Coal mines and coal mining activities result in the production of atmospheric particulate matter (PM), which is associated with environmental and human health effects. Environmental studies of air and water quality in southwest West Virginia provide evidence of air contamination and surface and ground water contamination around coal mining areas, including mountaintop mining (MTM) sites. However, there is a gap in research regarding characterization of PM around MTM areas and the health effects from PM in MTM areas. The objective of this project was to assess the potential health hazard of PM by characterizing atmospheric PM in coal and non-mining areas to identify PM elemental composition, concentration, size distribution to determine inhaled deposited dose, and environmental dry deposition.;Methods/Results: In the first study, particle size distribution and concentration data were collected to calculate deposited lung dose at MTM and non-mining sites. This study was divided into two parts to examine variability in particle size distribution and concentration measurements within sampling areas and seasonal variability within and between MTM and non-mining sites was evaluated. Particle number concentrations and deposited lung dose were elevated around the MTM sites demonstrating elevated risk to humans. In the second study, a primary analysis of semi-quantitative data was conducted to identify the most abundant elements contributing to coarse PM at MTM and non-mining sites. Crustal elements dominated all samples and MTM sites had elevated siliceous materials and the non-mining PM was primarily from combustion sources. The final study quantified environmental dry deposition for inorganic materials at mining and non-mining sites. Results from this study revealed the mining sites contained elevated flux estimates and elevated concentrations of crustal and anthropogenic inorganic materials.;Conclusions: Atmospheric PM at the MTM areas in this study pose an increased hazard to human health due to elevated dose to human lungs, particle count, and chemical composition. This research extends exposure assessment literature by directly estimating the inhaled dose and concentration of particles that residents of high disease rate areas receive. Furthermore, threats to the environment were noted due to elevated dry environmental deposition flux estimates for elements in PM depositing in the environment around mining areas. Our findings demonstrate the need to address air quality issues and regulate mining-related sources of PM in MTM areas to decrease health disparities in the Appalachian coal mining areas

How causal inference concepts can guide research into the effects of climate on infectious diseases

A pressing question resulting from global warming is how infectious diseases will be affected by climate change. Answering this question requires research into the effects of weather on the population dynamics of transmission and infection; elucidating these effects, however, has proven difficult due to the challenges of assessing causality from the predominantly observational data available in epidemiological research. Here, we show how concepts from causal inference -- the sub-field of statistics aiming at inferring causality from data -- can guide that research. Through a series of case studies, we illustrate how such concepts can help assess study design and strategically choose a study's location, evaluate and reduce the risk of bias, and interpret the multifaceted effects of meteorological variables on transmission. More broadly, we argue that interdisciplinary approaches based on explicit causal frameworks are crucial for reliably estimating the effect of weather and accurately predicting the consequences of climate change

The Benefits of Growth-Promoting Implants for Beef Cattle

Growth-promoting implants have been used in the cattle industry for decades. Their benefits allow cattle producers to become more sustainable by decreasing the amount of resources used. Resources such as water and land are decreased when using growth-promoting implants in beef cattle

Understanding the Effects of Trenbolone Acetate, Polyamine Precursors, and Polyamines on Proliferation, Protein Synthesis Rates, and the Abundance of Genes Involved in Myoblast Growth, Polyamine Biosynthesis, and Protein Synthesis in Murine Myoblasts

Research suggests that androgens increase skeletal muscle growth by modulating polyamine biosynthesis. As such, the objective of this study was to investigate effects of anabolic hormones, polyamine precursors, and polyamines relative to proliferation, protein synthesis, and the abundance of mRNA involved in polyamine biosynthesis, proliferation, and protein synthesis in C2C12 and Sol8 cells. Cultures were treated with anabolic hormones (trenbolone acetate and/or estradiol), polyamine precursors (methionine or ornithine), or polyamines (putrescine, spermidine, or spermine). Messenger RNA was isolated 0.5 or 1, 12, or 24 h post-treatment. The cell type had no effect (p \u3e 0.10) on proliferation, protein synthesis, or mRNA abundance at any time point. Each treatment increased (p \u3c 0.01) proliferation, and anabolic hormones increased (p = 0.04) protein synthesis. Polyamines increased (p \u3c 0.05) the abundance of mRNA involved in polyamine biosynthesis, proliferation, and protein synthesis. Treatment with polyamine precursors decreased (p \u3c 0.05) the abundance of mRNA involved in proliferation and protein synthesis. Overall, C2C12 and Sol8 myoblasts do not differ (p \u3e 0.10) in proliferation, protein synthesis, or mRNA abundance at the time points assessed. Furthermore, anabolic hormones, polyamines, and polyamine precursors increase proliferation and protein synthesis, and polyamines and their precursors alter the abundance of mRNA involved in growth

Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT)

AbstractIRTA1 (immunoglobulin superfamily receptor translocation-associated 1) is a novel surface B-cell receptor related to Fc receptors, inhibitory receptor superfamily (IRS), and cell adhesion molecule (CAM) family members and we mapped for the first time its distribution in human lymphoid tissues, using newly generated specific antibodies. IRTA1 was selectively and consistently expressed by a B-cell population located underneath and within the tonsil epithelium and dome epithelium of Peyer patches (regarded as the anatomic equivalents of marginal zone). Similarly, in mucosa-associated lymphoid tissue (MALT) lymphomas IRTA1 was mainly expressed by tumor cells involved in lympho-epithelial lesions. In contrast, no or a low number of IRTA1+ cells was usually observed in the marginal zone of mesenteric lymph nodes and spleen. Interestingly, monocytoid B cells in reactive lymph nodes were strongly IRTA1+. Tonsil IRTA1+ cells expressed the memory B-cell marker CD27 but not mantle cell-, germinal center-, and plasma cell-associated molecules. Polymerase chain reaction (PCR) analysis of single tonsil IRTA1+ cells showed they represent a mixed B-cell population carrying mostly mutated, but also unmutated, IgV genes. The immunohistochemical finding in the tonsil epithelial areas of aggregates of IRTA1+ B cells closely adjacent to plasma cells surrounding small vessels suggests antigen-triggered in situ proliferation/differentiation of memory IRTA1+ cells into plasma cells. Collectively, these results suggest a role of IRTA1 in the immune function of B cells within epithelia. (Blood. 2003;102: 3684-3692

Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19

The high incidence of thrombotic events suggests a possible role of the contact system pathway in COVID-19 pathology. Here, we demonstrate altered levels of factor XII (FXII) and its activation products in critically ill COVID-19 patients in comparison to patients with severe acute respiratory distress syndrome due to influenza virus (ARDS-influenza). Compatible with this data, we report rapid consumption of FXII in COVID-19, but not in ARDS-influenza, plasma. Interestingly, the lag phase in fibrin formation, triggered by the FXII activator kaolin, was not prolonged in COVID-19 as opposed to ARDS-influenza. Using confocal and electron microscopy, we showed that increased FXII activation rate, in conjunction with elevated fibrinogen levels, triggers formation of fibrinolysis-resistant, compact clots with thin fibers and small pores in COVID-19. Accordingly, clot lysis was markedly impaired in COVID-19 as opposed to ARDS-infleunza subjects. Dysregulatated fibrinolytic system, as evidenced by elevated levels of thrombin-activatable fibrinolysis inhibitor, tissue-plasminogen activator, and plasminogen activator inhibitor-1 in COVID-19 potentiated this effect. Analysis of lung tissue sections revealed wide-spread extra- and intra-vascular compact fibrin deposits in COVID-19 patients. Together, compact fibrin network structure and dysregulated fibrinolysis may collectively contribute to high incidence of thrombotic events in COVID-19

Recognition of microbial viability via TLR8 drives TFH cell differentiation and vaccine responses

Live attenuated vaccines are generally highly efficacious and often superior to inactivated vaccines, yet the underlying mechanisms of this remain largely unclear. Here we identify recognition of microbial viability as a potent stimulus for follicular helper T cell (TFH cell) differentiation and vaccine responses. Antigen-presenting cells (APCs) distinguished viable bacteria from dead bacteria through Toll-like receptor 8 (TLR8)-dependent detection of bacterial RNA. In contrast to dead bacteria and other TLR ligands, live bacteria, bacterial RNA and synthetic TLR8 agonists induced a specific cytokine profile in human and porcine APCs, thereby promoting TFH cell differentiation. In domestic pigs, immunization with a live bacterial vaccine induced robust TFH cell and antibody responses, but immunization with its heat-killed counterpart did not. Finally, a hypermorphic TLR8 polymorphism was associated with protective immunity elicited by vaccination with bacillus Calmette-Guérin (BCG) in a human cohort. We have thus identified TLR8 as an important driver of TFH cell differentiation and a promising target for TFH cell–skewing vaccine adjuvants

Immunogenecity of Modified Alkane Polymers Is Mediated through TLR1/2 Activation

Background: With the advancement of biomedical technology, artificial materials have been developed to replace diseased, damaged or nonfunctional body parts. Among such materials, ultra high molecular weight alkane or modified alkyl polymers have been extensively used in heart valves, stents, pacemakers, ear implants, as well as total joint replacement devices. Although much research has been undertaken to design the most non-reactive biologically inert polyethylene derivatives, strong inflammatory responses followed by rejection and failure of the implant have been noted. Methodology/Principal Findings: Purification of the alkane polymers from the site of inflammation revealed extensive ‘‘in vivo’ ’ oxidation as detected by fourier transformed infra-red spectroscopy. Herein, we report the novel observation that oxidized alkane polymers induced activation of TLR1/2 pathway as determined by ligand dependent changes in intrinsic tyrosine fluorescence intensity and NF-kB luciferase gene assays. Oxidized polymers were very effective in activating dendritic cells and inducing secretion of pro-inflammatory cytokines. Molecular docking of the oxidized alkanes designated ligand specificity and polymeric conformations fitting into the TLR1/2 binding grooves