Mast cells are key mediators in the pulmonary inflammatory response to formaldehyde exposure.

Formaldehyde (FA) is a common chemical linked to respiratory problems such as airway hyperresponsiveness and pulmonary inflammation. Due to its toxicological effects and ease of mass production, FA is also recognized as a significant chemical threat by the U.S.

Non-Genotoxic and Environmentally Relevant Lower Molecular Weight Polycyclic Aromatic Hydrocarbons Significantly Increase Tumorigenicity of Benzo[]pyrene in a Lung Two-Stage Mouse Model.

The World Health Organization has classified air pollution as a carcinogen, and polycyclic aromatic hydrocarbons (PAHs) are major components of air particulates of carcinogenic concern. Thus far, most studies focused on genotoxic high molecular weight PAHs; however, recent studies indicate potential carcinogenicity of the non-genotoxic lower molecular weight PAHs (LMW PAHs) that are found in indoor and outdoor air pollution as well as secondhand cigarette smoke. We hypothesize that LMW PAHs contribute to the promotion stage of cancer when combined with benzo[]pyrene (B[]P), a legacy PAH.

Reducing unnecessary preoperative testing through a comprehensive EMR based digital algorithm.

Background: We hypothesised that the implementation of an electronic medical record (EMR) embedded perioperative clinical decision support (CDS) application, Anesthesia Testing Guidelines (ATG), would result in at least a 10% reduction of unnecessary perioperative testing in patients undergoing elective surgeries.

Methods: The development and implementation of ATG occurred in several phases: 1) team development, 2) development of an embedded EMR application, 3) creation of ATG training and education toolkit, and 4) implementation involving promoting ATG through training and education, addressing challenges, and monitoring compliance. The proportions of patients with any overutilisation across 19 perioperative tests were compared between the baseline cohort and the ATG implementation cohort.

When Lightning Strikes: Sports and Recreational Activities Safety.

Lightning strikes and their sequela are well-known sources of injury associated with sports and outdoor activities. While mortality is relatively rare and has steadily decreased over the years, the potentially catastrophic effects make knowledge about lightning strike injuries continually relevant. The primary focus of lightning-related safety is prevention and newer literature over the last 2 years has been largely case reports.

Multi-Omics Analysis of Lung Tissue Demonstrates Changes to Lipid Metabolism during Allergic Sensitization in Mice.

Allergy and asthma pathogenesis are associated with the dysregulation of metabolic pathways. To understand the effects of allergen sensitization on metabolic pathways, we conducted a multi-omics study using BALB/cJ mice sensitized to house dust mite (HDM) extract or saline. Lung tissue was used to perform untargeted metabolomics and transcriptomics while both lung tissue and plasma were used for targeted lipidomics.

Occurrence of Occupational Injuries and Within Day Changes in Wet Bulb Temperature Among Sugarcane Harvesters.

Objective: Climate change has implications for human health worldwide, with workers in outdoor occupations in low- to middle-income countries shouldering the burden of increasing average temperatures and more frequent extreme heat days. An overlooked aspect of the human health impact is the relationship between heat exposure and increased risk of occupational injury. In this study, we examined the association between occupational injury occurrence and changes in outdoor temperatures through the workday among a cohort of Guatemalan sugarcane harvesters.

The Carcinogenic Properties of Overlooked yet Prevalent Polycyclic Aromatic Hydrocarbons in Human Lung Epithelial Cells.

The WHO classified air pollution as a human lung carcinogen and polycyclic aromatic hydrocarbons (PAHs) are components of both indoor (e.g., tobacco smoke and cookstoves) and outdoor (e.

Transcriptomics Underlying Pulmonary Ozone Pathogenesis Regulated by Inflammatory Mediators in Mice.

Ozone (O) is the predominant oxidant air pollutant associated with airway inflammation, lung dysfunction, and the worsening of preexisting respiratory diseases. We previously demonstrated the injurious roles of pulmonary immune receptors, tumor necrosis factor receptor (TNFR), and toll-like receptor 4, as well as a transcription factor NF-κB, in response to O in mice. In the current study, we profiled time-dependent and TNFR- and NF-κB-regulated lung transcriptome changes by subacute O to illuminate the underlying molecular events and downstream targets.

Mast Cells Promote Nitrogen Mustard-Mediated Toxicity in the Lung Associated With Proinflammatory Cytokine and Bioactive Lipid Mediator Production.

Sulfur mustard (SM) has been widely used as a chemical warfare agent including most recently in Syria. Mice exposed to SM exhibit an increase in pro-inflammatory cytokines followed by immune cell infiltration in the lung, however, the mechanisms leading to these inflammatory responses has not been completely elucidated. Mast cells are one of the first responding innate immune cells found at the mucosal surfaces of the lung and have been reported to be activated by SM in the skin.

Two-stage 3-methylcholanthrene and butylated hydroxytoluene-induced lung carcinogenesis in mice.

Lung cancer is one of the deadliest types of cancer and as such requires disease models that are useful for identification of novel pathways for biomarkers as well as to test therapeutic agents. Adenocarcinoma (ADC), the most prevalent type of lung cancer, is a subtype of non-small cell lung carcinoma (NSCLC) and a disease driven mainly by smoking. However, it is also the most common subtype of lung cancer found in non-smokers with environmental exposures.

Comparing the effects of an exposure to a polycyclic aromatic hydrocarbon mixture versus individual polycyclic aromatic hydrocarbons during monocyte to macrophage differentiation: Mixture exposure results in altered immune metrics.

Polycyclic aromatic hydrocarbons (PAHs) are generated by the incomplete combustion of carbon. Exposures correlate with systemic immune dysfunction and overall immune suppression. Real-world exposures to PAHs are almost always encountered as mixtures; however, research overwhelmingly centers on isolated exposures to a single PAH, benzo[a]pyrene (B[a]P).

Physicochemical characterization and genotoxicity of the broad class of carbon nanotubes and nanofibers used or produced in U.S. facilities.

Background: Carbon nanotubes and nanofibers (CNT/F) have known toxicity but simultaneous comparative studies of the broad material class, especially those with a larger diameter, with computational analyses linking toxicity to their fundamental material characteristics was lacking. It was unclear if all CNT/F confer similar toxicity, in particular, genotoxicity. Nine CNT/F (MW #1-7 and CNF #1-2), commonly found in exposure assessment studies of U.

Airborne PAHs inhibit gap junctional intercellular communication and activate MAPKs in human bronchial epithelial cell line.

Inhalation exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with various adverse health effects, including chronic lung diseases and cancer. Using human bronchial epithelial cell line HBE1, we investigated the effects of structurally different PAHs on tissue homeostatic processes, namely gap junctional intercellular communication (GJIC) and MAPKs activity. Rapid (<1 h) and sustained (up to 24 h) inhibition of GJIC was induced by low/middle molecular weight (MW) PAHs, particularly by those with a bay- or bay-like region (1- and 9-methylanthracene, fluoranthene), but also by fluorene and pyrene.

Mitsui-7, heat-treated, and nitrogen-doped multi-walled carbon nanotubes elicit genotoxicity in human lung epithelial cells.

Background: The unique physicochemical properties of multi-walled carbon nanotubes (MWCNT) have led to many industrial applications. Due to their low density and small size, MWCNT are easily aerosolized in the workplace making respiratory exposures likely in workers. The International Agency for Research on Cancer designated the pristine Mitsui-7 MWCNT (MWCNT-7) as a Group 2B carcinogen, but there was insufficient data to classify all other MWCNT.

Assessment of fine particles released during paper printing and shredding processes.

In this study, we investigated the airborne particles released during paper printing and paper shredding processes in an attempt to characterize and differentiate these particles. Particle characteristics were studied with real time instruments (RTIs) to measure concentrations and with samplers to collect particles for subsequent microscopy and cytotoxicity analysis. The particles released by paper shredding were evaluated for cytotoxicity by using in vitro human lung epithelial cell models.

Dysregulation of Gap Junction Function and Cytokine Production in Response to Non-Genotoxic Polycyclic Aromatic Hydrocarbons in an In Vitro Lung Cell Model.

Polycyclic aromatic hydrocarbons (PAHs), prevalent contaminants in our environment, in many occupations, and in first and second-hand smoke, pose significant adverse health effects. Most research focused on the genotoxic high molecular weight PAHs (e.g.

Early Mechanistic Events Induced by Low Molecular Weight Polycyclic Aromatic Hydrocarbons in Mouse Lung Epithelial Cells: A Role for Eicosanoid Signaling.

Low molecular weight polycyclic aromatic hydrocarbons (LMW PAHs; < 206.3 g/mol) are under regulated environmental contaminants (eg, secondhand smoke) that lead to gap junction dysregulation, p38 MAPK activation, and increased mRNA production of inflammatory mediators, such as cytokines and cyclooxygenase (COX2), in lung epithelial cells. However, the early mechanisms involving lipid signaling through the arachidonic acid pathway and subsequent eicosanoid production leading to these downstream events are not known.

Requirement for MUC5AC in KRAS-dependent lung carcinogenesis.

With more than 150,000 deaths per year in the US alone, lung cancer has the highest number of deaths for any cancer. These poor outcomes reflect a lack of treatment for the most common form of lung cancer, non-small cell lung carcinoma (NSCLC). Lung adenocarcinoma (ADC) is the most prevalent subtype of NSCLC, with the main oncogenic drivers being KRAS and epidermal growth factor receptor (EGFR).

Genomic and transcriptomic comparison of allergen and silver nanoparticle-induced mast cell degranulation reveals novel non-immunoglobulin E mediated mechanisms.

Mast cells represent a crucial cell type in host defense; however, maladaptive responses are contributing factors in the pathogenesis of allergic diseases. Previous work in our laboratory has shown that exposure to silver nanoparticles (AgNPs) results in mast cell degranulation via a non-immunoglobulin E (IgE) mechanism. In this study, we utilized a systems biology approach to identify novel genetic factors playing a role in AgNP-induced mast cell degranulation compared to the classical activation by antigen-mediated FcεRI crosslinking.

Toll-like receptor expression in human non-small cell lung carcinoma: potential prognostic indicators of disease.

Introduction: Lung cancer remains the highest cause of cancer mortality worldwide. Toll-like receptors (TLR) are innate immune receptors that have both pro- and anti-tumorigenic properties. Based on findings from epidemiological studies and in rodents, we hypothesized that elevated TLR expression would be a positive prognostic indicator of disease in non-small cell lung carcinoma patients.

Environmentally prevalent polycyclic aromatic hydrocarbons can elicit co-carcinogenic properties in an in vitro murine lung epithelial cell model.

Low molecular weight (LMW) polycyclic aromatic hydrocarbons (PAH) are the most abundant PAHs environmentally, occupationally, and are in cigarette smoke; however, little is known about their carcinogenic potential. We hypothesized that LMW PAHs act as co-carcinogens in the presence of a known carcinogen (benzo[a]pyrene (B[a]P)) in a mouse non-tumorigenic type II cell line (C10 cells). Gap junctions are commonly suppressed and inflammation induced during tumor promotion, while DNA-adduct formation is observed during the initiation stage of cancer.

Secondhand Smoke-Prevalent Polycyclic Aromatic Hydrocarbon Binary Mixture-Induced Specific Mitogenic and Pro-inflammatory Cell Signaling Events in Lung Epithelial Cells.

Low molecular weight polycyclic aromatic hydrocarbons (LMW PAHs; < 206.3 g/mol) are prevalent and ubiquitous environmental contaminants, presenting a human health concern, and have not been as thoroughly studied as the high MW PAHs. LMW PAHs exert their pulmonary effects, in part, through P38-dependent and -independent mechanisms involving cell-cell communication and the production of pro-inflammatory mediators known to contribute to lung disease.