Co-Therapy with S1P and Heparan Sulfate Derivatives to Restore Endothelial Glycocalyx and Combat Pro-Atherosclerotic Endothelial Dysfunction.

Endothelial cell (EC) glycocalyx (GCX) shedding due to disturbed blood flow and chemical factors leads to low-density lipoprotein infiltration and reduced nitric oxide synthesis, causing vascular dysfunction and atherosclerosis. This study evaluates a novel therapy combining sphingosine-1-phosphate (S1P) and heparin (heparan sulfate derivative). We hypothesized that heparin/S1P would repair mechanically damaged EC GCX in disturbed flow (DF) regions and restore anti-atherosclerotic mechanotransduction function, addressing cardiovascular disease.

Robust differential gene expression patterns in the prefrontal cortex of male mice exposed to an occupationally relevant dose of laboratory-generated wildfire smoke.

Wildfires have become common global phenomena concurrent with warmer and drier climates and are now major contributors to ambient air pollution worldwide. Exposure to wildfire smoke has been classically associated with adverse cardiopulmonary health outcomes, especially in vulnerable populations. Recent work has expanded our understanding of wildfire smoke toxicology to include effects on the central nervous system and reproductive function; however, the neurotoxic profile of this toxicant remains ill-explored in an occupational context.

Integrating local and distant radiation-induced lung injury: Development and validation of a predictive model for ventilation loss.

Background: Investigations on radiation-induced lung injury (RILI) have predominantly focused on local effects, primarily those associated with radiation damage to lung parenchyma. However, recent studies from our group and others have revealed that radiation-induced damage to branching serial structures such as airways and vessels may also have a substantial impact on post-radiotherapy (RT) lung function. Furthermore, recent results from multiple functional lung avoidance RT trials, although promising, have demonstrated only modest toxicity reduction, likely because they were primarily focused on dose avoidance to lung parenchyma.

The utility of hybrid in silico models of airflow and aerosol dosimetry in the lung.

The development and application of multi-scale models of the lung has significantly increased in recent years. These hybrid models merge realistic representations of the larger airways with lower-dimensional descriptions of the bronchioles and respiratory airways. Due to recent advancements, it is possible to calculate airflow and dosimetry throughout the entire lung, enabling model validation with human or animal data.

Impact of Wildfires on Cardiovascular Health.

Wildfire smoke (WFS) is a mixture of respirable particulate matter, environmental gases, and other hazardous pollutants that originate from the unplanned burning of arid vegetation during wildfires. The increasing size and frequency of recent wildfires has escalated public and occupational health concerns regarding WFS inhalation, by either individuals living nearby and downstream an active fire or wildland firefighters and other workers that face unavoidable exposure because of their profession. In this review, we first synthesize current evidence from environmental, controlled, and interventional human exposure studies, to highlight positive associations between WFS inhalation and cardiovascular morbidity and mortality.

Assessment of Left Lung Remodeling With Magnetic Resonance Imaging in a Murine Model Following Exposure to Douglas Fir Smoke.

Wildland firefighters (WLFFs) experience lung function decline due to occupational exposure to fire smoke. WLFFs typically do not wear respiratory personal protective equipment, and if they do, it is a simple bandana, which is not effective at filtering smoke. To pinpoint the biological underpinnings of abnormal respiratory function following 3-7 years of WLFF service, we exposed mice to Douglas fir smoke (DFS) over 8 weeks.

E-cigarette aerosol exposure effect on bone biomechanical properties in murine models.

Numerous studies have shown the detrimental health effects of tobacco smoking on bone volume and strength in human and animal models. Little is known regarding the impacts of e-cigarettes, a form of smoke-less nicotine intake, despite their growing population of users. This study uses murine models to evaluate the effects of exposure to e-cigarette aerosols (JUUL) on bone structure and strength through micro-CT imaging and mechanical testing.

Dosimetry Sensitivity in a Lower Dimensional Model of Patient-Specific Asthma Subjects.

Objective: Experimental uncertainty will impact in silico model calculations of aerosol delivery and deposition. Patient-specific dosimetry models are often parameterized based on medical imaging data, which contain inherent experimental variability.

Methods: Here, we created and parameterized 1D models of three subject-specific asthmatic subjects and randomly assigned perturbations of up to 15 % on airway diameter, segmental volume, and defected volume.

Prolonged smoldering Douglas fir smoke inhalation augments respiratory resistances, stiffens the aorta, and curbs ejection fraction in hypercholesterolemic mice.

While mounting evidence suggests that wildland fire smoke (WFS) inhalation may increase the burden of cardiopulmonary disease, the occupational risk of repeated exposure during wildland firefighting remains unknown. To address this concern, we evaluated the cardiopulmonary function in mice following a cumulative exposure to lab-scale WFS equivalent to a mid-length wildland firefighter (WLFF) career. Dosimetry analysis indicated that 80 exposure hours at a particulate concentration of 22 mg/m yield in mice the same cumulative deposited mass per unit of lung surface area as 3600 h of wildland firefighting.

Respiratory mechanics following chronic cigarette smoke exposure in the Apoe[Formula: see text] mouse model.

Even though cigarette smoking (CS) has been on the decline over the past 50 years, it is still the leading cause of preventable premature death in the United States. Preclinical models have investigated the cardiopulmonary effects of CS exposure (CSE), but the structure-function relationship in the respiratory system has not yet been fully explored. To evaluate these relationships, we exposed female apolipoprotein E-deficient (Apoe[Formula: see text]) mice to mainstream CS ([Formula: see text]) for 5 days/week over 24 weeks with room air as a control (AE, [Formula: see text]).

Pharmacological and physiological response in Apoe mice exposed to cigarette smoke or e-cigarette aerosols.

Objective: Electronic cigarettes (e-cigs) are popular nicotine delivery devices, yet the health effects remain unclear. To determine equivalent biomarkers, we characterized the immediate response in Apoe mice exposed to tank/box-mod e-cig (e-cig), pod e-cig (e-cig), or cig smoke.

Materials And Methods: Reproducible puff profiles were generated for each aerosol and delivered to Apoe mice via a nose-only exposure system.

Effect of moisture content and fuel type on emissions from vegetation using a steady state combustion apparatus.

Emission measurements are available in the literature for a wide variety of field burns and laboratory experiments, although previous studies do not always isolate the effect of individual features such as fuel moisture content (FMC). This study explores the effect of FMC on gaseous and particulate emissions from flaming and smouldering combustion of four different wildland fuels found across the United States. A custom linear tube-heater apparatus was built to steadily produce emissions in different combustion modes over a wide range of FMC.

Simulated Wildfire Smoke Significantly Alters Sperm DNA Methylation Patterns in a Murine Model.

Wildfires are now a common feature of the western US, increasing in both intensity and number of acres burned over the last three decades. The effects of this changing wildfire and smoke landscape are a critical public and occupational health issue. While respiratory morbidity due to smoke exposure is a priority, evaluating the molecular underpinnings that explain recent extrapulmonary observations is necessary.

A whole lung in silico model to estimate age dependent particle dosimetry.

Anatomical and physiological changes alter airflow characteristics and aerosol distribution in the developing lung. Correlation between age and aerosol dosimetry is needed, specifically because youth are more susceptible to medication side effects. In this study, we estimate aerosol dosages (particle diameters of 1, 3, and 5 [Formula: see text]m) in a 3 month-old infant, a 6 year-old child, and a 36 year-old adult by performing whole lung subject-specific particle simulations throughout respiration.

Structural and functional remodeling of the female mouse aorta due to chronic cigarette smoke exposure.

Despite a decline in popularity over the past several decades, cigarette smoking remains a leading cause of cardiovascular morbidity and mortality. Yet, the effects of cigarette smoking on vascular structure and function are largely unknown. To evaluate changes in the mechanical properties of the aorta that occur with chronic smoking, we exposed female apolipoprotein E-deficient mice to mainstream cigarette smoke daily for 24 wk, with room air as control.

Lung-derived HMGB1 is detrimental for vascular remodeling of metabolically imbalanced arterial macrophages.

Pulmonary disease increases the risk of developing abdominal aortic aneurysms (AAA). However, the mechanism underlying the pathological dialogue between the lungs and aorta is undefined. Here, we find that inflicting acute lung injury (ALI) to mice doubles their incidence of AAA and accelerates macrophage-driven proteolytic damage of the aortic wall.

Quantitative Method for Comparative Assessment of Particle Removal Efficiency of Fabric Masks as Alternatives to Standard Surgical Masks for PPE.

In response to the COVID-19 pandemic, cloth masks are being used to control the spread of virus, but the efficacy of these loose-fitting masks is not well known. Here, tools and methods typically used to assess tight-fitting respirators were modified to quantify the efficacy of community-produced and commercially produced fabric masks as personal protective equipment. Two particle counters concurrently sample ambient air and air inside the masks; mask performance is evaluated by mean particle removal efficiency and statistical variability when worn as designed and with a nylon overlayer, to independently assess fit and material.

Integrated Image-Based Computational Fluid Dynamics Modeling Software as an Instructional Tool.

Computational modeling of cardiovascular flows is becoming increasingly important in a range of biomedical applications, and understanding the fundamentals of computational modeling is important for engineering students. In addition to their purpose as research tools, integrated image-based computational fluid dynamics (CFD) platforms can be used to teach the fundamental principles involved in computational modeling and generate interest in studying cardiovascular disease. We report the results of a study performed at five institutions designed to investigate the effectiveness of an integrated modeling platform as an instructional tool and describe "best practices" for using an integrated modeling platform in the classroom.

Acute neuroradiological, behavioral, and physiological effects of nose-only exposure to vaporized cannabis in C57BL/6 mice.

The rapid increase of cannabis consumption reinforces the need to elucidate the health hazards of this practice. The presence of fine particulate matter in cannabis smoke and vapor poses a major concern, as it may contribute to cardiopulmonary disease. To facilitate the assessment of risks associated with cannabis inhalation, we developed and characterized a method for exposing mice to cannabis in a way that mimics the delivery of the drug to the airways of smokers.

Particle transport and deposition correlation with near-wall flow characteristic under inspiratory airflow in lung airways.

Exposure of lung airways to detrimental suspended aerosols in the environment increases the vulnerability of the respiratory and cardiovascular systems. In addition, recent developments in therapeutic inhalation devices magnify the importance of particle transport. In this manuscript, particle transport and deposition patterns in the upper tracheobronchial (TB) tree were studied where the inertial forces are considerable for microparticles.

Patient-specific modeling of aerosol delivery in healthy and asthmatic adults.

The magnitude and regional heterogeneity of airway obstructions in severe asthmatics is likely linked to insufficient drug delivery, as evidenced by the inability to mitigate exacerbations with inhaled aerosol medications. To understand the correlation between morphometric features, airflow distribution, and inhaled dosimetry, we perform dynamic computational simulations in two healthy and four asthmatic subjects. Models incorporate computed tomography-based and patient-specific central airway geometries and hyperpolarized He MRI-measured segmental ventilation defect percentages (SVDPs), implemented as resistance boundary conditions.

Patient-Specific Computational Simulations of Hyperpolarized 3He MRI Ventilation Defects in Healthy and Asthmatic Subjects.

Unlabelled: Combined, medical imaging data and respiratory computer simulations may facilitate novel insight into pulmonary disease phenotypes, including the structure/function relationships within the airways. This integration may ultimately enable improved classification and treatment of asthma. Severe asthma (15% of asthmatics) is particularly challenging to treat, as these patients do not respond well to inhaled therapeutics.

Regional flow and deposition variability in adult female lungs: A numerical simulation pilot study.

Background: Despite the promise of respiratory simulations improving diagnosis and treatment of pulmonary diseases, model predictions have yet to be translated into the clinical setting. Current state-of-the-art in silico models have not yet incorporated subject variability in their predictions of airflow distributions and extent of deposited particles. Until inter-subject variability is accounted for in lung modeling, it will remain impossible to translate model predictions into clinical practice.