Publications by authors named "Michael Yost"

152 Publications

Examining the role of wind in human illness due to pesticide drift in Washington state, 2000-2015.

Environ Health 2021 Mar 15;20(1):26. Epub 2021 Mar 15.

Department of Environmental and Occupational Health Sciences, University of Washington School of Public Health, Seattle, WA, USA.

Background: Pesticides play an important role in protecting the food supply and the public's health from pests and diseases. By their nature, pesticides can be toxic to unintended target organisms. Changing winds contribute to pesticide drift- the off-target movement of pesticides-and can result in occupational and bystander illness.

Methods: We systematically linked historical weather data to documented pesticide drift illnesses. We used Washington State Department of Health data to identify 252 drift events that included 690 confirmed cases of illness from 2000 to 2015. To characterize wind speed and direction at the time of the events, we paired these data with meteorological data from a network of 171 state weather stations. We report descriptive statistics and the spatio-temporal extent of drift events and compare applicator-reported weather conditions to those from nearby meteorological stations.

Results: Most drift events occurred in tree fruit (151/252 = 60%). Ground spraying and aerial applications accounted for 68% and 23% of events, respectively; 69% of confirmed cases were workers, and 31% were bystanders. Confirmed cases were highest in 2014 (129) from 22 events. Complete applicator spray records were available for 57 drift events (23%). Average applicator-reported wind speeds were about 0.9 m •sec (2 mi •hr) lower than corresponding speeds from the nearest weather station values.

Conclusions: Drift events result from a complex array of factors in the agricultural setting. We used known spatio-temporal aspects of drift and historical weather data to characterize these events, but additional research is needed to put our findings into practice. Particularly critical for this analysis is more accurate and complete information about location, time, wind speed, and wind direction. Our findings can be incorporated into new training materials to improve the practice of pesticide application and for better documentation of spray drift events. A precision agriculture approach offers technological solutions that simplify the task of tracking pesticide spraying and weather conditions. Public health investigators will benefit from improved meteorological data and accurate application records. Growers, applicators, and surrounding communities will also benefit from the explanatory and predictive potential of wind ramping studies.
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http://dx.doi.org/10.1186/s12940-021-00693-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958705PMC
March 2021

Distinct Ultrafine Particle Profiles Associated with Aircraft and Roadway Traffic.

Environ Sci Technol 2021 03 5;55(5):2847-2858. Epub 2021 Feb 5.

Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, Washington 98195, United States.

The Mobile ObserVations of Ultrafine Particles study was a two-year project to analyze potential air quality impacts of ultrafine particles (UFPs) from aircraft traffic for communities near an international airport. The study assessed UFP concentrations within 10 miles of the airport in the directions of aircraft flight. Over the course of four seasons, this study conducted a mobile sampling scheme to collect time-resolved measures of UFP, CO, and black carbon (BC) concentrations, as well as UFP size distributions. Primary findings were that UFPs were associated with both roadway traffic and aircraft sources, with the highest UFP counts found on the major roadway (I-5). Total concentrations of UFPs alone (10-1000 nm) did not distinguish roadway and aircraft features. However, key differences existed in the particle size distribution and the black carbon concentration for roadway and aircraft features. These differences can help distinguish between the spatial impact of roadway traffic and aircraft UFP emissions using a combination of mobile monitoring and standard statistical methods.
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http://dx.doi.org/10.1021/acs.est.0c05933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931448PMC
March 2021

Engineering a Chemically Defined Hydrogel Bioink for Direct Bioprinting of Microvasculature.

Biomacromolecules 2021 02 17;22(2):275-288. Epub 2020 Dec 17.

Department of Bioengineering, Clemson University, Clemson, South Carolina 29634-0002, United States.

Vascularizing printed tissues is a critical challenge in bioprinting. While protein-based hydrogel bioinks have been successfully used to bioprint microvasculature, their compositions are ill-defined and subject to batch variation. Few studies have focused on engineering proangiogenic bioinks with defined properties to direct endogenous microvascular network formation after printing. Here, a peptide-functionalized alginate hydrogel bioink with defined mechanical, rheological, and biochemical properties is developed for direct bioprinting of microvascularized tissues. An integrin-binding peptide (RGD) and a vascular endothelial growth factor-mimetic peptide with a protease-sensitive linker are conjugated onto a biodegradable alginate to synergistically promote vascular morphogenesis and capillary-scale endothelial tube formation. Partial ionic crosslinking before printing converts the otherwise unprintable hydrogel into a viscoelastic bioink with excellent printability and cytocompatibility. We use the bioink to fabricate a compartmentalized vascularized tissue construct, wherein we observe pericyte-endothelial cell colocalization and angiogenic sprouting across a tissue interface, accompanied by deposition of fibronectin and collagen in vascular and tissue components, respectively. This study provides a tunable and translational "off-the-shelf" hydrogel bioink with defined composition for vascularized bioprinting.
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http://dx.doi.org/10.1021/acs.biomac.0c00947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870577PMC
February 2021

Computer Modeling of Drug Delivery with Thermosensitive Liposomes in a Realistic Three-Dimensional Geometry.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:5021-5024

Thermosensitive liposomes (TSL) are nanoparticles that can encapsulate therapeutic drugs, and release those drugs when exposed to hyperthermic temperatures (>40 °C). Combined with localized hyperthermia, TSL enable focused drug delivery. In this study, we created a three-dimensional (3D) computer model for simulating delivery with TSL-encapsulated doxorubicin (TSL-Dox) to mouse tumors. A mouse hind limb was scanned by a 3D scanner and the resulting geometry was imported into finite element modeling software, with a virtual tumor added. Then, heating by a surface probe was simulated. Further, a drug delivery model was coupled to the heat transfer model to simulate drug delivery kinetics. For comparison, experimental studies in gel phantoms and in vivo fluorescence imaging studies in mice carrying lung tumor xenografts were performed. We report the tissue temperature profile, drug concentration profile and compare the experimental studies with the computer model. The thermistor produced very localized heating that resulted in highest drug delivery to regions near the probe. The average tumor temperature was 38.2˚C (range 34.4-43.4˚C), and produced an average tumor drug concentration of 11.8 µg/g (0.3-28.1 µg/g) after 15 min heating, and 25.6 µg/g (0.3-52 µg/g), after 60 min heating. The computer model reproduced the temperature profile compared to phantom experiments (mean error 0.71 °C, range 0.59-1.25 °C), as well as drug delivery profile as compared to in vivo studies. Our results suggest feasibility of using this approach to model drug delivery in preclinical studies with accurate model geometry.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176829DOI Listing
July 2020

Evolutionarily conserved sequence motif analysis guides development of chemically defined hydrogels for therapeutic vascularization.

Sci Adv 2020 Jul 8;6(28):eaaz5894. Epub 2020 Jul 8.

Bioengineering Department, Clemson University, Clemson, SC, USA.

Biologically active ligands (e.g., RGDS from fibronectin) play critical roles in the development of chemically defined biomaterials. However, recent decades have shown only limited progress in discovering novel extracellular matrix-protein-derived ligands for translational applications. Through motif analysis of evolutionarily conserved RGD-containing regions in laminin (LM) and peptide-functionalized hydrogel microarray screening, we identified a peptide (a1) that showed superior supports for endothelial cell (EC) functions. Mechanistic studies attributed the results to the capacity of a1 engaging both LM- and Fn-binding integrins. RNA sequencing of ECs in a1-functionalized hydrogels showed ~60% similarities with Matrigel in "vasculature development" gene ontology terms. Vasculogenesis assays revealed the capacity of a1-formulated hydrogels to improve EC network formation. Injectable alginates functionalized with a1 and MMPQK (a vascular endothelial growth factor-mimetic peptide with a matrix metalloproteinase-degradable linker) increased blood perfusion and functional recovery over decellularized extracellular matrix and (RGDS + MMPQK)-functionalized hydrogels in an ischemic hindlimb model, illustrating the power of this approach.
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http://dx.doi.org/10.1126/sciadv.aaz5894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455498PMC
July 2020

Biomaterials for Bioprinting Microvasculature.

Chem Rev 2020 Oct 1;120(19):10887-10949. Epub 2020 Sep 1.

Bioengineering Department, Clemson University, Clemson, South Carolina 29634, United States.

Microvasculature functions at the tissue and cell level, regulating local mass exchange of oxygen and nutrient-rich blood. While there has been considerable success in the biofabrication of large- and small-vessel replacements, functional microvasculature has been particularly challenging to engineer due to its size and complexity. Recently, three-dimensional bioprinting has expanded the possibilities of fabricating sophisticated microvascular systems by enabling precise spatiotemporal placement of cells and biomaterials based on computer-aided design. However, there are still significant challenges facing the development of printable biomaterials that promote robust formation and controlled 3D organization of microvascular networks. This review provides a thorough examination and critical evaluation of contemporary biomaterials and their specific roles in bioprinting microvasculature. We first provide an overview of bioprinting methods and techniques that enable the fabrication of microvessels. We then offer an in-depth critical analysis on the use of hydrogel bioinks for printing microvascularized constructs within the framework of current bioprinting modalities. We end with a review of recent applications of bioprinted microvasculature for disease modeling, drug testing, and tissue engineering, and conclude with an outlook on the challenges facing the evolution of biomaterials design for bioprinting microvasculature with physiological complexity.
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http://dx.doi.org/10.1021/acs.chemrev.0c00027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810139PMC
October 2020

A Simple Method to Test Mechanical Strain on Epithelial Cell Monolayers Using a 3D-Printed Stretcher.

Methods Mol Biol 2020 Aug 14. Epub 2020 Aug 14.

Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.

With the realization that mechanical forces mediate many biological processes and contribute to disease progression, researchers are focusing on developing new methods to understand the role of mechanotransduction in biological systems. Despite recent advances in stretching devices that analyze the effects of mechanical strain in vitro, there are still possibilities to develop new equipment. For example, many of these devices tend be expensive, whereas few have been designed to assess the effects of mechanical strain driven by the extracellular matrix (ECM) to epithelial cell monolayers and to cell-cell adhesion. In this chapter, we introduce a cost-efficient, user-friendly, 3D-printed stretching device that can be used to test the effects of mechanical strain on cultured epithelial cells. Evaluation of the device using speckle-tracking shows homogeneous strain distribution along the horizontal plane of membranes at 2.5% and 5% strains, supporting the reliability of the device. Since cell-cell junctions are mechanosensitive protein complexes, we hereby used this device to examine effects on cell-cell adhesion. For this, we used colon epithelial Caco2 cell monolayers that well-differentiate in culture and form mature adherens junctions. Subjecting Caco2 cells to 2.5% and 5% strain using our device resulted in significant reduction in the localization of the core adherens junction component E-cadherin at areas of cell-cell contact and its increased translocation to the cytoplasm, which in agreement with other methodologies showing that increased ECM-driven strain negatively affects cell-cell adhesion. In summary, we here present a new, cost-effective, homemade device that can be reliably used to examine effects of mechanical strain on epithelial cell monolayers and cell-cell adhesion, in vitro.
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http://dx.doi.org/10.1007/7651_2020_314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882006PMC
August 2020

Hypomethylating Agent Azacitidine Is Effective in Treating Brain Metastasis Triple-Negative Breast Cancer Through Regulation of DNA Methylation of Keratin 18 Gene.

Transl Oncol 2020 Jun 11;13(6):100775. Epub 2020 May 11.

Department of Biomedical Sciences, West Virginia School of Osteopathic Medicine, 400 Lee Street North, Lewisburg, WV. Electronic address:

Breast cancer patients presenting with symptomatic brain metastases have poor prognosis, and current chemotherapeutic agents are largely ineffective. In this study, we evaluated the hypomethylating agent azacitidine (AZA) for its potential as a novel therapeutic in preclinical models of brain metastasis of breast cancer. We used the parental triple-negative breast cancer MDA-MB-231 (231) cells and their brain colonizing counterpart (231Br) to ascertain phenotypic differences in response to AZA. We observed that 231Br cells have higher metastatic potential compared to 231 cells. With regard to therapeutic value, the AZA IC value in 231Br cells is significantly lower than that in parental cells (P < .01). AZA treatment increased apoptosis and inhibited the Wnt signaling transduction pathway, angiogenesis, and cell metastatic capacity to a significantly higher extent in the 231Br line. AZA treatment in mice with experimental brain metastases significantly reduced tumor burden (P = .0112) and increased survival (P = .0026) compared to vehicle. Lastly, we observed a decreased expression of keratin 18 (an epithelial maker) in 231Br cells due to hypermethylation, elucidating a potential mechanism of action of AZA in treating brain metastases from breast cancer.
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http://dx.doi.org/10.1016/j.tranon.2020.100775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225776PMC
June 2020

Assessing the Impact of Housing Features and Environmental Factors on Home Indoor Radon Concentration Levels on the Navajo Nation.

Int J Environ Res Public Health 2020 04 19;17(8). Epub 2020 Apr 19.

Department of Environmental & Occupational Health Sciences, University of Washington, Box 354695, 4225 Roosevelt Way NE, Seattle, WA 98195, USA.

Uranium is naturally found in the environment as a radioactive metal element with high concentrations in the Southwestern US. In this region is the Navajo Nation, which spans approximately 69,930 square kilometers. A decay product of uranium is radon gas, a lung carcinogen that has no color, odor, or taste. Radon gas may pass from soil into homes; and, indoor accumulation has been associated with geographical location, seasonality, home construction materials, and home ventilation. A home and indoor radon survey was conducted from November 2014 through May 2015, with volunteers who reported residence on the Navajo Nation. Home geolocation, structural characteristics, temperature (°C) during radon testing, and elevation (meters) were recorded. Short-term indoor radon kits were used to measure indoor radon levels. 51 homes were measured for indoor radon levels, with an arithmetic mean concentration of 60.5 Becquerels per cubic meter (Bq/m) (SD = 42.7). The mean indoor radon concentrations (Bq/m) by house type were: mobile, 29.0 (SD = 22.9); wood, 58.6 (SD = 36.0); hogan, 74.0 (SD = 0.0); homes constructed of cement and wood, 82.6 (SD = 3.5); and homes constructed of concrete and cement, 105.7 (SD = 55.8). A key observation is that house construction type appears to be associated with the mean home indoor radon concentration. This observation has been published in that the basic structural make-up of the home may affect home ventilation and therefore indoor radon concentration levels.
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http://dx.doi.org/10.3390/ijerph17082813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215699PMC
April 2020

Using Vehicles' Rendezvous for In Situ Calibration of Instruments in Fleet Vehicle-Based Air Pollution Mobile Monitoring.

Environ Sci Technol 2020 04 17;54(7):4286-4294. Epub 2020 Mar 17.

Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, Washington 98195, United States.

This study examines the feasibility of the in situ calibration of instruments for fleet vehicle-based mobile monitoring of ultrafine particles (UFPs) and black carbon (BC) by comparing rendezvous vehicle measurements. Two vehicles with identical makes and models of UFP and BC monitors as well as GPS receivers were sampled within 140 m of each other for 2 h in total during winter in Seattle, Washington. To identify an optimal intervehicle distance for rendezvous calibration, 6 different buffers within 0-140 m for UFP monitors and 5 different buffers within 0-90 m for BC monitors were chosen, and the results of calibration were compared against a reference scenario, which consisted of mobile colocation measurements with both sets of the UFP and BC monitors deployed in one of the vehicles. Results indicate that the optimal distances for rendezvous calibration are 10-80 m for UFP monitors and 0-30 m for BC monitors. In comparison with the mobile colocation calibration, the rendezvous calibration shows a normalized root mean squared deviation of 6-14% and a normalized mean absolute deviation of 4-8% for these monitors. Criteria for applying a rendezvous calibration approach are presented, and an extension of this approach to an instrumented fleet of mobile monitoring vehicles is discussed.
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http://dx.doi.org/10.1021/acs.est.0c00612DOI Listing
April 2020

Spray Drift from Three Airblast Sprayer Technologies in a Modern Orchard Work Environment.

Ann Work Expo Health 2020 01;64(1):25-37

Department of Environmental and Occupational Health Sciences, University of Washington School of Public Health, WA, USA.

Pesticide spray drift represents an important exposure pathway that may cause illness among orchard workers. To strike a balance between improving spray coverage and reducing drift, new sprayer technologies are being marketed for use in modern tree canopies to replace conventional axial fan airblast (AFA) sprayers that have been used widely since the 1950s. We designed a series of spray trials that used mixed-effects modeling to compare tracer-based drift volume levels for old and new sprayer technologies in an orchard work environment. Building on a smaller study of 6 trials (168 tree rows) that collected polyester line drift samples (n = 270 measurements) suspended on 15 vertical masts downwind of an AFA sprayer application, this study included 9 additional comparison trials (252 tree rows; n = 405 measurements) for 2 airblast tower sprayers: the directed air tower (DAT) and the multi-headed fan tower (MFT). Field-based measurements at mid (26 m) and far (52 m) distances showed that the DAT and MFT sprayers had 4-15 and 35-37% less drift than the AFA. After controlling for downwind distance, sampling height, and wind speed, model results indicated that the MFT [-35%; 95% confidence interval (CI): -22 and -49%; P < 0.001] significantly reduced drift levels compared to the AFA, but the DAT did not (-7%; 95% CI: -19 and 6%; P = 0.29). Tower sprayers appear to be a promising means by which to decrease drift levels through shorter nozzle-to-tree canopy distances and more horizontally directed aerosols that escape the tree canopy to a lesser extent. Substitution of these new technologies for AFA sprayers is likely to reduce the frequency and magnitude of pesticide drift exposures and associated illnesses. These findings, especially for the MFT, may fit United States Environmental Protection Agency's Drift Reduction Technology (DRT) one-star rating of 25-50% reduction. An 'AFA buyback' incentive program could be developed to stimulate wider adoption of new drift-reducing spray technologies. However, improved sprayer technologies alone do not eliminate drift. Applicator training, including proper sprayer calibration and maintenance, and application exclusion zones (AEZs) can also contribute to minimizing the risks of drift exposure. With regard to testing DRTs and establishing AEZs, our study findings demonstrate the need to define the impact of airblast sprayer type, orchard architecture, sampling height, and wind speed.
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http://dx.doi.org/10.1093/annweh/wxz080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175243PMC
January 2020

The Washington State Environmental Health Disparities Map: Development of a Community-Responsive Cumulative Impacts Assessment Tool.

Int J Environ Res Public Health 2019 11 13;16(22). Epub 2019 Nov 13.

Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.

Communities across Washington State have expressed the need for neighborhood-level information on the cumulative impact of environmental hazards and social conditions to illuminate disparities and address environmental justice issues. Many existing mapping tools have not explicitly integrated community voice and lived experience as an integral part of their development. The goals of this project were to create a new community-academic-government partnership to collect and summarize community concerns and to develop a publicly available mapping tool that ranks relative environmental health disparities for populations across Washington State. Using a community-driven framework, we developed the Washington Environmental Health Disparities Map, a cumulative environmental health impacts assessment tool. Nineteen regularly updated environmental and population indicators were integrated into the geospatial tool that allows for comparisons of the cumulative impacts between census tracts. This interactive map provides critical information for the public, agencies, policymakers, and community-based organizations to make informed decisions. The unique community-academic-government partnership and the community-driven framework can be used as a template for other environmental and social justice mapping endeavors.
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http://dx.doi.org/10.3390/ijerph16224470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888266PMC
November 2019

Use of benchmark dose models in risk assessment for occupational handlers of eight pesticides used in pome fruit production.

Regul Toxicol Pharmacol 2020 Feb 23;110:104504. Epub 2019 Oct 23.

University of Washington, United States.

The benchmark dose has been frequently recommended for the creation of points of departure for regulatory dose limits, but many regulations, including pesticide risk assessment and registration in the United States, continues to rely on NOAEL methods as the OECD toxicological standard methods recommend. This study used data from studies in support of pesticide registration for eight different compounds to build dose-response models and calculate benchmark doses and confidence limits. The results were compared to the NOAEL of the same study. A probabilistic estimate of dose was compared with all points of departure to demonstrate differences in the protective ability of each different selected limit. While neither the BMD/BMDL nor the NOAEL was consistently more protective, the advantage of using the BMD in quantifying the uncertainty of the point of departure is highlighted, and the feasibility of using current OECD-guideline studies for derivation of a BMD is demonstrated in these cases.
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http://dx.doi.org/10.1016/j.yrtph.2019.104504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937384PMC
February 2020

Evaluation of Disposable Protective Garments against Isocyanate Permeation and Penetration from Polyurethane Anticorrosion Coatings.

Ann Work Expo Health 2019 05;63(5):592-603

Department of Public Health, University of Massachusetts Lowell, One University Avenue, Lowell, MA, USA.

Background: Polyurethanes are a class of isocyanate-based organic coatings commonly used to control corrosion on high-value metallic structures. Despite their widespread use, dermal exposure to these isocyanate-containing coatings presents a significant occupational health risk to workers, including the development of allergic and irritant contact dermatitis and systemic sensitization. At present, little is known about the effectiveness of the protective garments commonly used to prevent dermal exposure to polyurethane coatings in construction trades.

Objectives: The primary objective of this study was to measure the permeation and penetration of isocyanates from polyurethane anticorrosion coatings though a selection of protective garments. In addition, a standardized spray procedure using a fixed-position spraying technique was evaluated as an option to minimize variability in coating application.

Methods: Five disposable garment materials were evaluated for resistance to isocyanates during this study: latex gloves (0.076 mm), nitrile gloves (0.078 mm), Tyvek coveralls (0.105 mm), polypropylene/polyethylene (PP/PE) coveralls (0.116 mm), and a cotton t-shirt (0.382 mm). A permeation test cell system was used to evaluate each garment material against two products: a polyurethane zinc-rich primer based on 4,4'-methylene diphenyl diisocyanate and an aliphatic finish coating based on prepolymers of 1,6-hexamethylene diisocyanate. Glass fiber filters pretreated with 1-(9-anthracenylmethyl)piperazine were used to collect penetrating isocyanates during the 120-min test period, which were analyzed by liquid chromatography-tandem mass spectrometry. Polytetrafluoroethylene loading filters were sprayed in series with permeation test cells and analyzed gravimetrically to assess the homogeneity of coating application.

Results: The latex gloves demonstrated the highest rate of isocyanate permeation of all evaluated garments during testing with both coatings (primer: 27.38 ng cm-2 min-1; finish coating: 7.39 ng cm-2 min-1). Nitrile gloves were much more resistant than latex gloves (primer: 1.89 ng cm-2 min-1; finish coating: 1.26 ng cm-2 min-1) and were not permeated by the finish coating until after 15 min. The PP/PE coverall provided the most consistent resistance to both coatings (primer: 0.08 ng cm-2 min-1; finish coating: 1.27 ng cm-2 min-1), whereas the Tyvek coverall was readily permeated by the primer (primer: 3.47 ng cm-2 min-1; finish coating: 0.87 ng cm-2 min-1). The cotton t-shirt was rapidly permeated by the primer during the first 5 min of exposure (primer: 146.65 ng cm-2 min-1; finish coating: 4.64 ng cm-2 min-1). In addition, the fixed-position spraying technique used during this study demonstrated a significant reduction in loading variability within each batch of test cells when compared to manual spray application.

Conclusion: Nitrile gloves demonstrated superior resistance to both isocyanate-containing coatings in comparison to latex gloves. Although both coverall materials were resistant to permeating isocyanate within the established thresholds, the PP/PE coverall provided more consistent resistance to both coatings. Owing to the cotton t-shirt's high rate of penetration with both coatings, it is recommended only as a secondary barrier. Study results showed that the use of fixed-position spray techniques provided consistent and reproducible results within each batch of test cells. Additional test design modifications are necessary to further reduce variability between batches and ensure more consistent coating thickness.
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http://dx.doi.org/10.1093/annweh/wxz032DOI Listing
May 2019

Real-Time Monitoring of Spray Drift from Three Different Orchard Sprayers.

Chemosphere 2019 May 21;222:46-55. Epub 2019 Jan 21.

Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.

In Washington State, half of all pesticide-related illnesses in agriculture result from drift, the off-target movement of pesticides. Of these, a significant proportion involve workers on another farm and orchard airblast applications. We compared the spray drift exposure reduction potential of two modern tower sprayers - directed air tower (DAT) and multi-headed fan tower (MFT), in relation to a traditional axial fan airblast (AFA) sprayer. We employed real-time particle monitors (Dylos DC1100) during a randomized control trial of orchard spray applications. Sections of a field were randomly sprayed by three alternating spray technologies - AFA, DAT and MFT - while monitors sampled particulate matter above and below the canopy at various downwind locations in a neighboring field. Geometric mean particle mass concentrations (PMC) outside the intended spray area were elevated during all applications at all of our sampling distances (16-74 m, 51-244 ft). After adjusting for wind speed and sampling height, the 75th percentile (95% confidence interval) PMC level was significantly greater during spray events than background levels by 105 (93, 120) μg/m, 49 (45, 54) μg/m and 26 (22, 31) μg/m during AFA, DAT and MFT applications, respectively. Adjusted PMC levels were significantly different between all three sprayers. In this study, tower sprayers significantly reduced spray drift exposures in a neighboring orchard field when compared to the AFA sprayer, with the MFT sprayer producing the least drift; however these tower sprayers did do not fully eliminate drift.
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http://dx.doi.org/10.1016/j.chemosphere.2019.01.092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472945PMC
May 2019

Vascular Tissue Engineering Using Scaffold-Free Prevascular Endothelial-Fibroblast Constructs.

Biores Open Access 2019 8;8(1):1-15. Epub 2019 Jan 8.

Department of Surgery, Medical University of South Carolina, Charleston, South Carolina.

Vascularization remains a substantial limitation to the viability of engineered tissue. By comparing vascularization dynamics of a self-assembled prevascular endothelial-fibroblast model to avascular grafts, we explore the vascularization rate limitations in implants at early time intervals, during which tissue hypoxia begins to affect cell viability. Scaffold-free prevascular endothelial-fibroblast constructs (SPECs) may serve as a modular and reshapable vascular bed in replacement tissues. SPECs, fibroblast-only spheroids (FOS), and silicone implants were implanted in 54 Sprague Dawley rats and harvested at 6, 12, and 24 h ( = 5 per time point and implant type). We hypothesized that the primary endothelial networks of the SPECs allow earlier anastomosis and increased vessel formation in the interior of the implant compared to FOS and silicone implants within a 24 h window. All constructs were encapsulated by an endothelial lining at 6 h postimplantation and SPEC internal cords inosculated with the host vascular network by this time point. SPECs had a significantly higher microvascular area fraction and branch/junction density of penetrating cords at 6-12 h compared with other constructs. In addition, SPECs demonstrated perivascular cell recruitment, lumen formation, and network remodeling consistent with vessel maturation at 12-24 h; however, these implants were poorly perfused within our observation window, suggesting poor lumen patency. FOS vascular characteristics (microvessel area and penetrating cord density) increased within the 12-24 h period to represent those of the SPEC implants, suggesting a 12 h latency in host response to avascular grafts compared to prevascular grafts. Knowledge of this temporal advantage in prevascular network self-assembly as well as an understanding of the current limitations of SPEC engraftment builds on our theoretical temporal model of tissue graft vascularization and suggests a crucial time window, during which technological improvements and vascular therapy can improve engineered tissue survival.
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http://dx.doi.org/10.1089/biores.2018.0039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327854PMC
January 2019

Real-time particle monitoring of pesticide drift from an axial fan airblast orchard sprayer.

J Expo Sci Environ Epidemiol 2019 04 13;29(3):397-405. Epub 2018 Nov 13.

Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.

In Washington State, a majority of reported pesticide-related illnesses and application-related complaints involve drift. We employed real-time particle monitors (Dylos) during a series of experimental spray events investigating drift. Sections of an orchard block were randomly sprayed by an axial fan airblast sprayer, while monitors sampled particulate matter above and below the canopy at various downwind locations. We found elevated particle mass concentrations (PMC) at all distances (16-74 m). The 75th percentile PMC while spraying was significantly greater than the control periods by 107 (95% CI 94-121) μg/m, after adjusting for sampler height and wind speed. The 75th percentile PMC below the canopy was significantly greater than above the canopy by 9.4 (95% CI 5.2-12) μg/m, after adjusting for spraying and wind speed. In a restricted analysis of the spray events, the 75th percentile PMC significantly decreased by 2.6 (95% CI -3.2 to -1.7) μg/m for every additional meter away from the edge of the spray quadrant, after adjusting for canopy height and wind speed. Our results were consistent with a larger study that performed passive sampling during the same spray events, suggesting that real-time monitoring can be used as a screening tool for pesticide drift. Compared with traditional methods of drift sampling, real-time monitoring is overall an easily employed, affordable sampling technique, and it can provide minute-by-minute measurements that can be coupled with meteorological measurements to better understand how changes in wind speed and direction affect drift.
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http://dx.doi.org/10.1038/s41370-018-0090-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469994PMC
April 2019

Spray Drift from a Conventional Axial Fan Airblast Sprayer in a Modern Orchard Work Environment.

Ann Work Expo Health 2018 11;62(9):1134-1146

Department of Environmental and Occupational Health Sciences, University of Washington School of Public Health, Seattle, WA, USA.

Pesticide spray drift represents an important cause of crop damage and farmworker illness, especially among orchard workers. We drew upon exposure characteristics from known human illness cases to design a series of six spray trials that measured drift from a conventional axial fan airblast sprayer operating in a modern orchard work environment. Polyester line drift samples (n = 270; 45 per trial) were suspended on 15 vertical masts downwind of foliar applications of zinc, molybdenum, and copper micronutrient tracers. Samples were analyzed using inductively coupled plasma mass spectrometry and resulting masses were normalized by sprayer tank mix concentration to create tracer-based drift volume levels. Mixed-effects modeling described these levels in the context of spatial variability and buffers designed to protect workers from drift exposure. Field-based measurements showed evidence of drift up to 52 m downwind, which is approximately 1.7 times greater than the 30 m (100 ft) 'Application Exclusion Zone' defined for airblast sprayers by the United States Environmental Protection Agency Worker Protection Standard. When stratified by near (5 m), mid (26 m), and far (52 m) distances, geometric means and standard deviations for drift levels were 257 (1.8), 52 (2.0), and 20 (2.3) µl, respectively. Fixed effect model coefficients showed that higher wind speed [0.53; 95% confidence interval (CI): 0.35, 0.70] and sampling height (0.16; 95% CI: 0.11, 0.20) were positively associated with drift; increasing downwind distance (-0.05; 95% CI: -0.06, -0.04) was negatively associated with drift. Random effects showed large within-location variability, but relatively few systematic changes for individual locations across spray trials after accounting for wind speed, height, and distance. Our study findings demonstrate that buffers may offer drift exposure protection to orchard workers from airblast spraying. Variables such as orchard architecture, sampling height, and wind speed should be included in the evaluation and mitigation of risks from drift exposure. Data from our study may prove useful for estimating potential exposure and validating orchard-based bystander exposure models.
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http://dx.doi.org/10.1093/annweh/wxy082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104543PMC
November 2018

Testing of Disposable Protective Garments Against Isocyanate Permeation From Spray Polyurethane Foam Insulation.

Ann Work Expo Health 2018 07;62(6):754-764

Department of Public Health, University of Massachusetts Lowell, One University Avenue, Lowell, MA, USA.

Background: Diisocyanates (isocyanates), including methylene diphenyl diisocyanate (MDI), are the primary reactive components of spray polyurethane foam (SPF) insulation. They are potent immune sensitizers and a leading cause of occupational asthma. Skin exposure to isocyanates may lead to both irritant and allergic contact dermatitis and possibly contribute to systemic sensitization. More than sufficient evidence exists to justify the use of protective garments to minimize skin contact with aerosolized and raw isocyanate containing materials during SPF applications. Studies evaluating the permeation of protective garments following exposure to SPF insulation do not currently exist.

Objectives: To conduct permeation testing under controlled conditions to assess the effectiveness of common protective gloves and coveralls during SPF applications using realistic SPF product formulations.

Methods: Five common disposable garment materials [disposable latex gloves (0.07 mm thickness), nitrile gloves (0.07 mm), vinyl gloves (0.07 mm), polypropylene coveralls (0.13 mm) and Tyvek coveralls (0.13 mm)] were selected for testing. These materials were cut into small pieces and assembled into a permeation test cell system and coated with a two-part slow-rise spray polyurethane foam insulation. Glass fiber filters (GFF) pretreated with 1-(9-anthracenylmethyl)piperazine) (MAP) were used underneath the garment to collect permeating isocyanates. GFF filters were collected at predetermined test intervals between 0.75 and 20.00 min and subsequently analyzed using liquid chromatography-tandem mass spectrometry. For each garment material, we assessed (i) the cumulative concentration of total isocyanate, including phenyl isocyanate and three MDI isomers, that effectively permeated the material over the test time; (ii) estimated breakthrough detection time, average permeation rate, and standardized breakthrough time; from which (iii) recommendations were developed for the use of similar protective garments following contamination by two-component spray polyurethane foam systems and the limitations of such protective garments were identified.

Results: Each type of protective garment material demonstrated an average permeation rate well below the ASTM method F-739 standardized breakthrough rate threshold of 100.0 ng/cm2 min-1. Disposable latex gloves displayed the greatest total isocyanate permeation rate (4.11 ng/cm2 min-1), followed by the vinyl and nitrile gloves, respectively. The Tyvek coverall demonstrated a greater average rate of isocyanate permeation than the polypropylene coveralls. Typical isocyanate loading was in the range of 900 to 15,000 ng MDI/cm2.

Conclusion: Permeation test data collected during this study indicated that each type of protective garment evaluated, provided a considerable level of protection (i.e. 10-110-fold reduction from the level of direct exposure) against the isocyanate component of the SPF insulation mixture. Nitrile gloves and polypropylene coveralls demonstrated the lowest rate of permeation and the lowest cumulative permeation of total isocyanate for each garment type.
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http://dx.doi.org/10.1093/annweh/wxy030DOI Listing
July 2018

Therapeutic Engineered Hydrogel Coatings Attenuate the Foreign Body Response in Submuscular Implants.

Ann Plast Surg 2018 06;80(6S Suppl 6):S410-S417

Department of Surgery, School of Medicine, University of South Carolina, Columbia.

Background: Biomedical devices are implanted into mammalian soft tissues to improve, monitor, or restore form or function. The utility of these implants is limited by the subsequent foreign body response (FBR), beginning with inflammation and terminating in a collagen envelope around the device, known as the capsule. This capsule then can contract and distort the shape of the device or limit its effectiveness in interacting with the surrounding host tissues. In the current study, we investigated the effect of therapeutic collagen-coated silicone discs in a rat model of the FBR.

Methods: A 3-dimensional printed mold was used to fabricate collagen-coated silicone discs incorporating 3 therapeutic agents: colchicine, a function-blocking antibody against interleukin 8 (IL-8) receptor B, and a powerful anti-inflammatory steroid, dexamethasone. Discs were implanted submuscularly into a well-characterized rat model of the FBR and evaluated for inflammatory response, fibrotic development, and cytokine release.

Results: Coated silicone discs exhibited reduced collagen deposition and little to no foreign body giant cells at the host-silicone interface when compared with the silicone-only group. Therapeutic hydrogels demonstrate a significant decrease in cellular infiltration into the coatings over the 2-week time point in contrast to therapeutic-free hydrogel coatings. Cytokine analysis revealed significant differences between therapeutic-free and therapeutic-containing coatings when compared with silicone-only controls. Levels of IL-1β, IL-6, monocyte chemotactic protein 1, and macrophage inflammatory protein 3α were affected 48 hours after implantation, while differences in IL-18, growth-regulated oncogene/keratinocyte chemoattractant, and macrophage inflammatory protein 3α were observed 1 week after implantation.

Conclusions: By utilizing the host's innate immune response, our engineered hydrogel coatings delivered therapeutic moieties directly to the implant microenvironment, thus delaying the FBR up to 2 weeks.
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http://dx.doi.org/10.1097/SAP.0000000000001347DOI Listing
June 2018

Microdissection of Primary Renal Tissue Segments and Incorporation with Novel Scaffold-free Construct Technology.

J Vis Exp 2018 03 27(133). Epub 2018 Mar 27.

Department of Surgery, Medical University of South Carolina;

Kidney transplantation is now a mainstream therapy for end-stage renal disease. However, with approximately 96,000 people on the waiting list and only one-fourth of these patients achieving transplantation, there is a dire need for alternatives for those with failing organs. In order to decrease the harmful consequences of dialysis along with the overall healthcare costs it incurs, active investigation is ongoing in search of alternative solutions to organ transplantation. Implantable tissue-engineered renal cellular constructs are one such feasible approach to replacing lost renal functionality. Here, described for the first time, is the microdissection of murine kidneys for isolation of living corticomedullary renal segments. These segments are capable of rapid incorporation within scaffold-free endothelial-fibroblast constructs which may enable rapid connection with host vasculature once implanted. Adult mouse kidneys were procured from living donors, followed by stereoscope microdissection to obtain renal segments 200 - 300 µm in diameter. Multiple renal constructs were fabricated using primary renal segments harvested from only one kidney. This method demonstrates a procedure which could salvage functional renal tissue from organs that would otherwise be discarded.
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http://dx.doi.org/10.3791/57358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933269PMC
March 2018

Constitutive modeling of compressible type-I collagen hydrogels.

Med Eng Phys 2018 03 1;53:39-48. Epub 2018 Feb 1.

University of South Carolina, Biomedical Engineering Program, Columbia, SC, USA; University of South Carolina School of Medicine, Department of Cell Biology and Anatomy, Columbia, SC, USA. Electronic address:

Collagen hydrogels have been used ubiquitously as engineering biomaterials with a biphasic network of fibrillar collagen and aqueous-filled voids that contribute to a complex, compressible, and nonlinear mechanical behavior - not well captured within the infinitesimal strain theory. In this study, type-I collagen, processed from a bovine corium, was fabricated into disks at 2, 3, and 4% (w/w) and exposed to 0, 10, 10, and 10 microjoules of ultraviolet light or enzymatic degradation via matrix metalloproteinase-2. Fully hydrated gels were subjected to unconfined, aqueous, compression testing with experimental data modeled within a continuum mechanics framework by employing the uncommon Blatz-Ko material model for porous elastic materials and a nonlinear form of the Poisson's ratio. From the Generalized form, the Special Blatz-Ko, compressible Neo-Hookean, and incompressible Mooney-Rivlin models were derived and the best-fit material parameters reported for each. The average root-mean-squared (RMS) error for the General (RMS = 0.13 ± 0.07) and Special Blatz-Ko (RMS = 0.13 ± 0.07) were lower than the Neo-Hookean (RMS = 0.23 ± 0.10) and Mooney-Rivlin (RMS = 0.18 ± 0.08) models. We conclude that, with a single fitted-parameter, the Special Blatz-Ko sufficiently captured the salient features of collagen hydrogel compression over most examined formulations and treatments.
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http://dx.doi.org/10.1016/j.medengphy.2018.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050051PMC
March 2018

Mobile and Fixed-Site Measurements To Identify Spatial Distributions of Traffic-Related Pollution Sources in Los Angeles.

Environ Sci Technol 2018 03 14;52(5):2844-2853. Epub 2018 Feb 14.

Department of Environmental and Occupational Health Sciences , University of Washington , Box 357234, Seattle , Washington 98198 , United States.

Mobile monitoring and fixed-site monitoring using passive sampling devices (PSD) are popular air pollutant measurement techniques with complementary strengths and weaknesses. This study investigates the utility of combining data from concurrent 2-week mobile monitoring and fixed-site PSD campaigns in Los Angeles in the summer and early spring to identify sources of traffic-related air pollutants (TRAP) and their spatial distributions. There were strong to moderate correlations between mobile and fixed-site PSD measurements of both NO and NO in the summer and spring (Pearson's r between 0.43 and 0.79), suggesting that the two data sets can be reliably combined for source apportionment. PCA identified the major TRAP sources as light-duty vehicle emissions, diesel exhaust, crankcase vent emissions, and an independent source of combustion-derived ultrafine particle emissions. The component scores of those four sources at each site were significantly correlated across the two seasons (Pearson's r between 0.58 and 0.79). Spatial maps of absolute principal component scores showed all sources to be most prominent near major roadways and the central business district and the ultrafine particle source being, in addition, more prominent near the airport. Mobile monitoring combined with fixed-site PSD sampling can provide high spatial resolution estimates of TRAP and can reveal underlying sources of exposure variability.
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http://dx.doi.org/10.1021/acs.est.7b04889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843188PMC
March 2018

Comparative Probabilistic Assessment of Occupational Pesticide Exposures Based on Regulatory Assessments.

Risk Anal 2018 06 6;38(6):1223-1238. Epub 2017 Nov 6.

Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA.

Implementation of probabilistic analyses in exposure assessment can provide valuable insight into the risks of those at the extremes of population distributions, including more vulnerable or sensitive subgroups. Incorporation of these analyses into current regulatory methods for occupational pesticide exposure is enabled by the exposure data sets and associated data currently used in the risk assessment approach of the Environmental Protection Agency (EPA). Monte Carlo simulations were performed on exposure measurements from the Agricultural Handler Exposure Database and the Pesticide Handler Exposure Database along with data from the Exposure Factors Handbook and other sources to calculate exposure rates for three different neurotoxic compounds (azinphos methyl, acetamiprid, emamectin benzoate) across four pesticide-handling scenarios. Probabilistic estimates of doses were compared with the no observable effect levels used in the EPA occupational risk assessments. Some percentage of workers were predicted to exceed the level of concern for all three compounds: 54% for azinphos methyl, 5% for acetamiprid, and 20% for emamectin benzoate. This finding has implications for pesticide risk assessment and offers an alternative procedure that may be more protective of those at the extremes of exposure than the current approach.
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http://dx.doi.org/10.1111/risa.12936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5936674PMC
June 2018

Eliminating glutaraldehyde from crosslinked collagen films using supercritical CO.

J Biomed Mater Res A 2018 Jan 26;106(1):86-94. Epub 2017 Sep 26.

Department of Chemical Engineering, University of South Carolina, Columbia, South Carolina, 29208.

Collagen has received considerable attention as a biomaterial for tissue engineering because of its low immunogenicity, controllable biodegradation, and ability to influence cell growth and proliferation. Frequently, collagen scaffolds require crosslinking to improve mechanical strength, requiring agents like glutaraldehyde that have high residual cytotoxicity. A novel method for extracting residual glutaraldehyde from crosslinked collagen films with supercritical carbon dioxide (CO ) is presented. CO is a nontoxic, nonflammable substance that is relatively inert and can be used to process biomaterials at mild pressures and physiologic temperatures. In this work, it was first determined that type I collagen is chemically compatible with both liquid and supercritical CO . Treated collagen showed minimal changes in physicochemical properties as determined by differential scanning calorimetry, gel electrophoresis, and circular dichroism. CO was subsequently used to extract residual glutaraldehyde from crosslinked collagen films. Glutaraldehyde concentration was reduced by over 95%, from over 20 ppm before treatment to about 1 ppm, in only 1 h. CO treatment caused negligible alteration of thermal stability but did significantly increase film stiffness and tensile strength. However, these changes were minor compared to heat-based removal of glutaraldehyde. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 86-94, 2018.
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http://dx.doi.org/10.1002/jbm.a.36209DOI Listing
January 2018

A Geographical Analysis of Emergency Medical Service Calls and Extreme Heat in King County, WA, USA (2007-2012).

Int J Environ Res Public Health 2017 08 20;14(8). Epub 2017 Aug 20.

Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA.

This research analyzed the relationship between extreme heat and Emergency Medical Service (EMS) calls in King County, WA, USA between 2007 and 2012, including the effect of community-level characteristics. Extreme heat thresholds for the Basic Life Support (BLS) data and the Advanced Life Support (ALS) data were found using a piecewise generalized linear model with Akaike Information Criterion (AIC). The association between heat exposure and EMS call rates was investigated using a generalized estimating equations with Poisson mean model, while adjusting for community-level indicators of poverty, impervious surface, and elderly population (65+). In addition, we examined the effect modifications of these community-level factors. Extreme-heat thresholds of 31.1 °C and 33.5 °C humidex were determined for the BLS and ALS data, respectively. After adjusting for other variables in the model, increased BLS call volume was significantly associated with occurring on a heat day (relative rate (RR) = 1.080, < 0.001), as well as in locations with higher percent poverty (RR = 1.066, < 0.001). No significant effect modification was identified for the BLS data on a heat day. Controlling for other variables, higher ALS call volume was found to be significantly associated with a heat day (RR = 1.067, < 0.001), as well as in locations with higher percent impervious surface (RR = 1.015, = 0.039), higher percent of the population 65 years or older (RR = 1.057, = 0.005), and higher percent poverty (RR = 1.041, = 0.016). Furthermore, percent poverty and impervious surface were found to significantly modify the relative rate of ALS call volumes between a heat day and non-heat day. We conclude that EMS call volume increases significantly on a heat day compared to non-heat day for both call types. While this study shows that there is some effect modification between the community-level variables and call volume on a heat day, further research is necessary. Our findings also suggest that with adequate power, spatially refined analyses may not be necessary to accurately estimate the extreme-heat effect on health.
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http://dx.doi.org/10.3390/ijerph14080937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580639PMC
August 2017

Design and Fabrication of a Three-Dimensional In Vitro System for Modeling Vascular Stenosis.

Microsc Microanal 2017 08 17;23(4):859-871. Epub 2017 Jul 17.

4Department of Biomedical Sciences,School of Medicine,University of South Carolina,Greenville,SC 29605,USA.

Vascular stenosis, the abnormal narrowing of blood vessels, arises from defective developmental processes or atherosclerosis-related adult pathologies. Stenosis triggers a series of adaptive cellular responses that induces adverse remodeling, which can progress to partial or complete vessel occlusion with numerous fatal outcomes. Despite its severity, the cellular interactions and biophysical cues that regulate this pathological progression are poorly understood. Here, we report the design and fabrication of a three-dimensional (3D) in vitro system to model vascular stenosis so that specific cellular interactions and responses to hemodynamic stimuli can be investigated. Tubular cellularized constructs (cytotubes) were produced, using a collagen casting system, to generate a stenotic arterial model. Fabrication methods were developed to create cytotubes containing co-cultured vascular cells, where cell viability, distribution, morphology, and contraction were examined. Fibroblasts, bone marrow primary cells, smooth muscle cells (SMCs), and endothelial cells (ECs) remained viable during culture and developed location- and time-dependent morphologies. We found cytotube contraction to depend on cellular composition, where SMC-EC co-cultures adopted intermediate contractile phenotypes between SMC- and EC-only cytotubes. Our fabrication approach and the resulting artery model can serve as an in vitro 3D culture system to investigate vascular pathogenesis and promote the tissue engineering field.
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http://dx.doi.org/10.1017/S1431927617012302DOI Listing
August 2017

Mechanism of action of the anti-inflammatory connexin43 mimetic peptide JM2.

Am J Physiol Cell Physiol 2017 Sep 12;313(3):C314-C326. Epub 2017 Jul 12.

Department of Surgery, General Surgery Division, Medical University of South Carolina, Charleston, South Carolina.

Connexin-based therapeutics have shown the potential for therapeutic efficacy in improving wound healing. Our previous work demonstrated that the connexin43 (Cx43) mimetic peptide juxtamembrane 2 (JM2) reduced the acute inflammatory response to a submuscular implant model by inhibiting purinergic signaling. Given the prospective application in improving tissue-engineered construct tolerance that these results indicated, we sought to determine the mechanism of action for JM2 in the present study. Using confocal microscopy, a gap-FRAP cell communication assay, and an ethidium bromide uptake assay of hemichannel function we found that the peptide reduced cell surface Cx43 levels, Cx43 gap junction (GJ) size, GJ communication, and hemichannel activity. JM2 is based on the sequence of the Cx43 microtubule binding domain, and microtubules have a confirmed role in intracellular trafficking of Cx43 vesicles. Therefore, we tested the effect of JM2 on Cx43-microtubule interaction and microtubule polymerization. We found that JM2 enhanced Cx43-microtubule interaction and that microtubule polymerization was significantly enhanced. Taken together, these data suggest that JM2 inhibits trafficking of Cx43 to the cell surface by promoting irrelevant microtubule polymerization and thereby reduces the number of hemichannels in the plasma membrane available to participate in proinflammatory purinergic signaling. Importantly, this work indicates that JM2 may have therapeutic value in the treatment of proliferative diseases such as cancer. We conclude that the targeted action of JM2 on Cx43 channels may improve the tolerance of implanted tissue-engineered constructs against the innate inflammatory response.
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http://dx.doi.org/10.1152/ajpcell.00229.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625091PMC
September 2017

Ozone-Related Respiratory Morbidity in a Low-Pollution Region.

J Occup Environ Med 2017 07;59(7):624-630

Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado (Drs Magzamen, Moore); Department of Environmental and Occupational Health Sciences (Drs Magzamen, Yost, Fenske, Karr); Department of Epidemiology (Dr Karr), University of Washington School of Public Health; Department of Pediatrics, University of Washington School of Medicine (Dr Karr), Seattle, Washington.

Objective: We evaluated the effects of ozone on respiratory-related hospital admissions in three counties in Washington State from 1990 to 2006. We further examined vulnerability to ozone by key demographic factors.

Method: Using linked hospital admission and ambient monitoring data, we estimated the age-, sex-, and health insurance-stratified associations between ozone (0 to 3 days' lag) and respiratory-related hospital admissions in King, Spokane, and Clark County, Washington.

Results: The adjusted relative risk (RR) for a 10 ppb increase in ozone at 3 days' lag was 1.04 (95% confidence interval [CI]: 1.02, 1.07) for Clark County, 1.03 (95% CI: 1.01, 1.05) for Spokane County, and 1.02 (95% CI: 1.01, 1.03) for King County. There was consistent evidence of effect modification by age.

Conclusion: Ozone at levels below federal standards contributes to respiratory morbidity among high-risk groups in Washington.
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http://dx.doi.org/10.1097/JOM.0000000000001042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503782PMC
July 2017

Ambient Air Quality Measurements from a Continuously Moving Mobile Platform: Estimation of Area-Wide, Fuel-Based, Mobile Source Emission Factors Using Absolute Principal Component Scores.

Atmos Environ (1994) 2017 Mar 21;152:201-211. Epub 2016 Dec 21.

University of Washington, Department of Environmental and Occupational Health Sciences, Box 357234, Seattle, WA 98195-7234, USA.

We have applied the absolute principal component scores (APCS) receptor model to on-road, background-adjusted measurements of NOx, CO, CO, black carbon (BC), and particle number (PN) obtained from a continuously moving platform deployed over nine afternoon sampling periods in Seattle, WA. Two Varimax-rotated principal component features described 75% of the overall variance of the observations. A heavy-duty vehicle feature was correlated with black carbon and particle number, whereas a light-duty feature was correlated with CO and CO. NO had moderate correlation with both features. The bootstrapped APCS model predictions were used to estimate area-wide, average fuel-based emission factors and their respective 95% confidence limits. The average emission factors for NOx, CO, BC and PN (14.8, 18.9, 0.40 g/kg, and 4.3×10 particles/kg for heavy duty vehicles, and 3.2, 22.4, 0.016 g/kg, and 0.19×10 particles/kg for light-duty vehicles, respectively) are consistent with previous estimates based on remote sensing, vehicle chase studies, and recent dynamometer tests. Information on the spatial distribution of the concentrations contributed by these two vehicle categories relative to background during the sampling period was also obtained.
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http://dx.doi.org/10.1016/j.atmosenv.2016.12.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059631PMC
March 2017