Evaluation of disposable protective garments against epoxy resin permeation and penetration from anti-corrosion coatings.

INTRODUCTION: Epoxy-based resin formulations are a frequent cause of allergic and irritant contact dermatitis in the construction and painting industries. Cases of epoxy resin contact dermatitis continue to persist across many sectors and are likely attributable to the growing use of epoxy products, including epoxy-based anti-corrosion coatings and inadequate skin protection. There are no published performance data against epoxy resins for garment materials and gloves to guide proper material selection in the workplace. OBJECTIVES: The objective of this study was to evaluate the resistance of 5 protective garment materials against permeation and penetration by bisphenol A diglycidyl ether and its higher oligomers found commonly in epoxy-based anti-corrosion coatings. METHODS: Five disposable garment materials were evaluated for resistance to bisphenol A diglycidyl ether monomers and oligomers during contact with epoxy-based anti-corrosion coatings, including latex gloves, nitrile gloves, Tyvek coveralls, polypropylene/polyethylene (PP/PE) coveralls, and a cotton T-shirt. A permeation test cell system was used to evaluate each garment material against an epoxy-based zinc-rich primer and an epoxy-based intermediate coating using a realistic application method. Glass fiber filters were used to collect permeating and penetrating epoxy resin during a 120-min test period. Bisphenol A diglycidyl ether quantification was performed with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Paint loading, coating thickness, and homogeneity were assessed on polytetrafluoroethylene filters sprayed in series in permeation test cells. RESULTS: Latex gloves provided the least resistance to permeation by BADGE in coating formulations, with a maximum cumulative permeation over the 2-h test interval of 21.7 ng cm-2 with the primer and 513.8 ng cm-2 with the intermediate coating product. Nitrile gloves were not permeated by either coating formulation. The Tyvek coveralls provided greater protection as compared to the PP/PE coveralls. The cotton T-shirt was penetrated by bisphenol A diglycidyl ether more frequently than any of the tested garment materials and resulted in a maximum cumulative penetration of 128 ng cm-2 with the primer and 28.0 ng cm-2 with the intermediate coating. CONCLUSION: Although all the garment materials evaluated during this study provided sufficient protection to prevent cumulative permeation in excess of the established acceptable permeation thresholds, the use of nitrile gloves and Tyvek coverall is highly recommended to minimize skin exposure to bisphenol A diglycidyl ether. We recommend cotton T-shirts to be used under Tyvek coveralls as a secondary layer of skin protection and for added comfort, but not as a primary protection layer.

Non-ionizing radiation modeling to predict ambient irradiance in work areas at an indoor cannabis farm.

Agricultural workers frequently experience potentially hazardous exposure to non-ionizing radiation from both solar and artificial sources, and measurement of this exposure can be expensive and impractical for large populations. This project develops and evaluates a vegetative radiative transfer model (VRTM) to predict irradiance in a grow room of an indoor cannabis farm. The model uses morphological characteristics of the crop, manufacturer provided lamp emissions data, and dimensional measurements of the grow room and cannabis hedgerows to predict irradiance. A linear regression comparing model predictions with the measurements taken by a visible light spectroradiometer had slopes within 23% of unity and R2 values above 0.88 for visible (400-700 nm), blue (400-500 nm), green (500-600 nm), and red (600-700 nm) wavelength bands. The excellent agreement between the model and the measured irradiance in the cannabis farm grow room supports the potential of using VRTMs to predict irradiance and worker exposure in agricultural settings. Because there is no mechanistic difference between visible and other non-ionizing wavelengths of radiation in regards to mechanisms of radiative transfer, the model developed herein for visible wavelengths of radiation should be generalizable to other radiation bands including infrared and ultraviolet radiation.

Untargeted Large Volume Hyperthermia Reduces Tumor Drug Uptake From Thermosensitive Liposomes.

GOAL: The impact of hyperthermia (HT) method on tumor drug uptake with thermosensitive liposomes (TSL) is not well understood. METHODS: We created realistic three-dimensional (3-D) computer models that simulate TSL-encapsulated doxorubicin (TSL-DOX) delivery in mouse tumors with three HT methods (thermistor probe (T), laser (L) and water bath (WB), at 15 min and 60 min HT duration), with corroborating in vivo studies. RESULTS: Average computer model-predicted tumor drug concentrations (µg/g) were 8.8(T, 15 min), 21.0(T, 60 min), 14.1(L, 15 min), 25.2(L, 60 min), 9.4(WB, 15 min), and 8.7(WB, 60 min). Tumor fluorescence was increased by 2.6 × (T) and 1.6 × (L) when HT duration was extended from 15 to 60 min (p < 0.05), with no increase for WB HT. Pharmacokinetic analysis confirmed that water bath HT causes rapid depletion of encapsulated TSL-DOX in systemic circulation due to the large heated tissue volume. CONCLUSIONS: Untargeted large volume HT causes poor tumor drug uptake from TSL.

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

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.

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

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.

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

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.

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

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.

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

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 IC50 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.

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

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/m3) (SD = 42.7). The mean indoor radon concentrations (Bq/m3) 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.

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

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.

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

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.

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

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.

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

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-1ß, 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.

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

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.

Passive Sampling for Indoor and Outdoor Exposures to Chlorpyrifos, Azinphos-Methyl, and Oxygen Analogs in a Rural Agricultural Community.

BACKGROUND: Recent studies have highlighted the increased potency of oxygen analogs of organophosphorus pesticides. These pesticides and oxygen analogs have previously been identified in the atmosphere following spray applications in the states of California and Washington. OBJECTIVES: We used two passive sampling methods to measure levels of the ollowing organophosphorus pesticides: chlorpyrifos, azinphos-methyl, and their oxygen analogs at 14 farmworker and 9 non-farmworker households in an agricultural region of central Washington State in 2011. METHODS: The passive methods included polyurethane foam passive air samplers deployed outdoors and indoors and polypropylene deposition plates deployed indoors. We collected cumulative monthly samples during the pesticide application seasons and during the winter season as a control. RESULTS: Monthly outdoor air concentrations ranged from 9.2 to 199 ng/m3 for chlorpyrifos, 0.03 to 20 ng/m3 for chlorpyrifos-oxon, < LOD (limit of detection) to 7.3 ng/m3 for azinphos-methyl, and < LOD to 0.8 ng/m3 for azinphos-methyl-oxon. Samples from proximal households (≤ 250 m) had significantly higher outdoor air concentrations of chlorpyrifos, chlorpyrifos-oxon, and azinphos-methyl than did samples from nonproximal households (p ≤ 0.02). Overall, indoor air concentrations were lower than outdoors. For example, all outdoor air samples for chlorpyrifos and 97% of samples for azinphos-methyl were > LOD. Indoors, only 78% of air samples for chlorpyrifos and 35% of samples for azinphos-methyl were > LOD. Samples from farmworker households had higher indoor air concentrations of both pesticides than did samples from non-farmworker households. Mean indoor and outdoor air concentration ratios for chlorpyrifos and azinphos-methyl were 0.17 and 0.44, respectively. CONCLUSIONS: We identified higher levels in air and on surfaces at both proximal and farmworker households. Our findings further confirm the presence of pesticides and their oxygen analogs in air and highlight their potential for infiltration of indoor living environments. Citation: Gibbs JL, Yost MG, Negrete M, Fenske RA. 2017. Passive sampling for indoor and outdoor exposures to chlorpyrifos, azinphos-methyl, and oxygen analogs in a rural agricultural community. Environ Health Perspect 125:333-341; http://dx.doi.org/10.1289/EHP425.

Inhibition of connexin 43 hemichannel-mediated ATP release attenuates early inflammation during the foreign body response.

BACKGROUND: In the last 50 years, the use of medical implants has increased dramatically. Failure of implanted devices and biomaterials is a significant source of morbidity and increasing healthcare expenditures. An important cause of implant failure is the host inflammatory response. Recent evidence implicates extracellular ATP as an important inflammatory signaling molecule. A major pathway for release of cytoplasmic ATP into the extracellular space is through connexin hemichannels, which are the unpaired constituents of gap junction intercellular channels. Blockade of hemichannels of the connexin 43 (Cx43) isoform has been shown to reduce inflammation and improve healing. We have developed a Cx43 mimetic peptide (JM2) that targets the microtubule-binding domain of Cx43. The following report investigates the role of the Cx43 microtubule-binding domain in extracellular ATP release by Cx43 hemichannels and how this impacts early inflammatory events of the foreign body reaction. METHODS: In vitro Cx43 hemichannel-mediated ATP release by cultured human microvascular endothelial cells subjected to hypocalcemic and normocalcemic conditions was measured after application of JM2 and the known hemichannel blocker, flufenamic acid. A submuscular silicone implant model was used to investigate in vivo ATP signaling during the early foreign body response. Implants were coated with control pluronic vehicle or pluronic carrying JM2, ATP, JM2+ATP, or known hemichannel blockers and harvested at 24 h for analysis. RESULTS: JM2 significantly inhibited connexin hemichannel-mediated ATP release from cultured endothelial cells. Importantly, the early inflammatory response to submuscular silicone implants was inhibited by JM2. The reduction in inflammation by JM2 was reversed by the addition of exogenous ATP to the pluronic vehicle. CONCLUSIONS: These data indicate that ATP released through Cx43 hemichannels into the vasculature is an important signal driving the early inflammatory response to implanted devices. A vital aspect of this work is that it demonstrates that targeted molecular therapeutics, such as JM2, provide the capacity to regulate inflammation in a clinically relevant system.

Implanted scaffold-free prevascularized constructs promote tissue repair.

To evaluate the anastomotic potential of prevascular tissue constructs generated from scaffold-free self-assembly of human endothelial and fibroblast cells, tissue constructs were implanted into athymic mice and immune-competent rats. Analysis of xenografts placed into hind limb muscle defects showed vascular anastomotic activity by 3 days after implantation and persisting for 2 weeks. Integration of the implanted prevascular tissue constructs with the host circulatory system was evident from presence of red blood cells in the implant as early as 3 days after implantation. Additionally, analysis of 3-day xenografts in the rat model showed activation of skeletal muscle satellite cells based on Pax-7 and MyoD expressions. We conclude that prevascular tissue constructs generated from scaffold-free self-assembly of human endothelial and fibroblast cells are a promising tool to provide both vascular supply and satellite cell activation toward the resolution of skeletal muscle injury.

Predicting academic performance in surgical training.

INTRODUCTION: During surgical residency, trainees are expected to master all the 6 competencies specified by the ACGME. Surgical training programs are also evaluated, in part, by the residency review committee based on the percentage of graduates of the program who successfully complete the qualifying examination and the certification examination of the American Board of Surgery in the first attempt. Many program directors (PDs) use the American Board of Surgery In-Training Examination (ABSITE) as an indicator of future performance on the qualifying examination. Failure to meet an individual program's standard may result in remediation or a delay in promotion to the next level of training. Remediation is expensive in terms of not only dollars but also resources, faculty time, and potential program disruptions. We embarked on an exploratory study to determine if residents who might be at risk for substandard performance on the ABSITE could be identified based on the individual resident's behavior and motivational characteristics. If such were possible, then PDs would have the opportunity to be proactive in developing a curriculum tailored to an individual resident, providing a greater opportunity for success in meeting the program's standards. METHODS: Overall, 7 surgical training programs agreed to participate in this initial study and residents were recruited to voluntarily participate. Each participant completed an online assessment that characterizes an individual's behavioral style, motivators, and Acumen Index. Residents completed the assessment using a code name assigned by each individual PD or their designee. Assessments and the residents' 2013 ABSITE scores were forwarded for analysis using only the code name, thus insuring anonymity. Residents were grouped into those who took the junior examination, senior examination, and pass/fail categories. A passing score of ≥70% correct was chosen a priori. Correlations were performed using logistic regression and data were also entered into a neural network (NN) to develop a model that would explain performance based on data obtained from the TriMetrix assessments. RESULTS: A total of 117 residents' TriMetrix and ABSITE scores were available for analysis. They were divided into 2 groups of 64 senior residents and 53 junior residents. For each group, the pass/fail criteria for the ABSITE were set at 70 and greater as passing and 69 and lower as failing. Multiple logistic regression analysis was complete for pass/fail vs the TriMetrix assessments. For the senior data group, it was found that the parameter Theoretical correlates with pass rate (p < 0.043, B = -0.513, exp(B) = 0.599), which means increasing theoretical scores yields a decreasing likelihood of passing in the examination. For the junior data, the parameter Internal Role Awareness correlated with pass/fail rate (p < 0.004, B = 0.66, exp(B) = 1.935), which means that an increasing Internal Role Awareness score increases the likelihood of a passing score. The NN was able to be trained to predict ABSITE performance with surprising accuracy for both junior and senior residents. CONCLUSION: Behavioral, motivational, and acumen characteristics can be useful to identify residents "at risk" for substandard performance on the ABSITE. Armed with this information, PDs have the opportunity to intervene proactively to offer these residents a greater chance for success. The NN was capable of developing a model that explained performance on the examination for both the junior and the senior examinations. Subsequent testing is needed to determine if the NN is a good predictive tool for performance on this examination.

Shift work and breast cancer among women textile workers in Shanghai, China.

PURPOSE: Although night-shift work has been associated with elevated risk of breast cancer in numerous epidemiologic studies, evidence is not consistent. We conducted a nested case-cohort study to investigate a possible association between shift work including a night shift and risk of breast cancer within a large cohort of women textile workers in Shanghai, China. METHODS: The study included 1,709 incident breast cancer cases and 4,780 non-cases. Data on historical shift work schedules were collected by categorized jobs from the factories, where the study subjects had worked, and then were linked to the complete work histories of each subject. No jobs in the factories involved exclusively night-shift work. Therefore, night shift was evaluated as part of a rotating shift work pattern. Hazard ratios and 95 % confidence intervals were calculated using Cox proportional hazards modeling adapted for the case-cohort design for years of night-shift work and the total number of nights worked. Additionally, analyses were repeated with exposures lagged by 10 and 20 years. RESULTS: We observed no associations with either years of night-shift work or number of nights worked during the entire employment period, irrespective of lag intervals. Findings from the age-stratified analyses were very similar to those observed for the entire study population. CONCLUSIONS: The findings from this study provide no evidence to support the hypothesis that shift work increases breast cancer risk. The positive association between shift work and breast cancer observed in Western populations, but not observed in this and other studies of the Chinese population, suggests that the effect of shift work on breast cancer risk may be different in Asian and Caucasian women.

Development of a passive air sampler to measure airborne organophosphorus pesticides and oxygen analogs in an agricultural community.

Organophosphorus pesticides are some of the most widely used insecticides in the US, and spray drift may result in human exposures. We investigate sampling methodologies using the polyurethane foam passive air sampling device to measure cumulative monthly airborne concentrations of OP pesticides chlorpyrifos, azinphos-methyl, and oxygen analogs. Passive sampling rates (m(3)d(-1)) were determined using calculations using chemical properties, loss of depuration compounds, and calibration with side-by-side active air sampling in a dynamic laboratory exposure chamber and in the field. The effects of temperature, relative humidity, and wind velocity on outdoor sampling rates were examined at 23 sites in Yakima Valley, Washington. Indoor sampling rates were significantly lower than outdoors. Outdoor rates significantly increased with average wind velocity, with high rates (>4m(3)d(-1)) observed above 8ms(-1). In exposure chamber studies, very little oxygen analog was observed on the PUF-PAS, yet substantial amounts chlorpyrifos-oxon and azinphos methyl oxon were measured in outdoor samples. PUF-PAS is a practical and useful alternative to AAS because it results in little artificial transformation to the oxygen analog during sampling, it provides cumulative exposure estimates, and the measured sampling rates were comparable to rates for other SVOCs. It is ideal for community based participatory research due to low subject burden and simple deployment in remote areas.