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142 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Histopathological characteristics of PRRS and expression profiles of viral receptors in the piglet immune system

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious viral disease that causes significant economic losses to the swine industry worldwide. PRRS virus (PRRSV) infection is a receptor-mediated endocytosis and replication process. The purpose of this study was to determine the localization and expression of four important PRRSV receptors in immunological organs of piglets. After piglets were infected with PRRSV, Hematoxylin and Eosin staining, immunofluorescence, and Western blot were used to perform histopathological examination and receptors distribution analysis. The results showed that PRRSV caused severe damage to the piglets’ immune organs, including atrophy of the thymus and swelling of lymph node. Histopathological lesions were mainly observed in the lung and lymph node and were characterized by interstitial pneumonia, collapsed follicles, exhaustion of germinal centers, and extensive hemorrhage. Immunofluorescence staining and Western blot results showed that the receptors of CD163 and NMHCII-A were mainly distributed in the thymus, hilar lymph nodes, and mesenteric lymph nodes. However, Sn and vimentin receptors were expressed at low levels in the immune organs of piglets. The distribution of the four receptors in the immune organs was more concentrated in the cortex but was more scattered in the medulla. Compared to the control group, the relative expression of the four receptors increased significantly in most immune organs after viral infection. In conclusion, our study examined the distribution and expression of four PRRSV receptors in immunological organs. We observed a significant increase in the expression of Sn, CD163, and vimentin following viral infection. These findings may provide potential targets for future antiviral reagent design or vaccine development.

Chen, Hong↗
DOE OSTI2024

Toward Smart, Automated Junctional Tourniquets—AI Models to Interpret Vessel Occlusion at Physiological Pressure Points

Hemorrhage is the leading cause of preventable death in both civilian and military medicine. Junctional hemorrhages are especially difficult to manage since traditional tourniquet placement is often not possible. Ultrasound can be used to visualize and guide the caretaker to apply pressure at physiological pressure points to stop hemorrhage. However, this process is technically challenging, requiring the vessel to be properly positioned over rigid boney surfaces and applying sufficient pressure to maintain proper occlusion. As a first step toward automating this life-saving intervention, we demonstrate an artificial intelligence algorithm that classifies a vessel as patent or occluded, which can guide a user to apply the appropriate pressure required to stop flow. Neural network models were trained using images captured from a custom tissue-mimicking phantom and an ex vivo swine model of the inguinal region, as pressure was applied using an ultrasound probe with and without color Doppler overlays. Using these images, we developed an image classification algorithm suitable for the determination of patency or occlusion in an ultrasound image containing color Doppler overlay. Separate AI models for both test platforms were able to accurately detect occlusion status in test-image sets to more than 93% accuracy. In conclusion, this methodology can be utilized for guiding and monitoring proper vessel occlusion, which, when combined with automated actuation and other AI models, can allow for automated junctional tourniquet application.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Evaluation of Deep Learning Model Architectures for Point-of-Care Ultrasound Diagnostics

Point-of-care ultrasound imaging is a critical tool for patient triage during trauma for diagnosing injuries and prioritizing limited medical evacuation resources. Specifically, an eFAST exam evaluates if there are free fluids in the chest or abdomen but this is only possible if ultrasound scans can be accurately interpreted, a challenge in the pre-hospital setting. In this effort, we evaluated the use of artificial intelligent eFAST image interpretation models. Widely used deep learning model architectures were evaluated as well as Bayesian models optimized for six different diagnostic models: pneumothorax (i) B- or (ii) M-mode, hemothorax (iii) B- or (iv) M-mode, (v) pelvic or bladder abdominal hemorrhage and (vi) right upper quadrant abdominal hemorrhage. Models were trained using images captured in 27 swine. Using a leave-one-subject-out training approach, the MobileNetV2 and DarkNet53 models surpassed 85% accuracy for each M-mode scan site. The different B-mode models performed worse with accuracies between 68% and 74% except for the pelvic hemorrhage model, which only reached 62% accuracy for all model architectures. These results highlight which eFAST scan sites can be easily automated with image interpretation models, while other scan sites, such as the bladder hemorrhage model, will require more robust model development or data augmentation to improve performance. With these additional improvements, the skill threshold for ultrasound-based triage can be reduced, thus expanding its utility in the pre-hospital setting.

47 OTHER INSTRUMENTATION↗
DOE OSTI2020

Economic Perspectives of Biogas Production via Anaerobic Digestion

As the demand for utilizing environment-friendly and sustainable energy sources is increasing, the adoption of waste-to-energy technologies has started gaining attention. Producing biogas via anaerobic digestion (AD) is promising and well-established; however, this process in many circumstances is unable to be cost competitive with natural gas. In this research, we provide a technical assessment of current process challenges and compare the cost of biogas production via the AD process from the literature, Aspen Plus process modeling, and CapdetWorks software. We also provide insights on critical factors affecting the AD process and recommendations on optimizing the process. We utilize four types of wet wastes, including wastewater sludge, food waste, swine manure, and fat, oil, and grease, to provide a quantitative assessment of theoretical energy yields of biogas production and its economic potential at different plant scales. Our results show that the cost of biogas production from process and economic models are in line with the literature with a potential to go even lower for small-scale plants with technological advancements. This research illuminates potential cost savings for biogas production using different wastes and guide investors to make informed decisions, while achieving waste management goals.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Development of a Modular Tissue Phantom for Evaluating Vascular Access Devices

Central vascular access (CVA) may be critical for trauma care and stabilizing the casualty. However, it requires skilled personnel, often unavailable during remote medical situations and combat casualty care scenarios. Automated CVA medical devices have the potential to make life-saving therapeutics available in these resource-limited scenarios, but they must be properly designed. Unfortunately, currently available tissue phantoms are inadequate for this use, resulting in delayed product development. Here, we present a tissue phantom that is modular in design, allowing for adjustable flow rate, circulating fluid pressure, vessel diameter, and vessel positions. The phantom consists of a gelatin cast using a 3D-printed mold with inserts representing vessels and bone locations. These removable inserts allow for tubing insertion which can mimic normal and hypovolemic flow, as well as pressure and vessel diameters. Trauma to the vessel wall is assessed using quantification of leak rates from the tubing after removal from the model. Lastly, the phantom can be adjusted to swine or human anatomy, including modeling the entire neurovascular bundle. Overall, this model can better recreate severe hypovolemic trauma cases and subject variability than commercial CVA trainers and may potentially accelerate automated CVA device development.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Torque Teno Sus Virus 1: A Potential Surrogate Pathogen to Study Pig-Transmitted Transboundary Animal Diseases

Understanding the epidemiology and transmission dynamics of transboundary animal diseases (TADs) among wild pigs (Sus scrofa) will aid in preventing the introduction or containment of TADs among wild populations. Given the challenges associated with studying TADs in free-ranging populations, a surrogate pathogen system may predict how pathogens may circulate and be maintained within wild free-ranging swine populations, how they may spill over into domestic populations, and how management actions may impact transmission. We assessed the suitability of Torque teno sus virus 1 (TTSuV1) to serve as a surrogate pathogen for molecular epidemiological studies in wild pigs by investigating the prevalence, persistence, correlation with host health status and genetic variability at two study areas: Archbold’s Buck Island Ranch in Florida and Savannah River Site in South Carolina. We then conducted a molecular epidemiological case study within Archbold’s Buck Island Ranch site to determine how analysis of this pathogen could inform transmission dynamics of a directly transmitted virus. Prevalence was high in both study areas (40%, n = 190), and phylogenetic analyses revealed high levels of genetic variability within and between study areas. Our case study showed that pairwise host relatedness and geographic distance were highly correlated to pairwise viral genetic similarity. Molecular epidemiological analyses revealed a distinct pattern of direct transmission from pig to pig occurring within and between family groups. Our results suggest that TTSuV1 is highly suitable for molecular epidemiological analyses and will be useful for future studies of transmission dynamics in wild free-ranging pigs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Structure and Antigenicity of the Porcine Astrovirus 4 Capsid Spike

Porcine astrovirus 4 (PoAstV4) has been recently associated with respiratory disease in pigs. In order to understand the scope of PoAstV4 infections and to support the development of a vaccine to combat PoAstV4 disease in pigs, we designed and produced a recombinant PoAstV4 capsid spike protein for use as an antigen in serological assays and for potential future use as a vaccine antigen. Structural prediction of the full-length PoAstV4 capsid protein guided the design of the recombinant PoAstV4 capsid spike domain expression plasmid. The recombinant PoAstV4 capsid spike was expressed in Escherichia coli, purified by affinity and size-exclusion chromatography, and its crystal structure was determined at 1.85 Å resolution, enabling structural comparisons to other animal and human astrovirus capsid spike structures. The recombinant PoAstV4 capsid spike protein was also used as an antigen for the successful development of a serological assay to detect PoAstV4 antibodies, demonstrating that the recombinant PoAstV4 capsid spike retains antigenic epitopes found on the native PoAstV4 capsid. These studies lay a foundation for seroprevalence studies and the development of a PoAstV4 vaccine for swine.

Virology↗
DOE OSTI2025

Vaccine Efficacy of a Replication-Competent Interferon-Expressing Porcine Reproductive and Respiratory Syndrome (PRRS) Virus Against NADC-34 Challenge

Background/Objectives: Porcine reproductive and respiratory syndrome virus (PRRSV) significantly impedes swine production due to rapid genetic variation and suppression of antiviral interferon (IFN) responses, leading to ineffective immunity. To address this, we developed IFNmix, a replication-competent PRRSV modified live vaccine (MLV) candidate co-expressing three Type I IFN subclasses (IFNα, IFNβ, IFNδ) to enhance antiviral immunity. Methods: In two independent in vivo experiments, we compared the protection of IFNmix and a commercial PRRSV MLV vaccine during challenge with a virulent PRRSV strain. Clinical signs, antibody and cytokine production, viral replication, and lung pathology in IFNmix-vaccinated pigs were compared to those of commercial PRRSV vaccines and controls. Results: Pigs vaccinated with IFNmix exhibited similar anti-PRRSV antibody development, serum viral loads, lung lesions, and cytokine responses post-challenge with the virulent NADC34 strain, with comparable or lower body temperatures and weight gain, to pigs vaccinated with the commercial vaccines. While IFNmix showed early viral load reduction compared to the commercial vaccine (Days 7–14 post-challenge), it demonstrated similar efficacy in controlling PRRSV replication and lung pathology. Conclusions: These findings suggest that IFNmix, by expressing multiple IFNs, can potentially enhance innate and adaptive immune responses, offering a promising approach to improving PRRSV vaccine efficacy. Further studies are needed to evaluate IFNmix against a broader range of PRRSV strains and to optimize its attenuation and immunogenicity.

Miller, Laura C. (ORCID:0000000289469416)↗
DOE OSTI2021

Sanitary Waste Landfill Effects on an Invasive Wild Pig Population

Being opportunistic omnivores, wild pigs (Sus scrofa) readily feed on edible garbage. Given the presence of substantial volumes of edible food waste, large multi-county and regional municipal sanitary waste landfills constitute attractive forage resources for pigs, providing a year-round anthropogenic source of potentially high-quality forage. Our objective was to assess the effects that a large regional landfill has on the local pigs foraging in that facility's waste disposal cells. The landfill, located on the United States Department of Energy's Savannah River Site (SRS) in South Carolina, USA, became operational in 1998 and pigs began foraging there in 2001. By 2009 >100 pigs/night were observed foraging in the landfill, suggesting landfill establishment may have important consequences for population dynamics, public safety, and disease transmission. We evaluated changes in body mass, fetal litter size, numbers of pigs removed, and wild pig-vehicle collisions (WPVCs) before (1980–2000) and after (2001–2019) pigs began foraging in the landfill on SRS. Body mass during the after period increased to a greater extent for pigs in the vicinity of the landfill compared to pigs on the rest of SRS. Fetal litter size increased for pigs in the vicinity of the landfill, whereas it remained unchanged on the rest of SRS. Our density surrogate (number of pigs harvested) increased around the landfill during the after period by 2.9 times, whereas on the rest of the site it only increased by 53%. No WPVCs occurred adjacent to the landfill before 2001, but WPVCs increased along the 2 major roads bordering the landfill after 2001. Effects of sanitary waste landfills on wild pig populations scavenging there can present unique challenges to population management, control, public safety, and disease transmission. Potential approaches to address these challenges could be exclusion fencing to prevent access to the landfill's waste disposal cells or enhanced placement of waste cell covers to reduce access.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Construction of extracellular matrix-based 3D hydrogel and its effects on cardiomyocytes

Highlights: • SOD and Triton X-100 could efficiently decellularize cells to get cardiac ECM. • Main proteins of cECM were fibronectin, collagen, elastin, fibrillin, laminin, etc. • 75% cECM-containing 3D hydrogel promoted cell proliferation and anti-apoptosis. • cECM3DH facilitated the differentiation of ESCs into CMs. • APcECM3DH was more conducive to NCM and ESC-derived CM maturation. Some discoveries resulted from 2-dimensional (2D) cultured cardiac cells have been disqualified in animal testing and later clinical trials. Extracellular matrix (ECM) plays a vital role in cardiac homeostasis, cardiac ECM (cECM)-based 3D cell cultures can mimics the physiological and pathological conditions in vivo closely, it is hopeful of addressing this challenge. Construction of cECM-based 3-dimensional (3D) hydrogel (cECM3DH) and its effects on cell behaviors were studied here. The results indicated that cellular compartments could be efficiently removed from heart tissue via sodium dodecyl sulfonate (SDS)- and Triton X-100-mediated decellularization, remaining the natural fibrous network structure and major proteins. 3D hydrogel consisted of 1 × 10{sup 7} cells/mL cells and 75% cECM could promote the proliferation and anti-apoptosis ability of human embryonic kidney (HEK)-293T cells. 0.25% trypsin or 0.20% collagenase was suitable to retrieve these cells from 3D hydrogel for further researches. Compared with 2D culture system, cECM3DH could significantly increase the proportion of GATA 4{sup +} cardiomyocytes (CMs) derived from heart tissue of neonatal mouse or induced differentiation of embryonic stem cells (ESCs) (P < 0.05) The expression levels of mature genes including cTnT, JCN, CaV1.2, MYL2, CASQ2, NCX1, and Cx43 of these CMs in adult pig cECM-based 3D hydrogel (APcECM3DH) were significantly higher than that in 2D culture system and in newborn piglet cECM-based 3D hydrogel (NPcECM3DH), respectively (P < 0.05). Therefore, cECM3DH supports the generation of primary CMs and ESC-derived CMs, APcECM3DH was more conducive to promoting CM maturation, which contributes to building 3D model for pathogenesis exploration, drug screening, and regenerative medicine of heart diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Comprehensive Economic Impacts ofWild Pigs on Producers of Six Crops in the South-Eastern US and California

Wild pigs (Sus scrofa) cause damage to agricultural crops in their native range as well as in the portions of the globe where they have been introduced. In the US, states with the highest introduced wild pig populations are Alabama, Arkansas, California, Florida, Georgia, Louisiana, Mississippi, Missouri, North Carolina, South Carolina, and Texas. The present study summarizes the first survey-based effort to value the full extent of wild pig damage to producers of six crops in these eleven US states. The survey was distributed by the USDA National Agricultural Statistical Service in the summer of 2022 to a sample of 11,495 producers of corn (Zea mays), soybeans (Glycine max), wheat (Triticum spp.), rice (Oryza sativa), peanuts (Arachis hypogaea), and sorghum (Sorghum bicolor) in these 11 states. Our findings suggest that the economic burden of wild pigs on producers of these crops is substantial and not limited to the direct and most identifiable categories of crop damage (i.e., production value lost due to depredation, trampling and rooting). We estimate that the annual cost to producers of these six crops in the surveyed states in 2021 was almost USD 700 million.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2024

Comparison of Intact Fish Skin Graft and Allograft as Temporary Coverage for Full-Thickness Burns: A Non-Inferiority Study

The extent and depth of burn injury may mandate temporary use of cadaver skin (allograft) to protect the wound and allow the formation of granulation tissue while split-thickness skin grafts (STSGs) are serially harvested from the same donor areas. However, allografts are not always available and have a high cost, hence the interest in identifying more economical, readily available products that serve the same function. This study evaluated intact fish skin graft (IFSG) as a temporary cover to prepare the wound bed for STSG application. Thirty-six full-thickness (FT) 5 × 5 cm burn wounds were created on the dorsum of six anesthetized Yorkshire pigs on day -1. To mimic the two-stage clinical situation, on day 0, wounds were excised down to a bleeding wound bed and a temporary cover (either IFSG or cadaver porcine skin) was applied; then, on day 7, wounds were debrided to a viable wound bed prior to the application of autologous 1.5:1 meshed STSG (mSTSG). Rechecks were performed on days 14, 21, 28, 45, and 60 with digital images, non-invasive measurements, and punch biopsies. The IFSG created a granulated wound bed receptive to the application of an mSTSG. FT burn wounds treated with an IFSG had similar outcome measures, including contraction rates, trans-epidermal water loss (TEWL) measurements, hydration, and blood perfusion levels, compared to cadaver skin-treated burn wounds. Pathology scoring indicated significant differences between the allograft- and IFSG-treated wounds on day 7, with the IFSG having increased angiogenesis, granulation tissue formation, and immune cells. Pathology scoring indicated no significant differences once mSTSGs were applied to wounds. The IFSG performed as well as cadaver skin as a temporary cover and was not inferior to the standard of care, suggesting the potential to transition IFSGs into clinical use for burns.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Detection and Characterization of Influenza A Virus Endemic Circulation in Suckling and Nursery Pigs Originating from Vaccinated Farms in the Same Production System

Inactivated influenza A virus (IAV) vaccines help reduce clinical disease in suckling piglets, although endemic infections still exist. The objective of this study was to evaluate the detection of IAV in suckling and nursery piglets from IAV-vaccinated sows from farms with endemic IAV infections. Eight nasal swab collections were obtained from 135 two-week-old suckling piglets from four farms every other week from March to September 2013. Oral fluid samples were collected from the same group of nursery piglets. IAV RNA was detected in 1.64% and 31.01% of individual nasal swabs and oral fluids, respectively. H1N2 was detected most often, with sporadic detection of H1N1 and H3N2. Whole-genome sequences of IAV isolated from suckling piglets revealed an H1 hemagglutinin (HA) from the 1B.2.2.2 clade and N2 neuraminidase (NA) from the 2002A clade. The internal gene constellation of the endemic H1N2 was TTTTPT with a pandemic lineage matrix. The HA gene had 97.59% and 97.52% nucleotide and amino acid identities, respectively, to the H1 1B.2.2.2 used in the farm-specific vaccine. A similar H1 1B.2.2.2 was detected in the downstream nursery. These data demonstrate the low frequency of IAV detection in suckling piglets and downstream nurseries from farms with endemic infections in spite of using farm-specific IAV vaccines in sows.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Determining Cs-137 Background body burdens for Wild Pigs At Savannah River Site

Savannah River Site (SRS) is a unique U.S. Department of Energy facility in that most of the 310-square miles of land has not be industrialized since operations began in 1953. This has allowed abundant, undisturbed vegetation structure to exists as well as an increase in herd sizes among wildlife populations onsite. Cs-137 is widespread across SRS due to the production of nuclear materials, but is mostly from global atmospheric fallout from nuclear weapons testing. Due to most of SRS being undisturbed land, the concentrations of Cs-137 are higher on site than off site. The SRS began conducting annual deer harvests that were open to the public beginning in 1965. All animals harvested during these hunts are monitored for Cs-137, which is measured using a Sodium Iodide detector. There has been an effective method for calculating the background Cs-137 body burden for the deer population at the SRS, developed by Gaines and Novak using data collected during hunts and gamma overflight data to determine the areas contaminated by site activities. For animals that have a Cs-137 concentration above the established background level, a dose is assigned to the hunter. By applying the same method for wild pigs using data collected from hunts, gamma overflight, and developing a site-specific home range of wild pigs, we were able to calculate the Cs-137 background body burden concentrations of wild pigs on site. Objectives: Develop site-specific home range for wild pigs at SRS; Determine the average concentrations of Cs-137 in wild pigs from background; Use Gaines and Novak method for determining background Cs-137 body burdens wild pigs on SRS. Methods and Materials: Development of site-specific home range of wild pigs was determined to be 2.5 miles using: Four studies conducted between 1969 and 1992 for the SRS wild pig population. (Mayer and Brisbin) The background compartments were determined using: Gamma overflight data showing contaminated areas; Site-specific home range of the wild pigs. Results and Conclusion: All data were generated through the JMP software to provide a histogram and summary statistics. The estimate of an upper tolerance limit for the background contamination with 95% confidence is 1.965 pCi/g for the wild pigs. This means that for wild pigs on SRS from the background compartments are expected to have Cs-137 concentrations of less than 1.965 pCi/g. The current background for the deer is 2.59 pCi/g. For the background compartments Cs-137 concentrations from 2012-2018: Mean: 0.815 pCi/g, Maximum: 2.341 pCi/g, Minimum: -0.704 pCi/g.

07 ISOTOPE AND RADIATION SOURCES↗