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At least 127 records · Page 7

Sandia Injury Biomechanics Laboratory Library

The Sandia Injury Biomechanics Laboratory (SIBL) Library is a collection of scripts and tools used to preprocess, process, and postprocess data for analysis of injury biomechanics data. SAND2020-3663 M Sandia National Laboratories is a multimission laboratory managed and operated by National Technology & Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525.

Hovey, Chad↗

In-situ X-ray Evaluation of Traumatic Brain Injury Dynamic Impacts (Final Report)

The goal of this project was to create an in-situ model of traumatic brain injury that allows for analysis of chronic traumatic encephalopathy (CTE) development. CTE is a neurodegenerative disease that occurs as a result of traumatic brain injuries. The resulting neurodegeneration and atrophying of cortical brain tissue develop as tau proteins build-up around small blood vessels and at the base of cortical sulci. Aggregation of tau proteins results in blood vessel damage and neurological function loss, leading to cortical tissue atrophy. This occurs only at some neuronal junctions in the brain after trauma. It has been conjectured that the geometrical distribution of force along neurons is responsible for initiation of tau deposition. However, to assess the validity of this proposition, it is necessary to analyze the mechanical response under dynamic loading associated with brain trauma in-situ

42 ENGINEERING↗

Biological Response Models: Predicting Injury and Mortality of Fish During Downstream Passage through Hydropower Facilities

This report describes the U.S. Department of Energy’s HydroPASSAGE project efforts to develop and collect biological response models for integration into the Biological Performance Assessment (BioPA) toolset and the Hydropower Biological Evaluation Toolset (HBET). These models help understand how fish are likely to respond during dam passage when exposed to hydraulic and physical stressors associated with turbines and other hydropower structures. When fish pass through hydropower facilities, they may encounter several stressors, of which the three most common are collision, rapid decompression, and fluid shear. Specialized equipment has been used to develop 99 biological response models for exposure to blade strike, rapid decompression, or fluid shear. The models were gathered from the literature or developed as part of this effort and include models for 31 different species of fish that have various predicted endpoints (i.e., injury or mortality). Among these models, considerable variation in susceptibility to the stressors has been observed from one species to another, and a species’ susceptibility to one stressor does not necessarily indicate similar susceptibility to another. Although several species have been examined, it is still unclear how many other species, which may have different morphological traits, may respond to these stressors, so further examination of the different species is needed. These models can and have been applied in several different cases, often using the BioPA toolset and HBET, to better understand the potential for injury and mortality that may occur during fish passage at hydropower facilities, including specific applications, such as turbine replacement, the installation of new turbines, or changing operations of currently installed turbines. As hydropower is continually developed to meet the electricity needs of society, tools such as HBET and BioPA, used with the integrated biological response models, will aid in the development of technologies and strategies that avoid, minimize, mitigate, or manage environmental effects.

13 HYDRO ENERGY↗

Laser ablation of human atherosclerotic plaque without adjacent tissue injury

Seventy samples of human cadaver atherosclerotic aorta were irradiated in vitro using a 308 nm xenon chloride excimer laser. Energy per pulse, pulse duration and frequency were varied. For comparison, 60 segments were also irradiated with an argon ion and an Nd:YAG laser operated in the continuous mode. Tissue was fixed in formalin, sectioned and examined microscopically. The Nd:YAG and argon ion-irradiated tissue exhibited a central crater with irregular edges and concentric zones of thermal and blast injury. In contrast, the excimer laser-irradiated tissue had narrow deep incisions with minimal or no thermal injury. These preliminary experiments indicate that the excimer laser vaporizes tissue in a manner different from that of the continuous wave Nd:YAG or argon ion laser. The sharp incision margins and minimal damage to adjacent normal tissue suggest that the excimer laser is more desirable for general surgical and intravascular uses than are the conventionally used medical lasers.

Grundfest, W. S.↗

Controlled environment life support system: Calcium-related leaf injuries on plants

Calcium related injuries to plants grown in controlled environments under conditions which maximize plant growth rates are described. Procedures to encourage movement of calcium into developing leaves of lettuce plants were investigated. The time course and pattern of calcium accumulation was determined to develop effective control procedures for this injury, termed tipburn. Procedures investigated were: (1) increasing the relative humidity to saturation during the dark period and altering root temperatures, (2) maximizing water stress during light and minimizing water stress during dark periods, (3) shortening the light-dark cycle lengths in combination with elevated moisture levels during the dark cycles, (4) reducing nutrient concentrations and (5) vibrating the plants. Saturated humidities at night increased the rate of growth and the large fluctuation in plant water potential encouraged calcium movement to the young leaves and delayed tipburn. Root temperature regulation between 15 and 26 C was not effective in preventing tipburn. Attempts to modulate water stress produced little variation, but no difference in tipburn development. Variations in light-dark cycle lengths also had no effect on calcium concentrations within developing leaves and no variation in tipburn development. Low concentrations of nutrient solution delayed tipburn, presumably because of greater calcium transport in the low concentration plants. Shaking of the plants did not prevent tipburn, but did delay it slightly.

Tibbitts, T. W.↗

Self Injury Inhibitor

There are approximately 50,000 autistic and retarded people in the United States alone, and many of them engage in self-injurious behavior, principally compulsive headbanging. Hope is offered by an automated unit, manufactured at Johns Hopkins University, called the Self-Injurious Behavior Inhibiting System (SIBIS). Components of SIBIS are stimulus module which is worn on upper arm or leg, and headgear which includes an impact detector and a transmitter on back of head. When there is a blow to the head it is sensed by impact detector which generates a coded signal that is automatically transferred to stimulus module which delivers a mild electrical stimulus to the skin for less than 1/10 of a second. Stimulus is sufficient to halt headbanging. Microprocessor computes impacts allowing measurement of patient progress.

Source record↗

Mechanical injury and repair of cells

OBJECTIVE: To concisely review the field of cell plasma membrane disruption (torn cell surface) and repair. MAIN POINTS: Plasma membrane disruption is a common form of cell injury under physiologic conditions, after trauma, in certain muscular dystrophies, and during certain forms of clinical intervention. Rapid repair of a disruption is essential to cell survival and involves a complex and active cell response that includes membrane fusion and cytoskeletal activation. Tissues, such as cardiac and skeletal muscle, adapt to a disruption injury by hypertrophying. Cells adapt by increasing the efficiency of their resealing response. CONCLUSION: Plasma membrane disruption is an important cellular event in both health and disease. The disruption repair mechanism is now well understood at the cellular level, but much remains to be learned at the molecular level. Cell and tissue level adaptational responses to the disruption either prevent its further occurrence or facilitate future repairs. Therapeutically useful drugs might result if, using this accumulating knowledge, chemical agents can be developed that can enhance repair or adaptive responses.

Review, Tutorial↗

Size of tuber propagule influences injury of 'Kennebec' potato plants by constant light

Chlorosis and necrotic spotting develop on the foliage of particular cultivars of potato (Solanum tuberosum L.) when grown under constant light. 'Kennebec', a cultivar severely injured by constant light when propagated from tissue-cultured plantlets, also was injured when plants were propagated from small tuber pieces (approximately 1 g). However, plants did not develop injury when propagated from large tuber pieces (approximately 100 g). Plants from large tuber pieces grew more rapidly than plants from small tuber pieces. The role of plant vigor and carbohydrate translocation in controlling injury development is discussed.

NASA Discipline Life Support Systems↗

Structural correlates of imbibitional injury in Typha pollen

The ultrastructure of Typha latifolia pollen was examined as a function of pollen moisture content and incubation temperature, in order to identify possible lesions induced by imbibitional chilling. A syndrome of structural traits was found which characterizes damaged grains. Compared to viable grains, the protoplast of damaged pollen has a higher proportion of its volume occupied by vesicles, and less volume occupied by cytoplasm. Damaged grains also tend to have dilated cisternae of endoplasmic reticulum, larger starch grains and lipid bodies, poorly preserved mitochondria and membranes, and, sometimes, numerous electron-dense globules associated with membranes. The percentage of grains exhibiting this damage syndrome correlates closely with the number of ungerminated grains in most samples, regardless of moisture content or incubation temperature. Injury due to rapid imbibition from the dry state or to imbibitional chilling appear to be similar structurally, regardless of whether the stresses are imposed singly or together. The injury is not confined to one cell component (e.g., mitochondria), but may involve a generalized disruption of membranes. These results suggest that similar stress responses are elicited by imbibition from the dry state and by imbibitional chilling.

NASA Program Space Biology↗

Dibutyryl cAMP effects on thromboxane and leukotriene production in decompression-induced lung injury

Decompression-induced venous bubble formation has been linked to increased neutrophil counts, endothelial cell injury, release of vasoactive eicosanoids, and increased vascular membrane permeability. These actions may account for inflammatory responses and edema formation. Increasing the intracellular cAMP has been shown to decrease eicosanoid production and edema formation in various models of lung injury. Reduction of decompression-induced inflammatory responses was evaluated in decompressed rats pretreated with saline (controls) or dibutyryl cAMP (DBcAMP, an analog of cAMP). After pretreatment, rats were exposed to either 616 kPa for 120 min or 683 kPa for 60 min. The observed increases in extravascular lung water ratios (pulmonary edema), bronchoalveolar lavage, and pleural protein in the saline control group (683 kPa) were not evident with DBcAMP treatment. DBcAMP pretreatment effects were also seen with the white blood cell counts and the percent of neutrophils in the bronchoalveolar lavage. Urinary levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were significantly increased with the 683 kPa saline control decompression exposure. DBcAMP reduced the decompression-induced leukotriene E4 production in the urine. Plasma levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were increased with the 683-kPa exposure groups. DBcAMP treatment did not affect these changes. The 11-dehydrothromboxane B2 and leukotriene E4 levels in the bronchoalveolar lavage were increased with the 683 kPa exposure and were reduced with the DBcAMP treatment. Our results indicate that DBcAMP has the capability to reduce eicosanoid production and limit membrane permeability and subsequent edema formation in rats experiencing decompression sickness.

Non-NASA Center↗

Suited Occupant Injury Potential During Dynamic Spacecraft Flight Phases

In support of the Constellation Space Suit Element [CSSE], a new space-suit architecture will be created for support of Launch, Entry, Abort, Microgravity Extra- Vehicular Activity [EVA], and post-landing crew operations, safety and, under emergency conditions, survival. The space suit is unique in comparison to previous launch, entry, and abort [LEA] suit architectures in that it utilizes rigid mobility elements in the scye (i.e., shoulder) and the upper arm regions. The suit architecture also utilizes rigid thigh disconnect elements to create a quick disconnect approximately located above the knee. This feature allows commonality of the lower portion of the suit (from the thigh disconnect down), making the lower legs common across two suit configurations. This suit must interface with the Orion vehicle seat subsystem, which includes seat components, lateral supports, and restraints. Due to the unique configuration of spacesuit mobility elements, combined with the need to provide occupant protection during dynamic vehicle events, risks have been identified with potential injury due to the suit characteristics described above. To address the risk concerns, a test series has been developed in coordination with the Injury Biomechanics Research Laboratory [IBRL] to evaluate the likelihood and consequences of these potential issues. Testing includes use of Anthropomorphic Test Devices [ATDs; vernacularly referred to as "crash test dummies"], Post Mortem Human Subjects [PMHS], and representative seat/suit hardware in combination with high linear acceleration events. The ensuing treatment focuses on test purpose and objectives; test hardware, facility, and setup; and preliminary results.

Dub, Mark O.↗

Musculoskeletal Changes, Injuries and Rehabilitation Associated with Spaceflight

The in-flight musculoskeletal database provides the foundation for directing operationally-relevant research in space medicine. This effort will enable medical operations to develop medical kits, training programs, and preventive medicine strategies for future CxP missions: a) Quantify medications and medical supplies for next-generation spacecraft. b) Objective data for engineers to determine weight requirements. Flight surgeons can make specific recommendations to astronauts based on injury data, such as emphasizing hand protection while in-flight. EVA and spacecraft engineers can examine evidence-based data on injuries and design countermeasures to help prevent them.

Scheuring, Richard A.↗

Abiotic Versus Biotic Pathogens: Replicative Growth in Host Tissues Key to Discriminating Between Biotoxic Injury and Active Pathogenesis

Life can be defined as a self-sustaining chemical system capable of undergoing Darwinian evolution; a self-bounded, self-replicating, and self-perpetuating entity [1]. This definition should hold for terrestrial as well as extraterrestrial life-forms. Although, it is reasonable to expect that a Mars life-form would be more adaptable to Mars-like conditions than to Earth-like environments, it remains possible that negative ecological or host interactions might occur if Mars microbiota were to be inadvertently released into the terrestrial environment. A biogenic infectious agent can be defined as a self-sustaining chemical system capable of undergoing Darwinian evolution and derives its sustenance from a living cell or from the by-products of cell death. Disease can be de-fined as the detrimental alteration of one or more ordered metabolic processes in a living host caused by the continued irritation of a primary causal factor or factors; disease is a dynamic process [2]. In contrast, an injury is due to an instantaneous event; injury is not a dynamic process [2]. A causal agent of disease is defined as a pathogen, and can be either abiotic or biotic in nature. Diseases incited by biotic pathogens are the exceptions, not the norms, in terrestrial host-microbe interactions. Disease induction in a plant host can be conceptually characterized using the Disease Triangle (Fig. 1) in which disease occurs only when all host, pathogen, and environ-mental factors that contribute to the development of disease are within conducive ranges for a necessary minimum period of time. For example, plant infection and disease caused by the wheat leaf rust fungus, Puccinia recondita, occur only if virulent spores adhere to genetically susceptible host tissues for at least 4-6 hours under favorable conditions of temperature and moisture [3]. As long as one or more conditions required for disease initiation are not available, disease symptoms will not develop.

Schuerger, Andrew C.↗

Microstructural Injury to Corpus Callosum and Intrahemispheric White Matter Tracts Correlate With Attention and Processing Speed Decline After Brain Radiation

The corpus callosum (CC) and intrahemispheric white matter tracts (IHWM) subserve critical aspects of attention and processing speed. We analyzed imaging biomarkers of microstructural injury within these regions and association with attention and processing speed performance before and after radiation therapy in primary brain tumor patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Normal Tissue Injury Induced by Photon and Proton Therapies: Gaps and Opportunities

Despite technological advances in radiation therapy (RT) and cancer treatment, patients still experience adverse effects. Proton therapy (PT) has emerged as a valuable RT modality that can improve treatment outcomes. Normal tissue injury is an important determinant of the outcome; therefore, for this review, we analyzed 2 databases: (1) clinical trials registered with ClinicalTrials.gov and (2) the literature on PT in PubMed, which shows a steady increase in the number of publications. Most studies in PT registered with ClinicalTrials.gov with results available are nonrandomized early phase studies with a relatively small number of patients enrolled. From the larger database of nonrandomized trials, we listed adverse events in specific organs/sites among patients with cancer who are treated with photons and protons to identify critical issues. The present data demonstrate dosimetric advantages of PT with favorable toxicity profiles and form the basis for comparative randomized prospective trials. A comparative analysis of 3 recently completed randomized trials for normal tissue toxicities suggests that for early stage non-small cell lung cancer, no meaningful comparison could be made between stereotactic body RT and stereotactic body PT due to low accrual (NCT01511081). In addition, for locally advanced non-small cell lung cancer, a comparison of intensity modulated RT with passive scattering PT (now largely replaced by spot-scanned intensity modulated PT), PT did not provide any benefit in normal tissue toxicity or locoregional failure over photon therapy. Finally, for locally advanced esophageal cancer, proton beam therapy provided a lower total toxicity burden but did not improve progression-free survival and quality of life (NCT01512589). The purpose of this review is to inform the limitations of current trials looking at protons and photons, considering that advances in technology, physics, and biology are a continuum, and to advocate for future trials geared toward accurate precision RT that need to be viewed as an iterative process in a defined path toward delivering optimal radiation treatment. A foundational understanding of the radiobiologic differences between protons and photons in tumor and normal tissue responses is fundamental to, and necessary for, determining the suitability of a given type of biologically optimized RT to a patient or cohort.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Preclinical Risk Evaluation of Normal Tissue Injury With Novel Radiosensitizers

Genotoxic damage induced by radiation triggers a highly coordinated DNA damage response, and molecular inhibitors of key nodes within this complex response network can profoundly enhance the antitumor efficacy of radiation. This is especially true for drugs targeting the catalytic subunit of DNA-dependent protein kinase, which is a core component of the nonhomologous end-joining DNA repair pathway, and ataxia telangiectasia mutated, which coordinates cell cycle arrest, apoptosis, and DNA repair functionalities after radiation exposure. Unlike the more modest in vitro radiosensitizing effects seen with classic sensitizing agents such as cisplatin, 5-fluorouracil, or taxanes, DNA-dependent protein kinase or ataxia telangiectasia mutated inhibitors provide much more robust sensitizing effects in vitro, as might be anticipated from targeting these key DNA repair modulators. However, patients with homozygous inactivating mutations of ataxia telangiectasia mutated or mice with homozygous defects in DNA-dependent protein kinase (severe combined immunodeficiency) have profoundly enhanced acute normal tissue radiation reactions. Therefore, there is significant potential that the combination of small molecule inhibitors of these kinases with radiation could cause similar dose-limiting acute normal tissue toxicities. Similarly, although less understood, inhibition of these DNA repair response pathways could markedly increase the risk of late radiation toxicities. Because these potent radiosensitizers could be highly useful to improve local control of otherwise radiation-resistant tumors, understanding the potential for elevated risks of radiation injury is essential for optimizing therapeutic ratio and developing safe and informative clinical trials. In this review, we will discuss 2 straightforward models to assess the potential for enhanced mucosal toxicity in the oral cavity and small intestine established in our laboratories. We also will discuss similar strategies for evaluating potential drug–radiation interactions with regard to increased risks of debilitating late effects.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

NIMA-related kinase 7 amplifies NLRP3 inflammasome pro-inflammatory signaling in microglia/macrophages and mice models of spinal cord injury

NIMA-related kinase-7 (NEK7) is a serine/threonine kinase that drives cell-cycle dynamics by modulating mitotic spindle formation and cytokinesis. It is also a crucial modulator of the pro-inflammatory effects of NOD-like receptor 3 (NLRP3) inflammasome. However, the role of NEK7 in microglia/macrophages post-spinal cord injury (SCI) is not well defined.

60 APPLIED LIFE SCIENCES↗

Tetramethylpyrazine inhibits neutrophil extracellular traps formation and alleviates hepatic ischemia/reperfusion injury in rat liver transplantation

Hepatic ischemia/reperfusion injury (IRI) is an adverse effect for liver transplantation which is characterized by immune response mediated inflammation. Recent studies report that neutrophil extracellular traps (NETs) are implicated in hepatic IRI. The aim of this study was to explore the mechanism of action of tetramethylpyrazine (TMP), the main chemical composition of Ligusticum chuanxiong in treatment of ischemic related diseases. Data showed that hepatic IRI increases the leak of alanine aminotransferase (ALT) and aspartate transaminase (AST), and stimulates formation of NETs. Extracellular DNA/NETs assay, hematoxylin-eosin (HE) staining, immunofluorescence assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and Western blot assay, showed that TMP significantly reduces formation of NETs and alleviates hepatic IRI. Moreover, TMP and Diphenyleneiodonium (DPI) suppressed ROS production in neutrophils. In addition, analysis showed that activation of NADPH oxidase plays a role in formation of NETs triggered by hepatic IRI. Notably, TMP inhibited formation of NETs though inhibition of NADPH oxidase. Additionally, Combination treatment using TMP and DPI was more effective compared with monotherapy of either of the two drugs. These findings show that combination therapy using TMP and DPI is a promising method for treatment hepatic IRI.

60 APPLIED LIFE SCIENCES↗