Experimental model and simulant for studying blast penetrating injury to the skin.

Energised fragments from explosions are the most common wounding mechanism in conflicts and terrorist attacks. Skin covers the vast majority of the human body and is therefore the first anatomical component to be penetrated by fragments, however, its resistance to penetration largely has not been taken into account in models of injury. In this study, an experimental model for ballistic testing of skin is established and a suitable skin simulant for studying resistance to penetration is determined.

Neuroimaging Findings in US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: US government personnel stationed internationally have reported anomalous health incidents (AHIs), with some individuals experiencing persistent debilitating symptoms.

Objective: To assess the potential presence of magnetic resonance imaging (MRI)-detectable brain lesions in participants with AHIs, with respect to a well-matched control group.

Design, Setting, And Participants: This exploratory study was conducted at the National Institutes of Health (NIH) Clinical Center and the NIH MRI Research Facility between June 2018 and November 2022.

Clinical, Biomarker, and Research Tests Among US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: Since 2015, US government and related personnel have reported dizziness, pain, visual problems, and cognitive dysfunction after experiencing intrusive sounds and head pressure. The US government has labeled these anomalous health incidents (AHIs).

Objective: To assess whether participants with AHIs differ significantly from US government control participants with respect to clinical, research, and biomarker assessments.

Filament formation drives catalysis by glutaminase enzymes important in cancer progression.

The glutaminase enzymes GAC and GLS2 catalyze the hydrolysis of glutamine to glutamate, satisfying the 'glutamine addiction' of cancer cells. They are the targets of anti-cancer drugs; however, their mechanisms of activation and catalytic activity have been unclear. Here we demonstrate that the ability of GAC and GLS2 to form filaments is directly coupled to their catalytic activity and present their cryo-EM structures which provide a view of the conformational states essential for catalysis.

Alone and together: current approaches to targeting glutaminase enzymes as part of anti-cancer therapies.

Metabolic reprogramming is a major hallmark of malignant transformation in cancer, and part of the so-called Warburg effect, in which the upregulation of glutamine catabolism plays a major role. The glutaminase enzymes convert glutamine to glutamate, which initiates this pathway. Inhibition of different forms of glutaminase (KGA, GAC, or LGA) demonstrated potential as an emerging anti-cancer therapeutic strategy.

The risk of fragment penetrating injury to the heart.

Injury due to the penetration of fragments into parts of the body has been the major cause of morbidity and mortality after an explosion. Penetrating injuries into the heart present very high mortality, yet the risk associated with such injuries has not been quantified. Quantifying this risk is key in the design of personal protection and the design of infrastructure.

Filament formation drives catalysis by glutaminase enzymes important in cancer progression.

The glutaminase enzymes GAC and GLS2 catalyze the hydrolysis of glutamine to glutamate, satisfying the 'glutamine addiction' of cancer cells. They are the targets of anti-cancer drugs; however, their mechanisms of activation and catalytic activity have been unclear. Here we demonstrate that the ability of GAC and GLS2 to form filaments is directly coupled to their catalytic activity and present their cryo-EM structures which provide an unprecedented view of the conformational states essential for catalysis.

Non-Lethal Blasts can Generate Cavitation in Cerebrospinal Fluid While Severe Helmeted Impacts Cannot: A Novel Mechanism for Blast Brain Injury.

Cerebrospinal fluid (CSF) cavitation is a likely physical mechanism for producing traumatic brain injury (TBI) under mechanical loading. In this study, we investigated CSF cavitation under blasts and helmeted impacts which represented loadings in battlefield and road traffic/sports collisions. We first predicted the human head response under the blasts and impacts using computational modelling and found that the blasts can produce much lower negative pressure at the contrecoup CSF region than the impacts.

High-resolution structures of mitochondrial glutaminase C tetramers indicate conformational changes upon phosphate binding.

The mitochondrial enzyme glutaminase C (GAC) is upregulated in many cancer cells to catalyze the first step in glutamine metabolism, the hydrolysis of glutamine to glutamate. The dependence of cancer cells on this transformed metabolic pathway highlights GAC as a potentially important therapeutic target. GAC acquires maximal catalytic activity upon binding to anionic activators such as inorganic phosphate.

New insights into the molecular mechanisms of glutaminase C inhibitors in cancer cells using serial room temperature crystallography.

Cancer cells frequently exhibit uncoupling of the glycolytic pathway from the TCA cycle (i.e., the "Warburg effect") and as a result, often become dependent on their ability to increase glutamine catabolism.

Penetration of Energized Metal Fragments to Porcine Thoracic Tissues.

Energized fragments from explosive devices have been the most common mechanism of injury to both military personnel and civilians in recent conflicts and terrorist attacks. Fragments that penetrate into the thoracic cavity are strongly associated with death due to the inherent vulnerability of the underlying structures. The aim of this study was to investigate the impact of fragment-simulating projectiles (FSPs) to tissues of the thorax in order to identify the thresholds of impact velocity for perforation through these tissues and the resultant residual velocity of the FSPs.

KRAS-dependent cancer cells promote survival by producing exosomes enriched in Survivin.

Mutations in KRAS frequently occur in human cancer and are especially prevalent in pancreatic ductal adenocarcinoma (PDAC), where they have been shown to promote aggressive phenotypes. However, targeting this onco-protein has proven to be challenging, highlighting the need to further identify the various mechanisms used by KRAS to drive cancer progression. Here, we considered the role played by exosomes, a specific class of extracellular vesicles (EVs) derived from the endocytic cellular trafficking machinery, in mediating the ability of KRAS to promote cell survival.

The Injury Mechanism of Traumatic Amputation.

Traumatic amputation has been one of the most defining injuries associated with explosive devices. An understanding of the mechanism of injury is essential in order to reduce its incidence and devastating consequences to the individual and their support network. In this study, traumatic amputation is reproduced using high-velocity environmental debris in an animal cadaveric model.

Characterizing upper limb function in the context of activities of daily living in CLN3 disease.

In CLN3 disease, impairments in motor function are frequently reported to have later onset compared to visual and cognitive decline, but upper limb motor function has yet to be explored in this population. In a cohort of 22 individuals with CLN3, we used a novel application of multiple measures to (1) characterize motor function, particularly of the upper limbs, in activities of daily living (ADLs), and (2) explore associations between motor function and age as well as visual ability, disease severity, and cognitive function, as evaluated by the Unified Batten Disease Rating Scale (UBDRS), a validated CLN3 disease measure. ADLs that required coordination, speed, and fine motor control were particularly challenging for children with CLN3 based on item-level performance across direct assessments (Jebsen-Taylor Hand Function Test [JTHFT] and MyoSet Tools) and caregiver reports (Pediatric Evaluation of Disability Inventory-Computer Adaptive Testing [PEDI-CAT] and Patient-Reported Outcomes Measurement Information System [PROMIS] Pediatric Upper Extremity).

Mapping the Risk of Fracture of the Tibia From Penetrating Fragments.

Penetrating injuries are commonly inflicted in attacks with explosive devices. The extremities, and especially the leg, are the most commonly affected body areas, presenting high risk of infection, slow recovery, and threat of amputation. The aim of this study was to quantify the risk of fracture to the anteromedial, posterior, and lateral aspects of the tibia from a metal fragment-simulating projectile (FSP).

A New Understanding of the Mechanism of Injury to the Pelvis and Lower Limbs in Blast.

Dismounted complex blast injury (DCBI) has been one of the most severe forms of trauma sustained in recent conflicts. This injury has been partially attributed to limb flail; however, the full causative mechanism has not yet been fully determined. Soil ejecta has been hypothesized as a significant contributor to the injury but remains untested.

Pelvic Protection Limiting Lower Limb Flail Reduces Mortality.

Pelvic blast injury is one of the most severe patterns of injury to be sustained by casualties of explosions. We have previously identified the mechanism of injury in a shock tube-mediated murine model, linking outward flail of the lower limbs to unstable pelvic fractures and vascular injury. As current military pelvic protection does not protect against lower limb flail, in this study we have utilized the same murine model to investigate the potential of novel pelvic protection to reduce injury severity.

Gelatine Backing Affects the Performance of Single-Layer Ballistic-Resistant Materials Against Blast Fragments.

Penetrating trauma by energized fragments is the most common injury from explosive devices, the main threat in the contemporary battlefield. Such devices produce projectiles dependent upon their design, including preformed fragments, casings, glass, or stones; these are subsequently energized to high velocities and cause serious injuries to the body. Current body armor focuses on the essential coverage, which is mainly the thoracic and abdominal area, and can be heavy and cumbersome.

The risk of fracture to the tibia from a fragment simulating projectile.

Penetrating injuries due to fragments energised by an explosive event are life threatening and are associated with poor clinical and functional outcomes. The tibia is the long bone most affected in survivors of explosive events, yet the risk of penetrating injury to it has not been quantified. In this study, an injury-risk assessment of penetrating injury to the tibia was conducted using a gas-gun system with a 0.

The activation loop and substrate-binding cleft of glutaminase C are allosterically coupled.

The glutaminase C (GAC) isoform of mitochondrial glutaminase is overexpressed in many cancer cells and therefore represents a potential therapeutic target. Understanding the regulation of GAC activity has been guided by the development of spectroscopic approaches that measure glutaminase activity in real time. Previously, we engineered a GAC protein (GAC(F327W)) in which a tryptophan residue is substituted for phenylalanine in an activation loop to explore the role of this loop in enzyme activity.

Restricting Lower Limb Flail is Key to Preventing Fatal Pelvic Blast Injury.

Pelvic vascular injury in the casualty of an explosive insult is a principal risk factor for increased mortality. The mechanism of injury has not previously been investigated in a physical model. In this study, a small-animal model of pelvic blast injury with a shock-tube mediated blast wave was utilised and showed that lower limb flail is necessary for an unstable pelvic fracture with vascular injury to occur.

Impairment of retinal function in yellow perch by metacercariae.

Histologic studies of fish from Douglas Lake, Cheboygan County, Michigan, USA show that spp. infect the lens of spottail shiners () and common shiners (). In contrast, infection was confined to the choroidal vasculature of yellow perch (), and the morphology of the pigment epithelium and retina in regions adjacent to the metacercariae was abnormal.

Experimental platforms to study blast injury.

Injuries sustained due to attacks from explosive weapons are multiple in number, complex in nature, and not well characterised. Blast may cause damage to the human body by the direct effect of overpressure, penetration by highly energised fragments, and blunt trauma by violent displacements of the body. The ability to reproduce the injuries of such insults in a well-controlled fashion is essential in order to understand fully the unique mechanism by which they occur, and design better treatment and protection strategies to alleviate the resulting poor long-term outcomes.

Fluorescent Sensing of a Nerve Agent Simulant with Dual Emission over Wide pH Range in Aqueous Solution.

A new 1,8-naphthalimide-based fluorescent probe for the detection of diethyl cyanophosphonate, a very common nerve agent simulant, is designed, synthesized, and characterized fully. The probe shows around 50-fold enhancement of fluorescence intensity over other nerve agent simulants. Importantly, the probe is able to work under aqueous conditions in a wide pH range.

Bioinorganic Chemistry of the Alkali Metal Ions.

The common Group 1 alkali metals are indeed ubiquitous on earth, in the oceans and in biological systems. In this introductory chapter, concepts involving aqueous chemistry and aspects of general coordination chemistry and oxygen atom donor chemistry are introduced. Also, there are nuclear isotopes of importance.