Fatality from Firework-Induced Trauma: A Case Report.

This case report presents the tragic death of a 56-year-old Slovenian woman who sustained fatal injuries from a stray firework during a New Year's Eve celebration in January 2024. The firework, launched by a relative, struck the woman in the right eye, causing extensive cranial and cerebral trauma. Despite immediate medical intervention, including attempted resuscitation, the woman was pronounced dead at the scene. The autopsy revealed severe damage, including fractures extending from the right orbital cavity to the occipital region and a penetrating brain injury affecting multiple regions of the brain. The case is complicated by the removal of the firework from the injury site before the arrival of emergency services, making the reconstruction of the exact sequence of events challenging. The findings emphasize the devastating consequences of fireworks-related injuries and the unique forensic challenges they present in determining the precise cause of death.

A big bang theory of big brain trauma.

One of the biggest neurophysiological science news headlines of the 2024 summer reported a critical link between post-traumatic stress disorder (PTSD), suicide, and brain injury from blast events in members of the elite US fighting force, Navy SEALS. Researchers from the Department of Defense/Uniformed Services University Brain Tissue Repository (DOD/USU BTR) had discovered a border of neural damage between the layers of white and gray matter comprising the cortical folds of service members' brains. Described as a distinctive anatomical line of astroglial scarring along the shared junctions of gray and white cellular zones of the brain, this tissue injury was unlike that observed for concussive brain trauma. Rather, it was consistent with blast biophysics of mammalian tissues. In this new study, the damage appears to be correlated with long-term, repeated exposure to blast waves from nearby explosions or firing weapons. A cascade of progressive unexplained behaviors, cognitive decline, and severe depression in the trained fighters ensued. This analysis suggested that repetitive, impulsive pressure waves traveling through the service members' heads and brains with each blast had compromised their cognitive centers, setting a downward trajectory in their mental and physical health.

[Forensic characteristic of damages caused by offensive grenades detonation]. / Sudebno-meditsinskaya kharakteristika povrezhdenii, prichinennykh pri vzryve nastupatel'nykh granat.

OBJECTIVE: To determine the specific morphological features of damages on the cloth and biological simulator of the human body in the detonation of RGD-5 and RGN fragmentation hand offensive grenades. MATERIAL AND METHODS: The study was carried out on the 12 targets from a biological simulator of the human body wrapped in cotton cloth by detonation of examined grenades at a distance of 50 cm and 1 m from the target. RESULTS: The character and features of damages of cloth and human body biological simulator, features of soot deposition made it possible to determine specific signs for each of examined offensive grenades types. CONCLUSIONS: The complex of obtained data allows to determine with high accuracy the detonation distance and the type of explosive device.

Additive effects of mild head trauma, blast exposure, and aging within white matter tracts: A novel Diffusion Tensor Imaging analysis approach.

Existing diffusion tensor imaging (DTI) studies of neurological injury following high-level blast exposure (hlBE) in military personnel have produced widely variable results. This is potentially due to prior studies often not considering the quantity and/or recency of hlBE, as well as co-morbidity with non-blast head trauma (nbHT). Herein, we compare commonly used DTI metrics: fractional anisotropy and mean, axial, and radial diffusivity, in Veterans with and without history of hlBE and/or nbHT. We use both the traditional method of dividing participants into 2 equally weighted groups and an alternative method wherein each participant is weighted by quantity and recency of hlBE and/or nbHT. While no differences were detected using the traditional method, the alternative method revealed diffuse and extensive changes in all DTI metrics. These effects were quantified within 43 anatomically defined white matter tracts, which identified the forceps minor, middle corpus callosum, acoustic and optic radiations, fornix, uncinate, inferior fronto-occipital and inferior longitudinal fasciculi, and cingulum, as the pathways most affected by hlBE and nbHT. Moreover, additive effects of aging were present in many of the same tracts suggesting that these neuroanatomical effects may compound with age.

Effect of blast orientation, multi-point blasts, and repetitive blasts on brain injury.

Explosions in the battlefield can result in brain damage. Research on the effects of shock waves on brain tissue mainly focuses on the effects of single-orientation blast waves, while there have been few studies on the dynamic response of the human brain to directional explosions in different planes, multi-point explosions and repetitive explosions. Therefore, the brain tissue response and the intracranial pressure (ICP) caused by different blast loadings were numerically simulated using the CONWEP method. In the study of the blast in different directions, the lateral explosion blast wave was found to cause greater ICP than did blasts from other directions. When multi-point explosions occurred in the sagittal plane simultaneously, the ICP in the temporal lobe increased by 37.8 % and the ICP in the parietal lobe decreased by 17.6 %. When multi-point explosions occurred in the horizontal plane, the ICP in the frontal lobe increased by 61.8 % and the ICP in the temporal lobe increased by 12.2 %. In a study of repetitive explosions, the maximum ICP of the second blast increased by 40.6 % over that of the first blast, and that of the third blast increased by 61.2 % over that of the second blast. The ICP on the brain tissue from repetitive blasts can exceed 200 % of that of a single explosion blast wave.

Macroscopic changes in aquaporin-4 underlie blast traumatic brain injury-related impairment in glymphatic function.

Mild traumatic brain injury (mTBI) has emerged as a potential risk factor for the development of neurodegenerative conditions such as Alzheimer's disease and chronic traumatic encephalopathy. Blast mTBI, caused by exposure to a pressure wave from an explosion, is predominantly experienced by military personnel and has increased in prevalence and severity in recent decades. Yet the underlying pathology of blast mTBI is largely unknown. We examined the expression and localization of AQP4 in human post-mortem frontal cortex and observed distinct laminar differences in AQP4 expression following blast exposure. We also observed similar laminar changes in AQP4 expression and localization and delayed impairment of glymphatic function that emerged 28 days following blast injury in a mouse model of repetitive blast mTBI. In a cohort of veterans with blast mTBI, we observed that blast exposure was associated with an increased burden of frontal cortical MRI-visible perivascular spaces, a putative neuroimaging marker of glymphatic perivascular dysfunction. These findings suggest that changes in AQP4 and delayed glymphatic impairment following blast injury may render the post-traumatic brain vulnerable to post-concussive symptoms and chronic neurodegeneration.

A Retrospective Analysis of Liraglutide (GLP-1 Agonist) Use in a Chinchilla (Chinchilla lanigera) Model of Auditory Blast Injury.

Chinchillas are a relatively novel research model compared with other rodent species. They require special considerations when it comes to their husbandry and daily care. Chinchillas tend to be shy animals that are well adapted to masking clinical signs of illness. These characteristics can make them a difficult species to maintain in a research setting. The authors' institution has maintained chinchillas and established standardized daily animal care procedures for them. Chinchillas are most commonly used for auditory research. They are often used to study the mechanism of different induced auditory conditions or injuries as well as exploration for potential alleviating treatments. Often, tested therapeutics have demonstrated potentially beneficial effects but have not been applied in the specific condition or injury of interest. The development of new applications for therapeutics can lead to groundbreaking discoveries, but testing of new therapeutic applications is often initially performed in an animal model without knowing how the therapeutic will behave in the species. During testing, unexpected adverse events may manifest that require more focused monitoring and supportive care. This scenario occurred when adverse effects were observed in a chinchilla blast-injury model after receiving an acylated glucagon-like peptide-1 (GLP-1) receptor agonist. The study involved evaluation of this therapeutic over an extended amount of time after inducing a controlled pressurized blast-injury followed by multiple repeated hearing tests under anesthesia. Chinchillas enrolled in the study exhibited several clinical signs including weight loss, lethargy, labored breathing, neurologic abnormalities, decreased appetite or decreased fecal output, and otitis. Five primary abnormalities were reported on pathology: aspiration pneumonia, hepatic steatosis, right ventricular dilation, pancreatitis, and tubulointerstitial nephritis. Initially abnormal clinical signs, early mortality rates, and pathology were attributed to multiple anesthetic events. However, a retrospective analysis evaluating the association of different study variable exposures in a stratified comparison demonstrated that the early mortality rates were actually associated with the therapeutic drug given for the first time in this species. In this study, we describe the detailed findings of the retrospective analysis and explore different strategies that can be incorporated to maintain good animal welfare and decrease early animal loss.

Meningeal Damage and Interface Astroglial Scarring in the Rat Brain Exposed to a Laser-Induced Shock Wave(s).

In the past decade, signature clinical neuropathology of blast-induced traumatic brain injury has been under intense debate, but interface astroglial scarring (IAS) seems to be convincing. In this study, we examined whether IAS could be replicated in the rat brain exposed to a laser-induced shock wave(s) (LISW[s]), a tool that can produce a pure shock wave (primary mechanism) without dynamic pressure (tertiary mechanism). Under certain conditions, we observed astroglial scarring in the subpial glial plate (SGP), gray-white matter junctions (GM-WM), ventricular wall (VW), and regions surrounding cortical blood vessels, accurately reproducing clinical IAS. We also observed shock wave impulse-dependent meningeal damage (dural microhemorrhage) in vivo by transcranial near-infrared (NIR) reflectance imaging. Importantly, there were significant correlations between the degree of dural microhemorrhage and the extent of astroglial scarring more than 7 days post-exposure, suggesting an association of meningeal damage with astroglial scarring. The results demonstrated that the primary mechanism alone caused the IAS and meningeal damage, both of which are attributable to acoustic impedance mismatching at multi-layered tissue boundaries. The time course of glial fibrillary acidic protein (GFAP) immunoreactivity depended not only on the LISW conditions but also on the regions. In the SGP, significant increases in GFAP immunoreactivity were observed at 3 days post-exposure, whereas in the GM-WM and VW, GFAP immunoreactivity was not significantly increased before 28 days post-exposure, suggesting different pathological mechanisms. With the high-impulse single exposure or the multiple exposure (low impulse), fibrotic reaction or fibrotic scar formation was observed, in addition to astroglial scarring, in the cortical surface region. Although there are some limitations, this seems to be the first report on the shock-wave-induced IAS rodent model. The model may be useful to explore potential therapeutic approaches for IAS.

Investigating neuropathological changes and underlying neurobiological mechanisms in the early stages of primary blast-induced traumatic brain injury: Insights from a rat model.

The utilization of explosives and chemicals has resulted in a rise in blast-induced traumatic brain injury (bTBI) in recent times. However, there is a dearth of diagnostic biomarkers and therapeutic targets for bTBI due to a limited understanding of biological mechanisms, particularly in the early stages. The objective of this study was to examine the early neuropathological characteristics and underlying biological mechanisms of primary bTBI. A total of 83 Sprague Dawley rats were employed, with their heads subjected to a blast shockwave of peak overpressure ranging from 172 to 421 kPa in the GI, GII, and GIII groups within a closed shock tube, while the body was shielded. Neuromotor dysfunctions, morphological changes, and neuropathological alterations were detected through modified neurologic severity scores, brain water content analysis, MRI scans, histological, TUNEL, and caspase-3 immunohistochemical staining. In addition, label-free quantitative (LFQ)-proteomics was utilized to investigate the biological mechanisms associated with the observed neuropathology. Notably, no evident damage was discernible in the GII and GI groups, whereas mild brain injury was observed in the GIII group. Neuropathological features of bTBI were characterized by morphologic changes, including neuronal injury and apoptosis, cerebral edema, and cerebrovascular injury in the shockwave's path. Subsequently, 3153 proteins were identified and quantified in the GIII group, with subsequent enriched neurological responses consistent with pathological findings. Further analysis revealed that signaling pathways such as relaxin signaling, hippo signaling, gap junction, chemokine signaling, and sphingolipid signaling, as well as hub proteins including Prkacb, Adcy5, and various G-protein subunits (Gnai2, Gnai3, Gnao1, Gnb1, Gnb2, Gnb4, and Gnb5), were closely associated with the observed neuropathology. The expression of hub proteins was confirmed via Western blotting. Accordingly, this study proposes signaling pathways and key proteins that exhibit sensitivity to brain injury and are correlated with the early pathologies of bTBI. Furthermore, it highlights the significance of G-protein subunits in bTBI pathophysiology, thereby establishing a theoretical foundation for early diagnosis and treatment strategies for primary bTBI.

Blunt force trauma and blast injuries to head and chest caused by a potent pyrotechnic device: a case report.

In times of peace and except for terrorist attacks, fatalities by explosions are rare. Fireworks have deadly potential, especially self-made or illegally acquired devices. The use of professional pyrotechnics by untrained persons poses a life-threatening hazard. We present a case of devastating blunt force and blast injuries to the head and chest of a young man. After ignition of a display shell (syn. a real shell or mortar shell) without the use of a launching pipe, the device hit the man's face, nearly simultaneously followed by the explosion of the burst charge. The autopsy revealed injuries to the face and forehead as well as extensive tissue structure damage and a massive contusion with a bloody edema of the lungs. Autopsy results are supplemented with CT imaging and 3D reconstruction of the fractured mid face, as well as histological and toxicological examinations. This case of a misused display shell demonstrates both its devastating destructive potential and the corresponding and rarely observed injury pattern.

Proteomic Changes in the Hippocampus after Repeated Explosive-Driven Blasts.

Repeated blast-traumatic brain injury (blast-TBI) has been hypothesized to cause persistent and unusual neurological and psychiatric symptoms in service members returning from war zones. Blast-wave primary effects have been supposed to induce damage and molecular alterations in the brain. However, the mechanisms through which the primary effect of an explosive-driven blast wave generate brain lesions and induce brain consequences are incompletely known. Prior findings from rat brains exposed to two consecutive explosive-driven blasts showed molecular changes (hyperphosphorylated-Tau, AQP4, S100ß, PDGF, and DNA-polymerase-ß) that varied in magnitude and direction across different brain regions. We aimed to compare, in an unbiased manner, the proteomic profile in the hippocampus of double blast vs sham rats using mass spectrometry (MS). Data showed differences in up- and down-regulation for protein abundances in the hippocampus of double blast vs sham rats. Tandem mass tag (TMT)-MS results showed 136 up-regulated and 94 down-regulated proteins between the two groups (10.25345/C52B8VP0X). These TMT-MS findings revealed changes never described before in blast studies, such as increases in MAGI3, a scaffolding protein at cell-cell junctions, which were confirmed by Western blotting analyses. Due to the absence of behavioral and obvious histopathological changes as described in our previous publications, these proteomic data further support the existence of an asymptomatic blast-induced molecular altered status (ABIMAS) associated with specific protein changes in the hippocampus of rats repeatedly expsosed to blast waves generated by explosive-driven detonations.

Model matters: Differential outcomes in traumatic optic neuropathy pathophysiology between blunt and blast-wave mediated head injuries.

Over 3 million people in the United States live with long-term disability because of a traumatic brain injury (TBI). The purpose of this study was to characterize and compare two different animal models of TBI (blunt head trauma and blast TBI) to determine common and divergent characteristics of these models. With recent literature reviews noting the prevalence of visual system injury in animal models of TBI, coupled with clinical estimates of 50-75% of all TBI cases, we decided to assess commonalities, if they existed, through visual system injury. A unilateral (left directed) blast and repeat blast model injury with coup-contra-coup injury patterns were compared to a midline blunt injury. Injuries were induced in adult male mice to observe and quantify visual deficits. Retinal ganglion cell loss and axonal degeneration in the optic tract, superior colliculus, and lateral geniculate nuclei were examined to trace injury outcomes throughout major vision-associated areas. Optokinetic response, immunohistochemistry, and western blots were analyzed. Where a single blunt injury produces significant visual deficits a single blast injury appears to have less severe visual consequences. Visual deficits after repeat blasts are similar to a single blast. Single blast injury induces contralateral damage to the right optic chiasm and tract whereas bilateral injury follows a single blunt TBI. Repeat blast injuries are required to see degeneration patterns in downstream regions similar to the damage seen in a single blunt injury. This finding is further supported by amyloid precursor protein (APP) staining in injured cohorts. Blunt injured groups present with staining 1.2 mm ahead of the optic nerve, indicating axonal breakage closer to the optic chiasm. In blast groups, APP was identifiable in a bilateral pattern only in the geniculate nucleus. Evidence for unilateral neuronal degeneration in brain tissue with bilateral axonal ruptures are pivotal discoveries in this model differentiation. Analysis of the two injury models suggests that there is a significant difference in the histological outcomes dependent on injury type, though visual system injury is likely present in more cases than are currently diagnosed clinically.

[Neurobehavioral effects of explosion exposure on acute and chronic traumatic brain injury in rats].

Objective: To explore the effect of nerve injury in rats by neurobehavioral experiments, in order to provide a model and idea for further clarification of the traumatic brain injury mechanism under explosion exposure. Methods: From May 2021 to August 2022, 160 SPF male rats were randomly divided into four groups, including control group, 60 kPa group (low intensity group), 90 kPa group (medium intensity group) and 120 kPa group (high intensity group). The blast induced traumatic brain injury (bTBI) model of rats was established by using the shock tube platform to simulate the shock wave parameters of the explosion overpressure of 60 kPa, 90 kPa and 120 kPa. Acute observation was carried out after 24 h and 7 d of explosive exposure, and chronic recovery observation was carried out after 28 d and 90 d. The time effect of shock wave brain injury in different situations was discussed by open field, light dark test, active avoidance test. Finally, the results of brain injury in rats were detected by pathological tissue staining. Results: After 24 h explosion exposure, compared with the control group, the rest time of rats in low and high intensity groups increased, the total movement distance decreased, and the number of visits to the camera obscura decreased, with statistical significance (P<0.05). After 7 days of exposure, compared with the control group, the rest time of rats in high intensity group increased, and the number of visits to the obscura decreased, with statistical significance (P<0.05). After 28 and 90 days of exposure, compared with the control group, there were no significant differences in rest time, total exercise distance and times of visiting the camera obscura in all intensity groups (P>0.05). After 24 h of explosive exposure, compared with the control group, the cell morphology of rats in each intensity group was normal, and no inflammatory cell infiltration was observed. Conclusion: In the acute phase (24 h) of blast exposure, rats have no desire to explore the outside world, and shock wave exposure may damage the neurological function of rats.

Systemic inflammation induced from remote extremity trauma is a critical driver of secondary brain injury.

Blast exposure, commonly experienced by military personnel, can cause devastating life-threatening polysystem trauma. Despite considerable research efforts, the impact of the systemic inflammatory response after major trauma on secondary brain injury-inflammation is largely unknown. The aim of this study was to identify markers underlying the susceptibility and early onset of neuroinflammation in three rat trauma models: (1) blast overpressure exposure (BOP), (2) complex extremity trauma (CET) involving femur fracture, crush injury, tourniquet-induced ischemia, and transfemoral amputation through the fracture site, and (3) BOP+CET. Six hours post-injury, intact brains were harvested and dissected to obtain biopsies from the prefrontal cortex, striatum, neocortex, hippocampus, amygdala, thalamus, hypothalamus, and cerebellum. Custom low-density microarray datasets were used to identify, interpret and visualize genes significant (p < 0.05 for differential expression [DEGs]; 86 neuroinflammation-associated) using a custom python-based computer program, principal component analysis, heatmaps and volcano plots. Gene set and pathway enrichment analyses of the DEGs was performed using R and STRING for protein-protein interaction (PPI) to identify and explore key genes and signaling networks. Transcript profiles were similar across all regions in naïve brains with similar expression levels involving neurotransmission and transcription functions and undetectable to low-levels of inflammation-related mediators. Trauma-induced neuroinflammation across all anatomical brain regions correlated with injury severity (BOP+CET > CET > BOP). The most pronounced differences in neuroinflammatory-neurodegenerative gene regulation were between blast-associated trauma (BOP, BOP+CET) and CET. Following BOP, there were few DEGs detected amongst all 8 brain regions, most were related to cytokines/chemokines and chemokine receptors, where PPI analysis revealed Il1b as a potential central hub gene. In contrast, CET led to a more excessive and diverse pro-neuroinflammatory reaction in which Il6 was identified as the central hub gene. Analysis of the of the BOP+CET dataset, revealed a more global heightened response (Cxcr2, Il1b, and Il6) as well as the expression of additional functional regulatory networks/hub genes (Ccl2, Ccl3, and Ccl4) which are known to play a critical role in the rapid recruitment and activation of immune cells via chemokine/cytokine signaling. These findings provide a foundation for discerning pathophysiological consequences of acute extremity injury and systemic inflammation following various forms of trauma in the brain.

Late chronic local inflammation, synaptic alterations, vascular remodeling and arteriovenous malformations in the brains of male rats exposed to repetitive low-level blast overpressures.

In the course of military operations in modern war theaters, blast exposures are associated with the development of a variety of mental health disorders associated with a post-traumatic stress disorder-related features, including anxiety, impulsivity, insomnia, suicidality, depression, and cognitive decline. Several lines of evidence indicate that acute and chronic cerebral vascular alterations are involved in the development of these blast-induced neuropsychiatric changes. In the present study, we investigated late occurring neuropathological events associated with cerebrovascular alterations in a rat model of repetitive low-level blast-exposures (3 × 74.5 kPa). The observed events included hippocampal hypoperfusion associated with late-onset inflammation, vascular extracellular matrix degeneration, synaptic structural changes and neuronal loss. We also demonstrate that arteriovenous malformations in exposed animals are a direct consequence of blast-induced tissue tears. Overall, our results further identify the cerebral vasculature as a main target for blast-induced damage and support the urgent need to develop early therapeutic approaches for the prevention of blast-induced late-onset neurovascular degenerative processes.

Single-nucleus profiling of adult mice sub-ventricular zone after blast-related traumatic brain injury.

Explosive blast-related traumatic brain injuries (bTBI) are common in war zones and urban terrorist attacks. These bTBIs often result in complex neuropathologic damage and neurologic complications. However, there is still a lack of specific strategies for diagnosing and/or treating bTBIs. The sub-ventricular zone (SVZ), which undergoes adult neurogenesis, is critical for the neurological maintenance and repair after brain injury. However, the cellular responses and mechanisms that trigger and modulate these activities in the pathophysiological processes following bTBI remain poorly understood. Here we employ single-nucleus RNA-sequencing (snRNA-seq) of the SVZ from mice subjected to a bTBI. This data-set, including 15272 cells (7778 bTBI and 7494 control) representing all SVZ cell types and is ideally suited for exploring the mechanisms underlying the pathogenesis of bTBIs. Additionally, it can serve as a reference for future studies regarding the diagnosis and treatment of bTBIs.

Progressive Transcriptional Changes in the Amygdala Implicate Neuroinflammation in the Effects of Repetitive Low-Level Blast Exposure in Male Rats.

Chronic mental health problems are common among military veterans who sustained blast-related traumatic brain injuries. The reasons for this association remain unexplained. Male rats exposed to repetitive low-level blast overpressure (BOP) exposures exhibit chronic cognitive and post-traumatic stress disorder (PTSD)-related traits that develop in a delayed fashion. We examined blast-induced alterations on the transcriptome in four brain areas (anterior cortex, hippocampus, amygdala, and cerebellum) across the time frame over which the PTSD-related behavioral phenotype develops. When analyzed at 6 weeks or 12 months after blast exposure, relatively few differentially expressed genes (DEGs) were found. However, longitudinal analysis of amygdala, hippocampus, and anterior cortex between 6 weeks and 12 months revealed blast-specific DEG patterns. Six DEGs (hyaluronan and proteoglycan link protein 1 [Hapln1], glutamate metabotropic receptor 2 [Grm2], purinergic receptor P2y12 [P2ry12], C-C chemokine receptor type 5 [Ccr5], phenazine biosynthesis-like protein domain containing 1 [Pbld1], and cadherin related 23 [Cdh23]) were found altered in all three brain regions in blast-exposed animals. Pathway enrichment analysis using all DEGs or those uniquely changed revealed different transcription patterns in blast versus sham. In particular, the amygdala in blast-exposed animals had a unique set of enriched pathways related to stress responses, oxidative phosphorylation, and mitochondrial dysfunction. Upstream analysis implicated tumor necrosis factor (TNF)α signaling in blast-related effects in amygdala and anterior cortex. Eukaryotic initiating factor eIF4E (EIF4e), an upstream regulator of P2ry12 and Ccr5, was predicted to be activated in the amygdala. Quantitative polymerase chain reaction (qPCR) validated longitudinal changes in two TNFα regulated genes (cathepsin B [Ctsb], Hapln1), P2ry12, and Grm2. These studies have implications for understanding how blast injury damages the brain and implicates inflammation as a potential therapeutic target.

Methodology of the INVestigating traIning assoCiated blasT pAthology (INVICTA) study.

BACKGROUND: Subconcussive blast exposure during military training has been the subject of both anecdotal concerns and reports in the medical literature, but prior studies have often been small and have used inconsistent methods. METHODS: This paper presents the methodology employed in INVestigating traIning assoCiated blasT pAthology (INVICTA) to assess a wide range of aspects of brain function, including immediate and delayed recall, gait and balance, audiologic and oculomotor function, cerebral blood flow, brain electrical activity and neuroimaging and blood biomarkers. RESULTS: A number of the methods employed in INVICTA are relatively easy to reproducibly utilize, and can be completed efficiently, while other measures require greater technical expertise, take longer to complete, or may have logistical challenges. CONCLUSIONS: This presentation of methods used to assess the impact of blast exposure on the brain is intended to facilitate greater uniformity of data collection in this setting, which would enable comparison between different types of blast exposure and environmental circumstances, as well as to facilitate meta-analyses and syntheses across studies.

A Long-Term Safety and Efficacy Report on Intravitreal Delivery of Adipose Stem Cells and Secretome on Visual Deficits After Traumatic Brain Injury.

Purpose: We compared intravitreal injection of human adipose stem cell concentrated conditioned media (ASC-CCM) to injection of live ASCs for their long-term safety and effectiveness against the visual deficits of mild traumatic brain injury (mTBI). Methods: We first tested different intravitreal ASC doses for safety. Other C57BL/6 mice then received focal cranial blast mTBI and were injected with the safe ASC dose (1000 cells/eye), ASC-CCM (∼200 ng protein/eye), or saline solution. At five and 10 months after blast injury, visual, molecular, and histological assessments evaluated treatment efficacy. Histological evaluation of eyes and other organs at 10 months after blast injury assessed safety. Results: Human ASCs at 1000 cells/eye were found to be safe, with >10,000 cells causing retinal damage. Blast-injured mice showed significant vision deficits compared to sham blast mice up to 10 months. Blast mice receiving ASC or ASC-CCM showed improved vision at five months but marginal effects at 10 months, correlated with changes in glial fibrillary acidic protein and proinflammatory gene expression in retina. Immunostaining for human IgG failed to detect ASCs in retina. Peripheral organs examined histologically at 10 months after blast injury were normal. Conclusions: Intravitreal injection of ASCs or ASC-CCM is safe and effective against the visual deficits of mTBI. Considering the unimproved glial response and the risk of retinal damage with live cells, our studies suggest that ASC-CCM has better safety and effectiveness than live cells for the treatment of visual dysfunction in mTBI. Translational Relevance: This study demonstrates the safety and efficacy of mesenchymal stem cell-based therapeutics, supporting them for phase 1 clinical studies.

Forensic pathological characteristics of explosion trauma in confined space terrorist mass fatalities classified with a 3-dimensional model.

BACKGROUND: Explosion fatalities are the severest type of violent crimes. These involve the use of explosive devices in terrorist like activities in confined spaces in civilian or military settings, with mass number of people present all around. A stark dearth of literature for the forensic interpretation of such catastrophes is astonishing. PURPOSE: Characterization of the pattern of the multitude of injuries in explosions in confined spaces as guide for investigations and growth of literature on this entity. METHODOLOGY: A review of the archives of the forensic examinations of mass fatalities due to an explosion in a metro car was undertaken. It was combined with the reconstruction of the events by developing a three-dimensional model of this incident that involved seventeen fatalities. RESULTS: All the decedents showed differential pattern of fatal injuries under the influence of damaging explosion factors (DEFs). The causative forces were characterized as gas-detonation (in all the cases), damaging effect by shock waves (59% of the cases), and impact of fragmentation and collision of the body (thrown off) with nearby objects. Traumatic effect due to shrapnel as well as blunt force was noted in 82% of the cases. Gross destruction of head due to combined effect of gas-detonation and fragmentation was seen in 29% of the cases. CONCLUSION: An interpretation of the nature and pattern of injuries in confined space explosions can help to estimate the location of deceased/s with respect to the epicenter and the type of DEFs.