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The majority of hip fractures have been reported to occur as a result of a fall with impact to the greater trochanter of the femur. Recently, we developed a novel cadaveric pendulum-based hip impact model and tested two cadaveric femur-pelvis constructs, embedded in a soft tissue surrogate. The outcome was a femoral neck fracture in a male specimen while a female specimen had no fracture. The aim of the present study was, first, to develop a methodology for constructing and assessing the accuracy of explicit Finite Element Models (FEMs) for simulation of sideways falls to the hip based on the experimental model. Second, to use the FEMs for quantifying the internal reaction forces and energy absorption in the hip during impact. Third, to assess the potential of the FEMs in terms of separating a femoral fracture endpoint from a non-fracture endpoint. Using a non-linear, strain rate dependent, and heterogeneous material mapping strategy for bone tissue in these models, we found the FEM-derived results to closely match the experimental test results in terms of impact forces and displacements of pelvic video markers up to the time of peak impact force with errors below 10%. We found the internal reaction forces in the femoral neck on the impact side to be approximately 35% lower than the impact force measured between soft tissue and ground for both specimens. In addition, we found the soft tissue to be the component that absorbed the largest part of the energy of the tissue types in the hip region. Finally, we found surface strain patterns derived from FEM results to match the fracture location and extent based on post testing x-rays of the specimens. This is the first study with quantitative data on the energy absorption in the pelvic region during a sideways fall.

Background Bicycling has the potential to improve fitness, diminish obesity, and reduce noise, air pollution, and greenhouse gases associated with travel. However, bicyclists incur a higher risk of injuries requiring hospitalization than motor vehicle occupants. Therefore, understanding ways of making bicycling safer and increasing rates of bicycling are important to improving population health. There is a growing body of research examining transportation infrastructure and the risk of injury to bicyclists. Methods We reviewed studies of the impact of transportation infrastructure on bicyclist safety. The results were tabulated within two categories of infrastructure, namely that at intersections (e.g. roundabouts, traffic lights) or between intersections on \"straightaways\" (e.g. bike lanes or paths). To assess safety, studies examining the following outcomes were included: injuries; injury severity; and crashes (collisions and/or falls). Results The literature to date on transportation infrastructure and cyclist safety is limited by the incomplete range of facilities studied and difficulties in controlling for exposure to risk. However, evidence from the 23 papers reviewed (eight that examined intersections and 15 that examined straightaways) suggests that infrastructure influences injury and crash risk. Intersection studies focused mainly on roundabouts. They found that multi-lane roundabouts can significantly increase risk to bicyclists unless a separated cycle track is included in the design. Studies of straightaways grouped facilities into few categories, such that facilities with potentially different risks may have been classified within a single category. Results to date suggest that sidewalks and multi-use trails pose the highest risk, major roads are more hazardous than minor roads, and the presence of bicycle facilities (e.g. on-road bike routes, on-road marked bike lanes, and off-road bike paths) was associated with the lowest risk. Conclusion Evidence is beginning to accumulate that purpose-built bicycle-specific facilities reduce crashes and injuries among cyclists, providing the basis for initial transportation engineering guidelines for cyclist safety. Street lighting, paved surfaces, and low-angled grades are additional factors that appear to improve cyclist safety. Future research examining a greater variety of infrastructure would allow development of more detailed guidelines.

Despite advances in the treatment of acute spinal cord injury (SCI), measures to mitigate permanent neurological deficits in affected patients are limited. Immediate post-trauma hemodynamic management of patients, to maintain blood supply and improve oxygenation to the injured spinal cord, is currently one aspect of critical care which clinicians can utilize to improve neurological outcomes. However, without a way to monitor the response of spinal cord hemodynamics and oxygenation in real time, optimizing hemodynamic management is challenging and limited in scope. This study aims to investigate the feasibility and validity of using a miniaturized multi-wavelength near-infrared spectroscopy (NIRS) sensor for direct transdural monitoring of spinal cord oxygenation in an animal model of acute SCI. Nine Yorkshire pigs underwent a weight-drop T10 contusion-compression injury and received episodes of ventilatory hypoxia and alterations in mean arterial pressure (MAP). Spinal cord hemodynamics and oxygenation were monitored throughout by a non-invasive transdural NIRS sensor, as well as an invasive intraparenchymal sensor as a comparison. NIRS parameters of tissue oxygenation were highly correlated with intraparenchymal measures of tissue oxygenation. In particular, during periods of hypoxia and MAP alterations, changes of NIRS-derived spinal cord oxygenated hemoglobin and tissue oxygenation percentage corresponded well with the changes in spinal cord oxygen partial pressures measured by the intraparenchymal sensor. Our data confirm that during hypoxic episodes and as changes occur in the MAP, non-invasive NIRS can detect and measure real-time changes in spinal cord oxygenation with a high degree of sensitivity and specificity.

Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS). How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI) induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone) from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI) behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI.

Traumatic brain injury (TBI) is a major worldwide healthcare problem. Despite promising outcomes from many preclinical studies, the failure of several clinical studies to identify effective therapeutic and pharmacological approaches for TBI suggests that methods to improve the translational potential of preclinical studies are highly desirable. Rodent models of TBI are increasingly in demand for preclinical research, particularly for closed head injury (CHI), which mimics the most common type of TBI observed clinically. Although seemingly simple to establish, CHI models are particularly prone to experimental variability. Promisingly, bioengineering-oriented research has advanced our understanding of the nature of the mechanical forces and resulting head and brain motion during TBI. However, many neuroscience-oriented laboratories lack guidance with respect to fundamental biomechanical principles of TBI. Here, we review key historical and current literature that is relevant to the investigation of TBI from clinical, physiological and biomechanical perspectives, and comment on how the current challenges associated with rodent TBI models, particularly those involving CHI, could be improved.

Background The annual incidence of traumatic brain injury (TBI) in the United States is over 2.5 million, with approximately 3–5 million people living with chronic sequelae. Compared with moderate-severe TBI, the long-term effects of mild TBI (mTBI) are less understood but important to address, particularly for contact sport athletes and military personnel who have high mTBI exposure. The purpose of this study was to determine the behavioural and neuropathological phenotypes induced by the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) model of mTBI in both wild-type (WT) and APP/PS1 mice up to 8 months post-injury. Methods Male WT and APP/PS1 littermates were randomized to sham or repetitive mild TBI (rmTBI; 2 × 0.5 J impacts 24 h apart) groups at 5.7 months of age. Animals were assessed up to 8 months post-injury for acute neurological deficits using the loss of righting reflex (LRR) and Neurological Severity Score (NSS) tasks, and chronic behavioural changes using the passive avoidance (PA), Barnes maze (BM), elevated plus maze (EPM) and rotarod (RR) tasks. Neuropathological assessments included white matter damage; grey matter inflammation; and measures of Aβ levels, deposition, and aducanumab binding activity. Results The very mild CHIMERA rmTBI conditions used here produced no significant acute neurological or motor deficits in WT and APP/PS1 mice, but they profoundly inhibited extinction of fear memory specifically in APP/PS1 mice over the 8-month assessment period. Spatial learning and memory were affected by both injury and genotype. Anxiety and risk-taking behaviour were affected by injury but not genotype. CHIMERA rmTBI induced chronic white matter microgliosis, axonal injury and astrogliosis independent of genotype in the optic tract but not the corpus callosum, and it altered microgliosis in APP/PS1 amygdala and hippocampus. Finally, rmTBI did not alter long-term tau, Aβ or amyloid levels, but it increased aducanumab binding activity. Conclusions CHIMERA is a useful model to investigate the chronic consequences of rmTBI, including behavioural abnormalities consistent with features of post-traumatic stress disorder and inflammation of both white and grey matter. The presence of human Aβ greatly modified extinction of fear memory after rmTBI.

Female, elderly, and obese individuals are at greater risk than male, young, and non-obese individuals for neck injury in otherwise equivalent automotive collisions. The development of effective safety technologies to protect all occupants requires high quality data from a range of biomechanical test subjects representative of the population at risk. Here we sought to quantify the demographic characteristics of the volunteers and post-mortem human subjects (PMHSs) used to create the available biomechanical data for the human neck during automotive impacts. A systematic literature and database search was conducted to identify kinematic data that could be used to characterize the neck response to inertial loading or direct head/body impacts. We compiled the sex, age, height, weight, and body mass index (BMI) for 999 volunteers and 110 PMHSs exposed to 5,431 impacts extracted from 63 published studies and three databases, and then compared the distributions of these parameters to reference data drawn from the neck-injured, fatally-injured, and general populations. We found that the neck biomechanical data were biased toward males, the volunteer data were younger, and the PMHS data were older than the reference populations. Other smaller biases were also noted, particularly within female distributions, in the height, weight, and BMI distributions relative to the neck-injured populations. It is vital to increase the diversity of volunteer and cadaveric test subjects in future studies in order to fill the gaps in the current neck biomechanical data. This increased diversity will provide critical data to address existing inequities in automotive and other safety technologies.

Background Glial fibrillary acidic protein (GFAP) has emerged as a promising fluid biomarker for several neurological indications including traumatic brain injury (TBI), a leading cause of death and disability worldwide. In humans, serum or plasma GFAP levels can predict brain abnormalities including hemorrhage on computed tomography (CT) scans and magnetic resonance imaging (MRI). However, assays to quantify plasma or serum GFAP in preclinical models are not yet available. Methods We developed and validated a novel sensitive GFAP immunoassay assay for mouse plasma on the Meso Scale Discovery immunoassay platform and validated assay performance for robustness, precision, limits of quantification, dilutional linearity, parallelism, recovery, stability, selectivity, and pre-analytical factors. To provide proof-of-concept data for this assay as a translational research tool for TBI and Alzheimer’s disease (AD), plasma GFAP was measured in mice exposed to TBI using the Closed Head Impact Model of Engineered Rotational Acceleration (CHIMERA) model and in APP/PS1 mice with normal or reduced levels of plasma high-density lipoprotein (HDL). Results We performed a partial validation of our novel assay and found its performance by the parameters studied was similar to assays used to quantify human GFAP in clinical neurotrauma blood specimens and to assays used to measure murine GFAP in tissues. Specifically, we demonstrated an intra-assay CV of 5.0%, an inter-assay CV of 7.2%, a lower limit of detection (LLOD) of 9.0 pg/mL, a lower limit of quantification (LLOQ) of 24.8 pg/mL, an upper limit of quantification (ULOQ) of at least 16,533.9 pg/mL, dilution linearity of calibrators from 20 to 200,000 pg/mL with 90–123% recovery, dilution linearity of plasma specimens up to 32-fold with 96–112% recovery, spike recovery of 67–100%, and excellent analyte stability in specimens exposed to up to 7 freeze-thaw cycles, 168 h at 4 °C, 24 h at room temperature (RT), or 30 days at − 20 °C. We also observed elevated plasma GFAP in mice 6 h after TBI and in aged APP/PS1 mice with plasma HDL deficiency. This assay also detects GFAP in serum. Conclusions This novel assay is a valuable translational tool that may help to provide insights into the mechanistic pathophysiology of TBI and AD.

Study Design Microstructural investigation of mechanical load induced acute disc herniation on five animal models. Objective To compare how spinal discs in different animal models herniate under a standardized complex compressive load. Summary of Background Data Animal models in disc herniation research offer reduced degeneration‐associated variability, lower cost, and greater availability compared to human specimens. However, there is limited consensus regarding which species is best suited for modeling human herniation, making a comprehensive comparison of species‐specific herniation mechanisms necessary. Materials and Methods A standardized shear and compressive load, designed to herniate intervertebral discs, was applied to isolated discs of five cadaveric animal models (n = 30, 6 specimens per group): bovine tail, bovine lumbar, ovine lumbar, porcine lumbar, and porcine cervical. The segments were flexed (7°), and a shear‐compressive load was applied at a crosshead displacement rate of 40 mm min−1, until a force drop, or a displacement limit was reached (~80% of disc height). Microstructural analysis was undertaken to identify failure modes. Results Clinically relevant herniation features were observed in all models—including endplate and annulus fibrosus (AF) tearing, AF delamination, vertebral body (VB) fracture, nucleus pulposus (NP) extrusion into VB, and radial NP movement. Bovine lumbar, porcine cervical, and porcine lumbar segments exhibited high rates of radial NP movement (84%, 100%, and 67%, respectively), with ovine lumbar discs displaying VB fracture (84%) and NP extrusions into the VB (67%). Bovine tail discs showed minimal damage but were characterized by sequential lamellar AF tears (67%). Conclusions Porcine cervical, bovine lumbar, and porcine lumbar discs are suitable for annulus‐failure herniation research, although porcine cervical discs may be the most appropriate due to exhibiting the highest rate of relevant damages. Ovine lumbar discs are relevant for studying endplate junction failure herniations, and bovine tail discs are appropriate for implant‐related studies.

[This corrects the article DOI: 10.1371/journal.pone.0200952.].