Design of a simplified cranial substitute with a modal behavior close to that of a human skull.

Individuals exposed to the propagation of shock waves generated by the detonation of explosive charges may suffer Traumatic Brain Injury. The mechanism of cranial deflection is one of many hypotheses that could explain the observed brain damage. To investigate this physical phenomenon in a reproducible manner, a new simplified cranial substitute was designed with a mechanical response close to that of a human skull when subjected to this type of loading. As a first step, a Finite Element Model was employed to dimension the new substitute. The objective was indeed to obtain a vibratory behavior close to that of a dry human skull over a wide range of frequencies up to 10 kHz. As a second step, the Finite Element Model was used together with Experimental Modal Analyses to identify the vibration modes of the substitute. A shaker excited the structure via a metal rod, while a laser vibrometer recorded the induced vibrations at defined measurement points. The results showed that despite differences in material properties and geometry, the newly developed substitute has 10/13 natural frequencies in common with those of dry human skulls. When filled with a simulant of cerebral matter, it could therefore be used in future studies as an approximation to assess the mechanical response of a simplified skull substitute to a blast threat.

Cerebral and cognitive modifications in retired professional soccer players: TC-FOOT protocol, a transverse analytical study.

INTRODUCTION: Soccer is the most popular sport in the world. This contact sport carries the risk of exposure to repeated head impacts in the form of subconcussions, defined as minimal brain injuries following head impact, with no symptom of concussion. While it has been suggested that exposure to repetitive subconcussive events can result in long-term neurophysiological modifications, and the later development of chronic traumatic encephalopathy, the consequences of these repeated impacts remain controversial and largely unexplored in the context of soccer players. METHODS AND ANALYSIS: This is a prospective, single-centre, exposure/non-exposure, transverse study assessing the MRI and neuropsychological abnormalities in professional retired soccer players exposed to subconcussive impacts, compared with high-level athletes not exposed to head impacts. The primary outcome corresponds to the results of MRI by advanced MRI techniques (diffusion tensor, cerebral perfusion, functional MRI, cerebral volumetry and cortical thickness, spectroscopy, susceptibility imaging). Secondary outcomes are the results of the neuropsychological tests: number of errors and time to complete tests. We hypothesise that repeated subconcussive impacts could lead to morphological lesions and impact on soccer players' cognitive skills in the long term. ETHICS AND DISSEMINATION: Ethics approval has been obtained and the study was approved by the Comité de Protection des Personnes (CPP) No 2021-A01169-32. Study findings will be disseminated by publication in a high-impact international journal. Results will be presented at national and international imaging meetings. TRIAL REGISTRATION NUMBER: NCT04903015.

Influence of double rods and interbody cages on range of motion and rod stress after spinopelvic instrumentation: a finite element study.

PURPOSE: To compare instrumentation configurations consisting of bilateral single or double rods and additional interbody cages (IBCs) at different levels in terms of Range of Motion (ROM) and distribution of von Mises stress in rods. METHODS: A previously validated L1-pelvis finite element model was used and instrumented with configurations consisting of single or double bilateral rods and IBCs at multiple levels. Pure moments of 7.5 N.m were applied to L1 in main directions in addition to a follower load of 280 N. Global, segmental ROM and distribution of von Mises stress in rods were studied. RESULTS: All configurations reduced segmental and global ROM from 50 to 100% compared to the intact spine. Addition of IBCs slightly increased ROM at levels adjacent to the IBC placement. The simple rod configuration presented the highest von Mises stress (457 MPa) in principal rods at L5-S1 in flexion. Doubling rods and IBC placement reduced this value and shifted the location of maximum von Mises stress to other regions. Among studied configurations, double rods with IBCs at all levels (L2-S1) showed the lowest ROM. Maximal von Mises stresses in secondary rods were lower in comparison to main rods. CONCLUSIONS: Double rods and IBCs reduced global and segmental ROM as well as von Mises stress in rods. The results suggest a possible benefit in using both strategies to minimize pseudarthrosis and instrumentation failure. However, increased ROM in adjacent levels and the shift of maximal von Mises stress to adjacent areas might cause complications elsewhere.

Development of a flexible instrumented lumbar spine finite element model and comparison with in-vitro experiments.

Surgical corrections of degenerative lumbar scoliosis and sagittal malalignment are associated with significant complications, such as rod fractures and pseudarthrosis, particularly in the lumbosacral junction. Finite element studies can provide relevant insights to improve performance of spinal implants. The aim of the present study was to present the development of non-instrumented and instrumented Finite Element Models (FEMs) of the lumbopelvic spine and to compare numerical results with experimental data available in the literature. The lumbo-pelvic spine FEM was based on a CT-scan from an asymptomatic volunteer representing the 50th percentile male. In a first step a calibration of mechanical properties was performed in order to obtain a quantitative agreement between numerical results and experimental data for defect stages of spinal segments. Then, FEM results were compared in terms of range of motion and strains in rods to in-vitro experimental data from the literature for flexible non-instrumented and instrumented lumbar spines. Numerical results from the calibration process were consistent with experimental data, especially in flexion. A positive agreement was obtained between FEM and experimental results for the lumbar and sacroiliac segments. Instrumented FEMs predicted the same trends as experimental in-vitro studies. The instrumentation configuration consisting of double rods and an interbody cage at L5-S1 maximally reduced range of motion and strains in main rods and thus had the lowest risk of pseudarthrosis and rod fracture. The developed FEMs were found to be consistent with published experimental results; therefore they can be used for further post-operative complication investigations.

Development of a detailed human neck finite element model and injury risk curves under lateral impact.

Advanced neck finite element modeling and development of neck injury criteria are important for the design of optimal neck protection systems in automotive and other environments. They are also important in virtual tests. The objectives of the present study were to develop a detailed finite element model (FEM) of the human neck and couple it to the existing head model, validate the model with kinematic data from legacy human volunteer and human cadaver impact datasets, and derive lateral impact neck injury risk curves using survival analysis from the upper and lower neck forces and moments. The detailed model represented the anatomy of a young adult mid-size male. It included all the cervical and first thoracic vertebrae, intervening discs, upper and lower spinal ligaments, bilateral facet joints, and passive musculature. Material properties were obtained from literature. Frontal, oblique, and lateral impacts to the distal end of the model was applied based on human volunteer and human cadaver experimental data. Corridor and cross-correlation methods were used for validation. The CORrelation and Analysis (CORA) score was used for objective assessments. Forces and moments were obtained at the occipital condyles (OC) and T1, and parametric survival analysis was used to derive injury risk curves to define human neck injury tolerance to lateral impact. The Brier Score Metric (BSM) was used to determine the hierarchical sequence among the injury metrics. The CORA scores for the lateral, frontal, and oblique impact loading conditions were 0.80, 0.91, and 0.87, respectively, for human volunteer data, and the mean score was 0.7 for human cadaver lateral impacts. Injury risk curves along with ±95% confidence intervals are given for all the four biomechanical metrics. The OC shear force was the optimal metric based on the BSM. A force of 1.5 kN was associated with the 50% probability level of AIS3+ neck injury. As a first step, the presented risk curves serve as human tolerance criteria under lateral impact, hitherto not available in published literatures, and they can be used in virtual testing and advancing restraint systems for improving human safety.

Epigenetics meets GPCR: inhibition of histone H3 methyltransferase (G9a) and histamine H3 receptor for Prader-Willi Syndrome.

The role of epigenetic regulation is in large parts connected to cancer, but additionally, its therapeutic claim in neurological disorders has emerged. Inhibition of histone H3 lysine N-methyltransferase, especially G9a, has been recently shown to restore candidate genes from silenced parental chromosomes in the imprinting disorder Prader-Willi syndrome (PWS). In addition to this epigenetic approach, pitolisant as G-protein coupled histamine H3 receptor (H3R) antagonist has demonstrated promising therapeutic effects for Prader-Willi syndrome. To combine these pioneering principles of drug action, we aimed to identify compounds that combine both activities, guided by the pharmacophore blueprint for both targets. However, pitolisant as selective H3R inverse agonist with FDA and EMA-approval did not show the required inhibition at G9a. Pharmacological characterization of the prominent G9a inhibitor A-366, that is as well an inhibitor of the epigenetic reader protein Spindlin1, revealed its high affinity at H3R while showing subtype selectivity among subsets of the histaminergic and dopaminergic receptor families. This work moves prominent G9a ligands forward as pharmacological tools to prove for a potentially combined, symptomatic and causal, therapy in PWS by bridging the gap between drug development for G-protein coupled receptors and G9a as an epigenetic effector in a multi-targeting approach.

Protection performance of bicycle helmets.

INTRODUCTION: The evaluation of head protection systems needs proper knowledge of the head impact conditions in terms of impact speed and angle, as well as a realistic estimation of brain tolerance limits. In current bicycle helmet test procedures, both of these aspects should be improved. METHOD: The present paper suggests a bicycle helmet evaluation methodology based on realistic impact conditions and consideration of tissue level brain injury risk, in addition to well known headform kinematic parameters. The method is then applied to a set of 32 existing helmets, leading to a total of 576 experimental impact tests followed by 576 numerical simulations of the brain response. RESULTS: It is shown that the most critical impacts are the linear-lateral ones as well as the oblique impact leading to rotation around the vertical axis (ZRot), leading both to around 50% risks of moderate neurological injuries. Based on this test method, the study enables us to compare the protection capability of a given helmet and eventually to compare helmets via a dedicated rating system.

Lung injury risk assessment during blast exposure.

Blast pulmonary trauma are common consequences of modern war and terrorism action. To better protect soldiers from that threat, the injury risk level when protected and unprotected must be assessed. Knowing from the literature that a possible amplification of the blast threat would be provided by some thoracic protective systems, the objective is to propose an original approach to correlate a measurable parameter on a manikin with a pulmonary risk level. Using a manikin whose response is correlated with the proposed tolerance limits should help in the evaluation of thoracic protective system regarding injury outcomes. A database including lung injury data from large mammals have been created, allowing the definition of iso-impulse tolerance limits from no lung injury to severe ones (∼60% of ecchymosis). As the use of this metric is not sufficient to evaluate the performance of protective systems on a manikin, the iso-impulse tolerance limits were associated with the thoracic response of post-mortem swine under blast loading. It was found that the lung injury threshold in terms of incident impulse is 58.3 kPa·ms, corresponding to a chest wall peak of acceleration/velocity/displacement of 7350 m/s2, 3.7 m/s and 6.4 mm respectively. Lung injuries are considered as severe (30-60% of ecchymosis) when the incident impulse exceed 232.8 kPa·ms, leading to a chest wall peak of acceleration/velocity/displacement of 79.7 km/s2, 14.7 m/s and 30.1 mm respectively. The defined lung tolerance limits are valid for a 50 kg swine (unprotected) exposed side-on to the blast threat and against a wall.

Evaluation of a novel bicycle helmet concept in oblique impact testing.

BACKGROUND: A novel bicycle helmet concept has been developed to mitigate rotational head acceleration, which is a predominant mechanism of traumatic brain injury (TBI). This WAVECEL concept employs a collapsible cellular structure that is recessed within the helmet to provide a rotational suspension. This cellular concept differs from other bicycle helmet technologies for mitigation of rotational head acceleration, such as the commercially available Multi-Directional Impact Protection System (MIPS) technology which employs a slip liner to permit sliding between the helmet and the head during impact. This study quantified the efficacy of both, the WAVECEL cellular concept, and a MIPS helmet, in direct comparison to a traditional bicycle helmet made of rigid expanded polystyrene (EPS). METHODS: Three bicycle helmet types were subjected to oblique impacts in guided vertical drop tests onto an angled anvil: traditional EPS helmets (CONTROL group); helmets with a MIPS slip liner (SLIP group); and helmets with a WAVECEL cellular structure (CELL group). Helmet performance was evaluated using 4.8 m/s impacts onto anvils angled at 30°, 45°, and 60° from the horizontal plane. In addition, helmet performance was tested at a faster speed of 6.2 m/s onto the 45° anvil. Five helmets were tested under each of the four impact conditions for each of the three groups, requiring a total of 60 helmets. Headform kinematics were acquired and used to calculate an injury risk criterion for Abbreviated Injury Score (AIS) 2 brain injury. RESULTS: Linear acceleration of the headform remained below 90 g and was not associated with the risk of skull fracture in any impact scenario and helmet type. Headform rotational acceleration in the CONTROL group was highest for 6.2 m/s impacts onto the 45° anvil (7.2 ± 0.6 krad/s2). In this impact scenario, SLIP helmets and CELL helmets reduced rotational acceleration by 22% (p = 0003) and 73% (p < 0.001), respectively, compared to CONTROL helmets. The CONTROL group had the highest AIS 2 brain injury risk of 59 ± 8% for 6.2 m/s impacts onto the 45° anvil. In this impact scenario, SLIP helmets and CELL helmets reduced the AIS 2 brain injury risk to 34.2% (p = 0.001) and 1.2% (p < 0.001), respectively, compared to CONTROL helmets. DISCUSSION: Results of this study are limited to a narrow range of impact conditions, but demonstrated the potential that rotational acceleration and the associated brain injury risk can be significantly reduced by the cellular WAVECEL concept or a MIPS slip liner. Results obtained under specific impact angles and impact velocities indicated performance differences between these mechanisms. These differences emphasize the need for continued research and development efforts toward helmet technologies that further improve protection from brain injury over a wide range a realistic impact parameters.

Development of a finite-element eye model to investigate retinal hemorrhages in shaken baby syndrome.

Retinal hemorrhages (RH) are among injuries sustained by a large number of shaken baby syndrome victims, but also by a small proportion of road accident victims. In order to have a better understanding of the underlying of RH mechanisms, we aimed to develop a complete human eye and orbit finite element model. Five occipital head impacts, at different heights and on different surfaces, and three shaking experiments were conducted with a 6-week-old dummy (Q0 dummy). This allowed obtaining a precise description of the motion in those two specific situations, which was then used as input for the eye model simulation. Results showed that four parameters (pressure, Von Mises stress and strain, 1st principal stress) are relevant for shaking-fall comparison. Indeed, in the retina, the softest shaking leads to pressure that is 4 times higher than the most severe impact (1.43 vs. 0.34 kPa). For the Von Mises stress, strain and 1st principal stress, this ratio rises to 4.27, 6.53 and 14.74, respectively. Moreover, regions of high stress and strain in the retina and the choroid were identified and compared to what is seen on fundoscopy. The comparison between linear and rotational acceleration in fall and shaking events demonstrated the important role of the rotational acceleration in inducing such injuries. Even though the eye model was not validated, the conclusion of this study is that compared to falls, shaking an infant leads to extreme eye loading as demonstrated by the values taken by the four mentioned mechanical parameters in the retina and the choroid.