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1.
J Biomech Eng ; 146(9)2024 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-38511299

RESUMO

Side and frontal airbag deployment represents the main injury mechanism to the upper extremity during automotive collisions. Previous dynamic injury limit research has been limited to testing the forearm at either the assumed most vulnerable location to fracture, the distal 1/3rd, or the midpoint. Studies have varied the surface to which impacts were applied, with no clear consensus on the site of greatest vulnerability. The unpredictability of airbag impact location, especially with altered hand positioning, limits the effectiveness of existing forearm injury limits determined from impacts at only one location. The current study quantified the effect of impacts at alternative locations on injury risk along the forearm using the THUMS FE model. Airbag-level impacts were simulated along the forearm on all four anatomical surfaces. Results showed the distal 1/3rd is not the most vulnerable location (for any side), indicating forearm fracture is not solely driven by area moment of inertia (as previously assumed). The posterior forearm was the weakest, suggesting that current test standards underestimate the fracture risk of the forearm. Linear regression models showed strong correlation between forearm fracture risk and bone geometry (cross-sectional area and area moment of inertia) as well as soft-tissue depth, potentially providing the ability to predict forearm injury tolerances for any location or forearm size. This study demonstrated the forearm's vulnerability to fracture from airbag deployments, indicating the need for safety systems to better address injury mechanisms for the upper limb to effectively protect drivers.


Assuntos
Air Bags , Traumatismos do Antebraço , Fraturas Ósseas , Humanos , Antebraço , Acidentes de Trânsito , Análise de Elementos Finitos
2.
J Alzheimers Dis ; 94(3): 977-991, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37355890

RESUMO

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is a master cytokine involved in a variety of inflammatory and neurological diseases, including Alzheimer's disease (AD). Therapies that block TNF-α proved ineffective as therapeutic for neurodegenerative diseases, which might be explained by the opposing functions of the two receptors of TNF (TNFRs): while TNFR1 stimulation mediates inflammatory and apoptotic pathways, activation of TNFR2 is related to neuroprotection. Despite the success of targeting TNFR2 in a transgenic AD mouse model, research that better mimics the human context is lacking. OBJECTIVE: The aim of this study is to investigate whether stimulation of TNFR2 with a TNFR2 agonist is effective in activating human TNFR2 and attenuating AD neuropathology in the J20xhuTNFR2-k/i mouse model. METHODS: Transgenic amyloid-ß (Aß)-overexpressing mice containing a human extracellular TNFR2 domain (J20xhuTNFR2-k/i) were treated with a TNFR2 agonist (NewStar2). After treatment, different behavioral tests and immunohistochemical analysis were performed to assess different parameters, such as cognitive functions, plaque deposition, synaptic plasticity, or microglial phagocytosis. RESULTS: Treatment with NewStar2 in J20xhuTNFR2-k/i mice resulted in a drastic decrease in plaque load and beta-secretase 1 (BACE-1) compared to controls. Moreover, TNFR2 stimulation increased microglial phagocytic activity, leading to enhanced Aß clearance. Finally, activation of TNFR2 rescued cognitive impairments and improved synaptic plasticity. CONCLUSION: Our findings demonstrate that activation of human TNFR2 ameliorates neuropathology and improves cognitive functions in an AD mouse model. Moreover, our study confirms that the J20xhuTNFR2-k/i mouse model is suitable for testing human TNFR2-specific compounds.


Assuntos
Doença de Alzheimer , Receptores Tipo II do Fator de Necrose Tumoral , Camundongos , Humanos , Animais , Receptores Tipo II do Fator de Necrose Tumoral/genética , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Receptores Tipo II do Fator de Necrose Tumoral/uso terapêutico , Doença de Alzheimer/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Camundongos Transgênicos , Peptídeos beta-Amiloides/metabolismo , Plasticidade Neuronal
3.
J Biomech Eng ; 144(9)2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35348623

RESUMO

Ballistic shields are used by military and police members in dangerous situations to protect the user against threats such as gunfire. When struck, the shield material deforms to absorb the incoming kinetic energy of the projectile. If the rapid back-face deformation contacts the arm, it can potentially impart a large force, leading to injury risk, termed behind armor blunt trauma (BABT). This work characterized the loading profiles due to the contact between the deforming back-face of the shield and the arm using a modified upper extremity anthropomorphic test device (ATD). This ATD measured forces at the hand, wrist, forearm, and elbow to compare the locational effects of the force transfer for future investigations of fracture risk. Two composite ballistic shields, both with the same ballistic protection rating, were investigated and had statistically different responses to the same impact conditions, indicating a further need for shield safety evaluation. Additionally, ballistic force curves were compared among stand-off distances, defined as the distance between the back-face of the shield and the front of the force sensor, where the peak impact force significantly decreased with increased stand-off. This study presents the first highly instrumented ATD upper limb capable of evaluating BABT and characterization of these loading profiles. This work demonstrates the importance of realistic boundary conditions as loading varies by anatomical location. Stand-off distance is an effective method to reduce loading and should be considered in future shield design iterations and standards that are developed using this device.


Assuntos
Ferimentos não Penetrantes , Humanos , Extremidade Superior
4.
J Biomech Eng ; 144(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34259862

RESUMO

Foot injuries as a result of automotive collisions are frequent and impactful. Anthropomorphic test devices (ATDs), used to assess injury risk during impact scenarios such as motor vehicle collisions, typically assess risk of foot/ankle injuries by analyzing data in tibia load cells. The peak axial force and the tibia index are metrics commonly used to evaluate risk of injury to the lower extremity but do not directly account for injury risk to the foot, or the risk of injury associated with out-of-position loading. Two ATDs, the Hybrid III lower leg and the Military Lower Extremity, were exposed to axial impacts at seven different ankle postures. An array of piezoresistive sensors located on the insole of a boot was employed during these tests to assess the load distribution variations among postures and between ATD models on the plantar surface of the foot. Both posture and ATD model affected the load distribution on the foot, highlighting the need for regional injury risk assessments in this vulnerable anatomical region. The increase in forefoot loading during plantarflexion was not reflected in the standard industry metrics of peak axial force or tibia index, suggesting that increased fracture risk to the forefoot would not be detected. The variations in load distribution between the models could also alter injury risk assessment in frontal collisions based on differences in attenuation. These data could be used for regional foot injury assessment and to inform the design of an improved ATD foot.


Assuntos
Traumatismos do Pé , Militares , Acidentes de Trânsito , Tornozelo/fisiologia , Fenômenos Biomecânicos , Humanos , Extremidade Inferior , Postura
5.
J Biomech Eng ; 141(2)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30383174

RESUMO

Lower leg injuries commonly occur in frontal automobile collisions, and are associated with high disability rates. Accurate methods to predict these injuries must be developed to facilitate the testing and improvement of vehicle safety systems. Anthropomorphic test devices (ATDs) are often used to assess injury risk by mimicking the behavior of the human body in a crash while recording data from sensors at discrete locations, which are then compared to established safety limits developed by cadaveric testing. Due to the difference in compliance of cadaveric and ATD legs, the force dissipating characteristics of footwear, and the lack of direct measurement of injury risk to the foot and ankle, a novel instrumented insole was developed that could be applied equally to all specimens both during injury limit generation and during safety evaluation tests. An array of piezoresistive sensors were calibrated over a range of speeds using a pneumatic impacting apparatus, and then applied to the insole of a boot. The boot was subsequently tested and compared to loads measured using ankle and toe load cells in an ATD, and found to have an average error of 10%. The sensors also provided useful information regarding the force distribution across the sole of the foot during an impact, which may be used to develop regional injury criteria. This work has furthered the understanding of lower leg injury prediction and developed a tool that may be useful in developing accurate injury criteria in the future for the foot and lower leg.

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