Low Expression of Lipoic Acid Synthase Aggravates Silica-Induced Pulmonary Fibrosis by Inhibiting the Differentiation of Tregs in Mice.

Aims: In addition to reducing the respiratory function, crystalline silica (SiO2) disturbs the immune response by affecting immune cells during the progression of silicosis. Regulatory T cell (Treg) differentiation may play a key role in the abnormal polarization of T helper cell (Th)1 and Th2 cells in the development of silicosis-induced fibrosis. Alpha-lipoic acid (ALA) has immunomodulatory effects by promoting Tregs differentiation. Thus, ALA may have a therapeutic potential for treating autoimmune disorders in patients with silicosis. However, little is known regarding whether ALA regulates the immune system during silicosis development. Results: We found that the expression levels of collagen increased, and the antioxidant capacity was lower in the Lias-/-+SiO2 group than in the Lias+/++SiO2 group. The proportion of Tregs decreased in the peripheral blood and spleen tissue in mice exposed to SiO2. The proportion of Tregs in the Lias-/-+SiO2 group was significantly lower than that in the Lias+/++SiO2 group. Supplementary exogenous ALA attenuates the accumulation of inflammatory cells and extracellular matrix in lung tissues. ALA promotes the immunological balance between Th17 and Treg responses during the development of silicosis-induced fibrosis. Innovation and Conclusion: Our findings confirmed that low expression of lipoic acid synthase aggravates SiO2-induced silicosis, and that supplementary exogenous ALA has therapeutic potential by improving Tregs in silicosis fibrosis.

Experimental model for civilian ballistic brain injury biomechanics quantification.

Biomechanical quantification of projectile penetration using experimental head models can enhance the understanding of civilian ballistic brain injury and advance treatment. Two of the most commonly used handgun projectiles (25-cal, 275 m/s and 9 mm, 395 m/s) were discharged to spherical head models with gelatin and Sylgard simulants. Four ballistic pressure transducers recorded temporal pressure distributions at 308kHz, and temporal cavity dynamics were captured at 20,000 frames/second (fps) using high-speed digital video images. Pressures ranged from 644.6 to -92.8 kPa. Entry pressures in gelatin models were higher than exit pressures, whereas in Sylgard models entry pressures were lower or equivalent to exit pressures. Gelatin responded with brittle-type failure, while Sylgard demonstrated a ductile pattern through formation of micro-bubbles along projectile path. Temporary cavities in Sylgard models were 1.5-2x larger than gelatin models. Pressures in Sylgard models were more sensitive to projectile velocity and diameter increase, indicating Sylgard was more rate sensitive than gelatin. Based on failure patterns and brain tissue rate-sensitive characteristics, Sylgard was found to be an appropriate simulant. Compared with spherical projectile data, full-metal jacket (FMJ) projectiles produced different temporary cavity and pressures, demonstrating shape effects. Models using Sylgard gel and FMJ projectiles are appropriate to enhance understanding and mechanisms of ballistic brain injury.

Moment-rotation responses of the human lumbosacral spinal column.

The objective of this study was to test the hypothesis that the human lumbosacral joint behaves differently from L1-L5 joints and provides primary moment-rotation responses under pure moment flexion and extension and left and right lateral bending on a level-by-level basis. In addition, range of motion (ROM) and stiffness data were extracted from the moment-rotation responses. Ten T12-S1 column specimens with ages ranging from 27 to 68 years (mean: 50.6+/-13.2) were tested at a load level of 4.0 N m. Nonlinear flexion and extension and left and right lateral bending moment-rotation responses at each spinal level are reported in the form of a logarithmic function. The mean ROM was the greatest at the L5-S1 level under flexion (7.37+/-3.69 degrees) and extension (4.62+/-2.56 degrees) and at the L3-L4 level under lateral bending (4.04+/-1.11 degrees). The mean ROM was the least at the L1-L2 level under flexion (2.42+/-0.90 degrees), L2-L3 level under extension (1.58+/-0.63 degrees), and L1-L2 level under lateral bending (2.50+/-0.75 degrees). The present study proved the hypothesis that L5-S1 motions are significantly greater than L1-L5 motions under flexion and extension loadings, but the hypothesis was found to be untrue under the lateral bending mode. These experimental data are useful in the improved validation of FE models, which will increase the confidence of stress analysis and other modeling applications.

Validation of a clinical finite element model of the human lumbosacral spine.

Very few finite element models on the lumbosacral spine have been reported because of its unique biomechanical characteristics. In addition, most of these lumbosacral spine models have been only validated with rotation at single moment values, ignoring the inherent nonlinear nature of the moment-rotation response of the spine. Because a majority of lumbar spine surgeries are performed between L4 and S1 levels, and the confidence in the stress analysis output depends on the model validation, the objective of the present study was to develop a unique finite element model of the lumbosacral junction. The clinically applicable model was validated throughout the entire nonlinear range. It was developed using computed tomography scans, subjected to flexion and extension, and left and right lateral bending loads, and quantitatively validated with cumulative variance analyses. Validation results for each loading mode and for each motion segment (L4-L5, L5-S1) and bisegment (L4-S1) are presented in the paper.

Effects of tissue preservation temperature on high strain-rate material properties of brain.

Postmortem preservation conditions may be one of factors contributing to wide material property variations in brain tissues in literature. The objective of present study was to determine the effects of preservation temperatures on high strain-rate material properties of brain tissues using the split Hopkinson pressure bar (SHPB). Porcine brains were harvested immediately after sacrifice, sliced into 2 mm thickness, preserved in ice cold (group A, 10 samples) and 37°C (group B, 9 samples) saline solution and warmed to 37°C just prior to the test. A SHPB with tube aluminum transmission bar and semi-conductor strain gauges were used to enhance transmitted wave signals. Data were gathered using a digital acquisition system and processed to obtain stress-strain curves. All tests were conducted within 4 h postmortem. The mean strain-rate was 2487±72 s(-1). A repeated measures model with specimen-level random effects was used to analyze log transformed stress-strain responses through the entire loading range. The mean stress-strain curves with ±95% confidence bands demonstrated typical power relationships with the power value of 2.4519 (standard error, 0.0436) for group A and 2.2657 (standard error, 0.0443) for group B, indicating that responses for the two groups are significantly different. Stresses and tangent moduli rose with increasing strain levels in both groups. These findings indicate that storage temperatures affected brain tissue material properties and preserving tissues at 37°C produced a stiffer response at high strain-rates. Therefore, it is necessary to incorporate material properties obtained from appropriately preserved tissues to accurately predict the responses of brain using stress analyses models, such as finite element simulations.

Biomechanics of polyaryletherketone rod composites and titanium rods for posterior lumbosacral instrumentation. Presented at the 2010 Joint Spine Section Meeting. Laboratory investigation.

OBJECT: Interest is increasing in the development of polyaryletherketone (PAEK) implants for posterior lumbar fusion. Due to their inherent physical properties, including radiolucency and the ability to customize stiffness with carbon fiber reinforcement, they may be more advantageous than traditional instrumentation materials. Customization of these materials may allow for the development of a system that is stiff enough to promote fusion, yet flexible enough to avoid instrumentation failure. To understand the feasibility of using such materials in posterior lumbosacral instrumentation, biomechanical performances were compared in pure moment and combined loadings between two different PAEK composite rods and titanium rods. METHODS: Four human cadaver L3-S1 segments were subjected to pure moment and combined (compressionflexion and compression-extension) loadings as intact specimens, and after L-4 laminectomy with complete L4-5 facetectomy. Pedicle screw/rod fixation constructs were placed from L-4 to S-1, and retested with titanium, pure poly(aryl-ether-ether-ketone) (PEEK), and carbon fiber reinforced PEEK (CFRP) rods. Reflective markers were fixed to each spinal segment. The range of motion data for the L3-S1 column and L4-5 surgical level were obtained using a digital 6-camera system. Four prewired strain gauges were glued to each rod at the level of the L-4 screw and were placed 90° apart along the axial plane of the rod to record local strain data in the combined loading mode. Biomechanical data were analyzed using the ANOVA techniques. RESULTS: In pure moment, when compared with intact specimens, each rod material similarly restricted motion in each mode of bending, except axial rotation (p < 0.05). When compared with postfacetectomy specimens, each rod material similarly restricted motion (p < 0.05) in all bending modes. In combined loading, rod stiffness was similar for each material. Rod strain was the least in the titanium construct, intermediate in the CFRP construct, and maximal in the pure PEEK construct. CONCLUSIONS: Pure PEEK and CFRP rods confer equal stiffness and resistance to motion in lumbosacral instrumentation when compared with titanium constructs in single-cycle loading. The carbon fiber reinforcement reduces strain when compared with pure PEEK in single-cycle loading. These biomechanical responses, combined with its radiolucency, suggest that the CFRP may have an advantage over both titanium and pure PEEK rods as a material for use in posterior lumbosacral instrumentation. Benchtop fatigue testing of the CFRP constructs is needed for further examination of their responses under multicycle loading.

Severe-to-fatal head injuries in motor vehicle impacts.

Severe-to-fatal head injuries in motor vehicle environments were analyzed using the United States Crash Injury Research and Engineering Network database for the years 1997-2006. Medical evaluations included details and photographs of injury, and on-scene, trauma bay, emergency room, intensive care unit, radiological, operating room, in-patient, and rehabilitation records. Data were synthesized on a case-by-case basis. X-rays, computed tomography scans, and magnetic resonance images were reviewed along with field evaluations of scene and photographs for the analyses of brain injuries and skull fractures. Injuries to the parenchyma, arteries, brainstem, cerebellum, cerebrum, and loss of consciousness were included. In addition to the analyses of severe-to-fatal (AIS4+) injuries, cervical spine, face, and scalp trauma were used to determine the potential for head contact. Fatalities and survivors were compared using nonparametric tests and confidence intervals for medians. Results were categorized based on the mode of impact with a focus on head contact. Out of the 3178 medical cases and 169 occupants sustaining head injuries, 132 adults were in frontal (54), side (75), and rear (3) crashes. Head contact locations are presented for each mode. A majority of cases clustered around the mid-size anthropometry and normal body mass index (BMI). Injuries occurred at change in velocities (DeltaV) representative of US regulations. Statistically significant differences in DeltaV between fatalities and survivors were found for side but not for frontal impacts. Independent of the impact mode and survivorship, contact locations were found to be superior to the center of gravity of the head, suggesting a greater role for angular than translational head kinematics. However, contact locations were biased to the impact mode: anterior aspects of the frontal bone and face were involved in frontal impacts while temporal-parietal regions were involved in side impacts. Because head injuries occur at regulatory DeltaV in modern vehicles and angular accelerations are not directly incorporated in crashworthiness standards, these findings from the largest dataset in literature, offer a field-based rationale for including rotational kinematics in injury assessments. In addition, it may be necessary to develop injury criteria and evaluate dummy biofidelity based on contact locations as this parameter depended on the impact mode. The current field-based analysis has identified the importance of both angular acceleration and contact location in head injury assessment and mitigation.

Finite element analysis of the forearm crutch during reciprocal and swing-through gait - biomed 2009.

A finite element analysis of a commercial forearm crutch for children during gait is presented. The geometric features of the crutch structure were acquired and modeled. The finite element model was created using shell elements based on the frame surfaces. Linear elastic material properties for aluminum alloy were utilized. Upper extremity kinetic data from reciprocal and swing-through gait patterns were applied to the model as boundary conditions and loads. Stress distributions during two gait patterns were determined. Stress distributions during swing-through gait were found to be statistically greater than those during reciprocal gait (p = 0.01). This work provides novel quantitative data to improve crutch design and stimulate further analyses of upper extremity (UE) joint loads during forearm crutch-assisted gait in children with spina bifida (myelomeningocele).

Finite element analysis of forearm crutches during gait in children with myelomeningocele.

A finite element analysis of a commercial forearm crutch for children during gait is presented. The geometric features of the crutch structure were acquired and modeled. The finite element model was created using shell elements based on the frame surfaces. Linear elastic material properties for aluminum alloy were utilized. Upper extremity kinetic data from reciprocal and swing-through gait patterns were applied to the model as boundary conditions and loads. Stress distributions during two gait patterns were determined. Stress distributions during swing-through gait were found to be statistically greater than those during reciprocal gait (p = 0.01). This work provides novel quantitative data to improve crutch design and stimulate further analyses of upper extremity joint loads during forearm crutch-assisted gait in children with myelomeningocele (spina bifida).

Development of a lumbosacral spine finite element model using intact and surgically altered spines - biomed 2009.

A previously developed three-dimensional lumbosacral spine finite element (FE) model was extended and validated using both in vitro intact and surgically altered data. Four cadaveric lumbosacral spine segments (L3-Sacrum) were tested under flexion-extension up to 8.0 Nm. Moment rotation responses were obtained using a motion analysis system. A L3-S1 FE model was developed by adding L3 vertebra, L3-L4 interverterbral disc, and corresponding ligaments into the previous L4-S1 FE model. The predicted moment rotation responses in flexion from both intact and surgically altered models were in good agreement with in vitro data whereas minor difference was found in the extension response. This work serves as a pilot study to use the current FE model to fully match more in vitro data including lateral bending, axial rotation, and compressionflexion.

Importance of physical properties of the human head on head-neck injury metrics.

OBJECTIVES: To demonstrate the importance of using specimen-specific head physical properties in head-neck dynamics. METHODS: Eight postmortem human subjects were subjected to side impact. A 9-axis accelerometer package was used to obtain head translational accelerations. After test, the head was isolated at the skull base, circumference, breadth, and length were obtained, and mass, center of gravity, and occipital condylar locations and moments of inertia were determined. Using specimen-specific and gathered accelerations, 3-dimensional head center of gravity accelerations and forces and moments at the occipital condyles were computed. Head physical properties were also extracted from regression equations using external dimensions of each subject. Using these properties and gathered kinematics, above-described accelerations and forces and moments were computed and compared with specimen-specific results. RESULTS: Head masses predicted by stature and total body mass were more in close agreement with specimen-specific data than head masses predicted by head circumference or head circumference and head length. The center of gravity to the occipital condyle vector was shorter in the literature-based dataset than the actual specimen-specific vector. Differences in moments of inertias between predicted and specimen-specific data ranged from -15 to 59 percent. Variations in peak antero-posterior shear, lateral shear, and axial force ranged from -12 to 46 percent, -21 to 78 percent, and -17 to 50 percent. Differences in peak lateral moment, sagittal moment, and axial torque ranged from -45 to 78 percent, -86 to 327 percent, and -96 to 112 percent. These were normalized using specimen-specific data. CONCLUSIONS: Considerable variations in physical properties and injury metrics between data obtained from literature-based regression equations and actual data for each specimen suggest the critical importance of specimen-specific data to accurately describe the biodynamic response and establish tolerance criteria. Because neck dynamics control head kinematics (and vice versa), these results emphasize the need to determine physical properties of each specimen following impact tests.

Muscle force sensitivity of a finite element fracture risk assessment model in osteogenesis imperfecta - biomed 2009.

Osteogenesis imperfecta (OI) is a heritable bone fragility disorder characterized by skeletal deformities and increased bone fragility. There is currently no established clinical method for quantifying fracture risk in OI patients. A method for developing a finite element model of the femur to assist in fracture risk assessment of a selected patient with OI type I was created. The material properties were based on nanoindentation testing of OI bone specimens collected during routine surgery. Dynamic data from clinical gait analysis was used to prescribe joint reaction forces and moments in a quasi-static model. Muscle forces were prescribed according to current literature. Von Mises stresses were analyzed across all seven phases of the gait cycle and analyzed for sensitivity to changes in muscle forces. The model showed that the patient with OI was not at current risk for fracture during normal gait. The highest stress levels occurred during mid stance and loading response. Maximum von Mises stresses were most sensitive to the gluteal muscles. Insight provided by the model may be useful for similar clinical applications, more refined model development and an improved ability for fracture prediction.

A fracture risk assessment model of the femur in children with osteogenesis imperfecta (OI) during gait.

Osteogenesis imperfecta (OI) is a heritable bone fragility disorder characterized by skeletal deformities and increased bone fragility. There is currently no established clinical method for quantifying fracture risk in OI patients. This study begins the development of a patient-specific model for femur fracture risk assessment and prediction based on individuals' gait analysis data, bone geometry from imaging and material properties from nanoindentation (Young's modulus=19 GPa, Poisson's ratio=0.3). Finite element models of the femur were developed to assess fracture risk of the femur in a pediatric patient with OI type I. Kinetic data from clinical gait analysis was used to prescribe loading conditions on the femoral head and condyles along with muscle forces on the bone's surface. von Mises stresses were analyzed against a fracture strength of 115 MPa. The patient with OI whose femur was modeled showed no risk of femoral fracture during normal gait. The highest stress levels occurred during the mid-stance and loading responses phases of gait. The location of high stress migrated throughout the femoral diaphysis across the gait cycle. Maximum femoral stress levels occurred during the gait cycle phases associated with the highest loading. The fracture risk (fracture strength/von Mises stress), however, was low. This study provides a relevant method for combining functional activity, material property and analytical methods to improve patient monitoring.

Internal and external responses of anterior lumbar/lumbosacral fusion: nonlinear finite element analysis.

STUDY DESIGN: Determination of external and internal responses of the human lumbosacral spine using a validated 3-dimensional finite element model. OBJECTIVE: The objective of the present study was to evaluate the range of motion, disc stress, and facet joint pressure owing to anterior fusion at L4-L5 or L5-S1 level and compare with the intact spine. SUMMARY OF BACKGROUND DATA: A significant majority of finite element models of anterior lumbar interbody fusion are primarily focused on upper and middle levels, whereas lower spinal levels are most commonly treated with surgery. METHODS: A 3-dimensional L4-S1 finite element model, validated in the entire nonlinear range of the moment-rotation response, was used to determine ranges of motion, disc stress, and facet joint contact pressure under normal and 2 surgical conditions with bone graft and porous tantalum. Biomechanical responses were compared under flexion and extension loading between the 2 fusions and fusion masses and at the fused and intact segments. RESULTS: Moment-rotation responses were nonlinear under all conditions. The range of motion at the caudal level was greater than the range of motion at the rostral level in the intact spine. The range of motion of the L4-S1 spine decreased more with the caudal than rostral fusion and more with the tantulum than bone under both loading modes. Facet joint pressures increased more with the rostral than caudal fusion. Stresses in the adjacent disc were greater with the caudal than rostral fusion under both modes of loading. CONCLUSIONS: At the fused level, the caudal fusion imparted additional rigidity under flexion to the lumbosacral joint. Both fusion masses added flexibility to the adjacent segment. Under both fusion masses, increased facet joint pressure in the lumbosacral joint indicates the susceptibility of this transitional joint to long-term biomechanics-induced consequences. Increased facet joint pressures with the rostral fusion indicate that the posterior complex responds with increased load sharing, and may predispose the spine to facet-related arthropathy. Increased stresses in the adjacent disc with the caudal fusion under both modes of loading imply the potential to disc-related changes owing to long-term physiologic loading.

Influence of total laminectomy on the mechanical behavior of lumbosacral spine.

An anatomically accurate validated three-dimensional finite element model was used to investigate the biomechanical effects of total laminectomy on the mechanical behavior of human lumbosacral spine. A total laminectomy was simulated at L4 or L5. Flexion, extension and lateral bending were applied using pure moment. Rotations were obtained under each loading mode. Maximum von Mises stresses in the annulus fibrosis under different loading were also obtained. It was found that L5 laminectomy has a greater influence on spinal column rotation. The maximum stress in the annulus increased significantly in L5 laminectomy model but not in the L4 model.

Effects of total facetectomy on the stability of lumbosacral spine.

In present study, an anatomically accurate, validated in the entirenonlinear domain, three-dimensional finite elementmodel was used to investigate the biomechanical effects of facetectomy on the stability of the human lumbosacral spine. Bilateral total facetectomy was simulated at L4-L5 and L5-S1 levels. Flexion, extension, and axial torsion were applied using pure moment protocols. Total facetectomy increased spinal instability significantly under extension and axial rotation and not under flexion.

Automating 3D meshing method for patient-specific modeling.

The purpose of this study was to develop an automating meshing method for patient-specific modeling. Three-dimensional geometries of two six-month-old infant heads were reconstructed from the CT data. Finite element meshes including cranial bone of skull, brain, and suture were generated. Both static and dynamic analyses were performed to verify the models. The study for blunt impact of infant head was performed by using these patient-specific models.