Anti-fibrillogenic and fibril destabilizing effects of metal ions on cystatin fibrils

Metals such as Cu²⁺, Fe³⁺, and Zn²⁺ are major contributors to the biology of a brain in stages of health, aging, and disease because of their unique effects on both protein structures (misfolding) and oxidative stress. The relationship between metal ions and neurodegenerative diseases is very complicated. Our study highlights how metal ions influence amyloid formation at low pH and on preformed amyloid fibrils. By using thioflavin T assay, ANS fluorescence, Congo red assay, circular dichroism, and microscopy to elucidate the effects of Cu²⁺, Fe³⁺, and Zn²⁺ on goat brain cystatin (GBC) aggregation at low pH. Results showed that Cu²⁺ and Fe³⁺ inhibit fibril formation of GBC by promoting amorphous aggregates. However, Zn²⁺ exclusively promotes fibril formation at low pH, leading to the formation of more ordered aggregates. Furthermore, the combined results of these complementary methods also suggested that Cu²⁺ and Fe³⁺ destabilize the β-sheet secondary structure of preformed amyloid fibrils of GBC.     

Finite element analysis of different loading conditions for implant-supported overdentures supported by conventional or mini implants

The effect of implants’ number on overdenture stability and stress distribution in edentulous mandible, implants and overdenture was numerically investigated for implant-supported overdentures. Three models were constructed. Overdentures were connected to implants by means of ball head abutments and rubber ring. In model 1, the overdenture was retained by two conventional implants; in model 2, by four conventional implants; and in model 3, by five mini implants. The overdenture was subjected to a symmetrical load at an angle of 20 degrees to the overdenture at the canine regions and vertically at the first molars. Four different loading conditions with two total forces (120, 300 N) were considered for the numerical analysis. The overdenture displacement was about 2.2 times higher when five mini implants were used rather than four conventional implants. The lowest stress in bone bed was observed with four conventional implants. Stresses in bone were reduced by 61% in model 2 and by 6% in model 3 in comparison to model 1. The highest stress was observed with five mini implants. Stresses in implants were reduced by 76% in model 2 and 89% increased in model 3 compared to model 1. The highest implant displacement was observed with five mini implants. Implant displacements were reduced by 29% in model 2, and increased by 273% in model 3 compared to model 1. Conventional implants proved better stability for overdenture than mini implants. Regardless the type and number of implants, the stress within the bone and implants are below the critical limits.     

Integration of multi-objective structural optimization into cementless hip prosthesis design: Improved Austin-Moore model

A new strategy of multi-objective structural optimization is integrated into Austin-Moore prosthesis in order to improve its performance. The new resulting model is so-called Improved Austin-Moore. The topology optimization is considered as a conceptual design stage to sketch several kinds of hollow stems according to the daily loading cases. The shape optimization presents the detailed design stage considering several objectives. Here, A new multiplicative formulation is proposed as a performance scale in order to define the best compromise between several requirements. Numerical applications on 2D and 3D problems are carried out to show the advantages of the proposed model.     

Partitioning of knee joint internal forces in gait is dictated by the knee adduction angle and not by the knee adduction moment

Medial knee osteoarthritis is a debilitating disease. Surgical and conservative interventions are performed to manage its progression via reduction of load on the medial compartment or equivalently its surrogate measure, the external adduction moment. However, some studies have questioned a correlation between the medial load and adduction moment. Using a musculoskeletal model of the lower extremity driven by kinematics–kinetics of asymptomatic subjects at gait midstance, we aim here to quantify the relative effects of changes in the knee adduction angle versus changes in the adduction moment on the joint response and medial/lateral load partitioning. The reference adduction rotation of 1.6° is altered by ±1.5° to 3.1° and 0.1° or the knee reference adduction moment of 17 N m is varied by ±50% to 25.5 N m and 8.5 N m. Quadriceps, hamstrings and tibiofemoral contact forces substantially increased as adduction angle dropped and diminished as it increased. The medial/lateral ratio of contact forces slightly altered by changes in the adduction moment but a larger adduction rotation hugely increased this ratio from 8.8 to a 90 while in contrast a smaller adduction rotation yielded a more uniform distribution. If the aim in an intervention is to diminish the medial contact force and medial/lateral load ratio, a drop of 1.5° in adduction angle is much more effective (causing respectively 12% and 80% decreases) than a reduction of 50% in the adduction moment (causing respectively 4% and 13% decreases). Substantial role of changes in adduction angle is due to the associated alterations in joint nonlinear passive resistance. These findings explain the poor correlation between knee adduction moment and tibiofemoral compartment loading during gait suggesting that the internal load partitioning is dictated by the joint adduction angle.     

Virtual traumatology of pregnant women: The PRegnant car Occupant Model for Impact Simulations (PROMIS)

This study report documents the development of a finite element (FE) model for analyzing trauma in pregnant women involved in road accidents and help the design of a specific safety device. The model is representative of a 50th percentile pregnant woman at 26 weeks of pregnancy in sitting position. To achieve this, the HUMOS 2 model, which has been validated in a wide range of dynamic tests, was scaled to the morphology of a woman in the 50th percentile and coupled with a model of gravid uterus. During scaling, special attention was paid to the pelvic region which is known to differ considerably in morphological terms between men and women. The gravid uterus model includes a placenta, a fetus, uterosacral ligaments and the amniotic fluid by means of fluid structure interaction formulation. The uterus and the female model were coupled using an original method whereby the growth of an uterus was simulated to compress the abdominal organs in a realistic manner. The model was validated based on experimental tests described in the literature. Additional tests based on abdominal loadings with a seatbelt on Post Mortem Human Surrogates (PMHS) coupled to silicone uterus were also performed.     

Temporal changes of mechanical signals and extracellular composition in human intervertebral disc during degenerative progression

In this study, a three-dimensional finite element model was used to investigate the changes in tissue composition and mechanical signals within human lumbar intervertebral disc during the degenerative progression. This model was developed based on the cell-activity coupled mechano-electrochemical mixture theory. The disc degeneration was simulated by lowering nutrition levels at disc boundaries, and the temporal and spatial distributions of the fixed charge density, water content, fluid pressure, Von Mises stress, and disc deformation were analyzed. Results showed that fixed charge density, fluid pressure, and water content decreased significantly in the nucleus pulposus (NP) and the inner to middle annulus fibrosus (AF) regions of the degenerative disc. It was found that, with degenerative progression, the Von Mises stress (relative to that at healthy state) increased within the disc, with a larger increase in the outer AF region. Both the disc volume and height decreased with the degenerative progression. The predicted results of fluid pressure change in the NP were consistent with experimental findings in the literature. The knowledge of the variations of temporal and spatial distributions of composition and mechanical signals within the human IVDs provide a better understanding of the progression of disc degeneration.     

Updated Lagrangian finite element formulations of various biological soft tissue non-linear material models: a comprehensive procedure and review

Simplified material models are commonly used in computational simulation of biological soft tissue as an approximation of the complicated material response and to minimize computational resources. However, the simulation of complex loadings, such as long-duration tissue swelling, necessitates complex models that are not easy to formulate. This paper strives to offer the updated Lagrangian formulation comprehensive procedure of various non-linear material models for the application of finite element analysis of biological soft tissues including a definition of the Cauchy stress and the spatial tangential stiffness. The relationships between water content, osmotic pressure, ionic concentration and the pore pressure stress of the tissue are discussed with the merits of these models and their applications.     

Mandibular biomechanics after marginal resection: Correspondences of simulated volumetric strain and skeletal resorption

Serious mandibular diseases such as tumor or osteonecrosis often require segmental or marginal mandibulectomy, the latter with improved outcome thanks to preserved mandibular continuity. Nevertheless, gradual osteolytic and/or osteosclerotic skeletal changes frequently indicate repetitive resections. Based on the fundamental adaptivity of bone to mechanical loads, the question arose whether resection-related anatomical alterations trigger relevant pathological skeletal adaptations. For a clinical case after mandibular box resection due to progressive osteoradionecrosis (ORN), routine biomechanical loading was simulated by finite element method, respecting pathology-related anatomy, tissue properties, and biting capacity. By 3D-visualization of the mandible’s pathological development from follow-up-CT’s over four years, remarkable correspondences of skeletal resorptions and increased unphysiological strain were revealed. Higher unphysiological load was correlated with more serious and earlier skeletal alterations. Three months post-operatively, serious buccal destruction at the distal resection corner occurred in correspondence with dominant tensile strain. At the resection, elevated strain caused by reduced alveolar height corresponded to skeletal compromise, observed 8–9 months post-operatively. ORN-related lesions, diagnosed before resection, entailed unphysiological strain coinciding with local skeletal alterations. Simulations with “healthy” instead of pathological tissue coefficients induced quantitative improvements of 25–33%, but without fundamental change. These results suggest a decisive contribution of resection-related biomechanical skeletal adaptations to this patient’s mandibular decline with hemimandibulectomy about 2.5 years after the first resection. However, mechanical stress concentrations in sharp angles as the distal resection corner and reduced stability due to decreased alveolar height generally bear the danger of pathological biomechanics and severe skeletal adaptations for patients after mandibular box resection.     

Combination of dual-energy computed tomography and iterative metal artefact reduction to increase general quality of imaging for radiotherapy patients with high dense materials. Phantom study

PurposeTo evaluate the use of pseudo-monoenergetic reconstructions (PMR) from dual-energy computed tomography, combined with the iterative metal artefact reduction (iMAR) method.MethodsPseudo-monoenergetic CT images were obtained using the dual-energy mode on the Siemens Somatom Definition AS scanner. A range of PMR combinations (70–130 keV) were used with and without iMAR. A Virtual Water™ phantom was used for quantitative assessment of error in the presence of high density materials: titanium, alloys 330 and 600. The absolute values of CT number differences (AD) and normalised standard deviations (NSD) were calculated for different phantom positions. Image quality was assessed using an anthropomorphic pelvic phantom with an embedded hip prosthesis. Image quality was scored blindly by five observers.ResultsAD and NSD values revealed differences in CT number errors between tested sets. AD and NSD were reduced in the vicinity of metal for images with iMAR (p < 0.001 for AD/NSD). For ROIs away from metal, with and without iMAR, 70 keV PMR and pCT AD values were lower than for the other reconstructions (p = 0.039). Similarly, iMAR NSD values measured away from metal were lower for 130 keV and 70 keV PMR (p = 0.002). Image quality scores were higher for 70 keV and 130 keV PMR with iMAR (p = 0.034).ConclusionThe use of 70 keV PMR with iMAR allows for significant metal artefact reduction and low CT number errors observed in the vicinity of dense materials. It is therefore an attractive alternative to high keV imaging when imaging patients with metallic implants, especially in the context of radiotherapy planning.     

Influence of Different Abutment Designs on the Biomechanical Behavior of One-Piece Zirconia Dental Implants and Their Surrounding Bone: A 3D-FEA

BackgroundIn a dental implant/bone system, the design factors affect the value and distributions of stress and deformations that plays a pivotal role on the stability, durability and lifespan of the implant/bone system.ObjectiveThe aim of this study was to compare the influence of different abutment designs on the biomechanical behavior of one-piece zirconia dental implants and their surrounding bone tissues using three-dimensional finite element analysis.MethodsA three-dimensional geometrical model of a zirconia dental implant and its surrounding bone tissue were created. The occlusal loading force applied to the prosthetic abutments was a combination of 114.6 N in the axial direction, 17.1 N in the lingual direction and 23.4 N toward the mesial direction where these components represent masticatory force of 118.2 N in the angle of approximately 75° to the occlusal plane.ResultsThe system included implant abutment Model 01 showed a decrease of 9.58%, 9.92% and 3.62% at least in the average value of maximum von Mises stress compared to Model 02, Model 03 and Model 04 respectively. The results also showed that the system included implant abutment Model 01 decreases the average value of maximum deformation of 16.96%, 7.17% and 9.47% at least compared to Model 02, Model 03 and Model 04 respectively.ConclusionThe one-piece zirconia dental implant abutment Model 01 presents a better biomechanical behavior in the peri-implant bone than others. It can efficiently distribute the applied load and present more homogeneous behavior of stress distribution and has less deformation than others, which will enhance the stability of implant/bone system and prolong its lifespan.