Musculoskeletal modelling of the human cervical spine for the investigation of injury mechanisms during axial impacts

This is the final version. Available from Public Library of Science via the DOI in this record.All relevant data are available at Figshare [https://figshare.com/projects/SILVESTROS_PLOS_ONE_SUPPORTING_DOCUMENTS/58280] and musculoskeletal models and relevant project information is available on the OpenSim SimTK repository [https://simtk.org/projects/csibath].Head collisions in sport can result in catastrophic injuries to the cervical spine. Musculoskeletal modelling can help analyse the relationship between motion, external forces and internal loads that lead to injury. However, impact specific musculoskeletal models are lacking as current viscoelastic values used to describe cervical spine joint dynamics have been obtained from unrepresentative quasi-static or static experiments. The aim of this study was to develop and validate a cervical spine musculoskeletal model for use in axial impacts. Cervical spine specimens (C2-C6) were tested under measured sub-catastrophic loads and the resulting 3D motion of the vertebrae was measured. Specimen specific musculoskeletal models were then created and used to estimate the axial and shear viscoelastic (stiffness and damping) properties of the joints through an optimisation algorithm that minimised tracking errors between measured and simulated kinematics. A five-fold cross validation and a Monte Carlo sensitivity analysis were conducted to assess the performance of the newly estimated parameters. The impact-specific parameters were integrated in a population specific musculoskeletal model and used to assess cervical spine loads measured from Rugby union impacts compared to available models. Results of the optimisation showed a larger increase of axial joint stiffness compared to axial damping and shear viscoelastic parameters for all models. The sensitivity analysis revealed that lower values of axial stiffness and shear damping reduced the models performance considerably compared to other degrees of freedom. The impact-specific parameters integrated in the population specific model estimated more appropriate joint displacements for axial head impacts compared to available models and are therefore more suited for injury mechanism analysis.Rugby Football Union (RFU) Injured Players Foundatio

Spine system equivalence: A new protocol for standardized multi-axis comparison tests

This is the final version of the paper.Accurately replicating the in-vivo loads of the spine is a critical aspect of in-vitro spine testing, but the complexity of this structure renders this challenging. The design and control capabilities of multi-axis spine systems vary considerably, and though recommendations have been made [1, 2], standardized in-vitro methods have not yet been established. As such, it is often difficult to compare different biomechanical studies [3]. The aim of this study was to use international standards [4, 5], and spine testing recommendations [1-3] to develop a standardized protocol for the evaluation of different multi-axis spinal test systems. The protocol was implemented on three six-axis spine systems, and the data used to establish stiffness and phase angle limits. [...]This research was supported by the Catherine Sharpe Foundation, the Enid Linder Foundation, the Higher Education Innovation Fund, and the University of Bath Alumni Fund

Antibiotic additives alter the static and viscoelastic properties of bone cements

Introduction: In arthroplasty antibiotics are added to bone cements to prevent deep infection. The static properties of plain and antibiotic laden cements have been extensively described in the literature [1]. Commercially available cements must perform above the minimum values set by ISO 5833:2002 [2]. However, no upper or lower limits are set for the viscoelastic properties of the cements, despite this being a recognised factor affecting the cement-implant performance [3]. The ability of acrylic bone cement to creep and stress relax in conjunction with forceclosed stems in hip arthroplasty affords protection of the vital bone-cement interface. With this design subsidence of the stem within the cement mantle over time does not lead to clinical failure [4]. Conversely, the clinical performance of shapeclosed stem designs can be negatively affected by cements demonstrating excessive creep. This study investigated the effect of antibiotic additives on the static and viscoelastic properties of PMMA cement. Materials and Methods: The mechanical and viscoelastic properties of Simplex P, Simplex Antibiotic and Simplex Tobramycin (Stryker, Limerick, IE) were investigated. This family of cements was chosen as they are characterised by the same polymeric base, that of Simplex P, the plain formulation, but contain different antibiotic additives. In particular Simplex Antibiotic contains 0.5g Erythromycin and 3 million I.U. Colistin, while in Simplex Tobramycin the only additive is 0.5g of Tobramycin. The static properties of the cements (compressive strength, bending strength and bending modulus) were assessed following ISO 5833:2002 [2], while stress relaxation and creep were assessed under quasi static conditions in a four pointbending configuration. The creep experiments were carried out using a custom made apparatus with the specimens positioned in a distilled water bath at 37 o

Dietary magnesium, not calcium, prevents vascular calcification in a mouse model for pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic calcification of connective tissue in skin, Bruch’s membrane of the eye, and walls of blood vessels. PXE is caused by mutations in the ABCC6 gene, but the exact etiology is still unknown. While observations on patients suggest that high calcium intake worsens the clinical symptoms, the patient organization PXE International has published the dietary advice to increase calcium intake in combination with increased magnesium intake. To obtain more data on this controversial issue, we examined the effect of dietary calcium and magnesium in the Abcc6−/− mouse, a PXE mouse model which mimics the clinical features of PXE. Abcc6−/− mice were placed on specific diets for 3, 7, and 12 months. Disease severity was measured by quantifying calcification of blood vessels in the kidney. Raising the calcium content in the diet from 0.5% to 2% did not change disease severity. In contrast, simultaneous increase of both calcium (from 0.5% to 2.0%) and magnesium (from 0.05% to 0.2%) slowed down the calcification significantly. Our present findings that increase in dietary magnesium reduces vascular calcification in a mouse model for PXE should stimulate further studies to establish a dietary intervention for PXE

Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder in which calcification of connective tissue leads to pathology in skin, eye and blood vessels. PXE is caused by mutations in ABCC6. High expression of this transporter in the basolateral hepatocyte membrane suggests that it secretes an as-yet elusive factor into the circulation which prevents ectopic calcification. Utilizing our Abcc6−/− mouse model for PXE, we tested the hypothesis that this factor is vitamin K (precursor) (Borst et al. 2008, Cell Cycle). For 3 months, Abcc6−/− and wild-type mice were put on diets containing either the minimum dose of vitamin K required for normal blood coagulation or a dose that was 100 times higher. Vitamin K was supplied as menaquinone-7 (MK-7). Ectopic calcification was monitored in vivo by monthly micro-CT scans of the snout, as the PXE mouse model develops a characteristic connective tissue mineralization at the base of the whiskers. In addition, calcification of kidney arteries was measured by histology. Results show that supplemental MK-7 had no effect on ectopic calcification in Abcc6−/− mice. MK-7 supplementation increased vitamin K levels (in skin, heart and brain) in wild-type and in Abcc6−/− mice. Vitamin K tissue levels did not depend on Abcc6 genotype. In conclusion, dietary MK-7 supplementation increased vitamin K tissue levels in the PXE mouse model but failed to counteract ectopic calcification. Hence, we obtained no support for the hypothesis that Abcc6 transports vitamin K and that PXE can be cured by increasing tissue levels of vitamin K

Anomalous structure of urinary glycosaminoglycans in patients with pseudoxanthoma elasticum (PXE)

Anomalous structure of urinary glycosaminoglycans in patients with pseudoxanthoma elasticum (PXE

Anomalous structure of urinary glycosaminoglycans in patients with pseudoxanthoma elasticum (PXE)

Anomalous structure of urinary glycosaminoglycans in patients with pseudoxanthoma elasticum (PXE

Dissection of human tropoelastin: supramolecular organization of polypeptide sequences coded by particular exons.

Polypeptide sequences encoded by some exons of the human tropoelastin gene (EDP, elastin-derived peptide) have been analysed for their ability to coacervate and to self-assembly. The great majority of them were shown to form organized structures, but only a few were indeed able to coacervate. Negative staining and rotary shadowing transmission electron microscopy showed the polypeptides to adopt a variety of supramolecular organization, from filaments, as those typical of tropoelastin, to amyloid-like fibers. The results obtained gave significant insight to the possible roles played by specific polypeptide sequences of tropoelastin