FEM Simulation of Non-Progressive Growth from Asymmetric Loading and Vicious Cycle Theory: Scoliosis Study Proof of Concept

Scoliosis affects about 1-3% of the adolescent population, with 80% of cases being idiopathic. There is currently a lack of understanding regarding the biomechanics of scoliosis, current treatment methods can be further improved with a greater understanding of scoliosis growth patterns. The objective of this study is to develop a finite element model that can respond to loads in a similar fashion as current spine biomechanics models and apply it to scoliosis growth. Using CT images of a non-scoliotic individual, a finite element model of the L3-L4 vertebra was created. By applying asymmetric loading in accordance to the ‘vicious cycle’ theory and through the use of a growth modulation equation it is possible to determine the amount of growth each region of the vertebra will undergo; therefore predict scoliosis growth over a period of time. This study seeks to demonstrate how improved anatomy can expand researchers current knowledge of scoliosis

The copper-transporting capacity of ATP7A mutants associated with Menkes disease is ameliorated by COMMD1 as a result of improved protein expression

Menkes disease (MD) is an X-linked recessive disorder characterized by copper deficiency resulting in a diminished function of copper-dependent enzymes. Most MD patients die in early childhood, although mild forms of MD have also been described. A diversity of mutations in the gene encoding of the Golgi-resident copper-transporting P1B-type ATPase ATP7A underlies MD. To elucidate the molecular consequences of the ATP7A mutations, various mutations in ATP7A associated with distinct phenotypes of MD (L873R, C1000R, N1304S, and A1362D) were analyzed in detail. All mutants studied displayed changes in protein expression and intracellular localization parallel to a dramatic decline in their copper-transporting capacity compared to ATP7A the wild-type. We restored these observed defects in ATP7A mutant proteins by culturing the cells at 30°C, which improves the quality of protein folding, similar to that which as has recently has been demonstrated for misfolded ATP7B, a copper transporter homologous to ATP7A. Further, the effect of the canine copper toxicosis protein COMMD1 on ATP7A function was examined as COMMD1 has been shown to regulate the proteolysis of ATP7B proteins. Interestingly, in addition to adjusted growth temperature, binding of COMMD1 partially restored the expression, subcellular localization, and copper-exporting activities of the ATP7A mutants. However, no effect of pharmacological chaperones was observed. Together, the presented data might provide a new direction for developing therapies to improve the residual exporting activity of unstable ATP7A mutant proteins, and suggests a potential role for COMMD1 in this process

Numerical Simulation of Asymmetrically Altered Growth as Initiation Mechanism of Scoliosis

The causes of idiopathic scoliosis are still uncertain; buckling is mentioned often, but never proven. The authors hypothesize another option: unilateral postponement of growth of MM Rotatores or of ligamentum flavum and intertransverse ligament. In this paper, both buckling and the two new theories of scoliotic initiation are studied using a new finite element model that simulates the mechanical behavior of the human spine. This model was validated by the stiffness data of Panjabi et al. (J. Biomech. 9:185–192, 1976). After a small correction of the prestrain of some ligaments and the MM Rotatores the model appeared to be valid. The postponement in growth was translated in the numerical model in an asymmetrical stiffness. The spine was loaded axially and the resulting deformation was analyzed for the presence of the coupling of lateral deviation and axial rotation that is characteristic for scoliosis. Only unilateral postponement of growth of ligamentum flavum and intertransverse ligament appeared to initiate scoliosis. Buckling did not initiate scoliosis

The molecular structure of monofluoroacetic acid

Monofluoroacetic acid was studied by microwave spectroscopy and electron diffraction. Two sets of rotational transitions were found, corresponding to two distinct conformations each having a plane of symmetry. From the dipole moments and from. results of isotopic substitution in the carboxyl group it was shown that in the “trans-conformation” the chain of atoms F-C-C-O-H is zig-zag, whereas in the “cis-conformation” it is cyclic. The bond distances and bond angles could only be determined from a combination of electron diffraction and microwave spectroscopy data. The inertial moments were taken as observed quantities in the electron diffraction least squares procedure, with weights estimated from the expected differences between the results of the two techniques. From microwave absorption coefficients the trans-conformation was found to be 604 ± 28 cal mole−1 lower in energy than the cis-conformation. A very rough estimate of about 6 kcal mole−1 is given for the height of the rotational barrier. These data are compared with the results of two semi-empirical quantum mechanical methods (EHT and CNDO/2)