Effect of size and location of simulated lytic lesions on the structural properties of human vertebral bodies, a micro-finite element study.

Currently, the Spinal Instability Neoplastic Score system is used in clinics to evaluate the risk of fracture in patients with spinal metastases. This method, however, does not always provide a clear guideline due to the complexity in accounting for the effect of metastatic lesions on vertebral stability. The aim of this study was to use a validated micro Finite Element (microFE) modelling approach to analyse the effect of the size and location of lytic metastases on the mechanical properties of human vertebral bodies. Micro Computed Tomography based microFE models were generated with and without lytic lesions simulated as holes within a human vertebral body. Single and multiple lytic lesions were simulated with four different sizes and in five different locations. Bone was assumed homogenous, isotropic and linear elastic, and each vertebra was loaded in axial compression. It was observed that the size of lytic lesions was linearly related with the reduction in structural properties of the vertebral body (reduction of stiffness between 3% and 30% for lesion volume between 4% and 35%). The location of lytic lesions did not show a clear effect on predicted structural properties. Single or multiple lesions with the same volume provided similar results. Locally, there was a homogeneous distribution of axial principal strains among the models with and without lytic lesions. This study highlights the potential of microFE models to study the effect of lesions on the mechanical properties of the human vertebral body.

Identification of the Photoreceptor Transcriptional Co-Repressor SAMD11 as Novel Cause of Autosomal Recessive Retinitis Pigmentosa.

Retinitis pigmentosa (RP), the most frequent form of inherited retinal dystrophy is characterized by progressive photoreceptor degeneration. Many genes have been implicated in RP development, but several others remain to be identified. Using a combination of homozygosity mapping, whole-exome and targeted next-generation sequencing, we found a novel homozygous nonsense mutation in SAMD11 in five individuals diagnosed with adult-onset RP from two unrelated consanguineous Spanish families. SAMD11 is ortholog to the mouse major retinal SAM domain (mr-s) protein that is implicated in CRX-mediated transcriptional regulation in the retina. Accordingly, protein-protein network analysis revealed a significant interaction of SAMD11 with CRX. Immunoblotting analysis confirmed strong expression of SAMD11 in human retina. Immunolocalization studies revealed SAMD11 was detected in the three nuclear layers of the human retina and interestingly differential expression between cone and rod photoreceptors was observed. Our study strongly implicates SAMD11 as novel cause of RP playing an important role in the pathogenesis of human degeneration of photoreceptors.