Effectiveness of preoperative planning in the restoration of balance and view in ankylosing spondylitis

Object. The object of this study was to assess the effectiveness of preoperative planning in the restoration of balance and view angle in patients treated with lumbar osteotomy in ankylosing spondylitis (AS). Methods. The authors prospectively analyzed 8 patients with a thoracolumbar kyphotic deformity due to AS that was treated using a closing wedge osteotomy (CWO) of the lumbar spine to correct sagittal imbalance and horizontal view. Preoperative planning to predict postoperative balance, defined by the sagittal vertical axis (SVA) and the sacral endplate angle (SEA), and the view angle, defined by the chin-brow to vertical angle (CBVA), was performed using the ASKyphoptan computational program. Results. All patients were treated with a CWO at level L-4 and improved in balance and view angle. The mean correction angle was 35° (range 24-47°). The postoperative SEA improved from 21 to 36° for a mean correction of 15°. In addition, the SVA and CBVA improved significantly. Note, however, that the postoperative results did not exactly reflect the predicted values of the analyzed parameters. Conclusions. Preoperative planning for the restoration of balance and view angle in AS improves understanding of the biomechanical and clinical effects of a correction osteotomy of the lumbar spine. The adaptation of basic clinical and biomechanical principles to restore balance is advised in such a way that the individual SEA is corrected by 15° (maximum 40°) in relation to the horizon and C-7 is balanced exactly above the posterosuperior corner of the sacrum

Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.

One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis

Activation Models for the Numerical Simulation of Cardiac Electromechanical Interactions

This contribution addresses the mathematical modeling and numerical approximation of the excitation-contraction coupling mechanisms in the heart. The main physiological issues are preliminarily sketched along with an extended overview to the relevant literature. Then we focus on the existing models for the electromechanical interaction, paying special attention to the active strain formulation that provides the link between mechanical response and electrophysiology. We further provide some critical insight on the expected mathematical properties of the model, the ability to provide physiological results, the accuracy and computational cost of the numerical simulations. This chapter ends with a numerical experiment studying the electromechanical coupling on the anisotropic myocardial tissue

Complete deletion of Apc results in severe polyposis in mice

The adenomatous polyposis coli (APC) gene product is mutated in the vast majority of human colorectal cancers. APC negatively regulates the WNT pathway by aiding in the degradation of β-catenin, which is the transcription factor activated downstream of WNT signaling. APC mutations result in β-catenin stabilization and constitutive WNT pathway activation, leading to aberrant cellular proliferation. APC mutations associated with colorectal cancer commonly fall in a region of the gene termed the mutation cluster region and result in expression of an N-terminal fragment of the APC protein. Biochemical and molecular studies have revealed localization of APC/Apc to different sub-cellular compartments and various proteins outside of the WNT pathway that associate with truncated APC/Apc. These observations and genotype–phenotype correlations have led to the suggestion that truncated APC bears neomorphic and/or dominant-negative function that support tumor development. To analyze this possibility, we have generated a novel allele of Apc in the mouse that yields complete loss of Apc protein. Our studies reveal that whole-gene deletion of Apc results in more rapid tumor development than the APC multiple intestinal neoplasia (Apc[superscript Min]) truncation. Furthermore, we found that adenomas bearing truncated Apc had increased β-catenin activity when compared with tumors lacking Apc protein, which could lead to context-dependent inhibition of tumorigenesis.Howard Hughes Medical InstituteNational Cancer Institute (U.S.) (Cancer Center Support Core Grant P30-CA14051