320 research outputs found

    Efficacy of Postoperative Radiograph for Evaluating the Prevertebral Soft Tissue Swelling after Anterior Cervical Discectomy and Fusion

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    Background: After surgery for degenerative spinal disease by the anterior approach, the degree of soft tissue swelling can be assessed simply using plain radiographs. However, there are little studies according to the surgical methods or extent of surgery, and no study had addressed the clinical meaning of swelling determined by plain radiography. The purpose of this study was to evaluate the clinical significance of prevertebral soft tissue swelling (PSTS) after anterior cervical fusion with plate fixation for the treatment of degenerative cervical spinal disorders. Methods: One hundred and thirty-five patients that underwent anterior cervical fusion with plate augmentation for degenerative cervical spondylosis were included in this study. PSTS differences were analyzed with respect to numbers of fusion segments and location of fusion. Cases were divided into two groups based on the amount of PSTS, and incidences of dyspnea, dysphagia, dysphonia were evaluated. Results: PSTS increments were significantly greater in patients that had undergone multi-level or high-level fusion. Complications of dyspnea, dysphagia and dysphonia were found more frequently in patients with marked PSTS group. Conclusions: Increments of PSTS after anterior cervical fusion for degenerative spinal disorders are greater and incidences of complications are higher in patients that undergo multi-level or high-level fusion. Thus, measurement of PSTS using consecutive cervical lateral radiographs after anterior cervical surgery is clinically meaningful procedure

    Cell Dispersal Influences Tumor Heterogeneity and Introduces a Bias in NGS Data Interpretation

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    Short and long distance cell dispersal can have a marked effect on tumor structure, high cellular motility could lead to faster cell mixing and lower observable intratumor heterogeneity. Here we evaluated a model for cell mixing that investigates how short-range dispersal and cell turnover will account for mutational proportions. We show that cancer cells can penetrate neighboring and distinct areas in a matter of days. In next generation sequencing runs, higher proportions of a given cell line generated frequencies with higher precision, while mixtures with lower amounts of each cell line had lower precision manifesting in higher standard deviations. When multiple cell lines were co-cultured, cellular movement altered observed mutation frequency by up to 18.5%. We propose that some of the shared mutations detected at low allele frequencies represent highly motile clones that appear in multiple regions of a tumor owing to dispersion throughout the tumor. In brief, cell movement will lead to a significant technical (sampling) bias when using next generation sequencing to determine clonal composition. A possible solution to this drawback would be to radically decrease detection thresholds and increase coverage in NGS analyses. © 2017 The Author(s)

    A Role for Alström Syndrome Protein, Alms1, in Kidney Ciliogenesis and Cellular Quiescence

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    Premature truncation alleles in the ALMS1 gene are a frequent cause of human Alström syndrome. Alström syndrome is a rare disorder characterized by early obesity and sensory impairment, symptoms shared with other genetic diseases affecting proteins of the primary cilium. ALMS1 localizes to centrosomes and ciliary basal bodies, but truncation mutations in Alms1/ALMS1 do not preclude formation of cilia. Here, we show that in vitro knockdown of Alms1 in mice causes stunted cilia on kidney epithelial cells and prevents these cells from increasing calcium influx in response to mechanical stimuli. The stunted-cilium phenotype can be rescued with a 5′ fragment of the Alms1 cDNA, which resembles disease-associated alleles. In a mouse model of Alström syndrome, Alms1 protein can be stably expressed from the mutant allele and is required for cilia formation in primary cells. Aged mice developed specific loss of cilia from the kidney proximal tubules, which is associated with foci of apoptosis or proliferation. As renal failure is a common cause of mortality in Alström syndrome patients, we conclude that this disease should be considered as a further example of the class of renal ciliopathies: wild-type or mutant alleles of the Alström syndrome gene can support normal kidney ciliogenesis in vitro and in vivo, but mutant alleles are associated with age-dependent loss of kidney primary cilia
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