Search

Type I thyroplasty is widely used to improve voice production in patients affected by unilateral vocal fold paralysis. Almost two-thirds of laryngologists report using Silastic® implants to medialize the vocal fold, with implant size, shape, and location determined experientially. However, post-surgical complications arising from this procedure (extrusion, migration, resizing) necessitate revision in 4.5–16% of patients. To improve initial surgical outcomes, we have developed a subject-specific modeling tool, PhonoSim, which uses model reconstruction from MRI scans to predict the optimal implantation location. Eleven vocal fold sample sides from eight larynges of New Zealand white rabbits were randomized to two groups: PhonoSim informed (n = 6), and control (no model guidance, n = 5). Larynges were scanned ex vivo in the abducted configuration using a vertical-bore 11.7 T microimaging system, and images were used for subject-specific modeling. The PhonoSim tool simulated vocal fold adduction for multiple implant location placements to evaluate vocal fold adduction at the medial surface. The best implant placement coordinates were output for the 6 samples in the PhonoSim group. Control placements were determined by the same surgeon based on anatomical landmarks. Post-surgical MRI scans were performed for all samples to evaluate medialization in implanted vocal folds. Results show that PhonoSim-guided implantation achieved higher vocal fold medialization relative to controls (28 to 55% vs. − 29 to 39% respectively, in the glottal area reduction), suggesting that this tool has the potential to improve outcomes and revision rates for type I thyroplasty.

Background Nephronophthisis (NPHP) as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK) rat. Results In this study, quantitative trait locus analysis was used to define a ~1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a)- related kinase 8 ( Nek8) gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1)-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation. Conclusions When assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins.