ABSTRACT
BACKGROUND: Forty years ago the actin cytoskeleton was determined to be disrupted in fibroblasts from persons with DNA repair-defective, hereditary colon cancer, with no clear connection between the cytoskeleton and DNA repair defects at that time. Recently, the large number of sequenced genomes has indicated that mammalian mutagenesis has a large stochastic component. As a result, large coding regions are large mutagen targets. Cytoskeletal protein-related coding regions (CPCRs), including extra-cellular matrix proteins, are among the largest coding regions in the genome and are indeed very commonly mutated in cancer. METHODS: To determine whether mutagen sensitivity of the actin cytoskeleton could be assessed experimentally, we treated tissue culture cells with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and quantified overall cytoskeleton integrity with rhodamine-phalloidin stains for F-actin. RESULTS: The above approach indicated cytoskeletal degradation with increasing mutagen exposure, consistent with increased mutagenesis of CPCRs in TCGA, smoker samples, where overall mutation rates correlate with CPCR mutation rates (R2 = 0.8694; p < 0.00001). In addition, mutagen exposure correlated with a decreasing cell perimeter to area ratio, raising questions about potential decreasing, intracellular diffusion and concentrations of chemotherapy drugs, with increasing mutagenesis and decreasing cytoskeleton integrity. CONCLUSION: Determination of cytoskeletal integrity may provide the opportunity to assess mutation burdens in nonclonal cell populations, such as in intact tissues, where DNA sequencing for heterogeneous mutation burdens can be challenging.
ABSTRACT
BACKGROUND: Volar plate fixation of distal radius fractures can result in soft tissue injuries. Abnormal contour of the dorsal cortex of the distal radius provides difficulties in discerning screw penetration on standard radiographs. The skyline and carpal shoot-through views are additional views to improve dorsal cortex visibility. We report on the sensitivity and specificity of determining screw protrusion with these views. METHODS: Seven fresh frozen cadavers were instrumented with a distal radius volar locking plate. Initial screw length was determined by depth gauge measurement. A dorsal dissection of the wrist was performed to detect screw penetration. Protruding screws were documented and replaced with screws of the appropriate length and deemed as baseline. Screws were then sequentially lengthened by 2 and 4 mm. Skyline and carpal shoot-through views were obtained at baseline, 2 mm, and 4 mm. The images were randomized and compiled into an untimed survey asking orthopedic surgeons to determine whether screws were penetrating through the dorsal cortex. RESULTS: Based on depth gauge measurements, 4 out of 44 (9.1%) volar plate locking screws penetrated the dorsal cortex, as confirmed with dorsal dissection. Sensitivities for the skyline and carpal shoot-through views were 75% and 86% ( P ≤ .001), respectively, for 2-mm protrusions, and 76% and 89% ( P ≤ .001), respectively, for 4-mm screw protrusions. Specificities were 85% and 84% for the skyline and shoot-through views, respectively. CONCLUSIONS: We believe that the carpal shoot-through view has utility and can be implemented to augment standard intraoperative views, and may decrease the incidence of screw protrusion resulting in soft tissue injuries.
