Demonstration of reduced levels in the expression of POSTN, an ECM gene, following resolution of disease, implicates POSTN, a potential pathogenesis indicator or biomarker of CRS disease activity and responsiveness to treatment.
unusual layered structure. Samples consisted of endogenous mucin-rich layers with occasional pockets of bacterial cells, which were found throughout the biofilm. A commercially available surfactant was used to disperse the upper layers of mucin to allow penetration by the nuclease into the deeper bacterial biofilm. In vitro studies with the nuclease against model organisms also showed effective breakup of biofilms. Conclusion:We have shown that characteristic tenacious sinus "biofilm" has an unusual microscopic structure. Bacteria appeared to be localized in foci and may have been responsible for stimulating a host response. We are developing methods to remove sinus biofilms using a microbial nuclease that breaks down DNA holding the biofilm together. Objective: Endoscopic sinus surgery (ESS) for chronic rhinosinusitis is a frequently performed surgical procedure. However, the mechanism by which it improves disease is unknown. We wished to determine patterns of changes in gene expression associated with resolution of disease following ESS in order to identify mechanisms implicated in resolution of disease. Rhinology/AllergyMethod: Twelve patients undergoing ESS for CRS were recruited. An epithelial sample from the frontal sinus was collected using a cytology brush at time of surgery and repeated 3 months after surgery. Microarray analysis of gene expression was performed using the Illumina Human HT-12 Beachip v3.Results: Both single gene expression analysis (using Limma package from Bioconductor software.) and gene set analysis (using Ingenuity Pathway Analysis software) were used to identify implicated genes and pathways (or networks), respectively. All patients resolved CRS with surgery. A total of 4707 genes or transcripts showed significant differential expression changes (pFDR). Healing was associated with increased expression of cytokines and transcription factors in the IL1B signaling pathway (IL8 (FC: 8.56; P = .00027) IL1B (FC: 4.21; P = .0008) NFkBIZ (FC: 2.27; P = .0008), innate immune signaling (IRAKs-1, -2, and -3, CD14, MD2, MyD88), and apoptosis (CASP3, BAK, BID). Conclusion:Resolution of CRS after ESS is characterized by marked upregulation of the IL-1B and innate immune signaling pathways and increased expression of pro-apoptosis genes. This supports the concept that microbial detection and clearance are impaired in CRS, and that strategies increasing immune activation may represent novel therapeutic opportunities. Rhinology/AllergyValidation of a low-Cost Sinus Surgery Task Trainer Matthew K. Steehler, MD (presenter); Hana Na; Michael Pfisterer; Hosai N. Hesham, MD; Sonya Malekzadeh, MD Objective: Assess the face, content, and construct validities of a low-cost sinus surgery task trainer in acquisition of skills for endoscopic sinus surgery.Method: Participants performed nasal endoscopy and 5 specific tasks using this model. Face and content validities were assessed based on the attendings' responses to a questionnaire evaluating the task trainer. Construct validity was determined by comparing ...
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