RESUMEN
PURPOSE: Reconstruction of nasal defects, particularly in the lower third of the nose, presents significant challenges due to the area's complex 3-dimensional structure and thicker, more sebaceous skin. The bilobed flap, a double transposition flap, has been a popular method for addressing these nasal defects. METHODS: This retrospective review examines a single surgeon's experience with bilobed flaps for nasal reconstruction over the last 15 years. Demographics, defect characteristics, intraoperative details, postoperative complications, and revisionary procedures were documented, and univariate and multivariate logistic regression analyses were used to assess complication rate associations. RESULTS: In all, 148 bilobed reconstructions were analyzed, with a mean patient age of 62.6 years and 46.0% male prevalence. The most common indication for the procedure was basal cell carcinoma following Mohs surgery, with the majority of the defects located on the lower third of the nose. The average defect size was 1.11 cm². Complications occurred in 52.0% of cases, including pincushioning, scar thickening, asymmetry, alar stenosis, and wound dehiscence. Reoperations and additional treatments such as dermabrasion, steroid injections, and laser therapy were frequently necessary to address these issues. Logistic regression analysis demonstrated significantly more postoperative complications when the defect was located on the lower third of the nose when compared with the upper two-thirds. CONCLUSIONS: While the bilobed flap can provide adequate skin coverage with perfect color match, it is associated with notable complications that impact esthetic outcomes. Proper patient selection and surgical technique are crucial for optimizing results.
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B cells provide protective immunity by secreting antibodies. When a B cell encounters its specific antigen, B-cell receptor (BCR) signaling initiates actin remodeling. This allows B cells to spread on antigen-bearing surfaces and find more antigen, which increases BCR signaling and facilitates B cell activation. The BCR activates multiple signaling pathways that target actin-regulatory proteins. Although the extracellular signal-regulated kinases ERK1 and ERK2 regulate actin-dependent processes in adherent cells, their role in BCR-induced actin remodeling had not been investigated. Here, we show that targeting ERK with chemical inhibitors or siRNA inhibits BCR-induced spreading in a murine B cell line.
RESUMEN
Inactive fusion variants of the CRISPR-Cas9 system are increasingly being used as standard methodology to study transcription regulation. Their ability to readily manipulate the native genomic loci is particularly advantageous. In this work, we serendipitously uncover the key cytokine IL6 as an off-target of the activating derivative of CRISPR (CRISPRa) while studying RP11-326A19.4, a novel long-non coding RNA (lncRNA). Increasing RP11-326A19.4 expression in HEK293T cells via CRISPRa-mediated activation of its promoter region induced genome-wide transcriptional changes, including upregulation of IL6, an important cytokine. IL6 was increased in response to distinct sgRNA targeting the RP11-326A19.4 promoter region, suggesting specificity. Loss of the cognate sgRNA recognition sites failed to abolish CRISPRa mediated activation of IL6 however, pointing to off-target effects. Bioinformatic approaches did not reveal predicted off-target binding sites. Off-target activation of IL6 was sustained and involved low level activation of known IL6 regulators. Increased IL6 remained sensitive to further activation by TNFα, consistent with the existence of independent mechanisms. This study provides experimental evidence that CRISPRa has discrete, unpredictable off-targeting limitations that must be considered when using this emerging technology.