Interferon Regulatory Factor 6 (IRF6) is a transcription factor that, in mammals, is required for the differentiation of skin, breast epithelium, and oral epithelium. However, the transcriptional targets that mediate these effects are currently unknown. In zebrafish and frog embryos Irf6 is necessary for differentiation of the embryonic superficial epithelium, or periderm. Here we use microarrays to identify genes that are expressed in the zebrafish periderm and whose expression is inhibited by a dominant-negative variant of Irf6 (dnIrf6). These methods identify Grhl3, an ancient regulator of the epidermal permeability barrier, as acting downstream of Irf6. In human keratinocytes, IRF6 binds conserved elements near the GHRL3 promoter. We show that one of these elements has enhancer activity in human keratinocytes and zebrafish periderm, suggesting that Irf6 directly stimulates Grhl3 expression in these tissues. Simultaneous inhibition of grhl1 and grhl3 disrupts periderm differentiation in zebrafish, and, intriguingly, forced grhl3 expression restores periderm markers in both zebrafish injected with dnIrf6 and frog embryos depleted of Irf6. Finally, in Irf6 deficient mouse embryos, Grhl3 expression in the periderm and oral epithelium is virtually absent. These results indicate that Grhl3 is a key effector of Irf6 in periderm differentiation.
Background
Free tissue transfer is a mainstay in reconstruction of complex head and neck defects. The purpose of this study was to determine if perioperative complications were more common in patients with body mass index (BMI) >30 kg/m2 undergoing free flap reconstruction.
Methods
A multi-institutional retrospective cohort was created. Medical complications, surgical complications, and procedural variables were recorded. Logistic regression was used to investigate univariate and multivariate associations between outcomes and predictors.
Results
Of 582 cases, 128 patients (22%) had BMI >30. Surgical complications occurred in 153 cases (26.3%), with an adjusted odds ratio (OR) for association of surgical complications with BMI >30 of 0.92 (p 5 .71). Medical complications occurred in 178 cases (30.6%), with an adjusted OR of 0.78 (p 5 .26). Age and advanced comorbidity status (Adult Comorbidity Evaluation-27 [ACE-27] 2 or 3) were associated with medical complications (p < .0001).
Conclusion
BMI >30 does not predict medical or surgical complications in patients undergoing head and neck free flap surgery.
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