MicroRNA-124-3p suppresses mouse lip mesenchymal cell proliferation through the regulation of genes associated with cleft lip in the mouse.

BACKGROUND: Cleft lip (CL), one of the most common congenital birth defects, shows considerable geographic and ethnic variation, with contribution of both genetic and environmental factors. Mouse genetic studies have identified several CL-associated genes. However, it remains elusive how these CL-associated genes are regulated and involved in CL. Environmental factors may regulate these genes at the post-transcriptional level through the regulation of non-coding microRNAs (miRNAs). In this study, we sought to identify miRNAs associated with CL in mice. RESULTS: Through a systematic literature review and a Mouse Genome Informatics (MGI) database search, we identified 55 genes that were associated with CL in mice. Subsequent bioinformatic analysis of these genes predicted that a total of 33 miRNAs target multiple CL-associated genes, with 20 CL-associated genes being potentially regulated by multiple miRNAs. To experimentally validate miRNA function in cell proliferation, we conducted cell proliferation/viability assays for the selected five candidate miRNAs (miR-124-3p, let-7a-5p, let-7b-5p, let-7c-5p, and let-7d-5p). Overexpression of miR-124-3p, but not of the others, inhibited cell proliferation through suppression of CL-associated genes in cultured mouse embryonic lip mesenchymal cells (MELM cells) isolated from the developing mouse lip region. By contrast, miR-124-3p knockdown had no effect on MELM cell proliferation. This miRNA-gene regulatory mechanism was mostly conserved in O9-1 cells, an established cranial neural crest cell line. Expression of miR-124-3p was low in the maxillary processes at E10.5, when lip mesenchymal cells proliferate, whereas it was greatly increased at later developmental stages, suggesting that miR-124-3p expression is suppressed during the proliferation phase in normal palate development. CONCLUSIONS: Our findings indicate that upregulated miR-124-3p inhibits cell proliferation in cultured lip cells through suppression of CL-associated genes. These results will have a significant impact, not only on our knowledge about lip morphogenesis, but also on the development of clinical approaches for the diagnosis and prevention of CL.

Complications, hospital length of stay, and readmission after total laryngectomy.

BACKGROUND: The purpose of this study was to describe the 30-day incidence of complications after total laryngectomy (TL) in a high-volume institution and their impact on the hospital length of stay (LOS) and readmission rates. METHODS: A retrospective cohort study of all patients who underwent TL at The University of Texas MD Anderson Cancer Center from January 1, 2010 through June 30, 2013 was conducted. The patient demographics, treatment history, LOS, and 30-day post-TL complications and readmissions were extracted from the medical record. Univariate associations were analyzed, and stepwise backward selection methods were used to fit multivariate models. RESULTS: Two hundred forty-five patients were included. Complications occurred in 83 patients (33.9%) and included 3 deaths (1.2%). Wound complications occurred in 53 patients (21.6%), and 34 were pharyngocutaneous fistulas (PCFs; 13.9% overall). Thirty-four patients (13.9%) were readmitted within 30 days. A multivariate analysis revealed the following: wound complications were associated with former (odds ratio [OR], 5.1; P = .03) and current smokers (OR, 5.8; P = .02), PCFs were associated with prior wide-field radiation (OR, 3.1; P = .01) but not prior narrow-field (larynx-only) radiation (OR, 1.4; P = .61), LOS was associated with the type of flap (P = .002) and postoperative hematomas (P = .05), and readmissions were associated with preoperative hypoalbuminemia (P = .003) and postoperative wound complications (P < .001). CONCLUSIONS: Complications occurred in approximately one-third of TL patients and particularly in patients with poor wound-healing risk factors such as prior smoking and radiation. As expected, LOS was longer among reconstructed patients. Readmission was associated with hypoalbuminemia and postoperative wound complications. These data can inform quality improvement efforts and the counseling of high-risk patients undergoing TL. Cancer 2017;123:1760-1767. © 2016 American Cancer Society.

Accuracy of Anatomical Depictions in Cone Beam Computed Tomography (CBCT)-Reconstructed Panoramic Projections Compared to Conventional Panoramic Radiographs: A Clinical Risk-Benefit Analysis.

INTRODUCTION: Two-dimensional (2D) radiographs are the standard of care for diagnosis and treatment planning in the day-to-day practice of dentistry. With the growing popularity of cone beam computed tomography (CBCT), it is now becoming the standard of care in many areas of general dentistry due to its ability to create non-linear projections from volumetric data. The CBCT-generated non-orthogonal radiographs can serve as easy-to-use 2D and three-dimensional (3D) diagnostic tools and offer a similar experience for diagnosis as conventional 2D images. The aim of this study is to compare the accuracy of conventional radiographs and CBCT-generated projections to identify relevant anatomic landmarks and their associated variants. METHODS: Thirty-two patients referred to the University of Connecticut School of Dental Medicine's Advanced Imaging Center were selected for this retrospective analysis. Nineteen anatomical landmarks were retrospectively assessed on conventional panoramic and CBCT scans generated panoramic radiographs using two different digital imaging and communications in medicine viewers. A total of 1,216 anatomical landmarks were evaluated by two oral and maxillofacial radiologists to assess the accuracy and consistency of the depiction of radiographic anatomy. RESULTS: There was a very good agreement between the two evaluators with a Cohen's kappa value of 0.934. McNemar change test concluded that the anatomical assessment values compared between conventional panoramic and CBCT-generated panoramic radiographs are similar. CONCLUSION: This study showed that CBCT-generated panoramic images are comparable to conventional panoramic radiographs in identifying anatomical landmarks typically evaluated using a conventional panoramic projection. In addition, they have the added advantage of having 3D information in the acquired volume to better evaluate the area of interest. In clinical situations where a mid- to large-volume CBCT scan is available, a simulated panoramic image can be generated using the CBCT volume, leaving exposure of the patient to the additional radiation of a panoramic image unnecessary.