Periodontitis is a chronic infectious disease driven by dysbiosis, an imbalance between commensal bacteria and the host organism. Periodontitis is a leading cause of tooth loss in adults and occurs in about 50% of the US population. In addition to the clinical challenges associated with treating periodontitis, the progression and chronic nature of this disease seriously affect human health. Emerging evidence suggests that periodontitis is associated with mechanisms beyond bacteria-induced protein and tissue degradation. Here, we hypothesize that bacteria are able to induce epigenetic modifications in oral epithelial cells mediated by histone modifications. In this study, we found that dysbiosis in vivo led to epigenetic modifications, including acetylation of histones and downregulation of DNA methyltransferase 1. In addition, in vitro exposure of oral epithelial cells to lipopolysaccharides resulted in histone modifications, activation of transcriptional coactivators, such as p300/CBP, and accumulation of nuclear factor-κB (NF-κB). Given that oral epithelial cells are the first line of defense for the periodontium against bacteria, we also evaluated whether activation of pathogen recognition receptors induced histone modifications. We found that activation of the Toll-like receptors 1, 2, and 4 and the nucleotide-binding oligomerization domain protein 1 induced histone acetylation in oral epithelial cells. Our findings corroborate the emerging concept that epigenetic modifications play a role in the development of periodontitis.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and is responsible for a quarter of a million deaths annually. The survival rate for HNSCC patients is poor, showing only minor improvement in the last three decades. Despite new surgical techniques and chemotherapy protocols, tumor resistance to chemotherapy remains a significant challenge for HNSCC patients. Numerous mechanisms underlie chemoresistance, including genetic and epigenetic alterations in cancer cells that may be acquired during treatment and activation of mitogenic signaling pathways, such as nuclear factor kappa-light-chain-enhancer-of activated B cell, that cause reduced apoptosis. In addition to dysfunctional molecular signaling, emerging evidence reveals involvement of cancer stem cells (CSCs) in tumor development and in tumor resistance to chemotherapy and radiotherapy. These observations have sparked interest in understanding the mechanisms involved in the control of CSC function and fate. Post-translational modifications of histones dynamically influence gene expression independent of alterations to the DNA sequence. Recent findings from our group have shown that pharmacological induction of post-translational modifications of tumor histones dynamically modulates CSC plasticity. These findings suggest that a better understanding of the biology of CSCs in response to epigenetic switches and pharmacological inhibitors of histone function may directly translate to the development of a mechanism-based strategy to disrupt CSCs. In this review, we present and discuss current knowledge on epigenetic modifications of HNSCC and CSC response to DNA methylation and histone modifications. In addition, we discuss chromatin modifications and their role in tumor resistance to therapy.

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Background: The osteocutaneous radial forearm free flap (OC-RFFF) has been proposed as a safe and reliable free flap for head and neck reconstruction with low donor site morbidity. The purpose of this study is to compare the late complications (>30 days) associated with using the OC-RFFF versus the free fibula flap (FFF) for mandibular reconstruction following oncologic segmental resection. Methods:We conducted a single-institution, retrospective study composed of patients who underwent oncologic microvascular composite mandibular reconstruction with either the OC-RFFF or FFF. The primary predictor variable was the type of free flap used. The outcome variable was late complication postoperatively (>30 days).Results: A total of 93 patients (28, OC-RFFF and 65, FFF) were analyzed. The majority of patients were male (62%) and with AJCC stage T4a disease (72%). Mean hospital length of stay was comparable between the two flap groups (p = .50). OC-RFFF was associated with more late complications (p = .03) compared to FFF. Nonunion occurred in 10.7% of OC-RFFF and 0% of FFF. Partial or complete flap failure was seen in 7.1% and 0% in the OC-RFFF and FFF, respectively. Two-year disease-free survival was comparable in both groups (p > .05). Conclusions:The results of this study suggest that the rate of nonunion and odds of having a late complication were significantly greater in the OC-RFFF compared to the FFF following oncologic mandibular reconstruction. However, flap success, early complications (<30 days), and length of hospital stay were comparable between the two flaps. | INTRODUCTIONComposite mandibular defects resulting from oral cancer may be reconstructed using a number of free vascularized bone flaps harvested from the fibula, scapula, ilium, or radius (Bak et al., 2010;Disa & Cordeiro, 2000). Additionally, although less commonly used, the medial femoral condyle, rib, humerus, and tibia have also been described as osseous donor sites associated with low failure rates and minimal donor site morbidity (Banaszewski et al., 2019;Brown et al., 2017;Mulholland et al., 2013). To date, there remains no randomized controlled trial or consensus on flap selection for composite mandibular defects. Instead, flap selection is made mostly on the surgeon's preference, training, experience, guided by existing outcomesbased research (Takushima et al., 2005). For many reconstructive

This aim of this study was to develop and evaluate a simulation program for dental students to supplement a lecture‐based medical emergencies course. Students' self‐reported knowledge, experience, confidence, and ability regarding medical emergencies were assessed as program outcomes. For three years (in 2014, 2015, and 2016), all second‐year students (N=333) at one U.S. dental school were randomly assigned to groups of 15 and participated in 15 simulated clinical scenarios. All students completed a 21‐item pre‐post survey and rated their knowledge, experience, and confidence using simulated emergencies. Following the intervention, students' ability to complete critical actions was also peer‐assessed using a ten‐item checklist. Four open‐ended questions were included on the post‐intervention survey for acquisition of additional data. For all years, students' self‐reported measurements significantly improved with high practical impact (p≤0.001, g=|0.62, 3.93|), with the exception of calling 911 (knowledge). Peer‐rated performance indicated the students were deficient (<75% success) in the following: inhaler use, dose of local anesthetic, dose of epinephrine, and EpiPen use. Content analysis of students' comments pointed to areas that need improvement but found high satisfaction with the program. These findings indicate that this program improved students' knowledge, experience, and confidence using simulated medical emergencies.