Histone methylation acts as an epigenetic regulator of chromatin activity through the modification of arginine and lysine residues on histones H3 and H4. In the case of lysine, this includes the formation of mono-, di-, or trimethyl groups, each of which is presumed to represent a distinct functional state at the cellular level. To examine the potential developmental roles of these modifications, we determined the global patterns of lysine methylation involving K9 on histone H3 and K20 on histone H4 in midgestation mouse embryos. For each lysine target site, we observed distinct subnuclear distributions of the mono- and trimethyl versions in 10T1/2 cells that were conserved within primary cultures and within the 3D-tissue architecture of the embryo. Interestingly, three of these modifications, histone H3 trimethyl K9, histone H4 monomethyl K20, and histone H4 trimethyl K20 exhibited marked differences in their distribution within the neuroepithelium. Specifically, both histone H3 trimethyl K9 and H4 monomethyl K20 were elevated in proliferating cells of the neural tube, which in the case of the K9 modification was limited to mitotic cells on the luminal surface. In contrast, histone H4 trimethyl K20 was progressively lost from these medial regions and became enriched in differentiating neurons in the ventrolateral neural tube. The inverse relationship of histone H4 K20 methyl derivatives is even more striking during skeletal and cardiac myogenesis where the accumulation of the trimethyl modification in pericentromeric heterochromatin suggests a role in gene silencing in postmitotic muscle cells. Importantly, our results establish that histone lysine methylation occurs in a highly dynamic manner that is consistent with their function in an epigenetic program for cell division and differentiation.

ObjectiveTo perform a systematic review of measurement tools utilized for the diagnosis of nasal septal deviation (NSD).MethodsElectronic database searches were performed using MEDLINE (from 1966 to second week of August 2013), EMBASE (from 1966 to second week of August 2013), Web of Science (from 1945 to second week of August 2013) and all Evidence Based Medicine Reviews Files (EBMR); Cochrane Database of Systematic Review (CDSR), Cochrane Central Register of Controlled Trials (CCTR), Cochrane Methodology Register (CMR), Database of Abstracts of Reviews of Effects (DARE), American College of Physicians Journal Club (ACP Journal Club), Health Technology Assessments (HTA), NHS Economic Evaluation Database (NHSEED) till the second quarter of 2013. The search terms used in database searches were ‘nasal septum’, ‘deviation’, ‘diagnosis’, ‘nose deformities’ and ‘nose malformation’. The studies were reviewed using the updated Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.ResultsOnline searches resulted in 23 abstracts after removal of duplicates that resulted from overlap of studies between the electronic databases. An additional 15 abstracts were excluded due to lack of relevance. A total of 8 studies were systematically reviewed.ConclusionsDiagnostic modalities such as acoustic rhinometry, rhinomanometry and nasal spectral sound analysis may be useful in identifying NSD in anterior region of the nasal cavity, but these tests in isolation are of limited utility. Compared to anterior rhinoscopy, nasal endoscopy, and imaging the above mentioned index tests lack sensitivity and specificity in identifying the presence, location, and severity of NSD.

Objectives/Hypothesis The free flap reconstructive protocols of the jaws have been refined over the years and presently are based on bone‐driven approaches that generally use the lower border of the mandible or the anterior surface of the maxilla as the templates for reconstruction because these contours are deemed important to the eventual cosmetic outcomes of patients. The ultimate goal of functional jaw reconstruction, however, is the reconstruction of the dental occlusion and oral rehabilitation. The purpose of the present study was to evaluate the Alberta reconstructive technique (ART), which is a new approach of occlusion‐driven jaw reconstruction with digitally planned immediate osseointegrated implant installation. Study Design Prospective cohort study. Methods This research study considers the ART's safety, effectiveness, accuracy, timeliness of reconstruction, aesthetic appeal, and cost‐effectiveness in comparison with the standard bone‐driven and delayed osseointegrated implant installation (BDD) protocol. Results The ART procedures were as safe and more effective at achieving full occlusal reconstruction and oral rehabilitation. The ART cohort of patients achieved oral rehabilitation in 21.4 month as compared to 73.1 months for the BDD cohort. There were no differences in the aesthetic appeal the two groups. The ART cost an average of $22,004 less than BDD and we calculated the quality adjusted life years gain to be between 2.14 and 4.04 in favour of ART. Conclusions The ART is a good option for patients with jaw defects. It provides a safe, effective, accurate, aesthetic, and cost‐effective reconstruction that restores form and function in a timely manner. Level of Evidence 2b Laryngoscope, 129:S1–S14, 2019

Primary surgical approaches offer the best survival outcomes in smokers with p16-positive cancers and in patients with p16-negative cancers. © 2015 Wiley Periodicals, Inc. Head Neck 38: E-E, 2016.

IntroductionsThe incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCCs) is rising in developed nations. Studies have shown that these virally mediated tumours are epidemiologically, clinically, and biologically different than other head and neck squamous cell carcinomas and traditional concepts of field cancerization may not apply to HPV-related oropharyngeal cancer.ObjectiveThe purpose of this study was to evaluate the rate of second primary tumors and the diagnostic yield of field cancerization work up in the upper aerodigestive tract in patients with HPV-related and HPV-unrelated oropharyngeal squamous cell carcinoma.DesignRetrospective review.SettingTertiary cancer care centers in Alberta.MethodsRetrospective review of 406 patients diagnosed with OPSCC in Alberta between 2005 and 2009. HPV-status of tumours was determined by tissue microarray using immunohistochemistry staining for p16.Main outcome measuresPrimary outcome: incidence of upper aerodigestive tract second primary tumours in p16-positive versus p16-negative OPSCC. Secondary outcomes: diagnostic yield of traditional field cancerization work-up in p16-positive versus negative patients.ResultsThe overall rate of SPTs was 7.4% (30/406). The incidence rate of SPTs was significantly lower in p16-positive patients (0.7 per 100 patient-yrs vs. 8.5 in p16-negative, p < 0.0001). Field cancerization work-up for synchronous lesions in the upper aerodigestive tract, including panendoscopy and whole-body PET-CT, had decreased diagnostic yield in p16-positive patients (2.8% vs. 10.2% in HPV-negative patients, p=0.02).ConclusionsPatients with HPV-related OPSCC, who are non-smokers have decreased risk of developing second primary tumours in the upper aerodigestive tract and have low yield on field cancerization work-up. This study provides further evidence that virally mediated OPSCC are distinct and may benefit from alternate diagnostic pathways.