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Tobacco smoking causes lung cancer.sup.1-3, a process that is driven by more than 60 carcinogens in cigarette smoke that directly damage and mutate DNA.sup.4,5. The profound effects of tobacco on the genome of lung cancer cells are well-documented.sup.6-10, but equivalent data for normal bronchial cells are lacking. Here we sequenced whole genomes of 632 colonies derived from single bronchial epithelial cells across 16 subjects. Tobacco smoking was the major influence on mutational burden, typically adding from 1,000 to 10,000 mutations per cell; massively increasing the variance both within and between subjects; and generating several distinct mutational signatures of substitutions and of insertions and deletions. A population of cells in individuals with a history of smoking had mutational burdens that were equivalent to those expected for people who had never smoked: these cells had less damage from tobacco-specific mutational processes, were fourfold more frequent in ex-smokers than current smokers and had considerably longer telomeres than their more-mutated counterparts. Driver mutations increased in frequency with age, affecting 4-14% of cells in middle-aged subjects who had never smoked. In current smokers, at least 25% of cells carried driver mutations and 0-6% of cells had two or even three drivers. Thus, tobacco smoking increases mutational burden, cell-to-cell heterogeneity and driver mutations, but quitting promotes replenishment of the bronchial epithelium from mitotically quiescent cells that have avoided tobacco mutagenesis. Whole-genome sequencing of normal bronchial epithelium from 16 individuals shows that tobacco smoking increases genomic heterogeneity, mutational burden and driver mutations, whereas stopping smoking promotes replenishment of the epithelium with near-normal cells., Author(s): Kenichi Yoshida [sup.1] , Kate H. C. Gowers [sup.2] , Henry Lee-Six [sup.1] , Deepak P. Chandrasekharan [sup.2] , Tim Coorens [sup.1] , Elizabeth F. Maughan [sup.2] , Kathryn [...]

The molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing or remaining static. The cellular basis of this clinical observation is unknown. Here, we profile the genomic, transcriptomic, and epigenomic landscape of CIS in a unique patient cohort with longitudinally monitored pre-invasive disease. Predictive modeling identifies which lesions will progress with remarkable accuracy. We identify progression-specific methylation changes on a background of widespread heterogeneity, alongside a strong chromosomal instability signature. We observed mutations and copy number changes characteristic of cancer and chart their emergence, offering a window into early carcinogenesis. We anticipate that this new understanding of cancer precursor biology will improve early detection, reduce overtreatment, and foster preventative therapies targeting early clonal events in lung cancer. A multi-omics survey of progressive compared to regressive carcinoma in situ lesions provides a molecular map of early lung cancer development., Author(s): Vitor H. Teixeira [sup.1] , Christodoulos P. Pipinikas [sup.1] [sup.2] , Adam Pennycuick [sup.1] , Henry Lee-Six [sup.3] , Deepak Chandrasekharan [sup.1] , Jennifer Beane [sup.4] , Tiffany J. [...]

Introduction: Oral cancer is the sixth most common cancer worldwide. According to scientific data on oral cancer, the epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK) are two important causative pathways responsible for cellular proliferation in oral cancer. In the current research, two chemical compounds, 3-O-methyl-d-glucose and squalene, identified in Wrightia tinctoria extract, were used to study their action on the EGFR and MAPK pathways using molecular docking to prevent oral cancer progression. Materials and Methods: A molecular docking analysis was carried out based on the chemical makeup and similarities of chemicals derived from the plant with the target oncogenic proteins EGFR and MAPK. Following protein synthesis by Biovia Discovery Studio Visualizer, ligands were imported for virtual screening using PyRx, a program for computational drug discovery for the virtual screening of libraries of compounds against therapeutic targets. Results: The molecular docking investigation between 3-O-methyl-d-glucose, squalene, and the oncogenic pathways EGFR and MAPK was conducted using the Biovia Discovery Studio Client 2021 and AutoDock Vina software. In contrast to squalene, which exhibited an inhibitory constant of 44.99 µM and a ligand efficacy of 0.20, 3-O-methyl-d-glucose had an effective inhibitory constant (10.5mM) on EGFR and MAPK. Both substances hindered the LSY721 binding site, which in turn suppressed the activity of oncogenic progression. Conclusion: 3-O-methyl-d-glucose and squalene found in W. tinctoria can inhibit the progressive activity of cancer-causing proteins (EGFR, MAPK) in oral cancer. 3-O-methyl-dglucose was found to inhibit the oncogenic proteins more efficiently than squalene. [ABSTRACT FROM AUTHOR]

Introduction: After fixed orthodontic treatment, following bracket removal, the debonding procedure should lead to restitutio ad integrum of the enamel or, at least, restore the enamel surface as closely as possible to its pretreatment condition. Adhesion of brackets in orthodontics is that they should be strong enough to prevent failure during all treatment but also low enough, so that enamel damage would be minimal during bracket removal after treatment.Material and Methods: A total of 60 premolars were collected and stored in distilled water. The extracted teeth were divided into two groups of 30 each, group A was to be bonded with self-cure adhesive while group B light cure adhesive was to be used. A standardised protocol was followed for adhering the brackets to the tooth surfaces. All the teeth were bonded with metal brackets (3M Unitek, Gemini Twin Brackets 0.022 slot). In group A, bonding adhesive (3M Unitek self cure adhesive primer) was applied. In group B, the bonding adhesive (3M Unitek light cure adhesive primer) was photopolymerized for 10 seconds after application.Results: Surface roughness of enamel as assessed by profilometry shows that light cure adhesive creates more roughness as compared to self cure adhesive. To conclude, self cure adhesive is clinically better than light cure adhesive.Discussion: In the present study enamel surface roughness were compared after debonding. Enamel surface roughness after bracket debonding depends on a host of factors, which include - brackets, adhesive used and method of remnant removal. [ABSTRACT FROM AUTHOR]

The article describes the operation of a protocol for evaluation of condylar position and morphology in symptomatic temporomandibular disorder (TMD) patients. The examination procedure to identify the area or structure of the masticatory system that shows breakdown or pathologic change is discussed. The case history is presented of a 27-year-old female complaining of irregular upper and lower front teeth and pain in the right temporomandibular joint (TMJ) region.

Background: Despite recent clinical guideline development, the best pathway of care for children with symptoms of obstructive sleep-disordered breathing (oSDB) is still debated. This systematic review aims to map the research in childhood oSDB that has been conducted so far to support further guideline development, identify evidence gaps, and guide future research., Methods: A systematic search was performed in PubMed, EMBASE, and the Cochrane Library from inception to November 26, 2015. All publications on childhood oSDB were included, irrespective of type and language. The annual number of publications in the field of oSDB was counted over all years; for those published since January 1, 2011 (ie, the date of the latest literature search of the American Academy of Pediatrics guideline), total and annual numbers of publications across main research themes and methodologies were calculated., Results: Of the 7,637 unique records retrieved, 5,871 publications were eligible for inclusion. There was an increase in annual publications since 2000, with 46% published since 2011. Most publications (61%) focused on individual treatment modalities, incidence, or prognosis. Few publications (2.7%) focused on health service delivery, outcomes, and health economics. Observational studies composed 78.5% of publications, 2.4% were randomized controlled trials, and 0.4% used a qualitative approach as their main methodology., Conclusions: A recent surge in research activity into childhood oSDB has improved the knowledge base for this condition; however, the lack of health services, health economics, and outcomes research impacts the applicability of evidence informing current guidance and leaves important questions for future research., Registration: PROSPERO: registration number CRD42015029291., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)