Master Regulators, Regulatory Networks, and Pathways of Glioblastoma Subtypes

Glioblastoma multiforme (GBM) is the most common malignant brain tumor. GBM samples are classified into subtypes based on their transcriptomic and epigenetic profiles. Despite numerous studies to better characterize GBM biology, a comprehensive study to identify GBM subtype-specific master regulators, gene regulatory networks, and pathways is missing. Here, we used FastMEDUSA to compute master regulators and gene regulatory networks for each GBM subtype. We also ran Gene Set Enrichment Analysis and Ingenuity Pathway Analysis on GBM expression dataset from The Cancer Genome Atlas Project to compute GBM- and GBM subtype-specific pathways. Our analysis was able to recover some of the known master regulators and pathways in GBM as well as some putative novel regulators and pathways, which will aide in our understanding of the unique biology of GBM subtypes

Inclusive education: pedagogical approach to online versus face-to-face teaching

In today’s educational landscape, active learning is often overlooked during lectures, seminars, and tutorials. The aim of this study was to investigate perceptions of online and face-to-face lecture formats and their impact on the learning experiences of undergraduate dental students in Years 3–5. This qualitative study was conducted to investigate the effectiveness of different lecture formats at the Institute of Dentistry for undergraduate dental students in Years 3–5. There were two specific questions asked to dental undergraduate students with additional free-text questions. In total, 120 of 221 undergraduate students participated in this study between October 2019 and February 2020, and only 42 participants included the free-text comments. Three core themes related to the blended learning approach were identified: (1) scheduled versus recorded lectures, (2) duration of academic lectures, and (3) neurodiversity and learning experiences. The results showed that the learners perceived the traditional didactic lectures as the least effective format. There is not a “one fits all” lecture format that would accommodate a neurodiversity-based approach that focuses on the strengths, abilities, and interests of students. Hybrid lecture formats in combination with online teaching coupled with small group tutorials could be suggested. There is a unique challenge in the post-COVID-19 era for both educators and learners due to the lack of clinical practice and heavy reliance on online methods of teaching in Dentistry. Therefore, the implication of these results on the planning and financing of programmes could be discussed in Higher Education

The antimicrobial effect of different vitamin D compounds on Streptococcus mutans and their impact on glycosyltransferase expression.

BACKGROUND: Streptococcus mutans is a virulent microorganism associated with dental caries. This in vitro study aimed to investigate the antimicrobial effects of Cholecalciferol (D3) and Doxercalciferol (D2), against S. mutans and on glycosyltransferase gene expression. METHODS: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of D3 and D2 for S. mutans were determined according to the Clinical Laboratory Standards Institute guidelines. The effect of the compounds on environmental pH in 1% w/v and 5% w/v sucrose broth cultures after 24 hours were assessed colorimetrically. Additionally, their impact on glycosyltransferases gene expression (GtfB, GtfC, GtfD) in 5% w/v sucrose culture was evaluated using quantitative real-time PCR. RESULTS: The MBCs of D3 and D2 were 83 µg/ml and 166 µg/ml respectively. Both compounds were effective in preventing the local pH drop <5.5 at ≥166 µg/ml in sucrose supplemented cultures. However, the compounds did not inhibit pH drop at MIC values. Notably, D2 upregulated GtfD expression significantly (p < 0.05) and downregulated GtfB and GtfC. CONCLUSION: Vitamin D2 and D3 inhibited S. mutans mediated pH drop in sucrose supplemented cultures and altered glycosyltransferase expression, suggesting potential therapeutic roles in dental caries prevention. Further research is needed to assess their full impact on S. mutans survival under environmental stresses

Systematic review on dental caries preventive and managing strategies among type 2 diabetic patients

PURPOSE: The purpose of this systematic review was to evaluate current evidence to prevent and manage dental caries in patients with type 2 diabetes mellitus (T2DM). METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the Participants, Intervention, Comparison, Outcomes and Study Design (PICOS) strategy was used to formulate a structured search: systematic search of PubMed, Cochrane Library, MEDLINE via Ovid, EMBASE, Scopus, Web of Science, and Lilacs without any date limit and/or language restrictions. Two independent reviewers performed data extraction and risk of bias assessments in the included studies. Data homogeneity was assessed according to interventions for treating dental caries in T2DM. Statistical analyses were performed with JMP(®). RESULTS: Two studies out of 909 were included in the systematic review. Only quantitative studies involving topical applications for management of dental caries in patients with T2DM were included. One study assessed the effect of intensive oral hygiene care program including toothbrushing and interdental cleaning using interproximal brushes and/or dental floss and supragingival debridement by dental hygienist with educational brochures in T2DM, while another investigated the immunologically active salivary substitutes with using Oral Hygiene Instructions (OHI), mouthwash, and moisturizing gel for 6 months. Intensive oral hygiene care program or immunologically active salivary substitutes with using OHI, mouthwash, and moisturizing gel for 6 months were reported to reverse/arrest dental caries in patients with T2DM. CONCLUSION: The current randomized controlled clinical trials demonstrated that regular extensive oral health education using interdental cleaning aids, mouthwash, moistening gel, and saliva substitutes including lactoperoxidase, lysozyme, glucose oxidase, and lactoferrin could control oral inflammation and contribute to the management of dental caries in patients with T2DM. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020197507, identifier: CRD42020197507

The effect of different concentrations of fluoride in toothpastes with or without bioactive glass on artificial root caries.

OBJECTIVE: To investigate the effect of different toothpastes either containing 5,000ppm-F, 1,450ppm-F or bioactive glass (BG) with 540ppm-F on artificial root carious lesions (ARCLs). METHOD: The crowns of 23 extracted sound teeth were removed leaving their roots only. Subsequently, each root was divided into four parts. A total of 15 sound root dentine (SRD) was left untreated as baseline. The ARCLs were developed for the remaining roots using demineralisation solution (pH-4.8). 15-ARCLs samples were then left untreated. The rest of samples were divided into four groups (n=15 each) and treated with Group-1(BG with 540ppm-F); Group-2(5,000ppm-F); Group-3(1,450ppm-F) and Group-4(deionised water). 13-day pH-cycling included using demineralisation solution for 6hrs, then placing samples into remineralisation solution (pH-7) for 16hrs. Each sample was brushed with the assigned toothpaste twice a day during pH-cycling. Fluoride concentrations at each time point were measured using F-ISE, whilst calcium (Ca2+) and phosphorus (P) ion release was determined using ICP-OES, KHN, XRD, 19F-MAS-NMR analyses. RESULTS: KHN showed significant surface changes for each group (p<0.001). The uptake of Ca2+ occurred at days 1-2, phosphorus ion loss was high when compared to the uptake in all groups. XRD showed presence of sharp diffraction lines evidencing apatite formation for Groups 1-3. 19F-MAS-NMR confirmed fluorapatite presence in Groups 1-3. CONCLUSION: All toothpastes were promising in fluorapatite formation. BG with 540ppm-F toothpaste released more ions (Ca2+and P) and reharden the artificial root carious lesions when compared to other groups. However, 1,450ppm-F toothpaste showed more fluoride-substituted apatite formation whilst 5,000ppm-F toothpaste had more fluorapatite formation. CLINICAL SIGNIFICANCE: Toothpaste containing BG with 540ppm-F, 5,000ppm-F and 1,450ppm-F toothpastes are likely to have a significant impact in reversing and arresting root caries. However, randomised controlled double-blinded clinical trials are required to translate these results into clinical practice

A systematic review on the effect of silver diamine fluoride for management of dental caries in permanent teeth.

OBJECTIVES: The objective of this review is to assess the available literature systematically related to the effect of silver diamine fluoride (SDF) for the management of occlusal and root carious lesions in permanent teeth regardless of age. MATERIALS AND METHODS: This systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Review and Meta-Analyses statement. A literature search was performed using PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, DOAJ, and Open Gray with no language restrictions up to December 2022. Three reviewers critically assessed the studies for eligibility. Any disputes between the reviewers were handled by a fourth independent reviewer. The quality assessment and data extraction of the studies were performed. RESULTS: A total of 2176 studies were screened. The titles and abstracts of the studies were then reviewed (n = 346), and 52 studies met the search criteria. Following the full-text review, 11 studies investigated the effect of SDF against other treatments such as chlorhexidine, sodium fluoride, ammonium bifluoride, tricalcium silicate paste, casein phosphopeptide amorphous calcium phosphate, glass ionomer cement (GIC) combined with fluoride varnish, resin-modified GIC, and atraumatic restorative treatment were assessed. CONCLUSIONS: Within the limitations of this review, the use of SDF is promising with high preventative fractions in permanent teeth of children and older populations when compared to other topical applications such as dental varnish containing sodium fluoride

Evaluation of toothpastes for treating root carious lesions - a laboratory-based pilot study.

BACKGROUND: Root caries is preventable and can be arrested at any stage of disease development. The aim of this study was to investigate the potential mineral exchange and fluorapatite formation within artificial root carious lesions (ARCLs) using different toothpastes containing 5,000 ppm F, 1,450 ppm F or bioactive glass (BG) with 540 ppm F. MATERIALS AND METHODS: The crowns of each extracted sound tooth were removed. The remaining roots were divided into four parts (n = 12). Each sample was randomly allocated into one of four groups: Group 1 (Deionised water); Group 2 (BG with 540 ppm F); Group 3 (1,450 ppm F) and Group 4 (5,000 ppm F). ARCLs were developed using demineralisation solution (pH 4.8). The samples were then pH-cycled in 13 days using demineralisation solution (6 h) and remineralisation solution (pH 7) (16 h). Standard tooth brushing was carried out twice a day with the assigned toothpaste. X-ray Microtomography (XMT) was performed for each sample at baseline, following ARCL formation and after 13-day pH-cycling. Scanning Electron Microscope (SEM) and 19F Magic angle spinning nuclear magnetic resonance (19F-MAS-NMR) were also performed. RESULTS: XMT results showed that the highest mineral content increase (mean ± SD) was Group 4 (0.09 ± 0.05), whilst the mineral content decreased in Group 1 (-0.08 ± 0.06) after 13-day pH-cycling, however there was evidence of mineral loss within the subsurface for Groups 1, 3 and 4 (p < 0.05). SEM scans showed that mineral contents within the surface of dentine tubules were high in comparison to the subsurface in all toothpaste groups. There was evidence of dentine tubules being either partially or completely occluded in toothpaste groups. 19F-MAS-NMR showed peaks between - 103 and - 104ppm corresponding to fluorapatite formation in Groups 3 and 4. CONCLUSION: Within the limitation of this laboratory-based study, all toothpastes were potentially effective to increase the mineral density of artificial root caries on the surface, however there was evidence of mineral loss within the subsurface for Groups 1, 3 and 4