B and T cell epitope-based peptides predicted from clumping factor protein of Staphylococcus aureus as vaccine targets.

Staphylococcus aureus infection is emerging as a global threat because of the highly debilitating nature of the associated disease's unprecedented magnitude of its spread and growing global resistance to antimicrobial medicines. Recently WHO has categorized these bacteria under the high global priority pathogen list and is one of the six nosocomial pathogens termed as ESKAPE pathogens which have emerged as a serious threat to public health worldwide. The development of a specific vaccine can stimulate an optimal antibody response, thus providing immunity against it. Therefore, in the present study efforts have been made to identify potential vaccine candidates from the Clumping factor surface proteins (ClfA and ClfB) of S. aureus. Employing the immunoinformatics approach, fourteen antigenic peptides including T-cell, B-cell epitopes were identified which were non-toxic, non-allergenic, high antigenicity, strong binding efficiency with commonly occurring MHC alleles. Consequently, a multi-epitope vaccine chimera was designed by connecting these epitopes with suitable linkers an adjuvant to enhance immunogenicity. Further, homology modeling and molecular docking were performed to construct the three-dimensional structure of the vaccine and study the interaction between the modeled structure and immune receptor (TLR-2) present on lymphocyte cells. Consequently, molecular dynamics simulation for 100 ns period confirmed the stability of the interaction and reliability of the structure for further analysis. Finally, codon optimization and in silico cloning were employed to ensure the successful expression of the vaccine candidate. As the targeted protein is highly antigenic and conserved, hence the designed novel vaccine construct holds potential against emerging multi-drug-resistant organisms.

Molecular insights to in vitro biocompatibility of endodontic Pulpotec with macrophages determined by oxidative stress and apoptosis.

Pulp therapy has been emerged as a one of the efficient therapies in the field of endodontics. Among different types of new endodontic materials, pulpotec has been materialized as a recognized material for vital pulp therapy. However, its efficacy has been challenged due to lack of information about its cellular biocompatibility. This study evaluates the mechanistic biocompatibility of pulpotec cement with macrophage cells (RAW 264.7) at cellular and molecular level. The biocompatibility was evaluated using experimental and computational techniques like MTT assay, oxidative stress analysis and apoptosis analysis through flow cytometry and fluorescent microscopy. The results showed concentration-dependent cytotoxicity of pulpotec cement extract to RAW 264.7 cells with an LC 50 of X/10-X/20. The computational analysis depicted the molecular interaction of pulpotec cement extract components with metabolic proteins like Sod1 and p53. The study revealed the effects of Pulpotec cement's extract, showing a concentration-dependent induction of oxidative stress and apoptosis. These effects were due to influential structural and functional abnormalities in the Sod1 and p53 proteins, caused by their molecular interaction with internalized components of Pulpotec cement. The study provided a detailed view on the utility of Pulpotec in endodontic applications, highlighting its biomedical aspects.

Nationwide Trends of Modern Endodontic Practices Related to Working Length, Instrumentation, Magnification, and Obturation: A Comparative Cross-Sectional Survey Comparing Endodontic and Non-Endodontic Specialties Practicing Root Canal Treatment in India.

Aim: The present study was designed to assess trends in contemporary endodontic practice regarding the techniques and materials used in endodontic therapy among dental practitioners from various regions of India. Methods: A cross-sectional questionnaire-based study was conducted amongst dentists who were pursuing postgraduates in endodontics (PG Endo) and other branches (PG-OB), specialists from other branches (MDS-OB) and specialists in endodontics (MDS-Endo) in various dental colleges representing East, West, North, South, and Central zones through an e-survey using Google forms. State-wise postgraduate dental college lists were obtained from the Dental Council of India (DCI) website. Using a multistage cluster random sampling method and considering the unanticipated response rate, emails were sent to 2100. A 29-item close-ended questionnaire, framed according to different aspects of endodontic treatment, was used to record the responses. Results: When the distribution of the groups of dentists was compared, the central zone had the highest number of PG-OB (44.2%) and the lowest number of MDS-Endo (8.4%). The electronic apex locator (EAL) method of working length determination has been reported less among MDS-Endo than MDS-OB. The difference between the usage of various methods for working length determination was significant among the different groups in all the zones. (p < 0.0001) Most MDS-Endo preferred the rotary method of instrumentation over the combination method for different zones. The majority of dental practitioners preferred a combination method of instrumentation. Conclusion: Zone-wise comparisons among dentists showed the majority of general dental practitioners preferred the combination method (radiographs and electronic apex locator) for working length determination. Most MDS-Endo preferred the rotary method of instrumentation over the combination method for different zones. All dental practitioners did not so commonly use magnification in all the zones. The single cone technique was the most opted by dental practitioners of all the zones.

The paradigm of miRNA and siRNA influence in Oral-biome.

Short nucleotide sequences like miRNA and siRNA have attracted a lot of interest in Oral-biome investigations. miRNA is a small class of non-coding RNA that regulates gene expression to provide effective regulation of post-transcription. On contrary, siRNA is 21-25 nucleotide dsRNA impairing gene function post-transcriptionally through inhibition of mRNA for homologous dependent gene silencing. This review highlights the application of miRNA in oral biome including oral cancer, dental implants, periodontal diseases, gingival fibroblasts, oral submucous fibrosis, radiation-induced oral mucositis, dental Pulp, and oral lichenoid disease. Moreover, we have also discussed the application of siRNA against the aforementioned disease along with the impact of miRNA and siRNA to the various pathways and molecular effectors pertaining to the dental diseases. The influence of upregulation and downregulation of molecular effector post-treatment with miRNA and siRNA and their impact on the clinical setting has been elucidated. Thus, the mentioned details on application of miRNA and siRNA will provide a novel gateway to the scholars to not only mitigate the long-lasting issue in dentistry but also develop new theragnostic approaches.

Biofilm modifiers: The disparity in paradigm of oral biofilm ecosystem.

A biofilm is a population of sessile microorganisms that has a distinct organized structure and characteristics like channels and projections. Good oral hygiene and reduction in the prevalence of periodontal diseases arise from minimal biofilm accumulation in the mouth, however, studies focusing on modifying the ecology of oral biofilms have not yet been consistently effective. The self-produced matrix of extracellular polymeric substances and greater antibiotic resistance make it difficult to target and eliminate biofilm infections, which lead to serious clinical consequences that are often lethal. Therefore, a better understanding is required to target and modify the ecology of biofilms in order to eradicate the infection, not only in instances of oral disorders but also in terms of nosocomial infections. The review focuses on several biofilm ecology modifiers to prevent biofilm infections, as well as the involvement of biofilm in antibiotic resistance, implants or in-dwelling device contamination, dental caries, and other periodontal disorders. It also discusses recent advances in nanotechnology that may lead to novel strategies for preventing and treating infections caused by biofilms as well as a novel outlook to infection control.

Phage delivered CRISPR-Cas system to combat multidrug-resistant pathogens in gut microbiome.

The Host-microbiome interactions that exist inside the gut microbiota operate in a synergistic and abnormal manner. Additionally, the normal homeostasis and functioning of gut microbiota are frequently disrupted by the intervention of Multi-Drug Resistant (MDR) pathogens. CRISPR-Cas (CRISPR-associated protein with clustered regularly interspersed short palindromic repeats) recognized as a prokaryotic immune system has emerged as an effective genome-editing tool to edit and delete specific microbial genes for the expulsion of bacteria through bactericidal action. In this review, we demonstrate many functioning CRISPR-Cas systems against the anti-microbial resistance of multiple pathogens, which infiltrate the gastrointestinal tract. Moreover, we discuss the advancement in the development of a phage-delivered CRISPR-Cas system for killing a gut MDR pathogen. We also discuss a combinatorial approach to use bacteriophage as a delivery system for the CRISPR-Cas gene for targeting a pathogenic community in the gut microbiome to resensitize the drug sensitivity. Finally, we discuss engineered phage as a plausible potential option for the CRISPR-Cas system for pathogenic killing and improvement of the efficacy of the system.

Diagnostic Accuracy of Pulp Vitality Tests and Pulp Sensibility Tests for Assessing Pulpal Health in Permanent Teeth: A Systematic Review and Meta-Analysis.

The current systematic review and meta-analysis was carried out to compare the diagnostic accuracy of pulp vitality and pulp sensibility tests in assessing pulpal health. PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, Google Scholar and Open Grey databases were searched and after assessing eligibility criteria the data were extracted. True-positive, false-positive, true-negative, false-negative, sensitivity and specificity values were extracted or calculated if not presented. Quality of studies was evaluated based on the QUADAS 2 tool. Meta-analysis was performed in MetaDTA (v2.0; Shinyapps, RStudio PBC, Boston, MA, USA) and Review Manager 5.3 (RevMan web; The Cochrane Collaboration, London, UK). Ten articles were included for qualitative synthesis and five for meta-analysis. The pooled diagnostic odds ratio for pulse oximeter (PO), electric pulp tester (EPT), cold test (CT) and heat test (HT) was 628.5, 10.75, 17.24 and 3.47, respectively. Pairwise comparison demonstrated a higher pooled mean sensitivity and specificity with PO compared with EPT. Comparison between PO and CT and between PO and HT also demonstrated a higher pooled mean sensitivity and specificity for PO. Summary points on receiver operating characteristic curves confirmed the ability of PO to correctly screen negatives in presenting patients as compared to EPT, CT and HT but no study was rated as good on quality assessment. PO can be considered as the most accurate diagnostic method as compared to EPT, CT and HT. This review provides information about the reliability and diagnostic accuracy of using pulp vitality and sensibility tests for assessing pulp status.

Efficacy of 4% articaine vs 2% lidocaine in mandibular and maxillary block and infiltration anaesthesia in patients with irreversible pulpitis: a systematic review and meta-analysis.

OBJECTIVE: The goal of this systematic review and meta-analysis is to determine the performance of 4% Articaine vs. 2% Lidocaine for mandibular and maxillary block and infiltration anaesthesia in patients with irreversible pulpitis (IP). METHODS: PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, Google Scholar, and Open Gray were used to conduct a thorough literature search. A manual search of the reference lists of the publications found was also carried out. Two reviewers critically evaluated the papers for inclusion and exclusion criteria, and data extraction was done on the selected publications. The Cochrane Collaboration Tool and the Minors checklist were used to assess the quality of the selected studies for randomised controlled trials (RCTs) and non-randomised studies, respectively. The RevMan software was used to perform a meta-analysis of the pooled data and subgroups according to the technique of anaesthetic solution delivery, as well as a sensitivity analysis (P < 0.05). RESULTS: A total of twenty-six papers were included in the qualitative synthesis, with twenty-two of them being included in the meta-analysis. There were fifteen studies with a low potential for bias, three with a moderate potential for bias, and seven with a high potential for bias. The combined results of the 19 trials in the tooth level unit revealed that 4% articaine had a success rate 1.37 times greater than 2% lidocaine for mandibular teeth (RR, 1.37; 95% CI [1.17-1.62]; P = 0.0002). For the maxillary buccal infiltration method, the combined results from the three trials revealed that 4% articaine resulted in a success rate 1.06 times greater than 2% lidocaine (RR, 1.06; 95% CI [0.95-1.2]; P = 0.3). Excluding subgroups with a single study in sensitivity analysis for mandibular teeth revealed a substantial improvement in the success rate of the articaine group in treating IP when compared to the lidocaine group. CONCLUSION: The findings of this meta-analysis back up the claim that articaine is more effective than lidocaine in providing anaesthesia in patients with IP. PROSPERO Registration No.: CRD42020204606 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020204606).

Modern endodontic practices among dentists in India: A comparative cross-sectional nation-based survey.

INTRODUCTION: More than 41,000 root canal treatments (RCTs) are performed every day and about 25 RCTs are performed every week by an endodontist. The success rate of endodontic treatment ranges between 86% and 98%; however, the failure rates cannot be ignored which can range up to 20% of the treated cases due to a varied number of reasons including incorrect adoption of working techniques and usage of inappropriate materials. The present study aimed at comparing the practices of various levels of dentists toward RCT in their daily practice. METHODOLOGY: A cross-sectional, descriptive, questionnaire-based study was conducted among the dental practitioners who have completed the Masters of Dental Surgery (MDS) curriculum in India and postgraduate students in various dental colleges in India. The sample size was achieved to be 1601 at the completion of the study. The response rate for the study was 80.05%. All the dentists practicing RCT either in the clinic or in the college and willing to participate in the study were included in the study. A self-structured questionnaire was used as study tool. SPSS was used to analyze the data. RESULTS: A total of 26.7% of the PG students (endodontists) used rubber dam. Majority of the dentists preferred hand instruments (62.36%) over rotary. Almost half (53.09%) of the postgraduates belonging to other branches reported to prescribe drugs. CONCLUSION: The present study showed a varied profile of the dentists with most of them following the basic protocols and techniques of international standards.

Bioactive Materials in Endodontics: An Evolving Component of Clinical Dentistry.

Achieving biocompatibility in a material requires an interdisciplinary approach that involves a sound knowledge of materials science, bioengineering, and biotechnology. The host microbial-material response is also critical. Endodontic treatment is a delicate procedure that must be planned and executed properly. Despite major advances in endodontic therapy in recent decades, clinicians are confronted with a complex root canal anatomy and a wide selection of endodontic filling materials that, in turn, may not be well tolerated by the periapical tissues and may evoke an immune reaction. This article discusses published reports of various bioactive materials that are used in endodontic therapy, including calcium hydroxide, mineral trioxide aggregate, a bioactive dentin substrate, calcium phosphate ceramics, and calcium phosphate cements.

The Efficacy of Tranexamic Acid in the Reduction of Incidence of Dry Socket: An Institutional Double Blind Study.

BACKGROUND: Alveolar osteitis (AO) is an important postoperative problem with an incidence of 20% to 35% especially prevalent after the removal of mandibular molars. Fibrinolysis with subsequent loss of blood clotting is believed to be the general cause of AO. OBJECTIVES: This study aims to evaluate the efficacy of tranexamic acid, an antifibrinolytic agent in comparison with a placebo with respect to the reduction of incidence of AO after the extraction of mandibular molars by using following parameters: Pain, disintegration of Clot, halitosis. MATERIALS AND METHODS: A double blind study consisted of 60 patients, who underwent routine dental extractions of mandibular molar teeth. Group A (30 patients) requiring routine dental extractions of mandibular teeth was randomly selected and was administered a dose of tranexamic acid orally (Pause 500mg) one hour prior to extraction of teeth. Gel foam soaked in tranexamic acid (160mg) was placed into the extraction socket postoperatively. A figure of eight silk suture was placed over the socket to secure the gelfoam. Group B (30 patients); a placebo (crocin) was given orally one hour prior to the extraction and gel foam soaked in saline was placed into the extraction socket postoperatively. A figure of eight silk suture was placed over the socket. Pain was rated individually by each patient at 3(rd), 7(th), 14(th) day after extraction and the results was statistically analysed. RESULTS: This study supports that the use of tranexamic acid both locally and systemically following the removal of the teeth reduces the incidence of AO associated with the extraction of mandibular molars. CONCLUSION: Tranexamic acid has several advantages also when used for simple dental extractions, namely: low cost and ready availability and therefore we recommend this treatment modality.