Current Scenario of Teledentistry in Public Healthcare in India

India is the largest democracy and the second most populated nation in the world. Although with 190,000   dentists, India ranks top in the absolute number of dental graduates, rural Indians and urban slums remain deprived of quality dental healthcare due to unequal distribution and access. About 1,000 telemedicine nodes have been established by Government/Private/Trust agencies to reinforce the national healthcare delivery system in India however an organised and dedicated teledentistry network is non-existent but for the Collaborative Digital Diagnosis System (CollabDDS). CollabDDS was developed in India for tele-consultation, diagnosis, remote education and as a data repository. It is a remote expert dental programme served between three dental schools with the Centre for Dental Education and Research at the All India Institute of Medical Sciences in New Delhi. There are some major challenges which exist and need to be addressed including lack of government initiatives, reimbursement schemes, data protection laws, technical infrastructure, advanced biological sensors, bandwidth support, orientation among doctors, and linguistic diversity, along with patients’ fear and unfamiliarity. With an area of 3,287 million km2, an urban-rural divide, inaccessible areas, the country is an ideal setting for the provision of eHealth. This paper highlights the present status, challenges and future of teledentistry in India

Comparative Analysis of Species-Specific Ligand Recognition in Toll-Like Receptor 8 Signaling: A Hypothesis

Toll-like receptors (TLRs) play a central role in the innate immune response by recognizing conserved structural patterns in a variety of microbes. TLRs are classified into six families, of which TLR7 family members include TLR7, 8, and 9, which are localized to endolysosomal compartments recognizing viral infection in the form of foreign nucleic acids. In our current study, we focused on TLR8, which has been shown to recognize different types of ligands such as viral or bacterial ssRNA as well as small synthetic molecules. The primary sequences of rodent and non-rodent TLR8s are similar, but the antiviral compound (R848) that activates the TLR8 pathway is species-specific. Moreover, the factors underlying the receptor's species-specificity remain unknown. To this end, comparative homology modeling, molecular dynamics simulations refinement, automated docking and computational mutagenesis studies were employed to probe the intermolecular interactions between this anti-viral compound and TLR8. Furthermore, comparative analyses of modeled TLR8 (rodent and non-rodent) structures have shown that the variation mainly occurs at LRR14-15 (undefined region); hence, we hypothesized that this variation may be the primary reason for the exhibited species-specificity. Our hypothesis was further bolstered by our docking studies, which clearly showed that this undefined region was in close proximity to the ligand-binding site and thus may play a key role in ligand recognition. In addition, the interface between the ligand and TLR8s varied depending upon the amino acid charges, free energy of binding, and interaction surface. Therefore, our current work provides a hypothesis for previous in vivo studies in the context of TLR signaling

Molecular Modeling-Based Evaluation of hTLR10 and Identification of Potential Ligands in Toll-Like Receptor Signaling

Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogens based on distinct molecular signatures. The human (h)TLR1, 2, 6 and 10 belong to the hTLR1 subfamilies, which are localized in the extracellular regions and activated in response to diverse ligand molecules. Due to the unavailability of the hTLR10 crystal structure, the understanding of its homo and heterodimerization with hTLR2 and hTLR1 and the ligand responsible for its activation is limited. To improve our understanding of the TLR10 receptor-ligand interaction, we used homology modeling to construct a three dimensional (3D) structure of hTLR10 and refined the model through molecular dynamics (MD) simulations. We utilized the optimized structures for the molecular docking in order to identify the potential site of interactions between the homo and heterodimer (hTLR10/2 and hTLR10/1). The docked complexes were then used for interaction with ligands (Pam3CSK4 and PamCysPamSK4) using MOE-Dock and ASEDock. Our docking studies have shown the binding orientations of hTLR10 heterodimer to be similar with other TLR2 family members. However, the binding orientation of hTLR10 homodimer is different from the heterodimer due to the presence of negative charged surfaces at the LRR11-14, thereby providing a specific cavity for ligand binding. Moreover, the multiple protein-ligand docking approach revealed that Pam3CSK4 might be the ligand for the hTLR10/2 complex and PamCysPamSK4, a di-acylated peptide, might activate hTLR10/1 hetero and hTLR10 homodimer. Therefore, the current modeled complexes can be a useful tool for further experimental studies on TLR biology

The effect of COVID-19 on orthodontic treatment demand and its delivery in India

Introduction: The ongoing pandemic has transformed the entire structural and functional framework of the world including the medical and dental healthcare services. The current study intends to examine the pattern of dynamically changing working conditions and orthodontic treatment delivery during the various phases of pandemic. Method: An online survey was conducted using Google form for orthodontic specialists practicing in India. Information regarding the impact of the pandemic on various aspects like patient turnover, treatment demand, clinical management, and new challenges faced were analysed through a self-designed close-ended questionnaire for two phases. Phase I (March 2020 to September 2020) corresponded to the onset of COVID 19 pandemic and lockdown, whereas the Phase II (October 2020 to March 2021) coincided with the time of Unlock and resumption of activities thereafter. Results: The parameters showing similar trend in Phases I and II included the willingness of ongoing orthodontic patients to report for appointments, choice of treatment modality, number and type of emergencies, cost of materials, guidelines for work, and duration of non-delivery of orthodontic procedures. The new patients reporting, complex orthodontic therapy, tele-consultation, and financial wellbeing showed an improvement while the usage of personal protective equipment kit, fear amongst orthodontists reduced in Phase II. Conclusions: Challenging situations warrant prudent measures to combat and continue the essential services, especially those related to the healthcare. A detailed analysis of the various phases of the ongoing pandemic will enable us to devise suitable measures to ensure uninterrupted orthodontic treatment even in such critical times

In silico approach to inhibition of signaling pathways of Toll-like receptors 2 and 4 by ST2L.

Toll-like receptors (TLRs) activate a potent immunostimulatory response. There is clear evidence that overactivation of TLRs leads to infectious and inflammatory diseases. Recent biochemical studies have shown that the membrane-bound form of ST2 (ST2L), a member of the Toll-like/IL-1 receptor superfamily, negatively regulates MyD88-dependent TLR signaling pathways by sequestrating the adapters MyD88 and Mal (TIRAP). Specifically, ST2L attenuates the recruitment of Mal and MyD88 adapters to their receptors through its intracellular TIR domain. Thus, ST2L is a potent molecule that acts as a key regulator of endotoxin tolerance and modulates innate immunity. So far, the inhibitory mechanism of ST2L at the molecular level remains elusive. To develop a working hypothesis for the interactions between ST2L, TLRs (TLR1, 2, 4, and 6), and adapter molecules (MyD88 and Mal), we constructed three-dimensional models of the TIR domains of TLR4, 6, Mal, and ST2L based on homology modeling. Since the crystal structures of the TIR domains of TLR1, 2 as well as the NMR solution structure of MyD88 are known, we utilized these structures in our analysis. The TIR domains of TLR1, 2, 4, 6, MyD88, Mal and ST2L were subjected to molecular dynamics (MD) simulations in an explicit solvent environment. The refined structures obtained from the MD simulations were subsequently used in molecular docking studies to probe for potential sites of interactions. Through protein-protein docking analysis, models of the essential complexes involved in TLR2 and 4 signaling and ST2L inhibiting processes were developed. Our results suggest that ST2L may exert its inhibitory effect by blocking the molecular interface of Mal and MyD88 adapters mainly through its BB-loop region. Our predicted oligomeric signaling models may provide a basis for the understanding of the assembly process of TIR domain interactions, which has thus far proven to be difficult via in vivo studies

Accuracy of 3D cephalometric measurements based on an automatic knowledge-based landmark detection algorithm

PURPOSE: To evaluate the accuracy of three-dimensional cephalometric measurements obtained through an automatic landmark detection algorithm compared to those obtained through manual identification. METHODS: The study demonstrates a comparison of 51 cephalometric measurements (28 linear, 16 angles and 7 ratios) on 30 CBCT (cone beam computed tomography) images. The analysis was performed to compare measurements based on 21 cephalometric landmarks detected automatically and those identified manually by three observers. RESULTS: Inter-observer ICC for each landmark was found to be excellent ([Formula: see text]) among three observers. The unpaired t-test revealed that there was no statistically significant difference in the measurements based on automatically detected and manually identified landmarks. The difference between the manual and automatic observation for each measurement was reported as an error. The highest mean error in the linear and angular measurements was found to be 2.63 mm ([Formula: see text] distance) and [Formula: see text] ([Formula: see text]-Me angle), respectively. The highest mean error in the group of distance ratios was 0.03 (for N-Me/N-ANS and [Formula: see text]). CONCLUSION: Cephalometric measurements computed from automatic detection of landmarks on 3D CBCT image were as accurate as those computed from manual identification

Morphological evaluation of mental foramen using cone-beam computed tomography: A retrospective observational study

Aim: This study aimed to assess the shape, size, symmetry, and location of mental foramen (MF) in relation to mandibular dental and skeletal landmarks using cone-beam computed tomography (CBCT). Methods: This retrospective observational study was performed on 135 CBCT images of 74 males (mean age 36.16 ± 13.49 years) and 61 females (mean age 37.13 ± 13.53 years). Two independent observers performed the morphometric measurements of MF using CBCT images using Invivo software. Independent t-test and Mann–Whitney test were employed to evaluate the gender differences. A comparison of categorical data was performed using Chi-square test. Intraclass correlation coefficient and Kappa statistics were used to assess interobserver reliability. Results: The most common horizontal and vertical location of MF was the long axis of the second premolars (52.2%) and below the bicuspid root apices (70%), respectively. The most common shape was round (56.6%). Significant gender differences were observed for the MF size (mean width 0.35 mm larger in males), the distance of MF to lower border of mandible (16.10 ± 1.77 mm in males and 14.81 ± 1.48 mm in females), and MF to pogonion (28 ± 2.13 mm in males and 26.62 ± 1.98 mm in females). The horizontal and vertical locations were bilaterally symmetrical in 67.4% and 79.26% of subjects, respectively. Conclusion: Right and left sides of the mandible require separate evaluations since there are differences in the location of the MF on each side. Gender differences were observed in location of MF in the relation to skeletal landmarks. Nevertheless, skeletal landmarks are reliable for locating the MF

Biomarkers in Body Fluids as Indicators of Skeletal Maturity: A Systematic Review and Meta-analysis

Objectives: This review aimed to critically appraise the evidence for biomarkers in blood serum, gingival crevicular fluid (GCF), saliva, and urine in comparison with standard radiographic indices for skeletal maturation assessment. Materials and Methods: A thorough literature search in multiple databases was conducted for biomarkers in body fluids for skeletal maturation assessed with cervical vertebrae in lateral cephalograms or on hand-wrist radiographs. Different combinations including free text, MeSH terms, and Boolean operators were used. Two researchers used strict inclusion and exclusion criteria to screen title, abstract, and full text, and used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 instrument for risk of bias assessment of individual studies. Meta-analysis was performed on eligible studies using RevMan 5 software. Results: A total of 344 articles were screened, of which 33 met the inclusion criteria and quality assessment. The skeletal maturity indicators included insulin-like growth factors (IGF-1), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), dehydroepiandrosterone sulfate (DHEAS), vitamin D binding protein (DBP), parathormone-related protein (PTHrP), osteocalcin, metalloproteins, and serotransferrin (TF) along with different metabolites. At puberty, a significant rise was seen in IGF-1, DBP, ALP, osteocalcin, TF, and BALP. However, the serum DHEAS and PTHrP increased from pre-pubertal to post-pubertal stages. Due to the data heterogeneity, a meta-analysis could be performed on seven studies in total on IGF-1 in serum and blood. Of these, five were included for data in males and six in females, and four studies on IGF-1 in serum and blood. A significant difference in IGF-1 levels was seen between stages of peak pubertal growth spurt (CS3 and CS4) and decelerating pubertal growth (CS5) compared with growth initiation stage (CS2). Conclusions: Pubertal growth spurts were correlated with peak serum IGF-1 and BALP in both sexes individually. Peak ALP levels in GCF were correlated with the pubertal spurt in a combined sample of males and females. Standard biofluid collection protocols and homogeneity in sampling and methodology are strongly recommended for future research