Quantifying variations associated with dental caries reveals disparity in effect allele frequencies across diverse populations.

BACKGROUND: Dental caries (DC) is a multifaceted oral condition influenced by genetic and environmental factors. Recent advancements in genotyping and sequencing technologies, such as Genome-Wide Association Studies (GWAS) have helped researchers to identify numerous genetic variants associated with DC, but their prevalence and significance across diverse global populations remain poorly understood as most of the studies were conducted in European populations, and very few were conducted in Asians specifically in Indians. AIM: This study aimed to evaluate the genetic affinity of effect alleles associated with DC to understand the genetic relationship between global populations with respect to the Indian context. METHODOLOGY: This present study used an empirical approach in which variants associated with DC susceptibility were selected. These variants were identified and annotated using the GWAS summary. The genetic affinity was evaluated using Fst. RESULTS: The effect of allele frequencies among different populations was examined, revealing variations in allele distribution. African populations exhibited higher frequencies of specific risk alleles, whereas East Asian and European populations displayed distinct profiles. South Asian populations showed a unique genetic cluster. CONCLUSION: Our study emphasises the complex genetic landscape of DC and highlights the need for population-specific research as well as validation of GWAS-identified markers in Indians before defining them as established candidate genes.

Guidelines for dental implants in the times of COVID-19.

Since the first reported case in December 2019, COVID-19 has become a worldwide pandemic. Although primarily a zoonotic infection, human-to-human transmission is well reported now and the mode of spread is mainly via respiratory droplets during direct contact or via surfaces contaminated with the virus as it remains viable on the surfaces for a long time. Direct communication and consistent exposure to body fluids such as blood and saliva and the fact that routinely done dental procedures generate aerosols predisposing dental professionals to serious risk for COVID-19 infection. Hence, to ensure the smooth working and safety of dental professionals as well as the patients, a set of directives are of paramount importance. Various guidelines have been released for the efficient operation of dental professionals; however, no such recommendations/directives have been laid out pertaining to dental implants in particular. Here, we are presenting a set of recommendations for managing urgent implant-related treatment procedures.

Design, Synthesis, and Investigation of the Pharmacokinetics and Anticancer Activities of Indenoisoquinoline Derivatives That Stabilize the G-Quadruplex in the MYC Promoter and Inhibit Topoisomerase I.

G-quadruplexes are noncanonical four-stranded DNA secondary structures. MYC is a master oncogene and the G-quadruplex formed in the MYC promoter functions as a transcriptional silencer and can be stabilized by small molecules. We have previously revealed a novel mechanism of action for indenoisoquinoline anticancer drugs, dual-downregulation of MYC and inhibition of topoisomerase I. Herein, we report the design and synthesis of novel 7-aza-8,9-methylenedioxyindenoisoquinolines based on desirable substituents and π-π stacking interactions. These compounds stabilize the MYC promoter G-quadruplex, significantly lower MYC levels in cancer cells, and inhibit topoisomerase I. MYC targeting was demonstrated by differential activities in Raji vs CA-46 cells and cytotoxicity in MYC-dependent cell lines. Cytotoxicities in the NCI-60 panel of human cancer cell lines were investigated. Favorable pharmacokinetics were established, and in vivo anticancer activities were demonstrated in xenograft mouse models. Furthermore, favorable brain penetration, brain pharmacokinetics, and anticancer activity in an orthotopic glioblastoma mouse model were demonstrated.

Associations among gene polymorphisms, crestal bone loss, and bone mineral density in patients receiving dental implants.

Objectives: Interleukin 1 (IL-1) and interleukin 6 (IL-6) gene polymorphisms have been suggested to be responsible for diminished bone mineral density (BMD) and high crestal bone loss (CBL) in some individuals. However, the effects of systemic BMD on variations in peri-implant CBL are unclear. Hence, this study was aimed at investigating the association of IL-1 and IL-6 gene polymorphisms with systemic BMD and CBL around dental implants. Methods: A total of 190 participants undergoing dental implantation in the mandibular posterior region were selected according to predetermined selection criteria and divided into a normal BMD group (NBD, 93 participants, T-score ≥ -1) and low BMD group (LBD, including both osteoporosis and osteopenia, 97 participants, T-score < -1 standard deviation) according to the BMD of the right femoral neck, measured with dual-energy X-ray absorptiometry. Dental implants were placed through the standard surgical protocol, and CBL was calculated after 6 months with cone beam computed tomography scans before second-stage surgery. Genotyping was performed on all participants for IL-1A-889 A/G, IL-1B-511G/A, IL-1B+3954, and IL-6-572 C/G gene polymorphisms. Results: The demographic and clinical characteristics of the participants in both groups were compared with t-test and chi-square test (χ2). The associations of NBD and LBD with the different genotypes and CBL was determined with odds ratios, and p < 0.05 was considered statistically significant. The frequency of IL-1B-511AA and IL-6-572 GG genotypes was significantly higher in LBD than in NBD (p < 0.05). In LBD, the IL-1B-511 AA (AA vs GA + GG; p ≤ 0.001) and IL-6-572 GG (GG vs CC + GC; p = 0.001) genotypes were significantly associated with higher peri-implant CBL. Conclusions: Individuals with the IL-1B-511 AA or IL-6-572 GG genotype had elevated risk of osteoporosis/osteopenia and were more susceptible to CBL around dental implants.

Synthesis and biological evaluation of Ribo 7-N/O/S pyrimidine 9-deaza C-nucleoside analogs as new antiviral agents for inhibiting HCV RNA-dependent RNA polymerases.

Hepatitis C infection is caused by the bloodborne pathogen hepatitis C virus (HCV) and can lead to serious liver diseases and, ultimately, death if the treatment is ineffective. This work reports the synthesis and preclinical evaluation of 7 novel 9-O/N/S pyrimidine nucleosides, including compound 12, the triphosphate of known compound 7b. The nucleosides are 9-deaza modifications of adenosine and guanosine with ß-2'-C-methyl substituent on the ribose. Within this series of compounds, a 9-deaza furopyrimidine analog of adenosine, compound 7b, showed high anti-HCV activity in vitro, good stability, low toxicity, and low genotoxicity when administrated in low doses, and an adequate pharmacokinetics profile. An improved synthesis of compound 7b compared to a previous study is also reported. Compound 12 was synthesized as a control to verify phosphorylation of 7b occurred in vivo.

Urinary metabolite signatures reflect the altered host metabolism in severe obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. The onset and progression of OSA are often linked with severe cardiovascular and metabolic comorbidities. At the same time, given the increasing prevalence of OSA, novel methods to screen OSA and its follow-up are needed. Untargeted metabolic profiling of OSA patients and healthy controls was planned to capture a snapshot of urinary metabolites and potential biomarkers using the gas chromatography-mass spectrometry (GC-MS) method.Polysomnography (PSG) confirmed severe OSA patients with AHI index ≥ 30 were considered for urine sample collection. The sample size was constituted of OSA (n = 36) and healthy controls (n = 36). Metabolite extraction and derivatization were performed and metabolomic analysis was performed by using GC-MS.The obtained data set was statistically analyzed using univariate and multivariate analysis. The Orthogonal partial least-squares discriminant analysis (OPLS-DA) was performed to screen differential metabolites between OSA patients and healthy controls.The metabolomic analysis revealed a total of 142 significantly altered metabolites of interest.Biomarker analysis allows for the creation of a list of putative urinary biomarkers including GABA, malic acid, glutamic acid, epichoric acid etc., with an accuracy of 99.8 % to 100 % for OSA screening. Subsequently, pathway analysis revealed that related biochemical pathways like the tricarboxylic acid cycle (TCA), glutamate/glutamine, amino acid and fatty acid metabolism, that are significantly interlinked with these metabolic biomarkers can play a crucial role in the pathogenesis of OSA. This study paves the way to undertake mass screening in a larger population to identify specific and reliable biomarkers.

A computed tomographic evaluation of effect of mandibular advancement device at two different horizontal jaw positions in patients with obstructive sleep apnea.

Statement of problem: Studies pertaining to the objective assessments of the efficacy of mandibular advancement device in patients with obstructive sleep apnea are scarce. Purpose: The purpose of this clinical study was to evaluate the effect of MAD at two different horizontal positions of mandible on upper airway dimensions through computed tomography. Material and methods: Twenty-nine consenting participants satisfying predetermined inclusion and exclusion criteria were enrolled and an adjustable two-piece MAD was fabricated at 50% maximum mandibular protrusion and after 4 weeks was adjusted to 70% protrusion. CT scans were obtained at baseline, 4 weeks after delivering MAD with 50% mandibular protrusion, and then after 4 weeks with 70% mandibular protrusion. Cross sectional area with diameters (lateral and anteroposterior) of upper airway was measured at three specific anatomic levels (retropalatal-RP, retroglossal-RG, and epiglottal-EG). Data were analyzed using the Student t-test for parametric analysis. Results: Intragroup comparison revealed a statistically significant increase in lateral & anteroposterior dimensions as well as cross sectional area at all three anatomical levels at 4 weeks after MAD with 50% mandibular protrusion compared with baseline and 4 weeks after MAD with 70% mandibular protrusion compared with baseline. However, the difference between lateral and anteroposterior dimensions with MAD at 70% protrusion compared with MAD at 50% protrusion was not statistically significant. The difference between cross-sectional area was found to be statistically significant. Conclusion: Mandibular advancement device at 70% mandibular protrusion is more effective compared with the device at 50% protrusion in relieving oropharyngeal obstruction seen in OSA.

Assessment of craniofacial growth in individuals with ectodermal dysplasia after complete denture rehabilitation: A preliminary study.

Aim: The main purpose was to evaluate the effect of complete denture rehabilitation on the jaw growth pattern in individuals with ectodermal dysplasia from an early age to maturity. Settings and Design: This was a prospective in vivo study performed in the Department of Prosthodontics, King George Medical University, Lucknow, India. Materials and Methods: Rehabilitation with three sets of conventional complete dentures was completed in an ectodermal dysplasia case at the age of 5, 10, and 17 years. Cephalometric and diagnostic cast analyses were the methods performed to evaluate jaw growth patterns. Linear and angular measurements obtained after denture rehabilitation were averaged and compared with mean standard values of nearly corresponding ages, as given by Sakamoto and Bolton. Conversely, alveolar ridge arch width and length were evaluated for their dimensional changes during the same age intervals. Statistical Analysis Used: Mann-Whitney U-test was used to check the difference between the groups. The significance of the level adopted was 5%. Results: Nasion-anterior nasal spine, anterior nasal spine-menton, anterior nasal spine-pterygomaxillary fissure, gonion-sella, and gonion-menton lengths were found to be not statistically significant than the mean standard values of nearly corresponding ages (P > 0.05). The decrease in facial plane angle, increase in Y-axis angle, and mandibular plane angle after complete denture rehabilitation were statistically significant when compared to their mean standard values (P < 0.05). Cast analysis showed more increase in the length compared to the width in both arches. Conclusion: Complete denture rehabilitation did not significantly affect the jaw growth pattern, although it improved facial esthetics and masticatory activity by establishing adequate vertical dimensions.

Mechanical failures of dental implants and supported prostheses: A systematic review.

Purpose: Though, mechanical dental implant and supported prosthesis failures are considered significant, a comprehensive evaluation is lacking. A systematic review analyzing different aspects related to such failures was therefore done. Methods: - Electronic search was carried out in PubMed/MEDLINE and Cochrane Library for articles published between 1981 and 2021. Articles were selected using predefined criteria. Data extraction was based on mechanical complications associated with dental implants, prosthetic implant failures, survival rate of implants, mechanical failure of implants placed in the maxilla and mandible, and mechanical complications associated with implant supported over dentures. Quality of included studies was assessed. Meta-analysis for heterogenicity testing, publication bias and implant failure assessment was conducted using MedCalc® Statistical Software version 19.7. Results: - Eighteen retrospective and prospective studies were included following PRISMA guidelines. Mechanical complications were more in the initial 9 years but reduced later. Abutment screw loosening was one of the more common mechanical complications (16.21%). Maxillary implant failure was greater compared to mandibular implant failure with an odds ratio of 4.66 (95% CI -3.21- 6.75). Failure of implant supported overdentures due to mechanical complications were 3% in the fixed effect, and 2.9% in the random effect model (P < 0.05). The overall prevalence of mechanical failure was between 5.6% and 7.7% (P < 0.05). Conclusion: Mechanical failures of implant and supported prosthesis have similar prevalence to biological and esthetic failures, and therefore need to be given due credence. Identifying specific factors contributing to such failures can help reduce incidence.

Association of interleukin-1, interleukin-6, collagen type I alpha 1, and osteocalcin gene polymorphisms with early crestal bone loss around submerged dental implants: A nested case control study.

STATEMENT OF PROBLEM: The reason for variations in peri-implant early crestal bone loss is unclear but may be due to genetic differences among individuals. PURPOSE: The purpose of this nested case control study was to investigate the association of single-nucleotide polymorphisms of interleukin-1, interleukin-6, collagen type I alpha1, and osteocalcin genes to early crestal bone loss around submerged dental implants. MATERIAL AND METHODS: Dental implants were placed in the mandibular posterior region (single edentulous space) of 135 participants selected according to predetermined selection criteria. Bone mineral density measurement by using dual energy X-ray absorptiometry, cone beam computed tomography scans at the baseline and after 6 months, and interleukin-1A-889 A/G (rs1800587), interleukin-1B-511 G/A (rs16944), interleukin-1B+3954 (rs1143634), interleukin-6-572 C/G (rs1800796), collagen type I alpha1 A/C (rs1800012), and osteocalcin C/T (rs1800247) genotyping were performed in all participants. Early crestal bone loss measured around dental implants was used to group participants into clinically significant bone loss (BL)>0.5 mm and clinically nonsignificant bone loss (NBL)≤0.5 mm. Early crestal bone loss was calculated as the mean of the difference of bone levels at the baseline and bone levels after 6 months as measured with cone beam computed tomography scans. The obtained data for basic characteristics, early crestal bone loss, and genotyping were tabulated and compared by using a statistical software program (α=.05). RESULTS: AA genotype and the A allele frequency of interleukin-1B-511 and GG genotype and the G allele frequency of interleukin-6-572 were significantly higher in BL than in NBL (P<.05). Multiple logistic analysis suggested that interleukin-1B-511 AA/GG+AG and interleukin-6-572 GG/CC+CG genotype expression were significantly associated with early crestal bone loss (AA/GG+AG; P=.014, GG/CC+CG; P=.047) around dental implants. Other risk factors were not significantly different (P>.05). CONCLUSIONS: Of the genes studied, individuals with interleukin-1B-511 AA (rs16944) or interleukin-6-572 GG (rs1800796) genotype had higher susceptibility to early crestal bone loss around dental implants.

Evaluation of mandibular advancement device placement based on levels of TNF-alpha in participants with obstructive sleep apnea: A clinical study.

STATEMENT OF PROBLEM: Objective assessments of the effect of mandibular advancement device on patients with obstructive sleep apnea are lacking. PURPOSE: The purpose of this clinical study was to compare levels of serum tumor necrosis factor alpha (TNF-alpha), Epworth Sleepiness Scale score, and Berlin Questionnaire score in patients with mild to moderate obstructive sleep apnea before and after treatment with a mandibular advancement device. MATERIAL AND METHODS: Twenty participants diagnosed with mild to moderate obstructive sleep apnea based on polysomnography testing were enrolled. A custom nonadjustable mandibular advancement device with 70% mandibular protrusion was provided for each participant for management of the obstructive sleep apnea. Evaluation of TNF-alpha levels was performed before treatment (baseline) and 3 and 6 months after starting mandibular advancement device therapy by using a Human TNF-alpha enzyme-linked immunoassay (ELISA) sandwich kit. The Epworth Sleepiness Scale and Berlin Questionnaire were also filled out by the participants at the same time intervals (α=.05). RESULTS: A statistically significant decline in the levels of TNF-alpha was observed at 3 and 6 months compared with baseline (P<.001). The Epworth Sleepiness Scale scores showed a statistically significant reduction at 3 and 6 months compared with baseline (P<.001). The risk of obstructive sleep apnea assessed by using the Berlin Questionnaire was found to be significantly reduced at 6 months compared with baseline (P=.001). CONCLUSIONS: Patients with mild to moderate obstructive sleep apnea showed reduced levels of TNF-alpha and Epworth Sleepiness Scale and Berlin Questionnaire scores when treated with a mandibular advancement device.

Synthesis of novel azasugar-containing 2'ß-C-Me 9-deaza nucleosides as potential anti-hepatitis C virus agents.

As a part of our ongoing discovery efforts exploring azasugar as agents for treating various unmet medical needs, we prepared analogs of azasugar as potential anti-hepatitis C virus (HCV) agents. Herein we describe the synthesis of novel 2'ß-C-Me 9-deazanucleoside azasugar analogs.

Emerging role of metabolomics for biomarker discovery in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by the complete or partial blockage of the upper airway passage during sleep which causes repetitive breaks in sleep and may result in excessive daytime sleepiness. OSA has been linked to various metabolic disorders and chronic health conditions, such as obesity, diabetes, hypertension, and depression. Profiling of alterations in metabolites and their regulation in OSA has been hypothesized to be an effective approach for early diagnosis and prognosis of OSA. Several studies have characterized metabolic fingerprints associated with sleep disorders. There is a lack of understanding of metabolite contents and their alterations in OSA that may help to identify specific biomarkers. The information provided in this review will help update new methodologies and interventions of high throughput advanced molecular/metabolomics tools which may clarify the metabolic aspects and mechanisms for improved management and treatment of OSA.

Clinical Outcomes of Titanium Zirconium and Titanium Dental Implants under Immediate Functional Loading in Posterior Mandibular Region.

BACKGROUND: Studies comparing the clinical performance of titanium zirconium (Ti-Zr) and titanium (Ti) dental implants subjected to immediate loading in the posterior mandibular region where occlusal forces are higher are sparse in the current literature. Hence, the study aimed to evaluate and compare the clinical outcomes of Ti-Zr and Ti dental implants under immediate functional loading in the mandibular posterior region. METHODS: Forty participants fulfilling the predetermined selection criteria were randomly grouped based on dental implant used; Titanium zirconium (Ti-Zr):20, and Titanium (Ti):20. Dental implants were placed through a standard full-thickness mucoperiosteal flap approach and loaded immediately fulfilling the principle of implant protective occlusion. Clinical parameters including crestal bone loss (CBL), modified plaque index (MPI), probing depth (PD) and modified sulcular bleeding index (MSBI) were measured at baseline and follow-up visits (4, 8, and 12 months). Obtained data were compared with standard tests such as the t-test, Chi-square test, and Mann-Whitney U test. RESULTS: On intergroup comparison, CBL was more in the Ti-Zr group as compared to the Ti group at 4 months (0.72 ± 0.16 mm versus 0.70 ± 0.13 mm), but it was less at 8 months (1.08 ± 0.16 mm versus 1.13 ± 0.13 mm) and 12 months (1.19 ± 0.17 mm versus 1.24 ± 0.12 mm) but the difference was not statistically significant (P > 0.05). Mann-Whitney test also revealed no statistically significant difference in MPI, PD and MSBI at 4 months, 8 months and 12 months recall (P > 0.05). CONCLUSIONS: CBL and periodontal parameters of Ti-Zr dental implants were found similar to Ti dental implants under immediate loading in the posterior mandibular region. However, further studies are needed to determine its long-term efficacy and cost-effectiveness.

A randomized controlled trial for evaluation of bone density changes around immediate functionally and nonfunctionally loaded implants using three-dimensional cone-beam computed tomography.

Aim: The aim of this study was to compare and assess bone density changes around immediate functionally and nonfunctionally loaded implants. Settings and design: In vivo comparative study. Materials and Methods: Sixty participants selected based on the predetermined inclusion and exclusion criteria received single tooth implants in mandible under two implant loading protocols: Immediate functionally loaded (IFL) and immediate nonfunctionally loaded (INFL). Randomization was done by computer-aided simple randomization procedure. Self-tapering, aggressive SLA implants were placed in the single tooth edentulous sites of mandible in both the groups. Three-dimensional cone-beam computed tomography (3D CBCT) was taken at baseline, 3 and 6 months postimplant placement. Quantitative analysis of the bone density was performed using 3D CBCT in three areas around the implants at crestal, middle, and apical regions of implants. Statistical Analysis Used: Quantitative data were summarized as mean ± standard deviation. Statistical analyses were performed using the SPSS software version 21.0 (SPSS Inc., Chicago, IL, USA) by unpaired t-test. Results: Bone density changes after implant placement in IFL group from baseline to 3 months were; crestal region (314.18 ± 71.69), middle (278.23 ± 70.17), apical (274.70 ± 59.79) and changes from 3 to 6 months were; crestal (-105.55 ± 39.60), middle (-114.80 ± 41.46), apical (-141.88 ± 69.58). Bone density changes after implant placement in INFL group from baseline to 3 months were crestal region (199.42 ± 47.97), middle (56.91 ± 10.39), apical (200.98 ± 67.43) and changes from 3 to 6 months were; crestal (-194.38 ± 75.30), middle (-204.40 ± 63.75), apical (-191.28 ± 62.33). Conclusions: It was concluded that INFL implant group showed better bone density when compared to IFL implant group.

To compare different non-surgical treatment modalities on treatment of obstructive sleep apnea: A systematic review and meta-analysis.

The study aimed to assess the effect of mandibular advancement device (MAD) in patients with obstructive sleep apnea for reduction in 24-h mean blood pressure, sleep quality, Apnea Hypopnea Index (AHI), and patient compliance, compared to continuous positive airway pressure (CPAP), other interventions, or no treatment. Three different databases such as PubMed, EMBASE, and CENTRAL were searched using different search terms till July 2021 as per the inclusion and exclusion criteria. After inclusion of studies, data extraction including risk of bias assessment was done. For each study, we used odds ratio, mean difference, and 95% confidence interval to assess and synthesize the outcomes. The quality of evidence was evaluated as per the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Twenty-one randomized controlled trials were included: 497 patients in the MAD group, 239 patients in the CPAP group, and 274 patients in the sham group. In MAD-CPAP comparison, the results favored CPAP in the reduction of AHI of 3.48 (1.76-5.19). However, unclear results were found for sleep quality measured as Epworth Sleepiness Scale (ESS), patient compliance, and 24-h mean blood pressure. In MAD-sham comparison, the results favored MAD in the reduction of AHI of - 8.39 (-10.90--5.88] and ESS of - 0.91 (-1.70--0.12) and favored sham in terms of patient compliance while, unclear results for 24-h mean blood pressure. The GRADE score indicated that the quality of evidence is very low, low, and moderate for different outcomes. CPAP in comparison to MAD and MAD in comparison to sham showed a significant AHI reduction. However, patient compliance and 24-h mean blood pressure were not significantly different in MAD-CPAP or MAD-sham. Quality of evidence is very low and low when MAD was compared with CPAP and sham, respectively, for AHI.

Identification of metabolic fingerprints in severe obstructive sleep apnea using gas chromatography-Mass spectrometry.

Objective: Obstructive sleep apnea (OSA) is considered a major sleep-related breathing problem with an increasing prevalence rate. Retrospective studies have revealed the risk of various comorbidities associated with increased severity of OSA. This study aims to identify novel metabolic biomarkers associated with severe OSA. Methods: In total, 50 cases of OSA patients (49.74 ± 11.87 years) and 30 controls (39.20 ± 3.29 years) were included in the study. According to the polysomnography reports and questionnaire-based assessment, only patients with an apnea-hypopnea index (AHI >30 events/hour) exceeding the threshold representing severe OSA patients were considered for metabolite analysis. Plasma metabolites were analyzed using gas chromatography-mass spectrometry (GC-MS). Results: A total of 92 metabolites were identified in the OSA group compared with the control group after metabolic profiling. Metabolites and their correlated metabolic pathways were significantly altered in OSA patients with respect to controls. The fold-change analysis revealed markers of chronic kidney disease, cardiovascular risk, and oxidative stress-like indoxyl sulfate, 5-hydroxytryptamine, and 5-aminolevulenic acid, respectively, which were significantly upregulated in OSA patients. Conclusion: Identifying these metabolic signatures paves the way to monitor comorbid disease progression due to OSA. Results of this study suggest that blood plasma-based biomarkers may have the potential for disease management.