Multivariate Mendelian randomization (MVMR) is a statistical technique that uses sets of genetic instruments to estimate the direct causal effects of multiple exposures on an outcome of interest. At genomic loci with pleiotropic gene regulatory effects, that is, loci where the same genetic variants are associated to multiple nearby genes, MVMR can potentially be used to predict candidate causal genes. However, consensus in the field dictates that the genetic instruments in MVMR must be independent (not in linkage disequilibrium), which is usually not possible when considering a group of candidate genes from the same locus. Here we used causal inference theory to show that MVMR with correlated instruments satisfies the instrumental set condition. This is a classical result by Brito and Pearl (2002) for structural equation models that guarantees the identifiability of individual causal effects in situations where multiple exposures collectively, but not individually, separate a set of instrumental variables from an outcome variable. Extensive simulations confirmed the validity and usefulness of these theoretical results even at modest sample sizes (nâ³500 -1000). Importantly, the causal effect estimates remain unbiased and their variance small when instruments are highly correlated. We applied MVMR with correlated instrumental variable sets at genome-wide significant loci for coronary artery disease (CAD) risk using expression Quantitative Trait Loci (eQTL) data from seven vascular and metabolic tissues in the STARNET study. Our method predicts causal genes at twelve loci, each associated with multiple colocated genes in multiple tissues. We confirm causal roles for PHACTR1 and ADAMTS7 in arterial tissues, among others. However, the extensive degree of regulatory pleiotropy across tissues and the limited number of causal variants in each locus still require that MVMR is run on a tissue-by-tissue basis, and testing all gene-tissue pairs with cis-eQTL associations at a given locus in a single model to predict causal gene-tissue combinations remains infeasible. Our results show that within tissues, MVMR with dependent, as opposed to independent, sets of instrumental variables significantly expands the scope for predicting causal genes in disease risk loci with pleiotropic regulatory effects. However, considering risk loci with regulatory pleiotropy that also spans across tissues remains an unsolved problem.
Aim: Evaluation of the efficacy of different obturating techniques and assessment of the presence of voids in different regions of the canal. Materials and Methods: Sixty permanent single-rooted teeth with complete, mature root apices without any anatomic variation having straight patent root canals were included in the present study. Access cavity preparation followed by biomechanical preparation was done. Samples were divided into three groups-Group A: Single cone obturation, Group B: GuttaFlow 2, and Group C: GuttaCore, and obturation was carried out. The samples after obturation were stored at 370°C and 100% humidity in an incubator for 7 days to give adequate time for obturating materials to set. Cone beam computed tomography was performed with i-cat Cb 500 machine. The voids were checked on the root canal wall. The statistical analysis was done and the data after the statistical analysis was presented. Result: GuttaCore obturators presented a lesser volume of voids followed by GuttaFlow 2 than the single cone techniques. Conclusion: All the obturation techniques presented an inadequacy of obturation when the pre- and post-obturated volume of the root canal space was calculated. However, no statistically significant obturated volume differences were found between single cone and GuttaFlow 2 or between GuttaFlow 2 and GuttaCore system.
Aim: The present study evaluated the antimicrobial efficacy of chlorhexidine gluconate (CHX), Nisin, and Amoxicillin/Clavulanic Acid (Augmentin) as an intracanal irrigant against Enterococcus faecalis (EF). Materials and Methods: Minimum Inhibitory Concentration (MIC) for EF against Nisin and Augmentin was determined by microbroth dilution technique. Time kill cycle (TKC) analysis was done for 0 MIC, ½ MIC, 1 MIC, and 2 MIC at 0 hour, 15 minutes, 30 minutes, and 45 minutes. At the end of each time period, dilutions were pipetted and swabs of agar plates were done. Incubation of agar plates was done at 37C for 24 hours. Colonies formed were counted. Results: The time kill curve analysis of EF for CHX, Nisin, and Augmentin at different concentrations and time periods showed a gradual decline in mean bacterial count between 0 and 45 minutes for CHX; this decline increases with increase in concentrations and time. Whereas in group Nisin, not much decline in bacterial count is noted for ½ MIC concentrations but a signification reduction of P < 0.001 after exposure to Nisin at 1 MIC ant 2 MIC concentrations. Group Augmentin showed not much reduction in bacterial count with increase in concentration and time. Conclusion: From this study, Nisin is found to be a promising agent in eliminating EF in comparison to other irrigants tested. However, the systemic effect of this irrigant, its biocompatibility, allergic potential, and bacterial resistance needs further investigation.
Aim: To evaluate the antimicrobial activity of PRP and PRF with and without nanosilver. Materials and Methods: The materials were tested in powdered form is nanosilver. The nanosilver particles was mixed to form with PRP and PRF so as to placed in a wells followed the groups are experimental groups; Group I: PRP + nanosilver particles, Group II: PRF + nanosilver and control group: PRP and PRF and normal saline. Silver nanoparticles was tested at concentrations of 50 µ gram per mL. The powder was prepared for each group with identical amount of the powder (milligram/mg) and then mixed with 1 milliliter liquid. The plates are then incubated at 37°C under appropriate atmospheric conditions (80% N2, 10% CO2, 10% H2) for 24 hours, 48 hours, and 72 hours under anaerobic conditions in a CO2 incubator. The diameters of the zones of bacterial and fungal growth inhibition around the wells containing the test substances are then recorded after the period of incubation. The inhibitory zone determined in millimeter by measuring scale the shortest distance between the outer margin of the well and initial microbial as well as fungal growth. The experiments were performed 20 times and the mean and standard deviations of the inhibitory zones were calculated. Result: Platelet rich fibrin is mixed with nanosilver particles showed higher antimicrobial efficacy than platelet rich plasma with nanosilver and simple platelet rich plasma and platelet rich fibrin are equivalent when it is placed against the anaerobic bacteria E.faecalis and yeast like fungi Candida albicans, respectively. Conclusion: Groups presented with antimicrobial efficacy in this order- Group IV > Group II > Group III > Group I.
