Mutant p53 Exploits Enhancers to Elevate Immunosuppressive Chemokine Expression and Impair Immune Checkpoint Inhibitors in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer without effective treatments. It is characterized by activating KRAS mutations and p53 alterations. However, how these mutations dysregulate cancer-cell-intrinsic gene programs to influence the immune landscape of the tumor microenvironment (TME) remains poorly understood. Here, we show that p53R172H establishes an immunosuppressive TME, diminishes the efficacy of immune checkpoint inhibitors (ICIs), and enhances tumor growth. Our findings reveal that the upregulation of the immunosuppressive chemokine Cxcl1 mediates these pro-tumorigenic functions of p53R172H. Mechanistically, we show that p53R172H associates with the distal enhancers of the Cxcl1 gene, increasing enhancer activity and Cxcl1 expression. p53R172H occupies these enhancers in an NF-κB-pathway-dependent manner, suggesting NF-κB's role in recruiting p53R172H to the Cxcl1 enhancers. Our work uncovers how a common mutation in a tumor-suppressor transcription factor appropriates enhancers, stimulating chemokine expression and establishing an immunosuppressive TME that diminishes ICI efficacy in PDAC.

Effect of Laser Therapy on Postoperative Pain and Endodontic Retreatment: A Systematic Review and Meta-Analysis.

BACKGROUND: Root canal re-treatment (RCR) cases are considered some of the most challenging cases in the field of endodontics, as they are mostly associated with various iatrogenic errors such as ledge formation, incomplete biomechanical preparation, file separation, and incomplete obturation. These iatrogenic errors lead to defective niches within root canals that may act as reservoirs for various viable microorganisms. Such residual microbial niches may cause postoperative pain even after thorough debridement and reshaping the canals, ultimately leading to a poor prognosis for the tooth. Nowadays, prevention of postoperative pain in re-treatment cases and prognosis are effectively managed by photobiomodulation therapy (PBMT). METHOD: Relevant studies in the English language published before November 2022 were identified using electronic databases like PubMed, SCOPUS, and EBSCO to conduct bibliographic research. This systematic review is based on 3 studies that were found eligible as per the inclusion and exclusion criteria. This systematic review is in accordance with PRISMA guidelines. RESULTS: The systematic review indicated a positive impact by significantly decreasing postoperative pain in RCR cases when treated with PBMT. The variation was statistically significant at 24 hours (P = .0002), 48 hours (P = .03), and 72 hours (P = .02). The mean difference at 24 hours was 0.65 (95% CI, 0.32-0.99), at 48 hours was 0.46 (95% CI, 0.05-0.87), and at 72 hours was 0.40 (95% CI, 0.07-0.74). There was no statistical heterogenicity at 24 hours (P > .05), but a medium heterogenicity was observed at 48 hours and 72 hours. PRACTICAL IMPLICATION: PBMT or low-level laser therapy has shown superior results as compared to the conventional pharmacologic approach in postoperative pain management in RCR cases.

Gingival Crevicular Fluid Levels of Neurokinin A and Substance P in Patients with Symptomatic Irreversible Pulpitis: A Systematic Review and Meta-Analysis.

Aims and Objectives: The levels of neuropeptides neurokinin A (NKA) and substance P (SP) in the gingival crevicular fluid of patients with symptomatic irreversible pulpitis (SIP) were evaluated using a comprehensive review and meta-analysis. Materials and Methods: The data bases of Pubmed, Scopus, EBSCOhost, Science Direct, Proquest and Cochrane library databases were thoroughly searched. The quality of the study was evaluated using the Joanna Briggs Criteria. Twenty four studies were listed following a thorough search of full texts, abstracts, and removal of duplicates. Only two of these papers were eligible for inclusion in the meta-analysis. Since the results obtained were in mean and standard deviation, the levels of neuropeptides in the test and control groups were examined using the meta-analysis. Results: When compared with healthy teeth, NKA was not significantly elevated in GCF of individuals with SIP (P = 0.06; odd ratio = 1.34 [-0.05 to 2.74] at 95% confidence interval [CI]). Additionally, there was no evidence of an association between SP and SIP (P = 0.08; odds ratio = 0.84 [-0.10 to 1.77] at 95% CI). Conclusion: This systematic research demonstrated that in individuals with SIP, NKA, and SP are not substantially linked. However, the lack of study in this area makes it evident that additional research is needed, particularly in relation to pulpal disorders and NKA.

Evaluation of postoperative pain using warm versus room temperature sodium hypochlorite as an irrigant in mandibular molars with irreversible pulpitis: A randomized controlled trial.

Introduction: The study evaluates and compare the effect of 3% warm NaOCl with NaOCl at room temperature in root canal irrigation on postoperative pain. Materials and Methods: In this randomized controlled trial, mandibular molars with symptomatic irreversible pulpitis in healthy 18-year-old patients and above were included. The sample consisted of 56 patients evaluating the postoperative pain, allocated randomly into 2 groups of 3% NaOCl at two different temperatures, i.e. at room temperature and at 60°C. Endodontic treatment was initiated for each group and instrumentation was done using MTwo rotary files. The final irrigation was performed according to the groups assigned. For each included tooth, preoperative and postoperative pain scores at 6, 12, 24, 48, and 72 h were collected through the Heft Parker Visual Analog Scale. Statistical analysis was performed using independent t-test, Chi-square test, Mann-Whitney U-test, and Friedman test followed by Wilcoxon test. Results: The mean percentage reduction in pain scores was significantly higher among the warm NaOCl group as compared to the control group at different time intervals (P < 0.001). The mean number of analgesics taken was significantly lower among the warm NaOCl group as compared to the control group (P < 0.001). Conclusion: The warm NaOCl group recorded less postoperative pain than the control group during the first 72 h following single-visit endodontic therapy.

Symptomatic Irreversible Pulpitis Induces Increased Levels of Human NLRP3 in Gingival Crevicular Fluid Compared to Saliva: A Case Control Observational Study.

INTRODUCTION: The goal of this case-control observational study was to compare the levels of the human nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing-3 (NLRP3) protein in the saliva and gingival crevicular fluid (GCF) of patients with symptomatic irreversible pulpitis (SIP) and healthy controls. METHODS: The 16 patients in the control group were matched with the 16 patients in the SIP group to create a total of 32 patients. In addition to saliva, GCF (n = 48) samples were collected from the involved tooth (n = 16), contralateral tooth (n = 16), and adjacent tooth (n = 16) in the SIP group. Saliva and GCF were taken from the healthy group as a baseline. An independent t-test was used for statistical analysis. The random-intercept model was used to compare the average NLRP3 levels in the SIP tooth, adjacent tooth, and contralateral tooth taking age as a covariate, and the P value was adjusted using Bonferroni correction. RESULTS: There were significantly higher levels of NLRP3 in the saliva of SIP patients (1.78 ± 1.14 ng/ml) compared to the healthy control (0.70 ± 0.70 ng/ml) and in the GCF of the involved tooth (5.72 ± 0.63 ng/ml) compared to healthy people (1.60 ± 0.42 ng/ml) (P < .001). In SIP patients the mean difference of NLRP3 levels between SIP and contralateral teeth was significant at 4.13 ng/ml (95% confidence interval, 3.52-4.70 P < .001) and a mean difference between adjacent teeth and contralateral teeth was significant at 3.53 ng/ml [95% confidence interval, 2.94-4.12 P < .001]. The NLRP3 in GCF and saliva had a negative association in the affected tooth but a negligible correlation in healthy controls. CONCLUSION: The NLRP3 inflammasome has the potential to be employed as a molecular diagnostic biomarker for pulpal disorders.

Salivary levels of NLRP3 protein are significantly raised in chronic periodontitis: A systematic review and meta-analysis of clinical studies.

Background: To date, there is no confirmatory diagnostic test that can identify the type of periodontal disease and the disease progress. With the advent of "molecular biomarkers," this systematic review and meta-analysis were designed with the sole purpose of identifying a novel biomarker, namely, nucleotide leucine rich repeat pyrin protein-3 (NLRP3) inflammasome which has already been extensively researched for chronic inflammatory and autoimmune diseases. Types of Studies Reviewed: Only case observational studies that evaluated the presence of human NLRP3 inflammasome in the saliva of patients with chronic periodontitis with no overlying systemic disease and compared the same to healthy patients to obtain quantitative data that can be statistically analyzed were included. The confirmatory test used in all the studies was the enzyme-linked immunosorbent assay. Results: The broad-based search led to a total of three articles that fulfilled the inclusion criteria so that a meta-analysis of the results could be carried out. Data reveal that NLRP3 levels are raised in chronic periodontitis cases (P = 0.05; relative risk = 1.05 [0.00-2.09]). The risk of bias assessment was carried out according to the Joanna Briggs Institute Critical Appraisal Checklist where ten-point criteria were outlined indicating a low risk of bias for three studies. Clinical Implications: NLPR3 inflammasome could be tested as a reliable biomarker in saliva to identify the type and progress of the periodontal disease.

Transcription factor antagonism regulates heterogeneity in embryonic stem cell states.

Gene expression heterogeneity underlies cell states and contributes to developmental robustness. While heterogeneity can arise from stochastic transcriptional processes, the extent to which it is regulated is unclear. Here, we characterize the regulatory program underlying heterogeneity in murine embryonic stem cell (mESC) states. We identify differentially active and transcribed enhancers (DATEs) across states. DATEs regulate differentially expressed genes and are distinguished by co-binding of transcription factors Klf4 and Zfp281. In contrast to other factors that interact in a positive feedback network stabilizing mESC cell-type identity, Klf4 and Zfp281 drive opposing transcriptional and chromatin programs. Abrogation of factor binding to DATEs dampens variation in gene expression, and factor loss alters kinetics of switching between states. These results show antagonism between factors at enhancers results in gene expression heterogeneity and formation of cell states, with implications for the generation of diverse cell types during development.

Influence of vehicle for calcium hydroxide on postoperative pain: a scoping review.

This review aims to identify the influence of the vehicle and its concentration used to carry calcium hydroxide (Ca(OH)2) medicament on postoperative pain. The protocol for this review was registered in the open science framework (Registration DOI-10.17605/OSF.IO/4Y8A9) and followed the guidelines provided by the Joanna Briggs Institute. Reporting was based on the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR). Literature screening and searches were performed on PubMed/Medline, Scopus, and EBSCO hosts. Furthermore, additional records were manually analyzed using various sources. The selected studies were published in English and included the use of any vehicle adjunct to Ca(OH)2 to evaluate postoperative pain using qualitative and quantitative pain assessment tools. Descriptive analysis was conducted to review the study design, vehicle elements, and their effects. A preliminary search yielded 7584 studies, of which 10 were included. According to the data collected, the most commonly used Ca(OH)2 vehicles were chlorhexidine (CHX), normal saline, and camphorated paramonochlorophenol/glycerine (CPMC/glycerine), which had a significant effect on postoperative pain. Among the included studies, six evaluated the effect of CHX as a vehicle. It was observed that a higher concentration of the vehicle (2%) showed a favorable response in reducing postoperative pain. A majority of studies have validated a positive consequence of using a vehicle on postoperative pain. Although higher vehicle concentrations were found to alter postoperative pain levels, the data were insufficient to draw a firm conclusion. Our scoping review indicates that further clinical studies should focus on using different vehicles at various concentrations and application times to check for feasible and safe exposure in addition to providing pain relief.

Comparison of healing assessments of periapical endodontic surgery using conventional radiography and cone-beam computed tomography: A systematic review.

Purpose: This systematic review aimed to compare assessments of the healing of periapical endodontic surgery using conventional radiography and cone-beam computed tomography (CBCT). Materials and Methods: This review of clinical studies was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. All articles published from 1990 to March 2020 pertaining to clinical and radiographic healing assessments after endodontic surgery using conventional radiography and CBCT were included. The question was "healing assessment of endodontic surgery using cone-beam computed tomography." The review was conducted by manual searching, as well as undertaking a review of electronic literature databases, including PubMed and Scopus. The studies included compared radiographic and CBCT assessments of periapical healing after periapical endodontic surgery. Results: The initial search retrieved 372 articles. The titles and abstracts of these articles were read, leading to the selection of 73 articles for full-text analysis. After the eligibility criteria were applied, 11 articles were selected for data extraction and qualitative analysis. The majority of studies found that CBCT enabled better assessments of healing than conventional radiography, suggesting higher efficacy of CBCT for correct diagnosis and treatment planning. A risk of bias assessment was done for 10 studies, which fell into the low to moderate risk categories. Conclusion: Three-dimensional radiography provides an overall better assessment of healing, which is imperative for correct diagnosis and treatment planning.

Anesthetic efficacy of supplemental intraligamentary injection in human mandibular teeth with irreversible pulpitis: a systematic review and meta-analysis.

BACKGROUND: Inferior alveolar nerve block (IANB) is known to have a lower success rate for anesthesia in patients with irreversible pulpitis. This calls for supplementary techniques to effectively anesthetize such patients. This systematic review aimed to evaluate the published literature for determining the success rate of anesthesia induction using post-IANB intraligamentary (IL) injection in the mandibular teeth of patients with symptomatic irreversible pulpitis. The review question was, "What is the success rate of IL injection in the mandibular teeth of patients with irreversible pulpitis as a supplementary technique for endodontic treatment?" METHODS: A thorough search of electronic databases and manual searches were performed. The protocol of the review was framed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and was registered in the International Prospective Register of Ongoing Systematic Reviews (PROSPERO) with a proper criterion for inclusion and exclusion of studies. The included studies were analyzed using the Cochrane Collaboration ''Risk of Bias'' tool. A meta-analysis that included a comparison of primary nerve block and supplemental IL injection was performed. The success rate was evaluated using the combined risk ratio (RR) with a random risk model. A funnel plot was created to measure publication bias. RESULTS: After all analyses, four studies were included. In the forest plot representation, RRs were 3.56 (95% CI: 2.86, 4.44), which were in favor of the supplemental IL injections. Statistical heterogeneity was found to be 0%. These values suggest that supplemental IL injections provide better success rates for anesthesia. CONCLUSION: According to the pooled qualitative and quantitative analyses, supplemental IL injections increased anesthetic efficacy.

Comparative evaluation of the force required to fracture coronal segments reattached using different methods.

BACKGROUND/AIM: Anterior teeth are prone to traumatic injuries. Their management is necessary in order to maintain the pulp and esthetics. Various methods have been reported for fragment reattachment of fractured teeth but there is no consensus on which is the best technique. The aim of this study was to compare the force required to fracture reattached fragments using polyethylene fibers in vertical grooves on the external surface of teeth, fiber-reinforced composite post and circumferential chamfer. MATERIAL AND METHODS: Forty-eight extracted maxillary central incisors were sectioned using a disk and randomly divided into 4 groups (n = 12): Group 1: control group, Group 2: reattachment followed by placement of two external vertical grooves on the labial surface and restored with polyethylene fibers and hybrid composite, Group 3: reattachment followed by two external vertical grooves and filled with fiber posts and composite, and Group 4: reattachment followed by circumferential chamfer at the fracture line and restored with composite. The forces required to fracture the reattached fragments were measured using a Universal testing machine. Data were analyzed using the Kruskal-Wallis test. Pairwise multiple comparison procedure was done using the Student-Newman-Keuls Method. RESULTS: The highest values for force required to fracture were observed in the fiber post group and the lowest in the Ribbond group (p < .05). The fiber post group had significantly different results compared to the Ribbond and Chamfer preparation groups (p < .05). However, the difference of rank between the fiber post and control groups was not significantly different (p > .05). CONCLUSION: The force required to fracture the fiber post group was closest to that of intact teeth followed by the chamfer and Ribbond groups, respectively.

Periodontal health of the geriatric population in old-age homes of Delhi, India.

BACKGROUND: Periodontal disease is one of the leading causes of tooth loss in the geriatric population. Assessment of periodontal disease in a population is an important step in planning effective prevention and control programs for periodontal disease. Therefore, a study was carried out in old-age homes of Delhi to assess the periodontal status of 65-74-year-old elderly and recommend interventions to improve their periodontal health. MATERIALS AND METHODS: A cross-sectional study was conducted among 464 elderly from old-age homes of Delhi. Periodontal health status of the participants was determined using the WHO oral health assessment form. Community Periodontal Index (CPI) and loss of attachment (LOA) were recorded. Collected data were analyzed using SPSS version 23. Chi-square test was used to determine statistically significant difference among CPI scores and LOA according to age and gender. P ≤ 0.05 was considered statistically significant. RESULTS: The result of the study showed that 25.4% of the elderly had healthy periodontium, 71.1% had a periodontal pocket of 6 mm or more, and 2.40% had a pocket depth of 4-5 mm. Around 36% had 6-8 mm LOA and 34.70% had 9-11 mm LOA. The difference between CPI scores among gender and age group was not significant (P = 0.20, P = 0.096). However, the difference among gender for LOA was found significant (P = 0.014). CONCLUSION: The results from this study show that periodontal health of elderly residing in old-age homes is very poor. The periodontal status of this population can be enhanced by special collaborative efforts from the government and various nongovernmental organizations toward preventive and curative periodontal health services.

Anesthetic efficacy of primary and supplemental buccal/lingual infiltration in patients with irreversible pulpitis in human mandibular molars: a systematic review and meta-analysis.

Achieving profound anesthesia in mandibular molars with irreversible pulpitis is a tedious task. This review aimed at evaluating the success of buccal/lingual infiltrations administered with a primary inferior alveolar nerve block (IANB) injection or as a supplemental injection after the failure of the primary injection in symptomatic and asymptomatic patients with irreversible pulpitis in human mandibular molars. The review question was "What will be the success of primary and supplemental infiltration injection in the endodontic treatment of patients with irreversible pulpitis in human mandibular molars?" We searched electronic databases, including Pubmed, Scopus, and Ebsco host and we did a comprehensive manual search. The review protocol was framed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. We included clinical studies that evaluated and compared the anesthetic outcomes of primary IANB with primary and/or supplementary infiltration injections. Standard evaluation of the included studies was performed and suitable data and inferences were assessed. Twenty-six studies were included, of which 13 were selected for the meta-analysis. In the forest plot representation of the studies evaluating infiltrations, the combined risk ratio (RR) was 1.88 (95% CI: 1.49, 2.37), in favor of the secondary infiltrations with a statistical heterogeneity of 77%. The forest plot analysis for studies comparing primary IANB + infiltration versus primary IANB alone showed a low heterogeneity (0%). The included studies had similar RRs and the combined RR was 1.84 (95% CI: 1.44, 2.34). These findings suggest that supplemental infiltrations given along with a primary IANB provide a better success rate. L'Abbe plots were generated to measure the statistical heterogeneity among the studies. Trial sequential analysis suggested that the number of patients included in the analysis was adequate. Based on the qualitative and quantitative analyses, we concluded that the infiltration technique, either as a primary injection or as a supplementary injection, given after the failure of primary IANB, increases the overall anesthetic efficacy.

Effect of intracanal cryotherapy on postendodontic pain: a systematic review and meta-analysis of randomized controlled trials.

This systematic review aimed to qualitatively and quantitatively evaluate the effectiveness of cryotherapy in the reduction of postendodontic pain. The review question was, "What will be the success rate of cryotherapy technique among human patients with postendodontic pain?". The review protocol was framed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Six studies were included in the review, and quantification of five studies was performed through a meta-analysis. In the forest plot representation of the studies comparing the control and cryotherapy groups in terms of the success rate in the management of postendodontic pain, the combined risk ratio (RR) was 0.80 (95% CI: 0.56 to 1.13) with a P value of 0.20. Based on the quantitative analysis, it can be suggested that intracanal cryotherapy does not play a significant role in reducing postendodontic pain.

Comparative Evaluation of the Marginal Fit of Inlays Fabricated by Conventional and Digital Impression Techniques: A Stereomicroscopic Study.

CONTEXT: Marginal fit being the prime concern of indirect restorations. Inlays can be either fabricated by conventional technique or computer-aided design and computer-aided manufacturing (CAD/CAM) techniques. CAD/CAM is the most evolving digital technique with faster, quicker, and precise results. AIMS: The aim of this study is to evaluate and compare the marginal fit of MOD inlays fabricated with two different CAD/CAM methods and conventional fabrication methods. SETTINGS AND DESIGN: Mesio-occlusal-distal preparation was done on a maxillary premolar typhodont tooth and divided into the following groups. Group A: 30 inlays were fabricated through the conventional impression technique. Group B: Preparation was scanning using an intraoral scanner followed by subtractive milling (Group B1) and subtractive milling of wax patterns (Group B2). Similarly, subgrouping was carried out for Group C except that an extraoral scanner was used. Occlusal and the cervical marginal fit were assessed using the replica technique and stereomicroscope. One-way ANOVA followed by Tukey honestly significant difference post hoc test for determining differences at a 95% level of confidence (P = 0.05). RESULTS: Group A had the highest marginal discrepancy in comparison to Group B and Group C at occlusal and cervical edges, whereas subtractive milling showed comparatively better results than subtractive milling of wax patterns at cervical edges and similar results at occlusal edges. CONCLUSIONS: Ceramic inlays fabricated by subtractive milling yielded better results.

Comparative evaluation of antibacterial efficacy of Allium sativum extract, aqueous ozone, diode laser, and 3% sodium hypochlorite in root canal disinfection: An in vivo study.

AIM: The present study aimed to individually evaluate and compare the aerobic and anaerobic antibacterial activity of Allium sativum extract, aqueous ozone, diode laser, and 3% sodium hypochlorite (NaOCl) as root canal irrigants. MATERIALS AND METHODS: Forty-eight patients were selected and randomly allocated to one of the four groups (n = 12 each) according to the irrigant to be used in each group. For each included tooth, the preirrigation and postirrigation (after irrigation with the test solution) samples were collected through sterile paper points and microbial culturing was done by swabbing on blood agar plates followed by incubation for aerobic and anaerobic bacteria. STATISTICAL ANALYSIS: Manual colony-forming units counting were done, and statistical analysis was performed. Analysis of variance (one-way) followed by post hoc test was performed as a parametric test to compare the difference between the groups for both aerobic and anaerobic bacteria. RESULTS: All the groups showed a statistically significant reduction in bacteria (P < 0.05). However, between the groups, the maximum reduction was seen with 3% NaOCl followed by diode laser, A. sativum extract, and least by aqueous ozone. CONCLUSION: A. sativum extract, aqueous zone, diode laser, and 3% NaOCl showed significant antibacterial activity against aerobic and anaerobic bacteria.

Assessment of Quality of Life of the Elderly Living in Rural and Urban Areas of Ambala District: A Comparative Study.

CONTEXT: Aging is a natural process which universally affects all the human beings in the society. As the geriatric population is quiet vulnerable, They might suffer from mental and physical disabilities which consequently threatens their independence. Quality of life among the geriatric population is a global concern as it reflects the status of health and of well being among the set population. AIMS: To assess the quality of life of elderly living in rural and urban areas and compare the role of socio-demographic factors influencing the quality of life of elderly. SETTINGS AND DESIGN: It is a Community based Cross sectional study conducted in urban and rural field practice areas of MMIMSR, Mullana. METHODS AND MATERIAL: Convenience sampling was used. A total of 200 elderly were included in the study. A pretested semi structured questionnaire was used. STATISTICAL ANALYSIS: Data was analysed using SPSS 20.0. RESULTS: According to the sex of the participants, male participants had a higher mean score for QOL as compared to the female participants. Higher mean score was found in each domain for the participants living with their spouses. CONCLUSIONS: The quality of life is better among the individuals who do not suffer from any chronic illness'. The health care services should be strengthened to provide for better healthcare to the elderlies for their morbid conditions.

Ormocer: An aesthetic direct restorative material; An in vitro study comparing the marginal sealing ability of organically modified ceramics and a hybrid composite using an ormocer-based bonding agent and a conventional fifth-generation bonding agent.

AIMS AND OBJECTIVES: To compare the marginal sealing ability of ormocer with a hybrid composite using an ormocer based bonding agent and a conventional fifth generation bonding agent. MATERIALS AND METHODS: Fifty four human premolars were randomly distributed into four test groups of 12 teeth each and two control groups of 3 teeth each. Class I occlusal preparation of 1.5 mm depth were made in each tooth. These were restored using the adhesive and restorative material according to the group. The restorations were finished using a standard composite finishing and polishing kit. Thermocycling between 5° C and 55°C was carried out. Having blocked the root apex and the entire tooth surface except 1 mm around the restoration margin, the teeth were immersed in 2% methylene blue for 48 hours, after which the dye penetration through the margins of each sample was studied under a stereomicroscope. RESULTS AND DISCUSSION: Group IV (Admira with Admira Bond) showed the minimum marginal leakage with a mean of 0.200 mm. Four samples in this group showed no microleakage at all and a maximum of 0.400 mm was seen in one sample. Group II (Spectrum TPH with Admira Bond) showed the maximum leakage with a mean of 0.433 mm. One sample showed as much as 1.00 mm of microleakage. Admira when used with Admira Bond showed lesser microleakage than Spectrum TPH used with Prime & Bond NT, the difference being statistically insignificant.