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Fractal analysis (FA) is a quantitative, objective and non-invasive method that facilitates the characterisation of the tissue architecture. This study aims to compare the periapical healing at 1-year follow-up by evaluating newly generated trabecular bone with FA after Mineral trioxide aggregate (MTA) plug and regenerative endodontic treatment (RET). A total of 55 asymptomatic teeth with a single-canal, open apex and periapical lesion, treated with MTA plug or RET, were evaluated retrospectively. After considering the inclusion/exclusion criteria, FA was conducted on 30 periapical images using the box-counting method. In both groups, a significant decrease was observed in the periapical lesion size at 1-year follow-up (p 0.01). However, there was no significant difference between the MTA plug and RET (p 0.01). Significantly higher fractal dimension values were detected at 1-year follow-up in both MTA plug and RET cases (p 0.01). However, the difference was not significant between the groups (p 0.01). Both procedures seem to improve periapical healing with a new resistant bone of similar density and complexity.

Hypoxia often occurs in inflammatory tissues, such as tissues affected by periodontitis and apical periodontitis lesions. Mitochondrial biogenesis can be disrupted in hypoxia. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a core factor required for mitochondrial biogenesis. Cementoblasts are root surface lining cells that play an integral role in cementum formation. There is a dearth of research on the effect of hypoxia on cementoblasts and underlying mechanisms, particularly in relation to mitochondrial biogenesis during the hypoxic process. In this study, we found that the expression of hypoxia inducible factor-1α was elevated in apical periodontitis tissues in vivo. In contrast, periapical lesions exhibited a reduction of PGC-1α expression. For in vitro experiments, cobalt chloride (CoCl

This study aimed to quantitatively and qualitatively determine the proteomic profile of apical periodontitis (AP) in type 2 diabetes mellitus (T2DM) patients in comparison with systemically noncompromised patients and to correlate the protein expression of both groups with their biological functions.The sample consisted of 18 patients with asymptomatic AP divided into two groups according to the presence of T2DM: diabetic group-patients with T2DM (n = 9) and control group-systemically healthy patients (n = 9). After sample collection, the root canal samples were prepared for proteomic analysis using reverse-phase liquid chromatography-mass spectrometry. Label-free quantitative proteomic analysis was performed by Protein Lynx Global Service software. Differences in protein expression between groups were calculated using t-test (p .05). Biological functions were analysed using the Homo sapiens UniProt database.A total of 727 human proteins were identified in all samples. Among them, 124 proteins common to both groups were quantified, out of which 65 proteins from the diabetic group showed significant differences compared with the control: 43 upregulated (p .05) and 22 downregulated (p .05) proteins. No significant differences in protein expression were seen for the remaining 59 proteins (p .05). Most proteins with differences in expression were related to immune/inflammatory response. Neutrophil gelatinase-associated lipocalin, Plastin-2, Lactotransferrin and 13 isoforms of immunoglobulins were upregulated. In contrast, Protein S100-A8, Protein S100-A9, Histone H2B, Neutrophil defensin 1, Neutrophil defensin 3 and Prolactin-inducible protein were downregulated.Quantitative differences were demonstrated in the expression of proteins common to diabetic and control groups, mainly related to immune response, oxidative stress, apoptosis and proteolysis. These findings revealed biological pathways that provide the basis to support clinical findings on the relationship between AP and T2DM.

PTEN-induced putative kinase 1 (PINK1) and Parkin E3 ubiquitin-protein ligase (Parkin) are critical for immune and inflammatory regulation in health and disease. PINK1 and Parkin have been confirmed to be involved in the progression of apical periodontitis by affecting mitophagy-related osteoblast apoptosis; however, the expression of PINK1 and Parkin in macrophages, one of the most important cells in apical periodontitis, remains unknown. This study aimed to investigate the expression of PINK1 and Parkin in human apical periodontitis lesions, as well as their possible localization in macrophages.Thirty-seven human periapical tissues, including periapical granulomas (PGs, n = 12), radicular cysts (RCs, n = 11) and healthy gingival tissues (n = 14) were examined. The inflammatory infiltrates of lesions were evaluated by haematoxylin staining, and the expression of PINK1 and Parkin was detected by immunohistochemistry. Double immunofluorescence was used to explore the colocalization of microtubule-associated protein 1 light chain 3 (LC3) and TOMM20, as well as the localization of PINK1 and Parkin, in macrophages of human apical periodontitis lesions. The ultrastructural morphology of mitochondria in human apical periodontitis lesions was visualized by transmission electron microscopy (TEM). Data were analysed by one-way anova with Student-Newman-Keul's test and the Mann-Whitney test. p .05 was considered statistically significant.Immunohistochemistry demonstrated a significantly higher expression of PINK1 and Parkin proteins in human apical periodontitis lesions than in healthy gingival tissues (p .0001), but no significant difference was demonstrated between PGs and RCs (p .05). The higher expression of LC3 and the presence of more LC3-TOMM20 double-positive cells were also observed in human apical periodontitis. Double-labelling analysis of PINK1, Parkin and LC3 with CD68 indicated that macrophage mitophagy might be present in the progression of human apical periodontitis. Finally, the results of TEM morphological analysis revealed the appearance of double-membraned mitophagosomes and vacuolated mitochondria in macrophage-like cells of apical periodontitis lesions.Our findings indicated that PINK1 and Parkin proteins were highly expressed in clinical apical periodontitis lesions.

The main aim of the study was to evaluate the inflammatory response and development of apical periodontitis in rats chronically treated with glucocorticoids.Male Wistar rats (Rattus novergicus) were randomly divided into two groups: the experimental group, which was treated with prednisone (5 mg/kg/day) and a control group, which was administered saline solution for 30 days before induction of apical periodontitis, continuing until the day of euthanasia days 0, 7, 14 and 28 after injury induction. The mandibles were subjected to histological evaluation to determine the size of the lesion, was also performed for the presence and absence of pulp necrosis, bone resorption and micro abscesses, and histomorphometric analyses were performed based on the number of polymorphonuclear cells and mononuclear cells. Histochemical analysis was also performed to assess the percentage of collagen fibres and their typification, in addition to immunohistochemistry for the inflammatory markers interleukin IL-1β, IL-6, TNF-α and TRAP.Despite after 7 days, there was no differences between groups, a significant increase in the root pulp necrosis (p = .001), micro-abscesses (p = .026) and the size of the apical lesion on the 14th day of treatment with prednisone (p = .008). On the same day, there was also an increase in the number of polymorphonuclear cells (p = .042) and cells immunostained for IL-1β (p = .006), IL-6 (p .001) and TRAP (p = .002) in animals treated with prednisone. The numbers of mononuclear cells also increase in 28 days (p = .025) and TNF-α ± increases in the prednisone group on the 7th day (p = .041). The prednisone group also showed a decrease in collagen after 14 (both type I [p = .041] and type III [p = .046]) and 28 type III (p = .002) days after the coronary opening.The glucocorticoids modified the development of experimental apical periodontitis induced in rats, causing an early increase in periapical bone resorption and pulp necrosis. These effects are associated with alterations in cytokine levels, in the inflammatory response and in collagen deposition, in the 14th day after injury induction.

This randomized clinical trial aimed to assess the effect of instrumentation kinematics (reciprocation or continuous rotation) on bacterial reduction, post-operative pain, and incidence of flare-ups after root canal treatment of single-rooted mandibular premolars with asymptomatic apical periodontitis.Sixty-six patients were included in this prospective, parallel, randomized clinical trial. Patients were randomly allocated into two groups (N = 33) according to the kinematics of the shaping instrument: WaveOne Gold (WO) used in reciprocation or One Shape (OS) used in continuous rotation. Under complete asepsis, bacterial samples were taken before (S1) and after (S2) a standard cleaning and shaping protocol. Evaluation of bacterial reduction was done by both culture technique and quantitative real-time polymerase chain reaction (qPCR) analysis. Post-operative pain was evaluated using the visual analogue scale (VAS) after 24, 48, and 72 h following treatment, while flare-ups were recorded as a binary outcome (Yes/No). Independent and paired t-tests were used for inter- and intra-group comparisons for bacterial count data, respectively. For post-operative pain score, inter-group comparisons were analyzed using the Mann-Whitney U-test while intra-group comparisons were analyzed using Friedman test followed by pairwise comparisons utilizing the Wilcoxon signed rank test with Bonferroni correction. The significance level was set at p ≤ .05 within all tests.All the allocated participants received the intervention and were analysed. The comparison between culture and qPCR methods showed that qPCR analysis demonstrated significantly higher pre-instrumentation baseline bacterial count (p .05). The percentage of bacterial reduction, detected by either method, significantly decreased after instrumentation using either rotation or reciprocation kinematics (p .05). However, the difference between the WOG or OS files was statistically non-significant (p .05). The intra-group comparisons showed a significant reduction in post-operative pain with time (p .05) for both groups. However, the inter-group comparison demonstrated that the difference in post-operative pain after the use of either WOG or OS was statistically non-significant (p .05). The incidence of flare-ups between both groups was also not-significant (p = 1).Shaping kinematics, either rotation or reciprocation motions, had no impact on bacterial reduction and the incidence of post-operative pain and flare-ups after root canal preparation of single-rooted premolars with asymptomatic apical periodontitis.

To investigate the effect of a continuing education course on technical quality and treatment outcome for root filled permanent teeth in Møre and Romsdal County, Norway.Fifty-two dentists employed in the Public Dental Service in Møre and Romsdal county, Norway, completed a two-day continuing education course in root canal treatment. Periapical radiographs of root filled teeth treated before and after the course, with at least one-year follow-up were identified and scored for technical quality and periapical status. Technical root filling quality was assessed by density and length and the treatment outcome by PAI scores. Treatment information was achieved from the county's electronic dental record system. Information regarding the dental practitioners' background and treatment procedure routines was collected by a questionnaire. Descriptive statistics analyses and mixed-effect logistic regression analyses were performed to evaluate the effect of the course.Radiographs were available for 224 teeth root filled before and for 221 teeth after the course. The proportion of teeth with adequate root filling quality was significantly lower after the course (p = .006), associated mainly with short root fillings (p .001). No significant differences were observed in treatment outcome. There were, however, large differences in treatment outcome amongst subgroups of dentists. Further, there was evidence of effect modification by the continuing education course on periapical outcome by patient's age (pA two-day continuing education course in root canal treatment attended by Public Dental Service dentists in Norway did not improve the technical quality of root fillings or periapical status associated with root filled teeth.

Endodontic microbiology deals with the study of the microbial aetiology and pathogenesis of pulpal and periradicular inflammatory diseases. Research in endodontic microbiology started almost 130 years ago and since then has mostly focussed on establishing and confirming the infectious aetiology of apical periodontitis, identifying the microbial species associated with the different types of endodontic infections and determining the efficacy of treatment procedures in eradicating or controlling infection. Diverse analytical methods have been used over the years, each one with their own advantages and limitations. In this review, the main features and applications of the most used technologies are discussed, and advice is provided to improve study designs in order to properly address the scientific questions and avoid setbacks that can compromise the results. Finally, areas of future research are described.

AIM: To compare the endodontic and periapical status of two similar adult Danish populations examined in 1997-1998 and 2007-2009, respectively.METHODOLOGY: Two populations from Aarhus County, Denmark (age range: 20-64 years) were randomly selected using the Danish Civil Registration System. Full-mouth intraoral radiographs (14 periapical, 2 bitewing) of 616 individuals in 1997-1998 (C1: 16 018 teeth) and 398 individuals in 2007-2009 (C2: 10 668 teeth) were taken to ascertain the number of teeth, presence of root fillings (RFs) and apical periodontitis (AP) using the periapical index (PAI). T-tests with unequal variances were used to assess differences between C1 and C2 with respect to age and the number of teeth. Multivariable and multinomial logistic regression analyses were used to assess the effect of cohort, age and tooth type on the prevalence and relative frequency of RFs and AP.RESULTS: Mean age and mean number of teeth were higher in C2 than C1 (age; C1: 42.3 years, C2: 44.6 years; p = .003), (teeth; C1: 26.0, C2: 26.8; p < .001). The prevalence of root filled teeth was lower in C2 than C1 (C1: 51.8%, C2: 45.0%; p = .03); however, the prevalence of AP was similar (C1: 42.0%, C2: 45.0%). The relative frequency of root filled teeth was lower in C2 than C1 (C1: 4.8%, C2: 3.6%; p = .004), although the individuals were older in C2. The relative frequency of AP was similar in the two cohorts (C1: 3.3%, C2: 3.6%; p = .42). The relative frequency of AP in non-root filled teeth doubled from 0.9% in C1 to 1.8% in C2. C2 had higher PAI scores than C1 for root filled and non-root filled teeth, despite age correction (p ≤ .0007).CONCLUSIONS: Two similar general Danish populations examined, respectively, in 1997-1998 and 2007-2009, were associated with a decreasing trend in the prevalence and relative frequency of RFs over the decade. There was no difference in relative frequency of AP in root filled teeth, but an increase in relative frequency of AP in non-root filled teeth. Further population-based studies including analysis of non-root filled teeth using the full-scale PAI and quality assessment of restorations are recommended.

AIM To describe the prevalence of periapical lesions, root canal treatments and coronal restorations on teeth adjacent to either implant- or natural tooth-supported crowns using cone-beam computed tomography (CBCT) assessment compared to nonadjacent teeth. METHODOLOGY A total of 1249 CBCT volumes were screened by five pre-calibrated observers in 11 health centres. A step-by-step screening protocol was implemented and reviewed every 3 months, and mandatory setting characteristics were established for all CBCT scans using dedicated visualization software. Intra- and inter-rater reliability tests were conducted. The prevalence of periapical lesions, root canal treatments and coronal restorations was recorded on both teeth adjacent and nonadjacent to implant- (predictor 1) or natural tooth-supported crowns (predictor 2). A binary logistic model (Generalizing Estimating Equations test) was used to verify whether the prevalence of periapical lesion, root canal filling and the tooth restorative status are altered when the assessed tooth is adjacent or not to an implant-supported crown (predictor 1); or to a natural tooth-supported crown (predictor 2). Odds ratio and confidence intervals for the dependent variables at both predictors were obtained. The significance level was set at .05. RESULTS A global sample of 22 899 teeth was included. Compared to nonadjacent teeth, the prevalence of periapical lesion, root canals treatments and restorative procedures when adjacent to implant-supported crowns was 10.7%, 19.6% and 22.9% higher, respectively, and when adjacent to tooth-supported crowns was 19.3%, 35.6% and 37.4% higher respectively. These results were significant only for variables root canal filling and coronal restoration (p

Wnts include more than 19 types of secreted glycoproteins that are involved in a wide range of pathological processes in oral and maxillofacial diseases. The transmission of Wnt signalling from the extracellular matrix into the nucleus includes canonical pathways and non-canonical pathways, which play an important role in tooth development, alveolar bone regeneration and related diseases. In recent years, with the in-depth study of Wnt signalling in oral and maxillofacial-related diseases, many new conclusions and perspectives have been reached, and there are also some controversies. This article aims to summarize the roles of Wnt signalling in various oral diseases, including periodontitis, dental pulp disease, jaw disease, cleft palate, and abnormal tooth development, to provide researchers with a better and more comprehensive understanding of Wnts in oral and maxillofacial diseases. This article is protected by copyright. All rights reserved.

OBJECTIVE Periapical granuloma is a common periodontitis type involving chronic inflammation; however, the efficacy of current therapies is limited. Its molecular pathogenesis also remains obscure. Forkhead box transcription factor class o3a (Foxo3a) and Fas-ligand (FasL) are associated with chronic inflammation. Therefore, in this study, we aimed to clarify the roles of Foxo3a and FasL in periapical granuloma pathophysiology. SUBJECTS AND METHODS Periapical lesions were obtained from patients during endodontic surgery and tooth extraction; those diagnosed with periapical granulomas using haematoxylin and eosin staining were further analysed. Immunohistochemical analysis was performed for Foxo3a and FasL, and real-time polymerase chain reaction was performed for FOXO3A, FASL and interleukin (IL)-1β. Healthy gingival tissues were also examined as controls. RESULTS Neutrophils, lymphocytes and plasma cells in the periapical granulomas, but not healthy tissues, expressed Foxo3a. Dual-colour immunofluorescence imaging revealed Foxo3a and FasL co-expression in leukocytes. FOXO3A, FASL and IL-1β mRNA levels in healthy gingival tissues were significantly lower than those in the periapical granulomas. Additionally, FOXO3A and IL-1β expressions were negatively correlated. CONCLUSIONS Phosphorylated Foxo3a may reduce IL-1β release by inhibiting apoptosis through FasL in periapical periodontitis and prevent exacerbation. Thus, Foxo3a is a potential therapeutic agent for periapical periodontitis.

This pilot study assessed the glycaemic control and the serum levels of inflammatory mediators in type 2 diabetes (T2DM) patients with apical periodontitis (AP). Thirty individuals were divided into four groups: Healthy (H); with AP (AP); with T2DM (T2DM); and with T2DM and AP (T2DM-AP). Demographic and pharmacological data were registered. The body mass index (BMI) and the levels of glycated haemoglobin (HbA1c) and IL-1β, IL-6, IL-10, CCL3 and CCL4 were evaluated. AP areas were determined radiographically. Mean age was 64 ± 12 years, with 63% females. Most T2DM patients were under treatment with metformin and antihypertensives. BMI and H1bAc were significantly higher in T2DM patients in relation to H and AP groups. The AP areas were larger in the T2DM-AP group, compared with the AP group. These preliminary findings suggest no influence of AP on glycaemic control or inflammatory levels amongst T2DM patients, although T2DM increased the AP severity.

Made available in DSpace on 2022-05-01T09:31:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Aim: To evaluate the effect of red wine consumption or its polyphenols on the inflammation/resorption processes associated with apical periodontitis in rats. Methodology: Thirty-two three-month-old Wistar rats had apical periodontitis induced in four first molars and were then arranged into four groups: control (C)—rats with apical periodontitis; wine (W)—rats with apical periodontitis receiving 4.28 ml/kg of red wine; resveratrol+quercetin (R+Q)—rats with apical periodontitis receiving 4.28 ml/kg of a solution containing 1.00 mg/L of quercetin and 0.86 mg/L of resveratrol and alcohol (ALC)—rats with apical periodontitis receiving the alcoholic dose contained in the wine. The oral gavage treatments were administered daily, from day 0 to day 45. On the 15th day, apical periodontitis was induced, and on the 45th day, the animals were euthanized. Histological, immunohistochemical (RANKL, OPG, TRAP, IL-10, TNF-⍺ and IL-1β) and micro-computed tomography for bone resorption analysis were performed in the jaws. The Kruskal–Wallis with Dunn's test was performed for nonparametric data, and the anova with Tukey's test for parametric data, p

AIM To investigate the association between experimentally induced apical periodontitis (AP) and heart function in hypertensive rats. METHODOLOGY Forty-eight normotensive Wistar albino and spontaneously hypertensive (SHR) rats were divided into four equal groups: control (C), normotensive with AP (AP), SHR and SHR with AP (SHR + AP). AP was induced on the first right mandibular molars by exposing the pulp chambers to the oral environment for four weeks and confirmed radiographically. Thereafter, the animals were sacrificed by cervical dislocation, whilst hearts were isolated and perfused according to the Langendorff technique gradually increasing coronary perfusion pressures 40-120 cmH2 O. The hemimandibles were analysed radiographically (mm2 and pixels) to verify the presence of AP. Biomarkers of cardiac oxidative stress (OS) were determined in coronary venous effluent and cardiac tissue homogenate. Cardiac tissue was analysed histopathologically for signs of heart damage (oedema, fibrosis and necrosis). All data were analysed by Kruskal-Wallis and one-way anova tests (p

Background: Regenerative endodontics has evolved in recent years with tissue engineering concepts in particular appearing promising. Endodontic tissue engineering (ETE) describes the various approaches based on the orthograde introduction of scaffolds or biomaterials (with or without cells) into the root canal to achieve pulp tissue regeneration. There are currently no systematic reviews investigating whether ETE is a suitable method for the treatment of endodontic disease in both mature and immature permanent teeth. Objectives: The purpose of this systematic review was to determine the effectiveness of ETE in permanent teeth with pulp necrosis in comparison with conventional endodontic treatment. Methods: We searched MEDLINE, Embase and the Cochrane Library for published reports as well as Google Scholar for grey literature up to November 2021. Included were studies of patients with permanent immature or mature teeth and pulp necrosis with or without signs of apical periodontitis (P) comparing ETE (I) with calcium hydroxide apexification, apical plug and root canal treatment (C) in terms of tooth survival, pain, tenderness, swelling, need for medication (analgesics and antibiotics), radiographic evidence of reduction in apical lesion size, radiographic evidence of normal periodontal ligament space, function (fracture and restoration longevity), the need for further intervention, adverse effects (including exacerbation, restoration integrity, allergy and discolouration), oral health-related quality of life (OHRQoL), presence of sinus tract and response to sensibility testing (O). An observation period of at least 12 months was mandatory (T) and the number of patients in human experimental studies or longitudinal observational studies had to be at least 20 (10 in each arm) at the end (S). Risk of bias was appraised using the Cochrane risk-of-bias (RoB 2) tool. Two authors independently screened the records, assessed full texts for eligibility and evaluated risk of bias. Heterogeneity of outcomes and limited body of evidence did not allow for meta-analysis. Results: Two randomized clinical trials investigating cell transplantation approaches with a total of 76 participants (40 treated immature teeth and 36 treated mature teeth) were included for qualitative analysis. Both studies had moderate concerns in terms of risk of bias. Due to the lack of homogeneity a meta-analysis was not possible. Tooth survival for ETE, root canal treatment and apexification was 100% after 12 months. Teeth treated with ETE showed a higher number of cases with positive pulpal responses to sensitivity tests and with blood perfusion compared with root canal treatment or apexification. Discussion: This systematic review highlights that there is limited evidence for ETE approaches. Even though the results of this review suggest a high survival with ETE in mature and immature teeth, there is a moderate risk of bias due to methodological limitations in the included studies, so the overall results should be interpreted with caution. Lack of a robust control group was a common problem during literature screening, and outcomes besides dental survival were reported inconsistently. Future clinical trials need to address methodical as well as assessment concerns and report long-term results. Conclusion: The benefits and high survival rates reported for ETE techniques suggest that this procedure might be an alternative to conventional procedures for permanent teeth with pulpal necrosis. However, more appropriate studies are needed to derive clinical recommendations. Registration: PROSPERO (CRD42021266350), PRISMA-2020 checklist, PRISMA-S checklist, full search documentation including database accession numbers of records found and details of RoB-assessment are publicly available from a research data repository (DOI: 10.5283/epub.52428): https://doi.org/10.5283/epub.52428

Background The association between adverse pregnancy outcomes (APOs) and maternal apical periodontitis remains unclear as it has not been examined rigorously or reviewed systematically. Objective To systematically review and critically evaluate the available evidence on the association of maternal apical periodontitis with several APOs. Methods A literature search was conducted using the following electronic databases: Clarivate Analytics' Web of Science, Scopus, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL), from inception to 25 February 2021, with no language restrictions. Observational studies including longitudinal clinical trials, cohort, case-control and cross-sectional studies of prospective and retrospective design were included. Articles with duplicate or overlapping results, abstract-only papers, case reports, case series, animal studies and reviews were excluded. Two independent reviewers were involved in study selection, data extraction and appraising the included studies; disagreements were resolved by a third reviewer. The Newcastle-Ottawa Scale (NOS) and the adapted form of the NOS were used to assess the quality for case-control and cross-sectional studies, respectively. Results Two case-control and one cross-sectional study were included in the current review. The included studies were published between 2015 and 2017, with a total of 1187 participating individuals with an approximate age range of 15 to 40 years. As the included studies reported different outcomes, the heterogeneity of data prevented a meta-analysis being undertaken. The overall quality of the evidence was 'Fair' for two out of three included studies, while one study was categorized as 'Good'. Discussion Two out of three included primary studies had a substantial number of methodological inconsistencies and flaws, and therefore caution should be exercised in interpreting the results of this systematic review because several important covariates were not considered in the original investigations. Conclusion Based on a limited volume and 'Fair' and 'Good' quality of evidence, a positive association between maternal apical periodontitis and APOs was observed. However, more 'Good' quality clinical studies are needed to confirm the results of the current review. Funding None REGISTRATION: PROSPERO database (CRD42-2191987).

AIM To explore the role of necroptosis in apical periodontitis (AP), this study investigated necroptosis in a Fusobacterium nucleatum (Fn)-induced AP model of Balb/c mice and explored related intracellular signalling pathways in L929 cells affected by Fn. METHODOLOGY For the in vivo experiments, expression of receptor-interacting protein kinase-3 (RIP3) was inhibited using an adeno-associated virus and then the Balb/c mice model of AP was established by injecting Fn into the root canal of the first mandibular molars. Bone loss and number of osteoclasts were measured via micro-computed tomography and tartrate-resistant acid phosphatase staining, respectively; expression of RIP3 and phosphorylated mixed lineage kinase domain-like protein (pMLKL) was detected by immunohistochemistry and western blotting; expression of mRNA of inflammatory cytokines was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). For the in vitro experiments, L929 cells transfected with RIP3-Mus-siRNA or negative control siRNA were co-cultured with Fn; thereafter, western blotting, detection of cell death and viability and qRT-PCR analyses were performed to assess the activation of necroptosis pathway and expression of mRNA of inflammatory cytokines. Data were analysed with unpaired t-test and one-way analysis of variance with significance set at p

Objectives We investigated the relation between expression of sirtuin 5 (SIRT5) in osteoblastic cells and progression of apical periodontitis. The role of SIRT5 in hypoxia-induced reactive oxygen species (ROS) formation and osteoblast apoptosis was also examined. Materials and methods Progression of rat apical periodontitis was monitored by conventional radiography and microcomputed tomography. SIRT5 and oxidative stress biomarker 8-OHdG in bone-lining cells were assessed by immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was used to demonstrate apoptosis. In primary human osteoblasts cultured under hypoxia, Western blot was used to analyze SIRT5 expression and cleavage of pro-caspase 3 and poly(ADP-ribose) polymerase (PARP). SIRT5 was overexpressed through lentiviral technique. ROS formation and mitochondrial membrane potential changes were assessed by MitoSOX-Red and JC-1 fluorescence, respectively. Immunofluorescence microscope was used to evaluate mitochondrial release of cytochrome c. Results In rat apical periodontitis, disease progression was accompanied by decreased expression of SIRT5, increased oxidative stress, and enhanced apoptosis in bone-lining cells. SIRT5 was suppressed in cultured osteoblasts under hypoxia. SIRT5 overexpression ameliorated hypoxia-enhanced ROS formation, mitochondrial depolarization, cytochrome c leakage, activation of caspase-3, and PARP fragmentation. Conclusions SIRT5 is able to alleviate hypoxia-enhanced osteoblast apoptosis. SIRT5 augmentation may have therapeutic potential for apical periodontitis.

For apical periodontitis treatments, a new method with the insertion of an electrode into the root canal of a tooth and application of a current at 500 kHz to sterilize the area by Joule heat has attracted attention. However, few studies have quantified the temperature increase in the root canal. This study aimed to investigate the basic characteristics of the temperature increase in a simple and standard tooth model when energizing a current at 500 kHz to the numerical tooth model with typical electrical and physical properties. We developed a numerical model of a standard tooth (dentin) and periodontal tissues consisting of an alveolar bone, cortical bone, and gingiva, and physiological saline in a root canal and calculated the temperature increase inside the numerical model by a coupled analysis of current and heat when a voltage was applied across the electrodes. The calculated results for the different applied voltages showed a temperature increase at the apical portion of the root canal, which increased with the applied voltage even for the same total supplied energy. The temperature increase occurred at the apical portion of the root canal as the tooth conductivity decreased. When the tooth conductivity was high, a current passed through the dentin, which led to a decrease in the temperature at the apical portion of the root canal. However, a chemical solution with a higher conductivity in the root canal tended to increase the temperature at the apical portion of the root canal, regardless of the tooth conductivity. More efficient approaches for increasing the spatial and temporal temperature for the tooth model target are needed. © 2021 Bioelectromagnetics Society.

AIM To examine the role of palmitic acid in lipopolysaccharide (LPS)-stimulated chemotaxis of macrophages and the potential contribution of saturated fatty acid in signalling during the pathogenesis of apical periodontitis. METHODOLOGY J774, a mouse macrophage cell line, was used in the experiments. After treatment with LPS, proteolytic maturation of sterol regulatory element-binding protein-1c (SREBP-1c) and expression of fatty acid synthase (FASN) were examined by Western analysis. Levels of palmitic acid were measured by reverse phase-high performance liquid chromatography-mass spectrometry. Knockdown of SREBP-1c and FASN was accomplished by small interfering RNA technology. Secretion of CC-chemokine ligand 2 (CCL2) and cellular chemotaxis were assessed by enzyme-linked immunosorbent assay and transwell migration assay, respectively. Sulfo-N-succinimidyl oleate (SSO) treatment was used to inhibit fatty acid signalling in vitro and also in a rat model of apical periodontitis. All data were first subjected to Levene's test. In vitro data were then analysed using ANOVA followed by Tukey's multiple comparison test. Data from animal experiments were analysed by independent t-tests. The significant level was set at 0.05. RESULTS LPS stimulated proteolytic maturation of SREBP-1c and FASN expression in macrophages and significantly enhanced palmitic acid synthesis (P

AIM To explore the mechanism of secreted frizzled-related protein I (sFRP1) involvement in the osteogenic differentiation of human periodontal ligament cells (hPDLCs) under inflammatory conditions. METHODOLOGY hPDLCs were cultured in an osteogenic differentiation-inducing medium (odi) and subjected to the stimulation of Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) with or without the inhibition of sFRP1. Quantitative real-time polymerase chain reaction, Western blot and enzyme-linked immunosorbent assay were carried out to evaluate the expression of osteogenic markers as well as the classic Wnt signalling pathway. Periapical periodontitis was induced in Wistar rats to further confirm the effect of sFRP1 inhibitor on bone loss in vivo. After the Shapiro-Wilk normality test, data were analysed by Student's paired t-test or one-way Anova test with a P value less than 0.05 as the level of statistical significance. RESULTS Significantly decreased mRNA and protein expression of osteogenic markers were detected in hPDLCs treated with P. gingivalis LPS during osteogenic induction (P

Retrograde peri-implantitis is a symptomatic complication, characterised by radiographic detection of bone loss at the periapex of the implant. The aim of this study was to investigate the possible endodontic aetiology, evaluating the effectiveness of surgical treatment without endodontic therapy of adjacent teeth. In the 10-year interval, three patients reported symptoms of retrograde peri-implantitis after a mean period of 30.6 days from implant placement. Mean follow-up after surgical procedures was 8.66 years, with an implant survival of 100%. Retrograde peri-implantitis was probably caused by colonisation of the apical surface of the implant by bacteria persisting in the area after endodontic failure/apical periodontitis, reactivated by drilling in the site. In all cases, the adjacent teeth remained vital during the years, showing that a direct cause-and-effect relationship between pulpal/periapical disease of adjacent teeth and retrograde peri-implantitis was never present.

AIM: To evaluate the efficacy of a prototype root canal dressing containing surface pre-reacted glass-ionomer (S-PRG) fillers on repairing induced periapical lesions in a rat model. Calcium hydroxide [Ca(OH)2 ] was applied as a comparison in the healing process. METHODOLOGY: The pulp chambers of the maxillary first molars in 64 male Wistar rats aged 16 weeks were opened to induce periapical lesions. After 28 days, the mesial canal of each tooth was prepared, irrigated with 2.5% sodium hypochlorite (NaOCl) only (control group: irrigation) or followed by the respective dressing [Ca(OH)2 group, irrigation + Ca(OH)2 ; S-PRG group, irrigation + S-PRG], and restored with composite resin for 3 or 7 days (10/group). Four rats with healthy molars were used as blank controls. Descriptive analysis of the periapical radiographs, haematoxylin and eosin staining, and immunohistochemical observation were performed 3 and 7 days after treatment. The periapical gray value, CD68 macrophages, and osteoclasts (cathepsin-K) were quantified and statistically analyzed with Tukey's honest significant difference test. A significant difference was achieved when p values were

This single-centre retrospective case-control study evaluated fractal dimension (FD) changes in radiographs of periapical lesions using a fractal analysis in healthy individuals and type 2 diabetes mellitus (DM) patients following root canal treatment.The study data consisted of two groups: the DM group which contained a total of 46 mandibular molar teeth in 37 patients with no systemic disease other than type 2 DM, and the control group which contained a total of 52 mandibular molar teeth in 41 patients without systemic disease. Periapical radiographs were obtained prior to root canal treatment and 1 year post-treatment. Fractal analysis was performed by selecting a region of interest on the periapical radiographs. For both groups, the FD changes in lesion area were calculated and compared. In addition, periapical status was evaluated using the periapical index (PAI) scores on periapical radiographs for both groups. Data were analysed using dependent-sample t-test, independent-sample t-test, Wilcoxon signed-rank test and Mann-Whitney U-test.In both groups, FD values were increased significantly 1 year post-treatment as compared with those prior to treatment (P 0.05). The time-dependent increase in FD was significantly greater in the control group (P 0.05). Time-dependent increases in FD did not differ between genders (P 0.05). There was a significant decrease in PAI scores in both type 2 DM and control groups depending on time (P 0.05). No significant difference was found between the groups in terms of time-related decreases in PAI scores (P 0.05).An increase in the FD of the periapical lesion area was observed 1 year after root canal treatment. DM had a negative effect on FD increase.

AIM To evaluate the association between the promoter region of defensin beta 1 (DEFB1) genetic polymorphisms and persistent apical periodontitis (PAP) in Brazilian patients. METHODOLOGY Seventy-three patients with post-treatment PAP (PAP group) and 89 patients with root filled teeth with healed and healthy periradicular tissues (healed group) were included (all teeth had apical periodontitis lesions at the beginning of the treatment). Patients who had undergone at least 1 year of follow-up after root canal treatment were recalled, and their genomic DNA was extracted from saliva. Two single nucleotide polymorphisms (SNPs) in DEFB1 at the g. -52G>A (rs1799946) and g. -20G>A (rs11362) positions were analysed using real-time polymerase chain reaction. The chi-squared test was performed, and the odds ratios were calculated using Epi Info 3.5.2. Logistic regression analysis in the codominant model, using the time of follow-up as a variable, was used to evaluate the SNP-SNP interaction. All tests were performed with an established alpha of 0.05 (P = 0.05). RESULTS For the rs11362 polymorphism in the codominant and recessive models, patients who carried two copies of the T allele had a significantly lower risk of developing PAP (P = 0.040 and P = 0.031, respectively). For the rs1799946 polymorphism in DEFB1 in the codominant and recessive models, carrying one copy of the T allele significantly increased the risk of developing PAP (P = 0.007 and P = 0.031, respectively). In the logistic regression, both polymorphisms were associated with PAP as well as the SNP-SNP interaction (P

Aim To describe four cases of an uncommon type of segmental root development after endodontic revitalization procedures. The formation, development and prognosis of this phenomenon are discussed, along with the causes and preventive measures. Summary This report describes one immature maxillary anterior tooth with an extensive periapical lesion after partial extrusion caused by trauma and three immature mandibular premolars with extensive periapical lesions after fracture of the dens evaginatus. All four teeth underwent revitalization procedures. During follow-up, an uncommon type of segmental root development was observed in each case, where the apical segment appeared to detach from the body of the root and developed separately. In all cases, the detached apical root segments continued to develop with a shape and structure similar to that of a normal root tip. However, further development of the root body did not appear to occur. The follow-up times of the present cases were 11, 60, 41 and 67 months, respectively. All four teeth remain intact and functioned normally without symptoms. Cases 2 and 3 displayed positive reactions to electrical pulp tests during follow-up. Key learning points Trauma and extensive periapical inflammation may result in the detachment of Hertwig's epithelial root sheath (HERS) and apical papilla from the root, thus creating a separate apical root segment. Formation of an apical root segment could be regarded as evidence of displacement of the HERS and apical papilla. Once this occurs, there is no chance that the main root of the tooth will develop into a normal-sized root. This type of segmental root development is always possible. If the teeth have suffered from severe trauma or have long-term and large periapical lesions before revitalization, the possibility of segmental root development should be considered. During the process of revitalization, intracanal bleeding is induced by rotating a pre-curved K-file 2 mm past the apical foramen. This procedure should be done gently to protect the apical structures and avoid iatrogenic factors that could lead to abnormal root development.

BACKGROUND Diabetes mellitus (DM) may affect the healing and survival of root filled teeth with periapical lesions. AIM To systematically analyse the available clinical literature to evaluate the association between DM and the prevalence of radiolucent periapical lesions in root filled teeth. The review question was 'Is there a difference between the root canal treatment healing outcome (in terms of presence or absence of radiolucent periapical lesions) in diabetic and non-diabetic patients?'. DATA SOURCES A systematic review of cross-sectional studies and prospective clinical trials was conducted according to the PRISMA checklist. The review involved a search of the electronic databases of PubMed, Scopus and EBSCO host. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS The research protocol was previously registered in the International Prospective Register of Ongoing Systematic Reviews (CRD42019130954) and included defined inclusion/exclusion criteria. The included studies were related to the root canal treatment outcome in diabetic patients in terms of periapical radiolucent lesions associated with root filled teeth. STUDY APPRAISAL AND SYNTHESIS The selected studies were critically analysed by two evaluators using the Joanna Briggs Institute Critical Appraisal tool. The pooled odds ratio (OR) was recognized as the primary outcome variable and measure of the effect for the occurrence of periapical lesions associated with root filled teeth of control and diabetic patients. The random-effects Mantel-Haenszel method was used, at a 95% confidence interval, to calculate the pooled OR. A funnel plot was created to evaluate possible sources of heterogeneity. RESULTS Ten studies published between 1989 and March 2019 were selected after thorough analysis and exclusion according to the strict criteria. Seven cross-sectional studies, 1 longitudinal and 2 prospective clinical studies were included. The pooled OR was calculated by comparing 773 diabetic subjects and 1133 control subjects. The pooled OR for the observational studies and clinical studies were 1.42 and 6.36, respectively. This value signified a high prevalence of periapical lesions in root filled teeth in diabetic subjects. LIMITATIONS There are limited prospective clinical trials on this topic. The majority of the included studies are observational. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS The data suggest a strong connection between the presence of periapical radiolucency on root filled teeth amongst diabetics as determined by the pooled OR.

This study aimed to assess regenerative treatment protocols for maturogenesis of immature teeth with apical periodontitis in dogs. Apical periodontitis was induced in immature premolars of 8 mongrel dogs teeth that were divided into 5 groups; regeneration via blood clotting (REG group); chitosan loaded with demineralised bone matrix (REG-CD group); chitosan loaded with dexamethazone corticosteroid (REG-CC group); and positive and negative control groups. All groups showed comparable apical hard tissue formation and significantly different from the control group. Results also showed decrease in inflammatory tissue reaction, bone resorption and periodontal ligament thickness. Tissue reaction and inflammatory infiltrates were significantly less in REG-CC group compared to others. Other parameters showed no significant difference. In conclusion, regenerative endodontic techniques using chitosan-based formulations have the potential to be used as an alternative for root maturation in teeth with apical periodontitis.

ObjectiveDental infections produce significant increases in systemic inflammatory responses manifested by cytokines and acute phase reactants. This study evaluated the postoperative C‐reactive protein (CRP) levels according to patients having teeth treated or not treated for apical periodontitis (AP) before heart valve surgery.Materials and MethodsPreoperative, postoperative third‐ and fifth‐day CRP levels, and the previous dental data of 91 patients were investigated. Whether the patients had been treated for AP and whether they used antibiotic prophylaxis for this treatment were determined by examining the previous data. The analysis of covariance (ANCOVA) was used for statistical analysis.ResultsThere were no statistically significant differences in the preoperative CRP levels and the third‐day CRP levels between all patients treated and those not treated for AP (p>0.05). The mean fifth‐day CRP levels of the patients with teeth treated for AP were significantly lower than those of the patients with teeth not treated for AP (p

AIM To assess the impact of two root canal treatment protocols on the oral health-related quality of life (OHRQoL) of patients in need of root canal treatment on their anterior teeth. METHODOLOGY The sample consisted of 120 participants (mean age: 34 years) enrolled in a pragmatic randomized clinical trial evaluating two root canal treatment protocols. Anterior teeth with nonvital pulps were allocated for root canal preparation with either hand files and filled with lateral compaction of gutta-percha (manual protocol) or canal preparation with a single file in a reciprocating movement and filled with a single cone technique (Reciproc protocol). OHRQoL data were assessed using the Oral Health Impact Profile instrument (OHIP-14), which was administered before the root canal intervention (baseline), and 6 and 12 months after treatment. Demographic and clinical characteristics of participants were collected at baseline. Data were analysed using bivariate analyses, Poisson univariate and multiple regression (α = 0.05). RESULTS The drop-out rate from baseline was 27% and 28% at 6 and 12 months after treatment, respectively. Both root canal protocols significantly enhanced patients' OHRQoL, regardless of the follow-up time (P

To evaluate the effects of alcohol and nicotine, when used alone or simultaneously, in the development of apical periodontitis induced in rats, using a correlative analytic approach with micro-CT, histological and immunohistochemical analysis.Twenty-eight male Wistar rats were arranged into four groups: Control, Nicotine, Alcohol and Alcohol + Nicotine. The alcohol groups were exposed to self-administration of a 25% alcohol solution, whilst the other groups drunk only filtered water. The nicotine groups received daily intraperitoneal injections of a solution with 0.19 μL of nicotine per mL, whilst the other groups received saline solution. The pulps of the left mandibular first molars were exposed for 28 days to induce periapical lesions. Throughout the experiment, drug administration was maintained, and the animals had their weight and solid and liquid consumption measured. After euthanasia, the mandibles were removed and the area, volume and major diameter of the periapical lesions were measured using micro-computed tomography images. The samples were submitted to histopathological evaluation and immunohistochemistry for RANKL and PTHrP. Statistical analysis was undertaken with a significance level of 5%. Nonparametric data were analysed using the Kruskal-Wallis test followed by Dunn's test, whilst one-way anova followed by Tukey's test was performed for parametric data.The alcohol groups had lower solid and liquid consumption and gained less weight when compared to the nonalcohol groups (P 0.05). The Alcohol + Nicotine group had lesions with significantly larger volume and area when compared to the other groups (P 0.05), whilst the Alcohol or Nicotine groups had significantly larger lesions than the control group (P 0.05). There was no significant difference in the largest diameter of the lesions amongst groups (P 0.05). The experimental groups had greater inflammatory response scores than the control group (P 0.05), and the representative samples had more pronounced immunoreaction against RANKL and PTHrP antibodies.Alcohol and nicotine consumption exacerbated the inflammatory response and the development of periradicular lesions in rats. The association of both substances enhanced their harmful effects.

AIM To investigate the presence, localization and the possible correlation of the fibroblast growth factor receptor-2 (FGFR2) with inflammatory resorption of cementum, periodontal ligament and alveolar bone during development of apical periodontitis in mice. METHODOLOGY Apical periodontitis was experimentally induced in mandibular first molars of mice by pulp exposure to the oral environment. Healthy teeth without pulp exposure were used as controls. At 7, 21 and 42 days following pulp exposure, the animals were euthanized and the jaws were prepared for analysis under conventional and fluorescence microscopy, immunohistochemistry (FGFR2), RT-PCR (RNAm levels of RANK, RANKL, OPG, Runx2 and cathepsin K) and enzyme histochemistry (cementoclasts and osteoclasts). Statistical analysis was performed by Kruskal-Wallis tests and Dunn's post hoc tests for multiple comparisons (α = 0.05) using SAS 9.4 software. RESULTS FGFR2-positive cells were not observed in the tissues surrounding healthy teeth but were observed in teeth with periapical lesions from seven days after root canal contamination. At days 21 and 42 after endodontic infection, the increase in periapical lesion size was accompanied by significantly enhanced expression of FGFR2 (P

Aim: To assess the impact of motion artefacts and motion-artefact correction on diagnostic accuracy of apical periodontitis (AP) in CBCT images. Methodology: Based on clinical and radiographic inspection of 40 formalin-fixated human jaw specimens, 77 roots in 45 teeth (molars and premolars), with various disease and treatment state, were selected. The specimens were mounted on a robot simulating 3-mm movement types (nodding, lateral rotation and tremor). CBCT images with and without (controls) movements were acquired in four CBCT units: without motion-artefact correction in Cranex 3Dx, Orthophos SL 3D, and Promax 3D Mid, and with motion-artefact correction in Promax 3D Mid and X1. Three observers blindly assessed (i) whether the images were interpretable and (ii) if AP was present (5-step probability index). Histopathology provided the reference standard for presence of AP. Weighted Kappa statistics described inter-observer agreement. Estimates of diagnostic accuracy were assessed by means of receiver operator characteristic (ROC) curve analysis. Area under the curve (AUC) provided a measure of accuracy, and paired-sample AUC difference tests compared differences amongst the CBCT units and movement types. Results: Observer agreement was substantial for control images, moderate for motion-artefact corrected images and fair for images without motion-artefact correction. When movement was present, motion-artefact correction reduced the percentage of images scored as noninterpretable or with uncertain disease state (score 3 in the 5-step probability index). Control images were not perfectly accurate (both false-positive and false-negative results were present; AUC 0.750–0.799). Images acquired with movement and without motion-artefact correction (AUC 0.541–0.709) were associated with significantly lower accuracy than control images (P

Background and objective Human cytomegalovirus (HCMV) has been associated with periodontitis and apical periodontitis. The objective of this systematic review was to evaluate the association between HCMV and periodontitis, and apical periodontitis of endodontic origin. Material and methods A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines and registered in the International prospective register of systematic reviews (PROSPERO). The search for potential studies was performed in MEDLINE via PubMed, Scopus, and SciELO. A quality assessment of the studies, publication bias analysis, and meta-analysis was performed. The results are presented in odds ratio with 95% confidence interval with the corresponding Forest plot. Sensitivity analysis was performed to evaluate the consistency of the results. Results Thirty-two studies were included in the quantitative and qualitative analyses. Of these, 26 were in periodontitis patients and 6 in apical periodontitis patients. Forest plot of combined studies revealed significant increased odds for periodontitis when subgingival HCMV was detected (OR 5.31; 95% CI 3.15-8.97). Sensitivity analysis based on quality of the included studies, showed consistent results. In contrast, the odds ratio for apical periodontitis when HCMV was detected from apical lesions was not statistically significant (OR 3.65; 95% CI 0.49-27.10). Conclusions The results from the meta-analysis indicate that HCMV is significantly associated with periodontitis. In contrast, HCMV infection is not associated with apical periodontitis.

Aim First, to determine the feasibility of using the low-density lipoprotein receptor knockout (LDLR KO) mouse model to study apical periodontitis (AP). Secondly, to investigate the causal relationship between AP and atherosclerosis. It was hypothesized that it would be feasible to induce AP and atherosclerosis in LDLR KO mice and find a difference in atherosclerosis between AP and Sham groups. Methodology Using a published methodology, AP was induced in LDLR KO mice by exposing the dental pulp of the four first molars (Tx). Shams received only anaesthesia. Mice were fed a high fat, Western-type diet (WTD), to induce atherosclerosis. At 16 weeks, mice were euthanized and aortas collected to measure atherosclerosis lesion burden (oil red O staining). Periapical lesions were validated using micro-CT and histology. Systemic inflammation was measured using a cytokine array. Results Both groups developed a similar degree of atherosclerosis (mean lesion area 7.46 ± 0.44% in the Tx group compared with 7.65 ± 0.46%, in the Sham group, P = 0.77), and a similar degree of inflammation. Periapical lesions (PALs) in all four molars were only identified in a small subset of Tx mice. Conclusions A novel mouse model, which combines AP and CVD, was created. This model allows investigation of the relationship between the two diseases, whilst avoiding other potential common confounders. Although no difference in the degree of atherosclerosis was found between the groups, more studies in which the number of periapical lesions, changes in systemic inflammation and the degree of atherosclerosis are correlated are necessary to ultimately determine the impact of AP on CVD.

Aim To evaluate the effect of intraorifice barriers and bases on the healing of apical periodontitis following root canal treatment in mandibular molars. Methodology A total of 120 permanent mandibular molars with necrotic pulps and periapical radiolucencies (PAI score ≥ 3) were recruited. Root canal treatment was performed in all teeth using a standard protocol, following which they were randomly allocated to one of the three treatment groups: intraorifice barrier group: coronal 3-mm gutta-percha was removed and replaced with glass-ionomer cement (GIC) barrier. The floor of the pulp chamber was then sealed with 2-mm-thick GIC base followed by final composite resin restoration; base group: received 2-mm-thick GIC base before placement of composite resin restoration; and control group: had pulp chamber entirely filled with composite resin only. Follow-up was done at 3, 6, 9 and 12 months. Combination of clinical and radiographic parameters were used to assess treatment outcome. The data were analysed using Kruskal-Wallis, chi-square and Wilcoxon signed-rank tests and logistic regression analysis. Results At the end of 12 months, the base group had the most favourable healing (97.1%), whilst the control group had the least favourable healing (83.8%). The intraorifice barrier group had healing of 92.1%. However, there was no significant difference in healing between groups at the end of the follow-up period (P > 0.05). Additional subgroup analysis revealed a nonsignificant effect of periodontal status and root filling level on periapical healing. Conclusion The use of an additional barrier under permanent restorations did not significantly improve the outcome of primary root canal treatment in posterior teeth after 12 months. However, its influence in the long term requires further evaluation.

The purpose of this systematic review was to assess the effect of occlusal reduction on post-operative pain following root canal treatment and was performed in accordance with the PRISMA statement being registered in the PROSPERO database (CRD42018089941). Two reviewers independently conducted a systematic literature search in the PubMed (MEDLINE), Dentistry & Oral Sciences Source and the Cochrane Library databases. Seven studies were included, of which three were used to perform meta-analysis for 6 days post-operative and the rest for qualitative synthesis. Three studies were assessed as low risk of bias, three as some concern, and one as high risk of bias. Occlusal reduction diminishes the post-operative pain (SMD -1.10 (95%CI -2.06, -0.15) I2 = 96.9%) at 6 days for teeth diagnosed as irreversible pulpitis, and, overall, likely reduces post-operative pain for patients presenting with irreversible pulpitis and/or symptomatic apical periodontitis. Future high-quality clinical trials are needed to better understand the role of occlusal reduction.

Aim This observational cohort study aimed: (i) to determine retrospectively after a 1- to 12-year follow-up period, the strength and independence of the association of various patient-, tooth- and treatment-related prognostic variables with the outcome of root canal treatment in patients with pre-therapeutic apical periodontitis; and (ii) to establish the concordance between those predictors evaluated by both cone-beam computed tomography (CBCT) and digital periapical radiography (DPR). Methodology The study cohort included 125 teeth in 84 individuals. The postoperative clinical signs/symptoms, plus DPR/CBCT-PAI estimations, were used to determine the healing outcome. For statistical analysis, results were dichotomized into completely healed periapical structures versus persistent disease cases. The association between candidate predictor variables with persistent disease was analysed individually and adjusted for confounders using a multivariate binary logistic regression model. Results The success rate was 53.6%. After logistic regression analysis, mandibular tooth location, periapical lesion size >10 mm, poor quality of the coronal restoration, lack of magnification/illumination, lack of disinfection of gutta-percha, time elapsed to definitive coronal restoration >1 week and poor density of root canal filling remained as robust predictors of failures. Concordance between DPR and CBCT scores varied from moderate to almost perfect agreement. Conclusions The findings of this study suggest that several tooth- and treatment-related predictor variables, including tooth location, periapical radiolucency size, quality of the coronal restoration, magnification/illumination, disinfection of gutta-percha, time elapsed to definitive coronal restoration, as well as, the density of root canal filling may act strongly and independently for determining the root canal treatment outcome in teeth with pre-therapeutic apical periodontitis.

Procedural accidents are eventualities that may occur during endodontic treatment because of lack of attention to detail or even unforeseeable situations. Knowledge of the root canal anatomy and its variations is a prerequisite for successful endodontic treatment. This case report describes an endodontic treatment where there was an intercurrence, generating deviation and perforation, which was solved with the aid of guided endodontics. A 37 years old, ASA1, was referred to the clinic for localisation and treatment of a calcified canal of the second right upper premolar. The tomographic images revealed the presence of only one canal and deviation with apical perforation. With the help of CBCT and CAD/CAM, it was possible to perform the guided access technique even after deviation and root perforation. Once again, this technique proved to be safe and predictable, allowing for a favourable prognosis in the long term.

This position statement on the management of deep caries and the exposed pulp represents the consensus of an expert committee, convened by the European Society of Endodontology (ESE). Preserving the pulp in a healthy state with sustained vitality, preventing apical periodontitis and developing minimally invasive biologically based therapies are key themes within contemporary clinical endodontics. The aim of this statement was to summarize current best evidence on the diagnosis and classification of deep caries and caries‐induced pulpal disease, as well as indicating appropriate clinical management strategies for avoiding and treating pulp exposure in permanent teeth with deep or extremely deep caries. In presenting these findings, areas of controversy, low‐quality evidence and uncertainties are highlighted, prior to recommendations for each area of interest. A recently published review article provides more detailed information and was the basis for this position statement (Bjørndal et al. 2019, International Endodontic Journal, doi:10.1111/iej.13128). The intention of this position statement is to provide the practitioner with relevant clinical guidance in this rapidly developing area. An update will be provided within 5 years as further evidence emerges.

AIM To investigate the expression of TP63 in apical periodontitis (AP) tissues and the association of single nucleotide polymorphisms (SNPs) in the TP63 gene with AP using a case-control dataset. METHODOLOGY Expression of TP63 in human AP lesions (apical abscess, radicular cyst, periapical granuloma) was evaluated using immunohistochemistry. A case-control association study was performed to assess the association of TP63 polymorphisms in individuals having AP with or without associated pain. Cases were defined as subjects with deep caries and AP (n = 151) and subjects with symptomatic apical periodontitis or acute apical abscess (n = 124). Subjects without AP (n = 169) and asymptomatic (n = 196) were used as controls, respectively. Saliva samples were collected as source of genomic DNA. Twelve SNPs in the TP63 gene were selected for genotyping using Taqman chemistry in real-time PCR. Data analysis was performed using PLINK software. The Bonferroni method was applied to correct for multiple testing; α ≤ 0.004 indicates significant differences between groups. RESULTS TP63 expression was evident in apical abscesses and radicular cysts, while weaker expression was observed in periapical granulomas. Positive expression was observed in mononuclear cells in the granulation tissues of all AP lesions. Regarding the presence of AP, a trend for allelic association was observed for rs16864812 and rs9810322 (P = 0.04) and rs9810322 genotypes were also nominally associated with AP under a dominant model (P = 0.04). When considering the presence of periapical pain, a trend for allelic and genotypic association was observed for rs10155037 (P = 0.03). Haplotypes were also associated with AP and periapical pain (P ≤ 0.05). CONCLUSIONS Apical periodontitis is a complex multifactorial condition and it is likely that multiple genes and environmental effects may influence its susceptibility, progression or both. TP63 variants may play a role in AP pathogenesis and susceptibility, individually or interactively with other genes. Additional studies in other populations and functional studies are needed to improve understanding of the role of TP63 in AP.

AIM To investigate the possible therapeutic effects of alpha-lipoic acid (ALA) in a model of chronic apical periodontitis in rats by analysing biochemical, histopathological and micro-CT parameters. METHODOLOGY The study was approved by the Animal Ethics Committee of the Near East University. Thirty-two Wistar rats were divided into four groups of eight rats each: Control Group; ALA Group; AP Group; AP + ALA Group. In the AP and AP + ALA groups, the pulp chambers of the mandibular first molars were surgically exposed and were left open to the oral environment for 4-weeks to allow the establishment of periapical lesions. The rats in the Control and AP groups were treated intraperitoneally with saline solution (with a daily dose of 100 mg kg-1 , for 28 days after periapical lesion induction). The rats in the ALA and AP + ALA groups were treated intraperitoneally with ALA (with a daily dose of 100 mg kg-1 , for 28 days after periapical lesion induction). After decapitation, the trunk blood was collected for the assessment of biochemical parameters. The mandibles were surgically removed and dissected for histopathologic analysis and further scanned with micro-CT. Groups of data were compared with a two-way analysis of variance (two-way anova) followed by Sidak's multiple comparison tests. Values of P

Biologic medications (BMs) are increasingly used for the management of systemic chronic inflammatory diseases. These diseases are often associated with a higher prevalence of apical periodontitis (AP) and periodontitis (P). The purpose of this systematic review was to ascertain the interactions between AP and/or P and BMs. The review was registered in the PROSPERO database (CRD42017054756). Electronic searches were performed on Pubmed Medline, Scopus and The Web of Science from their inception through to 20 March 2018. The references of the articles selected were checked. The keywords were chosen based on a pilot search, which aimed to find the most frequently prescribed BMs. The included studies were appraised qualitatively using appropriate tools. Thirty-five articles met the inclusion criteria, comprising 16 non-randomized clinical studies, 12 in vivo animal studies and 7 case reports. Quality of information was assessed as high in 18 articles, moderate in 16 articles and low in 1 article. BMs in patients suffering from chronic inflammatory diseases seems to inhibit the progression of AP and P, and to enhance the healing response to periodontal and endodontic treatment. A healthier condition of the periodontal tissues seems to be associated with a better response of the patient to BMs therapy.