Topological insight of immune-vascular distribution in peri-implantitis lesions.

OBJECTIVE: To characterize the distribution of macrophages, neutrophils, NK cells, and blood vessels in peri-implantitis compared to healthy aged gingiva samples. MATERIALS AND METHODS: This observational study included eight gingival samples from peri-implantitis and eight from periodontally healthy individuals. By immunofluorescence were identified neutrophils, NK cells, macrophages, and their pro-inflammatory or pro-healing phenotypes, and blood vessels. Two ROIs were designated as zone 1, connective tissue closest to the epithelium and zone 2, connective tissue over 200 microns from the rete ridges. Immune cells and vascular structures were quantified and characterized according to their distribution in both zones. RESULTS: Two peri-implantitis zones were characterized by unique macrophage phenotypes and blood vessel architecture. Blood vessels were larger in zone 2 in peri-implantitis. A greater number of NK cells and macrophages were found in peri-implantitis compared to healthy aged samples. A higher presence of pro-inflammatory macrophages was found in zone 1 compared to zone 2. A similar proportion of pro-inflammatory and pro-healing macrophages were found in zone 2. CONCLUSION: A specific distribution for pro-inflammatory macrophages and vascular architecture is observed in peri-implantitis. TNF-α colocalizes with macrophages in the connective tissue near rete ridges. NK cells are more abundant in peri-implantitis than in healthy samples.

Epidemiology of mid-buccal gingival recessions according to the 2018 Classification System in South America: Results from two population-based studies.

AIM: The aim of this investigation was to estimate the prevalence, severity and extent of mid-buccal gingival recessions (GRs; classified according to the 2018 Classification System) and to identify their risk indicators in the South American population. MATERIALS AND METHODS: Epidemiological data from two cross-sectional studies-performed on 1070 South American adolescents and 1456 Chilean adults-were obtained. All participants received a full-mouth periodontal examination by calibrated examiners. GR prevalence was defined as the presence of at least one mid-buccal GR ≥ 1 mm. GRs were also categorized into different recession types (RTs) according to the 2018 World Workshop Classification System. Analyses for RT risk indicators were also performed. All analyses were carried out at the participant level. RESULTS: The prevalence of mid-buccal GRs was 14.1% in South American adolescents and 90.9% in Chilean adults. In South American adolescents, the prevalence of RTs was 4.3% for RT1 GRs, 10.7% for RT2 GRs and 1.7% for RT3 GRs. In Chilean adults, the prevalence of RT1 GRs was 0.3%, while the prevalence of RT2 and RT3 GRs was 85.8% and 77.4%, respectively. Full-Mouth Bleeding Score (FMBS; <25%) was associated with the presence of RT1 GRs in adolescents. The risk indicators for RT2/RT3 GRs mainly overlapped with those for periodontitis. CONCLUSIONS: Mid-buccal GRs affected 14.1% of South American adolescents, whereas they affected most of the Chilean adult population (>90%). While RT1 GRs are more commonly observed in a non-representative cohort of South American adolescents (when compared to Chilean adults), the majority of Chilean adults exhibit RT2/RT3 GRs.

Polarization Profiles of T Lymphocytes and Macrophages Responses in Periodontitis.

Periodontitis is a multifactorial, chronic inflammatory disease affecting the supporting structures of teeth triggered by the complex interactions between a dysbiotic bacterial biofilm and the host's immune response that results in the characteristic loss of periodontal attachment and alveolar bone. The differential phenotypic presentations of periodontitis emerge from inter-individual differences in immune response regulatory mechanisms. The monocyte-macrophage system has a crucial role in innate immunity and the initiation of the T and B lymphocyte adaptive immune responses. Macrophages involve a heterogeneous cell population that shows wide plasticity and differentiation dynamics. In response to the inflammatory milieu, they can skew at the time of TLR ligation to predominant M1 -pro-inflammatory- or M2 -anti-inflammatory/healing- functional phenotypes. The perpetuation of inflammation by M1 macrophages leads to the recruitment of the adaptive immune response, promoting Th1, Th17, and Th22 differentiation, which are directly associated with periodontal breakdown. In contrast, M2 macrophages induce Th2 and Treg responses which are associated with periodontal homeostasis. In this article, we review the recent advances comprising the role of macrophages and lymphocyte polarization profiles and their reprogramming as potential therapeutic strategies. For this purpose, we reviewed the available literature targeting periodontitis, macrophage, and lymphocyte subpopulations with an emphasis in the later 5 years. The active reprogramming of macrophages and lymphocytes polarization crosstalk opens a promising area for therapeutic development.

Bioactive glass-ceramic bone repair associated or not with autogenous bone: a study of organic bone matrix organization in a rabbit critical-sized calvarial model.

OBJECTIVE: The aim of the study was to analyze bone matrix (BMX) organization after bone grafting and repair using a new bioactive glass-ceramic (Biosilicate®) associated or not with particulate autogenous bone graft. MATERIAL AND METHODS: Thirty rabbits underwent surgical bilateral parietal defects and divided into groups according to the materials used: (C) control-blood clot, (BG) particulate autogenous bone, (BS) bioactive glass-ceramic, and BG + BS. After 7, 14, and 30 days post-surgery, a fragment of each specimen was fixed in - 80 °C liquid nitrogen for zymographic evaluation, while the remaining was fixed in 10% formalin for histological birefringence analysis. RESULTS: The results of this study demonstrated that matrix organization in experimental groups was significantly improved compared to C considering collagenous organization. Zymographic analysis revealed pro-MMP-2, pro-MMP-9, and active (a)-MMP-2 in all groups, showing gradual decrease of total gelatinolytic activity during the periods. At day 7, BG presented more prominent gelatinolytic activity for pro-MMP-2 and 9 and a-MMP-2, when compared to the other groups. In addition, at day 7, a 53% activation ratio (active form/[active form + latent form]) was evident in C group, 33% in BS group, and 31% in BG group. CONCLUSION: In general, BS allowed the production of a BMX similar to BG, with organized collagen deposition and MMP-2 and MMP-9 disponibility, permitting satisfactory bone remodeling at the late period. CLINICAL RELEVANCE: The evaluation of new bone substitute, with favorable biological properties, opens the possibility for its use as a viable and efficient alternative to autologous bone graft.

CCR5Δ32 (rs333) polymorphism is associated with decreased risk of chronic and aggressive periodontitis: A case-control analysis based in disease resistance and susceptibility phenotypes.

Chronic and aggressive periodontitis are infectious diseases characterized by the irreversible destruction of periodontal tissues, which is mediated by the host inflammatory immune response triggered by periodontal infection. The chemokine receptor CCR5 play an important role in disease pathogenesis, contributing to pro-inflammatory response and osteoclastogenesis. CCR5Δ32 (rs333) is a loss-of-function mutation in the CCR5 gene, which can potentially modulate the host response and, consequently periodontitis outcome. Thus, we investigated the effect of the CCR5Δ32 mutation over the risk to suffer periodontitis in a cohort of Brazilian patients (total N=699), representative of disease susceptibility (chronic periodontitis, N=197; and aggressive periodontitis, N=91) or resistance (chronic gingivitis, N=193) phenotypes, and healthy subjects (N=218). Additionally, we assayed the influence of CCR5Δ32 in the expression of the biomarkers TNFα, IL-1ß, IL-10, IL-6, IFN-γ and T-bet, and key periodontal pathogens P. gingivalis, T. forsythia, and T. denticola. In the association analysis of resistant versus susceptible subjects, CCR5Δ32 mutant allele-carriers proved significantly protected against chronic (OR 0.49; 95% CI 0.29-0.83; p-value 0.01) and aggressive (OR 0.46; 95% CI 0.22-0.94; p-value 0.03) periodontitis. Further, heterozygous subjects exhibited significantly decreased expression of TNFα in periodontal tissues, pointing to a functional effect of the mutation in periodontal tissues during the progression of the disease. Conversely, no significant changes were observed in the presence or quantity of the periodontal pathogens P. gingivalis, T. forsythia, and T. denticola in the subgingival biofilm that could be attributable to the mutant genotype.

Influence of TNF-α-308 G/A gene polymorphism on temporomandibular disorder.

INTRODUCTION: Tumor necrosis factor alpha (TNF-α) levels are significantly upregulated in the synovial fluid of patients with temporomandibular joint disorder (TMD). The TNF-α influences pain generation and maintenance. Therefore, the aim of this study was to investigate the influence of single nucleotide polymorphism TNFA-308 (rs1800629) on TMD risk and on the pressure pain threshold. METHODS: The genotypic and allelic frequencies of candidate single nucleotide polymorphisms were compared among 152 TMD patients and 91 sex- and age-matched healthy subjects in the control group using the real-time polymerase chain reaction technique. The pressure pain threshold in the temporomandibular joint, anterior fascicle of the temporal muscle, masseter muscle, and Achilles tendon were recorded with an algometer. After the pressure test, all participants received a complete physical examination, including masticatory muscle evaluation, temporomandibular joint palpation, and assessment of mandibular range of motion. RESULTS: The TNFA-308 polymorphism is positively associated with TMD. Subjects with TMD had a 2.87 (95% confidence interval, 1.256-6.569) times greater chance of having the GA genotype than did the control group. Rare A-allele homozygotes demonstrated decreased pain sensitivity for the temporomandibular joint and anterior fascicle of the temporal muscle in the pressure pain threshold test compared with ancestral allele homozygotes. CONCLUSIONS: This study presents an unprecedented association between the TNFA-308 (rs1800629) polymorphism and TMD. Future studies are needed to enlighten the association between TNFA-308 G/A single nucleotide polymorphism and mechanical pain sensitivity.

Matrix metalloproteinases regulate extracellular levels of SDF-1/CXCL12, IL-6 and VEGF in hydrogen peroxide-stimulated human periodontal ligament fibroblasts.

Periodontitis is a highly prevalent infectious disease characterized by the progressive inflammatory destruction of tooth-supporting structures, leading to tooth loss. The underling molecular mechanisms of the disease are incompletely understood, precluding the development of more efficient screening, diagnostic and therapeutic approaches. We investigated the interrelation of three known effector mechanisms of the cellular response to periodontal infection, namely reactive oxygen species (ROS), matrix metalloproteinases (MMPs) and cytokines in primary cell cultures of human periodontal ligament fibroblast (hPDLF). We demonstrated that ROS increase the activity/levels of gelatinolytic MMPs, and stimulate cytokine secretion in hPDLF. Additionally, we proved that MMPs possesses immune modulatory capacity, regulating the secreted levels of cytokines in ROS-stimulated hPDLF cultures. This evidence provides further insight in the molecular pathogenesis of periodontitis, contributing to the future development of more effective therapies.

Two-Step Periosteal Releasing Incision for Tension-Free Flap Closure After Implant Placement With Simultaneous Guided Bone Regeneration.

We evaluated the effect of periosteal-releasing incisions on flap displacement in anterior maxillary sites following implant placement and simultaneously guided bone regeneration. Thirty patients, each requiring a single dental implant and guided bone regeneration in the maxillary esthetic zone, were recruited. After full-thickness flap elevation, the displacement of the flap was measured under a standardized tension of 1 Ncm. Then, a 2-step periosteal releasing incision was placed in the internal aspect of the flap, and the displacement was remeasured using the same standardized tension. Keratinized tissue width and mucosal thickness at the surgical site were recorded. Patient-reported outcomes were assessed at the 7- and 14-day recall visits. Flap displacement (primary outcome) was calculated before and after periosteal-releasing incisions. Multivariable linear regression models were used to evaluate the influence of mucosal thickness on flap displacement and adjusted for Keratinized tissue width. Primary wound closure was achieved in all patients. The mean difference in flap coronal displacement before and after the periosteal-releasing incisions was 8.2 mm (p < .0001). Adjusted regression models showed no association between mucosal thickness and keratinized tissue width with the amount of flap displacement (p = .770). Patient-reported outcome measures for pain, swelling, and bleeding amounted to 1.28 ± 1.93, 1.36 ± 1.87, and 0.0 ± 0.0 at 7 days and 0.11 ± 0.57, 0.56 ± 1.03, and 0.0 ± 0.0 at 14 days, respectively. Periosteal-releasing incisions using the 2-step procedure described here are a predictable technique to obtain coronal flap displacements >8 mm without increased surgical complications.

Pilot Study: Periosteal Mattress Sutures as an Alternative to Pins and Screws in Guided Bone Regeneration in the Esthetic Zone.

OBJECTIVES: To quantify the buccal bone thickness, area, and perimeter following guided bone regeneration (GBR) using stabilizing periosteal sutures. The loss in hard tissue volume may impair proper implant placement. GBR has been used to regenerate the lost alveolar ridge prior to or at the same time as dental implant placement. The most important factor for GBR success is graft stability. The periosteal mattress suture (PMS) stabilizing technique is an alternative to pins and screws to stabilize bone grafting material and has the advantage of not requiring the removal of the fixing devices. MATERIALS AND METHODS: A CBCT was acquired before and 6 months after surgery from six patients who underwent GBR with the PMS stabilizing technique. Images were analyzed for buccal bone thickness, area, and perimeter. RESULTS: The mean change in buccal bone thickness was 3.42 mm (± 1.31 SD) and proved statistically significant (P = .005). The mean change in bone crest area also proved statistically significant (P = .001). No significant difference was found in bone perimeter (P = .12). CONCLUSIONS: The PMS technique delivered optimal results without clinical complications. This study shows the potential of this technique as an alternative to pins or screws for graft stabilization in the esthetic zone.

Performance of the 2017 AAP/EFP case definition compared with the CDC/AAP definition in population-based studies.

BACKGROUND: Classification of the periodontal conditions is indispensable for epidemiological data in order to guide situational awareness and therapeutic strategies. The new classification of periodontal diseases and conditions introduced by the American Academy of Periodontology and the European Federation of Periodontology (AAP/EFP), however, has not yet been applied to population-based studies. The aim of the present study was to compare the prevalence of periodontitis between the AAP/EFP and the CDC/AAP classification system and to evaluate the accuracy of the new AAP/EFP classification system against the CDC/AAP case definition for population-based studies. METHODS: Epidemiological data from two cross-sectional studies were obtained. One of them was a population-based study on Chilean adults (1.456 individuals; 35-44 years; 65-74 years) and the other one a sample of adolescents (1.070 individuals; 15-19 years) from five countries; Argentina, Chile, Colombia, Ecuador, and Uruguay. All participants had undergone full-mouth periodontal examination by calibrated examiners. Epidemiological datasets were analyzed according to the AAP/EFP and the CDC/AAP case definitions. The accuracy of the AAP/EFP definition was examined by assessing the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating curve (ROC) using the CDC/AAP case definition as the reference standard. RESULTS: According to the AAP/EFP, the prevalence of periodontitis in adolescents was 75.6%. The majority of the adolescents were classified either as Stage I (39.2%) or Stage II (28.2%). By using the CDC/AAP classification the prevalence of periodontitis in adolescents was 27.2%. The most common form of periodontitis with the CDC/AAP classification was moderate periodontitis (15.3%) followed by mild periodontitis (11.4%). The AAP/EFP revealed high sensitivity in moderate (95.7%) and severe periodontitis (100%) as well as a moderate (75%) to high specificity (92%) in moderate and severe periodontitis, respectively. The PPV was 41.6% in moderate and 5.7% in severe periodontitis whereas the NPV was high in both categories (moderate = 99%; severe = 100%). The AUC was 0.91 (95% CI = 0.89-0.93). In adults, the prevalence of periodontitis was 99% according to the AAP/EFP. The majority of adults were classified as Stage IV (81.3%) whereas Stage III amounted to 12.8%. By using the CDC/AAP classification, the prevalence of periodontitis in adults was 88.3% and the most common form of periodontitis was moderate periodontitis (57.2%) followed by severe periodontitis (29.7%). In adults, the AAP/EFP revealed high sensitivity for moderate (99.7%) and severe periodontitis (100%), but low specificity for both categories (moderate = 6.8%; severe = 8.3%). The PPV was 88.7% in moderate and 31.7% in severe periodontitis. The NPV was high in both categories (moderate = 76.5%; severe = 100%). The AUC was 0.57 (95% CI = 0.53-0.62). CONCLUSIONS: This study revealed a clear discrepancy in the prevalence of periodontitis between the AAP/EFP and the CDC/AAP classification when using epidemiological data. The 2017 AAP/EFP classification system performs well when compared to the CDC/AAP case definition in identifying adolescents with periodontitis. The AAP/EFP system seems less accurate in adults with high prevalence of periodontitis.

Developing a protocol for a preventive oral health exam for elderly people (EDePAM) using E-Delphi methodology.

The aim of this study was to develop a Preventive Oral Health Exam for Elderly People (EDePAM), using the e-Delphi technique, to diagnose oral health problems in people 65 or older. The e-Delphi technique was used with experts in multiple stages, and in a final workshop, where an agreement on an examination protocol was reached for diagnosing dental caries, oral mucosa lesions, periodontal diseases, and masticatory function disorders. Quantitative analyses of all the rounds of the e-Delphi method were conducted. It was agreed that the International Caries Detection and Assessment System (ICDAS) should be used together with a modified version of the Nyvad criteria to detect and assess caries lesions. It was also agreed that an assessment was needed of the different factors involved in determining caries risk, namely socioeconomic level, access to fluoride, level of dependence/functionality, salivary flow, history of head and neck cancer treatment, use of medications that decrease salivary flow, diet, use of removable dental prostheses, exposure of root surfaces, and caries history. Furthermore, patients would be required to undergo an examination of the oral mucosa, where any existing lesion should be described in terms of its clinical appearance, location, and risk potential. It was also agreed that an assessment of masticatory function should be performed using the Leake index, together with chewing-gum combined with a color scale to categorize masticatory performance. The number of pairs of occluding antagonist teeth was considered as the best predictor of masticatory function. The 2018 classification by the American Academy of Periodontology (AAP) / European Federation of Periodontology (EFP) was accepted as the standard to assess periodontal status, and it was agreed that this assessment should include an evaluation of clinical attachment loss and bleeding on probing. The novel EDePAM was considered as appropriate for conducting a functional assessment of oral health by providing a comprehensive diagnosis of oral diseases.

Periodontal Treatment Protocol for Decompensated Diabetes Patients.

Background: Decompensated diabetes is associated with a higher prevalence and severity of periodontitis and poorer response to periodontal therapy. It is conceivable that periodontal therapy may cause systemic and local complications in this type of patients. The aim of the present study was to identify and describe the best available evidence for the treatment of periodontitis in decompensated diabetics. Material and methods: An expert committee including participants from different areas gathered to discuss and develop a treatment guideline under the guidance of the Cochrane Associate Center, Faculty of Dentistry, University of Chile. In total, four research questions were prepared. The questions prepared related to decompensated diabetic patients (glycated hemoglobin >8) were, (1) Does the exposure to periodontal treatment increase the risk of infectious or systemic complications? (2) Does the antibiotic treatment or prophylaxis, compared to not giving it, reduce infectious complications? (3) Does the exposure to periodontal treatment, compared to no treatment, reduce the glycated hemoglobin levels (HbA1c)? Last question was related to diabetic patients, (4) Does the exposure to a higher level of HbA1c, compared to stable levels, increase the risk of infectious complications? Based on these questions, a search strategy was developed using MEDLINE and EPISTEMONIKOS. Only systematic reviews were considered. Results: For question 1, the search yielded 12 records in EPISTEMONIKOS and 23 in MEDLINE. None of these studies addressed the question. For question 2, the search yielded 58 records in EPISTEMONIKOS and 11 in MEDLINE. None of these studies addressed the question. For question 3, the search yielded 16 records in EPISTEMONIKOS and 11 in MEDLINE. Thirteen addressed the question. For question 4, the search yielded 7 records in EPISTEMONIKOS and 9 in MEDLINE. One addressed the question. Conclusions: In decompensated diabetic patients, there is lack of scientific information about risk of infectious or systemic complications as a result of periodontal treatment and about the impact of antibiotic treatment or prophylaxis on reduction if infectious complications. A defined HbA1c threshold for dental and periodontal treatment in diabetic patients has yet to be determined. Finally, periodontal treatment does have an impact on HbA1c levels.

Impact of COVID-19 Pandemic on Quality of Life of Type II Diabetes Patients With Periodontitis.

Background: Confinement due to the COVID-19 pandemic has made dental treatments impossible in Chile and many other countries, including diabetic patients with periodontitis. The aim of the present study was to evaluate the impact of periodontal therapy in terms of oral health-related quality of life (OHRQoL) during the COVID-19 pandemic in a cohort of diabetic patients with periodontitis. Material and Methods: Thirty-eight diabetic patients with stage III-IV periodontitis, enrolled for periodontal therapy, were screened. Periodontal clinical parameters including clinical attachment loss (CAL), probing pocket depth (PPD) and bleeding on probing (BOP) as well as glycated hemoglobin (HbA1c) were evaluated at baseline and 3 months follow-up prior the pandemic. The OHRQoL changes by means of Oral Health Impact Profile (OHIP-14) and a self-reported oral health questionnaire were assessed at baseline (prior pandemic) and during the pandemic via telemonitoring. Results: Thirty-one patients received non-surgical periodontal therapy prior to the pandemic. Out of the 31 patients, four died due to COVID-19 resulting in 27 patients available for telemonitoring at the time of the pandemic. Periodontal therapy significantly improved CAL, PPD and BOP (p < 0.05) but not HbA1c (p > 0.05) between baseline and 3 months follow-up pior to the pandemic. Total OHIP-14 scores significantly improved between baseline and the middle of pandemic (intragroup comparison p = 0.00411). In particular, OHIP-14 scores related to the "Physical pain" (intragroup comparison p = 0.04) and "Psychological disability" (intragroup comparison p = 0.00) significantly improved between baseline and the middle of pandemic. Conclusions: In diabetic type II patients with periodontitis periodontal therapy tends to improve the oral health-related quality of life despite the COVID-19 pandemic.

Periodontal disease and its impact on general health in Latin America. Section I: Introduction part I.

A high level of general and oral health are invaluable assets, a factor not always considered a basic human right for their better life quality. The mouth is a critical point of contact with the external environment, which is established when we talk, chew, swallow and when food digestion begins. From a perspective of the human condition, the mouth is crucial for the integration of sound, social appearance of the individual, and is one of the fundamental components of overall health. Therefore, not having an adequate level of oral health affects self-esteem, quality of life and people's general well-being.

Effect of periodontal treatment in patients with periodontitis and diabetes: systematic review and meta-analysis.

OBJECTIVE: The evidence is inconclusive regarding the effect of periodontal treatment on glycemic control and systemic inflammation in patients with type 2 diabetes (T2D) and periodontitis. To evaluate the effect of scaling and root planing (SRP) on the metabolic control and systemic inflammation of patients with type 2 diabetes (T2D). METHODOLOGY: A literature search was conducted using the MEDLINE database via PubMed and the Cochrane Central Register of Controlled Trials, from their oldest records up to July 2018. Only randomized clinical trials (RCT) were considered eligible for evaluating the effect of periodontal treatment on markers of metabolic control [glycated hemoglobin (HbA1C)] and systemic inflammation [C-reactive protein (CRP)] in patients with T2D. The quality of the studies was evaluated using the Cochrane Collaboration risk assessment tool. Meta-analyses were performed for HbA1c and CRP using random effects models. The size of the overall intervention effect was estimated by calculating the weighted average of the differences in means (DM) between the groups in each study. Heterogeneity was assessed using the Q-statistic method (x2 and I²). The level of significance was established at p<0.05. RESULTS: Nine RCT were included. SRP was effective in reducing HbA1c [DM=0.56 (0.36-0.75); p<0.01] and CRP [DM=1.89 (1.70-2.08); p<0.01]. No heterogeneity was detected (I2=0%, p>0.05). CONCLUSIONS: SRP has an impact on metabolic control and reduction of systemic inflammation of patients with T2D.

Protocolo de validación del instrumento Examen Dental Preventivo del Adulto Mayor / Validation protocol for the Preventive Dental Examination of the Elderly instrument

Los desafíos del envejecimiento de la población y la acumulación de daño oral nos obligan a desarrollar herramientas diagnosticas validas y confiables que nos permitan caracterizar a la población, evaluar sus necesidades terapéuticas, planificar intervenciones significativas y realizar seguimiento de su condición. Con este propósito realizamos una revisión sistemática de la literatura relevante para establecer una metódica secuencial para la validación de la herramienta diagnostica Examen Dental Preventivo del Adulto Mayor. Seleccionamos 48 artículos relevantes, cuya heterogeneidad impidió la realización de un metaanálisis. Sin embargo, los artículos seleccionados fueron sometidos a una síntesis cuantitativa analítica, que nos permitió identificar los dominios y estrategias relevantes para la validación y proponer un protocolo de cinco fases secuenciales que presentamos en extenso en el presente artículo.

The challenges of population aging and the accumulation of oral damage force us to develop valid and reliable diagnostic tools to characterize the population, evaluate their therapeutic needs, plan significant interventions, and monitor their condition post treatment. We carried out a systematic review of the relevant literature to establish a sequential method for the validation of the Preventive Dental Examination of the Elderly diagnostic tool. We selected 48 relevant articles, whose heterogeneity prevented us from performing a meta-analysis. However, the selected articles were subjected to an analytical quantitative synthesis, which allowed us to identify the relevant domains and strategies for validation and then propose a protocol of five sequential phases that we present in detail in this article.

WNT gene polymorphisms and predisposition to apical periodontitis.

Single nucleotide polymorphisms (SNPs) in WNT genes may impact gene/protein function and contribute to individual predisposition to apical periodontitis (AP). Here, we investigated the association of SNPs in/nearby WNT3, WNT3A, WNT5A, WNT8A, WNT9B and WNT11 genes with AP using a case-control dataset. Cases were defined as individuals with deep caries and AP (n = 188); controls had deep caries and no AP (n = 230). Genotyping was performed using Taqman chemistry in real time PCR. Data analyses was performed using Fisher Exact tests assuming a Bonferroni correction threshold value of 0.005. Single-SNP association analysis revealed a trend for association with WNT3 rs9890413 genotypes (P = 0.009) under a dominant model and allelic association for WNT3A rs1745420 (P = 0.009). Haplotypes involving WNT3-WNT9B-WNT3A alleles were also significantly associated with AP (P ≤ 0.003). Luciferase reporter assays showed higher transcriptional activity (1.4-fold) with the alternate G allele in rs1745420. Expression of WNT3, WNT3A and WNT5A in AP tissues was significantly higher than in control tissues, and inversely correlated with the expression of SERPINB1, COL1A1 and TIMP1 (P < 0.05). Our results suggest that WNT genes have a role in modulating AP and polymorphisms in these genes may increase susceptibility to AP.

Investigating Potential Correlations between Endodontic Pathology and Cardiovascular Diseases Using Epidemiological and Genetic Approaches.

INTRODUCTION: Apical periodontitis (AP) and cardiovascular diseases (CVDs) are chronic conditions triggered by an inflammatory process and sharing similar pathogeneses and molecular players. Previous studies have suggested that AP may perpetuate a systemic inflammation state and, in turn, contribute to CVD. In this study, we investigated the potential association between endodontic pathology and CVD using epidemiological and genetic approaches. METHODS: Epidemiologic analysis was performed by querying the medical and dental records of >2 million patients. We retrieved information on positive/negative history for endodontic pathologies and CVDs using diagnostic and treatment codes from a dental school-based and a hospital-based patient electronic health record system. A case-control genetic association study was also performed; 10 single nucleotide polymorphisms in genes identified as strongly associated with CVDs were genotyped in 195 cases with AP and 189 control individuals without AP. Data analyses were performed using the chi-square and Fisher exact tests. P ≤.05 indicates significant difference between groups. RESULTS: Significant associations were found between the presence of endodontic pathology and a history of hypertension, myocardial infarction, cerebrovascular accident, pacemaker, congestive heart failure, heart block, deep vein thrombosis, and cardiac surgery (0.0001 ≤ P ≤ .008). A modest association was found for heart murmur and atrial fibrillation (P = .04). A trend toward positive association (P = .05) was also found between AP and a single nucleotide polymorphism in KCNK3, a gene known to be involved in increased susceptibility to hypertension. CONCLUSIONS: Significant associations were found between endodontic pathology and various CVDs and CVD-related risk factors, particularly hypertension. A trend toward a positive association was also found between AP and KCNK3, suggesting that common genetic variations may underlie different diseases. Additional studies with larger sample sizes have the potential to elucidate common mechanisms underlying AP and CVD.

Osteoimmunology of Oral and Maxillofacial Diseases: Translational Applications Based on Biological Mechanisms.

The maxillofacial skeleton is highly dynamic and requires a constant equilibrium between the bone resorption and bone formation. The field of osteoimmunology explores the interactions between bone metabolism and the immune response, providing a context to study the complex cellular and molecular networks involved in oro-maxillofacial osteolytic diseases. In this review, we present a framework for understanding the potential mechanisms underlying the immuno-pathobiology in etiologically-diverse diseases that affect the oral and maxillofacial region and share bone destruction as their common clinical outcome. These otherwise different pathologies share similar inflammatory pathways mediated by central cellular players, such as macrophages, T and B cells, that promote the differentiation and activation of osteoclasts, ineffective or insufficient bone apposition by osteoblasts, and the continuous production of osteoclastogenic signals by immune and local stromal cells. We also present the potential translational applications of this knowledge based on the biological mechanisms involved in the inflammation-induced bone destruction. Such applications can be the development of immune-based therapies that promote bone healing/regeneration, the identification of host-derived inflammatory/collagenolytic biomarkers as diagnostics tools, the assessment of links between oral and systemic diseases; and the characterization of genetic polymorphisms in immune or bone-related genes that will help diagnosis of susceptible individuals.

HGMB1 and RAGE as Essential Components of Ti Osseointegration Process in Mice.

The release of the prototypic DAMP High Mobility Group Box 1 (HMGB1) into extracellular environment and its binding to the Receptor for Advanced Glycation End Products (RAGE) has been described to trigger sterile inflammation and regulate healing outcome. However, their role on host response to Ti-based biomaterials and in the subsequent osseointegration remains unexplored. In this study, HMGB1 and RAGE inhibition in the Ti-mediated osseointegration were investigated in C57Bl/6 mice. C57Bl/6 mice received a Ti-device implantation (Ti-screw in the edentulous alveolar crest and a Ti-disc in the subcutaneous tissue) and were evaluated by microscopic (microCT [bone] and histology [bone and subcutaneous]) and molecular methods (ELISA, PCR array) during 3, 7, 14, and 21 days. Mice were divided into 4 groups: Control (no treatment); GZA (IP injection of Glycyrrhizic Acid for HMGB1 inhibition, 4 mg/Kg/day); RAP (IP injection of RAGE Antagonistic Peptide, 4 mg/Kg/day), and vehicle controls (1.5% DMSO solution for GZA and 0.9% saline solution for RAP); treatments were given at all experimental time points, starting 1 day before surgeries. HMGB1 was detected in the Ti-implantation sites, adsorbed to the screws/discs. In Control and vehicle groups, osseointegration was characterized by a slight inflammatory response at early time points, followed by a gradual bone apposition and matrix maturation at late time points. The inhibition of HMGB1 or RAGE impaired the osseointegration, affecting the dynamics of mineralized and organic bone matrix, and resulting in a foreign body reaction, with persistence of macrophages, necrotic bone, and foreign body giant cells until later time points. While Control samples were characterized by a balance between M1 and M2-type response in bone and subcutaneous sites of implantation, and also MSC markers, the inhibition of HMGB1 or RAGE caused a higher expression M1 markers and pro-inflammatory cytokines, as well chemokines and receptors for macrophage migration until later time points. In conclusion, HMGB1 and RAGE have a marked role in the osseointegration, evidenced by their influence on host inflammatory immune response, which includes macrophages migration and M1/M2 response, MSC markers expression, which collectively modulate bone matrix deposition and osseointegration outcome.