Clinical efficacy of soft-tissue augmentation on tissue preservation at immediate implant sites: A randomized controlled trial.

AIM: This randomized controlled trial aimed to investigate the efficacy of soft-tissue augmentation (STA) with a subepithelial connective tissue graft (SCTG) or an acellular dermal matrix (ADM) on reducing tissue alterations at an immediate implant site. MATERIALS AND METHODS: This trial had three groups: (i) immediate implant with SCTG (ICT group); (ii) immediate implant with ADM (IAD group); (iii) immediate implant without STA (control group). Forty-six patients were randomly assigned to each group. Implants were placed at the maxillary anterior or premolar areas and restored after the 6-month visit. Clinical outcomes, including buccal soft-tissue contour, peri-implant mucosal level, soft-tissue thickness and keratinized tissue width, were measured at baseline and at 3-, 6- and 12-month follow-up visits. Radiographic bone levels were measured at baseline and at 6- and 12-month follow-up visits. Patient-reported outcomes were also collected. RESULTS: STA procedures increased peri-implant mucosal thickness and maintained buccal soft-tissue contours. Compared to the control group, STA groups did not prevent peri-implant mucosal recession or interproximal bone resorption. Generally, no significant differences in clinical outcomes were detected between the ICT and IAD groups. Most patients were highly satisfied with the immediate implant procedure and outcomes without significant differences between groups. CONCLUSIONS: STA at immediate implant sites enhanced soft-tissue thickness and maintained soft-tissue contours but did not prevent peri-implant mucosal recession or interproximal bone resorption. Long-term follow-up should be performed since these results were reported for only up to 1 year.

Application of deep machine learning for the radiographic diagnosis of periodontitis.

OBJECTIVE: Successful application of deep machine learning could reduce time-consuming and labor-intensive clinical work of calculating the amount of radiographic bone loss (RBL) in diagnosing and treatment planning for periodontitis. This study aimed to test the accuracy of RBL classification by machine learning. MATERIALS AND METHODS: A total of 236 patients with standardized full mouth radiographs were included. Each tooth from the periapical films was evaluated by three calibrated periodontists for categorization of RBL and radiographic defect morphology. Each image was pre-processed and augmented to ensure proper data balancing without data pollution, then a novel multitasking InceptionV3 model was applied. RESULTS: The model demonstrated an average accuracy of 0.87 ± 0.01 in the categorization of mild (< 15%) or severe (≥ 15%) bone loss with fivefold cross-validation. Sensitivity, specificity, positive predictive, and negative predictive values of the model were 0.86 ± 0.03, 0.88 ± 0.03, 0.88 ± 0.03, and 0.86 ± 0.02, respectively. CONCLUSIONS: Application of deep machine learning for the detection of alveolar bone loss yielded promising results in this study. Additional data would be beneficial to enhance model construction and enable better machine learning performance for clinical implementation. CLINICAL RELEVANCE: Higher accuracy of radiographic bone loss classification by machine learning can be achieved with more clinical data and proper model construction for valuable clinical application.

Altered human alveolar bone gene expression in type 2 diabetes-A cross-sectional study.

OBJECTIVE: The objective of this cross-sectional study is to investigate alveolar bone gene expression in health and diabetes through ribonucleic acid (RNA) sequencing and bioinformatics analysis. BACKGROUND: It is relatively unknown how type 2 diabetes modulates gene expression in alveolar bone in humans. Clinical concern regarding increased implant failure rate in patients with diabetes has been discussed in the literature. Previous studies in animal models and humans have suggested an imbalance between the genes regulating bone formation with data suggesting bone resorption in diabetes. However, there is lack of data regarding a comprehensive gene expression from human alveolar bone in diabetes. METHODS: Alveolar bone was collected from healthy and type 2 diabetic subjects undergoing periodontal and implant surgeries. The homogenized RNA sample was then extracted and analyzed for quantity and quality. RNA samples were further purified using ribosomal RNA depletion technique and processed for RNA sequencing and analysis. Expression levels for mRNAs were performed by calculating FPKM ([total_exon_fragments/mapped reads (millions) × exon length (kB)]), and differentially expressed mRNAs were selected with log2 (fold change) >1 or log2 (fold change) ≤1 and with a parametric F test comparing nested linear models. RESULTS: Eighteen bone samples (10 healthy, 8 patients with diabetes) were analyzed for gene expression. The mean age and HbA1c% of healthy versus diabetic subjects were as follows: age (55.3 ± 17.5 vs 63.9 ± 8.7 years) and HbA1c% (5.6 ± 0.29 vs 7.3 ± 2.4), respectively. Sequencing analysis showed that expression of genes that regulate bone turnover like TGFB1, LTBP4, IGF1, BMP2, BMP4, BMP6, SMAD1, RUNX2, MCSF, and THRA was significantly downregulated in diabetes samples compared with healthy controls with overall reduced expression of genes in the bone regulation pathway in patients with diabetes. Bioinformatics analysis for the altered genes highlighted several pathways related to bone homeostasis and inflammation in diabetes. Periodontitis did not affect the gene expression pattern based on diabetes status. CONCLUSIONS: Altered expression of genes due to downregulation of certain pathways that are involved in bone turnover and inflammation suggests that overall wound healing and bone homeostasis may be compromised in type 2 diabetes.

Flowcharts improve periodontal diagnosis by dental and dental hygiene students.

Background: In 2017, the American Academy of Periodontology and the European Federation of Periodontology updated the classification of periodontal and peri-implant diseases and conditions. The goal of the present crossover study was to develop straightforward, illustrative flowcharts and determine their impact on the accuracy and speed of diagnosing periodontal conditions by predoctoral dental students (DS) and dental hygiene students (DHS). Methods: Two flowcharts (a decision-tree flowchart and one based on the periodontal disease/condition entity) were developed using updated diagnostic determinants proposed by the 2017 classification. A total of 26 second-, third-, and fourth-year DS (DS2, DS3, and DS4, respectively) and second-year DHS (DHS2) took a mock examination consisting of 10 periodontal clinical cases. The participants first diagnosed periodontal conditions using only their curricula-based knowledge (control) and then using the flowcharts (test). They also completed an optional post-examination questionnaire to provide feedback on the flowcharts. Statistical significance was detected at p ≤ 0.05. Results: Combined test groups had significantly higher accuracy in diagnosing periodontal conditions compared to controls (73.5% vs 50.0%, respectively), with the most substantial improvement in DS2 (66.3% vs 30%, respectively) and DHS2 (70.0% vs 41.4%, respectively). Combined test groups also completed the examination more quickly compared to controls (14.92 vs 20.85 minutes, respectively). The participants provided positive feedback and constructive criticism on the flowcharts, and also suggested converting them into application software. Conclusion: The flowcharts significantly improved the accuracy of diagnosing periodontal conditions in academic settings, especially among junior, less experienced participants.

Contexte: En 2017, l'Académie américaine de parodontologie et la Fédération européenne de parodontologie ont mis à jour leur classification des maladies et des affections parodontales et péri-implantaires. L'objectif de la présente étude croisée était de créer des organigrammes simples et représentatifs et de déterminer leur effet sur l'exactitude et la vitesse de diagnostic des affections parodontales par les étudiants en médecine dentaire, prédoctorat(ÉD) et les étudiants en hygiène dentaire (ÉHD). Méthodes: Deux organigrammes (un organigramme d'arbre décisionnel et un graphique basé sur l'entité de la maladie ou de l'affection parodontale) ont été élaborés à l'aide des déterminants diagnostiques actualisés, comme proposés dans la classification de 2017. Un total de 26 étudiants de deuxième, troisième et quatrième année (ÉD2, ÉD3 et ÉD4, respectivement) en médecine dentaire et des étudiants de deuxième année en hygiène dentaire (ÉHD2) ont passé un examen fictif portant sur 10 cas cliniques parodontaux. Les participants ont d'abord diagnostiqué les affections parodontales en utilisant seulement leurs connaissances fondées sur leur programme d'études (témoins) et en utilisant ensuite les organigrammes (tests). Ils ont aussi rempli un questionnaire optionnel après avoir passé l'examen afin de fournir des commentaires sur les organigrammes. La signification statistique a été décelée à p ≤ 0,05. Résultats: Les groupes de tests combinés avaient une exactitude considérablement plus élevée dans le diagnostic des affections parodontales par rapport aux groupes témoins (73,5 % contre 50,0 %, respectivement), et l'amélioration la plus importante était chez les ÉD2 (66,3 % contre 30 %, respectivement) et les ÉHD2 (70,0 % contre 41,4 %, respectivement). Les groupes de tests combinés ont aussi terminé l'examen plus rapidement par rapport aux groupes témoins (14,92 contre 20,85 minutes, respectivement). Les participants ont fourni des commentaires positifs et des critiques constructives sur les organigrammes et ont aussi suggéré de les convertir en logiciels d'application. Conclusion: Les organigrammes ont considérablement amélioré l'exactitude du diagnostic des affections parodontales dans les milieux d'enseignement, surtout chez les participants débutants et moins expérimentés.

Fixed Orthodontic Retainers Do Not Seem to Adversely Affect Periodontal Health.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: The effects of fixed orthodontic retainers on periodontal health: A systematic review. Arn M, Dristas K, Pandis N, Kloukos D. Am J Orthod Dentofacial Orthop 2020;157:156-64. SOURCE OF FUNDING: Information is not available and the authors did state any specific funding for this study and report no potential conflicts of interest. TYPE OF STUDY/DESIGN: Systematic review.

Distinct Profiles of Specialized Pro-resolving Lipid Mediators and Corresponding Receptor Gene Expression in Periodontal Inflammation.

Polyunsaturated fatty acid-derived specialized pro-resolving lipid mediators (SPMs) play an important role in modulating inflammation. The aim of the study was to compare profiles of SPMs, SPM related lipid mediators and SPM receptor gene expression in gingiva of subjects with periodontitis to healthy controls. A total of 28 subjects were included; 13 periodontally healthy and 15 periodontitis before or after non-surgical periodontal therapy. Gingival tissues were collected from two representative posterior teeth prior to and 8 weeks after scaling and root planning; only once in the healthy group. Lipid mediator-SPM metabololipidomics was performed to identify metabolites in gingiva. qRT-PCR was performed to assess relative gene expression (2-ΔΔCT) of known SPM receptors. Intergroup comparisons were made using Wilcoxon tests. Thirty-six omega-6 or omega-3 fatty acid-derived lipid mediators and seven receptor genes were identified in gingiva. Profiles of lipid mediators and receptor gene expression were significantly different between the three groups. Levels of six lipid mediators, 5-HETE, 15-HETE, 15(S)-HEPE, 4-HDHA, 7-HDHA, and 17-HDHA in periodontitis before treatment were significantly higher than in periodontitis after treatment. The expression of BLT1 in the healthy group was significantly higher than periodontitis subjects before and after treatment. The expression of GPR18 in periodontitis before treatment was significantly higher than in periodontitis after treatment while the expression of GPR32 in periodontitis before treatment was significantly lower than in periodontitis after treatment. Elevated levels of SPM biosynthetic pathway markers in periodontitis subjects before treatment indicated inflammation induced pro-resolution activity in gingiva, but receptors for these molecules were deficient in periodontitis pre-treatment suggesting that failure of resolution of inflammation contributes to excess, chronic inflammation in periodontitis.

Persons With Thalassemia Major May Have Increased Risk of Gingival Inflammation.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Periodontal condition of patients with thalassemia major: A systematic review and meta-analysis. Akcali A, Yildiz MS, Akcali Z, Huck O, Friedmann A. Arch Oral Biol 2019;102:113-21. SOURCE OF FUNDING: Information is not available and the authors state that no specific funding was available for this study. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.

A comparison study: Periodontal practice approach of dentists and dental hygienists.

OBJECTIVES: The aim of this study was to investigate periodontal practice methods of dentists and dental hygienists to compare their knowledge and treatment approach in managing periodontal disease. METHODS: An electronic survey was designed to assess and capture three aspects of data: (a) knowledge of periodontics; (b) practice approaches in non-surgical periodontal therapy; and (c) factors affecting clinical care. The survey was distributed to dentists and dental hygienists who graduated from the same dental school within 5 years (2012-2016). Results were analysed by chi-square test, Fisher's exact test and logistic regression model. RESULTS: Out of total 117 participants, 111 of them reported their profession (n = 77 in the dental programme, n = 34 in the dental hygiene programme). The results showed no statistical difference in basic periodontal knowledge between dentists and dental hygienists (P = .12). Only 13% of the surveyed population identified appropriate recall intervals for periodontal maintenance and more dental hygienists reported periodontal re-evaluations being performed within their offices compared with dentists (91% vs 70%, P = .02). Almost half of the participants who reportedly performed periodontal re-evaluations (46%) charged for the re-evaluation procedure, despite it not being covered by dental insurance. More hygienists reported being familiar with and performing adjunct therapy compared to dentists in the study (P < .01). CONCLUSION: In general, dentists and hygienists in the study were found to have similar periodontal knowledge and practice approaches. However, differences in performing periodontal re-evaluation and adjunct therapy were significant. Further studies are needed to investigate clinical barriers that impact evidence-based periodontal care.

The aging population: demographics and the biology of aging.

Epidemiologic studies show that 11% of the world's population is over 60 years of age; this is projected to increase, by 2050, to 22% of the population. Oral aging is a current focus of several organizations including the Federation Dentaire Internationale, the World Health Organization and the American and Japanese Dental Associations. In their Tokyo Declaration, the Japanese Association identified the elderly population as one of its main target groups. One of the WHO goals is for each person to retain more than 20 teeth by age 80, despite the fact that the prevalence of periodontal disease is continuously rising as the population is aging. Every species has its own characteristic lifespan, which is determined by its evolutionary history and is modified by multiple diverse factors, including biological mechanisms. In humans, the gradual accumulation of products of cellular metabolism and extensive DNA damage contribute to the aging process. Aging is thought to be associated with a low-grade inflammatory phenotype in mammals, called 'inflammaging', and is the result of autophagic capacity impairing so-called 'housekeeping activities' in the cells, resulting in protein aggregation, mitochondrial dysfunction and oxidative stress. Delayed stem-cell proliferation, associated with aging, may impact the maintenance and survival of a living being, but excessive proliferation could also result in depleted reserves of stem cells. Studies are needed to address the association of delayed cell proliferation and wound healing with the onset of periodontal diseases and response to treatment. The effects of systemic diseases, medications, psychological effects and decreased interest or ability in performing oral-hygiene practices are thought to result in periodontal diseases, and ultimately in tooth loss, in aged individuals. Together with an aging population comes a responsibility for 'healthy' and 'successful' aging. This article describes the changing global demographic profile and the effects of an aging society on the prevalence and incidence of periodontal diseases. We review the definitions of normal and successful aging, the principles of geriatric medicine and the highlights of biological aging at cellular, tissue and systems levels.

IPLA2 mRNA expression by human neutrophils in type 2 diabetes and chronic periodontitis.

Type 2 diabetes mellitus (T2D) is becoming increasingly prevalent worldwide and complications of T2D cause significant systemic and dental morbidity in the susceptible individual. Although T2D has been linked as a significant risk factor for chronic periodontitis (CP), molecular mechanisms explaining the pathogenesis and inflammatory impact of CP in T2D are lacking. iPLA2 is the calcium-independent form of phospholipase A2. In previous studies, we demonstrated that iPLA2 enzyme activity is altered in T2D. The purpose of this study was to elucidate the level of the iPLA2 abnormality in T2D by measuring messenger RNA levels in T2D-associated CP. A total of 53 healthy and T2D subjects with CP were recruited for this study. The clinical periodontal exam included probing pocket depth, clinical attachment levels and bleeding on probing. Peripheral venous blood was collected and neutrophils were isolated. Real time polymerase chain reaction was used to quantify iPLA2 mRNA in neutrophils from healthy controls and people with diabetes. Results revealed that the prevalence of moderate to severe CP was increased in people with T2D. The iPLA, mRNA levels in diabetics with different severity of CP were not significantly different compared to healthy controls; 1.07 vs 0.97 (mild CP), 1.07 vs 0.85 (moderate CP) and 1.07 vs 1.05 (severe CP). Collectively, the data suggest that levels of iPLA2 mRNA in T2D are not different than in health and are not directly influenced by periodontal disease status. The impact of inflammation on iPLA2 regulation is at the level of activation of the enzyme rather than expression at the mRNA level.

Impaired phagocytosis in localized aggressive periodontitis: rescue by Resolvin E1.

Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18) surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 µM) and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A(4). Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1-100 nM), rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression.

Diabetes-induced oxidative stress is mediated by Ca2+-independent phospholipase A2 in neutrophils.

Neutrophils from people with poorly controlled diabetes present a primed phenotype and secrete excessive superoxide. Phospholipase A(2) (PLA(2))-derived arachidonic acid (AA) activates the assembly of NADPH oxidase to generate superoxide anion. There is a gap in the current literature regarding which PLA(2) isoform regulates NADPH oxidase activation. The aim of this study was to identify the PLA(2) isoform involved in the regulation of superoxide generation in neutrophils and investigate if PLA(2) mediates priming in response to pathologic hyperglycemia. Neutrophils were isolated from people with diabetes mellitus and healthy controls, and HL60 neutrophil-like cells were grown in hyperglycemic conditions. Incubating neutrophils with the Ca(2+)-independent PLA(2) (iPLA(2)) inhibitor bromoenol lactone (BEL) completely suppressed fMLP-induced generation of superoxide. The nonspecific actions of BEL on phosphatidic acid phosphohydrolase-1, p47(phox) phosphorylation, and apoptosis were ruled out by specific assays. Small interfering RNA knockdown of iPLA(2) inhibited superoxide generation by neutrophils. Neutrophils from people with poorly controlled diabetes and in vitro incubation of neutrophils with high glucose and the receptor for advanced glycation end products ligand S100B greatly enhanced superoxide generation compared with controls, and this was significantly inhibited by BEL. A modified iPLA(2) assay, Western blotting, and PCR confirmed that there was increased iPLA(2) activity and expression in neutrophils from people with diabetes. AA (10 microM) partly rescued the inhibition of superoxide generation mediated by BEL, confirming that NADPH oxidase activity is, in part, regulated by AA. This study provides evidence for the role of iPLA(2) in enhanced superoxide generation in neutrophils from people with diabetes mellitus and presents an alternate pathway independent of protein kinase C and phosphatidic acid phosphohydrolase-1 hydrolase signaling.

Novel regenerative strategies to enhance periodontal therapy outcome.

BACKGROUND: Chronic periodontitis is a widely prevalent inflammatory condition of the supporting tissues of the teeth and is characterized by loss of teeth with an associated risk of systemic complications. Regenerative therapies such as guided tissue and bone regeneration form an important armamentarium in periodontics with a high degree of outcome predictability in certain ideal clinical scenarios. OBJECTIVE/METHODS: This review elaborates novel tissue regenerative treatment modalities based on sound understanding of developmental biology, tissue engineering, inflammation and wound healing. We focus on the role of biological mediators such as growth factors, gene-based therapy, cell therapy and pro-resolution lipid mediators in the regeneration of lost bone or periodontium. RESULTS/CONCLUSIONS: These therapies have the potential to regenerate both periodontium and bone, aiding in the treatment of even clinically challenging cases.

Priming of neutrophil oxidative burst in diabetes requires preassembly of the NADPH oxidase.

Hyperglycemia associated with diabetes mellitus results in the priming of neutrophils leading to oxidative stress that is, in part, responsible for diabetic complications. p47phox, a NADPH oxidase cytosolic subunit, is a key protein in the assembly of the NADPH oxidase leading to superoxide generation. Little is known about the priming mechanism of oxidative pathways in neutrophils of people with diabetes. In this study, the kinetics of p47phox activation was investigated by comparing neutrophils from diabetic and healthy subjects, and the mechanism of hyperglycemia-induced changes was studied by using neutrophil-like HL-60 cells as a model. In resting neutrophils from diabetic subjects, p47phox prematurely translocates to the cell membrane and preassembles with p22phox, a NADPH oxidase membrane subunit. This premature p47phox translocation and preassembly with p22phox were also observed in HL-60 cells cultured with high glucose (HG; 25 mM) and with the specific ligand for the receptor for advanced glycation end products (RAGE), S100B. Phosphorylation of ERK1/2, but not p38 MAPK, was the primary signaling pathway, as evidenced by PD98059 suppressing the translocation of p47phox in HL-60 cells incubated with HG and S100B. HL-60 cells cultured in HG and S100B exhibited a 1.8-fold increase in fMLP-induced superoxide generation compared with those cultured in normal glucose (5.5 mM). These data suggest that HG and increased AGE prime neutrophils and increase oxidative stress inducing the translocation of p47phox to the cell membrane and preassembly with p22phox by stimulating a RAGE-ERK1/2 pathway.