Clinical efficacy of early and delayed loading implants: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Whether early loaded implants have similar clinical outcomes to delayed loaded implants is unclear. PURPOSE: The purpose of this systematic review and meta-analysis was to compare the outcomes of early and delayed loading dental implants. MATERIAL AND METHODS: Comprehensive searches of the MEDLINE, EMBASE, and Ovid databases were enriched by hand searches. Only human randomized controlled trials (RCTs) that compared the clinical efficacy of early and delayed loading were included. The survival rates and marginal bone level (MBL) changes were pooled and analyzed by risk ratios (RRs) and weighted mean differences (WMDs), respectively. The subgroup analyses, which were based on the Mantel-Haenszel and inverse-variance methods, included the types of prosthesis, implant time, occlusion, number of missing teeth, operation methods, dental position, healing methods, and type of first restoration. A funnel plot was used for heterogeneity analysis. RESULTS: Eighteen trials were included from the initial 601 articles. The dental implant survival rates for the early and delayed loading were similar (P>.05). Regarding the marginal bone level changes, the 2 loading protocols also reached a comparable clinical outcome (P>.05). CONCLUSIONS: Early implant loading should achieve the same clinical efficacy as the delayed loading method.

Evaluation of modified cold-atmospheric pressure plasma (MCAP) for the treatment of peri-implantitis in beagles.

OBJECTIVE: To assess the effect of adjunctive use of modified cold-atmospheric pressure plasma (MCAP) to surgically mechanical debridement (MD) on peri-implantitis (PI) in beagles. MATERIAL AND METHODS: Bilateral mandibles of beagles with PI, which induced by cotton ligature twined with steel in sub-marginal around the implant, were randomly divided into two groups: MD in conjunction with 2% CHX irrigation (control group) and MD with adjunctive intervention of MCAP (plasma group). Sulcus bleeding index (SBI), probing depth (PD) and bone height (BH) were examined before and after intervention using computed tomography and histological staining. Additionally, interleukin (IL)-1ß, IL-6 and IL-17 levels in peri-implant sulcular fluid (PISF) were measured by ELISA. RESULTS: A significant improvement in SBI, PD and BH was found in the plasma group (p < .05) when compared with the control group after three months of intervention. In addition, IL-1ß and IL-17, but not IL-6 levels decreased (p < .05) in the plasma group compared with the control group after intervention. CONCLUSIONS: The adjunctive use of MCAP to MD for PI can enhance bone formation around the implant and inhibit the inflammatory response. The application of MCAP could be considered a favourable adjunct to MD for PI.

Cofilin 2 Acts as an Inflammatory Linker Between Chronic Periodontitis and Alzheimer's Disease in Amyloid Precursor Protein/Presenilin 1 Mice.

Increasing evidence has shown a correlation between chronic periodontitis (CP) and Alzheimer's disease (AD). Nevertheless, there is still a lack of direct evidence, and especially key molecules to connect the two diseases. This study aims to investigate potential protein links between CP and AD within the inflammatory aspect. The hippocampus of CP model mice and controls were collected, and changes in protein expression were evaluated using two-dimensional differential in-gel electrophoresis (2D-DIGE) analysis combined with liquid chromatography tandem mass spectrometry. A total of 15 differentially expressed proteins were identified in CP model mice, as compared with the controls. Among them, S100-A9, transthyretin, Cofilin 2, peroxiredoxin 2, and lipocalin-2 were validated by Western blot according to their dual function both in inflammation and AD. Based on 2D-DIGE analysis, CP animal model had higher levels of S100-A9, Cofilin 2, peroxiredoxin 2, and lipocalin-2 compared to controls. The level of Cofilin 2, one of the well-established proteins in the pathology of AD, was strongly correlated with the time course of CP pathology, indicating a specific molecular correlation between CP and AD. Moreover, the in vivo results showed the level of Cofilin 2 increased significantly along with a prominent increase of the phosphorylation of protein phosphatase 2 (PP2A) and tau protein in the cell lysates of Porphyromonas gingivalis (P.g-LPS)-treated SK-N-SH APPwt cells. Cofilin 2 inhibition resulted in a sharp decrease in PP2A dependent of tau phosphorylation. Furthermore, tumor growth factor (TGF)-ß1 was one of the most important inflammatory cytokines for the Pg-LPS-induced Cofilin 2 upregulation in SK-N-SH APPwt cells. These results showed inflammation served as the bond between CP and AD, whereas inflammatory related proteins could be the key linkers between the two diseases. Determining the association between CP and AD at the molecular mechanism will not only hold the direct evidence of the association between the two diseases but also provide a new way of preventing and treating AD: the effective prevention and treatment of CP could serve as a useful method to alleviate the development of AD.

Chronic Periodontitis and Alzheimer Disease: A Putative Link of Serum Proteins Identification by 2D-DIGE Proteomics.

Increasing evidence indicates Chronic Periodontitis (CP) is a comorbidity of Alzheimer's disease (AD), which is the most common form of age-related dementia, and for the latter, effective diagnostic and treatment strategies are lacking. Although inflammation is present in both diseases, the exact mechanisms and cross-links between CP and AD are poorly understood; and a direct association between the two has not been reported. This study aimed to identify a direct serum proteins link between AD and CP. Two-dimensional differential in-gel electrophoresis was employed to analyze serum samples from 12 CP patients and 12 age-matched controls. Furthermore, to determine the molecular link between CP and AD, neuroblastoma SK-N-SH APPwt cells were treated with 1 µg/ml of lipopolysaccharide from Porphyromonas gingivalis (P.g-LPS). Ten differentially expressed proteins were identified in CP patients. Among them, nine proteins were up-regulated, and one protein was down-regulated. Of the 10 differentially expressed proteins, five proteins were reportedly involved in the pathology of AD: Cofilin-2, Cathepsin B, Clusterin, Triosephosphate isomerase, and inter-alpha-trypsin inhibitor heavy chain H4 (ITI-H4). Western blotting indicated significantly higher expression of Cofilin-2, Cathepsin B, and Clusterin and lower expression of ITI-H4 in the CP group than in the Control group. The serum concentration of Cathepsin B has a good correlation with MMSE scores. Moreover, the protein level of Cathepsin B (but not that of ADAM10 and BACE1) increased significantly along with a prominent increase in Aß1-40 and Aß1-42 in the cell lysates of P.g-LPS-treated SK-N-SH APPwt cells. Cathepsin B inhibition resulted in a sharp decrease in Aß1-40 and Aß1-42 in the cell lysates. Furthermore, TNF-α was one of the most important inflammatory cytokines for the P.g-LPS-induced Cathepsin B upregulation in SK-N-SH APPwt cells. These results show that CP and AD share an association, while Cathepsin B could be a key link between the two diseases. The discovery of the identical serum proteins provides a potential mechanism underlying the increased risk of AD in CP patients, which could be critical for elucidating the pathophysiology of AD.

Prognostic implication of proteomic profiles in head and neck squamous cell carcinoma.

BACKGROUND AND OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is one of the malignant cancers with poor prognosis. However, clinicopathologic and histological criteria were finite to predict the prognosis of HNSCC. We aimed to characterize the proteomic profile of prognosis from HNSCC patients. MATERIAL AND METHODS: Reverse phase protein array (RPPA) data in HNSCC were downloaded from The Cancer Proteome Atlas (TCPA). Independent prognostic-related proteins (IPP) were screened by Cox regression model and Kaplan-Meier methods. IPP signature (IPPS) including selected proteins was conducted for prognostic prediction for HNSCC. Protein-protein network analysis and gene ontology (GO) enrichment were used to identify related functional proteins and pathways. RESULTS: Based on the IPP, IPPS for HNSCC was constructed: risk score = (1.541* IRF1) + (1.460 * SMAD4) + (1.396 * LKB1) + (0.746* Cyclin E2) + (0.618* Paxillin) + (0.499* p-PEA-15 (Ser116)). The IPPS in HNSCC showed good predictive performance (area under curve = 0.779) with moderate sensitivity and specificity. Protein-protein network analysis and functional enrichment indicated an implication of response to decreased oxygen levels in HNSCC. CONCLUSION: The identified proteomic signature might function as a prognostic tool for the management of HNSCC and provide novel target for the treatment of HNSCC.

Expression Profiling and Cell Type Classification Analysis in Periodontitis Reveal Dysregulation of Multiple lncRNAs in Plasma Cells.

OBJECTIVE: Periodontitis is a chronic inflammatory disease with a downregulated immune response. The mechanisms of the immune response, especially regarding immune-related long non-coding RNAs (lncRNAs), in periodontitis remain unclear. This study aimed to analyze the immune cell landscapes and immune-related transcriptome expression in periodontitis. MATERIALS AND METHODS: The periodontitis-related microarray data set GSE16134 was downloaded from the Gene Expression Omnibus database. Then, the proportions of the infiltrated immune cell subpopulations were evaluated by Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT). Differentially expressed immune-related genes (DEMGs) and lncRNAs were analyzed by the "limma" package in R software. Co-expression of DEMGs and lncRNAs in immune cell subpopulations was evaluated. Gene set enrichment analysis (GSEA) was performed to identify alterations in immune function through potential pathways. RESULTS: Increased numbers of plasma cells were observed in periodontitis-affected tissues versus those of healthy tissues, while T cells were downregulated. A total of 51 DEMGs were identified, and 12 immune-related signaling pathways were enriched by GSEA, most of which were related to the stimulation and function of B cells and T cells. Only 3 differentially upregulated lncRNAs (FAM30A, GUSBP11, and LINC00525) were screened for the regulation of the immune response. Besides, the level of lncRNAs (FAM30A, GUSBP11, and LINC00525) expression were positively correlated with the fraction of plasma cells in periodontitis. CONCLUSION: The discovery of differentially expressed immune-related transcriptomes in periodontitis lesions helps to explain the regulation of the immune mechanism in the development of periodontitis.

Updated Evidence of Association Between Periodontal Disease and Incident Erectile Dysfunction.

INTRODUCTION: The relationship between periodontal disease (PD) and erectile dysfunction (ED) is still conflicting. AIM: To investigate whether a link between PD and ED exists, and if so, the degree to which it is significant. METHODS: The search strategy included using electronic databases and hand searching works published up to June 2018. MEDLINE via PubMed, EMBASE, Proceedings Web of Science, and Current Contents Connect were searched by 2 independent reviewers. Case-control, cohort, or cross-sectional studies including patients with measures of periodontitis and ED were included in the analysis. Quality assessments and sensitivity analysis of selected studies were performed. MAIN OUTCOME MEASURE: The strength of the association between PD and the prevalence of ED was evaluated. RESULTS: 5 case-control studies with 213,076 participants met the eligibility criteria and were included in the meta-analysis. Patients with PD were 2.85-fold more likely to be diagnosed with ED (OR = 2.85, 95% CI = [1.83, 4.46]). Asian men were reported to be 3.07 times more likely to be at greater risk for the prevalence of ED. Moreover, studies with high quality and case-control design showed 2 times higher risk for ED in PD (OR = 2.44, 95% CI = [1.44, 4.14]). However, the present evidence was not robust enough owing to the high heterogeneity and instability in sensitivity analysis. CLINICAL IMPLICATIONS: Patients with PD may have increased risk of ED, suggesting that dental hygiene should be of concern to clinicians when managing patients with ED. STRENGTH & LIMITATIONS: This article includes a large literature search to confirm the evidence that PD increases the occurrence of ED. However, there are several confounders, such as age and the type of ED, that failed to be adjusted and that generate bias and affect the correlation between the incidence of ED and PD. CONCLUSION: This system review and meta-analysis strengthens the evidence that PD might have important clinical implications for risk stratification of ED. Zhou X, Cao F, Lin Z. Updated evidence of association between periodontal disease and incident erectile dysfunction. J Sex Med 2019;16:61-69.

Decreased Hemoglobin Concentration and Iron Metabolism Disorder in Periodontitis: Systematic Review and Meta-Analysis.

Background: Periodontitis is a chronic inflammatory disease with a possible infectious component. Anemia of inflammation (AI) occurring in various chronic diseases alters the hemoglobin (Hb) concentration and iron status. Currently, the association between periodontitis and AI is still controversial. The aim of this study was to assess the alterations of the level of hematological parameters and iron metabolism markers in patients with or without periodontitis. Methods: Electronic databases (MEDLINE, EMBASE, and Cochrane) were searched to identify publications about anemia and periodontitis. Subgroup analyses regarding gender, extent of periodontitis, and sample size were performed using STATA 12.1. Results: Sixteen studies were included in this meta-analysis. Pooled results showed a decrease in Hb [standardized mean difference (SMD) = -0.76, 95% CI = (-1.15, -0.37)], red blood cell [SMD = -0.69, 95% CI = (-1.09, -0.29)], hematocrit [SMD = -1.13, 95% CI = (-1.69, -0.57)], mean corpuscular volume [SMD = -0.16, 95% CI = (-0.32, -0.01)], and mean corpuscular Hb [SMD = -0.16, 95% CI = (-0.28, -0.04)], but upregulation in erythrocyte sedimentation rate [SMD = 0.63, 95% CI = (0.06, 1.19)]. In addition, patients with periodontitis had a higher level of hepcidin [SMD = 0.59, CI = (0.05, 1.12)] and decreased level of transferrin [SMD = -4.6, CI = (-13.1, -3.90)], with high heterogeneity. Conclusion: This meta-analysis indicates that periodontitis decreases Hb concentration and disturbs the balance of iron metabolism, which confirms strength of association between periodontitis and the development tendency of AI, especially for severe periodontitis. More unbiased cohort studies with larger sample sizes are still warranted to make a definitive judgment in the future.

Bactericidal effect of plasma jet with helium flowing through 3% hydrogen peroxide against Enterococcus faecalis.

The aim of the present study was to assess the antimicrobial activity of plasma jet with helium (He) flowing through 3% hydrogen peroxide in root canals infected with Enterococcus faecalis. A total of 42 single-rooted anterior teeth were prepared, sterilized, inoculated with an E. faecalis suspension and incubated for 7 days. Next, the teeth were randomly divided into six experimental groups (including groups treated by plasma jet with or without He for different time durations) and one control group treated without plasma. The number of surviving bacteria in each canal was determined by counting the colony forming units (CFU)/ml on nutrient agar plates. The results indicated that statistically significant reduction in CFU/ml (P<0.005) existed for all treatment groups relative to the control group. The greatest reductions in CFU/ml were observed for Group 3 (7.027 log unit reduction) and Group 2 (6.237 log unit reduction), which were treated by plasma jet sterilization with He flowing through 3% hydrogen peroxide for 4 min or for 2 min, respectively. In addition, the reduction in Group 3 was significantly greater compared with that in Group 2 or in the groups treated by plasma jet sterilization without He flowing through 3% hydrogen peroxide for 1, 2 or 4 min. In conclusion, plasma jet with or without He flowing through 3% hydrogen peroxide can effectively sterilized root canals infected with E. faecalis and should be considered as an alternative method for root canal disinfection in endodontic treatments.

Effects of non-equilibrium plasma in the treatment of ligature-induced peri-implantitis.

AIM: To evaluate the effects of non-equilibrium plasma in the treatment of ligature-induced peri-implantitis in beagle dogs. MATERIALS AND METHODS: Six beagles received 12 implants installed in the position of the fourth mandibular premolars. Ligature-induced peri-implantitis was initiated at 3 months post-implantation. When approximately 40% of the supporting bone was lost, the ligatures were removed. The implants were subjected to the muco-periosteal scaling and chlorhexidine irrigation with or without plasma irrigation. Three months later, clinical, radiographic and microbiological analyses were performed. Block biopsies were prepared for micro-CT and histomorphometric analysis. The primary outcome was the difference in bone healing of peri-implant sites, and the secondary outcomes included changes in clinical parameters (SBI, PD) and bacterial detection. RESULTS: At baseline, no significant differences were observed between the two groups. At 3 months post-treatment, the plasma group showed a significantly higher bone level than the control group (p < 0.05), a significantly decreased detection of bacteria (Porphyromonas gingivalis and Tannerella forsythia) (p < 0.05), and a significant improvement in clinical examination (p < 0.05). CONCLUSIONS: Within the limits of this study, non-equilibrium plasma treatment as an adjunct to the conventional therapy is a feasible approach for the treatment of peri-implantitis.

Bacterial-killing effect of atmospheric pressure non-equilibrium plasma jet and oral mucosa response.

Recently, plasma sterilization has attracted increasing attention in dental community for the atmospheric pressure non-equilibrium plasma jet (APNPs), which is driven by a kilohertz pulsed DC power, may be applied to the dental and oral diseases. However, it is still in doubt whether APNPs can effectively kill pathogenic bacteria in the oral cavity and produce no harmful effects on normal oral tissues, especially on normal mucosa. The aim of this study was to evaluate the bacterial-killing effect of APNPs in the biofilms containing a single breed of bacteria (Porphyromonas gingivalis, P.g.), and the pathological changes of the oral mucosa after treatment by APNPs. P.g. was incubated to form the biofilms in vitro, and the samples were divided into three groups randomly: group A (blank control); group B in which the biofilms were treated by APNPs (the setting of the equipment: 10 kHz, 1600 ns and 8 kV); group C in which the biofilms were exposed only to a gas jet without ignition of the plasma. Each group had three samples and each sample was processed for up to 5 min. The biofilms were then fluorescently stained, observed and photographed under a laser scanning confocal microscope. In the animal experiment, six male Japanese white rabbits were divided into two groups randomly (n=3 in each group) in terms of the different post-treatment time (1-day group and 5-day group). The buccal mucosa of the left side and the mucosa of the ventral surface of the tongue were treated by APNPs for 10 min in the same way as the bacterial biofilm experiment in each rabbit, and the corresponding mucosa of the other sides served as normal control. The clinical manifestations of the oral mucosa were observed and recorded every day. The rabbits were sacrificed one or five day(s) after APNPs treatment. The oral mucosa were harvested and prepared to haematoxylin and eosin-stained sections. Clinical observation and histopathological scores were used to assess mucosal changes. The results showed the obvious P.g. biofilms were formed at 10 days, and most of the bacteria in groups A and C were alive under a laser scanning confocal microscope, but the bacteria in the group B were almost all dead. In animal experiment, no ulcers, anabrosis and oral mucositis were found in both the 1-day and 5-day groups. The average mucous membrane irritation index was -0.83 and -0.67 in the 1-day and 5-day groups, respectively, suggesting that no intense mucosal membrane irritation responses occurred. It was concluded that APNPs could effectively kill P.g. in the biofilms and did not cause any pathological changes in the normal mucosa, suggesting that the plasma jet (APNPs) may be applied to oral diseases as a novel sterilization device in the future.

Bacterial-killing Effect of Atmospheric Pressure Non-equilibrium Plasma Jet and Oral Mucosa Response / 华中科技大学学报（医学）（英德文版）

Recently,plasma sterilization has attracted increasing attention in dental community for the atmospheric pressure non-equilibrium plasma jet (APNPs),which is driven by a kilohertz pulsed DC power,may be applied to the dental and oral diseases.However,it is still in doubt whether APNPs can effectively kill pathogenic bacteria in the oral cavity and produce no harmful effects on normal oral tissues,especially on normal mucosa.The aim of this study was to evaluate the bacterial-killing effect of APNPs in the biofilms containing a single breed of bacteria (Porphyromonas gingivalis,Pg.),and the pathological changes of the oral mucosa after treatment by APNPs.Pg.was incubated to form the biofilms in vitro,and the samples were divided into three groups randomly:group A (blank control);group B in which the biofilms were treated by APNPs (the setting of the equipment:10 kHz,1600 ns and 8 kV); group C in which the biofilms were exposed only to a gas jet without ignition of the plasma.Each group had three samples and each sample was processed for up to 5 min.The biofilms were then fluorescently stained,observed and photographed under a laser scanning confocal microscope.In the animal experiment,six male Japanese white rabbits were divided into two groups randomly (n=3 in each group) in terms of the different post-treatment time (1-day group and 5-day group).The buccal mucosa of the left side and the mucosa of the ventral surface of the tongue were treated by APNPs for 10 min in the same way as the bacterial biofilm experiment in each rabbit,and the corresponding mucosa of the other sides served as normal control.The clinical manifestations of the oral mucosa were observed and recorded every day.The rabbits were sacrificed one or five day(s) after APNPs treatment.The oral mucosa were harvested and prepared to haematoxylin and eosin-stained sections.Clinical observation and histopathological scores were used to assess mucosal changes.The results showed the obvious P.g.biofilms were formed at 10 days,and most of the bacteria in groups A and C were alive under a laser scanning confocal microscope,but the bacteria in the group B were almost all dead.In animal experiment,no ulcers,anabrosis and oral mucositis were found in both the 1-day and 5-day groups.The average mucous membrane irritation index was -0.83 and -0.67 in the 1-day and 5-day groups,respectively,suggesting that no intense mucosal membrane irritation responses occurred.It was concluded that APNPs could effectively kill P.g.in the biofilms and did not cause any pathological changes in the normal mucosa,suggesting that the plasma jet (APNPs) may be applied to oral diseases as a novel sterilization device in the future.