Association between geniquin therapy and the risk of developing periodontal disease in patients with primary Sjögren's syndrome: A population-based cohort study from Taiwan.

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease that causes dysfunction of salivation and harmful oral conditions. The association between periodontal disease (PD) and pSS with or without geniquin therapy remains controversial. This study evaluated the association between geniquin therapy and the risk of subsequent development of PD in pSS patients. From Taiwan's National Health Insurance Research Database, we selected a control cohort of 106,818 pSS patients, followed up from 2000 to 2015, matched (1:4) by age and index year with 427,272 non-pSS patients. We also analyzed 15,149 pSS patients receiving geniquin therapy (cohort 1) and 91,669 pSS patients not receiving geniquin therapy (cohort 2). After adjusting for confounding factors, multivariate Cox proportional hazards regression analysis was used to compare the risk of PD over the 15-year follow-up. In the control cohort, 11,941 (11.2%) pSS patients developed PD compared to 39,797 (9.3%) non-pSS patients. In cohorts 1 and 2, 1,914 (12.6%) pSS patients receiving geniquin therapy and 10,027 (10.9%) pSS patients not receiving geniquin therapy developed PD. The adjusted hazard ratio (HR) for subsequent PD in pSS patients was 1.165 (95% confidence interval [CI] = 1.147-1.195, p < 0.001) and in pSS patients receiving geniquin therapy was 1.608 (95% CI = 1.526-1.702, p < 0.001). The adjusted HR for PD treatment was 1.843. Patients diagnosed with pSS showed an increased risk of developing subsequent PD and receiving PD treatment than patients without pSS, while pSS patients receiving geniquin therapy showed even higher risks.

Titanium Surfaces with a Laser-Produced Microchannel Structure Enhance Pre-Osteoblast Proliferation, Maturation, and Extracellular Mineralization In Vitro.

The clinical success of dental titanium implants is profoundly linked to implant stability and osseointegration, which comprises pre-osteoblast proliferation, osteogenic differentiation, and extracellular mineralization. Because of the bio-inert nature of titanium, surface processing using subtractive or additive methods enhances osseointegration ability but limits the benefit due to accompanying surface contamination. By contrast, laser processing methods increase the roughness of the implant surface without contamination. However, the effects of laser-mediated distinct surface structures on the osteointegration level of osteoblasts are controversial. The role of a titanium surface with a laser-mediated microchannel structure in pre-osteoblast maturation remains unclear. This study aimed to elucidate the effect of laser-produced microchannels on pre-osteoblast maturation. Pre-osteoblast human embryonic palatal mesenchymal cells were seeded on a titanium plate treated with grinding (G), sandblasting with large grit and acid etching (SLA), or laser irradiation (L) for 3-18 days. The proliferation and morphology of pre-osteoblasts were evaluated using a Trypan Blue dye exclusion test and fluorescence microscopy. The mRNA expression, protein expression, and protein secretion of osteogenic differentiation markers in pre-osteoblasts were evaluated using reverse transcriptase quantitative polymerase chain reaction, a Western blot assay, and a multiplex assay, respectively. The extracellular calcium precipitation of pre-osteoblast was measured using Alizarin red S staining. Compared to G- and SLA-treated titanium surfaces, the laser-produced microchannel surfaces enhanced pre-osteoblast proliferation, the expression/secretion of osteogenic differentiation markers, and extracellular calcium precipitation. Laser-treated titanium implants may enhance the pre-osteoblast maturation process and provide extra benefits in clinical application.

Improving performance of deep learning models using 3.5D U-Net via majority voting for tooth segmentation on cone beam computed tomography.

Deep learning allows automatic segmentation of teeth on cone beam computed tomography (CBCT). However, the segmentation performance of deep learning varies among different training strategies. Our aim was to propose a 3.5D U-Net to improve the performance of the U-Net in segmenting teeth on CBCT. This study retrospectively enrolled 24 patients who received CBCT. Five U-Nets, including 2Da U-Net, 2Dc U-Net, 2Ds U-Net, 2.5Da U-Net, 3D U-Net, were trained to segment the teeth. Four additional U-Nets, including 2.5Dv U-Net, 3.5Dv5 U-Net, 3.5Dv4 U-Net, and 3.5Dv3 U-Net, were obtained using majority voting. Mathematical morphology operations including erosion and dilation (E&D) were applied to remove diminutive noise speckles. Segmentation performance was evaluated by fourfold cross validation using Dice similarity coefficient (DSC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV). Kruskal-Wallis test with post hoc analysis using Bonferroni correction was used for group comparison. P < 0.05 was considered statistically significant. Performance of U-Nets significantly varies among different training strategies for teeth segmentation on CBCT (P < 0.05). The 3.5Dv5 U-Net and 2.5Dv U-Net showed DSC and PPV significantly higher than any of five originally trained U-Nets (all P < 0.05). E&D significantly improved the DSC, accuracy, specificity, and PPV (all P < 0.005). The 3.5Dv5 U-Net achieved highest DSC and accuracy among all U-Nets. The segmentation performance of the U-Net can be improved by majority voting and E&D. Overall speaking, the 3.5Dv5 U-Net achieved the best segmentation performance among all U-Nets.

The secreted protein DEL-1 activates a ß3 integrin-FAK-ERK1/2-RUNX2 pathway and promotes osteogenic differentiation and bone regeneration.

The integrin-binding secreted protein developmental endothelial locus-1 (DEL-1) is involved in the regulation of both the initiation and resolution of inflammation in different diseases, including periodontitis, an oral disorder characterized by inflammatory bone loss. Here, using a mouse model of bone regeneration and in vitro cell-based mechanistic studies, we investigated whether and how DEL-1 can promote alveolar bone regeneration during resolution of experimental periodontitis. Compared with WT mice, mice lacking DEL-1 or expressing a DEL-1 variant with an Asp-to-Glu substitution in the RGD motif ("RGE point mutant"), which does not interact with RGD-dependent integrins, exhibited defective bone regeneration. Local administration of DEL-1 or of its N-terminal segment containing the integrin-binding RGD motif, but not of the RGE point mutant, reversed the defective bone regeneration in the DEL-1-deficient mice. Moreover, DEL-1 (but not the RGE point mutant) promoted osteogenic differentiation of MC3T3-E1 osteoprogenitor cells or of primary calvarial osteoblastic cells in a ß3 integrin-dependent manner. The ability of DEL-1 to promote in vitro osteogenesis, indicated by induction of osteogenic genes such as the master transcription factor Runt-related transcription factor-2 (Runx2) and by mineralized nodule formation, depended on its capacity to induce the phosphorylation of focal adhesion kinase (FAK) and of extracellular signal-regulated kinase 1/2 (ERK1/2). We conclude that DEL-1 can activate a ß3 integrin-FAK-ERK1/2-RUNX2 pathway in osteoprogenitors and promote new bone formation in mice. These findings suggest that DEL-1 may be therapeutically exploited to restore bone lost due to periodontitis and perhaps other osteolytic conditions.

Accuracy of Implant Placement with a Navigation System, a Laboratory Guide, and Freehand Drilling.

PURPOSE: Computer-aided surgery under navigation system guidance is widely applied in dental implant procedures. However, the accuracy of drilling with such navigation systems has not been comparatively evaluated alongside those of laboratory guide-based and freehand drilling. Therefore, this study aimed to compare the accuracies of these three drilling systems. MATERIALS AND METHODS: A navigation system, a laboratory guide, and freehand drilling were used to drill 150 holes on 30 cast models. Two master models-one each for the maxilla and mandible-were prepared with the idea of placing five implants per cast. After drilling five holes on each cast, postoperative cone beam computed tomography images were acquired to measure the magnitude of errors. RESULTS: The navigation system and laboratory guide were more accurate than freehand placement with respect to total errors at the entry and apex, lateral error at the apex, and angular error. The navigation system was more accurate than the laboratory guide with respect to angular error. Laboratory guide-based drilling was more accurate than freehand drilling in terms of lateral error at entry. CONCLUSION: In comparison with the laboratory guide and freehand placement, the navigation system exhibited lower angular and axial errors. Despite its higher accuracy, the navigation system requires the operator to pay greater attention.

Er:YAG Laser for Surgical Crown Lengthening: A 6-Month Clinical Study.

This study evaluated use of a solid-state laser to avoid the flap technique and suturing. An Er:YAG laser was used in 26 consecutive patients referred for osseous crown lengthening in 32 posterior teeth. The distance from the planned restoration margin to the alveolar crest (B) satisfied a 3-mm dentogingival complex. No tissue necrosis and no significant change in the distance from the gingival margin to B or probing depth were detected at 3 and 6 months. Minimally invasive Er:YAG laser surgery decreases the time needed to establish the gingival margin necessary for definitive restoration.

Are Chronic Periodontitis and Gingivitis Associated with Dementia? A Nationwide, Retrospective, Matched-Cohort Study in Taiwan.

BACKGROUND: Chronic periodontitis and gingivitis are associated with various diseases; however, their impact on dementia is yet to be elucidated. This study is aimed at investigating the association between chronic periodontitis and gingivitis, and the risk of developing dementia. METHODS: A total of 2,207 patients, with newly diagnosed chronic periodontitis and gingivitis between January 1, 2000 and December 31, 2000, were selected from the National Health Insurance Research Database of Taiwan, along with 6,621 controls matched for sex and age. After adjusting for confounding factors, Cox proportional hazards analysis was used to compare the risk of developing dementia during the 10-year follow-up period. RESULTS: Of the study subjects, 25 (1.13%) developed dementia compared to 61 (0.92%) in the control group. Cox proportional hazards regression analysis revealed that the study subjects were more likely to develop dementia (hazard ratio (HR) 2.085, 95% CI 1.552-4.156, p < 0.001). After adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the HR for dementia was 2.54 (95% CI 1.297-3.352, p = 0.002). CONCLUSIONS: Patients with chronic periodontitis and gingivitis have a higher risk of developing dementia. However, further studies on other large or national data sets are required to support the current findings.

The association between temporomandibular disorders and joint hypermobility syndrome: a nationwide population-based study.

OBJECTIVES: This study aims to investigate the risk factors of temporomandibular disorders (TMDs), including disc or non-disc-related disorders, and joint hypermobility syndrome (JHS) retrospectively and to analyze the factors by estimating the magnitude of the association between the two conditions using a nationwide population-based dataset. MATERIALS AND METHODS: A total of 975,788 eligible patients' de-identified data were obtained from a representative database composed of one million of Taiwan's population since 2004 to 2008. All associated factors, such as gender, age, facial trauma, and psychosis, which correlated with TMDs and JHS were examined. Multiple logistic regression modeling adjusted for confounding variables to determine the odds ratio of variables that made an important contribution to TMDs and JHS. RESULTS: For all TMDs patients, only 1.47% patients had disc-related disorders. For all JHS patients, only 3.85% patients are diagnosed with concomitant TMDs. Statistically significant association was observed between joint hypermobility and TMDs. Furthermore, the prevalence of JHS patients shows significant difference within TMD subgroups, in which 9.52% of JHS patients have disc disorders and 90.48% of JHS patients do not. All associated factors, such as gender, age, JHS, facial trauma, and psychosis, had a significant impact on the TMDs. Interestingly, patients with TMJ articular disc disorders are 6.7 times more likely to be diagnosed with JHS compared to patients without disc-related disorders. CONCLUSIONS: Our results confirm that there is a significant positive association between TMDs and JHS, highlighting that patients with disc-related TMDs are more likely to experience JHS than patients with TMDs without disc disorders. CLINICAL RELEVANCE: Individuals with TMD associated with JHS should be carefully evaluated by inter-disciplinary specialists as these factors may eventually have impact on the prognosis of TMDs and JHS.

Protumoral effect of macrophage through Axl activation on mucoepidermoid carcinoma.

OBJECTIVE: This study aims to test the potential involvement of Axl signaling in the protumoral effect of tumor-associated macrophages (TAMs) in mucoepidermoid carcinoma (MEC). MATERIALS AND METHODS: We carried out cocultured experiments by incubation of MEC cells (UTMUC-1) and macrophages (THP-1) and examined Axl activation status. The expression of MMPs and behavior change were examined in UT-MUC-1 cells. The effect of Axl signaling on co-cultured cancer cells was further investigated by knockdown Axl expression and suppression by Axl-specific inhibitor R428. RESULTS: Activation of Axl signaling and increased expression and activity of MMP-2 and MMP-9 along with increased invasion/migration ability in MEC cells were observed when co-cultured with TAMs. Upon knockdown of Axl in MEC or addition of R428 in the co-cultured system, these co-cultured effects were diminished. CONCLUSION: TAMs play a protumoral role in MEC via activation of the Axl signaling pathway, up-regulating MMPs expression, and increasing invasion/migration ability.

The national-scale cohort study on bisphosphonate-related osteonecrosis of the jaw in Taiwan.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potential side effect of bisphosphonate therapy. This Taiwanese national-scale cohort study aimed to investigate its incidence and risk of development by using a qualified control group with different demographic factors (age/gender), dental (tooth extraction/periodontal therapy) and medical (jaw radiotherapy) treatments, delivery routes (oral/intravenous), and diseases (diabetes/osteoporosis/cancer). METHODS: Data (n=958,136) from January 1, 2006 through December 31, 2008 were sourced from the Longitudinal Health Insurance Database 2005 of Taiwan. Cases of BRONJ were identified by three criteria modified from the definition proposed by the American Association of Oral and Maxillofacial Surgeons. The Cox proportional-hazards regression model and Kaplan-Meier estimates were used to analyse the results. RESULTS: The incidence densities of ONJ in the unexposed and bisphosphonate-exposed cohorts were estimated as 4.4 and 73.5 per 100,000 person-years, respectively (relative risk=16.8; 95% CI=6.0-37.5; P<0.001). Multivariate analysis revealed strong associations of delivery route, tooth extraction, and oral cancer with ONJ (hazard ratios=51.4 for oral bisphosphonates, 153.3 for intravenous bisphosphonates, 5.3 for tooth extraction, and 278.1 for oral cancer). CONCLUSIONS: These results not only demonstrate the incidence and relative risk of bisphosphonate-related ONJ in Taiwan but also indicate that tooth extraction and oral cancer may have a major impact on its development. CLINICAL SIGNIFICANCE: Physicians should be aware of individual patient risk factors before prescribing bisphosphonates. Bisphosphonate treatment is justified in the amelioration of life-threatening conditions in patients in whom ONJ would only affect quality of life.

Factors affecting treatment decisions and outcomes of root-resected molars: a nationwide study.

BACKGROUND: Treatment of furcation-involved molars presents a clinical challenge. This study retrospectively investigates the demographic parameters affecting treatment decisions and outcomes of root-resected molars using a nationwide population-based dataset. METHODS: De-identified data from 471 eligible patients were obtained from a representative cohort composed of 1 million of Taiwan's population. Demographic factors that influence treatment decisions and outcomes of root-resected teeth were examined. Cox regression was performed to statistically analyze the factors. RESULTS: The overall survival rate for root-resected molars was 91.1%. The survival times of the extracted and surviving teeth were 303.0 ± 274.6 and 551.8 ± 327.2 days, respectively (P <0.001). The analyzed patient-related factors, such as living district, urbanization level, medical institution, and monthly income, have remarkable influence on treatment decisions; however, there is no statistically significant difference in survival rate between root-resected molars receiving flap surgery and those that do not (P = 0.504). After adjusting for other factors, patients aged >74 years have 3.33 times (hazard ratio = 3.33; 95% CI = 1.04 to 10.66; P = 0.043) higher rates of molar extraction than younger counterparts. CONCLUSIONS: The overall survival rate of root-resected molars was satisfactory. Patients with advanced age (>74 years) had a higher risk of extraction occurrence on resected molars. Patient-related factors may influence the treatment decision of whether molars receive flap surgery. These findings suggest that demographic factors should be carefully evaluated before and after performing root-resection procedures because these factors may eventually impact the outcome of root-resected molars.