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Many studies have investigated the transcriptome profiles of dental stem cells for regenerative medicine. However, such studies use bulk RNA and do not consider cell-level heterogeneity. Here, we investigated the characteristics and heterogeneity of human dental pulp stem cells (hDPSCs) and human periodontal ligament stem cells (hPDLSCs) at the single-cell level and examined the differences between them.hDPSCs and hPDLSCs were obtained from caries-free premolars (n = 2). Single-cell RNA sequencing of hDPSCs and hPDLSCs was performed using a Single Emulsion Systems (Dolomite Microfluidics, Royston, UK) droplet microfluidic device and the Illumina NextSeq550 system (Illumina, San Diego, CA). Data alignment was performed using STAR v2.4.0, and further analysis was performed using the Seurat, singleR, and clusterProfiler packages in R (R Foundation for Statistical Computing, Vienna, Austria).hDPSCs and hPDLSCs were separated into 3 clusters. hDPSCs mainly exhibited osteogenic and neurogenic cell populations. The main populations of hPDLSCs comprised osteogenic and myofibroblastic populations. hPDLSCs showed high "scores" for osteogenic gene expression, whereas hDPSCs had high neurogenic and endogenic scores.Single-cell RNA sequencing of hDPSCs and hPDLSCs revealed that the genes were expressed in specific clusters. The results of these analyses can be used as reference databases and valuable resources for further research in dental therapeutics.

Objective This study aimed to evaluate the following null hypothesis: there are no differences in the morphology of the temporomandibular joint (TMJ) structures in relation to vertical and sagittal cephalometric patterns. Methods This retrospective study was performed with 131 participants showing no TMJ symptoms. The participants were divided into Class I, II, and III groups on the basis of their sagittal cephalometric relationships and into hyperdivergent, normodivergent, and hypodivergent groups on the basis of their vertical cephalometric relationships. The following measurements were performed using cone-beam computed tomography images and compared among the groups: condylar volume, condylar size (width, length, and height), fossa size (length and height), and condyle-to-fossa joint spaces at the anterior, superior, and posterior condylar poles. Results The null hypothesis was rejected. The Class III group showed larger values for condylar width, condylar height, and fossa height than the Class II group (p < 0.05). Condylar volume and superior joint space in the hyperdivergent group were significantly smaller than those in the other two vertical groups (p < 0.001), whereas fossa length and height were significantly larger in the hyperdivergent group than in the other groups (p < 0.01). The hypodivergent group showed a greater condylar width than the hyperdivergent group (p < 0.01). The sagittal and vertical cephalometric patterns showed statistically significant interactions for fossa length and height. Conclusions TMJ morphology differed across diverse skeletal cephalometric patterns. The fossa length and height were affected by the interactions of the vertical and sagittal skeletal patterns.

Background and Overview Orthodontic miniscrews have become popular tools for providing temporary anchorage during orthodontic treatment. Although they are easy to insert, damage to the periodontal ligament or dental root during insertion is an unfavorable iatrogenic complication. Root perforation during miniscrew insertion in human teeth has been reported in a few articles. In this article, the authors describe the spontaneous repair of an iatrogenic root perforation in a mandibular first molar that occurred during insertion of an orthodontic miniscrew in a young girl undergoing orthodontic treatment. Case Description A 15-year-old girl with malocclusion was undergoing orthodontic treatment when the mesial root of her mandibular right first molar was damaged by an orthodontic miniscrew. The miniscrew and corresponding bracket were immediately removed to avoid any unnecessary forces on the tooth. Because the pulp remained vital without any additional damage and infection for 6 months, orthodontic treatment was resumed and completed in 9 months without any pulp damage or unfavorable symptoms. Serial periapical radiographs and cone-beam computed tomographic images showed that the injured area was surrounded by reparative tissue without any apical lesion. Conclusions and Practical Implications The findings of this case suggest that immediate removal of unnecessary forces provides an environment for spontaneous repair in cases of iatrogenic root perforation by orthodontic miniscrews, even when the damage involves the pulp. If force stimulation is avoided for a certain period, which was 6 months in this case, it may be possible to complete the orthodontic treatment without unfavorable symptoms.

The miniscrew-assisted rapid palatal expander (MARPE) has extended not only skeletal effects with fewer dental changes and but also the age limit of nonsurgical maxillary expansion treatment. Amid its gaining popularity in clinical orthodontics, our current understanding of treatment effectiveness, efficiency, and stability needs to be reassessed. In this review article, the authors have attempted to evaluate MARPE from various aspects with a focus on recent studies.

Objective: A number of epidemiological studies have reported that decreased serum bilirubin, an endogenous antioxidant, is associated with cardiovascular disease. However, previous Mendelian randomization analyses conducted using a single sample have shown no evidence of association. Approach and Results: A 2-sample summary Mendelian randomization study was performed by obtaining exposure and outcome data from separate nonoverlapping samples. We utilized data from the KoGES (Korean Genome and Epidemiology Study; n=25 406) and KCPS-II (Korean Cancer Prevention Study-II; n=14 541) biobank for serum bilirubin and stroke, respectively. Using KoGES, a total of 1784 single nucleotide polymorphisms associated with serum bilirubin levels were discovered using a genome-wide significance threshold ( P −8 ), of which 10 single nucleotide polymorphisms were identified as independent ( R 2 P =0.046). This association increased in magnitude when restricting the analysis to ischemic stroke cases (odds ratio, 0.302 [95% CI, 0.105–0.868]; P =0.026). Conclusions: Our findings provide evidence of significant causal relationship between high levels of bilirubin and decreased stroke risk in Korean population in agreement with observational approaches. This highlights the potential for bilirubin to serve as a therapeutic target for oxidative stress-related diseases such as stroke and suggests that previous findings were not a consequence of unmeasured confounding.

Aim This prospective clinical study evaluated the clinical performance of managing cracked teeth with reversible pulpitis through a combination of internal and external splinting and investigated factors that can affect pulp survival after splinting. Methodology Thirty-four teeth diagnosed with cracks and reversible pulpitis were enrolled and treated with bidirectional crack splinting: 1) immediate splinting with a stainless-steel band; 2) internal splinting with crack line removal and resin filling; and 3) external splinting with a temporary crown followed by final crown setting. If the symptoms remained/recurred, root canal treatment was performed. Patients were followed up at 3, 6, and 12 months, then annually thereafter. Kaplan-Meier survival analysis to calculate the survival of the treated teeth and Cox univariate proportional hazards regression model to investigate prognostic factors were performed. Results Twenty-nine (97%) teeth were followed up for up to 4 years. The pulp survival rate was 72% after banding and 91% after final crown cementation. No tooth was extracted (100% tooth survival rate). In the univariate Cox proportional hazard test, pain on percussion was the only statistically significant factor (hazard ratio = 11.77). Teeth with pain on percussion at the first visit had a pulp survival rate of 46% during the follow-up period. In comparison, their counterparts without pain had a 94% pulp survival rate. Conclusions Bidirectional splinting successfully managed cracked teeth with reversible pulpitis. Pain on percussion (mechanical allodynia) may be an important factor in deciding whether to attempt root canal treatment on symptomatic cracked teeth. A step-by-step approach with bidirectional crack splinting should be encouraged for a cracked tooth with a vital pulp without mechanical allodynia rather than preemptive root canal treatment.

Introduction Appropriate occlusal forces can prevent ankylosis after tooth replantation or transplantation. However, the “proper occlusal forces” on periodontal ligament (PDL) healing have not yet been defined due to insufficient in vitro studies and uncertain in vitro models. Herein, we presented a mechanical vibration device as an in vitro model to determine such favorable occlusal forces. Methods Human periodontal ligament stem cells (hPDLSCs) were exposed to mechanical vibration force with 4 frequencies (30, 90, 150, and 210 rpm). Cell viability and the expression of osteogenic differentiation-related genes and proteins were tested in vitro. The calvarial transplantation experiment was performed to assess the bone formation ability of 150 rpm mechanical vibration stimulation (MVS). Results MVS at 150 and 210 rpm significantly reduced cell viability in the early stages. The 150-rpm MVS decreased osteogenic marker expression at the early time point (3 days) but had no harmful effects at the late time point (14 days). Furthermore, hPDLSC cell sheets treated with 150-rpm MVS had potential to decrease bone formation in rat calvarial defects serendipitously and facilitated functional PDL-like tissue formation. Conclusions We found that MVS at a frequency of 150 rpm could provide a strategy for a transient reduction in the osteogenic potential of hPDLSCs and promote PDL-like tissue formation. Thus, 150-rpm MVS could be used as a controllable proper occlusal force to prevent ankylosis and promote PDL healing after tooth replantation or transplantation.

BackgroundWe investigated the safety and immunogenicity of two recombinant COVID-19 DNA vaccine candidates in first-in-human trials. GX-19 contains plasmid DNA encoding SARS-CoV-2 spike protein, and GX-19N contains plasmid DNA encoding SARS-CoV-2 receptor binding domain (RBD) foldon and nucleocapsid protein (NP) as well as plasmid DNA encoding SARS-CoV-2 spike protein.MethodsTwo open-label phase 1 trials of GX-19 and GX-19N safety and immunogenicity were performed in healthy adults aged 19–55 years. GX-19 trial participants received two vaccine injections (1·5 mg or 3·0 mg, 1:1 ratio) four weeks apart. GX-19N trial participants received two 3·0 mg vaccine injections four weeks apart.FindingsBetween June 17 and July 30 and December 28 and 31, 2020, 40 and 21 participants were enrolled in the GX-19 and GX-19N trials, respectively. Thirty-two participants (52·5%) reported 80 treatment-emergent adverse events (AE) after vaccination. All solicited AEs were mild except one case of moderate fatigue reported in the 1·5 mg GX-19 group. Binding antibody responses increased after vaccination in all groups. The geometric mean titers (GMTs) of spike-binding antibodies on day 57 were 85·74, 144·20, and 201·59 in the 1·5 mg, 3·0 mg GX-19 groups and the 3·0 mg GX-19N group, respectively. In GX-19N group, neutralizing antibody response (50% neutralizing titer using FRNT) significantly increased after vaccination, but GMT of neutralizing antibody on day 57 (37.26) was lower than those from human convalescent serum (288.78). GX-19N induced stronger T cell responses than GX-19. The magnitude of GX-19N-induced T cell responses was comparable to those observed in the convalescent PBMCs. GX-19N induced both SARS-CoV-2 spike- and NP-specific T cell responses, and the amino acid sequences of 15-mer peptides containing NP-specific T cell epitopes identified in GX-19N-vaccinated participants were identical with those of diverse SARS-CoV-2 variantsInterpretationGX-19N is safe, tolerated and induces humoral and broad SARS-CoV-2-specific T cell response which may enable cross-reactivity to emerging SARS-CoV-2 variants.FundingThis research was supported by Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HQ20C0016, Republic of Korea).Research in contextEvidence before this studyTo overcome the COVID-19 outbreak, the development of safe and effective vaccines is crucial. Despite the successful clinical efficacy of the approved vaccines, concerns exist regarding emerging new SARS-CoV-2 variants that have mutated receptor binding domains in the spike protein. We searched PubMed for research articles published up to May 1, 2021, using various combinations of the terms “COVID-19” or “SARS-CoV-2”, “vaccine”, and “clinical trial”. No language or data restrictions were applied. We also searched theClinicalTrials.govregistry and World Health Organization (WHO) draft landscape of COVID-19 candidate vaccines for ongoing trials of COVID-19 vaccines up to May 1, 2021. Ten DNA-based vaccines, including the vaccine candidate reported here, are in ongoing clinical trials. Among these, safety and immunogenicity results were reported from only one phase 1 trial of a DNA vaccine against SARS-CoV-2 (INO-4800). INO-4800 demonstrated favorable safety and tolerability and was immunogenic, eliciting humoral and/or cellular immune responses in all vaccinated subjects. There is only one ongoing clinical trial of a vaccine against SARS-CoV-2 variants (mRNA-1273.351).Added value of this studyThis is the first-in-human phase 1 trial in healthy adults of a recombinant DNA vaccine for COVID-19 (GX-19N) containing the coding regions of both the spike and nucleocapsid proteins. This trial showed that GX-19N is safe, tolerated, and able to induce both humoral and cellular responses. A two-dose vaccination of 3·0 mg GX-19N (on days 1 and 29) induced significant humoral and cellular responses. The neutralizing geometric mean titers in individuals vaccinated with GX-19N were lower than those of human convalescent sera. However, the GX-19N group showed increased T cell responses, which was similar to those analyzed using convalescent PBMCs. Furthermore, GX-19N induced not only SARS-CoV-2 spike-specific T cell responses but also broad nucleocapsid-specific T cell responses, which were also specific to SARS-CoV-2 variants.Implications of all the available evidenceIt is important to note that GX-19N contains a plasmid encoding both the spike and nucleocapsid proteins, and that it showed broad SARS-CoV-2-specific T cell responses, which may allow cross-reactivity with emerging SARS-CoV-2 variants. Based on these safety and immunogenicity findings, GX-19N was selected for phase 2 immunogenicity trials.

Introduction The aim of this study was to evaluate the height growth of Class I and III orthodontic patients according to the Fishman skeletal maturation index (SMI) and to compare it with that of a general population. Methods The study sample included 81 Class I and 71 Class III adolescents who had height measurements and hand-wrist radiographs taken annually and categorized according to SMI. Height completion rate, residual height, height increase per sequential SMI stage, and height velocity were analyzed. Sex differences were evaluated and comparisons between Class I and Class III groups were made. In addition, the height of orthodontic patients was indirectly compared with that of the general population. Results In boys and girls, height completion rate was >90% at SMI 6, residual height was fewer than 10 cm at SMI 7, and height increase per sequential SMI stage was greatest from SMI 6 to SMI 7. Height velocity was greatest from SMI 5 to SMI 6 in boys and from SMI 4 to SMI 5 in girls. Conclusions There was no significant difference in body height parameters for all SMI stages between Class I and Class III adolescents. Adolescents who had orthodontic treatment were not shorter in stature at growth completion compared with the general population.

The present study aimed at evaluating serum immunoglobulin G (IgG) avidity to Porphyromonas gingivalis in elderly patients with mild and severe chronic periodontitis. The avidity of antibodies against P. gingivalis present in the sera of 18 patients with mild chronic periodontitis and 18 patients with severe chronic periodontitis was evaluated using an ammonium thiocyanate-dissociated enzyme-linked immunosorbent assay (ELISA). The results showed that the mean absorbance value in serum IgG antibody titers was significantly higher in the severe chronic periodontitis group than in the mild chronic periodontitis group (198 ± 35 ELISA unit [EU] vs. 142 ± 32 EU, p < 0.01). However, there was no significant difference between the two groups in antibody avidity (65 ± 57 EU vs. 54 ± 27 EU). These findings suggest that humoral immune responses to P. gingivalis between mild and severe chronic periodontitis in elderly patients are characterized by the differences in the quantity rather than the quality of the antibodies.

OBJECTIVE The aim of this study was to investigate the dynamics of alveolar bone formation and healing pattern after the removal of orthodontic temporary anchorage devices (TADs). METHODS Miniscrews (N = 32) were inserted into the buccal inter-radicular alveolar bone in beagle dogs. Afterward, miniscrews were removed at different time points during a 13-week period and six different in vivo fluorescent markers were injected at 1, 2, 6, 8, 10, and 12 weeks. Serial changes in bone apposition at the removal and intact control sites were evaluated using μCT, histology, and bone histomorphometry. RESULTS Gradual bone apposition at the TAD removal site was noted with bone volume/tissue volume (BV/TV) reaching the level of the control alveolar bone by 7 weeks. Histologically, newly formed woven bone was detected within the removal site which was distinct from the surrounding pre-existing alveolar bone at 13 weeks. Accelerated mineral apposition rate (MAR) and bone formation rate (BFR) were noted between 2 and 6 weeks in the removal site (P

Objectives: To determine whether the success rate and primary stability of surface-treated miniscrews differ from those of nontreated miniscrews. Materials and Methods: Patients who required one or more miniscrews for the same reason in each quadrant were recruited into a single-blinded, split-mouth, randomized, controlled trial with a 1:1 allocation ratio. Self-drilling miniscrews with two surface types were used: those with no surface treatment, and those with an acid-etched surface treatment. The cumulative success rate and primary stability of each type of miniscrew were examined, and factors potentially affecting the success and failure of miniscrews were investigated. Results: Forty patients were included in the study, with a total of 98 orthodontic miniscrews. The overall success rate was 88.8%, and the respective success rates for acid-etched and machined surface miniscrews were 91.8% and 85.7%. The respective mean insertion torques were 13.62 ± 5.95 N·cm and 13.38 ± 4 N·cm, and periotest values measured immediately after insertion were −0.50 ± 2.77 for acid-etched miniscrews and −0.28 ± 3.36 for machined surface miniscrews. There was no significant difference in the mean insertion torques and periotest values according to surface treatment and jaw. Conclusions: Neither the success rate nor the primary stability of acid-etched surface miniscrews and machined surface miniscrews differed significantly. There is a high possibility that miniscrews will fall out in patients who have an open bite or those who require total distalization.

Background This meta-analytic study explored the relationship between the risk of type 2 diabetes mellitus (T2DM) and bisphenol A concentrations. Methods The Embase and Medline (PubMed) databases were searched, using relevant keywords, for studies published between 1980 and 2018. A total of 16 studies, twelve cross-sectional, two case-control and one prospective, were included in the meta-analysis. The odds ratio (OR) and its 95% confidence interval (CI) were determined across the sixteen studies. The OR and its 95% CI of diabetes associated with bisphenol A were estimated using both fixed-effects and random-effects models. Results A total of 41,320 subjects were included. Fourteen of the sixteen studies included in the analysis provided measurements of urine bisphenol A levels and two study provided serum bisphenol A levels. Bisphenol A concentrations in human bio-specimens showed positive associations with T2DM risk (OR 1.28, 95% CI 1.14, 1.44). A sensitivity analysis indicated that urine bisphenol A concentrations were positively associated with T2DM risk (OR 1.20, 95% CI 1.09, 1.31). Conclusions This meta-analysis indicated that Bisphenol A exposure is positively associated with T2DM risk in humans. Electronic supplementary material The online version of this article (10.1186/s12902-018-0310-y) contains supplementary material, which is available to authorized users.

Background and aims A few studies examined association between familial hypercholesterolemia (FH) and atherosclerotic cardiovascular disease (ASCVD) in Asians with low levels of serum cholesterol. The objectives of this study were to estimate the prevalence of familial hypercholesterolemia phenotype (FH-P) and examined their associations with cardiovascular mortality among Korean population. Methods The Korea National Health and Nutrition Examination Survey (KNHANES) data and data from a cohort study were used to obtain the prevalence estimate of FH-P and the association of FH-P with mortality, respectively. A cohort study included 502,966 individuals who visited health promotion centers and were given a medical examination from 1994 to 2004. FH-P was defined using the Make Early Diagnosis to Prevent Early Death (MEDPED) criteria and the modified MEDPED which substracted 20 mg/dL from original MEDPED. Results FH-P prevalences defined by MEDPED and modified MEDPED among KNHANES were 0.11% and 0.25%. After 14.6-year follow-up, 23,413 deaths (3888 ASCVD) were observed. Overall, FH-P defined by MEDPED showed weaker associations with mortality compared with modified MEDPED. The hazard ratios (95% confidence intervals) of FH-P defined by modified MEDPED were 1.74 (1.46–2.07) for all-cause death, 2.18 (1.51–3.14) for ASCVD, and 2.06 (1.66–2.56) for non-cancer. Of note, the hazard ratios for all-cause death was 5.27 (2.62–10.57) among women aged less than 50 years. Conclusions FH-P increased all-cause and ASCVD mortality. Long-term follow-up studies with detailed information on cause of mortality are necessary to confirm these findings. Subjects with FH are at high risk for death and need appropriate treatment and management.

To elucidate genetic factors affecting orthodontic treatment duration, we employed targeted next-generation sequencing on DNA from the saliva of 117 patients undergoing orthodontic treatment after premolar extraction. The clinical characteristics of patients were summarized, and the association of clinical variables with treatment duration was assessed. Patients whose treatment duration deviated from the average were classified into an extreme long group or an extreme short group. We identified single nucleotide polymorphisms (SNPs) significantly enriched in the two groups via targeted sequencing. Nine SNPs (six genes) were significantly enriched in both groups. In the extreme long group, the frequency of the CC genotypes of WNT3A, SPP1 (rs4754, rs9138), and TNFSF11, the TT genotype of SPP1 (rs1126616), as well as the GG genotype of SFRP2 was significantly higher than in the short group. In the extreme short group, the TC genotype of SPP1, the AA genotype of P2RX7, the CT genotype of TNFSF11, and the AG genotype of TNFRSF11A tended to exhibit higher frequency than in the long group. Taken together, we identified genetic polymorphisms related to treatment duration in Korean orthodontic patients undergoing premolar extraction. Accurate prediction of the treatment period through further research will be of great aid to patients as well as orthodontists.

Background Obstructive sleep apnea syndrome (OSAS) is being observed in an increasing number of cases. It can be diagnosed using several methods such as polysomnography. Objectives To overcome the challenges of time and cost faced by conventional diagnostic methods, this paper proposes computational fluid dynamics (CFD) and machine-learning approaches that are derived from the upper-airway morphology with automatic segmentation using deep learning. Method We adopted a 3D UNet deep-learning model to perform medical image segmentation. 3D UNet prevents the feature-extraction loss that may occur by concatenating layers and extracts the anteroposterior coordination and width of the airway morphology. To create flow characteristics of the upper airway training data, we analyzed the changes in flow characteristics according to the upper-airway morphology using CFD. A multivariate Gaussian process regression (MVGPR) model was used to train the flow characteristic values. The trained MVGPR enables the prompt prediction of the aerodynamic features of the upper airway without simulation. Unlike conventional regression methods, MVGPR can be trained by considering the correlation between the flow characteristics. As a diagnostic step, a support vector machine (SVM) with predicted aerodynamic and biometric features was used in this study to classify patients as healthy or suffering from moderate OSAS. SVM is beneficial as it is easy to learn even with a small dataset, and it can diagnose various flow characteristics as factors while enhancing the feature via the kernel function. As the patient dataset is small, the Monte Carlo cross-validation was used to validate the trained model. Furthermore, to overcome the imbalanced data problem, the oversampling method was applied. Result The segmented upper-airway results of the high-resolution and low-resolution models present overall average dice coefficients of 0.76±0.041 and 0.74±0.052, respectively. Furthermore, the classification accuracy, sensitivity, specificity, and F1-score of the diagnosis algorithm were 81.5%, 89.3%, 86.2%, and 87.6%, respectively. Conclusion The convenience and accuracy of sleep apnea diagnosis are improved using deep learning and machine learning. Further, the proposed method can aid clinicians in making appropriate decisions to evaluate the possible applications of OSAS.

Summary Background Survival outcomes for patients with recurrent or advanced cervical cancer are poor. Pembrolizumab has been approved for the treatment of recurrent or metastatic cervical cancer, with an overall response rate of 14·3%. GX-188E vaccination has been shown to induce human papillomavirus (HPV) E6-specific and E7-specific T-cell responses and cervical lesion regression in patients with cervical precancer. We aimed to investigate whether a combination of GX-188E therapeutic DNA vaccine plus pembrolizumab showed antitumour activity against recurrent or advanced cervical cancer. Methods In this open-label, single-arm, phase 2 trial, patients with recurrent or advanced, inoperable cervical cancer, who were aged 18 years or older with Eastern Cooperative Oncology Group performance status of 0 or 1 and histologically confirmed recurrent or advanced HPV-positive (HPV-16 or HPV-18) cervical cancer, and who had progressed after available standard-of-care therapy were recruited from seven hospitals in South Korea. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, and 19, with one optional dose at week 46 that was at the investigator's discretion, and intravenous pembrolizumab 200 mg every 3 weeks for up to 2 years or until disease progression. The primary endpoint was the overall response rate within 24 weeks assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1 in patients who received at least 45 days of treatment 45 days of treatment with at least one post-baseline tumour assessment, and this is the report of a planned interim analysis. This trial is registered with ClinicalTrials.gov , NCT03444376 . Findings Between June 19, 2018, and March 20, 2020, 36 patients were enrolled and received at least one dose of the study treatment. 26 patients were evaluable for interim activity assessment, with at least one post-baseline tumour assessment at week 10. At the data cutoff date on March 30, 2020, median follow-up duration was 6·2 months (IQR 3·5–8·1). At 24 weeks, 11 (42%; 95% CI 23-63) of 26 patients achieved an overall response; four (15%) had a complete response and seven (27%) had a partial response. 16 (44%) of 36 patients had treatment-related adverse events of any grade and four (11%) had grade 3–4 treatment-related adverse events. Grade 3 increased aspartate aminotransferase, syncope, pericardial effusion, and hyperkalaemia, and grade 4 increased alanine aminotransferase were reported in one patient each. No treatment-related deaths were reported. Interpretation Treatment with GX-188E therapeutic vaccine plus pembrolizumab for patients with recurrent or advanced cervical cancer was safe and treatment-related adverse events were manageable. This combination therapy showed preliminary antitumour activity in this interim analysis, which could represent a new potential treatment option for this patient population. This trial is ongoing. Funding National OncoVenture.

This study was performed to investigate the changes in gene expression in periodontal ligament (PDL) cells following mechanical stimulus through RNA sequencing. In this study, premolars extracted for orthodontic treatment were used. To stimulate the PDL cells, an orthodontic force of 100&times, g was applied to the premolar (experimental group, n = 11), whereas the tooth on the other side was left untreated (control group, n = 11). After the PDL cells were isolated from the extracted teeth, gene set enrichment analysis (GSEA), differentially expressed gene (DEG) analysis, and real-time PCR were performed to compare the two groups. GSEA demonstrated that gene sets related to the cell cycle pathway were upregulated in PDL. Thirteen upregulated and twenty downregulated genes were found through DEG analysis. Real-time PCR results confirmed that five upregulated genes (CC2D1B, CPNE3, OPHN1, TANGO2, and UAP-1) and six downregulated genes (MYOM2, PPM1F, PCDP1, ATP2A1, GPR171, and RP1-34H18.1-1) were consistent with RNA sequencing results. We suggest that, from among these eleven genes, two upregulated genes, CPNE3 and OPHN1, and one downregulated gene, PPM1F, play an important role in PDL regeneration in humans when orthodontic force is applied.

ObjectiveThe purpose of this study was to evaluate the effects of miniscrew insertion angle and vertical facial type on the interradicular miniscrew-root distance available for molar distalization.Materials and methodsCone-beam computed tomography images of 60 adults with skeletal Class I occlusion exhibiting hyperdivergent (n = 20), normodivergent (n = 20), and hypodivergent (n = 20) facial types were used. Placement of a 6-mm long, 1.5-mm diameter, tapered miniscrew was simulated at a site 4 mm apical to the cementoenamel junction, with insertion angles of 0°, 30°, 45°, and 60° relative to the transverse occlusal plane. The shortest linear distance between the miniscrew and anterior root at four interradicular sites was measured: maxillary second premolar and first molar (Mx 5-6), maxillary first and second molars (Mx 6-7), mandibular second premolar and first molar (Mn 5-6), and mandibular first and second molars (Mn 6-7).ResultsMiniscrew-root distance significantly increased as the insertion angle increased from 0° to 60°. In the mandible, the distances significantly differed among vertical facial types, increasing in the following order: hyperdivergent, normodivergent, and hypodivergent. The minimum mean distance was found in the Mx 6-7 (30°; 0.86±0.35 mm), and the maximum mean distance was found in the Mn 5-6 (60°; 2.64±0.56 mm). The rates of miniscrews located buccally outside the root distalization path were up to 70% and 55% when the miniscrews were placed at 60° insertion angles in the Mx 5-6 and Mn 5-6 regions, respectively.ConclusionsMiniscrew-root distance increased significantly with the increased insertion angle, and the amount of increase was affected by the miniscrew placement site and vertical facial type. To ensure adequate distalization of the posterior segment, the miniscrew should be inserted at an angle in the interradicular area between the second premolar and first molar.

Introduction The aim of this study was to evaluate the dentofacial transverse dimensions of subjects with different sagittal facial patterns using 3-dimensional cone-beam computed tomography images. Methods Cone-beam computed tomography images of 63 men and 80 women were divided into skeletal Class I, Class II, and Class III groups. Skeletal and dental evaluations were made on frontal views and coronal cross-sections of the images. Independent 2-sample t tests and 1-way analysis of variance followed by post hoc Tukey tests were used for sex and group differences. Pearson correlation analysis was used to identify factors related to changes in ANB angle. Results The Class II subjects did not show differences in maxillomandibular width and maxillary width compared with Class I subjects; however, their maxillary molars were more lingually tipped. The Class III subjects showed greater maxillomandibular width differences and smaller maxillary widths and maxillary buccolingual alveolar widths at midroot level compared with Class I subjects. The maxillary molars were buccally inclined, and the mandibular molars were lingually compensated in Class III subjects. The ANB angle showed positive correlations with jugal process width, maxillary width, and maxillary buccolingual alveolar width at midroot level as well as mandibular molar buccal inclination; negative correlations were found in maxillomandibular width difference, mandibular width at midroot level, and maxillary molar buccal inclination. Conclusions A relative comparison of Class I, Class II, and Class III subjects showed that dental compensation had occurred to overcome the transverse skeletal discrepancies in the maxillary posterior segments of Class II and Class III subjects. This could escalate unidentified periodontal and functional problems in the long term. Future studies of transverse dentofacial dimensions, including periodontal evaluations and occlusal forces, would be useful for delivering proper orthodontic treatment for skeletal Class II and Class III subjects.

Objective To investigate treatment stability of miniscrew-anchored maxillary distalization in Class II malocclusion. Materials and Methods This retrospective study included a distalization (n = 19) and a control (n = 19) group; a patient group with minor corrections served the control. Lateral cephalograms of 38 adult patients were taken before (T0), immediately after (T1), and 3–4 years after (T2) treatment. Horizontal and vertical movement and tipping of the maxillary first molars (U6) and central incisors (U1) were measured along with skeletal craniofacial parameters at three time points to compare the two groups regarding the achieved treatment effects and their stability. Results Total arch distalization therapy led to 4.2 mm of distal movement of U6 without distal crown tipping (0.6° of axis change) and 3.3° of occlusal plane steepening. Over an average retention period of 42 months, maxillary total arch distalization provided high stability of treatment results, showing the same amount of mesial movement (0.7 mm) as the control group. Conclusions In Class II treatment, miniscrew-anchored maxillary total arch distalization can provide stable distal movement of the maxillary first molars and central incisors.

Objectives: To investigate the incidence of and contributing factors to open gingival embrasures between the central incisors after orthodontic treatment. Materials and Methods: One hundred posttreatment patients (29 men and 71 women; mean age, 24.7 years) were divided retrospectively into occurrence and nonoccurrence groups based on intraoral photographs. Based on the severity, the occurrence group was further divided into mild, moderate, and severe groups. Parameters from periapical radiographs, superimposed lateral cephalograms, and study models were compared between the occurrence and the nonoccurrence groups by using independent t-tests and were also analyzed on the basis of severity via analysis of variance. Logistic regression analysis was performed to identify the contributing factors to open gingival embrasures. Results: The incidence of open gingival embrasures between the central incisors was 22% and 36% in the maxilla and the mandible, respectively. Lingual movement of the incisors, distance from the contact point to the alveolar crest after treatment, antero-posterior overlap of the two central incisors before treatment in the maxilla, and distance from the contact point to the alveolar crest after treatment in the mandible were significantly associated with the occurrence of open gingival embrasures (P < .05). In the mandible, the amount of intrusion was significantly related to severity (P < .05). Conclusions: The incidence of open gingival embrasures following orthodontic tooth movement is high. Therefore, attention should be paid to the contributing factors to prevent or reduce the occurrence of open gingival embrasures.

PurposeThe purpose of this systematic review and meta-analysis is to explore the factors associated with medication engagement among older adults (≥60 years) with diabetes.MethodsFive databases (PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and Scopus) were systematically searched to identify studies examining the association between factors and medication engagement among older diabetes patients. A study met inclusion for meta-analysis if the prevalence of medication engagement or factor was reported in ≥2 studies and the frequency or strength of association was either reported or able to be computed. Quality appraisal was performed with the Downs and Black tool.ResultsOf 538 retrieved studies, 33 (20 cohort and 13 cross-sectional) were included for systematic review; of these, 22 met criteria for meta-analysis. Findings from meta-analysis show that women (odds ratio [OR], 0.92; 95% CI, 0.86-0.97), those with depression (OR, 0.73; 95% CI, 0.62-0.87), and those with higher out-of-pocket spending for prescription drugs (OR, 0.87; 95% CI, 0.80-0.94) were less likely to take diabetes medication when compared with men, those without depression, and those with lower out-of-pocket costs, respectively. Older age (OR, 1.13; 95% CI, 1.00-1.27) was associated with better engagement to diabetes medication.ConclusionsOf 4 identified factors, 2 are modifiable. Recent policy efforts to decrease the cost burden of prescribed medication for older adults, such as Medicare Part D, may remove this barrier to medication engagement. Routine screening for depression among older adults with diabetes should be included as part of usual care to facilitate an integrated treatment approach.

5511 Background: Pembrolizumab was approved for the treatment of recurrent or metastatic cervical cancer, based on 14.3% of objective response rate (ORR) in patients with PD-L1 expression (CPS≥1). GX-188E vaccination has been shown to induce human papillomavirus (HPV) E6- and E7-specific T-cell responses. We aimed to investigate whether a combination of GX-188E (Tirvalimogene teraplasmid) therapeutic DNA vaccine plus pembrolizumab showed antitumor activity against recurrent or advanced cervical cancer. Methods: In this open-label, single-arm, phase 2 trial, patients with recurrent or advanced cervical cancer, who were aged over 18 years with ECOG PS of 0 or 1, HPV-16 or HPV-18 and histologically confirmed positive cervical cancer, and who had progressed after standard-of-care therapy were recruited from nine hospitals in South Korea. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, 19, and optional dose at week 46, and intravenous pembrolizumab 200 mg every 3 weeks for up to 2 years or until disease progression. The primary endpoint was the Best Overall Response Rate assessed by the investigator using RECIST version 1.1. Results: To date, a total of 52 patients have been enrolled and received at least one study treatment, and this interim analysis was performed after obtaining at least one post-baseline tumor assessment data from 48 patients. Median age was 52 (range, 27-79) years and 46.2% had ECOG PS 1. At the data cutoff date on January 11, 2021, median follow-up duration was 6.2 months (range; 1.7- 24.2 months). According to investigator evaluation, 15 (31.3%) of 48 patients achieved best overall response; 5 (10.4 %) patients had a complete response (CR) and 10 (20.8 %) had a partial response (PR). Especially, this combination treatment showed higher response rate, 48.0 %, in patients with PD-L1 positive, HPV-16 and squamous cell carcinoma. Median PFS was 4.1 months (range; 1.3-24.2) and median OS was 16.7 months (range; 1.7-24.2). In this clinical trial with cervical cancer patients, GX-188E in combination with pembrolizumab has shown an improved median PFS and OS than the monotherapy of pembrolizumab (KEYNOTE-158). 17 (32.7%) of 52 patients had treatment-related adverse events of any grade and two (3.8%) had grade 3 or 4 treatment-related adverse events; increased aspartate aminotransferase or alanine aminotransferase. No treatment-related deaths were reported. Conclusions: GX-188E vaccine combined with pembrolizumab in recurrent/advanced cervical cancer was safe and tolerable, and showed an enhanced clinical response rate compared with pembrolizumab alone in particular in patients with PD-L1 positive, HPV-16 and squamous cell carcinoma. The combination therapy could represent a new potential treatment option for this patient population. Clinical trial information: NCT03444376.

OBJECTIVE The purpose of this study was to compare the changes induced in the pharyngeal airway space by orthodontic treatment with bodily retraction of the mandibular incisors and mandibular setback surgery without extraction. METHODS This retrospective study included 63 adult patients (32 men and 31 women). Thirty-three patients who had been treated via four-bicuspid extraction and bodily retraction of the mandibular incisors (incisor retraction, IR group) were compared with 30 patients who had been treated via mandibular setback surgery (MS group) without extraction. Lateral cephalograms were acquired and analyzed before (T1) and after treatment (T2). RESULTS The superior pharyngeal airway space did not change significantly in either group during treatment. The middle pharyngeal airway space decreased by 1.15 ± 1.17 mm and 1.25 ± 1.35 mm after treatment in the IR and MS groups, respectively, and the decrease was comparable between the two groups. In the MS group, the inferior pharyngeal airway space (E-IPW) decreased by 0.88 ± 1.67 mm after treatment (p < 0.01). The E-IPW was larger in the MS group than in IR group at T1, but it did not differ significantly between the two groups at T2. No significant correlation was observed between changes in the pharyngeal airway space and the skeletal and dental variables in each group. CONCLUSIONS The middle pharyngeal airway space decreased because of the posterior displacement of the mandibular incisors and/or the mandibular body. The E-IPW decreased only in the MS group because of the posterior displacement of only the mandibular body.

Orthodontic treatment of a complex case that involves retained deciduous mandibular second molars with missing permanent successors is challenging. Usually, congenitally missing teeth are manifested with other dental anomalies that further complicate orthodontic treatment, such as retained deciduous teeth, impactions, transpositions and peg-shaped lateral incisors. Even though the long term prognosis of the retained deciduous tooth is not fully predictable, if the teeth are in good condition, the patient and clinician may incline towards a decision to preserve the deciduous teeth as long as possible. This case report demonstrates that deciduous teeth, in this case the mandibular second molars and maxillary canine, can be incorporated into final occlusion with clinically stable long-term results.

Objective Miniscrew-assisted rapid palatal expansion (MARPE) is a means for expanding the basal bone without surgical intervention in young adults. Here, we assessed the differences in dental, alveolar, and skeletal measurements taken before (T0), immediately after (T1), and 1 year after (T2) MARPE. Methods Twenty-four patients (mean age, 21.6 years) who had undergone MARPE and cone-beam computed tomography at T0, T1, and T2 were included. Changes in the following parameters were compared using paired t-tests: intercusp, interapex, alveolar, nasal floor, and nasal cavity widths; inclination of the first molar (M1) and its alveolus; and thickness and height of the alveolar bone. A linear mixed-effects model was used to determine variables that affected periodontal changes in the M1. Results MARPE produced significant increases in most measurements during T0-T2, despite relapse of some measurements during T1-T2. The alveolar thickness decreased on the buccal side, but increased on the palatal side. The alveolar crest level at the first premolar moved apically. Changes in the thickness and height of the alveolar bone were affected by the corresponding initial values. Conclusions MARPE can be used as an effective tool for correcting maxillomandibular transverse discrepancy, showing stable outcomes 1 year after expansion.

Objective: The purpose of this study was to investigate the diagnostic aspects, contributing conditions, and predictive key factors associated with ectopic eruption of maxillary second molars. Material and Methods: This retrospective study evaluated the study models, lateral cephalographs, and panoramic radiographs of 40 adult subjects (20 men, 20 women) with bilateral ectopic eruption and 40 subjects (20 men, 20 women) with normal eruption of the maxillary second molars. Studied variables were analyzed statistically by independent t-tests, univariate and multivariate logistic regression analysis, followed by receiver-operating characteristic analysis. Results: Tooth widths of bilateral lateral incisors, canines, and premolars were wider in the ectopic group, which resulted in greater arch lengths. The ANB angle and maxillary tuberosity distance (PTV-M1, PTV-M2) were smaller in the ectopic group. The long axes of the maxillary molars showed significant distal inclination in the ectopic group. The multivariate logistic regression analysis showed that three key factors—arch length, ANB angle, and PTV-M1 distance—were significantly associated with ectopic eruption of the second molars. The area under the curve (AUC) was the largest for the combination of the three key factors with an AUC greater than 0.75. PTV-M1 alone was the single factor that showed the strongest association with ectopic eruption (AUC = 0.7363). Conclusions: An increase in arch length, decrease in ANB angle, and decrease in maxillary tuberosity distance to the distal aspect of the maxillary first molar (PTV-M1) were the most predictive factors associated with ectopic eruption of maxillary second molars.

Background/Aims The aim of this study was to investigate the protective effect of açaí against azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colorectal cancer development. Methods The effect of açaí on tumorigenesis was assessed by evaluating tumor incidence, multiplicity and invasiveness in the mouse colon. The levels of myeloperoxidase (MPO) and proinflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, and IL-6) were measured via enzyme-linked immunosorbent assay. Protein levels of cyclooxygenase 2 (COX-2), proliferating cell nuclear antigen (PCNA), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad) and cleaved-caspase-3 were assessed by immunoblotting. Results Administration of pellets containing 5% açaí powder reduced the incidences of both colonic adenoma and cancer (adenoma, 23.1% vs 76.9%, respectively, p=0.006; cancer, 15.4% vs 76.9%, respectively, p=0.002). In the açaí-treated mice, the MPO, TNF-α, IL-1β and IL-6 levels in the colon were significantly down-regulated. Açaí inhibited PCNA and Bcl-2 expression and increased Bad and cleaved-caspase-3 expression. In vitro studies demonstrated that açaí treatment reduced lipopolysaccharide-induced expression of TNF-α, IL-1β, IL-6 and COX-2 in murine macrophage RAW 264.7 cells. Conclusions Açaí demonstrated protective effects against AOM/DSS-induced colon carcinogenesis, which suggests that the intake of açaí may be beneficial for the prevention of human colon cancer.

Transverse maxillary deficiency is a common pathological condition. Patients suffering from this pathology often have narrowed airways compared to healthy humans. To cure such an anatomic defective position, a new method, the Miniscrew-Assisted Rapid Maxillary Expansion (MARME), has been developed. In previous studies, the effects of this treatment on respiration have been analyzed by examining the volume of a nasal cavity and the corresponding nasopharynx before and after treatment. In this study the fluid mechanical effects of MARME treatment on the respiratory flow and on the breathing capability are analyzed numerically. The realistic three-dimensional geometries of the nasal cavity employed for the simulation are reconstructed from Computer Tomography images. The flow within these geometries is simulated using a thermal Lattice-Boltzmann method. The results confirm that the respiratory resistance and the average wall-shear stress decrease after the MARME treatment. The heating capability, however, deteriorates.

Background The lack of anti-fibrotic agents targeting intestinal fibrosis is a large unmet need in inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis. Previous studies have found that perinatal tissue (umbilical cord, UC; placenta, PL)-derived mesenchymal stem cells (MSCs) reduce fibrosis in several organs. However, their effects on human intestinal fibrosis are poorly understood. This study investigated the anti-fibrogenic properties and mechanisms of MSCs derived from UC and PL (UC/PL-MSCs) on human primary intestinal myofibroblasts (HIMFs). Methods The HIMFs were treated with TGF-β1 and co-cultured with UC/PL-MSCs. We used a small molecular inhibitor CCG-100602 to examine whether serum response factor (SRF) and its transcriptional cofactor myocardin-related transcription factor A (MRTF-A) are involved in TGF-β1-induced fibrogenic activation in HIMFs. The anti-fibrogenic mechanism of UC/PL-MSCs on HIMFs was analyzed by detecting the expression of RhoA, MRTF-A, and SRF in HIMFs. Results UC/PL-MSCs reduced TGF-β1-induced procollagen1A1, fibronectin, and α-smooth muscle actin expression in HIMFs. This anti-fibrogenic effect was more apparent in the UC-MSCs. TGF-β1 stimulation increased the expressions of RhoA, MRTF-A, and SRF in the HIMFs. TGF-β1 induced the synthesis of procollagen1A1, fibronectin, and α-smooth muscle actin through a MRTF-A/SRF-dependent mechanism. Co-culture with the UC/PL-MSCs downregulated fibrogenesis by inhibition of RhoA, MRTF-A, and SRF expression. Conclusions UC/PL-MSCs suppress TGF-β1-induced fibrogenic activation in HIMFs by blocking the Rho/MRTF/SRF pathway and could be considered as a novel candidate for stem cell-based therapy of intestinal fibrosis.

Obstructive sleep apnea (OSA) is a common sleep breathing disorder. With the use of computational fluid dynamics (CFD), this study provides a quantitative standard for accurate diagnosis and effective surgery based on the investigation of the relationship between airway geometry and aerodynamic characteristics. Based on computed tomography data from patients having normal geometry, 4 major geometric parameters were selected and a total of 160 idealized cases were modeled and simulated. We created a predictive model using Gaussian process regression (GPR) through a data set obtained through numerical method. The results demonstrated that the mean accuracy of the overall GPR model was ~72% with respect to the CFD results for the realistic upper airway model. A support vector machine model was also used to identify the degree of OSA symptoms in patients as normal-mild and moderate and severe. We achieved an accuracy of 82.5% with the training data set and an accuracy of 80% with the test data set.NEW & NOTEWORTHY There have been many studies on the analysis of obstructive sleep apnea (OSA) through computational fluid dynamics and finite element analysis. However, these methods are not useful for practical medical applications because they have limited information for OSA symptom. This study employs the machine learning algorithm to predict flow characteristics quickly and to determine the symptoms of the patient's OSA. The overall Gaussian process regression model's mean accuracy was ~72%, and the accuracy for the classification of OSA was >80%.

BACKGROUND The aim of this study was to investigate the effect of N-methyl-N-nitrosourea (MNU) treatment followed by chronic Helicobacter pylori SS1 and H. felis colonization on the stomachs of C57BL/6 mice. The role of MNU and Helicobacter species in gastric carcinogenesis was also elucidated. METHODS A total of 69 C57BL/6 mice at 4 weeks of age were divided into 6 groups according to MNU treatment and H. pylori SS1 or H. felis infection. The mice were sacrificed at 21 and 50 weeks. The degree of inflammation was determined by histopathology. The levels of gastric mucosal myeloperoxidase, TNF-α, and interleukin-1β (IL-1β) were measured by ELISA. RESULTS In the H. felis groups with or without MNU, the incidence of gastric tumors was 21.1% and 35.0% at 21 and 50 weeks, respectively. No gastric tumors were observed in all control mice. At 50 weeks, 37.5% of gastric adenoma cases were observed in the H. felis alone and MNU + H. felis groups. Furthermore, 12.5% of gastric adenocarcinoma cases were observed in the MNU alone and MNU + H. felis groups. The gastric mucosal IL-1β level was significantly higher in the MNU + H. felis group at 21 weeks and H. felis group at 50 weeks, respectively, than that for control mice (P < 0.05). However, the effect of MNU on H. pylori SS1-induced gastric carcinogenesis was low compared to that on H. felis. CONCLUSIONS Administration of MNU before H. felis infection provokes severe inflammation through IL-1β, and eventually induces gastric cancer. However, the role of MNU in H. pylori SS1-induced gastric carcinogenesis model is minor.

Background/Aims: The aim of this study was to evaluate the effect of the synthetic S-allyl-L-cysteine (SAC) PMK-S005 on gastric acid secretion, inflammation, and antioxidant enzymes in aging rats. Methods: The rats were divided into four groups at 31 weeks of age and were continuously fed a diet containing a vehicle control, PMK-S005 (5 or 10 mg/kg), or lansoprazole (5 mg/kg). Gastric acid secretion and connective tissue thickness of the lamina propria were evaluated at 74 weeks and 2 years of age. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and COX-2 levels were measured by using enzyme-linked immunosorbent assays (ELISAs) or Western blot assays. Levels of antioxidant enzymes, including heme oxyganase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), were also measured. Results: As the rats aged, gastric acid secretion significantly decreased, and the connective tissue of the lamina propria increased. However, 74-week-old rats in the PMK-S005 group exhibited greater levels of gastric acid secretion than those of the control and lansoprazole groups. The increase of TNF-α, IL-1β, and COX-2 expression in 74-week and 2-year-old control rats were inhibited by PMK-S005. In addition, the decrease in HO-1 and NQO-1 protein expression that occurred with aging was inhibited by PMK-S005 in the 74-week-old rats. Conclusions: These results suggest that PMK-S005 has therapeutic potential as an antiaging agent to ameliorate age-related gastric acid secretion, inflammation, and oxidative stress in the stomach. (Gut Liver 2016;10:749-756)

This study was performed to evaluate the long-term changes in mandibular width, lower facial width, and ramus angulation after intraoral vertical ramus osteotomy (IVRO) and to identify the factors influencing these changes. This retrospective study included 53 consecutive patients with mandibular prognathism who underwent IVRO with (n=33) or without (n=20) Le Fort I osteotomy. Postero-anterior cephalograms and frontal facial photographs obtained before, 1 month after, and at least 24 months after IVRO were used for measurements. A linear mixed model and paired t-tests were used to analyze temporal changes and the associated influencing factors. The mandibular width increased immediately after surgery (P0.05), but decreased continuously thereafter. The ramus angulation showed negligible change within the first month (P0.05) and decreased thereafter up to approximately 36 months. The amounts of mandibular setback and posterior impaction and the length of time postoperative influenced these changes. The lower facial width changed, although inconsistently, within 3mm over time (P0.05). In conclusion, the mandibular width increased after IVRO but seemed to normalize within approximately 3 years. The lower facial width did not reflect underlying skeletal changes. Therefore, long-term transverse changes after IVRO can be considered clinically irrelevant.

This case report describes the successful treatment of severely impacted mandibular second molars with severe apical root resorption of the mandibular first molars. The vertically impacted second molars were orthodontically moved (using orthodontic mini-implants) without additional root resorption of the first molars. The orthodontic treatment provided a satisfactory and stable outcome by improving the periodontium surrounding the first and second molars. The treatment also eliminated the need for prosthetic treatment by preserving the first and second molars.

Prophylactic removal of impacted third molars is a common procedure in dentistry, but the necessity of routine extraction is still controversial. When impacted third molars caused severe apical root resorption of the second molars, orthodontic traction of the third molars after extraction of the damaged second molars could minimize alveolar bone defect and preserve the patient’s natural teeth. By well-planned orthodontic treatment, functional occlusion was established avoiding extraction of the impacted teeth and eliminating the possibility of a large bone defect after extraction.

Tooth autotransplantation is a treatment option that has the potential to restore masticatory function and esthetics to edentulous spaces resulting from extracted teeth. The purpose of this study was to investigate the prognostic factors and clinical outcomes for autotransplanted teeth with complete root formation.Patients who had received tooth autotransplantation in the Department of Conservative Dentistry, Yonsei University Dental Hospital, Seoul, Korea, from July 2001 to August 2010 were electronically searched, and a total of 105 cases of autotransplanted teeth met the inclusion criteria. Tooth survival, inflammatory root resorption (IRR), ankylosis, and related prognostic factors were assessed by using the survival analysis that was based on clinical and radiographic examination.The cumulative tooth survival rate was 68.2% at 12 years after the tooth autotransplantation. According to the Cox proportional hazard regression analysis, patient age, donor position, and extraoral time were significantly associated with tooth survival (P.05). Donor extraction type was significantly associated with IRR (P.05), and transplantation timing and initial stability were significantly associated with ankylosis (P.05) CONCLUSIONS: Patients less than 45 years of age, maxillary donor teeth, and an extraoral time of less than 15 minutes were associated with significantly higher tooth survival. Surgical extraction of the donor tooth was associated with a significantly higher incidence of IRR. Immediate transplantation after the extraction of the recipient site's tooth and low initial stability were associated with a significantly lower incidence of ankylosis.

Glucocorticoids effectively mediate the resolution of inflammation, but long-term use of glucocorticoids inevitably causes metabolic side effects. However, it is unknown if metabolic effectors such as Dexras1, a dexamethasone-stimulated protein, play a role in the anti-inflammatory outcome of dexamethasone. Here, we demonstrate that Dexras1 is required for the dexamethasone-induced upregulation of annexin A1 expression, but is not involved in the reduction of inflammation as evidenced by decreased pro-inflammatory parameters. In the absence of Dexras1, lipopolysaccharide (LPS)-induced interleukin-6 expression was suppressed when murine macrophage RAW264.7 cells were treated with dexamethasone. Similar observations were made in the blood of Dexras1 knockout mice. Furthermore, dexamethasone suppressed the LPS-stimulated increase of NFκB-p65 in both control and Dexras1-absent RAW264.7 cells. Interestingly, depletion of Dexras1 resulted in the loss of pERK production. These results suggest that Dexras...

Background: Dextran sodium sulfate (DSS)-induced colitis mouse model is used for research of inflammatory bowel disease. The aim of this study was to establish the adequate conditions for DSS mice model, and to find useful tool to measure inflammation. Methods: The 2.5% DSS was administered to six male C57BL/6 mice and 4% DSS to eight mice at 5 or 9 weeks of age. Each group was consisted of 6 mice with control group in which vehicle was administered instead of DSS. The mice were sacrificed on the 7th day after DSS or vehicle administration. Body weight, diarrhea, and hematochezia were recorded daily. Disease activity index (DAI) score which was composed of body weight change, diarrhea, and hematochezia was measured every day. Colon length was measured after sacrifice and colon mucosal level of interleukin 1 beta (IL-1β) was measured by ELISA assay. Histological score was compared between ascending and descending colon in the DSS group. Results: Colon length of five- and nine-week DSS group was significantly shorter than each control group but there was no statistical significance depending on DSS concentration or age. DAI score of 4% DSS group in nine-week was significantly higher than that five-week (P = 0.012) but there was no difference between 2.5% and 4% DSS group. The level of IL-1β in DSS mice was much higher than control group (P < 0.01), but there was no difference among several DSS groups. The histological score was higher in the descending colon than in the ascending colon but there was no statistical difference between each pair of DSS groups. Conclusions: The 4% DSS mice in nine-week was adequate for DSS-induced colitis model. DAI score was useful tool and descending colon was more appropriate site for histological evaluation of colitis than ascending colon.

Objective: To evaluate the morphologic features and the relative position of the incisive canal with regard to the maxillary incisor roots using computed tomography (CT). Materials and Methods: Morphologic evaluation of the incisive canal and its proximity to the maxillary central incisors were measured using CT images of 38 adults with skeletal and dental class I normal occlusion. Linear measurements were performed on the axial cross-sectional images corresponding to three vertical levels, the palatal opening of the incisive canal (L1), midlevel between the opening level and the root apex of the maxillary central incisors (L2), and the root apex of the maxillary central incisors (L3). Results: The percentage of subjects with an incisive canal width greater than the interroot distance of the central incisors was 86.8% and 63.2% at levels L1 and L2, respectively. The anteroposterior distance between the maxillary incisor roots and the boarder of the incisive canal was approximately 5–6 mm at levels L1 and L2. Conclusion: The anteroposterior distance between the maxillary central incisor roots and the incisive canal was approximately 5–6 mm. More than 60% of the subjects had an incisive canal width greater than the interroot distance. Evaluation of the proximity of the incisive canal to the maxillary incisors, along with its dimensional characteristics, may be helpful when a considerable amount of maxillary retraction is planned.

Purpose: Pembrolizumab was approved for the treatment of patients with relapsed or metastatic cervical cancer with disease progression on or after chemotherapy, whose tumors express PD-L1 (CPS≥1), with a 14.3% objective response rate (ORR) by the U.S. FDA in 2018 (KEYNOTE-158). Combination of pembrolizumab with GX-188E, a DNA vaccine targeting HPV 16 and 18 types is expected to show synergistic anti-tumor effects presumably by antigen-specific CD8+ T cell responses induced by GX-188E DNA vaccine. The objectives of this interim analysis are to assess preliminary anti-tumor efficacy, safety and tolerability. Patients and Design: This is a prospective, open-label, phase II study in patients with advanced, inoperable or metastatic cervical cancer, ECOG PS 0-1, positivity for HPV 16 and/or 18 types who have failed all available standard-of-care (SoC) therapies including surgery, chemotherapy and radiotherapy or who have refused those (≥2 lines). Patients received GX-188E 2 mg intramuscularly, seven times at weeks 1, 2, 4, 7, 13, 19, and 46, with pembrolizumab 200 mg IV every three weeks for up to 2 years or until progression. This interim analysis was performed after obtaining at least one post baseline tumor assessment data from 22 patients (approximately 50% of total patients to be enrolled in Phase II). Results: Among 24 patients treated, 22 patients were evaluable for anti-tumor efficacy. Median age was 52 (range, 27-68) years and 37.5% had ECOG PS 1. As of the Dec 11, 2019 data cutoff, the median follow-up duration was 5.3 months (range; 0.9-16.3 months). ORR was 45.5%, with 5 CRs and 5 PRs. Additionally, one patient had SD at week 14. Median PFS was 4.1 months (range; 1.7-not reached). Median DoR and OS have not been reached. Treatment related AEs occurred in 54.2% of patients with grade 1 or 2 and 12.5% of patients with grade 3-4. The most common treatment related AEs classified by system organ class were gastrointestinal disorders (20.8%) and respiratory, thoracic and mediastinal disorders (16.7%), which were similar to those of pembrolizumab monotherapy. In contrast to pembrolizumab monotherapy, combined therapy showed therapeutic effect in PD-L1 negative tumor. Conclusions: Pembrolizumab combined with GX-188E demonstrated a higher response rate than pembrolizumab monotherapy in patients with cervical cancer showing great synergy regardless of PD-L1 expression. The safety profile was manageable and similar to that of pembrolizumab monotherapy. Further evaluation of anti-tumor response and antigen specific immune response is ongoing in a larger number of patients with and without PD-L1 expression. Citation Format: Sooyoung Hur, Jong Sup Park, Yong-Man Kim, Myong Cheol Lim, Jae Hong No, Byoung-Gie Kim, Jae-Kwan Lee, Chi Heum Cho, Yoon-Jeong Choi, You Suk Suh, Jung Won Woo, Young Chul Sung. Efficacy and safety results of pembrolizumab combined with GX-188E, a therapeutic DNA vaccine administration in patients with HPV 16- and/or 18- positive advanced cervical cancer: Phase II interim analysis results [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT033.

Background Identifying changes in serum metabolites before the occurrence of acute myocardial infarction (AMI) is an important approach for finding novel biomarkers of AMI. Methods In this prospective cohort study, serum samples obtained from patients at risk of AMI (n = 112) and non-risk controls (n = 89) were tested using high-resolution metabolomics (HRM). Partial least-squares discriminant analysis (PLS-DA), along with univariate analysis using a false discovery rate (FDR) of q = 0.05 were performed to discriminate metabolic profiles and to determine significantly different metabolites between healthy control and AMI risk groups. Results PLS-DA significantly separated the AMI risk sera from control sera. The metabolites associated with amino acid biosynthesis, 2-oxocarboxylic acid, tryptophan, and amino sugar and nucleotide sugar metabolism pathways were mainly elevated in patients at risk of AMI. Further validation and quantification by MS/MS showed that tryptophan, carnitine, L-homocysteine sulfinic acid (L-HCSA), and cysteic acid (CA) were upregulated, while L-cysteine and L-cysteine sulfinic acid (L-CSA) were downregulated, specifically among AMI risk sera. Additionally, these discriminant metabolic profiles were not related to hypertension, smoking or alcoholism. Conclusion In conclusion, detecting upregulated L-HCSA and CA along with carnitine among patients at risk for AMI could serve as promising non-invasive biomarkers for early AMI detection.