Antithrombotic Therapy Increases the Risk of Bleeding after Endoscopic Submucosal Dissection for Early Gastric Cancer: A Propensity Score-Matched Analysis.

Whether antithrombotic agent (ATA) usage increases the risk of gastric post-endoscopic submucosal dissection (ESD) bleeding remains controversial. The aim of this study was to elucidate the effects of usage, type, and cessation timing of ATA on post-ESD bleeding. A total of 4775 early gastric cancer patients undergoing ESD were analyzed; 1:3 propensity score matching between ATA and non-ATA groups resulted in 318 and 767 matched patients in each group, respectively. Outcomes were compared between the two groups using a generalized estimating equation method. After matching, post-ESD bleeding rates in ATA users and non-users were 9.1% and 4.2%, respectively (p = 0.001). In multivariable analysis, ATA usage was independently associated with an increased risk of post-ESD bleeding (adjusted odds ratio: 2.28, 95% confidence interval: 1.34-3.86). Both the continued or insufficient cessation groups and the sufficient cessation group had an increased incidence of post-ESD bleeding compared to their matched controls (12.5% versus 5.2%, p = 0.048; 8.1% versus 3.9%, p = 0.014). Post-ESD bleeding rates in antiplatelet agent users were significantly higher than those of their matched controls (8.3% versus 4.2%, p = 0.010). ATA usage increased the risk of post-ESD bleeding even after its sufficient cessation. Careful observation after ESD is required regardless of the cessation status of ATA.

Characterization of Physical and Biological Properties of a Caries-Arresting Liquid Containing Copper Doped Bioglass Nanoparticles.

Silver diamine fluoride (SDF) is an outstanding dental material for arresting and preventing caries, but some drawbacks, such as high flowability due to low viscosity and cytotoxicity to the pulp, have been reported. To overcome these problems, copper-doped bioactive glass nanoparticles (CuBGns) were combined with SDF. After synthesis, CuBGns were examined by physical analysis and added in SDF at different weight/volume% (SDF@CuBGn). After assessing physical properties (viscosity and flowability) of SDF@CuBGn, physicochemical properties (morphology before and after simulated body fluid (SBF) immersion and ion release) of SDF@CuBGn-applied hydroxyapatite (HA) discs were evaluated. Biological properties were further evaluated by cytotoxicity test to pulp stem cells and antibacterial effect on cariogenic organisms (Streptococcus mutans and Staphylococcus aureus). Combining CuBGns in SDF increased the viscosity up to 3 times while lowering the flowability. More CuBGns and functional elements in SDF (Ag and F) were deposited on the HA substrate, even after SBF immersion test for 14 days, and they showed higher Cu, Ca, and Si release without changing F and Ag release. Cell viability test suggested lower cytotoxicity in SDF@CuBGn-applied HA, while CuBGns in SDF boosted antibacterial effect against S. aureus, ~27% in diameter of agar diffusion test. In conclusion, the addition of CuBGn to SDF enhances viscosity, Ag and F deposition, and antibacterial effects while reducing cell toxicity, highlighting the role of bioactive CuBGns for regulating physical and biological effects of dental materials.

Improvement of Biological Effects of Root-Filling Materials for Primary Teeth by Incorporating Sodium Iodide.

Therapeutic iodoform (CHI3) is commonly used as a root-filling material for primary teeth; however, the side effects of iodoform-containing materials, including early root resorption, have been reported. To overcome this problem, a water-soluble iodide (NaI)-incorporated root-filling material was developed. Calcium hydroxide, silicone oil, and NaI were incorporated in different weight proportions (30:30:X), and the resulting material was denoted DX (D5~D30), indicating the NaI content. As a control, iodoform instead of NaI was incorporated at a ratio of 30:30:30, and the material was denoted I30. The physicochemical (flow, film thickness, radiopacity, viscosity, water absorption, solubility, and ion releases) and biological (cytotoxicity, TRAP, ARS, and analysis of osteoclastic markers) properties were determined. The amount of iodine, sodium, and calcium ion releases and the pH were higher in D30 than I30, and the highest level of unknown extracted molecules was detected in I30. In the cell viability test, all groups except 100% D30 showed no cytotoxicity. In the 50% nontoxic extract, D30 showed decreased osteoclast formation compared with I30. In summary, NaI-incorporated materials showed adequate physicochemical properties and low osteoclast formation compared to their iodoform-counterpart. Thus, NaI-incorporated materials may be used as a substitute for iodoform-counterparts in root-filling materials after further (pre)clinical investigation.

Investigating the Effects of Conditioned Media from Stem Cells of Human Exfoliated Deciduous Teeth on Dental Pulp Stem Cells.

Pulp regeneration has recently attracted interest in modern dentistry. However, the success ratio of pulp regeneration is low due to the compromising potential of stem cells, such as their survival, migration, and odontoblastic differentiation. Stem cells from human exfoliated deciduous teeth (SHED) have been considered a promising tool for regenerative therapy due to their ability to secrete multiple factors that are essential for tissue regeneration, which is achieved by minimally invasive procedures with fewer ethical or legal concerns than those of other procedures. The aim of this study is to investigate the potency of SHED-derived conditioned media (SHED CM) on dental pulp stem cells (DPSCs), a major type of mesenchymal stem cells for dental pulp regeneration. Our results show the promotive efficiency of SHED CM on the proliferation, survival rate, and migration of DPSCs in a dose-dependent manner. Upregulation of odontoblast/osteogenic-related marker genes, such as ALP, DSPP, DMP1, OCN, and RUNX2, and enhanced mineral deposition of impaired DPSCs are also observed in the presence of SHED CM. The analysis of SHED CM found that a variety of cytokines and growth factors have positive effects on cell proliferation, migration, anti-apoptosis, and odontoblast/osteogenic differentiation. These findings suggest that SHED CM could provide some benefits to DPSCs in pulp regeneration.

Machine Learning Model to Stratify the Risk of Lymph Node Metastasis for Early Gastric Cancer: A Single-Center Cohort Study.

Stratification of the risk of lymph node metastasis (LNM) in patients with non-curative resection after endoscopic resection (ER) for early gastric cancer (EGC) is crucial in determining additional treatment strategies and preventing unnecessary surgery. Hence, we developed a machine learning (ML) model and validated its performance for the stratification of LNM risk in patients with EGC. We enrolled patients who underwent primary surgery or additional surgery after ER for EGC between May 2005 and March 2021. Additionally, patients who underwent ER alone for EGC between May 2005 and March 2016 and were followed up for at least 5 years were included. The ML model was built based on a development set (70%) using logistic regression, random forest (RF), and support vector machine (SVM) analyses and assessed in a validation set (30%). In the validation set, LNM was found in 337 of 4428 patients (7.6%). Among the total patients, the area under the receiver operating characteristic (AUROC) for predicting LNM risk was 0.86 in the logistic regression, 0.85 in RF, and 0.86 in SVM analyses; in patients with initial ER, AUROC for predicting LNM risk was 0.90 in the logistic regression, 0.88 in RF, and 0.89 in SVM analyses. The ML model could stratify the LNM risk into very low (<1%), low (<3%), intermediate (<7%), and high (≥7%) risk categories, which was comparable with actual LNM rates. We demonstrate that the ML model can be used to identify LNM risk. However, this tool requires further validation in EGC patients with non-curative resection after ER for actual application.

Outdoor Localization Using BLE RSSI and Accessible Pedestrian Signals for the Visually Impaired at Intersections.

One of the major challenges for blind and visually impaired (BVI) people is traveling safely to cross intersections on foot. Many countries are now generating audible signals at crossings for visually impaired people to help with this problem. However, these accessible pedestrian signals can result in confusion for visually impaired people as they do not know which signal must be interpreted for traveling multiple crosses in complex road architecture. To solve this problem, we propose an assistive system called CAS (Crossing Assistance System) which extends the principle of the BLE (Bluetooth Low Energy) RSSI (Received Signal Strength Indicator) signal for outdoor and indoor location tracking and overcomes the intrinsic limitation of outdoor noise to enable us to locate the user effectively. We installed the system on a real-world intersection and collected a set of data for demonstrating the feasibility of outdoor RSSI tracking in a series of two studies. In the first study, our goal was to show the feasibility of using outdoor RSSI on the localization of four zones. We used a k-nearest neighbors (kNN) method and showed it led to 99.8% accuracy. In the second study, we extended our work to a more complex setup with nine zones, evaluated both the kNN and an additional method, a Support Vector Machine (SVM) with various RSSI features for classification. We found that the SVM performed best using the RSSI average, standard deviation, median, interquartile range (IQR) of the RSSI over a 5 s window. The best method can localize people with 97.7% accuracy. We conclude this paper by discussing how our system can impact navigation for BVI users in outdoor and indoor setups and what are the implications of these findings on the design of both wearable and traffic assistive technology for blind pedestrian navigation.

High HbA1c is associated with decreased 6-month survival and poor outcomes after out-of-hospital cardiac arrest: a retrospective cohort study.

BACKGROUND: To evaluate the associations between glycated hemoglobin (HbA1c) at admission and 6-month mortality and outcomes after out-of-hospital cardiac arrest (OHCA) treated by hypothermic targeted temperature management (TTM). METHODS: This single-center retrospective cohort study included adult OHCA survivors who underwent hypothermic TTM from December 2011 to December 2019. High HbA1c at admission was defined as a level higher than 6%. Poor neurological outcomes were defined as cerebral performance category scores of 3-5. The primary outcome was 6-month mortality. The secondary outcome was the 6-month neurological outcome. Descriptive statistics, log-rank tests, and multivariable regression modeling were used for data analysis. RESULTS: Of the 302 patients included in the final analysis, 102 patients (33.8%) had HbA1c levels higher than 6%. The high HbA1c group had significantly worse 6-month survival (12.7% vs. 37.5%, p < 0.001) and 6-month outcomes (89.2% vs. 73.0%, p = 0.001) than the non-high HbA1c group. Kaplan-Meier analysis and the log-rank test showed that the survival time was significantly shorter in the patients with HbA1c > 6% than in those with HbA1c ≤6%. In the multivariable logistic regression analysis, HbA1c > 6% was independently associated with 6-month mortality (OR 5.85, 95% CI 2.26-15.12, p < 0.001) and poor outcomes (OR 4.18, 95% CI 1.41-12.40, p < 0.001). CONCLUSIONS: This study showed that HbA1c higher than 6% at admission was associated with increased 6-month mortality and poor outcomes in OHCA survivors treated with hypothermic TTM. Poor long-term glycemic management may have prognostic significance after cardiac arrest.

Discovery and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer.

BACKGROUND: Biomarkers are needed for noninvasive early detection of gastric cancer (GC). We investigated salivary extracellular RNA (exRNA) biomarkers as potential clinical evaluation tools for GC. METHODS: Unstimulated whole saliva samples were prospectively collected from 294 individuals (163 GC and 131 non-GC patients) who underwent endoscopic evaluation at the Samsung Medical Center in Korea. Salivary transcriptomes of 63 GC and 31 non-GC patients were profiled, and mRNA biomarker candidates were verified with reverse transcription quantitative real-time PCR (RT-qPCR). In parallel, microRNA (miRNA) biomarkers were profiled and verified with saliva samples from 10 GC and 10 non-GC patients. Candidate biomarkers were validated with RT-qPCR in an independent cohort of 100/100 saliva samples from GC and non-GC patients. Validated individual markers were configured into a best performance panel. RESULTS: We identified 30 mRNA and 15 miRNA candidates whose expression pattern associated with the presence of GC. Among them, 12 mRNA and 6 miRNA candidates were verified with the discovery cohort by RT-qPCR and further validated with the independent cohort (n = 200). The configured biomarker panel consisted of 3 mRNAs (SPINK7, PPL, and SEMA4B) and 2 miRNAs (MIR140-5p and MIR301a), which were all significantly down-regulated in the GC group, and yielded an area under the ROC curve (AUC) of 0.81 (95% CI, 0.72-0.89). When combined with demographic factors, the AUC of the biomarker panel reached 0.87 (95% CI, 0.80-0.93). CONCLUSIONS: We have discovered and validated a panel of salivary exRNA biomarkers with credible clinical performance for the detection of GC. Our study demonstrates the potential utility of salivary exRNA biomarkers in screening and risk assessment for GC.

CD4+ T-cell-dependent goblet cell proliferation and expulsion of Gymnophalloides seoi from the intestine of C57BL/6 mice.

Mechanisms for the spontaneous worm expulsion from the host intestine are not well understood in gastrointestinal trematode models. We studied the role of CD4+ T-helper cells in mediating goblet cell hyperplasia and expulsion of Gymnophalloides seoi from the intestines of C57BL/6 (resistant) and ICR (susceptible) mice. C57BL/6 mice expelled all G. seoi worms within 4 days post-infection (PI), while ICR mice did not completely expel worms until day 7 PI. This difference in worm expulsion was associated with high numbers of mucosal goblet cells in C57BL/6 mice along with alteration of the mucin quality, with changes in the terminal sugar chain and high levels of IL-4 and IL-5 mRNA expression in mesenteric lymph nodes. Adoptive transfer of mucosal CD4+ T-helper cells to syngeneic mice elicited strong goblet cell hyperplasia and a notably accelerated worm expulsion. However, this T-helper cell transfer had no relationship with the alteration of mucin quality. The results showed that CD4+ T-helper cells play an important role as a mediator of goblet cell hyperplasia, but not for functional activation of goblet cells. It is suggested that both T-cell dependent and independent mechanisms operate for expulsion of G. seoi from the mouse intestine.

Procedure-related musculoskeletal symptoms in gastrointestinal endoscopists in Korea.

AIM: To determine the prevalence and risk factors of work-related musculoskeletal disorders in gastrointestinal endoscopists in Korea. METHODS: A survey of musculoskeletal symptoms, using a self-administered questionnaire, was conducted on 55 endoscopists practicing in general hospitals or health promotion centers. RESULTS: Forty-nine (89.1%) endoscopists reported musculoskeletal pain on at least one anatomic location and 37 (67.3%) endoscopists complained of pain at rest. Twenty-six (47.3%) endoscopists had severe musculoskeletal pain defined as a visual analogue score greater than 5.5. Factors related to the development of severe pain were (1) standing position during upper endoscopy, (2) specific posture/habit during endoscopic procedures, and (3) multiple symptomatic areas. Finger pain was more common in beginners, whereas shoulder pain was more common in experienced endoscopists. Sixteen percent of symptomatic endoscopists have modified their practice or reduced the number of endoscopic examinations. Only a few symptomatic endoscopists had sought professional consultation with related specialists. CONCLUSION: The prevalence of musculoskeletal pain in endoscopists is very high. The location of pain was different between beginners and experienced endoscopists. Measures for the prevention and adequate management of endoscopy-related musculoskeletal symptoms are necessary.

Methylation of p16INK4A and mitotic arrest defective protein 2 (MAD2) genes in gastric marginal-zone B-cell lymphomas.

BACKGROUND: Products of cyclin-dependent kinase inhibitor p16(INK4A)and mitotic arrest defective protein 2 (MAD2) genesare key regulator proteins at the G1 restriction point and mitotic checkpoint of the cell cycle. The objective of this study was to investigate the role of promoter methylation of p16(INK4A) and MAD2 genes in gastric marginal-zone B-cell lymphoma (MZBCL). MATERIALS AND METHODS: Gastric biopsies from 40 patients were analyzed by methylation-specific polymerase chain reaction, and the methylation status was compared with the results of BCL10 expression and t(11;18)(q21;q21) translocation. RESULTS AND CONCLUSION: p16(INK4A) was methylated in 30 of 40 MZBCLs (75%). The lymphomas with p16(INK4A) methylation tended to be negative for t(11;18)(q21;q21) (p = 0.011). MAD2 gene was methylated in 23 of 38 MZBCLs (61%). Lymphomas with MAD2 gene methylation more frequently expressed BCL10 (p = 0.037). These methylation profiles suggest that p16(INK4A) and MAD2 gene may play a role in the pathogenesis of MZBCL via different pathways; MAD2 gene is Helicobacter pylori independent with a close association with BCL10 while p16(INK4A) is H. pylori dependent with an inverse correlation with the t(11;18)(q21;q21) translocation.

Endoscopic mucosal resection of early gastric cancer: Experiences in Korea.

Endoscopic mucosal resection (EMR) has been established as one of the treatment options for early gastric cancer (EGC). However, there are many uncertain areas such as indications of EMR, best treatment methods, management of complications and follow-up methods after the procedure. Most studies on this topic have been carried out by researchers in Japan. In Korea, gastric cancer is the most common malignant disease, and the second leading cause of cancer death. In these days, EMR for EGC is widely performed in many centers in Korea. In this review, we will provide an overview of the techniques and outcomes of EMR in Korea.

Resistance of Lactobacillus plantarum KCTC 3099 from Kimchi to oxidative stress.

The antioxidative capacity of two lactic acid bacteria isolated from Kimchi, a Korean fermented food, was evaluated by measuring the resistance to reactive oxygen species (ROS) and compared with that of Lactobacillus rhamnosus GG as a positive control. Both intact cells and cell-free extracts of Lactobacillus plantarum KCTC 3099 exhibited higher antioxidative activity in inhibiting lipid peroxidation among the strains evaluated with an inhibitory level of 38.6% and 48.5%, respectively. To evaluate the resistance of the two lactic acid bacteria to ROS, we tested their survival in the presence of 1 mM hydrogen peroxide, 0.4 mM hydroxyl radicals, and superoxide anions induced by 10 mM paraquat. L. plantarum KCTC 3099 was viable even after 8 hours in the presence of both 1 mM hydrogen peroxide and 0.4 mM hydroxyl radicals. Moreover, the survival of L. plantarum KCTC 3099 was not affected by superoxide anions generated by using paraquat, indicating that it has resistance to superoxide anions. To define the antioxidative mechanism, superoxide dismutase (SOD) and metal ion chelating activities were determined. L. plantarum KCTC 3099 presented little SOD activity, but had the higher level of chelating activity for both Fe2+ and Cu2+ metal ions at 13.6 ppm and 23.9 ppm, respectively. These results suggested that the antioxidative capacity of L. plantarum KCTC 3099 is apparently caused by chelating metal ions rather than by SOD activation.