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Abstract Smart windows, capable of tailoring light transmission, can significantly reduce energy consumption in building services. While mechano-responsive windows activated by strains are promising candidates, they face long-lasting challenges in which the space for the light scatterer’s operation has to be enlarged along with the window size, undermining the practicality. Recent attempts to tackle this challenge inevitably generate side effects with compromised performance in light modulation. Here, we introduce a cuttlefish-inspired design to enable the closing and opening of pores within the 3D porous structure by through-thickness compression, offering opacity and transparency upon release and compression. By changing the activation mode from the conventional in-plane to through-thickness direction, the space requirement is intrinsically decoupled from the lateral size of the scatterer. Central to our design is the asymmetry of pore orientation in the 3D porous structure. These inclined pores against the normal direction increase the opaqueness upon release and improve light modulation sensitivity to compression, enabling transmittance regulation upon compression by an infinitesimal displacement of 50 μm. This work establishes a milestone for smart window technologies and will drive advancements in the development of opto-electric devices.

Background/Aims: This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. Methods: The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Results: Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Conclusions: Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.

Background/Aims: Although guidelines exist regarding the evaluation and management of patients with chronic constipation (CC), little is known about real-world clinical practice patterns. This study aimed to evaluate the various practices used to manage CC patients in various clinical settings in South Korea. Methods : A nationwide web-based survey was conducted, randomly selecting gastroenterologists and non-gastroenterologists. The 25-item questionnaire included physicians’ perceptions and practices regarding the available options for diagnosing and managing CC patients in Korea. Results : The study participants comprised 193 physicians (86 gastroenterologists, 44.6%) involved in the clinical management of CC patients. The mean clinical experience was 12 years. Only 21 of 193 respondents (10.9%) used the Rome criteria when diagnosing CC. The Bristol Stool Form Scale was used by 29% of the respondents (56/193), while the digital rectal examination was performed by 11.9% of the respondents (23/193). Laboratory testing and colonoscopies were performed more frequently by gastroenterologists than by non-gastroenterologists (both p=0.001). Physiologic testing was used more frequently by gastroenterologists (p=0.046), physicians at teaching hospitals, and physicians with clinical experience ≤10 years (both p

Background/Aims This study aimed to evaluate the characteristics of endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasonography (EUS)-related adverse events (AEs) that eventually lead to medical disputes or claims on medical professional liability. Methods Medical disputes for ERCP/EUS-related AEs filed in the Korea Medical Dispute Mediation and Arbitration Agency between April 2012 and August 2020 were evaluated using corresponding medical records. AEs were categorized into three sections: procedure-related, sedation-related, and safety-related AEs. Results Among a total of 34 cases, procedure-related AEs were 26 (76.5%; 12 duodenal perforations, 7 post-ERCP pancreatitis, 5 bleedings, 2 perforations combined with post-ERCP pancreatitis); sedation-related AEs were 5 (14.7%; 4 cardiac arrests, 1 desaturation), and safety-related AEs were 5 (8.8%; 1 follow-up loss for stent removal, 1 asphyxia, 1 fall). Regarding clinical outcomes, 20 (58.8%) were fatal and eventually succumbed to AEs. For the types of medical institutions, 21 cases (61.8%) occurred at tertiary or academic hospitals, and 13 (38.2%) occurred at community hospitals. Conclusions The ERCP/EUS-related AEs filed in Korea Medical Dispute Mediation and Arbitration Agency showed distinct features: duodenal perforation was the most frequent AE, and clinical outcomes were fatal, resulting in at least more than permanent physical impairment.

Graphite tattoos are rarely reported because they are mainly caused by an accidental injury or habits during childhood that cause a pencil to penetrate the oral mucosa. Unlike other pigmentations, it stains layers that are deeper than the subepithelial and mucosal layers, and in most cases, it takes the form of a grayish black macule. This case report describes depigmentation with the denudation technique that was followed by a novel approach of using platelet-rich fibrin to cover exposed bone. A 41-year-old male patient presented with an aesthetic complaint from a grayish black staining on the labial gingiva near the maxillary central and lateral incisors. The lesion was diagnosed as a graphite tattoo due to the patient’s history of sticking his gum with pencils when he was young. The entire pigmented gingiva was surgically removed and covered with two layers of PRF membrane to protect the exposed bone surface and provide an extracellular matrix for migration of gingival fibroblasts. Healing patterns were observed at 1, 2, 4, and 8 weeks, and satisfactory clinical and aesthetic results were obtained. Creeping attachment was observed at 8 years postop, and there was no recurrence for a long-term period of 13 years.

Abstract Background/Aims Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Ultrasound, the most used tool for diagnosing NAFLD, is operator-dependent and shows suboptimal performance in patients with mild steatosis. However, few studies have been conducted on whether alternative noninvasive methods are useful for diagnosing mild hepatic steatosis. Also, little is known about whether noninvasive tests are useful for grading the severity of hepatic steatosis or the degree of intrahepatic inflammation. Therefore, we aimed to evaluate whether the HSI, the FLI and HU values in CT could be used to discriminate mild hepatic steatosis and to evaluate the severity of hepatic steatosis or the degree of intrahepatic inflammation in patients with low-grade fatty liver disease using liver biopsy as a reference standard. Methods Demographic, laboratory, CT imaging, and histological data of patients who underwent liver resection or biopsy were analyzed. The performance of the HSI, HU values and the FLI for diagnosing mild hepatic steatosis was evaluated by calculating the area under the receiver operating characteristic curve. Whether the degree of hepatic steatosis and intrahepatic inflammation could be predicted using the HSI, HU values or the FLI was also analyzed. Moreover, we validate the results using magnetic resonance imaging proton density fat fraction as an another reference standard. Results The AUROC for diagnosing mild hepatic steatosis was 0.810 (p

Objective Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one’s physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. Methods Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. Results Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. Conclusion This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

Recently, reactive materials have been developed for penetrative projectiles to improve impact resistance and energy capacity. However, the design of a reactive material structure, involving shape and size, is challenging because of difficulties such as high non-linearity of impact resistance, manufacturing limitations of reactive materials and high expenses of penetration experiments. In this study, a design optimization methodology for the reactive material structure is developed based on the finite element analysis. A finite element model for penetration analysis is introduced to save the expenses of the experiments. Impact resistance is assessed through the analysis, and result is calibrated by comparing with experimental results. Based on the model, topology optimization is introduced to determine shape of the structure. The design variables and constraints of the optimization are proposed considering the manufacturing limitations, and the optimal shape that can be manufactured by cold spraying is determined. Based on the optimal shape, size optimization is introduced to determine the geometric dimensions of the structure. As a result, optimal design of the reactive material structure and steel case of the penetrative projectile, which maximizes the impact resistance, is determined. Using the design process proposed in this study, reactive material structures can be designed considering not only mechanical performances but also manufacturing limitations, with reasonable time and cost.

Background/Aims L-carnitine is potentially beneficial in patients with hepatic encephalopathy (HE). We aimed to evaluate the impact of L-carnitine on the quality of life and liver function in patients with liver cirrhosis and covert HE. Methods We conducted an investigator-initiated, prospective, multi-center, double-blind, randomized phase III trial in patients with covert HE. A total of 150 patients were randomized 1:1 to L-carnitine (2 g/day) or placebo for 24 weeks. Changes in quality of life and liver function were assessed at 6 months. The model for end-stage liver disease (MELD), the 36-Item Short Form Survey (SF-36), the psychometric hepatic encephalopathy score (PHES), and the Stroop Test were evaluated in all patients. Results The total SF-36 score significantly improved in the L-carnitine group after 24 weeks (difference: median, 2; interquartile range, 0 to 11; p < 0.001); however, these values were comparable between the two groups. Furthermore, there was a significant ordinal improvement in PHES scores among patients with minimal HE who were in the L-carnitine group (p = 0.007). Changes in the total carnitine level also positively correlated with improvements in the Stroop test in the L-carnitine group (color test, r = 0.3; word test, r = 0.4; inhibition test, r = 0.5; inhibition/switching test, r = 0.3; all p < 0.05). Nevertheless, the MELD scores at week 24 did not differ between the groups. Conclusions Twenty-four weeks of L-carnitine supplementation was safe but ineffective in improving quality of life and liver function.

Background/Aims: Biliary complications including biliary strictures and bile leaks are the most common complications that occur after liver transplantation (LT). Endoscopic treatment with endoscopic retrograde cholangiography (ERC) is considered the first-line treatment, and percutaneous transhepatic cholangiography (PTC) can serve as an alternative or rescue therapy. However, nationwide clinical data on the frequency of ERC and PTC following LT have not yet been investigated. Methods: Using the nationwide claims database, we investigated patients who underwent LT between 2012 and 2014 in Korea and followed them until 2015. We analyzed the prevalence and characteristics of patients and biliary procedures, including ERC and PTC implemented after LT. Results: A total of 3,481 patients underwent LT during the 3-year study period. Among them, 3.0% of patients underwent biliary intervention postoperatively during the same hospitalization period, and 21.4% of patients received biliary intervention later on after initially being discharged from the hospital following LT. A total of 16.9% and 12.1% of patients underwent ERC and PTC after LT, respectively. The median period from LT to the first biliary intervention was 7.8 months (interquartile range, 3.5 to 14.6 months), and these patients underwent an average of 3.2±2.8 biliary procedures during the follow-up period. Patients undergoing living donor LT were more than twice as likely to undergo biliary procedures as those undergoing deceased donor LT (25.5% vs 12.1%). Conclusions: Approximately one-fourth of patients in Korea who underwent LT subsequently underwent ERC or PTC. Compared with deceased donor LT patients, those undergoing living donor LT underwent more biliary interventions and were more difficult to treat.

This review introduces the updated Chicago Classification ver. 4.0 for esophageal motility disorders using metrics from high-resolution manometry (HRM). The Chicago Classification ver. 4.0 was developed by 52 diverse international experts using validated methodologies over 2 years. Key updates in Chicago Classification ver. 4.0 include: 1) a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, 2) a refined definition of esophagogastric junction outflow obstruction, and 3) emphasis on supportive testing with barium esophagogram with tablet and/or functional lumen imaging probe.

Background/Aims Systemic sclerosis (SSc) is associated with a wide range of gastrointestinal (GI) changes. The University of California–Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) instrument is a self-administered GI assessment instrument for patients with SSc. We developed a Korean version of the UCLA SCTC GIT 2.0 instrument and evaluated its reliability and internal consistency. Methods The participants were 37 Korean patients with SSc. Translation and cross-cultural adaptation of the UCLA SCTC GIT 2.0 were performed according to international standardized guidelines. We evaluated reproducibility by calculating the intraclass correlation coefficients and assessed the internal consistency of the Korean version of the UCLA SCTC GIT 2.0. We assessed its construct validity by evaluating its correlations with the Short Form Health Survey version 2 and EQ-5D scores by means of Spearman correlation analyses. Results Patients with SSc were mostly women (89.19%) with a mean age of 52.2 years, median disease duration of 24 months, and median modified Rodnan total skin score of 4. The median total GIT score on the UCLA SCTC GIT 2.0 was 0.3. The UCLA SCTC GIT 2.0 Korean version showed excellent internal consistency (Cronbach’s α of total GIT score = 0.863). Most domains of the ULCA SCTC GIT 2.0 were correlated with those of the EuroQol (EQ)-5D score. Conclusions The Korean version of the UCLA SCTC GIT 2.0 has acceptable internal consistency, reliability, and validity. Therefore, it can be used to assess GIT involvement in Korean patients with SSc.

Background/Aims This study aimed to determine the current status of facilities, equipment, and personnel for endoscopic sedation from endoscopy units of representative hospitals in South Korea. Methods A questionnaire survey was conducted on 50 qualified endoscopy units accredited by the Korean Society of Gastrointestinal Endoscopy. Results All included endoscopy units had regulations and educational programs regarding sedation training for endoscopists and nursing personnel. There present one assisting nurse during endoscopy in 35 units (70%) and at least two nurses in 12 units (24.0%). All endoscopy units had examination rooms equipped with oxygen supply and suction systems. Endoscopist-directed sedation was performed in 48 units (96.0%). Propofol-based sedation was the most used sedation method. All units had a separate recovery bay. The daily number of patients per bed was greater than 10 in 17 units (34.0%). In 26 (52.0%) units, a single nurse cared for ≥10 patients per day. All the units fulfilled the discharge criteria. Conclusions This study presents data regarding endoscopic sedation clinical practice in 50 endoscopy units in South Korea. This study presents the current status of endoscopic sedation clinical practice in 50 qualified endoscopy units accredited by the KSGE, which provide excellent quality management.

A training dataset that is limited to a specific endoscope model can overfit artificial intelligence (AI) to its unique image characteristics. The performance of the AI may degrade in images of different endoscope model. The domain adaptation algorithm, i.e., the cycle-consistent adversarial network (cycleGAN), can transform the image characteristics into AI-friendly styles. We attempted to confirm the performance degradation of AIs in images of various endoscope models and aimed to improve them using cycleGAN transformation. Two AI models were developed from data of esophagogastroduodenoscopies collected retrospectively over 5 years: one for identifying the endoscope models, Olympus CV-260SL, CV-290 (Olympus, Tokyo, Japan), and PENTAX EPK-i (PENTAX Medical, Tokyo, Japan), and the other for recognizing the esophagogastric junction (EGJ). The AIs were trained using 45,683 standardized images from 1,498 cases and validated on 624 separate cases. Between the two endoscope manufacturers, there was a difference in image characteristics that could be distinguished without error by AI. The accuracy of the AI in recognizing gastroesophageal junction was >0.979 in the same endoscope-examined validation dataset as the training dataset. However, they deteriorated in datasets from different endoscopes. Cycle-consistent adversarial network can successfully convert image characteristics to ameliorate the AI performance. The improvements were statistically significant and greater in datasets from different endoscope manufacturers [original → AI-trained style, increased area under the receiver operating characteristic (ROC) curve, P-value: CV-260SL → CV-290, 0.0056, P = 0.0106; CV-260SL → EPK-i, 0.0182, P = 0.0158; CV-290 → CV-260SL, 0.0134, P < 0.0001; CV-290 → EPK-i, 0.0299, P = 0.0001; EPK-i → CV-260SL, 0.0215, P = 0.0024; and EPK-i → CV-290, 0.0616, P < 0.0001]. In conclusion, cycleGAN can transform the diverse image characteristics of endoscope models into an AI-trained style to improve the detection performance of AI.

A piezoelectric energy harvester (PEH) transduces mechanical energy into electrical energy, which can be utilized as an energy source for self-powered or low-power devices. Therefore, maximizing the power of a PEH is a crucial design objective. It is well known that structural designs are firstly conducted for controlling resonance characteristics, and then circuit designs are pursued through impedance matching for improving power. However, a PEH contains solid mechanics, electrostatics, and even a circuit-coupled multi-physics system. Therefore, this research aims to design a PEH considering a circuit-coupled multi-physics. As a design process, a conceptual design is developed by topology optimization, and a detailed design is developed sequentially by applying size optimization as a post-processing step to refine the conceptual design results for manufacturable design. In the two optimization processes, design optimizations of a structure coupled with circuit resistor are performed to maximize the power, where the electrical and mechanical interactions between PZT, substrate, and circuit resistor are simultaneously considered. Additionally, stress constraints are also added for structural safety to ensure operational life of PEH. As a result of the proposed design methodology, a manufacturable design of PEH having maximum power and operational life is obtained with power density of 6.61 μWg−2mm−3.

Background/Aims Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) can serve as biomarkers for diagnosing and assessing disease activity in ulcerative colitis (UC). We investigated their clinical significance in UC. Methods We analyzed 48 patients with UC who underwent measurement of fecal calprotectin (FC) and endoscopy and 96 age- and sex-matched healthy controls. NLR and PLR were compared between the patients and healthy controls. The endoscopic activity was divided into 2 groups: group 1 (mild to moderate inflammation) and group 2 (severe inflammation) according to the Mayo endoscopic subscore in UC. Results To diagnose UC, the optimal cutoff of NLR and PLR was 2.26 (sensitivity 54.2%; specificity 90.6%; positive likelihood ratio 5.778, 95% confidence interval [CI] 2.944–11.339; area under the curve [AUC] 0.774, 95% CI, 0.690–0.859) and 179.8 (sensitivity 35.4%; specificity 90.6%; positive likelihood ratio 3.778, 95% CI 1.821–7.838; AUC 0.654, 95% CI 0.556–0.753), respectively. The optimal cutoff to differentiate group 1 and group 2 was 3.44, 175.9, and 453 µg/g for NLR, PLR, and FC, respectively (sensitivity, 63.6% vs. 90.9% vs. 81.8%; specificity, 81.1% vs. 78.4% vs. 73.0%; positive likelihood ratio, 3.364 vs. 4.205 vs. 3.027; AUC, 0.714 vs. 0.897 vs. 0.813). PLR had the highest AUC and positive likelihood ratio. Conclusions NLR and PLR help differentiate patients with UC from healthy controls. NLR, PLR, and FC indicate endoscopic activity and may reflect intestinal mucosal conditions.

Background: Malignant biliary obstruction (MBO) is usually caused by biliary tract cancer or pancreatic cancer. This study was performed to summarize the current situation regarding palliative endoscopic retrograde biliary drainage (ERBD) for MBO in Korea and to determine its clinical significance by analyzing representative nationwide data. Methods: Patients that underwent palliative ERBD for MBO between 2012 and 2015 were identified using the Health Insurance Review and Assessment database, which covers the entire Korean population. We assessed clinical characteristics and complications and compared the clinical impacts of initial metal and plastic stenting in these patients. Results: A total of 9,728 subjects (mean age, 65 ± 11.4 years; male, 61.4%) were identified and analyzed. The most common diagnosis was malignant neoplasm of liver and intrahepatic bile ducts (32.1%) and this was followed by extrahepatic or Ampulla of Vater cancer and pancreatic cancer. Initial plastic stent(s) placement was performed in 52.9% of the study subjects, and metal stent(s) placement was performed in 23.3%. The number of sessions of endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage (PTBD) was significantly higher in patients that underwent initial plastic stenting than in patients that underwent metal stenting (2.2 ± 1.7 vs 1.8 ± 1.4, P < 0.0001), but rates of post-ERCP pancreatitis, hospital days, and time to second ERCP or PTBD were not significantly different. Conclusion: This nationwide assessment study suggests that initial metal stenting is associated with fewer sessions of total ERCP or PTBD following the initial procedure, despite the preference for initial plastic stenting in Korea.

Abstract Circulating tumor cells (CTCs) are receiving a great amount of scientific interest as a diagnostic biomarker for various types of cancer. Despite the recent progress in the development of highly sensitive CTC isolation devices, post-capture analysis of CTCs is still hindered by technical challenges associated with their rarity. Herein, we present a multi-modal CTC screening platform which is capable to analyze CTCs and CTC-derived extracellular vesicles (EVs), simultaneously from a single sample. Cytochalasin B (CB) treatment promotes cells to release large number of EVs from their surface, as demonstrated by CB-treated cells (5 µg/mL for 3 h) secreting 3.5-fold more EVs, compared to the non-treated cells. CB further generates 1.7-fold more EVs from the cells captured on our CTC filtration device (the fabric filter), compared to those from the cell culture flasks, owing to its multiple pore structure design which reduces the non-specific binding of EVs. Both CB-treated cancer cells and CB-induced EVs are found to overexpress tumor-associated markers, demonstrating a potential for the development of CTC dual-screening platform. Collectively, the results presented in this study reveal that our multi-modal cancer screening platform can synergistically improve the reliability and efficacy of the current CTC analysis systems.

Endoscopic quality indicators can be classified into three categories, namely facilities and equipment, endoscopic procedures, and outcome measures. In 2019, the Korean Society of Gastrointestinal Endoscopy updated the accreditation of qualified endoscopy unit assessment items for these quality indicators to establish competence and define areas of continuous quality improvement. Here, we presented the updated program guidelines on the facilities, procedures, and performance of the accredited endoscopy unit. Many of these items have not yet been validated. However, the updated program will help in establishing competence and defining areas of continuous quality improvement in Korean endoscopic practice.

Abstract Background Protein kinase C iota (PKCι) and protein kinase C zeta (PKCζ) are two atypical protein kinase (aPKC) enzymes that contribute to cell proliferation and cancer development. The Hippo/YAP pathway is commonly disrupted and upregulated in cancers. Herein, the expression patterns and clinical relevance of PKCι and PKCζ are evaluated in relation to YAP, a downstream effector of Hippo, in lung adenocarcinoma (LAC). The protein and mRNA expression levels of PKCι, PKCζ, YAP, and their phosphorylated forms, namely p-PKCι, p-PKCζ and p-YAP, are evaluated in relation to clinicopathological factors, including patient survival. Methods A total of 200 primary LAC tissue samples were examined by immunohistochemistry for PKCι, p-PKCι, PKCζ, p-PKCζ, YAP, and p-YAP protein expression. Sixty pairs of LAC and non-neoplastic lung tissue samples were assessed for PRKCI, PRKCZ, and YAP mRNA levels. PKCι, p-PKCι, PKCζ, and p-PKCζ protein expression were evaluated by Western blot analysis in the PC9 and PC9/GR LAC cell lines with YAP modulation. Results LAC demonstrated cytoplasmic PKCι, p-PKCι, PKCζ, and p-PKCζ immunostaining patterns. Positive aPKC protein expressions were related with poor patient survival. Especially, increased p-PKCι protein expression was significantly correlated with higher pathological stage and shortened overall survival. YAP overexpression contributes phosphorylation of PKCι and PKCζ protein expression in the LAC cell line. Conclusions PKCι and PKCζ are related to YAP in LAC. PKCι and PKCζ play distinct roles in LAC; specifically, p-PKCι overexpression is suggested to underlie factors that indicate a poor prognosis.

KRISO (Korea Research Institute of Ship & Ocean Engineering) started a project to develop the core algorithms for autonomous intervention using an underwater robot in 2017. This paper introduces the development of the robot platform for the core algorithms, which is an ROV (Remotely Operated Vehicle) type with one 7-function manipulator. Before the detailed design of the robot platform, the 7E-MINI arm of the ECA Group was selected as the manipulator. It is an electrical type, with a weight of 51 kg in air (30 kg in water) and a full reach of 1.4 m. To design a platform with a small size and light weight to fit in a water tank, the medium-size manipulator was placed on the center of platform, and the structural analysis of the body frame was conducted by ABAQUS. The robot had an IMU (Inertial Measurement Unit), a DVL (Doppler Velocity Log), and a depth sensor for measuring the underwater position and attitude. To control the robot motion, eight thrusters were installed, four for vertical and the rest for horizontal motion. The operation system was composed of an on-board control station and operation S/W. The former included devices such as a 300 VDC power supplier, Fiber-Optic (F/O) to Ethernet communication converter, and main control PC. The latter was developed using an ROS (Robot Operation System) based on Linux. The basic performance of the manufactured robot platform was verified through a water tank test, where the robot was manually operated using a joystick, and the robot motion and attitude variation that resulted from the manipulator movement were closely observed.

Background/Aims We evaluated the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) in patients with chronic hepatitis C virus (HCV) infection on hemodialysis. Methods : We performed a single-arm, multicenter prospective study. Twenty-one chronic hemodialysis patients with HCV infection were prospectively enrolled from February 2016 to April 2017. We evaluated the virological responses at weeks 4, 12, and 24 (end of treatment [EOT]) and the sustained virological response at 12 weeks after the EOT (SVR12). The tolerability and safety of the drugs were also assessed. Results : None of the 20 patients had the NS5A resistance-associated variant (NS5A RAV), and one patient was indeterminate for the NS5A RAV. Seventeen patients (80%) completed the 24 weeks of treatment with DCV and ASV. Four patients discontinued the study prior to week 12. In an intention-to-treat analysis, the SVR12 was 76.1%. In a per-protocol analysis, patients who completed DCV and ASV treatment achieved an SVR12 of 100%. DCV and ASV were well tolerated by the majority of patients. Three patients discontinued treatment due to adverse events (AEs) including dizziness, dyspnea, and neutropenia. The patient with indeterminate NS5A RAV showed viral breakthrough and discontinued treatment. Conclusion : s DCV and ASV combination therapy in chronic hemodialysis patients with HCV infection achieved a high SVR12 rate with few AEs. To maximize the SVR12 rate, it is important to identify candidates by baseline RAV testing. Close monitoring of the safety and tolerability of DCV and ASV may be necessary in HCV-infected patients on hemodialysis. (ClinicalTrials.gov ID NCT02580474)

Faults in vehicle sensor connectors are crucial to the safety of a vehicle. Once the connector is loosened according to the reduction of its contact forces, its electrical contact resistance may be increased, causing unexpected errors in sensor systems. However, such error mechanisms have enormously diverse causes that have not yet been identified. This study proposes a process to analyze the causes influencing the connector contact force and resistance by employing a combination of numerical and experimental methods. Specifically, the causes of variation of contact force are numerically analyzed and their influence on the electrical contact resistance is experimentally studied. Precise 3D models of a commercial vehicle sensor connector are developed based on a 3D tomography, and a 3D finite element (FE) simulation is employed to estimate the connector contact force, considering plastic deformation. After classifying potential causes into three categories, two major factors are selected: manufacturing tolerance occurring during the connector manufacturing process and plastic deformation occurring during the vehicle maintenance process. The factors are observed to substantially reduce the contact force (by ~14.6 or 19%). The impact of the reduced contact force is validated in sequential experiments, and exhibits a nonlinear relationship between the contact force and corresponding contact resistance. In addition, the experiments also consider simulated manufacturing and maintenance factors, and demonstrate an increased contact resistance by the functions of the decreased contact force with minor measurement errors (

Background: Myofibroblasts are known to play a key role in the development of idiopathic pulmonary fibrosis (IPF). Two drugs, pirfenidone and nintedanib, are the only approved therapeutic options for IPF, but their applications are limited due to their side effects. Thus, curative IPF drugs represent a huge unmet medical need. Methods: A mouse hepatic stellate cell (HSC) line was established that could robustly differentiate into myofibroblasts upon treatment with TGF-β. Eupatilin was assessed in diseased human lung fibroblasts from IPF patients (DHLFs) as well as in human lung epithelial cells (HLECs). The drug's performance was extensively tested in a bleomycin-induced lung fibrosis model (BLM). Global gene expression studies and proteome analysis were performed. Findings: Eupatilin attenuated disease severity of BLM in both preventative and therapeutic studies. The drug inhibited the in vitro transdifferantiation of DHLFs to myofibroblasts upon stimulation with TGF-β. No such induction of the in vitro transdifferantiation was observed in TGF-β treated HLECs. Specific carbons of eupatilin were essential for its anti-fibrotic activity. Eupatilin was capable of dismantling latent TGF-β complex, specifically by eliminating expression of the latent TGF-β binding protein 1 (LTBP1), in ECM upon actin depolymerization. Unlike eupatilin, pirfenidone was unable to block fibrosis of DHLFs or HSCs stimulated with TGF-β. Eupatilin attenuated phosphorylation of Smad3 by TGF-β. Eupatilin induced myofibroblasts to dedifferentiate into intermediate HCS-like cells. Interpretation: Eupatilin may act directly on pathogenic myofibroblasts, disarming them, whereas the anti-fibrotic effect of pirfenidone may be indirect. Eupatilin could increase the efficacy of IPF treatment to curative levels. Keywords: Chromone scaffold, Epithelial–mesenchymal transition, Stem cells, Idiopathic pulmonary fibrosis, Myofibroblasts, Dedifferentiation

Background/Aims: The primary aims of this study were to evaluate the content quality of YouTube videos on exercises to help relieve constipation and to assess whether the video source, exercise types, and popularity affected their quality. Methods: Eight gastroenterologists independently evaluated the exercises presented in the constipation YouTube videos for seven items: image quality, usefulness in relieving constipation (quality 1), usefulness for general physical health (quality 2), difficulty in following, activity intensity, fun, and overall quality. Raters were asked open-ended questions to evaluate the strengths and weaknesses of the videos. Five-point ordinal scales were used to score each item aforementioned, with the exception of image quality and overall quality that used a six-point Likert scale. Results : The 20 videos had a mean length of 268 seconds and a mean viewership of 32,694. The most common video source was commercial (n=10), and the most common type of physical activity was yoga (n=11). The median values of image quality, quality 1, quality 2, difficulty in following, activity intensity, fun, and overall quality were 3, 2, 2, 2, 2, 2, and 2, respectively. Yoga videos had significantly higher median quality 1 values (3) compared with massage videos (2, adjusted p=0.006) and others videos (2, adjusted p

ABSTRACT A multifunctional autoprocessing repeats-in-toxin (MARTX) toxin plays an essential role in the virulence of many pathogens, including a fulminating human pathogen Vibrio vulnificus. H-NS and HlyU repress and derepress expression of the MARTX toxin gene rtxA in V. vulnificus, respectively. However, little is known about other regulatory proteins and environmental signals involved in rtxA regulation. In this study, we found that a leucine-responsive regulatory protein (Lrp) activates rtxA by binding directly and specifically to the rtxA promoter, PrtxA. Phased hypersensitivity resulting from DNase I cleavage of the PrtxA regulatory region suggests that Lrp probably induces DNA bending in PrtxA. Lrp activates PrtxA independently of H-NS and HlyU, and leucine inhibits Lrp binding to PrtxA and reduces the Lrp-mediated activation. Furthermore, a cyclic AMP receptor protein (CRP) represses PrtxA, and exogenous glucose relieves the CRP-mediated repression. Biochemical and mutational analyses demonstrated that CRP binds directly and specifically to the upstream region of PrtxA, which presumably alters the DNA conformation in PrtxA and thus represses rtxA. Moreover, CRP represses expression of lrp and hlyU by binding directly to their upstream regions, forming coherent feed-forward loops with Lrp and HlyU. In conclusion, expression of rtxA is controlled by a regulatory network comprising CRP, Lrp, H-NS, and HlyU in response to changes in host environmental signals such as leucine and glucose. This collaborative regulation enables the elaborate expression of rtxA, thereby enhancing the fitness and pathogenesis of V. vulnificus during the course of infection. IMPORTANCE A MARTX toxin, RtxA, is an essential virulence factor of many pathogens, including Vibrio species. H-NS and HlyU repress and derepress, respectively, rtxA expression of a life-threatening pathogen, Vibrio vulnificus. We found that Lrp directly activates rtxA independently of H-NS and HlyU, and leucine inhibits the Lrp-mediated activation of rtxA. Furthermore, we demonstrated that CRP represses rtxA but derepresses in the presence of exogenous glucose. CRP represses rtxA not only directly by binding to upstream of rtxA but also indirectly by repressing lrp and hlyU. This is the first report of a regulatory network comprising CRP, Lrp, H-NS, and HlyU, which coordinates the rtxA expression in response to environmental signals such as leucine and glucose during infection. This elaborate regulatory network will enhance the fitness of V. vulnificus and contribute to its successful infection within the host.

Although circulating cell-free DNA (cfDNA) is a promising biomarker for the diagnosis and prognosis of various tumors, clinical correlation of cfDNA with gastric cancer has not been fully understood. To address this, we developed a highly sensitive cfDNA capture system by integrating polydopamine (PDA) and silica. PDA-silica hybrids incorporated different molecular interactions to a single system, enhancing cfDNA capture by 1.34-fold compared to the conventional silica-based approach (p = 0.001), which was confirmed using cell culture supernatants. A clinical study using human plasma samples revealed that the diagnostic accuracy of the new system to be superior than the commercially available cfDNA kit, as well as other serum antigen tests. Among the cancer patients, plasma cfDNA levels exhibited a good correlation with the size of a tumor. cfDNA was also predicative of distant metastasis, as the median cfDNA levels of metastatic cancer patients were ~60-fold higher than those without metastasis (p = 0.008). Furthermore, high concordance between tissue biopsy and cfDNA genomic analysis was found, as HER2 expression in cfDNA demonstrated an area under ROC curve (AUC) of 0.976 (p

Abstract Circulating tumor cells have emerged as biomarkers for estimating the tumor burden and metastatic potential of cancer patients. However, to date, most of studies and applications of circulating tumor cells have been conducted and applied to epithelial cancers such as breast, colorectal, and prostate tumor. The only FDA-cleared method, CellSearch, makes use of antibody against epithelial surface protein expressed on CTCs, thus obstructing wide application for various cancers with non-epithelial and semi-epithelial characteristics including renal cell carcinoma. Due to rarity and ambiguity of CTCs, designed experiment including non-biased CTC isolation and subsequent cytopathological study for finding applicable immunomarkers are urgently needed for clinical use of CTCs for less-studied cancers. Here, in order to construct the fundamental step for CTC diagnosis without limitation of its epithelial characteristics, we present the simple and novel method which incorporate both label-free CTC isolation and pathological study using hydrogel-based cell block formation. Six cell lines from lung, ovarian, kidney cancers were used to make cell block and analyzed by conventional immunocytochemical staining method to find the candidate markers for CTC. Especially for renal cancer, the physically isolated CTCs were further immunocytochemically examined with the screened candidate markers by cell block construction, and verified their clinical utility using blood samples from patients with renal cell carcinoma. This comprehensive study demonstrates that the present approach can be used to find the potential markers for any type of cancers regardless of their epithelial characteristics and isolate the specific type of CTCs in label-free manners.

Background/Aims Sofosbuvir plus ribavirin is a standard treatment for patients infected with chronic hepatitis C virus (HCV) genotype 2 in Korea. The purpose of this study was to examine the efficacy and safety of this treatment in Korean patients with chronic HCV genotype 2 infection. Methods We retrospectively analyzed clinical data of patients treated with sofosbuvir plus ribavirin for chronic HCV genotype 2 from May 2016 to December 2017 at eight hospitals located in the Daejeon-Chungcheong area. Results A total of 172 patients were treated with sofosbuvir plus ribavirin. Of them, 163 patients completed the treatment, and 162 patients were tested for sustained virologic response 12 weeks after treatment discontinuation (SVR12). Mean age was 59.6±12.3 years (27–96), and 105 (64.4%) patients were female. Of the total patients, 49 (30.1%) were diagnosed with cirrhosis, and 31 of them were treated for 16 weeks. Sofosbuvir plus ribavirin was the first-line treatment for 144 (88.3%) patients. Eleven (6.7%) patients were intolerant to previous interferon-based treatment. Eight (5.0%) patients relapsed after interferon-based treatment. HCV RNA non-detection rate at 4, 8, and 12 weeks was 97.5%, 99.1%, and 99.3%, respectively, and SVR12 was 98.8% (161/163). During treatment, 18 (11.0%) patients had to reduce their administrated dose of ribavirin because of anemia. One patient stopped the treatment because of severe anemia. Other adverse events, including dizziness, indigestion, and headache, were found in 26 (16.0%) patients. Conclusions A 12-16 week treatment with sofosbuvir plus ribavirin is remarkably effective and well tolerated in Korean patients with chronic HCV genotype 2 infection.

When liver disease is severe, the prognosis can be worse if the patient is malnourished. Adequate nutritional support for patients with liver diseases can improve the patient’s condition and prognosis. In the case of liver cirrhosis, malnutrition can occur due to a variety of causes, including poor oral intake, maldigestion, malabsorption, associated renal disease, and metabolic abnormalities. For a nutritional assessment, it is important to check the dietary intake, change in body composition, including anthropometry, and a functional assessment of muscle. Counselling and oral or enteral nutrition is preferred over parenteral nutrition as in other diseases. If esophageal varices are present, care should be taken when installing a feeding tube, but if there are ascites, percutaneous endoscopic gastrostomy is contraindicated because of the risk of complications. Calories of 30-35 kcal/kg/day and protein from 1.2 to 1.5 g/kg/day are appropriate. Protein restriction is unnecessary unless the hepatic encephalopathy is severe. A late evening snack and branched chain amino acids can be helpful. In the case of cholestasis, the supply of manganese and copper should be restricted. Sarcopenia in patients with liver cirrhosis is also prevalent and associated with the prognosis.

Circulating tumor cells (CTCs) are extremely low-frequency cells in the bloodstream. As those cells have detached from the primary tumor tissues and it circulates throughout the whole body, they are considered as promising diagnostic biomarkers for clinical application. However, the analysis of CTC is often restricted due to their rarity and heterogeneity, as well as their short-term presence. Here we proposed formalin-fixed, paraffin-embedded (FFPE) CTC block method, in combination manner with the hydrogel core-mediated CTC accumulation and conventional paraffin tissue block preparation. The hydrogel core specifically captures and releases cancer cells with high efficiency with an immunoaffinity manner. An additional shell structure protects the isolated cancer cells during the FFPE CTC block preparation process. The fabricated FFPE CTC block was sectioned and cytopathologically investigated just the same way as the conventional tissue block. Our results demonstrate that rare cells such as CTCs can also be prepared for FFPE cell blocks and shows great promise for cytopathological CTC studies.

Background: Circulating tumor DNA (ctDNA) and exosome have been widely researched in the field of medical technology and diagnosis platforms. The purpose of our study was to improve the capturing properties of ctDNA and exosome, which involved combining two beads using approaches that may provide a new method for cancer diagnoses. Methods: We present a dual isolation system including a polydopamine (PDA)–silica-coated alginate bead for circulating tumor DNA (ctDNA) capture and an anti-CD63 immobilized bead for exosome capture. We examined the ctDNA mutation in pre-operative plasma samples obtained from 91 colorectal cancer (CRC) patients using a droplet digital PCR (ddPCR). Results: The area under the curve (AUROC) of ctKRAS G12D mutation in the buffy coat was 0.718 (95% CI: 0.598−0.838; p = 0.001). Patients with CRC that had unmethylation of MLH1 and MSH2 showed significantly higher buffy coat ctKRAS G12D mutations, ascites ctKRAS G12D mutations, miR-31-5, and mixed scores than the patients with a methylation of MLH1 and MSH2. Conclusion: Our proposed alginate bead using the specific gravity-free method suggests that the screening of mutated ctKRAS DNA and miR-31-5 by liquid biopsy aids in identifying the patients, predicting a primary tumor, and monitoring in the early detection of a tumor.

Heat stress induces the hypothalamic-pituitary-adrenal (HPA) axis activation, influences biological responses, and reduces energy metabolism. Geongangbuja-tang (GBT) and its components, Zingiberis Rhizoma (ZOR) and Aconiti Lateralis Radix Preparata (ALRP) have been used to induce energy metabolism; however, the effects of GBT and its ingredients on heat-induced inflammatory responses have not yet been investigated. In this study, we performed an open-field test to evaluate locomotor activity in mice. To assess the effects of GBT and its ingredients on inflammation, the protein levels of c-fos, pro-inflammatory cytokines, and cortisol were measured in the mouse hypothalamus and serum. The results showed that GBT alleviated locomotive activity and reduced c-fos levels in a dose-dependent manner under the heat exposure. After investigating the active constituent of GBT, we found that compared to GBT and ZOR, ALRP significantly suppressed c-fos expression under heat stress. Subsequently, ALRP decreased the expression of pro-inflammatory cytokines, such as interleukin-9 and -13 and prostaglandin, under the heat stress in the mouse hypothalamus. Moreover, treatment with ALRP inhibited cortisol secretion in the mouse serum following heat exposure. These results indicate that GBT and its active component, ALRP, could be the thermoregulatory agents that regulate the HPA axis.

Abstract Background Previous studies have associated the Interleukin-1 (IL-1) gene clusters polymorphisms with the risk of primary open-angle glaucoma (POAG). However, the results were not consistent. Here, we performed a meta-analysis to evaluate the role of IL-1 gene clusters polymorphisms in POAG susceptibility. Methods PubMed, EMBASE and Cochrane Library (up to July 15, 2017) were searched by two independent investigators. All case-control studies investigating the association between single-nucleotide polymorphisms (SNPs) of IL-1 gene clusters and POAG risk were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for quantifying the strength of association that has been involved in at least two studies. Results Five studies on IL-1β rs16944 (c. -511C > T) (1053 cases and 986 controls), 4 studies on IL-1α rs1800587 (c. -889C > T) (822 cases and 714 controls), and 4 studies on IL-1β rs1143634 (c. +3953C > T) (798 cases and 730 controls) were included. The results suggest that all three SNPs were not associated with POAG risk. Stratification analyses indicated that the rs1143634 has a suggestive associated with high tension glaucoma (HTG) under dominant (P = 0.03), heterozygote (P = 0.04) and allelic models (P = 0.02), however, the weak association was nullified after Bonferroni adjustments for multiple tests. Conclusions Based on current meta-analysis, we indicated that there is lack of association between the three SNPs of IL-1 and POAG. However, this conclusion should be interpreted with caution and further well designed studies with large sample-size are required to validate the conclusion as low statistical powers.

Background/Aims: Although the role of capsule endoscopy (CE) in Crohn's disease (CD) has expanded, CE is not used routinely for diagnosing and evaluating CD in Korea. We aimed to investigate current patterns of practice and evaluate the clinical significance of the use of CE in CD in Korean patients.Methods: Among 651 CE procedures performed for various indications, we retrospectively analyzed the medical records of patients who underwent CE in 57 cases of suspected CD (sCD) and 14 cases of established CD (eCD).Results: In the sCD group, CE was most commonly used for the initial diagnosis of CD (54.4%). Capsule retention was found in only 1 patient in the eCD group (1/71, 1.4%). In the sCD group, 28.1% of patients were diagnosed with CD on the basis of CE findings; other diseases diagnosed included tuberculous enteritis (7.0%), non-steroidal anti-inflammatory drug-induced enteropathy (5.3%), and other enteritis (17.5%). Only 11.5% of patients with eCD (14/122) underwent CE. The indication for CE in the 14 patients with eCD was to assess disease extent and activity. The overall diagnostic yield of CE was 59.7%. Therapeutic strategies were changed in 70.2% of patients in the sCD group and 50% of those in the eCD group based on CE findings.Conclusions: In clinical practice, CE was most commonly indicated for the initial diagnosis of CD and was not generally performed in patients with eCD. CE appears to be an effective diagnostic modality for evaluating sCD and is useful for determining therapeutic strategies for patients with sCD and those with eCD.

Background/AimsWe evaluated whether manometric subtype is associated with treatment outcome in patients with achalasia treated by peroral endoscopic myotomy (POEM).Methods : High-resolution manometry data and Eckardt scores were collected from 83 cases at two tertiary referral centers where POEM is performed. Manometric tracings were classified according to the three Chicago subtypes.Results : Among the 83 cases, 48 type I, 24 type II, and 11 type III achalasia cases were identified. No difference was found in pre-POEM Eckardt score, basal lower esophageal sphincter (LES) pressure, or integrated relaxation pressure (IRP) among the type I, type II, and type III groups. All three patient groups showed a significant improvement in post-POEM Eckardt score (6.1±2.1 to 1.5±1.5, p=0.001; 6.8±2.2 to 1.2±0.9, p=0.001; 6.6±2.0 to 1.6±1.4, p=0.011), LES pressure (26.1±13.8 to 15.4±6.8, p=0.018; 32.3±19.0 to 19.2±10.4, p=0.003; 36.8±19.2 to 17.5±9.7, p=0.041), and 4s IRP (21.5±11.7 to 12.0±8.7, p=0.007; 24.5±14.8 to 12.0±7.6, p=0.002; 24.0±15.7 to 11.8±7.1, p=0.019) at a median follow-up of 16 months.Conclusion : sPOEM resulted in a good clinical outcome for all manometric subtypes.

Background/Aims The combination of daclatasvir (DCV) and asunaprevir (ASV) has demonstrated a high sustained virologic response at 12 weeks (SVR12) and a low rate of adverse events in previous clinical studies. The purpose of this study was to clarify the results of treatment and side effects in Korean patients with chronic hepatitis C virus (HCV) genotype Ib infection. Methods We retrospectively analyzed clinical data from chronic HCV genotype Ib patients treated with DCV+ASV from August 2015 to September 2016 at five hospitals in the Daejeon-Chungcheong area. Results A total of 152 patients were examined for resistance associated variants (RAVs). Among them, 15 (9.9%) were positive for Y93 and one (0.7%) was positive for L31. Of 126 patients treated with DCV+ASV, 83 patients completed treatment and 76 patients were included in safety and efficacy analysis. Five (6.6%) were positive for Y93 and 12 (15.8%) exhibited cirrhotic change. DCV+ASV was the first-line treatment for 58 (76.3%) patients. Eleven (14.5%) patients relapsed after previous treatment that included interferon and seven (9.2%) of these patients were found to be intolerant of interferon. Adverse events occurred in 10 (13.2%) patients and two patients stopped the medication because of severe itching and skin rash. SVR12 was 89.5% (68/76) in all patients and 91.5% (65/71) in RAV-negative patients. Conclusions DCV+ASV showed good efficacy in patients with HCV Ib infection in Korea. Close monitoring is needed for severe adverse events and treatment failure, which were uncommon.

Abstract Biliary cystadenomas are benign but potentially malignant cystic neoplasm. The preferred treatment is radical resection because it is difficult to differentiate a benign from a malignant biliary cystadenoma. A 40 year-old woman presented with moderate abdominal discomfort. Esophageal varix was found up to mid-esophagus on endoscopy. She has no prior history of liver disease or chronic alcohol ingestion. About 15cm sized biliary cystadenoma was diagnosed by ultrasonography, computed tomography and magnetic resonance imaging. Serum level of bilirubin, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase and tumor marker were elevated. The patient underwent US-guided aspiration. Tumor markers from the aspirated fluid are increased. Left hepatectomy was performed to completely remove the cyst. Histology of the resected specimen confirmed a biliary cystadenoma of the liver with ovary-like stroma. Without prior history of liver disease or chronic alcoholic ingestion, incidental finding of esophageal varix could show an important clue for diagnosis of biliary cystadenoma.

β-Lactamase-mediated resistance to β-lactam antibiotics has been significantly threatening the efficacy of these clinically important antibacterial drugs. Although some β-lactamase inhibitors are prescribed in combination with β-lactam antibiotics to overcome this resistance, the emergence of enzymes resistant to current inhibitors necessitates the development of novel β-lactamase inhibitors. In this study, we evaluated the inhibitory effect of dinucleotides on an extended-spectrum class C β-lactamase, AmpC BER. Of the dinucleotides tested, NADPH, a cellular metabolite, decreased the nitrocefin-hydrolyzing activity of the enzyme with a Ki value of 103 μM in a non-covalent competitive manner. In addition, the dissociation constant (KD) between AmpC BER and NADPH was measured to be 40 μM. According to our in vitro susceptibility study based on growth curves, NADPH restored the antibacterial activity of ceftazidime against a ceftazidime-resistant Escherichia coli BER strain producing AmpC BER. Remarkably, a single dose of combinatory treatment with NADPH and ceftazidime conferred marked therapeutic efficacy (100% survival rate) in a mouse model infected by the E. coli BER strain although NADPH or ceftazidime alone failed to prevent the lethal bacterial infection. These results may offer the potential of the dinucleotide scaffold for the development of novel β-lactamase inhibitors.

Background: A simple classification for the relevance of lesions (P0, P1, and P2; no bleeding potential, less likely to bleed, and more likely to bleed, respectively) based on capsule endoscopy (CE) findings has been used. This study aimed at investigating rebleeding rates and predictive factors of P0 and P1 lesions after obtaining negative findings in both, CE and computed tomography (CT), for patients with obscure gastrointestinal bleeding (OGIB). Methods: Among 193 patients resulted in negative CE findings defined as P0 or P1 lesions, 84 patients with negative results on CT images were enrolled in this study. The rebleeding rates and predictive factors were assessed in the P0 and P1 groups. Results: Overall rebleeding rate in patients with negative CT and CE was 17.9%; 18.4% in the P0 group; 17.4% in the P1 group within a median follow-up duration of 18.5 months. In the P0 and P1 groups, the cumulative rebleeding rates were 9.2%, 25.4%, and 25.4%, and 6.9%, 11.8%, and 18.6% at 12, 24, and 60 months, respectively (p = 0.97). There were no independent rebleeding associated factors in the P0 group, whereas Charlson comorbidity index (CCI) (hazard ratio (HR) = 2.019, 95% confidence interval (CI): 1.158–3.519, p = 0.013), and initial low hemoglobin (Hb) level (p = 0.037) were independent predictive factors responsible for rebleeding in the P1 group. Conclusions: Despite having negative findings on CT and CE, patients with OGIB have a significant potential rebleeding risk. Although there was no significant difference in rebleeding rates between the P0 and P1 groups on CE, the P1 group, with CCI or low initial Hb level, should be cautiously observed after the first bleeding episode.

Background : /Aims: This study evaluated the eradication rate of levofloxacin-containing rescue therapy by treatment duration in patients in whom previous first- and second-line treatment failed.Methods : : Fifty-five patients with persistent Helicobacter pylori infection after first-line therapy and second-line therapy were studied in a single referral academic center. We compared the eradication rates by the treatment duration of third-line therapy.Results : : Of 55 patients, 12 (21.8%) received rescue therapy for seven days, 24 (43.6%) received rescue therapy for 10 days, and 19 (34.5%) received rescue therapy for 14 days. The eradication rates of therapy with levofloxacin were 65.5% in the 55 enrolled patients and 73.5% in the 49 patients who underwent follow-up testing. In cases where follow-up testing was performed, the eradication rate of 7-day therapy was 58.3%, of 10-day 68.2%, and of 14-day therapy 93.3%. Eradication rate of 14-day therapy was higher than 7-day (p=0.06) and 10-day (p=0.108), but chance could not be ruled out in the difference among groups.Conclusion : s: This study showed somewhat increasing of H. pylori eradication rate by extending the duration of levofloxacin-containing rescue therapy to 14 days. (Korean J Gastroenterol 2016;68:260-264)

BackgroundGastrointestinal symptoms are common in patients with type 2 diabetes mellitus (T2DM). The prevalence of gastroesophageal reflux disease (GERD) in Korea appears to be increasing. Some studies have shown that T2DM is a risk factor for symptomatic GERD. However, this possibility is still debated, and the pathogenesis of GERD in T2DM is not yet fully understood. The aim of this study was to analyze the prevalence and risk factors (including autonomic neuropathy) of GERD in patients with T2DM.MethodsThis cross-sectional case-control study enrolled T2DM patients (n=258) and healthy controls (n=184). All participants underwent physical examinations and laboratory tests. We evaluated medical records and long-term diabetes complications, including peripheral and autonomic neuropathy in patients with T2DM. Esophagogastroduodenoscopy was performed in all patients. The Los Angeles (LA) classification was used to grade GERD. GERD was defined as LA grade A (or higher) or minimal change with GERD symptoms. GERD symptoms were examined using a frequency scale. Data were expressed as mean±standard error. Independent t-tests or chi-square tests were used to make comparisons between groups.ResultsThe prevalence of GERD (32.6% vs. 35.9%, P=0.266) and GERD symptoms (58.8% vs. 59.2%, P=0.503) was not significantly different between T2DM patients and controls. We found no significant differences between T2DM patients with GERD and T2DM patients without GERD with respect to diabetic complications, including autonomic neuropathy, peripheral neuropathy, duration of DM, and glucose control.ConclusionThe prevalence of GERD in patients with T2DM showed no difference from that of controls. GERD was also not associated with peripheral and cardiovascular autonomic neuropathy, age, or duration of DM in patients with T2DM.

Background : /Aims: Pyogenic liver abscess (PLA) is a life-threatening condition, despite advances in diagnostic technology and strategies for treatment. A strong predictor of mortality in this condition is septic shock. This study describes clinical, biochemical, and radiologic features in patients with PLA with or without septic shock, with the intent of describing risk factors for septic shock. Methods : : Of 358 patients with PLA enrolled, 30 suffered septic shock and the remaining 328 did not. We reviewed the medical records including etiologies, underlying diseases, laboratory, radiologic and microbiologic findings, methods of treatment and treatment outcomes. Results : : The case fatality rate was 6.1%. In univariate analysis, the presence of general weakness, mental change, low platelet level, prolonged PT, high BUN level, high creatinine level, low albumin level, high AST level, high CRP level, abscess size ＞6 cm, the presence of gas-forming abscess, APACHE II score ≥20, and the presence of Klebsiella pneumoniae infection were significantly associated with septic shock. Multivariate analysis showed the presence of mental change (p=0.004), gas-forming abscess (p=0.012), and K. pneumoniae infection (p=0.027) were independent predictors for septic shock. Conclusion : s: The presence of mental change, gas-forming abscess, and K. pneumoniae infection were independent predictors for septic shock in patients with PLA. (Korean J Gastroenterol 2016;67:245-252)

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease in the elderly and the patients suffer from uncontrolled movement disorders due to loss of dopaminergic (DA) neurons on substantia nigra pars compacta (SNpc). We previously reported that transplantation of human fetal midbrain-derived neural precursor cells restored the functional deficits of a 6-hydroxy dopamine (6-OHDA)-treated rodent model of PD but its low viability and ethical issues still remain to be solved. Albeit immune privilege and neural differentiation potentials suggest mesenchymal stem cells (MSCs) from various tissues including human placenta MSCs (hpMSCs) for an alternative source, our understanding of their therapeutic mechanisms is still limited. To expand our knowledge on the MSC-mediated PD treatment, we here investigated the therapeutic mechanism of hpMSCs and hpMSC-derived neural phenotype cells (hpNPCs) using a PD rat model. Whereas both hpMSCs and hpNPCs protected DA neurons in the SNpc at comparable levels, the hpNPC transplantation into 6-OHDA treated rats exhibited longer lasting recovery in motor deficits than either the saline or the hpMSC treated rats. The injected hpNPCs induced delta-like ligand (DLL)1 and neurotrophic factors, and influenced environments prone to neuroprotection. Compared with hpMSCs, co-cultured hpNPCs more efficiently protected primary neural precursor cells from midbrain against 6-OHDA as well as induced their differentiation into DA neurons. Further experiments with conditioned media from hpNPCs revealed that the secreted factors from hpNPCs modulated immune responses and neural protection. Taken together, both DLL1-mediated contact signals and paracrine factors play critical roles in hpNPC-mediated improvement. First showing here that hpMSCs and their neural derivative hpNPCs were able to restore the PD-associated deficits via dual mechanisms, neuroprotection and immunosuppression, this study expanded our knowledge of therapeutic mechanisms in PD and other age-related diseases.

The aim of this study was to investigate the association between tear film and meibomian gland parameters in patients with normal tension glaucoma (NTG), who underwent topical prostaglandin analog (PGA) monotherapy, and medication compliance.Ocular surface disease index (OSDI), Schirmer's test, tear film break-up time (TBUT), keratoepitheliopathy (KEP) score with fluorescein, and meibomian gland parameters were assessed in 45 eyes of 45 patients with NTG (NTG group), who received topical PGA monotherapy for more than 1 year. The results were compared to those of 40 eyes of 40 normal subjects (control group). Medication compliance was assessed by an 8-item Morisky Medication Adherence Scale (MMAS-8). Multiple logistic regression analysis was used to identify the factors associated with medication compliance.There was a significant difference in OSDI (P = 0.043), Schirmer's test (P < 0.001), TBUT (P < 0.001), KEP score (P = 0.015) and all meibomian gland parameters (all P < 0.001) between two groups. When the NTG group was divided into compliant and non-compliant groups based on the scores of MMAS-8, 30 (75%) patients were classified into the compliant group. Multiple logistic regression analysis revealed that the lid margin score (OR, 0.256; 95% CI, 0.072-0.908, P = 0.035), meibum score (OR, 0.144; 95% CI, 0.023-0.915, P = 0.04), and meibo score (OR, 0.344; 95% CI, 0.140-0.845, P = 0.02) were significant factors associated with compliance in patients with NTG. The meibomian gland parameters showed a negative correlation with medication compliance (all P < 0.005).Malfunction of the meibomian glands can be an important clinical finding associated with compliance of PGA monotherapy in patients with NTG.