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Objectives Peak exposure to extremely low-frequency magnetic fields (ELF-MF) among semiconductor workers was characterized by type of factory, operation, and job. Methods A portable EMDEX meter was used to monitor the ELF-MF exposure of 117 semiconductor workers who are involved in wafer fabrication (fab) and assembly operations. ELF-MF measurements were logged every 3 s and categorized by process and job or activity during working hours. Two values of 0.5 and 1 μT were adopted subjectively as cutoff values of peak exposure levels based on a literature review. Results All semiconductor workers who were involved in diffusion, ion implanter operation, module, and chip test were exposed to ELF-MF higher than 0.5 μT during their entire working time. Engineers who maintained electric facilities in the semiconductor operations were exposed to the highest ELF-MF peak levels (2.5 μT on average above 0.5 μT and 3.6 μT on average above 1 μT). Operators working in chip testing showed the highest daily contribution of their peak levels to their daily average ELF-MF exposure levels (98.1% and 83.9%). In contrast, chemical mechanical planarization engineers, wafer test operators, and administrative workers outside clean rooms showed average exposure to less than 0.5 μT and a low proportion of duration of time exposed above either the 0.5 μT or 1 μT peak level points, along with a low daily contribution of peak exposure levels (16.0, 11.9, and 18.7%). Conclusions Most of the activities and working locations next to machines generating ELF-MF in semiconductor operations showed high contributions of ELF-MF peak exposure to daily exposure dose despite their relative minor fraction of workers’ daily time.

The purpose of this study is to construct a job-exposure matrix for lead that accounts for industry and work processes within industries using a nationwide exposure database.We used the work environment measurement data (WEMD) of lead monitored nationwide from 2015 to 2016. Industrial hygienists standardized the work process codes in the database to 37 standard process and extracted key index words for each process. A total of 37 standardized process codes were allocated to each measurement based on an automated key word search based on the degree of agreement between the measurement information and the standard process index. Summary statistics, including the arithmetic mean, geometric mean, and 95th percentile level (X95), was calculated according to industry, process, and industry process. Using statistical parameters of contrast and precision, we compared the similarity of exposure groups by industry, process, and industry process.The exposure intensity of lead was estimated for 583 exposure groups combined with 128 industry and 35 process. The X95 value of the "casting" process of the "manufacture of basic precious and non-ferrous metals" industry was 53.29 μg/mWe evaluated the exposure intensities of lead by combination of industry and process. The results will be helpful in determining more accurate information regarding exposure in lead-related epidemiological studies.

The torque and fanning techniques allow for multiple areas within pancreatic lesions to be targeted using different maneuvers and can, hence, enhance diagnostic outcomes. We compared the diagnostic performance of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) for pancreatic masses using the torque and fanning techniques.This multicenter randomized trial enrolled a total of 160 consecutive patients who underwent EUS-FNB for solid pancreatic tumors using either the torque or fanning technique. Three passes were permitted for each lesion, and the technique sequence was randomly assigned as either torque first or fanning first with the standard technique as a reference.The median quality score of the histological samples was significantly higher in the torque and fanning group than in the standard group (p .001). Furthermore, the torque technique provided improved sensitivity of 93.38% and accuracy of 94.30%. The standard technique provided diagnostic sensitivity of 68.84% and accuracy of 72.96%, while the fanning technique showed sensitivity of 91.85% and accuracy of 93.04%.The new torque technique enables the acquisition of better-quality samples and can potentially increase the diagnostic outcomes in the EUS-FNB of pancreatic solid masses, with the same recommendations as those for the fanning technique.

Background and Aims: Various guidewires are used for biliary cannulation, and each one has its own characteristics affecting its effectiveness. This study aimed to measure the basic properties and evaluate the effectiveness of a newly developed 0.025-inch guidewire for selective biliary cannulation. Methods: A total of 190 patients at five referral hospitals were randomly allocated to undergo selective biliary cannulation using the newly developed guidewire (NGW group, n = 95) or a conventional guidewire (CGW group, n = 95). The primary outcome was the selective biliary cannulation rate in naïve papillae. The secondary outcome was to measure the NGW basic properties, compare them with those of the CGW, and analyze the importance of basic property differences. Results: There were no significant differences between the groups in the baseline characteristics. The primary outcome (75.8% vs. 84.2%, p = 0.102) and adverse event rate (6.3% vs. 4.2%, p = 0.374) were similar in both groups. However, compared with the CGW group, the NGW group showed a higher number of ampulla contacts (2.58 vs. 2.02, p = 0.011) and longer cannulation time (216.5 vs. 135.1 s, p = 0.016). Furthermore, the NGW group had higher maximum friction (34.6 ± 1.34 vs. 30.2 ± 4.09), lower stiffness, and better elastic resiliency. In the multivariate analysis, a curved-tip GW (OR = 0.26, 95% CI 0.11–0.62, p = 0.002) and normal papillary shape (OR = 0.39, 95% CI 0.17–0.86, p = 0.021) were contributing factors for successful selective biliary cannulation. Conclusions: The NGW group had high friction and low stiffness, characteristics affecting biliary cannulation. Clinically, the NGW group had similar success and adverse event rates as the CGW, but they showed a higher number of ampulla contacts and longer cannulation time.

This study aimed to identify the major industries and jobs with the highest proportion of workers' compensation (WC) claims for COVID-19, characterize COVID-19 WC claims in terms of their demographic properties and disease severity, and identify factors influencing the approval of COVID-19 WC claims as occupational disease. A total of 488 workers who submitted COVID-19-related claims to the Korea Workers' Compensation and Welfare Service (KWCWS) from January 2020 to July 2021 were analyzed. A Fisher's exact test was employed to associate the severity of COVID-19 infection with demographic properties. The highest proportion of all COVID-19 WC claims compensated as occupational disease (N=462) were submitted by healthcare workers (HCW=233, 50%), while only 9% (N=41) of the total originated from manufacturing industries. The 5% (N=26) of the COVID-19 WC claims accepted were evaluated as severe (N=15) and acute respiratory distress syndrome (N=9). A total of 71% (N=329) of the COVID-19 patients compensated (N=462) were from workplaces with infection clusters. A total of 26 WC cases were rejected for various reasons, including unclear infection routes, infection at private gatherings (including within families), no diagnosis, and more. Given our findings, we suggest an official system should be established to detect and compensate more job-associated infectious diseases like COVID-19.

There is general acceptance that a diagnosis of acute pancreatitis requires two of the following three features: 1) epigastric or upper abdominal pain characteristic of acute pancreatitis, 2) serum amylase and/or lipase ≥3 times the upper limit of normal, and 3) characteristic findings of acute pancreatitis on abdominal images such as ultrasonography, computed tomography (CT) or magnetic resonance imaging. Other pancreatic diseases and acute abdomen have been ruled out before making a diagnosis of acute pancreatitis. Serum lipase may be more useful than serum amylase because serum lipase is thought to be more sensitive and specific than serum amylase in the diagnosis of acute pancreatitis. Contrast-enhanced CT scan is the best imaging technique to rule out the conditions that masquerade as acute pancreatitis, to diagnose the severity of acute pancreatitis, and to identify complications of pancreatitis. The etiology of acute pancreatitis should be made clear as soon as possible to decide treatment policy of acute pancreatitis or to prevent the recurrence of pancreatitis. The etiology of acute pancreatitis in an emergency situation should be assessed by clinical history, laboratory tests such as serum liver function tests, measurement of serum calcium and serum triglycerides and ultrasonography. A differentiation of gallstone-induced acute pancreatitis should be given top priority in its etiologic diagnosis because early endoscopic retrograde cholangiopancreatography should be considered if a complication of cholangitis and a prolonged passage disorder of the biliary tract are suspected.

Endoscopic retrograde cholangiopancreatography (ERCP) is challenging in patients undergoing Roux-en-Y (REY) reconstruction; although balloon-assisted enteroscopy is the first-line treatment, it is not always available considering equipment and expertise. We aimed to evaluate the feasibility of using a cap-assisted colonoscope as the primary approach for ERCP in REY reconstruction. We included 47 patients with REY who underwent ERCP using a cap-assisted colonoscope between January 2017 and February 2022. The primary outcome was intubation success for ERCP using a cap-assisted colonoscope during REY reconstruction. The secondary outcomes were cannulation success, procedure-related adverse events, and variables affecting successful intubation. Comparing side-to-side jejunojejunostomy (SS-JJ) and side-to-end jejunojejunostomy (SE-JJ) groups, the intubation success rate using a cap-assisted colonoscope in the SS-JJ group was higher than that in the SE-JJ group (34 of 38 (89.5%) vs. 1 of 9 (11.1%), p < 0.001). Successful intubation was achieved in 37 (97.4%) and 8 (88.9%) patients in the SS-JJ and SE-JJ groups, respectively, after applying the rescue technique using a balloon-assisted enteroscope for failed ERCP using only a colonoscope. No perforation occurred. Multivariable analysis showed that SS-JJ was a predictive factor for successful intubation (odds ratio [95% confidence interval] = 37.06 [3.91–925.56], p = 0.005). Usage of a cap-assisted colonoscope can be crucial for ERCP in patients undergoing REY reconstruction. Anatomically, SS-JJ can facilitate easy and accurate identification of the afferent limb and a highly successful ERCP using a cap-assisted colonoscope.

Background In a previous study, we estimated exposure prevalence and the number of workers exposed to carcinogens by industry in Korea. The present study aimed to evaluate the optimal exposure intensity indicators of airborne lead exposure by comparing to blood lead measurements for the future development of the carcinogen exposure intensity database. Methods Data concerning airborne lead measurements and blood lead levels were collected from nationwide occupational exposure databases, compiled between 2015 and 2016. Summary statistics, including the arithmetic mean (AM), geometric mean (GM), and 95th percentile level (X95) were calculated by industry both for airborne lead and blood lead measurements. Since many measurements were below the limits of detection (LODs), the simple replacement with half of the LOD and maximum likelihood estimation (MLE) methods were used for statistical analysis. For examining the optimal exposure indicator of airborne lead exposure, blood lead levels were used as reference data for subsequent rank correlation analyses. Results A total of 19,637 airborne lead measurements and 32,848 blood lead measurements were used. In general, simple replacement showed a higher correlation than MLE. The results showed that AM and X95 using simple replacement could be used as optimal exposure intensity indicators, while X95 showed better correlations than AM in industries with 20 or more measurements. Conclusion Our results showed that AM or X95 could be potential candidates for exposure intensity indicators in the Korean carcinogen exposure database. Especially, X95 is an optimal indicator where there are enough measurements to compute X95 values.

Unlike in normal cells, ursodeoxycholic acid (UDCA) causes apoptosis rather than protection in cancer cells. Aim of this study was to demonstrate whether UDCA actually inhibits proliferation and induces apoptosis in bile duct cancer cells; the effect of UDCA on the expression of COX-2, PI3K/AKT, ERK, and EGFR; how UDCA affects cancer cell invasiveness and metastasis, since these effects are not established in bile duct cancer cells. SNU-245 cells (human extrahepatic bile duct cancer cells) were cultured. MTT assays were performed to evaluate the effect of UDCA on the cell proliferation. A cell death detection enzyme-linked immunosorbent assay and a caspase-3 activity assay were used to determine apoptosis. Western blot analysis measured expression levels of various proteins. The invasiveness of the cancer cells was evaluated by invasion assay. In cultured bile duct cancer cells, UDCA suppressed cell proliferation in bile duct cancer cells by inducing apoptosis and p53 activation, blocking deoxycholic acid (DCA)-induced activated EGFR-ERK signaling and COX-2, inhibiting DCA-induced activated PI3K-AKT signaling, and suppressing the invasiveness of bile duct cancer cells. In addition, a MEK inhibitor impaired UDCA-induced apoptosis in bile duct cancer cells. UDCA has antineoplastic and apoptotic effects in bile duct cancer cells. Thus, UDCA could be a chemopreventive agent in patients with a high risk of cancer, and/or a therapeutic option that enhances other chemotherapeutics.

This study assessed whether cholecystectomy is a risk factor for newly developed T2DM in Korean population.There is a lack of evidence that cholecystectomy is independently associated with insulin resistance and T2DM.This study included all patients aged20 years who had undergone cholecystectomy from 2010 to 2015 (n=55,166) and age- and sex-matched control subjects without cholecystectomy (n=110,332) using the National Health Insurance Service database. They were followed up until the date of newly developed T2DM or study end and the incidence of T2DM was traced over a maximum observation period of 7 years.Overall, 55,166 patients who underwent cholecystectomy and 110,332 age- and sex-matched controls were followed up for approximately 4.7 years, during which, incident T2DM occurred in 5,982 (3.61%) patients. Cholecystectomy was associated with 20% higher risk of T2DM after adjustment for all covariates. The cumulative incidence of T2DM also significantly increased in the cholecystectomy group for approximately 7 years (P0.001). The adjusted hazard ratio (HR) for T2DM was the highest in the group with both cholecystectomy and obesity using the control without both cholecystectomy and obesity as a reference (HR=1.41, 95% confidence interval [CI]: 1.29-1.56). The group with cholecystectomy without obesity showed comparable risk of incident T2DM compared with the group without cholecystectomy with obesity (HR=1.29, 95% CI: 1.20-1.40 for cholecystectomy without obesity and HR=1.24, 95% CI: 1.14-1.36 for control with obesity).This results provide evidence that cholecystectomy is associated with an increased risk of newly developed T2DM in Korean population. Further research is required to elucidate the mechanism of the association between cholecystectomy and incident diabetes.

Prophylactic pancreatic stenting effectively reduces the rate and severity of post-ERCP pancreatitis (PEP) in the precut technique; however, studies on the optimal type and duration of the stent are still lacking. This prospective study evaluated the incidence and severity of PEP and the rate of spontaneous stent dislodgement in patients undergoing transpancreatic precut sphincterotomy (TPS) accompanied by prophylactic pancreatic stenting with an unflanged plastic stent (4F × 5 cm) for difficult biliary cannulation. A total of 247 patients with naïve papilla were enrolled in this study, and data were collected prospectively. In the final analysis, 170 and 61 patients were included in the standard cannulation technique and TPS groups, respectively. The incidence of PEP in the standard cannulation technique and TPS groups was 3.5% and 1.6% (p = 0.679), respectively. The technical success rate of selective biliary cannulation in the TPS group was 91.8%. The spontaneous dislodgement rate of the prophylactic plastic stent was 98.4%. In conclusion, an unflanged pancreatic stent (4F × 5 cm) placement in TPS for patients with failed standard cannulation technique is a safe and effective measure due to low adverse events and few additional endoscopic procedures for removing the pancreatic duct (PD) stent.

Common bile duct (CBD) stone is one of the most frequent biliary diseases. Recurrence after the complete removal of CBD stones is high, and we aim to evaluate the rate and risk factors for symptomatic recurrence of CBD stones after endoscopic retrograde cholangiopancreatography (ERCP). We, retrospectively, reviewed the database of patients who underwent ERCP for CBD stones and subsequent cholecystectomy between January 2015 and December 2017 at a tertiary hospital. The recurrence of symptomatic CBD stones was defined as the presence of a CBD stone with related symptoms at least 6 months after the ERCP procedure. The primary outcomes were recurrence of symptomatic CBD stones and its risk factors. Among the 362 enrolled patients, 60 experienced a symptomatic recurrence of CBD stones between 6 months and 5 years after the procedure. The mean duration of follow-up was 32.3 ± 8.1 months. The patients with recurrences were older and had a longer follow-up duration. Low insertion of the cystic duct (HR = 2.893, p = 0.016), distal CBD angulation (HR = 1.015, p = 0.034), maximum CBD diameter (HR = 1.070, p = 0.012), number of ERCP sessions at first admission (HR = 1.558, p = 0.032), and cannulation time (HR = 1.030, p = 0.008) were the independent risk factors for symptomatic recurrent CBD stones. Patients with risk factors, especially those with low cystic duct insertion, are more prone to symptomatic recurrent CBD stones and should be followed more carefully.

Background: There is insufficient information regarding the optimal guidewire for managing malignant hilar biliary obstruction (MHBO). Therefore, a newly designed 0.025-inch guidewire was compared with the conventional 0.035-inch guidewire for selective cannulation of both intrahepatic ducts (IHDs) in patients with MHBO. Methods: Patients were randomly enrolled into the curved type newly designed 0.025-inch guidewire group (0.025 group) or the curved type conventional 0.035-inch guidewire group (0.035 group). The primary outcome was the selective cannulation rate of IHD. If the assigned guidewire failed to pass the stricture within 5 min, the crossover guidewire was selected. If the crossover guidewire failed to cross the stricture within the next 5 min, it was judged as a failed selective cannulation of both IHDs. Results: A total of 90 patients were enrolled (0.025 group, n = 47; 0.035 group, n = 43). There was no significant difference in baseline characteristics between the groups regarding sex, age, BMI, obstruction level, and clinical presentation. Four patients (8.5%) in the 0.025 group the cannulation of the IHD failed and the conventional 0.035-inch guidewire was substituted in a second attempt; the 0.035-inch guidewire failed to cross the stricture in all four patients. In the 0.035 group, eleven patients (25.6%) failed to achieve selective cannulation of IHD, and the 0.025-inch guidewire was substituted; the newly designed 0.025-inch guidewire crossed the stricture in ten of these (10/11, 90.9%). The selective cannulation rate of IHD was significantly higher in the 0.025 group (95.1% vs. 85.5%, p = 0.043). Conclusions: The 0.025 group exhibited a higher success rate for selective cannulation of both IHDs in MHBO than did the 0.035 group.

Backgrounds/aims PPARγ, farnesoid X receptor (FXR) and CYP7A1 are associated with solubility of bile. This study was performed to understand a mechanism and interactions of statin-induced PPARγ, PGC-1α and HNF-4α related to the statin-induced activation of FXR and CYP7A1, and verify whether the mevalonate pathway is involved in the mechanism. Methods MTT assays were performed using cultured human Hep3B cells to determine the effect of atorvastatin on the cell proliferation. Expression levels of indicated proteins were measured using Western blotting assays by inhibiting the protein expression or not. Results Atorvastatin increased expression of PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. PPARγ ligand of troglitazone upregulated the expression of PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. Silencing of PPARγ, PGC1α, and HNF4α using respective siRNA demonstrated that atorvastatin-induced FXR and CYP7A1 activation required sequential action of PPARγ /PGC-1α/HNF-4α. The silencing of PPARγ completely inhibited atorvastatin-induced PGC-1α expression, and the PGC1α silencing partially inhibited atorvastatin-induced PPARγ expression. The inhibition of HNF4α did not affect atorvastatin-induced PPARγ expression, but partially inhibited atorvastatin-induced PGC-1α expression. Besides, mevalonate completely reversed the effect of atorvastatin on PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1. Conclusions Atorvastatin induces FXR and CYP7A1 activation as a result of sequential action of PPARγ/PGC-1α/HNF-4α in human hepatocytes. We propose that atorvastatin enhances solubility of cholesterol in bile by simultaneously activating of FXR and CYP7A1.

Objective To prevent occupational cancers, carcinogen exposure surveillance systems have been developed in many countries. This study aimed to develop a carcinogen exposure database specific to South Korea. Methods Twenty known human carcinogens were selected for this study. The International Standard Classification of Industry was used for a classification scheme of industries. Three nationwide occupational exposure databases, the Work Environment Measurement Database, the Special Health Examination Database, and the Work Environment Condition Survey, were used to calculate reference exposure prevalence estimates by carcinogen and industry. Then, 37 professional industrial hygienists with at least 19 years of field experience provided their own exposure prevalence estimates, after reviewing the abovementioned reference estimates derived from three data sources. The median value of the experts’ estimates was used as the final exposure prevalence. Finally, the number of exposed workers was computed by multiplying the final exposure prevalence by the number of workers extracted from the 2010 national census data by carcinogen and industry. Results The exposure prevalence and the number of exposed workers were calculated according to 20 carcinogen and 228 minor industrial groups, assuming year 2010 circumstances. The largest population was exposed to welding fumes (326 822 workers), followed by ultraviolet radiation (238 937 workers), ionizing radiation (168 712 workers), and mineral oil mist (146 798 workers). Conclusions Our results provide critical data on carcinogen exposure for the prevention of occupational cancers.

Objectives This study explored the relationship between shift intensity and insomnia among hospital nurses. Methods The participants were 386 female hospital nurses who underwent a special health examination for night workers in 2015. The Korean Insomnia Severity Index (ISI), indices of shift work intensity, and other covariates such as amount of exercise, level of alcohol consumption, employment duration, and hours worked were extracted from the health examination data. The indices for shift intensity were (1) number of 3 consecutive night shifts and (2) number of short recovery periods after a previous shift, both assessed over the prior 3 months. Multiple logistic regression analysis adjusted for the aforementioned covariates was performed to evaluate the association of shift intensity with insomnia, defined as an ISI score of ≥8. Results The nurses with insomnia tended to be younger (p=0.029), to have worked 3 consecutive night shifts more frequently (pl0.001), to have experienced a greater number of short recovery periods after the previous shift (p=0.021), and to have worked for more hours (p=0.006) than the nurses without insomnia. Among the other variables, no statistically significant differences between groups were observed. Experiences of 3 or more consecutive night shifts (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.29 to 4.20) and 3 or more short recovery periods (OR, 2.01; 95% CI, 1.08 to 3.73) were associated with increased odds of insomnia. Conclusions The results suggest that decreasing the shift intensity may reduce insomnia among hospital nurses working rotating shifts.

Epithelial-mesenchymal transition (EMT) features are associated with pathological severity in the progression and metastasis of various cancer types, including bile duct cancer (BDC). Our previous study demonstrated that ursodeoxycholic acid (UDCA) blocked the EGFR-MAPK signaling pathway and inhibited the invasion of BDC cells. The present study was performed to determine whether UDCA inhibits EMT and promotes the expression of E-cadherin to inhibit the invasion and aggressiveness of BDC. In addition, the present study aimed to confirm that the primary mechanism of inhibition of EMT by UDCA is related to the EGFR axis. Human extrahepatic BDC cells were cultured. The effect of UDCA on cell proliferation was evaluated using MTT assays. A cell death ELISA kit was used to measure apoptosis, and western blot assays or immunofluorescence staining assays measured the expression levels of various target proteins. The mRNA expression of Slug and ZEB1 was evaluated via reverse transcription-quantitative PCR. The invasiveness of BDC cells was estimated by invasion assays and western blot assays for focal adhesion kinase (FAK). UDCA inhibited the proliferation of BDC cells as effectively as gefitinib (an EGFR inhibitor), and the combination of UDCA and gefitinib revealed an additive effect on the proliferation of cells. UDCA and gefitinib induced apoptosis, and the combination of UDCA and gefitinib demonstrated an additive effect on apoptosis in BDC cells. UDCA restored the E-cadherin expression inhibited by EGF and suppressed N-cadherin expression increased by EGF as effectively as gefitinib. UDCA suppressed the Slug and ZEB1 mRNA expression induced by EGF in BDC cells. UDCA suppressed the invasiveness of BDC cells and FAK expression linked to the invasiveness of BDC. In conclusion, UDCA enhanced E-cadherin expression and suppressed N-cadherin expression through inhibition of the EGF-EGFR axis, contributing to the inhibition of EMT and invasiveness in BDC cells. Therefore, UDCA may be applied as an adjuvant or palliative antineoplastic agent and as a therapeutic option to enhance the effect of other chemotherapeutics.

Linked color imaging (LCI), a novel image-enhanced endoscopy, can make it easy to recognize differences in mucosal color. It may be helpful for diagnosing H. pylori associated gastritis and H. pylo...

Obesity has become a major medical and public health problem worldwide. Recent studies have shown that obesity is a chronic disease that is associated with many diseases, such as gallstone disease, acute pancreatitis, fatty liver, and digestive cancer. Obesity is also a risk factor for the formation of cholesterol gallstones. Clinical and epidemiological studies have suggested that obesity is positively associated with the risk of gallbladder cancer. Obesity may modulate the lipid and endogenous hormones metabolism, affect gallbladder motility, increase the risk of gallstones, and increased the risk of gallbladder cancer. In addition, obesity has been considered a risk factor for pancreatic diseases, including pancreatitis and pancreatic cancer. Obese patients develop systemic and local complications of acute pancreatitis more frequently. Several epidemiologic studies have suggested an association of pancreatic cancer with high body mass and lack of physical activity. This study reviewed the literature on obesity and pancreatobiliary disease in terms of epidemiology and mechanism.

OBJECTIVES Successful biliary cannulation is a prerequisite and important component of endoscopic retrograde cholangiopancreatography, but conventional cannulation methods (CCMs) have a postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) rate of 14.1% in patients at high risk for PEP. The aim of this study was to evaluate the effectiveness and safety of needle-knife fistulotomy (NKF), compared with a CCM, when used for primary biliary access in patients at high risk for developing PEP. METHODS A total of 207 patients with one or more risk factors for PEP were prospectively enrolled. The patients were randomly allocated to one of 2 groups according to the primary biliary cannulation technique (NKF or CCM). We compared biliary cannulation success rates, cannulation and procedure times, and the incidence of adverse events, including PEP, between the groups. RESULTS The mean number of PEP risk factors was similar between the groups (NKF, 2.2 ± 1.0; CCM, 2.2 ± 0.9). PEP occurred in 8 patients in the CCM group and in no patients in the NKF group (9.2% vs 0%, P < 0.001). The rates of other adverse events did not differ between the groups. The biliary cannulation success rate was high in the NKF group, but relatively low in the CCM group, possibly because of the stringent failure criteria aimed at reducing PEP. However, the mean cannulation and total procedural times were longer in the NKF group than in the CCM group. DISCUSSION NKF is an effective and safe procedure to gain primary biliary access in patients at high risk for developing PEP. ClinicalTrials.gov, NCT02916199.

Background/Aims: We aim to evaluate the effects of auranofin, a known antioxidant, on hepatic steatosis, inflammation, and fibrosis, contributing to non-alcoholic steatohepatitis (NASH) development in vivo and in vitro.Methods: Transcriptome analysis of LX-2 cells was that expression patterns of genes changed by auranofin, and their related pathways were estimated. We used the gene set enrichment analysis (GSEA) program to determine the pathway involved in overall genetic change. In vitro, LX-2 and HepG2 cells were treated with transforming growth factor (TGF)-β1 and palmitic acid (PA), respectively, and the antifibrotic and antiadipogenic effect function of auranofin was evaluated.Results: Transcriptome analysis revealed that auranofin decreased the expression of 15 genes, including thrombospondin 1, endothelin 1 (ET-1), fibronectin 1, and LOX. The molecular functions of these genes are involved in collagen binding. GSEA of the overall gene expression pattern revealed that many genes increased in the reactive oxygen species pathway and decreased in the inflammatory response. Auranofin decreased nuclear factor kappa B (NF-κB) and IκBα in TGF-β1-induced LX-2 cells, thereby reducing ET-1 and fibrosis. Furthermore, increased pNRF2 in PA-induced HepG2 cells led to increased antioxidant marker expression and decreased lipid accumulation. In the bile duct ligation model mice, auranofin reduced the fibrosis area and increased the survival rate. Auranofin reduced liver fibrosis and lipid accumulation in NASH model mice fed on a Western diet.Conclusions: Auranofin inhibits lipogenesis and fibrosis formation and is a proposed candidate for NASH treatment.

Occupational cancer is a global health issue. The Korean CARcinogen EXposure (K-CAREX), a database of CARcinogen EXposure, was developed for the Korean labor force to estimate the number of workers exposed to carcinogens by industry. The present study aimed to estimate the intensity of exposure to carcinogens by industry, in order to supply complementary information about CARcinogen EXposure intensity to the K-CAREX.We used nationwide workplace monitoring data from 2014 to 2016 and selected target carcinogens based on the K-CAREX list. We computed the 95th percentile levels of measurements for each industry by carcinogens. Based on the 95th percentile level relative to the occupational exposure limit, we classified the CARcinogen EXposure intensity into five exposure ratings (1-5) for each industry.The exposure ratings were estimated for 21 carcinogenic agents in each of the 228 minor industry groups. For example, 3,058 samples were measured for benzene in the manufacturing industry of basic chemicals. This industry was assigned a benzene exposure rating of 3.We evaluated the CARcinogen EXposure ratings across industries in Korean workers. The results will provide information on the exposure intensity to carcinogens for integration into the K-CAREX. Furthermore, it will aid in prioritizing control efforts and identifying industries of concern.

Direct endoscopic necrosectomy (DEN) using a lumen-apposing metal stent (LAMS) is a standard therapy for the management of symptomatic walled-off necrosis (WON). Here, we demonstrated the efficacy of the routine placement of long plastic stents after a DEN session to treat laterally extended WON. Patients (n = 6) with symptomatic laterally extended WON who underwent DEN after long plastic stent placement were included. The primary endpoint was clinical efficacy of the procedure. The technical and clinical success rates were 100% without major adverse events. The WON extended to the pelvic cavity or pericolic area, and the WON size was between 18.6 and 35.8 cm in length. The median number of DEN sessions was 10 (range 6–16), and two or three long plastic stents were placed after every DEN session. Only one patient suffered from pneumoperitoneum during DEN, which spontaneously resolved within 20 min. Placement of a long plastic stent after DEN using LAMS is a minimally invasive and effective treatment for symptomatic laterally extended WON. Further studies are needed to define the indications and most suitable patients.

Several clinical studies have suggested a strong correlation between cholecystectomy and the incidence of non-alcoholic fatty liver disease (NAFLD) although the exact correlation and causal relationship are unclear. This study aimed to investigate whether cholecystectomy increases the incidence of NAFLD or aggravates pre-existing NAFLD.Standard diet-fed and high-fat (HF) diet-fed mice were subjected to sham operation and cholecystectomy. In study 1, 20 standard diet-fed C57BL/6N mice were sacrificed at months 1, 2, and 4 post-surgery. Meanwhile, in study 2, 25 HF diet-induced NAFLD C57BL/6N mice were biopsied at months 2 and 3 post-surgery and sacrificed at month 6 post-surgery. The hepatic fatty acid and bile acid metabolic pathways and the hepatic bile composition were evaluated.The bodyweight and biochemical parameters (hepatic enzyme, triglyceride, and cholesterol levels) were not significantly different between the standard diet-fed sham and cholecystectomy groups. The NAFLD activity score and the levels of hepatocyte apoptosis markers (Krt18 expression and DNA fragmentation) and de novo lipid synthesis genes were not significantly different between the standard diet-fed sham and cholecystectomy groups. Cholecystectomy did not exacerbate hepatic steatosis, inflammation, and ballooning in the HF diet-fed mice. Hepatic bile acid composition was not markedly different in the sham and cholecystectomy groups fed on standard or HF diet. Cholecystectomy significantly downregulatedCholecystectomy did not increase the incidence of NAFLD in standard diet-fed mice. Additionally, NAFLD incidence was not significantly different between the HF diet-fed sham and cholecystectomy groups. Furthermore, the histological parameters were not markedly different between the sham and cholecystectomy groups fed on standard or HF diet. These findings suggest that cholecystectomy does not induce NAFLD.

High-throughput screening data from the Tox21 database is used for prioritizing hazardous chemicals and building in silico-based toxicity prediction models. One of the Tox21 dataset, peroxisome proliferator-activated receptor-gamma (PPARγ), a nuclear receptor superfamily, identified various endpoints in HEK293 cells. PPARγ mediates various toxic effects when its receptors are activated or inhibited by ligands such as thiazolidinedione and GW9662. In this study, an orthogonal assay was constructed to verify the effectiveness of the Tox21 PPARγ data, and the effect of highly reliable data on in silico model construction was investigated. The orthogonal assay was a reporter gene assay based on the PPARγ ligand binding domain in CV-1 cells. Only 39% of agonists and 55% of antagonists had similar responses in CV-1 and HEK293 cells. Thus, the effectiveness of Tox21 data on PPARγ may vary depending on the cell line. However, in silico PLS-DA analysis with only high-reliability data (i.e., the same response in both cell lines), yielded more accurate prediction of the activity of potential chemical ligands, despite the small number of samples. Thus, obtaining reliable chemical screening data for PPARγ through orthogonal analysis, even for only limited chemicals, supports the construction of highly predictive in silico models with improved screening efficiency.

두 유형의 소비자가 있고 기업이 보상액을 결정할 수 있는 시장에서의 최저가격보상제의 효과를 분석한다. 차액보다 적게 보상해 주는 보상제는 실시되지 않으며 차액보다 많이 보상해주는 제도의 효과는 보상액의 크기에 상관없이 동일하다. 차액만큼 보상해 주는 보상제는 충성스런 소비자가 많지 않으면 항상 실시되며 보상제 실시로 이윤이 같거나 증가한다. 차액만큼 보상해주는 보상제와 차액보다 많이 보상해 주는 보상제의 차이점은 충성스런 소비자의 수가 적은 경우 발생한다. 첫째, 충성스런 소비자의 수가 매우 적으면 차액보다 많이 보상해주는 제도는 실시되지 않는다. 둘째, 충성스런 소비자의 수가 적당히 적은 경우, 가격에 민감한 소비자의 수요가 탄력적이면 차액보다 많이 보상해 주는 보상제가 실시되지만 이윤이 감소한다. 따라서 기업은 차액보다 많이 보상해주는 경우에 죄수의 딜렘마에 놓일 수 있다. 마지막으로 기업이 보상액을 결정할 수 있는 경우, 충성스런 소비자가 적으면 차액만큼 보상해 주는 제도가 실시되지만, 많으면 보상제는 실시되지 않는다. 충성스런 소비자의 수가 많지도 적지도 않으면 두 보상제는 동일하며, 보상제가 실시된다.

BACKGROUND AND AIM Receptor-interacting serine/threonine kinase 3 and mixed lineage kinase domain-like pseudokinase (MLKL) have gained attention as apoptosis alternate cell death signaling molecules. We aimed to evaluate the role of MLKL in non-alcoholic fatty liver disease (NAFLD). METHODS Hepatic tissue MLKL expression was compared between NAFLD patients and healthy controls. High-fat diet was fed to wild-type and MLKL-knockout (KO) mice for 12 weeks. Brown adipose fat tissue was measured by [18 F]-fluorodeoxyglucose positron emission tomography. Energy expenditure was measured by indirect calorimetry. Anti-MLKL effects were also evaluated in in vitro setting using U937 and HepG2 cells. RESULTS Hepatic tissue MLKL expression increased in NAFLD patients compared with healthy controls. MLKL expression increased according to the degree of steatosis, ballooning, and inflammation. High-fat diet-fed MLKL-KO mice displayed decreased alanine aminotransferase, triglycerides, liver weight, NAFLD activity score (6.3 vs 3.5, P

To understand the role of aryl hydrocarbon receptor (AHR) isoforms in avian species, we investigated the functional characteristics of two AHR isoforms (designated as jcAHR1 and jcAHR2) of the jungle crow (Corvus macrorhynchos). Two amino acid residues corresponding to Ile324 and Ser380 (high sensitive type) in chicken AHR1 that are known to determine dioxin sensitivity were Ile325 and Ala381 (moderate sensitive type) in jcAHR1 and Val306 and Ala362 (low sensitive type) in jcAHR2. The quantitative comparison of the two jcAHR mRNA expression levels in a Tokyo jungle crow population showed that jcAHR2 accounted for 92.4% in the liver, while jcAHR1 accounted for only 7.6%. Both in vitro-expressed jcAHR1 and jcAHR2 proteins exhibited a specific binding to [3H]-labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Transactivation potencies for jcAHR1 and jcAHR2 in in vitro reporter gene assays were measured in jcAHR-expressed cells exposed to 16 dioxins and related compounds (DRCs). Both jcAHR1 and jcAHR2 were activated in a congener- and an isoform-specific manner. EC50 value of TCDD for jcAHR2 (0.61 nM) was six-fold higher than that for jcAHR1 (0.098 nM), but jcAHR2 had higher transactivation efficacy than jcAHR1 in terms of the magnitude of response. The high transactivation efficacy of jcAHR2 in DRCs is in contrast to that of AHR2s in other avian species with low transactivation efficacy. Molecular docking simulations of TCDD with in silico jcAHR1 and jcAHR2 homology models showed that the two sensitivity-decisive amino acids indirectly controlled TCDD-binding modes through their surrounding amino acids. Deletion assays of jcAHR2 revealed that 736–805 amino acid residues in the C-terminal region were critical for its transactivation. We suggest that jcAHR2 plays a critical role in regulating the AHR signaling pathway, at least in its highly expressed organs.

Background/Aims: Metformin has been found to have antineoplastic activity in some cancer cells. This study was performed to determine whether metformin inhibits the proliferation of bile duct cancer cells by inducing apoptosis and its effects on the expression of gene-related proteins involved in cancer growth. Methods: Human extrahepatic bile duct cancer cells (SNU-245 and SNU-1196) were cultured. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to determine the effect of metformin on the cell proliferation. Apoptosis was measured by a cell death detection enzyme-linked immunosorbent assay and a caspase-3 activity assay. Expression levels of various proteins, with or without specific small interfering ribonucleic acid-induced gene disruption, were measured by Western blot analysis. The migratory activity of the cancer cells was evaluated by wound healing assay. Results: Metformin suppressed cell proliferation in bile duct cancer cells by inducing apoptosis. Metformin inhibited mammalian target of rapamycin (mTOR) by activation of tuberous sclerosis complex 2 (TSC-2) through phosphorylation of adenosine monophosphate-activated protein kinase at threonine-172 (AMPKThr172). Hyperglycemia impaired metformin-induced AMPKThr172 activation and enhanced phosphorylation of AMPK at serine-485 (AMPKSer485). Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia. Conclusions: Metformin has antineoplastic effects in bile duct cancer, and hyperglycemic environment interrupts the effect of metformin. In addition, AMPK and IGF-1R play a key role in the proliferation of bile duct cancer cells.

OBJECTIVES Diagnosis of reflux esophagitis according to the Los Angeles classification minimal change (LA-M) has a low inter-observer agreement. We aimed to investigate whether the inter-observer agreement of reflux esophagitis was better when expert endoscopists read the endoscopic images, or when the linked color imaging (LCI) or blue laser imaging (BLI)-bright mode was used. In addition, whether the inclusion of LA-M in the definition of reflux esophagitis affected the consistency of the diagnosis was investigated. METHODS During upper endoscopy, endoscopic images of the gastroesophageal junction were taken using white light imaging (WLI), BLI-bright, and LCI modes. Four expert endoscopists and four trainees reviewed the images to diagnose reflux esophagitis according to the modified LA classification. RESULTS The kappa values for the inter-observer variability for the diagnosis of reflux esophagitis were poor to fair among the experts (κ = 0.22, 0.17, and 0.27 for WLI, BLI-bright, and LCI, respectively) and poor among the trainees (κ = 0.18, 0.08, and 0.14 for WLI, BLI-bright, and LCI). The inter-observer variabilities for the diagnosis of reflux esophagitis excluding LA-M were fair to moderate (κ = 0.42, 0.35, and 0.42 for WLI, BLI-bright, and LCI) among the expert endoscopists and moderate among the trainees (κ = 0.48, 0.43, and 0.51 for WLI, BLI-bright, and LCI). CONCLUSIONS The inter-observer agreement for the diagnosis of reflux esophagitis was very low for both the expert endoscopists and the trainees, even using BLI-bright or LCI mode. However, when reflux esophagitis LA-M was excluded from the diagnosis of esophagitis, the degree of inter-observer agreement increased.

Tris(2-chloroethyl) phosphate (TCEP) is an organophosphate flame retardant that used in textiles, industrial materials, and furniture to delay the spread of fire after ignition. TCEP has been detected in the tissues and eggs of fish and birds. However, there are no studies regarding the effects of TCEP on avian embryos. In the present study, we investigated the developmental toxicity of TCEP exposure on chicken embryos in a shell-less incubation system, which enables in situ observation. Chicken embryos were treated with graded doses of TCEP (50, 250, and 500 nmol/g egg) on incubation day 0. The survival rate, morphological biometrics, heart rate, and length and branch number of extraembryonic blood vessels were measured on incubation days 3–9. Survival rates were reduced from incubation day 3 and were significantly decreased until day 9. Body length, head + bill length and eye diameter were significantly reduced by TCEP exposure. Regarding skeletal effects, spine length was decreased in a dose-dependent manner on day 9. Body weight on day 9 significantly reduced in all TCEP treatment groups. These results suggest that TCEP exposure to >50 nmol/g egg retards development in chicken embryos. TCEP exposure to 500 nmol/g egg significantly increased heart weight to body weight ratio in the embryos. More than 250 nmol/g egg of TCEP significantly reduced the heart rate of embryos in the early developmental stage. The formation of extraembryonic blood vessels and the number of erythrocytes were significantly reduced even with 50 nmol/g egg of TCEP. These findings suggest that TCEP exposure specifically affects the cardiovascular system in chicken embryos, which leads to developmental delay. The results of this study also demonstrate that the shell-less incubation system can be used to continuously monitor the effects of chemicals on developing avian embryos.

Refractory functional dyspepsia (RFD) is diagnosed when symptoms persist for at least 6 months despite at least two medical treatments. No consensus treatment guidelines exist. The implicated causes of functional biliary dyspepsia are a narrowed cystic duct, Sphincter of Oddi dysfunction, microlithiasis, and gallbladder dyskinesia. We investigated the treatment effects of litholytic agents. RFD patients were prospectively enrolled in six tertiary medical centers. All subjects took chenodeoxycholic and ursodeoxycholic acids (CNU) twice daily for 12 weeks. We monitored their medication adherence, laboratory results, and complications. The 7-point global symptom scale test scores were determined before and after treatment. Of the 52 patients who were prospectively screened, 37 were included in the final analysis. The mean age was 51.3 years: 14 were males, and 23 were females. Before treatment, the mean number and duration of symptoms were 2.4 and 48.2 months, and a mean of 3.3 FD-related drugs were taken. The mean CNU adherence was 95.3%. The mean global symptom scale score decreased from 5.6 pretreatment to 2.6 posttreatment. The symptom improvement rate was 94.6% (35 out of 37 patients). The only adverse event was mild diarrhea (10.8%) that was resolved after conservative management. Conclusions: CNU improved the symptoms of RFD patients who did not respond to conventional medications. Litholytic agents are good treatment options for patients with RFD and biliary dyspepsia secondary to biliary microlithiasis. Further prospective, large-scale mechanistic studies are warranted.

Sarcopenia is considered an important factor affecting the prognosis of cancer patients. Only complete surgical resection confers the chance of curing cholangiocarcinoma with sarcopenia. However, the prognosis is poor, even for patients who undergo surgical resection. Data from 13 trials of patients with sarcopenia and intrahepatic cholangiocarcinoma (ICC) or perihilar cholangiocarcinoma (PHC) were collected and reviewed. During all trials, sarcopenia was assessed using the psoas muscle or total skeletal muscle at the L3 level on cross-sectional images. The data showed heterogeneity among the subjects and treatment options and discrepancies in methods of measuring muscle mass and setting the cut-off level. Despite conflicting results regarding morbidity, mortality, and recurrence, sarcopenia may be associated with poor overall survival and recurrence-free survival (RFS) for ICC patients. The impact of sarcopenia on the morbidity of ICC patients remains unclear. The impact of PHC on morbidity, mortality, and RFS is also unclear. Further well-designed studies are needed to elucidate the effects of sarcopenia on ICC and PHC.

Linked color imaging (LCI), a novel image-enhanced endoscopy, can make it easy to recognize differences in mucosal color. It may be helpful for diagnosingUpper endoscopy was performed for 100 patients using white light imaging (WLI) and LCI. During the exam, endoscopic video was recorded. It was then analyzed by four expert endoscopists. They reviewed these videos for endoscopic diagnosis of atrophic gastritis, metaplastic gastritis, nodular gastritis andKappa values for the inter-observer variability among the four endoscopists were fair to moderate under WLI and fair to good under LCI. Sensitivity, specificity, positive predictive value and negative predictive value for diagnosingLCI has better diagnostic accuracy for