In Silico and In Vitro multiple analysis approach for screening naturally derived ligands for red seabream aryl hydrocarbon receptor.

The aryl hydrocarbon receptor (AHR) is a key ligand-dependent transcription factor that mediates the toxic effects of compounds such as dioxin. Recently, natural ligands of AHR, including flavonoids, have been attracting physiological and toxicological attention as they have been reported to regulate major biological functions such as inflammation and anti-cancer by reducing the toxic effects of dioxin. Additionally, it is known that natural AHR ligands can accumulate in wildlife tissues, such as fish. However, studies in fish have investigated only a few ligands in experimental fish species, and the AHR response of marine fish to natural AHR ligands of various other structures has not been thoroughly investigated. To explore various natural AHR ligands in marine fish, which make up the most fish, it is necessary to develop new screening methods that consider the specificity of marine fish. In this study, we investigated the response of natural ligands by constructing in vitro and in silico experimental systems using red seabream as a model species. We attempted to develop a new predictive model to screen potential ligands that can induce transcriptional activation of red seabream AHR1 and AHR2 (rsAHR1 and rsAHR2). This was achieved through multiple analyses using in silico/ in vitro data and Tox21 big data. First, we constructed an in vitro reporter gene assay of rsAHR1 and rsAHR2 and measured the response of 10 representatives natural AHR ligands in COS-7 cells. The results showed that FICZ, Genistein, Daidzein, I3C, DIM, Quercetin and Baicalin induced the transcriptional activity of rsAHR1 and rsAHR2, while Resveratrol and Retinol did not induce the transcriptional activity of rsAHR isoforms. Comparing the EC50 values of the respective compounds in rsAHR1 and rsAHR2, FICZ, Genistein, and Daidzein exhibited similar isoform responses, but I3C, Baicalin, DIM and Quercetin show the isoform-specific responses. These results suggest that natural AHR ligands have specific profiling and transcriptional activity for each rsAHR isoform. In silico analysis, we constructed homology models of the ligand binding domains (LBDs) of rsAHR1 and rsAHR2 and calculated the docking energies (U_dock values) of natural ligands with measured in vitro transcriptional activity and dioxins reported in previous studies. The results showed a significant correlation (R2=0.74(rsAHR1), R2=0.83(rsAHR2)) between docking energy and transcriptional activity (EC50) value, suggesting that the homology model of rsAHR1 and rsAHR2 can be utilized to predict the potential transactivation of ligands. To broaden the applicability of the homology model to diverse compound structures and validate the correlation with transcriptional activity, we conducted additional analyses utilizing Tox21 big data. We calculated the docking energy values for 1860 chemicals in both rsAHR1 and rsAHR2, which were tested for transcriptional activation in Tox21 data against human AHR. By comparing the U_dock energy values between 775 active compounds and 1085 inactive compounds, a significant difference (p<0.001) was observed between the U_dock energy values in the two groups, suggesting that the U_dock value can be applied to distinguish the activation of compounds. Furthermore, we observed a significant correlation (R2=0.45) between the AC50 of Tox21 database and U_dock values of human AHR model. In conclusion, we calculated equations to translate the results of an in silico prediction model for ligand screening of rsAHR1 and rsAHR2 transactivation. This ligand screening model can be a powerful tool to quantitatively estimate AHR transactivation of major marine agents to which red seabream may be exposed. The study introduces a new screening approach for potential natural AHR ligands in marine fish, based on homology model-docking energy values of rsAHR1 and rsAHR2, with implications for future agonist development and applications bridging in silico and in vitro data.

Assessment of Occupational Health Risks for Maintenance Work in Fabrication Facilities: Brief Review and Recommendations.

Background: This study focuses on assessing occupational risk for the health hazards encountered during maintenance works (MW) in semiconductor fabrication (FAB) facilities. Objectives: The objectives of this study include: 1) identifying the primary health hazards during MW in semiconductor FAB facilities; 2) reviewing the methods used in evaluating the likelihood and severity of health hazards through occupational health risk assessment (OHRA); and 3) suggesting variables for the categorization of likelihood of exposures to health hazards and the severity of health effects associated with MW in FAB facilities. Methods: A literature review was undertaken on OHRA methodology and health hazards resulting from MW in FAB facilities. Based on this review, approaches for categorizing the exposure to health hazards and the severity of health effects related to MW were recommended. Results: Maintenance workers in FAB facilities face exposure to hazards such as debris, machinery entanglement, and airborne particles laden with various chemical components. The level of engineering and administrative control measures is suggested to assess the likelihood of simultaneous chemical and dust exposure. Qualitative key factors for mixed exposure estimation during MW include the presence of safe operational protocols, the use of air-jet machines, the presence and effectiveness of local exhaust ventilation system, chamber post-purge and cooling, and proper respirator use. Using the risk (R) and hazard (H) codes of the Globally Harmonized System alongside carcinogenic, mutagenic, or reprotoxic classifications aid in categorizing health effect severity for OHRA. Conclusion: Further research is needed to apply our proposed variables in OHRA for MW in FAB facilities and subsequently validate the findings.

Development of occupation-based exposure matrix of lead for Korean workers: challenges and opportunities.

OBJECTIVES: Industry- and occupation-based carcinogen exposure matrices play a pivotal role in preventing occupational cancer. While the Korean CARcinogen EXposure (K-CAREX) has been developed in recent years to assess exposure prevalence and intensity by industry, the feasibility of constructing an occupation-based exposure matrix remains unexplored. Hence, the objective of this study is to explore the potential of combining the nationwide work environment measurement database (WEMD) and the special health examination database (SHED) to develop a comprehensive occupation-based exposure matrix. METHODS: The WEMD provides information on airborne lead measurements, including industry codes, but it does not include data related to occupations. In contrast, the SHED contains information on both occupation and blood lead levels. By integrating these 2 databases, we attempted to assess airborne lead exposure levels by occupation. Additionally, we performed a rank correlation analysis to compare the airborne exposure levels with corresponding blood lead levels according to occupation. RESULTS: A total of 35 425 workers who both wore air samplers for lead and underwent special health examinations for lead were extracted between 2019 and 2021. An occupation-based exposure matrix was developed to evaluate the intensity of lead exposure across a range of occupations, encompassing 51 minor occupations and 70-unit occupations. Rank correlation analyses showed strong positive correlations between airborne lead and blood lead measurements according to occupation. CONCLUSIONS: Our study findings suggest that combining 2 nationwide surveillance databases can be an effective approach for creating an occupation-based exposure matrix. However, our results also highlight several limitations that need to be addressed in future studies to improve the accuracy and reliability of such matrices.

Clinical impact of pancreatic steatosis measured by CT on the risk of post-ERCP pancreatitis: a multicenter prospective trial.

BACKGROUND AND AIMS: Pancreatic steatosis (PS) may be a risk factor for acute pancreatitis. Whether it is also a risk factor for post-ERCP pancreatitis (PEP) has not been evaluated. This study aimed to determine the impact of PS on PEP development. METHODS: This multicenter prospective trial enrolled 786 consecutive patients who underwent contrast-enhanced abdominal CT and subsequent first-time ERCP. PS was evaluated based on pancreatic attenuation on unenhanced CT images. The risk of PS for the development of PEP was evaluated using a logistic regression model. RESULTS: Of 527 patients included in the study, 157 (29.8%) had PS and 370 (70.2%) did not. At 24 hours after ERCP, there was a significant difference in the PEP identified in 22 patients (14.0%) in the PS group and 23 patients (6.2%) in the "no PS" (NPS) group (P = .017). Diabetes and hypertension were more common in the PS group than in the NPS group; no differences in dyslipidemia were found. Patients with PS had a higher risk for the development of PEP than those with NPS (odds ratio, 2.09; 95% confidence interval, 1.08-4.03). No other variables were identified as risk factors for PEP. CONCLUSIONS: PS is a significant risk factor for PEP for which preventive measures should be considered. Standardized measurement protocols to assess PS by CT are needed. (Clinical trial registration number: KCT0006068.).

Gallbladder perforation in acute acalculous vs. calculous cholecystitis: a retrospective comparative cohort study with 10-year single-center experience.

BACKGROUND: Gallstones are a well-known risk factor for acute cholecystitis. However, their role as a risk factor for gallbladder perforation (GBP) remains unclear. Therefore, this study aimed to determine the effect of gallstones on the development of GBP. MATERIALS AND METHODS: This large-scale retrospective cohort study enrolled consecutive patients who underwent cholecystectomy for acute cholecystitis. The primary endpoint was the role of gallstones as a risk factor for developing GBP. Secondary endpoints included the clinical characteristics of GBP, other risk factors for GBP, differences in clinical outcomes between patients with acalculous cholecystitis (AC) and calculous cholecystitis (CC), and the influence of cholecystectomy timing. RESULTS: A total of 4497 patients were included in this study. The incidence of GBP was significantly higher in the AC group compared to the CC group (5.6% vs. 1.0%, P<0.001). However, there were no differences in ICU admission and hospital stay durations. The incidence of overall complications was significantly higher in the AC group than in the CC group (2.2% vs. 1.0%, P<0.001). Patients with AC had a higher risk of developing GBP than those with CC (odds ratio, 5.00; 95% confidence interval, 2.94-8.33). In addition, older age (≥60 y), male sex, comorbidities, poor performance status, and concomitant acute cholangitis were associated with the development of GBP. Furthermore, the incidence of GBP was significantly higher in the delayed cholecystectomy group than in the early cholecystectomy group (2.0% vs. 0.9%, P<0.001). CONCLUSIONS: AC is a significant risk factor for GBP. Furthermore, early cholecystectomy can significantly reduce GBP-related morbidity and mortality.

Evaluation on the sex-specific association between cigarette smoke exposure and inflammation markers - C-reactive protein and white blood cell count.

INTRODUCTION: Cigarette smoke increases peripheral white blood cell (WBC) count. However, the dose-dependent association between smoking and C-reactive protein (CRP), an important inflammatory marker, has been reported inconsistent. Here, we evaluated the associations between smoking and CRP using both smoking questionnaires and urine cotinine as exposure markers. METHODS: The Korea National Health and Nutrition Examination Survey data were used for analyzing the associations. Multiple regression analyses were performed to examine the associations between cigarette smoke exposure, as assessed by questionnaires and urine cotinine, and health effects, as measured by CRP and WBC count, controlling for potential confounders. The confounders, including age, sex, body mass index, blood pressure, cholesterol, glucose, alanine aminotransferase, and uric acid, were selected a priori based on the literature. RESULTS: A total of 11,435 participants were included for analysis. For the exposure-response relationship, the results indicated a significant increase in CRP levels in male smokers compared to male non-smokers (p=0.002), whereas no significant increase was found in female smokers compared to female non-smokers (p=0.680). For the dose-response relationship, a significant positive association was observed between urine cotinine and CRP in male smokers (p=0.018), whereas no significant association was found in female smokers (p=0.508). WBC count consistently showed significant exposure-response and dose-response relationships in both sexes. CONCLUSIONS: WBC count was found to be a consistent effect marker of cigarette smoke exposure, while the association between CRP level and smoking was inconsistent and varied by sex. The sex-specific response to cigarette smoke exposure warrants further exploration in future studies. IMPLICATION: Cigarette smoke exposure is known to increase inflammation and has been thought to increase C-reactive protein (CRP), a significant inflammation marker. However, recent studies have reported conflicting results regarding the dose-dependent association between cigarette smoke exposure and CRP. This study found that the association between smoking and CRP is inconsistent and varies by sex, showing significant exposure-response in men but not in women. Furthermore, the study suggests that white blood cell count is a more consistent marker for cigarette smoke exposure.

Evaluation of Temporal Trends of Lead Exposure in Korean Workers Using Workplace Monitoring Data.

BACKGROUND: Lead, which is widely used in various industrial settings, is a major health hazard for manufacturing workers. Therefore, control of lead exposure has been implemented in an effort to prevent lead-related health problems. In this study, our aim was to evaluate temporal trends in occupational lead exposure in Korean lead workers using data from monitoring of workplace exposure. METHODS: A nationwide work environment monitoring database, data from a work environment monitoring institution, and data extracted from a review paper were utilized. Different versions of standard industrial classification codes were aligned with the 10th Korean Standard Industrial Classification, which is generally consistent with the 4th revision of the International Standard Industrial Classification. The multiple data sources were combined and temporal trends over the period from 1994-2021 were estimated. In addition, separate estimation of temporal trends in the storage battery manufacturing industry over the period from 1987-2021 was also performed. RESULTS: A total of 444,296 personal airborne lead measurements were used for the estimation process. The temporal trends in occupational exposure to lead declined by -6% annually over the study period. In particular, levels of lead exposure in the storage battery manufacturing industry showed a steeper decline of -12% annually. CONCLUSIONS: Findings of our study showed that occupational exposure to lead declined over the period from 1994 to 2021 in Korea. However, adverse effects of exposure to lead on health should be regarded with caution. The results will be useful in conduct of epidemiological studies examining lead-related effects on health.

Efficacy of a Newly Developed Guidewire for Selective Biliary Cannulation: A Multicenter Randomized Controlled Trial.

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.

Comparison of Two Types of Guidewires for Malignant Hilar Biliary Obstruction by Endoscopic Retrograde Cholangiopancreatography: A Randomized Controlled Trial.

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.

Characteristics of Peak Exposure of Semiconductor Workers to Extremely Low-Frequency Magnetic Fields.

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.

Successful Intubation Using a Cap-Assisted Colonoscope for Endoscopic Retrograde Cholangiopancreatography in Patients Undergoing Roux-en-Y Reconstruction.

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.

Placement of Plastic Stents after Direct Endoscopic Necrosectomy through a Novel Lumen-Apposing Metal Stent for Effective Treatment of Laterally Extended Walled-Off Necrosis: A Pilot Study.

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.

Characteristics of workers' compensation claim applications for COVID-19 infections in South Korea.

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.

EUS-guided tissue acquisition using a novel torque technique is comparable with that of the fanning technique for solid pancreatic lesions: A multicenter randomized trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Cholecystectomy Increases the Risk of Type 2 Diabetes in the Korean Population: Data From the National Health Insurance Cooperation Health Checkup 2010-2017.

OBJECTIVE: This study assessed whether cholecystectomy is a risk factor for newly developed type 2 diabetes mellitus (T2DM) in the Korean population. BACKGROUND: There is a lack of evidence that cholecystectomy is independently associated with insulin resistance and T2DM. METHODS: This study included all patients aged more than 20 years who had undergone cholecystectomy from 2010 to 2015 (n=55,166) and age-matched 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. RESULTS: Overall, 55,166 patients who underwent cholecystectomy and 110,332 age-matched and sex-matched controls were followed up for ∼4.7 years, during which, incident T2DM occurred in 5982 (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 ∼7 years ( P <0.001). 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 the 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). CONCLUSIONS: These results provide evidence that cholecystectomy is associated with an increased risk of newly developed T2DM in the Korean population. Further research is required to elucidate the mechanism of the association between cholecystectomy and incident diabetes.

A Pilot Establishment of the Job-Exposure Matrix of Lead Using the Standard Process Code of Nationwide Exposure Databases in Korea.

Background: 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. Methods: 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. Results: 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/m3, exceeding the occupational exposure limit of 50 µg/m3. Regardless of the limitation of the minimum number of samples in the exposure group, higher contrast was observed when the exposure groups were by industry process than by industry or process. Conclusion: We 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.

Ursodeoxycholic acid inhibits epithelial-mesenchymal transition, suppressing invasiveness of bile duct cancer cells: An in vitro study.

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.

The Safety and Efficacy of an Unflanged 4F Pancreatic Stent in Transpancreatic Precut Sphincterotomy for Patients with Difficult Biliary Cannulation: A Prospective Cohort Study.

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.