Relieving Anxiety Through Virtual Reality Prior to Endoscopic Procedures

Purpose: Endoscopic procedures can cause anxiety, which can lead to more uncomfortable, difficult, and incomplete procedures, in addition to greater use of sedative medication. Here, we investigate whether exposing patients to virtual reality (VR) prior to endoscopic procedures can reduce their anxiety levels. Materials and methods: Forty patients at Gangnam Severance Hospital were enrolled and divided into the VR group and the control group. Patients in the VR group were exposed to VR prior to their procedure to alleviate anxiety. The primary data outcomes were State-Trait Anxiety Inventory (STAI), pain score, satisfaction with sedation, and satisfaction with the procedure. Results: The mean STAI-state and STAI-trait did not differ significantly between the control group and the VR group. While defining a high anxiety STAI score as ≥45 in an STAI-state, the proportion of patients with high anxiety at baseline was 35% and increased to 50% prior to the procedure in the control group. However, in the VR group, the proportion of patients with high anxiety at baseline was 60% and decreased to 50% prior to the procedure. The proportion changes of patients with high anxiety in the STAI-state exhibited a significant difference between the control and VR groups (p=0.007). Furthermore, patients' satisfaction with sedation was significantly greater in the VR group compared to the control group (p=0.017). Conclusion: VR exposure may relieve patients' anxiety levels prior to endoscopic procedures, but further well-designed placebo-controlled studies are needed. VR, an inexpensive, easily available, and non-invasive method, also improved the satisfaction with sedation of endoscopic procedures.ope

Rebleeding Rate and Risk Factors for Rebleeding after Device-Assisted Enteroscopy in Patients with Obscure Gastrointestinal Bleeding: A KASID Multicenter Study

Introduction: The impact of device-assisted enteroscopy (DAE) on long-term rebleeding in patients with obscure gastrointestinal bleeding (OGIB) exhibiting detectable small-bowel lesions remains unclear. We investigated the long-term rebleeding rate and predictive factors for DAE in patients with OGIB. Method: Patients with OGIB with small bowel lesions detected through DAE were enrolled at three Korean tertiary hospitals. Predictive risk factors associated with rebleeding were analyzed using the Cox regression analysis. Results: From April 2008 to April 2021, 141 patients were enrolled, including 38 patients (27.0%) with rebleeding. The rebleeding rates at 1, 2, and 3 years were 25.0%, 29.6%, and 31.1%, respectively. The Cox regression analysis revealed that multiple small-bowel lesions (hazard ratio [HR]: 2.551, 95% confidence interval [CI]: 1.157-5.627, p = 0.020), the need for more than five packed red blood cells (RBC) transfusions (HR: 2.704, 95% CI: 1.412-5.181, p = 0.003), and ulcerative lesions (HR: 1.992, 95% CI: 1.037-3.826, p = 0.039) were positively associated with rebleeding. Therapeutic interventions for patients with detectable lesions, overt bleeding (vs. occult bleeding), comorbidities, and medications were not associated with rebleeding. Conclusion: More than 25% of patients with OGIB having detectable small-bowel lesions had rebleeding. Patients with multiple lesions, a requirement of more than five packed RBC transfusions, and ulcerative lesions were associated with a higher risk of rebleeding.ope

Probe-Based Confocal Laser Endomicroscopy versus White-Light Endoscopy with Narrow-Band Imaging for Predicting and Collecting Residual Cancer Tissue in Patients with Gastric Cancer Receiving Chemotherapy

In cases of progression despite chemotherapy, collecting gastric cancer (GC) tissues might be helpful for molecular biology research or the development of new target drugs for treating cases that are refractory to chemotherapy. Chemotherapy, however, may reduce or alter the distribution of GC tissue on the surface, making the detection of GC tissue during upper endoscopy challenging. Probe-based confocal laser endomicroscopy (pCLE) is a new technology that enables histological diagnosis by magnifying the mucous membrane to a microscopic level. Here, we evaluated whether pCLE could increase the yield of endoscopic biopsy for GC compared to white-light endoscopy (WLE) with magnifying narrow-band imaging (M-NBI) in GC patients receiving chemotherapy with its powerful imaging technique. Patients underwent WLE/M-NBI and pCLE for the detection of residual GC for the purpose of response evaluation or clinical trial registration. After WLE/M-NBI and pCLE, each residual GC lesion was biopsied for histological analysis. A total of 23 patients were enrolled between January 2018 and June 2020. Overall, pCLE showed significantly higher sensitivity and negative predictive value than WLE/M-NBI. The accuracy of pCLE was superior to that of WLE/M-NBI. Moreover, pCLE showed better predictive ability for residual GC than WLE/M-NBI, while WLE/M-NBI and pCLE showed inconsistent results. pCLE diagnosed residual GC more accurately than WLE/M-NBI, which resulted in an increased number of GC tissues collected during the endoscopic biopsy.ope

Association of immune-mediated inflammatory diseases with depression and anxiety in patients with type 2 diabetes: A nationwide population-based study

Objective: Patients with type 2 diabetes (T2DM) are at a high risk of developing depression and anxiety. To better stratify the risk, we aimed to assess whether the presence of immune-mediated inflammatory diseases (IMIDs) confers a higher risk of depression and anxiety in these patients. Methods: Patients with T2DM without prior depression or anxiety who underwent national health examination between 2009 and 2012 (n = 1,612,705) were enrolled from the nationwide health check-up data from Korean National Health Insurance Service. The outcome events were incident depression and anxiety, defined as International Classification of Diseases, 10th Revision codes F32–F33 and F40–F41, respectively. Multivariable Cox proportional hazard regression analyses were conducted to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) according to the existence of IMIDs. Results: Over an average follow-up time of 6.4 years, existence of gut IMIDs was associated with a higher risk of depression (aHR: 1.28 [95% CI: 1.08–1.53]) and anxiety (1.22 [1.06–1.42]). Existence of joint IMIDs was associated with a higher risk of depression (1.34 [1.31–1.37]) and anxiety (1.31 [1.29–1.34]). Existence of skin IMID was associated with a higher risk of depression (1.18 [1.14–1.23]) and anxiety (1.13 [1.09–1.16]). The effect sizes of IMIDs on depression and anxiety were larger in those with ≥ 2 IMIDs (1.42 [1.19–1.69] and 1.49 [1.29–1.72], respectively) than in those with one IMID (1.30 [1.27–1.32] and 1.26 [1.24–1.28], respectively). Conclusion: In patients with T2DM, presence of IMIDs was associated with a higher risk of depression and anxiety. More stringent attention and screening for anxiety and depression should be encouraged in patients with T2DM and comorbid IMIDs due to clinical implications of sychological distress on patientreported outcomes and prognosis.ope

Predictors of Complete Response in Patients with Hepatocellular Carcinoma Treated with Trans-Arterial Radioembolization

Background: Trans-arterial radioembolization (TARE) has shown promising results in treating hepatocellular carcinoma (HCC). We identified independent predictors of radiological complete response (CR) in patients with intrahepatic HCC who were treated with TARE. Methods: Patients with intrahepatic HCC treated with TARE between 2011 and 2017 were recruited. CR was defined according to the modified Response Evaluation Criteria in Solid Tumors. Cox regression analysis was used to determine independent predictors of CR. Results: The median age of study participants (83 men and 19 women) was 64.3 years. The mean survival after TARE was 55.5 months, and 21 (20.6%) patients died during the study period. Patients who achieved CR (14 patients, 13.7%) had significantly higher serum albumin level (median 4.1 vs. 3.9 g/dL), lower total bilirubin level (median 0.6 vs. 0.7 mg/dL), lower aspartate aminotransferase level (median 30.0 vs. 43.0 IU/L), lower alkaline phosphatase level (median 79.0 vs. 103.0 IU/L), lower alpha-fetoprotein level (median 12.7 vs. 39.9 ng/mL), lower des-gamma-carboxyprothrombin level (median 575.5 vs. 2772.0 mAU/mL), lower model for end-stage liver disease (MELD) score (median 6.0 vs. 7.0), and smaller maximal tumor diameter (median 6.3 vs. 9.0 cm) compared to those who did not achieve CR (all p < 0.005). Multivariate Cox regression analysis showed that lower MELD score (hazard ratio (HR) = 0.436, p = 0.015) and maximal tumor size < 9 cm (HR = 11.180, p = 0.020) were independent predictors of an increased probability of radiological CR after TARE. Conclusions: Low MELD score and small maximal tumor size were independently associated with an increased probability of CR after TARE in patients with intrahepatic HCC.ope

Triglyceride-glucose index is associated with gastroesophageal reflux disease and erosive reflux disease: a health checkup cohort study

The triglyceride-glucose (TyG) index was proposed as a useful marker of metabolic syndrome. Insulin resistance, the main mechanism underlying metabolic syndrome, is related to gastroesophageal reflux disease (GERD). This study aimed to elucidate the association between the TyG index and GERD/erosive reflux disease (ERD). We retrospectively reviewed the electronic medical records of patients who underwent gastroduodenoscopy at a checkup center. The calculation of TyG index used following formula: ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). We divided the patients into four groups according to the TyG index quartile (Q). We evaluated the relationship between the alteration of the TyG index and GERD in patients who received health checkups two times. Among the 52,605 enrolled patients, 3073 (5.8%) and 434 (0.8%) were diagnosed with GERD and ERD, respectively. The odds ratios (ORs) for GERD in the TyG index progressively increased across quartiles (P < 0.001): Q2 (OR = 2.477), Q3 (OR = 3.013), and Q4 (OR = 4.027) compared with Q1, which was used as a reference, respectively. Those for ERD also progressively increased across quartiles (P < 0.001): Q2 (OR = 4.264), Q3 (OR = 4.841), and Q4 (OR = 7.390) compared with Q1, respectively. Moreover, the degree of TyG index increase during the first and second tests in the GERD group was more prominent than in the control group (P = 0.001). In conclusion, the higher TyG index was significantly associated with GERD. The TyG index may be a novel predictive biomarker of GERD and ERD.ope

Risk of all-cause and cause-specific mortality associated with immune-mediated inflammatory diseases in Korea

Objective: Immune-mediated inflammatory disease (IMID) is associated with an increased risk of mortality. It is unclear whether the higher mortality is attributable to the IMIDs themselves or to the higher prevalence of comorbidities in IMIDs. We aimed to investigate whether IMIDs per se confer a higher risk of mortality. Methods: From the Korean National Health Insurance Service-National Sample Cohort database, this population-based cohort study included 25,736 patients newly diagnosed with IMIDs between January 2007 and December 2017, and 128,680 individuals without IMIDs who were matched for age, sex, income, hypertension, type 2 diabetes, dyslipidemia, and the Charlson comorbidity index. All individuals were retrospectively observed through December 31, 2019. The outcomes included all-cause and cause-specific mortalities. Adjustments for age, sex, and comorbidities were performed using multivariable Cox proportional hazard regression analyses, and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the outcomes were estimated. Results: The adjusted risk of all-cause mortality was significantly lower in patients with IMIDs than that in those without (aHR, 0.890; 95% CI, 0.841-0.942). Regarding cause-specific mortality, cancer-specific (aHR, 0.788; 95% CI, 0.712-0.872) and cardiovascular disease-specific (aHR, 0.798; 95% CI, 0.701-0.908) mortalities were the two causes of death that showed significantly lower risks in patients with IMIDs. A similar trend was observed when organ based IMIDs were analyzed separately (i.e., gut, joint, and skin IMIDs). Conclusion: After adjusting for comorbidities, IMIDs were associated with a lower risk of all-cause mortality compared to those without IMIDs. This was attributable to the lower risks of cancer-and cardiovascular disease-specific mortalities.ope

Cardiovascular Risk Is Elevated in Lean Subjects with Nonalcoholic Fatty Liver Disease

Background/aims: : Nonalcoholic fatty liver disease (NAFLD) and obesity are independently associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality in patients with NAFLD. Many NAFLD patients are lean, but their ASCVD risk compared to obese subjects with NAFLD is unclear. Methods: Data from the 2008 to 2011 Korea National Health and Nutrition Examination Surveys database were analyzed (n=4,786). NAFLD was defined as a comprehensive NAFLD score ≥40 or a liver fat score ≥-0.640. ASCVD risk was evaluated using the American College of Cardiology/ American Heart Association guidelines. Results: The frequency of subjects without NAFLD, with obese NAFLD, and with lean NAFLD was 62.4% (n=2,987), 26.6% (n=1,274), and 11.0% (n=525), respectively. Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of a high ASCVD risk (mean 15.6±14.0, 51.6%) than those with obese NAFLD and without NAFLD (mean 11.2±11.4, 39.8%; mean 7.9±10.9, 25.5%; all p<0.001). Subjects with lean NAFLD and significant liver fibrosis showed a significantly higher odds ratio for a high risk for ASCVD than those with obese NAFLD with or without significant liver fibrosis (odds ratio, 2.60 vs 1.93; p=0.023). Conclusions: Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of high risk for ASCVD than those with obese NAFLD. Similarly, lean subjects with significant liver fibrosis had a higher probability of ASCVD than obese subjects in the subpopulation with NAFLD.ope

Human INO80 와 결합하는 BRCA1 association protein-1 과 Ran binding protein-9 단백질의 발견

INO80 complex is a recent member of the ATP-dependent chromatin remodeling complex family. The yeast INO80 (yINO80) complex have been shown to play roles in non-transcriptional nuclear processes such as DNA repair and replication. Our laboratory has recently found that human INO80 (hINO80) is directly implicated in microtubule assembly and chromosome segregation in addition to DNA repair and replication. hINO80 localizes at replication forks overlapping with PCNA during S phase and associates with microtubules during mitosis. Knockdown of hINO80 leads to impaired DNA replication and defective spindle assembly followed by abnormal chromosome segregation. In an effort to understand the mechanisms underlying the functions of hINO80 in such diverse chromosomal processes, our laboratory carried out yeast two-hybrid screening and identified a large number of cellular proteins to interact with hINO80. Among those, I choose four proteins for further investigation, which were the catalytic subunit of SWI/SNF chromatin remodeling complex (BRG1), centrosomal protein 70 kDa (CEP70), BRCA1 associated protein-1 (BAP1) and Ran GTPase binding protein 9 (RanBP9). First, I performed immunoprecipitation experiments and found that, whereas neither BRG1 nor CEP70 interacts with hINO80, BAP1 and RanBP9 both interact with hINO80. Then, I performed immunofluorescence microscopy, and found that BAP1 forms foci overlapping with hINO80 in the nucleus during S phase and that RanBP9 associates with microtubules overlapping with hINO80 during mitosis. These results suggest that BAP1 and RanBP9 work together with hINO80 to function in DNA replication and microtubule assembly, respectively.;INO80는 ATP를 가수분해할 때 나오는 에너지를 이용하여nucleosome의 구조를 바꿀 수 있는 chromatin remodeling complex중에 최근에 밝혀진 family이다. 효모에서 밝혀진 INO80 은 다른 ATP-dependent chromatin remodeling complex 와 마찬가지로 전사조절에 관계 될 뿐 아니라, DNA 이중나선 절단을 복구하는데 있어서도 직접적으로 관련이 있으며 DNA 복제에도 직접 관계한다는 것이 밝혀졌다. 인간의 INO80 는 효모 INO80 와 homology 를 가지고 있으며 실험실에서의 최근 연구를 통해서 정상적인 세포주기 진행과 microtubule assembly 에서 중요한 역할을 할 뿐만 아니라 DNA 복제와 염색체 분리에도 직접적으로 관련이 있다는 것을 밝혔다. 이러한 인간 INO80 기능의 메커니즘은 아직 명확하게 밝혀지지 않았다. 본 논문에서는 인간 INO80 와 결합하는 단백질을 찾기 위해 실험실에서 진행한 yeast two-hybrid screening 을 통해 밝혀진 71개의 유전자 중 BRG1, CEP70, BAP1, RanBP9 의 4 종류 단백질을 선택하여 인간세포 내에서 결합하는지 알아보았다. 먼저 인간세포인 293T 내에서 면역침전반응을 통해 BRG1 과 CEP70 은 인간 INO80 와 결합하지 않는 것을 확인하였고, BAP1과 RanBP9 은 인간 INO80 와 결합하는 것을 확인하였다. 이 결과를 확증하기 위해 면역형광법을 이용하여 세포 내에서 각각의 단백질의 위치를 확인해 보는 실험을 수행하였다. 이 실험을 통해 BAP1 은 S 기 동안 복제 지점에서 인간 INO80 와 겹치는 foci 를 형성하는 것을 확인했고, RanBP9 은 M 기 동안 microtubule 과 인간 INO80 와 결합하는 것을 확인했다. 이 결과는 BAP1 과 RanBP9 은 인간 INO80 와 함께 각각 DNA 복제, microtubule assembly 에 기능 할 것이라는 가능성을 시사한다. 앞으로 좀 더 면밀한 연구를 통해 이러한 단백질이 어떻게 인간 INO80 와 함께 작용하여 DNA 복제, microtubule assembly, 염색체 분리에 작용하는지 밝혀야 할 것이다.Ⅰ. INTRODUCTION = 1 Ⅱ. MATERIALS AND METHODS = 8 1. Antibodies = 8 2. Cell culture and transfection = 8 3. Cytosolic protein extraction and western blot analysis = 9 4. Immunoprecipitation experiments = 9 5. Confocal immunofluorescense microscopy = 10 Ⅲ. RESULTS = 12 1. Yeast two-hybrid screening for proteins interacting with hINO80 = 12 2. BRG1 does not interact with hINO80 = 20 3. CEP 70 does not interact with hINO80 = 23 4. Bap1 interacts with hINO80 in IP experiments = 26 5. Bap1 forms nuclear foci overlapping with hINO80 during the S phase = 29 6. RanBP9 interacts with hINO80 in IP experiments = 32 7. RanBP9 associates with microtubules and hINO80 at the centrosome during mitosis = 35 Ⅳ. DISCUSSION = 41 Ⅴ. REFERENCES = 45 국문초록 = 5

Possible Neuroprotective Effects of p-Coumaric acid on the Responses of SH-SY5Y and HT22 cells

산화 스트레스는 프리라디컬을 만들어 세포에 손상을 입히는 것으로 알려져 있다. 세포질과 세포막에 존재하는 NQO1과 b5R은 Nrf2/Keap1 pathway에 의해 조절되는 세포막 산화환원 조절 효소의 한 종류로, 항산화 능력이 있어 신경세포에서 스트레스 반응에 관여한다. 그러나 아직 신경세포에서 NOQ1 혹은 b5R을 활성화하여 ROS를 낮추고 세포 생존율을 올려주는 물질에 대한 연구는 많지 않다. 본 연구에서는 콩과 혹은 난초과 식물이나 두릅 등에서 추출 가능한 천연물질인 p-coumaric acid 을 신경세포에 적용하여 나타나는 영향을 조사하였다. 먼저 이 물질을 농도 별로 처리하였고, 단백질 발현과 세포 반응 결과에 따라 적정 농도를 결정하였다. p-coumaric acid를 처리한 경우 인간 신경아세포종 세포(SH-SY5Y)에서는 NQO1의 발현이, 마우스 해마유래 세포(HT22)에서는 b5R의 발현이 증가했다. 여기에 독성물질로 미토콘드리아 저해제인 rotenone과 해당작용 저해제 2-deoxyglucose를 첨가한 결과, rotenone에서 농도 비례적인 방어 효과를 보였다. 그러나, 2-deoxyglucose에서는 p-coumaric acid 농도에 따른 경향성이 발견되지 않았다. 이 결과들을 종합하면 일반적으로 알려진 바와 같이 NQO1 혹은 b5R의 발현이 증가되면 미토콘드리아의 기능이 향상된다. 본 연구에서는 이 물질이 NQO1 혹은 b5R의 발현 정도를 증가시키고, 미토콘드리아 활성을 높여주어 산화 스트레스 발생이 감소한다는 것을 확인했다. 또한 세포 생존율 및 미토콘드리아 독성 물질에 대한 방어능력이 향상되었다.;Oxidative stress is well known to cause damage in cells by inducing free radicals. To counteract against such stress, the antioxidant activity of NADH-quinone oxidoreductase 1 (NQO1) and cytochrome b5 reductase (b5R), two redox enzymes of the plasma membrane (PM) regulated by the Nrf2/Keap1 pathway, adjust cellular responses of stress mechanisms in neuronal cells. However, the factor activating NOQ1 or b5R which leads to the decrease in reactive oxygen species (ROS) and a subsequent increase in cell viability in neuronal cells is yet to be discovered. In this study, the effects of p-coumaric acid (CA), the phytochemical ingredient from Angraecum fragans or Melilotus officinalis Lam, on neuronal cells are revealed. Using various concentrations of the chemical, the optimal level of concentration was determined by protein expression and cellular responses. Results showed p-coumaric acid induces NQO1 in human neuroblastoma cells (SH-SY5Y) and b5R in mouse hippocampal cells (HT22). The result of adding rotenone, a mitochondria inhibitor, and 2-deoxyglucose, a glycolysis inhibitor, to p-coumaric acid-treated cells, revealed that the protective effect of cells towards rotenone increased vi proportionately to p-coumaric acid concentration. On the other hand, it was recorded that p-coumaric acid concentration dependency was not evident in 2-deoxyglucose conditions. Overall, it is generally accepted that the increased expression of NQO1 or b5R improves mitochondrial functions. Findings of this study suggest that p-coumaric acid induces NQO1 or b5R expression and thus enhances mitochondria activity which mediates the protection process against oxidative stresses. In short, cell viability and defence capacity towards mitochondrial damage may be enhanced.I. Introduction 1 II. Materials and Methods 5 1. Materials 5 2. Cell culture 5 3. Trypan blue exclusion assay 6 4. Analysis of cell toxicity 6 5. Measurement of ROS level 6 6. Preparation of protein sample 7 7. Immunoblot analysis 7 8. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging capacity test 8 9. Statistical analysis 8 III. Results 9 1. Free radical scavenging ability of p-coumaric acid 9 2. NQO1 or b5R induction in p-coumaric acid-treated cells 13 3. Effects of p-coumaric acid on the cell viability and protective capacity in response to toxin 17 4. ROS production in control or p-coumaric acid-treated cells 25 5. The comparison of PARP cleavage between control and p-coumaric acid-treated cells with toxin 29 IV. Discussion 32 V. References 36 VI. Abstract (in Korean) 4