2019 Tabletop Exercise for Laboratory Diagnosis and Analyses of Unknown Disease Outbreaks by the Korea Centers for Disease Control and Prevention

Objectives@#The Korea Centers for Disease Control and Prevention has published “A Guideline for Unknown Disease Outbreaks (UDO).” The aim of this report was to introduce tabletop exercises (TTX) to prepare for UDO in the future. @*Methods@#The UDO Laboratory Analyses Task Force in Korea Centers for Disease Control and Prevention in April 2018, assigned unknown diseases into 5 syndromes, designed an algorithm for diagnosis, and made a panel list for diagnosis by exclusion. Using the guidelines and laboratory analyses for UDO, TTX were introduced. @*Results@#Since September 9th , 2018, the UDO Laboratory Analyses Task Force has been preparing TTX based on a scenario of an outbreak caused by a novel coronavirus. In December 2019, through TTX, individual missions, epidemiological investigations, sample treatments, diagnosis by exclusions, and next generation sequencing analysis were discussed, and a novel coronavirus was identified as the causal pathogen. @*Conclusion@#Guideline and laboratory analyses for UDO successfully applied in TTX. Conclusions drawn from TTX could be applied effectively in the analyses for the initial response to COVID-19, an ongoing epidemic of 2019 - 2020. Therefore, TTX should continuously be conducted for the response and preparation against UDO.

Epidemiological Characteristics of COVID-19 Outbreak at Fitness Centers in Cheonan, Korea

Background@#In February 2020, a coronavirus disease 2019 (COVID-19) outbreak was reported in fitness centers in Cheonan, Korea. @*Methods@#From February 24 to March 13, an epidemiological investigation was conducted on the fitness center outbreak. All those who were screened were tested for severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) using real-time reverse transcriptase polymerase chain reaction. Contacts were traced and self-isolated for 14 days. We determined the epidemiological characteristics of confirmed cases of SARS-CoV-2 infection, and estimated the time-dependent reproduction number to assess the transmission dynamics of the infection. @*Results@#A total of 116 cases were confirmed, and 1,687 contacts were traced. The source cases were 8 Zumba instructors who led aerobics classes in 10 fitness centers, and had the largest average number of contacts. A total of 57 Zumba class participants, 37 of their family members, and 14 other contacts were confirmed as cases. The attack rate was 7.3%. The contacts at Zumba classes and homes had a higher attack rate than other contacts. The mean serial interval (± standard deviation) were estimated to be 5.2 (± 3.8) days. The time-dependent reproduction number was estimated to be 6.1 at the beginning of the outbreak, but it dropped to less than 1, 2 days after the epidemiological investigation was launched. @*Conclusion@#The results suggest that the COVID-19 outbreak was effectively contained with rigorous contact tracing, isolating, and testing in combination with social distancing without a lock-down.

Huge Intramural Duodenal Hematoma Complicated with Obstructive Jaundice following Endoscopic Hemostasis / 대한소화기학회지

Intramural hematoma of the duodenum is a relatively unusual complication associated with the endoscopic treatment of bleeding peptic ulcers. Intramural hematomas are typically resolved spontaneously with conservative treatment alone. We report a case of an intramural duodenal hematoma following endoscopic hemostasis with epinephrine injection therapy, which was associated with transient obstructive jaundice in a patient undergoing hemodialysis. The patient developed biliary sepsis due to obstruction of the common bile duct secondary to the huge hematoma. He was treated with fluoroscopy-guided drainage catheter insertion, which spontaneously resolved the biliary sepsis through conservative treatment in 6 weeks. Fluoroscopy-guided drainage may impact the treatment of intramural hematomas that involve life-threatening complications.

Suggestion of Learning Objectives in Social Dental Hygiene: Oral Health Administration Area / 치위생과학회지

The purpose of this study is to propose learning objectives in social dental hygiene by analyzing and reviewing learning objectives in oral health administration area of the existing public oral health. This study is a cross-sectional study. The subjects of the study selected with convenience extraction were 15 members of the social dental hygiene subcommittee of the Korean Society of Dental Hygiene Science. Data collection was conducted by self-filling questionnaire. The research tool is from 48 items of A division in the book of learning objectives in the dental hygienist national examination, and this study classified each of them into ‘dental hygiene job relevance’, ‘dental hygiene competency relevance’, ‘timeliness’, and ‘value discrimination of educational goal setting’ to comprise 192 items. Also, to collect expert opinions, this study conducted Delphi survey on 7 academic experts. Statistical analysis was performed using the IBM SPSS Statistics ver. 23.0 program (IBM Co., Armonk, NY, USA). Recoding was performed according to the degree of relevance of each learning objective and frequency analysis was performed. This study removed 18 items from the whole learning objectives in the dental hygienist national examination in the oral health administration area of public oral health. Fifteen revisions were made and 15 existing learning objectives were maintained. Forty-five learning objectives were proposed as new social dental hygiene learning objectives. The topics of learning objectives are divided into social security and medical assistance, oral health care system, oral health administration, and oral health policy. As a result of this study, it was necessary to construct the learning objectives of social dental hygiene in response to changing situation at the time. The contents of education should be revised in order of revision of learning objectives, development of competency, development of learning materials, and national examination.

Anti-bacterial effects of enzymatically-isolated sialic acid from glycomacropeptide in a Helicobacter pylori-infected murine model

BACKGROUND/OBJECTIVES: Helicobacter pylori (H. pylori) colonization of the stomach mucosa and duodenum is the major cause of acute and chronic gastroduodenal pathology in humans. Efforts to find effective anti-bacterial strategies against H. pylori for the non-antibiotic control of H. pylori infection are urgently required. In this study, we used whey to prepare glycomacropeptide (GMP), from which sialic acid (G-SA) was enzymatically isolated. We investigated the anti-bacterial effects of G-SA against H. pylori in vitro and in an H. pylori-infected murine model. MATERIALS/METHODS: The anti-bacterial activity of G-SA was measured in vitro using the macrodilution method, and interleukin-8 (IL-8) production was measured in H. pylori and AGS cell co-cultures by ELISA. For in vivo study, G-SA 5 g/kg body weight (bw)/day and H. pylori were administered to mice three times over one week. After one week, G-SA 5 g/kg bw/day alone was administered every day for one week. Tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and IL-10 levels were measured by ELISA to determine the anti-inflammatory effects of G-SA. In addition, real-time PCR was performed to measure the genetic expression of cytotoxin-associated gene A (cagA). RESULTS: G-SA inhibited the growth of H. pylori and suppressed IL-8 production in H. pylori and in AGS cell co-cultures in vitro. In the in vivo assay, administration of G-SA reduced levels of IL-1β and IL-6 pro-inflammatory cytokines whereas IL-10 level increased. Also, G-SA suppressed the expression of cagA in the stomach of H. pylori-infected mice. CONCLUSION: G-SA possesses anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect in an experimental H. pylori-infected murine model. G-SA has potential as an alternative to antibiotics for the prevention of H. pylori infection and H. pylori-induced gastric disease prevention.

Cilostazol inhibits insulin-stimulated expression of sterol regulatory binding protein-1c via inhibition of LXR and Sp1

Hepatic steatosis is common in obese individuals with hyperinsulinemia and is an important hepatic manifestation of metabolic syndrome. Sterol regulatory binding protein-1c (SREBP-1c) is a master regulator of lipogenic gene expression in the liver. Hyperinsulinemia induces transcription of SREBP-1c via activation of liver X receptor (LXR) and specificity protein 1 (Sp1). Cilostazol is an antiplatelet agent that prevents atherosclerosis and decreases serum triglyceride levels. However, little is known about the effects of cilostazol on hepatic lipogenesis. Here, we examined the role of cilostazol in the regulation of SREBP-1c transcription in the liver. The effects of cilostazol on the expression of SREBP-1c and its target genes in response to insulin or an LXR agonist (T0901317) were examined using real-time RT-PCR and western blot analysis on cultured hepatocytes. To investigate the effect of cilostazol on SREBP-1c at the transcriptional level, transient transfection reporter assays and electrophoretic mobility shift assays (EMSAs) were performed. Cilostazol inhibited insulin-induced and LXR-agonist-induced expression of SREBP-1c and its downstream targets, acetyl-CoA carboxylase and fatty acid synthase, in cultured hepatocytes. Cilostazol also inhibited activation of the SREBP-1c promoter by insulin, T0901317 and Sp1 in a luciferase reporter assay. EMSA analysis showed that cilostazol inhibits SREBP-1c expression by repressing the binding of LXR and Sp1 to the promoter region. These results indicate that cilostazol inhibits insulin-induced hepatic SREBP-1c expression via the inhibition of LXR and Sp1 activity and that cilostazol is a negative regulator of hepatic lipogenesis.

A Case of Peliosis Hepatis Mimicking Metastatic Lesions of Increasing Size

Peliosis hepatis, an uncommon vascular condition, is characterized by multiple blood-filled cavities distributed throughout the liver. Computed tomography and magnetic resonance imaging findings of peliosis hepatis are nonspecific. A 40-year-old woman presented with multiple hepatic cystic masses. Two years later, the number and sizes of the masses had increased. We suspected metastatic hepatic disease and performed a liver biopsy. Histological examination revealed dilatation of hepatic sinusoids and multiple blood-filled cavities throughout the liver parenchyma. Thus, a diagnosis of peliosis hepatis was confirmed.

Development and validation of a simple index system to predict nonalcoholic fatty liver disease / 대한간학회지

BACKGROUND/AIMS: Abdominal ultrasonography is useful for the detection and diagnosis of nonalcoholic fatty liver disease (NAFLD). The aims of this study were to establish a predictive model for the selection of subjects for abdominal ultrasonography for the diagnosis of NAFLD and to assess validity of the model. METHODS: The subjects included 901 people who visited the health examination center of the Busan Medical Center. We conducted multiple logistic regression analyses of potential risk factors to identify independent risk factors for NAFLD, and developed an index system. RESULTS: Four independent risk factors were identified. The index system was developed by assigning 1 clinical scoring point to approximately 0.7 logistic regression coefficients to each factor as follows: alanine aminotransferase/aspartate aminotransferase ratio >1.5 (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.21-4.07; P=0.010), 1 point; gamma-glutamyl transpeptidase >50 (OR, 2.15; 95% CI, 1.13-4.07; P=0.019), 1 point; triglyceride >150 mg/dL (OR, 1.92; 95% CI, 1.14-3.24; P=0.015), 1 point; 23 kg/m2< or =BMI<25 kg/m2 (OR, 3.68; 95% CI, 2.05-6.63; P<0.001), 2 points; and BMI 25 kg/m2 (OR, 7.65; 95% CI, 4.29-13.62; P<0.001), 3 points. The area under the receiver operating characteristics curve was 0.797 (95% CI, 0.751-0.842), and when 3 points was used as a cut-off value, the sensitivity and specificity were 71.7% and 75.9%, respectively. CONCLUSIONS: NAFLD can be predicted through the clinical application of the index system established herein. If abdominal ultrasonography is used for high-risk patients, NAFLD will be diagnosed and managed in its early stage.

Novel LMNA Gene Mutation in a Patient With Atypical Werner's Syndrome

Hutchinson-Gilford progeria syndrome (HGPS) and Werner's syndrome are representative types of progeroid syndrome. LMNA (Lamin A/C) gene mutation with atypical Werner's syndrome have recently been reported. Atypical Werner's syndrome with the severe metabolic complications, the extent of the lipodystrophy is associated with A133L mutation in the LMNA gene and these patients present with phenotypically heterogeneous disorders. We experienced a 15-yr-old Korean female with progeroid features, generalized lipodystrophy, hypertriglyceridemia, fatty liver, steatohepatitis, and type 2 diabetes mellitus. Skin fibroblasts from the patient showed marked abnormal nuclear morphology, compared with that from normal persons. Gene analysis revealed that this patient had T506del of exon 2 in the LMNA gene. We report here the first case of atypical Werner's syndrome with frameshift mutation that was caused by T506del.

Association of the Polymorphisms in the PSMA6 (rs1048990) and PSMB5 (rs2230087) Genes with Type 2 Diabetes in Korean Subjects / 당뇨병

BACKGROUND: The 26S ubiquitin-proteasome system (UPS) is a principal proteolytic pathway of intracellular molecules regulating apoptosis, cell cycle, cell proliferation or differentiation, inflammation and etc. The recent study suggests that the rs1048990 (C/G) polymorphism of the proteasome subunit alpha type 6 (PSMA6) gene is associated with the increase of the risk of myocardial infarction by the dysregulation of IkappaB degradation. We hypothesized that 26S UPS is important in the development of insulin resistance and type 2 diabetes (T2DM) by controlling the degradation of IkappaB and insulin receptor substances as a substrate. We therefore investigated whether the rs1048990 (C/G) polymorphism of PSMA6 gene and the rs2230087 (G/A) polymorphism of proteasome subunit beta type 5 gene (PSMB5), that is chymotrypsin-like protease determining the rate of proteolysis, are associated with susceptibility to T2DM in Korean subjects. METHODS: We examined the polymorphisms of these genes in 309 diabetic subjects and 170 non-diabetic controls. The polymorphisms of rs1048990 (C/G) and rs2230087 (G/A) were genotyped by real-time PCR. RESULTS: The frequency of the G allele of rs1048990 (C/G) and the A allele of rs2230087 (G/A) polymorphisms was significantly higher in diabetic patients (28% and 13%) compared to that in controls (13% and 1%; P = 0.000 and P = 0.000, respectively). Logistic regression analysis of the rs1048990 (C/G) polymorphism showed that the odds ratio (OR) (adjusted for age, smoking, waist circumference, fasting plasma glucose, systolic blood pressure, HDL-C, triglyceride, and total cholesterol) was 3.93 (95% confidence interval [CI], 2.35-6.59; P = 0.000) for the G allele and 5.09 (95% CI, 2.71-9.57; P = 0.000) for CG and GG genotype when compared with the CC genotype. Logistic regression analysis of the rs2230087 (G/A) polymorphism showed that the adjusted OR was 5.70 (95% CI, 1.63-19.98; P = 0.007) for the A allele and 6.08 (95% CI, 1.66-22.29; P = 0.006) for GA and AA genotype when compared with the GG genotype. In multiple logistic regression analysis with T2DM as the independent Variable rs1048990 (C/G) and rs2230087 (G/A) polymorphisms were the predictor for T2DM. CONCLUSION: We suggest that the G allele of rs1048990 (C/G) polymorphism and the A allele of rs2230087 (G/A) polymorphism may be genetic risk factor to type 2 diabetes mellitus in Korean subjects.

Hypermethylation of p16(INK4a) in Korean Non-small Cell Lung Cancer Patients

Promoter hypermethylation of the p16(INK4a) gene was investigated in 81 sets of samples of tumor tissue and adjacent normal tissue from Korean patients with primary lung cancer, using the modified real-time polymerase chain reaction (PCR)/ SYBR Green detection method. The results showed hypermethylation of p16(INK4a) in 27.2% of tumor tissues, and in 11.1% of adjacent normal tissue. No significant association was found between the overall aberrant methylation in tumor and corresponding normal specimens (r=0.137, p=0.219). In 22 cases with p16(INK4a) hypermethylation in tumor tissues, only 4 (18.1%) cases were found to have a hypermethylated normal tissue specimen. The findings of this study show that smoking can influence the methylation level of the promoter region of p16(INK4a), and that this occurs in tumor tissues more frequently than in normal tissues. Other clinicopathological characteristics, including age, sex, tumor stage, and histologic type were not found to be correlated with p16(INK4a) methylation.

Serum adiponectin concentration according to visceral fat amount and its relationship of metabolic risk factors in premenopausal obese women / 대한내과학회지

BACKGROUND: Adiponectin is adipose specific protein, which we considered to have metabolic and endocrine function in metabolic syndrome including obesity and insulin resistance. We measured serum adiponectin concentrations and compared them with body fat distribution and metabolic risk factors. METHODS: 112 premenopausal obese women were participated in this study. We measured plasma adiponectin concentration and metabolic risk factors such as fasting glucose and insulin, triglyceride, systolic blood pressure (SBP) and diastolic blood pressure (DBP). Subcutaneous adipose tissue area (SAT) and visceral adipose tissue area (VAT) were determined by computed tomography. Body mass index (BMI), waist to hip ratio (WHR) and homeostasis model assessment (HOMA-IR) were calculated. RESULTS: Serum adiponectin concentration was inversely correlated with fasting insulin level, HOMA-IR, triglyceride, SBP, DBP, WHR, BMI and VAT, whereas HDL-cholesterol was positively correlated (all p values<0.05). VAT, SBP, and HDL-cholesterol level were independent variables of serum adiponectin concentrations. CONCLUSION: The present study demonstrates that decreased plasma level of adiponectin is significantly associated with metabolic risk factors including body fat distribution; serum adiponectin level is determined by VAT, whereas SAT has no relation with serum adiponectin level.

Fine Needle Aspiration Cytology of the Salivary Gland: An analysis of 221 cases / 대한세포병리학회지

Fine needle aspiration cytology of the salivary lesions was performed on 221 patients at Soonchunhyang University Hospital for 10 years. Of 221 aspirates, 6 aspirates(2.7%) were inadequate, 116 cases(52.5%) were non-neoplastic lesions, 76(34.4%) cases were benign neoplasms and 23 cases(10.4%) were malignant neoplasms. The cytologic diagnoses could be correlated with histologic findings in 58 cases. FNAC correctly discriminated between neoplastic and nonneoplastic lesions in fifty-seven lesions and failed in a case, and overall accuracy, sensitivity, and specificity were 98.3%, 98.0%, and 100.0%. FNAC correctly discriminated malignant neoplasms from benign neoplastic/non- neoplastic lesions in fifty-three cases and failed in five cases, and overall accuracy, sensitivity, and specificity were 91.3%, 72.7%, and 95.7%. Among three false negative cases, two mucoepidermoid carcinomas were misdiagnosed as mucocele and benign neoplasm, and an acinic cell carcinoma were misdiagnosed as Warthin's tumor. Two false positive cases were a Warthin's tumor misdiagnosed as squamous cell carcinoma and a pleomorphic adenoma misinterpretated as suggestive of malignancy. In conclusion, diagnostic accuracy of FNAC of salivary lesions is high, and the possibilities of low grade mucoepidermoid carcinoma and acinic cell carcinoma should be considered on hypocellular smears with mucoid or fluidy background.