Background and Objectives: Currently, safety pharmacological tests for the central nervous system depend on animal behavioral analysis. However, due to the subjectivity of behavioral analysis and differences between species, there is a limit to appropriate nervous system toxicity assessment, therefore a new neurotoxicity assessment that can simulate the human central nervous system is required. Methods: and Results: In our study, we developed an in vitro neurotoxicity assessment focusing on neuronal function. To minimize the differences between species and fast screening, hiPSC-derived neurons and a microelectrode array (MEA) that could simultaneously measure the action potentials of the neuronal networks were used. After analyzing the molecular and electrophysiological characters of our neuronal network, we conducted a neurotoxicity assessment on neurotransmitters, neurotoxicants, illicit drugs, and new psychoactive substances (NPS). We found that most substances used in our experiments responded more sensitively to our MEA-based neurotoxicity assessment than to the conventional neurotoxicity assessment. Also, this is the first paper that evaluates various illicit drugs and NPS using MEA-based neurotoxicity assessment using hiPSC-derived neurons. Conclusions Our study expanded the scope of application of neurotoxicity assessment using hiPSC-derived neurons to NPS, and accumulated evaluation data of various toxic substances for hiPSC-derived neurons.

Background: Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification. Methods: Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier). Results: On WHO classification, H&E staining exhibited ‘fair agreement’ (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems. Conclusions Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

BACKGROUND: High doses of methotrexate (MTX) are often used in various chemotherapy protocols to treat acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) in children, but its delayed elimination increases the occurrence of adverse events, such as bone marrow suppression. The aim of this study was to investigate the elimination of MTX at 24 and 48 hours. METHODS: We retrospectively analyzed electronic medical records of ALL or NHL pediatric patients who received 5 g/m² MTX infusion over 24 hours (between June, 2012 and July, 2018) at the Yonsei University Health System, Korea. The delayed elimination of MTX concentrations was assessed with 100 or 150 µM MTX at 24 hours, and 2 or 5 µM at 48 hours. RESULTS: Among the 85 MTX cycles administered, 23 cycles were classified in delayed elimination group, and 62 cycles showed normal elimination. At 24 hours, the delayed elimination group with MTX concentration > 100 µM showed higher percentage than group with MTX concentration < 100 µM (45.8% vs. 19.7%, p = 0.015). However, no differences were observed at 150 µM MTX (p = 0.66). At 48 hours, the delayed elimination was higher than the normal elimination at both concentration baselines (p < 0.001 at 2 µM, p = 0.024 at 5 µM). CONCLUSIONS: MTX concentrations greater than 100 µM show high probability of delayed elimination at 24 hours. When MTX levels are above normal, leucovorin and hydration regimens should be continued to prevent delayed elimination.
Bone Marrow ; Child ; Drug Therapy ; Electronic Health Records ; Humans ; Korea ; Leucovorin ; Lymphoma ; Lymphoma, Non-Hodgkin ; Methotrexate ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies

BACKGROUND: Posaconazole is a broad-spectrum triazole antifungal agent and the most recommended prophylactic antifungal agent for patients with acute myeloid leukemia (AML) undergoing induction chemotherapy. In this study, we evaluated the status and effectiveness of posaconazole as a prophylactic antifungal agent in pediatric patients receiving induction chemotherapy for AML. METHODS: We retrospectively reviewed the electronic medical records of 36 pediatric patients with AML (between January 2013 and September 2017) at the Yonsei University Health System. Invasive fungal disease (IFD) was assessed as the primary endpoint of prophylactic antifungal effect. The secondary endpoints were incidence of fever, persistent fever despite the use of broad-spectrum antibiotics for 72 h, alteration of antifungal agent, intensive care unit admission, and death within 100 days. RESULTS: Among the 36 patients, 18 patients used posaconazole, 12 were treated with suspension formula, and 6 of them were treated with tablets. Eighteen patients did not use antifungal agents prophylactically. The mean number of days of posaconazole administration was 26.8±16 days. IFD occurred in 2/18 (11.1%) patients in the no prophylaxis group and in 1/18 (5.6%) patients in the posaconazole group (p=0.49). CONCLUSION: Posaconazole is expected to be useful for the prevention of IFD in pediatric patients with AML undergoing induction chemotherapy. Prospective studies of the effectiveness of posaconazole prophylaxis should be conducted in more pediatric patients in the future.
Anti-Bacterial Agents ; Antifungal Agents ; Electronic Health Records ; Fever ; Humans ; Incidence ; Induction Chemotherapy* ; Intensive Care Units ; Leukemia, Myeloid, Acute* ; Pediatrics ; Prospective Studies ; Retrospective Studies ; Tablets

BACKGROUND: From May to July 2015, the Republic of Korea experienced the largest outbreak of Middle East respiratory syndrome (MERS) outside the Arabian Peninsula. A total of 186 patients, including 36 deaths, had been diagnosed with MERS-coronavirus (MERS-CoV) infection as of September 30th, 2015. MATERIALS AND METHODS: We obtained information of patients who were confirmed to have MERS-CoV infection. MERS-CoV infection was diagnosed using real-time reverse-transcriptase polymerase chain reaction assay. RESULTS: The median age of the patients was 55 years (range, 16 to 86). A total of 55.4% of the patients had one or more coexisting medical conditions. The most common symptom was fever (95.2%). At admission, leukopenia (42.6%), thrombocytopenia (46.6%), and elevation of aspartate aminotransferase (42.7%) were observed. Pneumonia was detected in 68.3% of patients at admission and developed in 80.8% during the disease course. Antiviral agents were used for 74.7% of patients. Mechanical ventilation, extracorporeal membrane oxygenation, and convalescent serum were employed for 24.5%, 7.1%, and 3.8% of patients, respectively. Older age, presence of coexisting medical conditions including diabetes or chronic lung disease, presence of dyspnea, hypotension, and leukocytosis at admission, and the use of mechanical ventilation were revealed to be independent predictors of death. CONCLUSION: The clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. However, the overall mortality rate (20.4%) was lower than that in previous reports. Enhanced surveillance and active management of patients during the outbreak may have resulted in improved outcomes.
Antiviral Agents ; Aspartate Aminotransferases ; Coronavirus Infections* ; Disease Outbreaks ; Dyspnea ; Extracorporeal Membrane Oxygenation ; Fever ; Humans ; Hypotension ; Leukocytosis ; Leukopenia ; Lung Diseases ; Middle East Respiratory Syndrome Coronavirus ; Middle East* ; Mortality ; Pneumonia ; Polymerase Chain Reaction ; Republic of Korea* ; Respiration, Artificial ; Thrombocytopenia

Background: DNA prevalence and type distribution of human papillomavirus (HPV) varies geographically. We investigated HPV prevalence and type distribution in Korean women using the MyHPV DNA chip testing. Methods: A total of 2,368 women from five regions of the country underwent Pap smear examination and MyHPV chip testing. Results: Overall HPV positivity was 15.8% and 78.4% in women with normal and abnormal cytology, respectively. High-risk HPV infection was strongly correlated with cytological atypia. In women with abnormal cytology, the five most common HPV types were 16, 58, 18, 52, and 56/53, and HPV16 was significantly the most common type in most geographical regions. After HPV16, HPV58, and 52 were the next most frequently detected types. Women with normal cytology, in contrast, showed heterogeneity in HPV type distribution. High-grade intraepithelial lesions infected with HPV16, 18, 31 or 45 are more likely to progress to carcinoma. Conclusions: The HPV chip test can provide useful data regarding HPV positivity and type. The most common HPV type in Korean women with abnormal cytology is HPV16, with HPV58 and 52 being frequently present. Our data may have important implications for vaccination programs and the development of cervical screening.
Cervix Uteri ; DNA ; Female ; Genotype ; Humans ; Mass Screening ; Oligonucleotide Array Sequence Analysis ; Population Characteristics ; Prevalence ; Republic of Korea ; Vaccination ; Vaginal Smears

Continuous renal replacement therapy (CRRT) has been used increasingly for the management of renal failure in hemodynamically unstable and critically ill patients. CRRT requires anticoagulation, usually with heparin, to prevent clotting in the extracorporeal circuit. Systemic heparinization is associated with a high rate of bleeding when used during CRRT in critically ill patients. We applied regional citrate anticoagulation for CRRT to two critically ill patients with high bleeding risk using calcium containing commercial solutions. We conclude that regional citrate anticoagulation with commercial calcium containing solution can be used alternative to heparin for CRRT in patients with high bleeding risk.
Calcium ; Citric Acid* ; Critical Illness ; Hemodiafiltration* ; Hemorrhage ; Heparin ; Humans ; Renal Insufficiency ; Renal Replacement Therapy

Crohn's disease is a condition of chronic inflammation potentially involving any location of the alimentary tract from mouth to anus. Numerous extraintestinal manifestations can also be present. Urologic complications of inflammatory bowel disease are seen in up to 25% of patients, but renal parenchymal disease has been rarely reported. IgA nephropathy is recognized worldwide as a most common form of primary glomerulonephritis. Clinical manifestations vary, ranging from microscopic hematuria to nephrotic syndrome. Recently, IgA nephropathy associated with systemic diseases has been reported. We describe a case of a 22 year-old man with Crohn's disease associated with IgA nephropathy. At the age of 8 years, microscopic hematuria appeared. After fourteen years, he presented with melena, mild fever, recurrent oral ulcer, microscopic hematuria and proteinuria. Colonoscopic examination revealed characteristic features of Crohn's disease such as multiple ulcers. Microscopic findings showed superficial ulceration with small noncaseating granulomas. Renal biopsy revealed IgA nephropathy. The patient was treated with oral prednisolone, olsalazine, and metronidazole followed by maintenance therapy with sulfasalazine and azathioprine resulting in clinical improvement of Crohn's disease and IgA nephropathy.
Adult ; Crohn Disease/*complications/pathology ; Glomerulonephritis, IGA/*complications/pathology ; Humans ; Male

BACKGROUND: This study was to evaluate a nationwide nosocomial infection rate and antimicrobial resistance in intensive care units(ICUs) in Korea. METHODS: The study was carried out at 16 university-affiliated teaching hospitals from July through October 2004. We performed a prospective multicenter study to investigate nosocomial infection rates, device-associated infection rated, and causative pathogens and their antimicrobial resistance. RESULTS: The urinary tract was the most commonly involved site. Nosocomial infection rate was 12.48 in medical. ICU (MICU), 9.59 in medical surgical ICU (MSICU), 14.76 in surgical ICU (MSICU), and 11.60 in other lCU. Device-associated infection rates were as follow: 1) rates of urinary catheter-associated urinary tract infection were 4.26 in MICU, 3.17 in SICU, 4.88 in MSICU, and 5.87 in other ICU; 2) rates of central line-associated bloodstream infection were 3.24 in MICU, 1.56 in SlCU, 2.36 in MSICU, and 1.78 in other ICU; 3) rates of ventilator-associated pneumonia were 3.61 in MlCU, 13.05 in SICU, 1.68 in MSICU, and 4.84 in other lCU. Staphylococcus aureus was the most frequently identified microorganism in this study; 93% of S. aurues were resistant to methicillin; 17% of Pseudomonas aeruginosa isolated were resistant to imipenem; 11% of Enterococcus faecium and 18% of Enterococcus faecalis showed resistance to vancomycin. Over a half of Acinetobacter spp, Stenotrophomonas maltophilia, Klebsiella pneumoniae, and Escherichia coli showed resistant to fluoroquinolone. Conclusion: This study shows the seriousness of antimicrobial resistance and the importance of infection control in the lCU in Korea. This study should provide a theoretical strategy to enforce the infection control.
Acinetobacter ; Cross Infection* ; Enterococcus faecalis ; Enterococcus faecium ; Escherichia coli ; Hospitals, Teaching ; Hospitals, University* ; Imipenem ; Infection Control ; Intensive Care Units* ; Critical Care* ; Klebsiella pneumoniae ; Korea* ; Methicillin ; Pneumonia, Ventilator-Associated ; Prospective Studies ; Pseudomonas aeruginosa ; Staphylococcus aureus ; Stenotrophomonas maltophilia ; Urinary Tract ; Urinary Tract Infections ; Vancomycin

Sialoadhesin (Sn) expression has been demonstrated on murine and rat macrophages in lymphatic organs and is recognized by the monoclonal antibody (mAb) ED3 in the rat. Sialoadhesin (Siglec-1), the ED3 antigen in the rat, is a subtype of sialic acid -binding Ig-like lectins (Siglecs) that bind specifically to sialic acid-containing structures such as selectins and was originally identified as the sheep erythrocyte receptor (SER) responsible for sialic acid-dependent binding of native sheep erythrocytes (SE) to resident murine bone marrow macrophages in rosetting assays. The aim of the present study was to investigate the expression and potential function of sialoadhesin in the stratified squamous epithelium of the rat tongue, esophagus and skin. The expression of sialoadhesin was demonstrated by immunohistochemical analysis with the mAb ED3. This study demonstrated not only the presence of sialoadhesin on the basal epithelial cells of the stratified epithelium in normal rat tongue, esophagus and skin but also its upregulated expression on these cells in CY-treated rats. The results of the present study shed some light on the potential function of sialoadhesin in the basal epithelial cells of the stratified epithelium. Further studies may provide more insight into the role of sialoadhesin in the epithelial stem cells.
Animals ; Bone Marrow ; Cyclophosphamide* ; Epithelial Cells* ; Epithelium* ; Erythrocytes ; Esophagus ; Lectins ; Macrophages ; N-Acetylneuraminic Acid ; Rats* ; Selectins ; Sheep ; Sialic Acid Binding Ig-like Lectin 1 ; Skin ; Stem Cells ; Tongue ; Up-Regulation*