BACKGROUND: Parkinson disease (PD) is caused by selective cell death of dopaminergic neurons in the substantia nigra. An early onset form of PD, autosomal recessive juvenile parkinsonism has been associated with a mutation in the parkin gene. The function of parkin is known to remove misfolding proteins and protect cell death. We aimed to investigate the role of parkin against oxidative stress in neuronal cells. METHODS: Parkin knockout embryonic stem cells (PKO ES cells) were differentiated into neurons by adherent monolayer culture method. Oxidative stress was induced by the treatment of 1-methyl-4-phenylpyridinium (MPP+) in neurons derived from wild type and PKO ES cells, and cell viability was examined by MTT assay. After exposure to MPP+, Tuj1-positive cell population was compared between PKO and wild type cells by fluorescence activated cell sorter (FACS) analysis. The activated caspase3 protein level was also measured by Western blot analysis, FACS and immunocytochemistry. RESULTS: There was no difference in the efficiency of neuronal differentiation between wild type and PKO ES cells. After exposure to MPP+, no significant differences were found in cell viability and Tuj1-positive cell population between the two groups determined by MTT assay and FACS analysis, respectively. The activated caspase3 protein levels examined by Western blot analysis, FACS and immunocytochemistry were not changed in PKO cells compared with those of wild type cells after MPP+ treatment. CONCLUSION: These results suggest that PKO neuronal cells including dopaminergic neurons are not sensitive to caspase3-dependent cell death pathway during the response against MPP+-induced oxidative stress.
1-Methyl-4-phenylpyridinium ; Blotting, Western ; Cell Death ; Cell Survival ; Dopaminergic Neurons ; Embryonic Stem Cells ; Fluorescence ; Immunohistochemistry ; Neurons ; Oxidative Stress* ; Parkinson Disease ; Parkinsonian Disorders ; Substantia Nigra

OBJECTIVE: To localize the site of motor points within human biceps brachii muscles through surface mapping using electrophysiological method. METHOD: We recorded the compound muscle action potentials of each lattice of the biceps brachii in 40 healthy subjects. Standardized reference lines were made as the following: 1) a horizontal reference line (elbow crease) and 2) a vertical reference line connecting coracoid process and mid-point of the horizontal reference line. The Compound muscle action potentials were mapped in reference to the standardized reference lines. The locations of motor points were mapped to the skin surface, in the ratio to the length of the vertical and the half of the horizontal reference lines. RESULTS: The motor point of the short head of biceps was located at 69.0+/-4.9% distal and 19.1+/-9.5% medial to the mid-point of horizontal reference line. The location of the motor point of the long head of the biceps was 67.3+/-4.3% distal and 21.4+/-8.7% lateral. The motor point of the short head of the biceps was located more medially and distally in the male subjects compared to that in the female (p<0.05). CONCLUSION: This study showed electrophysiological motor points of the biceps brachii muscles through surface mapping. This data might improve the clinical efficacy and the feasibility of motor point targeting, when injecting botulinum neurotoxin in biceps brachii.
Action Potentials ; Botulinum Toxins ; Female ; Head ; Humans ; Male ; Muscles ; Skin

OBJECTIVE: To localize the site of motor points within human biceps brachii muscles through surface mapping using electrophysiological method. METHOD: We recorded the compound muscle action potentials of each lattice of the biceps brachii in 40 healthy subjects. Standardized reference lines were made as the following: 1) a horizontal reference line (elbow crease) and 2) a vertical reference line connecting coracoid process and mid-point of the horizontal reference line. The Compound muscle action potentials were mapped in reference to the standardized reference lines. The locations of motor points were mapped to the skin surface, in the ratio to the length of the vertical and the half of the horizontal reference lines. RESULTS: The motor point of the short head of biceps was located at 69.0+/-4.9% distal and 19.1+/-9.5% medial to the mid-point of horizontal reference line. The location of the motor point of the long head of the biceps was 67.3+/-4.3% distal and 21.4+/-8.7% lateral. The motor point of the short head of the biceps was located more medially and distally in the male subjects compared to that in the female (p<0.05). CONCLUSION: This study showed electrophysiological motor points of the biceps brachii muscles through surface mapping. This data might improve the clinical efficacy and the feasibility of motor point targeting, when injecting botulinum neurotoxin in biceps brachii.
Action Potentials ; Botulinum Toxins ; Female ; Head ; Humans ; Male ; Muscles ; Skin

PURPOSE: Comorbidities have been considered a mortality risk factor in pediatric critical care patients. We studied the characteristics and prognostic factors of children without comorbidities who were admitted to the intensive care unit (ICU) due to respiratory failure. METHODS: We reviewed the medical charts of patients (< 18 years) admitted to the ICU for respiratory support in a single tertiary center between January 2006 and December 2016. Patients with comorbidities and perioperative statuses were excluded. RESULTS: Of the 4,712 ICU patients, 73 (1.5%) were included in this study. The median age was 31 months (8–57) and 51 (69.9%) were boys. Twenty-nine patients (39.7%) presented with pneumonia, 14 (19.2%) with acute respiratory distress syndrome (ARDS), and 11 (15.1%) with obstructive airway disease. The median duration of ICU hospitalization was 5 days (2–14.5), and 45 of the 73 patients (61.6%) needed mechanical ventilation. Mortality was 13.7% (10/73). None of the patients with pneumonia or obstructive airway disease died. The most frequent cause of death was ARDS (5 of 10, 50%). In adjusted analysis, the extent of extrapulmonary organ dysfunction was significantly associated with mortality (odds ratio, 2.89; 95% confidence interval, 1.17–7.11; P=0.023). CONCLUSION: The mortality rate of previously healthy pediatric patients needing respiratory support in the ICU should not be negligible. Multiple organ dysfunctions might be a significant risk factor for mortality in such patients.
Cause of Death ; Child* ; Comorbidity ; Critical Care* ; Hospitalization ; Humans ; Intensive Care Units* ; Mortality ; Pneumonia ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult ; Respiratory Insufficiency ; Risk Factors

Objective: To generate a Korean version of the Oxford Cognitive Screen (K-OCS) and obtain cutoff scores that determine the impairment of each subdomain. Post-stroke cognitive impairment (PSCI) negatively impacts the rehabilitation process and independence in daily life. Its obscure manifestations require effective screening for appropriate rehabilitation. However, in most rehabilitation clinics, psychological evaluation tools for Alzheimer’s dementia have been used without such considerations. The OCS is a screening assessment tool for PSCI and vascular dementia that can evaluate the cognitive domains most often affected by stroke, including language, attention, memory, praxis, and numerical cognition. It comprises 10 subtasks and enables quick and effective cognitive evaluation. Methods: The K-OCS, which considers Korea’s unique cultural and linguistic characteristics, was developed with the approval and cooperation of the original author. Enrollment of participants without disabilities was announced at Duksung Women’s University, Yongin Sevrance Hospital, CHA Bundang Medical Center. The study was conducted between September 2020 and March 2022 on 97 male and female participants aged ≥30 years. Results: All the 97 participants completed the task. In this study, the 5th percentile score was presumed to be the cutoff value for each score, and the values are provided here. The cutoff score for each OCS subtask was similar to that of the original British version. Conclusion We suggest the usability of the K-OCS as a screening tool for PSCI by providing the cutoff value of each subtask.

PURPOSE: Hepatocyte growth factor (HGF) stimulates proliferation, migration, and morphogenesis of epithelial cells by specifically binding to its receptor c-met. Abnomalities of the c-met oncogene have been studied in cancers of many organs including thyroid, lung, pancreas, and stomach. However, little is known about the clinical significance of c-met oncogene abnormalities in colorectal carcinomas. In this study, we investigated over- expression of the c-met protein in colorectal adenomas and adenocarcinomas, and analyzed the clinicopathologic significance of this over-expression. METHODS: Expression of the c-met protein localized in colorectal adenoma and adenocarcinoma tissues was analyzed by using immunohistochemistry. The results were compared with clinicopathologic parameters to find clinical correlation. RESULTS: c-met protein was detected in 42.5% (17/40) of colorectal cancers and in 10.0% (4/40) of colorectal adenomas (P= 0.001). In colorectal cancer, the proportion of expression of c-met protein was 0% (0/40) in stage I, 47.6% (10/40) in stage II, 53.8% (7/40) in stage III and, 0% (0/40) in stage IV. c-met protein expression was 18.8% (3/40) in tumors with invasion into the muscularis propria (MP), and 58.3% (14/40) in tumors with invasion beyond the MP. The depth of tumor invasion was a statistically significant factor (P=0.022) for c-met expression. CONCLUSIONS: The c-met protein expression was related to the depth of invasion of colorectal cancer and showed a significant difference in its rate of expression between adenoma and adenocarcinomas.
Adenocarcinoma ; Adenoma* ; Colorectal Neoplasms* ; Epithelial Cells ; Hepatocyte Growth Factor ; Immunohistochemistry ; Lung ; Morphogenesis ; Oncogenes ; Pancreas ; Stomach ; Thyroid Gland

Background: Liver fibrosis is an early stage of liver cirrhosis. As a reversible lesion before cirrhosis, liver failure, and liver cancer, it has been a target for drug discovery. Many antifibrotic candidates have shown promising results in experimental animal models; however, due to adverse clinical reactions, most antifibrotic agents are still preclinical. Therefore, rodent models have been used to examine the histopathological differences between the control and treatment groups to evaluate the efficacy of anti-fibrotic agents in non-clinical research. In addition, with improvements in digital image analysis incorporating artificial intelligence (AI), a few researchers have developed an automated quantification of fibrosis. However, the performance of multiple deep learning algorithms for the optimal quantification of hepatic fibrosis has not been evaluated. Here, we investigated three different localization algorithms, mask R-CNN, DeepLabV3+, and SSD, to detect hepatic fibrosis. Results: 5750 images with 7503 annotations were trained using the three algorithms, and the model performance was evaluated in large-scale images and compared to the training images. The results showed that the precision values were comparable among the algorithms. However, there was a gap in the recall, leading to a difference in model accuracy. The mask R-CNN outperformed the recall value (0.93) and showed the closest prediction results to the annotation for detecting hepatic fibrosis among the algorithms. DeepLabV3+ also showed good performance; however, it had limitations in the misprediction of hepatic fibrosis as inflammatory cells and connective tissue. The trained SSD showed the lowest performance and was limited in predicting hepatic fibrosis compared to the other algorithms because of its low recall value (0.75). Conclusions We suggest it would be a more useful tool to apply segmentation algorithms in implementing AI algorithms to predict hepatic fibrosis in non-clinical studies.

The drug repurposing strategy has been applied to the development of emergency COVID-19 therapeutic medicines. Current drug repurposing approaches have been directed against RNA polymerases and viral proteases. Recently, we found that the inhibition of the interaction between the SARS-CoV-2 structural nucleocapsid (N) and spike (S) proteins decreased viral replication. In this study, drug repurposing candidates were screened by in silico molecular docking simulation with the SARS-CoV-2 structural N protein. In the ChEMBL database, 1994 FDA-approved drugs were selected for the in silico virtual screening against the N terminal domain (NTD) of the SARS-CoV-2 N protein. The tyrosine 109 residue in the NTD of the N protein was used as the center of the ligand binding grid for the docking simulation. In plaque forming assays performed with SARS-CoV-2 infected Vero E6 cells, atovaquone, abiraterone acetate, and digoxin exhibited a tendency to reduce the size of the viral plagues without affecting the plaque numbers. Abiraterone acetate significantly decreased the accumulation of viral particles in the cell culture supernatants in a concentration-dependent manner. In addition, abiraterone acetate significantly decreased the production of N protein and S protein in the SARS-CoV-2-infected Vero E6 cells. In conclusion, abiraterone acetate has therapeutic potential to inhibit the viral replication of SARS-CoV-2.

Background: Atopic dermatitis (AD) is a heterogeneous disease with different age of onset, disease course, clinical symptoms, severity, and risk of comorbidity. The characteristics of children with AD also vary by age or country. However, little is known about the clinical characteristics of AD in Korean school-aged children and adolescents. Furthermore, there are few studies on phenotypic differences according to onset age. This study aimed to explore the clinical characteristics and phenotypes according to onset age and severity of AD in children and adolescents in Korea. Methods: AD patients aged 6–18 years who presented to 18 hospitals nationwide were surveyed.The patients were examined for disease severity by pediatric allergy specialists, and data on history of other allergic diseases, familial allergy history, onset age, trigger factors, lesion sites,treatment history and quality of life were collected. The results of the patient’s allergy test were also analyzed. The patients were classified into infancy-onset (< 2 years of age), preschoolonset (2–5 years of age), and childhood-onset (≥ 6 years of age) groups. Study population was analyzed for clinical features according to onset-age groups and severity groups. Results: A total of 258 patients with a mean age of 10.62 ± 3.18 years were included in the study. Infancy-onset group accounted for about 60% of all patients and presented significantly more other allergic diseases, such as allergic rhinitis and asthma (P = 0.002 and P = 0.001, respectively). Food allergy symptoms and diagnoses were highly relevant to both earlier onset and more severe group. Inhalant allergen sensitization was significantly associated with both infancy-onset group and severe group (P = 0.012 and P = 0.024, respectively). A family history of food allergies was significantly associated with infancyonset group (P = 0.036). Severe group was significantly associated with a family history of AD, especially a paternal history of AD (P = 0.048 and P = 0.004, respectively). Facial (periorbital, ear, and cheek) lesions, periauricular fissures, hand/foot eczema, and xerosis were associated with infancy-onset group. The earlier the onset of AD, the poorer the quality of life (P = 0.038). Systemic immunosuppressants were used in only 9.6% of the patients in the severe group. Conclusion This study analyzed the clinical features of AD in Korean children and adolescents through a multicenter nationwide study and demonstrated the phenotypic differences according to onset age and severity. Considering the findings that the early-onset group is more severe and accompanied by more systemic allergic diseases, early management should be emphasized in young children and infants.