Purpose: Tubulinopathy represents a group of disorders caused by variants in tubulin genes, which present with a wide spectrum of brain malformations. This study was conducted to provide insight into the phenotypic and genetic spectra of tubulinopathy within the Korean pediatric population. Methods: Among individuals who underwent genetic testing at a pediatric neurology clinic between June 2011 and December 2021, 15 patients with tubulin gene variants were retrospectively recruited. Clinical features, genetic information, and brain imaging findings were retrospectively reviewed. Results: The genetic spectra of the patients included TUBA1A (n=5, 33.3%), TUBB4A (n=6, 40.0%), TUBB3 (n=2, 13.3%), TUBB (n=1, 6.7%), and TUBB2A (n=1, 6.7%) variants. Two novel mutations were identified: a c.497A>G; p.(Lys166Arg) variant in TUBA1A and a c.907G>C; p.(Ala303Pro) variant in TUBB. All 15 patients exhibited developmental delays, with a broad spectrum of severity. Other common manifestations included microcephaly (n=10; 66.7%) and seizures (n=9; 60%). A review of the neuroimaging data revealed a range of findings that were both genotype-specific and overlapping across genotypes. In cases of TUBA1A mutation (n=5), four patients (80%) presented with pachygyria and polymicrogyria, while three (60%) displayed cerebellar hypoplasia and dysplasia. All patients with TUBB4A variants (n=6) exhibited hypomyelination, and three (50%) had cerebellar dysplasia. Conclusion This study represents the first cohort analysis of tubulin gene mutations associated with tubulinopathy in a Korean pediatric population. It suggests that these mutations can produce a broad spectrum of neurodevelopmental and neuroimaging findings and should be considered within the differential diagnosis in relevant clinical scenarios.

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused significant changes. This study aimed to investigate the impact of COVID-19 on patients with chronic pain. Methods: Patients with chronic pain from 23 university hospitals in South Korea participated in this study. The anonymous survey questionnaire consisted of 25 questions regarding the following: demographic data, diagnosis, hospital visit frequency, exercise duration, time outside, sleep duration, weight change, nervousness and anxiety, depression, interest or pleasure, fatigue, daily life difficulties, and self-harm thoughts. Depression severity was evaluated using the Patient Health Questionnaire-9 (PHQ-9). Logistic regression analysis was used to investigate the relationship between increased pain and patient factors. Results: A total of 914 patients completed the survey, 35.9% of whom had decreased their number of visits to the hospital, mostly due to COVID-19. The pain level of 200 patients has worsened since the COVID-19 outbreak, which was more prominent in complex regional pain syndrome (CRPS). Noticeable post-COVID-19 changes such as exercise duration, time spent outside, sleep patterns, mood, and weight affected patients with chronic pain. Depression severity was more significant in patients with CRPS. The total PHQ-9 average score of patients with CRPS was 15.5, corresponding to major depressive orders. The patients’ decreased exercise duration, decreased sleep duration, and increased depression were significantly associated with increased pain. Conclusions COVID-19 has caused several changes in patients with chronic pain.During the pandemic, decreased exercise and sleep duration and increased depression were associated with patients’ increasing pain.

Purpose: Tumor radioresistance and dose-limiting toxicity restrict the curative potential of radiotherapy, requiring novel approaches to overcome the limitations and augment the efficacy. Here, we investigated the effects of signal transducer and activator of transcription 3 (STAT3) activation and autophagy induction by irradiation on antiapoptotic proteins and the effectiveness of the BH3 mimetic ABT-737 as a radiosensitizer using K-ras mutant non-small cell lung cancer (NSCLC) cells and a Kras G12D :p53 fl/fl mouse (KP mouse) model. Materials and Methods: A549 and H460 cells were irradiated, and the expression of Bcl-2 family proteins, JAK/STAT transcriptional pathway, and autophagic pathway were evaluated by immunoblotting. The radiosensitizing effects of ABT-737 were evaluated using A549 and H460 cell lines with clonogenic assays and also by a KP mouse model with microcomputed tomography and immunohistochemistry. Results: In A549 and H460 cells and mouse lung tissue, irradiation-induced overexpression of the antiapoptotic molecules BclxL, Bcl-2, Bcl-w, and Mcl-1 through JAK/STAT transcriptional signaling induced dysfunction of the autophagic pathway. After treatment with ABT-737 and exposure to irradiation, the number of surviving clones in the cotreatment group was significantly lower than that in the group treated with radiation or ABT-737 alone. In the KP mouse lung cancer model, cotreatment with ABT-737 and radiation-induced significant tumor regression; however, body weight changes in the combination group were not significantly different, suggesting that combination treatment did not cause systemic toxicity. Conclusion These findings supported the radiosensitizing activity of ABT-737 in preclinical models, and suggested that clinical trials using this strategy may be beneficial in K-ras mutant NSCLC.

PURPOSE: Childhood asthma has a considerable social impact and economic burden, especially in severe asthma. This study aimed to identify the proportion of childhood asthma severity and to evaluate associated factors for greater asthma severity. METHODS: This study was performed on 667 children aged 5–15 years with asthma from the nationwide 19 hospitals in the Korean childhood Asthma Study (KAS). Asthma was classified as mild intermittent, mild persistent, and moderate/severe persistent groups according to the National Asthma Education and Prevention Program recommendations. Multinomial logistic regression models were used to identify the associated factors for greater asthma severity. RESULTS: Mild persistent asthma was most prevalent (39.0%), followed by mild intermittent (37.6%), moderate persistent (22.8%), and severe persistent asthma (0.6%). Onset later than 6 years of age (adjusted odds ratio [aOR], 1.69 for mild persistent asthma; aOR, 1.92 for moderate/severe persistent asthma) tended to increase asthma severity. Exposure to environmental tobacco smoke (aOR, 1.53 for mild persistent asthma; aOR, 1.85 for moderate/severe persistent asthma), and current dog ownership with sensitization to dog dander (aOR, 5.86 for mild persistent asthma; aOR, 6.90 for moderate/severe persistent asthma) showed increasing trends with greater asthma severity. Lower maternal education levels (aOR, 2.32) and no usage of an air purifier in exposure to high levels of outdoor air pollution (aOR, 1.76) were associated with moderate/severe persistent asthma. CONCLUSIONS: Modification of identified environmental factors associated with greater asthma severity might help better control childhood asthma, thereby reducing the disease burden due to childhood asthma.
Air Filters ; Air Pollution ; Animals ; Asthma ; Child ; Dander ; Dogs ; Education ; Environmental Exposure ; Humans ; Logistic Models ; Odds Ratio ; Ownership ; Risk Factors ; Smoke ; Social Change ; Tobacco

Purpose: Single-photon emission computed tomography/computed tomography (SPECT/CT) is an advanced hybrid nuclear medicine technology that generates both functional and anatomical images in a single study. As utilization of SPECT/CT in Korea has been increasing, the purpose of this study was to survey its application of cardiac and skeletal SPECT/CT imaging for protocol optimization. Methods: We surveyed CT protocols established for cardiac and skeletal SPECT/CT. We searched the guidelines for the CT protocols for SPECT/CT and reviewed the literature recently published. Results: Among 36 hybrid SPECT scanners equipped with four or more multi-channel detector CTs (MDCTs), 18 scanners were used to perform cardiac studies at both very low current CT (30–80 mA; 11.1%) and ultra-low current CT (13–30 mA; 88.9%). Among the 33 canners, very low current (≤ 80 mA) CT or low current CT (80–130 mA) was used in 23.5%, and 41.8% for spine disorders, and in 36.4% or 30.3% for foot/ankle disorders, respectively. In the CT reconstructions, slice thickness of 5 mm for cardiac studies was most commonly used (94.4%); thinner slices (0.6–1.0 mm) for spine and foot/ankle studies were used in 24.2% and 45.5%, respectively. We also reviewed the international guidelines. Conclusions The results and current recommendations will be helpful for optimizing CT protocols for SPECT/CT. Optimization of SPECT/CT protocols will be required for generating the proper strategy for the specific lesions and clinical purpose.

OBJECTIVES: Psychiatric staffs may experience excessive work stress, burnout, and reduced job satisfaction in clinical settings. This can increase chances of diminishing their overall working efficiency or having difficulty managing their own mental health. The purpose of this study was to investigate the effect of group mindfulness- based cognitive therapy(MBCT) on job stress, burnout, self-efficacy, resilience, and job satisfaction. METHODS: Twenty eight psychiatric staffs who agreed to participate in the study were included. Self-report questionnaires were used to measure job stress, burnout, resilience, self-efficacy, and job satisfaction. To examine the effects of group MBCT, the scores were compared before and after MBCT. RESULTS: Work stress and burnout scale scores were significantly decreased after group MBCT. Resilience, job satisfaction, and self-efficacy scale scores were significantly increased after group MBCT. CONCLUSIONS: In the current study, group MBCT for psychiatric staffs helped to reduce their work stress and burnout, and, as well, helped to improve resilience, self-efficacy, and job satisfaction. This suggests that, in mental health treatment settings, psychiatric staffs can improve their mental health through group MBCT. Improving mental health of psychiatric staff may also have a positive impact on their patients.
Cognitive Therapy* ; Humans ; Job Satisfaction ; Mental Health

BACKGROUND: OneTouch Diabetes Management Software (OTDMS) is an efficient way to track and monitor the blood glucose level. It is possible to download data from the OneTouch Ultra via the meter's data port, and to transform the numbers of the blood glucose level into a graph, a chart, or statistics. The objectives of this study were to evaluate whether the use of OTDMS in consultation hours would improve patients' knowledge of diabetes mellitus (DM), compliance, satisfaction with doctor and medical treatment, doctor-patient reliability, and glucose control. METHODS: All patients were randomized into either the OTDMS group using OneTouch Ultra or the control groups not using it. Both groups had conventional DM education and only the OTDMS group used data from OTDMS as explanation materials during consultation hours. At enrollment and after 6 months, we performed a questionnaire survey consisting of the diabetes knowledge test, items for compliance of treatment, patient's satisfaction, doctor-patient reliability, and glycosylated hemoglobin (HbA1c). RESULTS: We analyzed 6-month follow-up data from 92 patients (OTDMS 42 vs. control 50). Both groups showed significant improvements in HbA1c, diabetes knowledge, compliance, reliability, and satisfaction after 6 months. However, there were no significant differences between OTDMS and control groups overall. Only "weekly frequency of checking blood glucose level" of compliance and "trying to follow doctor's order" of reliability showed better results in the OTDMS group. CONCLUSION: Using the OTDMS system for explanation during consultation hours seems to be more helpful to improve patient's compliance and reliability, especially for checking blood glucose level and trying to follow the doctor's order.
Blood Glucose ; Compliance ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Disease Management ; Education ; Follow-Up Studies ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Self Care

Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their inter-assay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.
Citric Acid* ; Colitis ; Cytochrome P-450 CYP1A2 ; Cytochrome P-450 Enzyme System* ; Cytochromes* ; Drug Discovery ; Enzyme Induction* ; Fireflies ; Hepatocytes ; Humans* ; Isoenzymes ; Liver ; Luciferases ; Luminescence ; Luminescent Measurements* ; Mass Screening ; Mesalamine* ; Metabolism ; RNA, Messenger

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 muM in patch clamp assay and increased the heart rate and blood pressure (76 Deltabpm in heart rate and 51 DeltammHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 muM and 30 muM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.
Action Potentials ; Animals ; Blood Pressure ; Cardiovascular System ; Counterfeit Drugs ; Dogs ; Heart Rate ; HEK293 Cells ; Inhibitory Concentration 50 ; Pharmaceutical Preparations ; Pharmacology* ; Purkinje Fibers ; Rabbits ; Telemetry