Establishment of Neurotoxicity Assessment Using Microelectrode Array (MEA) with hiPSC-Derived Neurons and Evaluation of New Psychoactive Substances (NPS)

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.

Cooperative Subtype Switch of Thyroid Hormone Receptor and Nuclear Receptor Corepressor Related Epithelial–Mesenchymal Transition in Papillary Thyroid Cancer

Background and Objectives@#Although thyroid hormones affect human cancer progression, the regulatory mechanism of thyroid hormone receptors in carcinogenesis has not been elucidated. This study aimed to evaluate the expression pattern of the thyroid hormone receptor (TR) and its corepressors, and to investigate the clinical and biological functions of TR. @*Materials and Methods@#Transcriptomic and clinical data for thyroid cancer were downloaded from The Cancer Genome Atlas. Paraffin-embedded tissue sections from patients who underwent thyroidectomy were used for immunohistochemistry. BCPAP cells were treated with T3 to investigate the thyroid hormone target genes. Thyroid hormone receptor alpha (THRA) and Thyroid hormone receptor beta (THRB) were knocked down by transient siRNA transfection. @*Results@#THRA and THRB expression was lower in thyroid cancer tissues than in normal tissues. However, strong focal staining of TRβ was observed in the invasive front. High THRB expression was associated with high Silencing Mediator for Retinoid or Thyroid hormone receptor (SMRT) expression, older age, a high MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) score, more aggressive histological subtypes, more frequent extra-thyroidal extension, and advanced TNM stage. THRB expression was positively correlated with Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A), L1 Cell Adhesion Molecule (L1CAM), and Lysyl Oxidase (LOX) expression. Thyroid hormone-induced HIF1A, L1CAM, and LOX upregulation was abolished by siTHRB but not siTHRA in BCPAP cells. High SMRT and high THRB groups (SMRT/THRB) presented more aggressive clinical features and showed an upregulation of HIF1A, L1CAM, and LOX, as well as of epithelial-mesenchymal transition (EMT)-related genes, causing changes in the tumor microenvironment. @*Conclusion@#Cooperative subtype switching from NCOR1/THRA to SMRT/THRB was thus related to aggressive clinical and molecular features, possibly related to EMT and EMT-related tumor microenvironment.

A Case of Anterior Cervical Intramuscular Schwannoma in the Strap Muscle / 대한이비인후과학회지

Schwannoma, also known as neurilemmoma, is a benign neoplasm that originates from any nerves wrapped with a sheath made of Schwann cells. Schwannoma occurring in the head and neck region is not rare, but schwannomas of the anterior neck, especially ansa cervicalis, are extremely rare that only 7 cases have been reported to date worldwide. Although rare, it should be considered in differential diagnosis of anterior cervical mass and may be confused with other cervical and thyroid mass. We report a case of intramuscular schwannoma in the sternohyoid muscle. Preoperative diagnosis was established with an ultrasound-guided core needle biopsy. Although it was removed entirely without connection to any other nerves identified or any complication, clinically, the mass was thought to be derived from the nerve. To our knowledge, this is the first case of the intramuscular schwannoma occurring from ansa cervicalis reported in the literature.

Lead, Mercury, and Cadmium Exposure in the Korean General Population

BACKGROUND: Lead (Pb), mercury (Hg), and cadmium (Cd) are well-known environmental pollutants. They are unnecessary in the biological processes of humans. This study was performed to estimate the representative background exposure levels to the metals by measuring concentrations in whole blood of the Korean general population. METHODS: This population-based cross-sectional study included 4,000 subjects (1,886 males and 2,114 females) 0–83 years of age in 2010 and 2011. Adult subjects (≥ 19 years of age) were collected by sex- and age-stratified probability method, and preschool- and school-aged subjects were recruited by a cluster sampling method. Written consent was provided prior to blood sampling. Pb and Cd blood concentrations were determined by a flameless atomic absorption spectrophotometry, and blood Hg was analyzed by a direct Hg analyzer. RESULTS: The geometric mean, median and 95th percentile of blood Pb was 1.82 µg/dL, 1.83 µg/dL, and 3.78 µg/dL, respectively. The respective values were 2.92 µg/L, 2.87 µg/L, 9.12 µg/L for Hg, and 0.56 µg/L, 0.59 µg/L, 2.20 µg/L for Cd. Blood Pb and Hg were higher in males than in females, but no sex difference was observed, respectively, in subjects 0–4 years of age for Pb and in subjects less than 20 years for Hg. However, blood Cd was higher in females than in males and no sex difference was observed in subjects < 30 years of age. CONCLUSION: This study provides representative data of human exposure to Pb, Hg, and Cd covering whole age groups of the general population in Korea.

Effectiveness of Self-directed Learning on Competency in Physical Assessment, Academic Self-confidence and Learning Satisfaction of Nursing Students / 기본간호학회지

PURPOSE: Competency in physical assessment is an important component of nursing practice. However, some physical assessment skills are not being utilized within the current teacher-centered, content-heavy curriculum. This study was conducted to identify the effects of student-centered, self-directed learning in the physical assessment class. METHODS: An experimental study with a post-test only control group design was used to compare an intervention group that was provided self-directed learning classes and a control group that was provided traditional lecture and practice classes. Competency in physical assessment, academic self-confidence, and learning satisfaction were evaluated. Collected data were analyzed using χ²-test (Fisher's exact test) and independent t-test. RESULTS: Competency in physical assessment was significantly higher in the experimental group. However, academic self-confidence and learning satisfaction were not significantly different between the groups. CONCLUSION: The findings in this study indicate that self-directed learning can improve nursing students competency in physical assessment and that self-directed learning is a good education method to improve nursing students' competency in physical assessment during clinical practice and perform quality patient care by making active use of physical assessment skills.

Falcarindiol from Angelica koreana Down-regulated IL-8 and Up-regulated IL-10 in Colon Epithelial Cells

Angelica koreana is an important medicinal plant for some locals in East Asia including Korea. A few reports have shown the efficacy of its phytochemical constituents. We have isolated and purified one compound falcarindiol (FAL) from the methanolic extract of A. koreana roots. At concentrations from to 1 µM to 25 µM, the FAL isolated from the roots of A. koreana exerted no significant cytotoxicity and down-regulated LPS-stimulated pro-inflammatory cytokine IL-8 in colon epithelial cells, while up-regulating anti-inflammatory cytokine IL-10. In addition, the FAL decreased the expression of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 protein by Western blot analysis. Colon epithelial cells play pivotal roles in regulating the colon immune system and thus FAL is expected to be candidate agent as therapeutic potential for the treatment of inflammatory bowel disease (IBD) by modulating LPS-induced inflammation in colon epithelial cells.

Effects of Self-directed Feedback Practice using Smartphone Videos on Basic Nursing Skills, Confidence in Performance and Learning Satisfaction

PURPOSE: This study was done to verify effects of a self-directed feedback practice using smartphone videos on nursing students' basic nursing skills, confidence in performance and learning satisfaction. METHODS: In this study an experimental study with a post-test only control group design was used. Twenty-nine students were assigned to the experimental group and 29 to the control group. Experimental treatment was exchanging feedback on deficiencies through smartphone recorded videos of nursing practice process taken by peers during self-directed practice. RESULTS: Basic nursing skills scores were higher for all items in the experimental group compared to the control group, and differences were statistically significant ["Measuring vital signs" (t= - 2.10, p =.039); "Wearing protective equipment when entering and exiting the quarantine room and the management of waste materials" (t= - 4.74, p <.001) "Gavage tube feeding" (t= - 2.70, p =.009)]. Confidence in performance was higher in the experimental group compared to the control group, but the differences were not statistically significant. However, after the complete practice, there was a statistically significant difference in overall performance confidence (t= - 3.07. p =.003). Learning satisfaction was higher in the experimental group compared to the control group, but the difference was not statistically significant (t= - 1.67, p =.100). CONCLUSION: Results of this study indicate that self-directed feedback practice using smartphone videos can improve basic nursing skills. The significance is that it can help nursing students gain confidence in their nursing skills for the future through improvement of basic nursing skills and performance of quality care, thus providing patients with safer care.

Risk Factors of Postoperative Hypocalcemia after Total Thyroidectomy of Papillary Thyroid Carcinoma Patients / 대한내분비외과학회지

PURPOSE: Postoperative hypocalcemia is a common complication of thyroidectomy. This study evaluated the incidence and predisposing risk factors for postoperative permanent hypocalcemia after total thyroidectomy. METHODS: There were 1,247 consecutive patients undergoing total thyroidectomy and complete treatment and observation for differentiated thyroid cancer between January 2012 to December 2012 who were enrolled in this study. Patients were divided into two groups, those remaining normalcalcemic (Group I-824 pts) and those who had hypocalcemia requiring treatment (Groups II-423 pts). Group II was subdivided into a transient hypocalcemic group (Group IIA-409 pts) and a permanent hypocalcemic group (Group IIB-14 pts). RESULTS: Female gender, thyroiditis, preserved parathyroid number, lateral lymph node metastasis, RAI treatment, preoperative parathyroid hormone and preoperative vitamin D were significantly associated with the development of postoperative hypocalcemia by multivariate analysis. Comparing patients with transient versus permanent hypocalcemia, tumor size and multiplicity were significantly related to the development of permanent hypocalcemia by multivariate analysis. RAI treatment and parathyroid hormone level on the postoperative third day were significantly related to recovery from transient hypocalcemia to normo-calcemia. CONCLUSION: Risk factors of postoperative hypocalcemia were associated with preoperative patient factors and advanced thyroid cancer. Advanced thyroid cancer was a risk factor for permanent hypocalcemia. To prevent postoperative hypocalcemia, we should focus on patient condition and need to preserve parathyroid gland more carefully in thyroid surgery.

Changes in cerebral oxygen saturation and early postoperative cognitive function after laparoscopic gastrectomy: a comparison with conventional open surgery / 대한마취과학회지

BACKGROUND: Laparoscopic gastrectomy requires a reverse-Trendelenburg position and prolonged pneumoperitoneum and it could cause significant changes in cerebral homeostasis and lead to cognitive dysfunction. We compared changes in regional cerebral oxygen saturation (rSO2), early postoperative cognitive function and hemodynamic variables in patients undergoing laparoscopic gastrectomy with those patients that underwent conventional open gastrectomy. METHODS: Sixty patients were enrolled in this study and the patients were distributed to receive either laparoscopic gastrectomy (laparoscopy group, n = 30) or open conventional gastrectomy (open group, n = 30). rSO2, end-tidal carbon dioxide tension, hemodynamic variables and arterial blood gas analysis were monitored during the operation. The enrolled patients underwent the mini-mental state examination 1 day before and 5 days after surgery for evaluation of early postoperative cognitive function. RESULTS: Compared to baseline value, rSO2 and end-tidal carbon dioxide tension increased significantly in the laparoscopy group after pneumoperitoneum, whereas no change was observed in the open group. No patient experienced cerebral oxygen desaturation or postoperative cognitive dysfunction. Changes in mean arterial pressure over time were significantly different between the groups (P < 0.001). CONCLUSIONS: Both laparoscopic and open gastrectomy did not induce cerebral desaturation or early postoperative cognitive dysfunction in patients under desflurane anesthesia. However, rSO2 values during surgery favoured laparoscopic surgery, which was possibly related to increased cerebral blood flow due to increased carbon dioxide tension and the effect of a reverse Trendelenburg position.

Preoperative Ultrasonographic Evaluation in Detecting Extrathyroidal Extension and Risk Factors of Extrathyroidal Extension in Papillary Thyroid Carcinoma / 대한내분비외과학회지

PURPOSE: Extrathyroidal extension (ETE) is one of the risk factors to be considered when deciding on operation extent and radioiodine ablation in differentiated thyroid carcinoma. Ultrasonography (USG) is the most widely used imaging modality in preoperative evaluation of thyroid carcinoma; however, few studies regarding accuracy of USG in preoperative evaluation of ETE have been reported. In this study, we investigated the accuracy of preoperative USG in detection of ETE and evaluated other risk factors associated with permanent ETE. METHODS: We reviewed the medical records of 349 consecutive patients who underwent curative thyroidectomy for differentiated thyroid carcinoma. Preoperative USG findings according to percent of contact and disruption of thyroid capsule were evaluated and compared with the permanent pathology. Clinicopathologic characteristics were investigated for assessment of the risk factors associated with ETE. RESULTS: ETE was identified in permanent pathology of 68 (19.5%) patients. When we defined the ETE on preoperative USG as more than 25% contact with the adjacent capsule, the positive predictive value (PPV) and negative predictive value (NPV) were 43.03% and 90.73%, respectively. Size of the nodule and preoperative USG findings with the percent of contact with adjacent capsule and capsule disruption showed an association with ETE on permanent pathology. However, in multivariate analysis, only size of the nodule and capsule disruption on USG were identified as risk factors for prediction of ETE on permanent pathology. CONCLUSION: Capsule disruption on preoperative USG can provide useful predictive information about permanent ETE. Another risk factor associated with ETE was size of nodule in differentiated thyroid carcinoma.