Alzheimer’s disease (AD) is a neurodegenerative disease characterized by neuronal cell death and memory impairment. Corticosterone (CORT) is a glucocorticoid hormone produced by the hypothalamic-pituitary-adrenal axis in response to a stressful condition. Excessive stress and high CORT levels are known to cause neurotoxicity and aggravate various diseases, whereas mild stress and low CORT levels exert beneficial actions under pathophysiological conditions. However, the effects of mild stress on AD have not been clearly elucidated yet. In this study, the effects of low (3 and 30 nM) CORT concentration on Aβ25-35-induced neurotoxicity in SH-SY5Y cells and underlying molecular mechanisms have been investigated. Cytotoxicity caused by Aβ25-35 was significantly inhibited by the low concentration of CORT treatment in the cells. Furthermore, CORT pretreatment significantly reduced Aβ25-35-mediated pro-apoptotic signals, such as increased Bim/Bcl-2 ratio and caspase-3 cleavage. Moreover, low concentration of CORT treatment inhibited the Aβ25-35-induced cyclooxygenase-2 and pro-inflammatory cytokine expressions, including tumor necrosis factor-α and interleukin-1β. Aβ25-35 resulted in intracellular accumulation of reactive oxygen species and lipid peroxidation, which were effectively reduced by the low CORT concentration. As a molecular mechanism, low CORT concentration activated the nuclear factor-erythroid 2-related factor 2, a redox-sensitive transcription factor mediating cellular defense and upregulating the expression of antioxidant enzymes, such as NAD(P)H:quinone oxidoreductase, glutamylcysteine synthetase, and manganese superoxide dismutase. These findings suggest that low CORT concentration exerts protective actions against Aβ25-35-induced neurotoxicity and might be used to treat and/or prevent AD.

Subclinical hypothyroidism (SCH), characterized by elevated serum thyroid-stimulating hormone (TSH) levels and normal free thyroxine levels, usually presents without symptoms, and is often discovered incidentally during routine blood test. The Task Force of the Korean Thyroid Association Committee of Clinical Practice Guidelines has established a guideline to evaluate and manage SCH; the guideline emphasizes the implementation of diagnostic criteria based on the TSH reference range for Koreans and focuses on the proven health benefits of levothyroxine (LT4) treatment. Based on the Korea National Health and Nutrition Examination Survey (2013-2015), serum TSH level of 6.8 mIU/L is considered the reference value for SCH. SCH can be categorized as mild (TSH 6.8-10.0 mIU/L) or severe (TSH ＞10.0 mIU/L), and patients are classified as adults (age ＜70 years) or elderly patients (age ≥70years) depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, along with the thyroid peroxidase antibody test, preferably 2-3 months after the initial evaluation. Usually, LT4 treatment is not recommended for mild SCH in adults; however, treatment is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and can be considered for coexisting dyslipidemia. LT4 treatment is not recommended for mild or even severe SCH in elderly patients, in general. Patients with SCH who receive LT4 treatment, the LT4 dosage should be personalized, and serum TSH levels should be monitored to ensure optimal LT4 dosage (dosage that is neither excessive nor insufficient). Patients with SCH who do not receive LT4 treatment require periodic follow-up at appropriate testing intervals determined by disease severity. The guideline also provides several educational points applicable in clinical settings.

Background: Generally, lactate levels > 2 mmol/L represent hyperlactatemia, whereas lactic acidosis is often defined as lactate > 4 mmol/L. Although hyperlactatemia is common finding in liver transplant (LT) candidates, association between lactate and organ failures with Acute-on-chronic Liver Failure (ACLF) is poorly studied. We searched the important variables for pre-LT hyperlactatemia and examined the impact of preoperative hyperlactatemia on early mortality after LT. Methods: A total of 2,002 patients from LT registry between January 2008 and February 2019 were analyzed. Six organ failures (liver, kidney, brain, coagulation, circulation, and lung) were defined by criteria of EASL-CLIF ACLF Consortium. Variable importance of preoperative hyperlactatemia was examined by machine learning using random survival forest (RSF). Kaplan-Meier Survival curve analysis was performed to assess 90-day mortality. Results: Median lactate level was 1.9 mmol/L (interquartile range: 1.4, 2.4 mmol/L) and 107 (5.3%) patients showed > 4.0 mmol/L. RSF analysis revealed that the four most important variables for hyperlactatemia were MELD score, circulatory failure, hemoglobin, and respiratory failure. The 30-day and 90-day mortality rates were 2.7% and 5.1%, whereas patients with lactate > 4.0 mmol/L showed increased rate of 15.0% and 19.6%, respectively. Conclusion About 50% and 5% of LT candidates showed pre-LT hyperlactatemia of > 2.0 mmol/L and > 4.0 mmol/L, respectively. Pre-LT lactate > 4.0 mmol/L was associated with increased early post-LT mortality. Our results suggest that future study of correcting modifiable risk factors may play a role in preventing hyperlactatemia and lowering early mortality after LT.

Acacetin, which is present in damiana (Turnera diffusa) and black locust (Robinia pseudoacacia), has several pharmacologic activities such as antioxidant, anti-inflammatory, and anti-proliferative effects on cancer cells. However, the effect of acacetin on head and neck cancers has not been clearly established. This study aimed to examine the effects of acacetin on cell growth and apoptosis induction in FaDu human pharyngeal carcinoma cells. These were investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, Live/Dead cell assay, 4′,6-diamidino-2-phenylindole dihydrochloride staining, caspase-3 and caspase-7 activation assay, and immunoblotting in FaDu cells. Acacetin induced FaDu cell death in a dose-dependent manner, with an estimated IC50 value of 41.9 µM, without affecting the viability of L-929 mouse fibroblasts as normal cells. Acacetin treatment resulted in nuclear condensation in the FaDu cells. It promoted the proteolytic cleavage of procaspase-3, -7, -8, and -9 with increasing amounts of the cleaved caspase isoforms in FaDu cells. Acacetin-induced apoptosis in FaDu cells was mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting showed downregulation of the anti-apoptotic mitochondrial proteins Bcl-2 and Bcl-xL, but upregulation of the mitochondria-dependent pro-apoptotic proteins Bax and Badin FaDu cells after acacetin treatment. These findings indicate that acacetin inhibits cell proliferation and induces apoptotic cell death in FaDu human pharyngeal carcinoma cells via both the death receptor-mediated extrinsic apoptotic pathway and the mitochondria-mediated intrinsic apoptotic pathway.

Möbius syndrome is a rare congenital condition, characterized by abducens and facial nerve palsy, resulting in limitation of lateral gaze movement and facial diplegia. However, to our knowledge, there have been few studies on evaluation of cranial nerves, on MR imaging in Möbius syndrome. Herein, we describe a rare case of Möbius syndrome representing limitation of lateral gaze, and weakness of facial expression, since the neonatal period. In this case, high-resolution MR imaging played a key role in diagnosing Möbius syndrome, by direct visualization of corresponding cranial nerves abnormalities.
Cranial Nerves ; Facial Expression ; Facial Nerve ; Magnetic Resonance Imaging ; Paralysis

BACKGROUND AND OBJECTIVES: Anaplastic thyroid carcinoma (ATC) is commonly related with concurrent differentiated thyroid carcinoma (DTC). We aimed to examine the clinicopathologic characteristics, prognosis and gene expression of DTC with anaplastic foci. MATERIALS AND METHODS: Eighteen patients with DTC with anaplastic foci were enrolled in this study. To compare the clinicopathologic characteristics and prognosis of anaplastic foci subjects with conventional ATC or DTC, we additionally included 12 ATC and 1030 DTC patients who diagnosed during same period. Immunohistochemistry was performed to check the gene expression in anaplastic foci and DTC component. RESULTS: In anaplastic foci group, tumor size was larger (2.5±1.3 vs. 1.2±0.9 cm, p=0.001), distant metastasis was more frequent (11.1 vs. 0%, p=0.000) and 1-year survival rate was low (88.9 vs. 100%, p=0.000) than DTC group. In contrast, compared with ATC group, anaplastic foci group showed younger age at diagnosis (50±16 vs. 63±18 years, p=0.039), smaller tumor size (2.5±1.3 vs. 3.8±1.4 cm, p=0.027), less distant metastasis (11.1 vs. 41.7%, p=0.084) and longer 1-year survival rate (88.9 vs. 25.0%, p=0.001). Expression of p53 protein was observed in 100% of anaplastic foci, ATC and 12.5% of papillary thyroid carcinoma component. CONCLUSION: DTC with foci of anaplastic transformation has a worse prognosis than DTC, but a better prognosis than ATC. Our results support that DTC with anaplastic foci was intermediate state from DTC to ATC.
Diagnosis ; Gene Expression ; Humans ; Immunohistochemistry ; Neoplasm Metastasis ; Prognosis* ; Survival Rate ; Thyroid Carcinoma, Anaplastic ; Thyroid Gland* ; Thyroid Neoplasms* ; Tumor Suppressor Protein p53

The purpose of this pictorial essay is to illustrate the multimodality imaging findings of a wide spectrum of radiation-induced complications of breast cancer in the sequence of occurrence. We have classified radiation-induced complications into three groups based on the time sequence of occurrence. Knowledge of these findings will allow for the early detection of complications as well as the ability to differentiate tumor recurrence.
Breast Neoplasms/*radiotherapy ; *Diagnostic Imaging ; Female ; Humans ; Radiation Injuries/*diagnosis ; Radiotherapy/*adverse effects

BACKGROUND: Computed tomography(CT) is currently considered as the initial imaging procedure of choice for the localization of pheochromocytomas in most of the cases. 131I-or 123I-Metaiodobenzylguanidine scintigraphy(MIBG scan) was proven to be a highly specific tool for the detection of adrenal and extra-adrenal pheochromocytomas, but was less sensitive than CT. The present study is aimed to evaluate the usefulness of a MIBG scan in diagnosis and localization of pheochromocytoma when compared to CT. METHODS: We retrospectively evaluated 27 patients who underwent a MIBG scan for a pheochromocytoma at the Seoul National University Hospital from the year 2000 and 2002. According to the pathological and clinical findings, in 16 the patients pheochromocytoma was confirmed to be positive and the rest 11 of the patients were excluded from the study. RESULTS: Pheochromocytomas was identified in 16 patients. Eleven of them were localized in adrenal gland and 5 were extra-adrenal lesions. The sensitivity to MIBG scan in adrenal lesions and extra-adrenal lesions, was 72%(8/11) and 40%(2/5) respectively. In our study, the overall sensitivity to MIBG scan was 62%(10/16), and overall specificity was 90.9%(10/11). By CT four were identified to have equivocal biochemical abnormalities, but were definite and extraadrenal tumors by MIBG scan showed abnormal uptakes in two of them. CONCLUSION: The MIBG scan was especially useful in 2 of the 27 patients but we had no experienced about the additional benefits of a MIBG scan in the other 25 cases. Our results reveal that a MIBG scan should be performed carefully for the diagnosis and localization of a pheochromocytoma, while considering cost and time of operation.
3-Iodobenzylguanidine* ; Adrenal Glands ; Diagnosis ; Humans ; Pheochromocytoma* ; Retrospective Studies ; Sensitivity and Specificity ; Seoul

BACKGROUND: To understand the mechanism of aging-related changes of the thyroid, the differentiated functions and growth of thyroid cells in response to TSH were investigated using aged or young thyrocytes. METHODS: FRTL-5 cells, with less than 10 or more than 45 passages, were used. After treatment with 1 U/L TSH or 1-100 mM NaI, the cAMP generation, iodide uptake, cellular proliferation or the expression of NIS mRNA or protein were measured. Sprague-Dawley rats were sacrificed at 5 and 16 weeks and 23 months, and their thyroids used for Northern blot analysis or immunohistochemistry of NIS. RESULTS: There were no differences in cAMP generation, iodide uptake, the proportions of G1/M or S phase, or intracellular DNA contents between the young and aged cells at basel levels. After TSH stimulation, these were increased in dose-dependent manners, with larger increments in the young cells. The changes in the NIS mRNA expression were similar in both the young and aged cells, but to a greater extent in the young cells. A similar phenomenon was observed in rat. However, the amount or intracellular distribution of NIS protein was not different. There was also no difference in the function or expression of NIS after treatment with a high dose of iodide. CONCLUSION: The aging-related decrease in the generation of cAMP might be thought of as one of the mechanisms of the decrement of iodide uptake or cellular proliferation with aging. The decreased expression of NIS mRNA seems to be the most important mechanism for the decreased iodide uptake capacity
Aging ; Animals ; Blotting, Northern ; Cell Proliferation ; DNA ; Immunohistochemistry ; Rats ; Rats, Sprague-Dawley ; RNA, Messenger ; S Phase ; Thyroid Gland*