Background: A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study. Methods: Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases. Conclusion KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

Background: A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study. Methods: Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases. Conclusion KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

Objective: Alzheimer’s disease (AD) is the most common type of dementia and the prevalence rapidly increased as the elderly population increased worldwide. In the contemporary model of AD, it is regarded as a disease continuum involving preclinical stage to severe dementia. For accurate diagnosis and disease monitoring, objective index reflecting structural change of brain is needed to correctly assess a patient’s severity of neurodegeneration independent from the patient’s clinical symptoms. The main aim of this paper is to develop a random forest (RF) algorithm-based prediction model of AD using structural magnetic resonance imaging (MRI). Methods: We evaluated diagnostic accuracy and performance of our RF based prediction model using newly developed brain segmentation method compared with the Freesurfer’s which is a commonly used segmentation software. Results: Our RF model showed high diagnostic accuracy for differentiating healthy controls from AD and mild cognitive impairment (MCI) using structural MRI, patient characteristics, and cognitive function (HC vs. AD 93.5%, AUC 0.99; HC vs. MCI 80.8%, AUC 0.88). Moreover, segmentation processing time of our algorithm (<5 minutes) was much shorter than of Freesurfer’s (6–8 hours). Conclusion Our RF model might be an effective automatic brain segmentation tool which can be easily applied in real clinical practice.

Apurinic/apyrimidinic endonuclease 1 (APE1) is an enzyme responsible for the initial step in the base excision repair pathway and is known to be a potential drug target for treating cancers, because its expression is associated with resistance to DNA-damaging anticancer agents. Although several inhibitors already have been identified, the identification of novel kinds of potential inhibitors of APE1 could provide a seed for the development of improved anticancer drugs. For this purpose, we first classified known inhibitors of APE1. According to the classification, we constructed two distinct pharmacophore models. We screened more than 3 million lead-like compounds using the pharmacophores. Hits that fulfilled the features of the pharmacophore models were identified. In addition to the pharmacophore screen, we carried out molecular docking to prioritize hits. Based on these processes, we ultimately identified 1,338 potential inhibitors of APE1 with predicted binding affinities to the enzyme.
Antineoplastic Agents ; Classification ; DNA Repair ; Molecular Docking Simulation

BACKGROUND: Electromyography and acceleromyography are common neuromuscular monitoring devices. However, questions still remain regarding the use of acceleromyography in children. This study compared the calibration success rates and intubation conditions in children after obtaining the maximal blockade depending on each of the devices METHODS: Children, 3 to 6 years old, were randomly allocated to the TOF-Watch SX acceleromyography group or the NMT electromyography group. The induction was performed with propofol, fentanyl, and rocuronium. The bispectral index and 1 Hz single twitch were monitored during observation. The calibration of the each device was begun when the BIS dropped to 60. After successful calibration, rocuronium 0.6 mg/kg was injected. A tracheal intubation was performed when the twitch height suppressed to 0. The rocuronium onset time (time from administration to the maximal depression of twitch height) and intubating conditions were rated in a blinded manner. RESULTS: There was no difference in the calibration success rates between the two groups; and the calibration time in the electromyography group (16.7 +/- 11.0 seconds) was shorter than the acceleromyography group (28.1 +/- 13.4 seconds, P = 0.012). The rocuronium onset time of the electromyography group (73.6 +/- 18.9 seconds) was longer than the acceleromyography group (63.9 +/- 18.8 seconds, P = 0.042) and the intubation condition of the electromyography group (2.27 +/- 0.65) was better than the acceleromyography group (1.86 +/- 0.50, P = 0.007). CONCLUSIONS: Electromyography offers a better compromise than acceleromyography with respect to the duration of calibration process and surrogate for the optimal time of tracheal intubation in children.
Anesthesia, General* ; Calibration ; Child* ; Child, Preschool ; Depression ; Electromyography* ; Fentanyl ; Humans ; Intubation ; Neuromuscular Monitoring ; Propofol ; Prospective Studies*

BACKGROUND: The present study evaluated the efficacy of a combination of ibandronate and cholecalciferol on the restoration of the levels of 25-hydroxyvitamin D (25[OH]D) and various bone markers in postmenopausal women with osteoporosis. METHODS: This was a randomized, double-blind, active-controlled, prospective 16-week clinical trial conducted in 20 different hospitals. A total of 201 postmenopausal women with osteoporosis were assigned randomly to one of two groups: the IBN group, which received a once-monthly pill containing 150 mg ibandronate (n=99), or the IBN+ group, which received a once-monthly pill containing 150 mg ibandronate and 24,000 IU cholecalciferol (n=102). Serum levels of 25(OH)D, parathyroid hormone (PTH), and various bone markers were assessed at baseline and at the end of a 16-week treatment period. RESULTS: After 16 weeks of treatment, the mean serum levels of 25(OH)D significantly increased from 21.0 to 25.3 ng/mL in the IBN+ group but significantly decreased from 20.6 to 17.4 ng/mL in the IBN group. Additionally, both groups exhibited significant increases in mean serum levels of PTH but significant decreases in serum levels of bone-specific alkaline phosphatase and C-telopeptide of type 1 collagen (CTX) at 16 weeks; no significant differences were observed between the groups. However, in subjects with a vitamin D deficiency, IBN+ treatment resulted in a significant decrease in serum CTX levels compared with IBN treatment. CONCLUSION: The present findings demonstrate that a once-monthly pill containing ibandronate and cholecalciferol may be useful for the amelioration of vitamin D deficiency in patients with postmenopausal osteoporosis. Moreover, this treatment combination effectively decreased serum levels of resorption markers, especially in subjects with a vitamin D deficiency, over the 16-week treatment period.
Alkaline Phosphatase ; Cholecalciferol* ; Collagen Type I ; Female ; Humans ; Osteoporosis* ; Osteoporosis, Postmenopausal ; Parathyroid Hormone ; Prospective Studies ; Vitamin D Deficiency

BACKGROUND/AIMS: Follicular thyroid carcinoma (FTC) and Hurthle cell carcinoma (HCC) of the thyroid are relatively uncommon thyroid malignancies in iodine-sufficient areas. In this study we evaluated the clinical behavior, prognostic factors and treatment outcomes of FTC and HCC in Korea. METHODS: This multicenter study included 483 patients with FTC and 80 patients with HCC who underwent an initial surgery between 1995 and 2006 in one of the four tertiary referral hospitals in Korea. We evaluated clinicopathological factors associated with distant metastases and recurrence during a median of 6 years of follow-up. RESULTS: HCC patients were significantly older (49 years vs. 43 years; p < 0.001) and had more lymphovascular invasions (22% vs. 14%; p = 0.03) compared with FTC patients. Distant metastases were confirmed in 40 patients (8%) in the FTC group and in two patients (3%) in the HCC group (p = 0.07). Distant metastases were significantly associated with older age, widely invasive cancer and extrathyroidal invasion. Only 14 patients (3%) had recurrent disease and there was no significant difference between FTC and HCC groups (p = 0.38). Recurrence was associated with larger tumor size and cervical lymph node metastasis. CONCLUSIONS: HCC patients were older and had more lymphovascular invasions than FTC patients. However, FTC and HCC patients had similar initial clinicopathological features. Older age, wide invasiveness and extrathyroidal invasion were independent risk factors for predicting distant metastases in FTC and HCC patients.
Adenocarcinoma, Follicular/*epidemiology/secondary/surgery ; Adult ; Age Factors ; *Diet ; Female ; Humans ; *Iodine ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; *Nutritional Status ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Tertiary Care Centers ; Thyroid Neoplasms/*epidemiology/pathology/surgery ; Thyroidectomy ; Time Factors ; Treatment Outcome

BACKGROUND: There are many studies regarding the effects of insulin on bone metabolism and changes in bone mineral density (BMD) in the setting of diabetes. The effect of prediabetes on BMD is not known. METHODS: A total of 802 men participated in the Korea Rural Genomic Cohort Study (in Geumsan County). According to the results of an oral glucose tolerance test, subjects were classified into normal, prediabetic, and diabetic categories. One hundred twenty-four subjects diagnosed with type 2 diabetes were excluded, leaving 678 subjects for the study inclusion. BMD was estimated with a quantitative ultrasonometer. RESULTS: The average BMD T scores of normal and prediabetic subjects were -1.34 +/- 1.42 and -1.33 +/- 1.30, respectively; there was no significant difference in the BMD T scores between these groups. The BMD T score was inversely associated with age and positively correlated with body weight, body mass index, total cholesterol, low density lipoprotein cholesterol, and HbA1c. On multiple linear regression analysis, low density lipoprotein cholesterol was the only statistically significant variable for prediabetes (beta = 0.007, P = 0.005). On the stepwise regression analysis, age (beta = -0.026, P < 0.001), the body mass index (beta = 0.079, P < 0.001), and low density lipoprotein cholesterol (beta = 0.004, P = 0.016) were significant variables for prediabetes. CONCLUSIONS: There was no significant difference in the BMD T score between the normal and prediabetic subjects. Further studies are needed regarding the association of fracture risk and changes in BMD with the development of overt diabetes.
Body Mass Index ; Body Weight ; Bone Density ; Cholesterol ; Cholesterol, LDL ; Cohort Studies ; Glucose Tolerance Test ; Humans ; Insulin ; Korea ; Linear Models ; Lipoproteins ; Male ; Prediabetic State

Previous studies have demonstrated that rottlerin, a specific PKCdelta inhibitor, potentiates death receptor- mediated apoptosis through a cytochrome c-dependent or -independent pathway. However, its ability to regulate necrotic cell death, as well as the underlying mechanism, remains unknown. We found that in murine fibrosarcoma L929 cells, treatment with rottlerin protected the cells against TNF-induced necrosis, whereas it sensitized the cells to apoptosis induced by co-treatment with Hsp90 inhibitor geldanamycin and TNF, in a manner independent of its ability to inhibit PKC-delta. TNF treatment induced rapid accumulation of mitochondrial superoxide (O2") through the Nox1 NADPH oxidase when cells undergo necrosis. Moreover, pretreatment with rottlerin failed to induce the GTP-bound form of small GTPase Rac1 by TNF treatment, and subsequently suppressed mitochondrial O2(-) production and poly(ADP-ribose) polymerase activation, thus inhibiting necrotic cell death. Therefore, our study suggests that Nox1 NADPH oxidase is a new molecular target for anti-necrotic activity of rottlerin upon death-receptor ligation.
Acetophenones/*pharmacology ; Animals ; Benzopyrans/*pharmacology ; Cell Death/*drug effects ; Cell Line, Tumor ; Mice ; Protein Kinase Inhibitors/*pharmacology ; Superoxides/metabolism ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors/pharmacology