Objective: We investigated the frequency of depressive disorders in the elderly with normal cognition (NC), mild cognitive impairment (MCI) and dementia patients living in the community to find out the association between cognitive disorders and depressive disorders in the community dwelling elderly. Methods: 6,262 baseline study subjects from November 2010 through October 2012 were enrolled based on the Korean longitudinal study on cognitive aging and dementia which is the first nationwide multi-center population based prospective cohort study in Korea. Diagnosis of MCI, dementia, major depressive disorder (MDD), minor depressive disorder (mDD) and subsyndromal depression (SSD) was made by psychiatrists with expertise in dementia based on the appropriate diagnostic criteria. Results: 4,303 NC, 1,737 MCI, 222 dementia were enrolled. The frequency of MDD, mDD, SSD were highest in dementia and lowest in NC and showed significant difference among three groups. The odds ratio also increased significantly in MCI and dementia compared with NC showing highest odds ratio in dementia. Conclusion Our findings propose that MCI and dementia in the community dwelling elderly were significantly associated with various types of depressive disorders showing highest association tendency in dementia.

BACKGROUND/AIMS: Pancreatic cancer has a very poor prognosis, and early diagnosis is a way to increase the survival rate of patients. The purpose of this study was to develop pancreatic cancer-specific peptides for imaging studies. METHODS: Three pancreatic cancer cell lines, MIA PaCa-2, UACC-462, and BxPC-3, and a control cell line, CCD841, were used. Biopannings were performed on MIA PaCa-2 using a phage display library. After this, the peptides were synthesized and labeled with fluorescein isothiocyanate (FITC). Immunocytochemistry (ICC), enzyme-linked immunosorbent assay (ELISA), and fluorescence-activated cell sorter (FACS) were performed to examine the specific binding. To examine its therapeutic applications, a photosensitizer, chlorin e6 (Ce6), was conjugated on the peptide and photodynamic therapy was performed. Cell survival was investigated using a [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] assay. RESULTS: After three biopannings, the phages were amplified from 1.4×104 to 3.2×105 plaque-forming units. The most strongly binding phage was selected from the ELISA and ICC results. FITC-labeled peptide, M5, in the three pancreatic cancer cell lines showed significantly higher immunofluorescence in the ICC experiments than that of CCD841. The higher binding ability to MIA PaCa-2 cells was confirmed from FACS analysis, which showed a right shift compared to CCD841. M5 bound to Ce6 showed a significantly lower cell survival rate than that of Ce6 alone in photodynamic therapy, which was observed consistently as a change in the tumor size and fluorescence intensity in MIA PaCa-2 cell-implanted animal models. CONCLUSIONS: This study showed that the noble peptide, M5, binds specifically to the pancreatic cancer cell line, MIA PaCa-2. The M5 peptide has potential use in future optical diagnostic and therapeutic purposes.
Bacteriophages ; Cell Line ; Cell Survival ; Early Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Fluorescein ; Fluorescence ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Models, Animal ; Pancreatic Neoplasms ; Peptides ; Photochemotherapy ; Prognosis ; Survival Rate

BACKGROUND/AIMS: Pancreatic cancer has a very poor prognosis, and early diagnosis is a way to increase the survival rate of patients. The purpose of this study was to develop pancreatic cancer-specific peptides for imaging studies.METHODS: Three pancreatic cancer cell lines, MIA PaCa-2, UACC-462, and BxPC-3, and a control cell line, CCD841, were used. Biopannings were performed on MIA PaCa-2 using a phage display library. After this, the peptides were synthesized and labeled with fluorescein isothiocyanate (FITC). Immunocytochemistry (ICC), enzyme-linked immunosorbent assay (ELISA), and fluorescence-activated cell sorter (FACS) were performed to examine the specific binding. To examine its therapeutic applications, a photosensitizer, chlorin e6 (Ce6), was conjugated on the peptide and photodynamic therapy was performed. Cell survival was investigated using a [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] assay.RESULTS: After three biopannings, the phages were amplified from 1.4×104 to 3.2×105 plaque-forming units. The most strongly binding phage was selected from the ELISA and ICC results. FITC-labeled peptide, M5, in the three pancreatic cancer cell lines showed significantly higher immunofluorescence in the ICC experiments than that of CCD841. The higher binding ability to MIA PaCa-2 cells was confirmed from FACS analysis, which showed a right shift compared to CCD841. M5 bound to Ce6 showed a significantly lower cell survival rate than that of Ce6 alone in photodynamic therapy, which was observed consistently as a change in the tumor size and fluorescence intensity in MIA PaCa-2 cell-implanted animal models.CONCLUSIONS: This study showed that the noble peptide, M5, binds specifically to the pancreatic cancer cell line, MIA PaCa-2. The M5 peptide has potential use in future optical diagnostic and therapeutic purposes.
Bacteriophages ; Cell Line ; Cell Survival ; Early Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Fluorescein ; Fluorescence ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Models, Animal ; Pancreatic Neoplasms ; Peptides ; Photochemotherapy ; Prognosis ; Survival Rate

PURPOSE: This study was performed to evaluate the compliance with, and adequacy of, the Korean national guidelines which had been recommended until 2011 for isolation of patients with group 1 nationally notifiable infectious diseases (NNIDs), namely cholera, typhoid fever, paratyphoid fever, shigellosis, and enterohemorrhagic Escherichia coli (EHEC) infection. MATERIALS AND METHODS: We evaluated the clinical and microbiological characteristics of confirmed cases of group 1 NNIDs and compliance with the guidelines in 20 Korean hospitals nationwide in 2000-2010. We also compared the Korean guidelines with international guidelines. RESULTS: Among 528 confirmed cases (8 cases of cholera, 232 of typhoid fever, 81 of paratyphoid fever, 175 of shigellosis, and 32 EHEC infections), strict compliance with the Korean guideline was achieved in only 2.6% to 50.0%, depending on the disease. While the Korean guidelines recommend isolation of all patients with group 1 NNIDs, international guidelines recommend selective patient isolation and screening for fecal shedding, depending on the type of disease and patient status. CONCLUSION: Compliance with the previous national guidelines for group 1 NNIDs in Korea was generally very low. Further studies are needed to evaluate whether compliance was improved after implementation of the new guideline in 2012.
Cholera ; Communicable Disease Control ; Communicable Diseases* ; Compliance* ; Dysentery, Bacillary ; Enterohemorrhagic Escherichia coli ; Guideline Adherence ; Humans ; Korea* ; Mass Screening ; Methods ; Paratyphoid Fever ; Patient Isolation ; Typhoid Fever

PURPOSE: Thyroid ultrasonography (US) is a useful diagnostic tool in the evaluation of diffuse thyroid disease (DTD), whereas shearwave elastography is a dynamic technique that can provide information about tissue hardness by using acoustic shearwaves remotely induced by a focused ultrasonic beam. This study aims at investigating the role of conventional US and shearwave elastography in the diagnosis of asymptomatic patients with DTD. MATERIALS AND METHODS: Fifty-seven patients who underwent both conventional US and shearwave elastography were included in this study. Interobserver variability of the three radiologists in assessment of underlying thyroid echogenicity on conventional US was analyzed. Diagnostic performances for diagnosing DTD on conventional US and shearwave elastography were calculated and compared. RESULTS: Fair agreement was observed in the identification of DTD with conventional US (kappa value=0.27). The area under the receiver operating characteristic curve (Az) were 0.52-0.585 on conventional US by three radiologists. The Az values when using the mean and maximum elasticity values as a diagnostic criteria for DTD were 0.619 and 0.59 on shearwave elastography. Patients with DTD showed higher mean [24.1+/-10 kilo-Pascals (kPa)] and maximum (36.4+/-13.3 kPa) elasticity values on shearwave elastography when compared to the normal group (23.4+/-10.8 kPa and 33.7+/-12.4 kPa, respectively), although without statistical significance (p=0.802 and p=0.452, respectively). CONCLUSION: Conventional US did not show reliable interobserver agreement in the diagnosis of DTD. Although not statistically significant, shearwave elastography may provide additional information in the diagnosis of DTD. Therefore, larger prospective studies are needed to define the values of shearwave elastography for diagnosing DTD.
Adult ; Elasticity Imaging Techniques/*methods ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Thyroid Diseases/*ultrasonography ; Thyroid Gland/*ultrasonography ; Ultrasonography/*methods

Although formaldehyde (FA) is known to be a major allergen responsible for allergic contact dermatitis, there are conflicting reports regarding correlation between FA exposure and interleukin (IL-4) expression. To investigate whether allergic responses including IL-4 expression were induced by repeated dermal exposure to low dose FA, alterations in the luciferase signal and allergic phenotypes were measured in IL-4/Luc/CNS-1 transgenic (Tg) mice containing luciferase cDNA under control of the IL-4 promoter after exposure to 4% FA for 2 weeks. High levels of luciferase were detected in the abdominal region of the whole body and submandibular lymph node (SLN) of FA treated mice. Additionally, the ear thickness and IgE concentration were significantly upregulated in the FA treated group when compared with the acetone olive oil (AOO) treated group. FA treated mice showed enhanced auricular lymph node (ALN) weight, epidermis and dermis thickness, and infiltration of inflammatory cells. Furthermore, the expression of IL-6 among T helper 2 cytokines was higher in the FA treated group than the AOO treated group, while vascular endothelial growth factor (VEGF) levels remained constant. Overall, the results presented herein provide additional evidence that various allergic responses may be successfully induced in IL-4/Luc/CNS-1 Tg mice after exposure to low dose FA for 2 weeks. The luciferase signal under the IL-4 promoter may reflect general indicators of the allergic response induced by exposure to low dose FA.
Acetone ; Animals ; Cytokines ; Dermatitis, Allergic Contact ; Dermis ; DNA, Complementary ; Ear ; Epidermis ; Formaldehyde* ; Immunoglobulin E ; Interleukin-4 ; Interleukin-6 ; Interleukins ; Luciferases ; Lymph Nodes ; Mice ; Mice, Transgenic* ; Olea ; Phenotype ; Vascular Endothelial Growth Factor A ; Olive Oil

To investigate the toxic effects of cheonggukjang (CKJ) manufactured using mixed cultures of Bacillus subtilis MC31 and Lactobacillus sakei 383 on the liver and kidney of ICR mice, an alteration on the related markers including body weight, organ weight, urine composition, liver pathology and kidney pathology were analyzed after oral administration at dosage of 25, 50 and 100 mg/kg body weight/day of CKJ for 14 days. Any significant toxicity was not observed on the body and organ weight, clinical phenotypes, urine parameters and mortality in the CKJ-treated group compared with the vehicle-treated group. Also, liver toxicity analysis revealed no significant increase in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) or lactate dehydrogenase (LDH) in response to CKJ. Additionally, the specific pathological features induced by most toxic compounds were not observed upon liver histological analysis. Furthermore, kidney toxicological analysis revealed that blood urea nitrogen (BUN) and the serum creatinine (Cr) levels and pathological features on histological sections did not differ significantly between the vehicle- and CKJ-treated groups. Overall, these results suggest that CKJ does not induce any specific toxicity in liver and kidney organs of ICR at dose of 100 mg/kg body weight/day as no observed adverse effect level (NOAEL).
Administration, Oral ; Alanine Transaminase ; Alkaline Phosphatase ; Animals ; Aspartate Aminotransferases ; Bacillus subtilis* ; Blood Urea Nitrogen ; Body Weight ; Creatinine ; Kidney* ; L-Lactate Dehydrogenase ; Lactobacillus* ; Liver* ; Mice ; Mice, Inbred ICR* ; Mortality ; No-Observed-Adverse-Effect Level ; Organ Size ; Pathology ; Phenotype ; Soybeans*

Loperamide has long been known as an opioid-receptor agonist useful as a drug for treatment of diarrhea resulting from gastroenteritis or inflammatory bowel disease as well as to induce constipation. To determine and characterize putative biomarkers that can predict constipation induced by loperamide treatment, alteration of endogenous metabolites was measured in the serum of Sprague Dawley (SD) rats treated with loperamide for 3 days using 1H nuclear magnetic resonance (1H NMR) spectral data. The amounts and weights of stool and urine excretion were significantly lower in the loperamide-treated group than the No-treated group, while the thickness of the villus, crypt layer, and muscle layer was decreased in the transverse colon of the same group. The concentrations of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatinine (Cr) were also slightly changed in the loperamide-treated group, although most of the serum components were maintained at a constant level. Furthermore, pattern recognition of endogenous metabolites showed completely separate clustering of the serum analysis parameters between the No-treated group and loperamide-treated group. Among 35 endogenous metabolites, four amino acids (alanine, glutamate, glutamine and glycine) and six endogenous metabolites (acetate, glucose, glycerol, lactate, succinate and taurine) were dramatically decreased in loperamide-treated SD rats. These results provide the first data pertaining to metabolic changes in SD rats with loperamide-induced constipation. Additionally, these findings correlate the changes in 10 metabolites with constipation.
Amino Acids ; Animals ; Aspartate Aminotransferases ; Biomarkers ; Colon, Transverse ; Constipation* ; Creatinine ; Diarrhea ; Gastroenteritis ; Glucose ; Glutamic Acid ; Glutamine ; Glycerol ; Inflammatory Bowel Diseases ; L-Lactate Dehydrogenase ; Lactic Acid ; Loperamide ; Magnetic Resonance Spectroscopy ; Metabolomics* ; Rats* ; Succinic Acid ; Weights and Measures

OBJECTIVE: The objective of this retrospective study was to develop and validate a simple diagnostic prediction model by using ultrasound (US) features of thyroid nodules obtained from multicenter retrospective data. MATERIALS AND METHODS: Patient data were collected from 20 different institutions and the data included 2000 thyroid nodules from 1796 patients. For developing a diagnostic prediction model to estimate the malignant risk of thyroid nodules using suspicious malignant US features, we developed a training model in a subset of 1402 nodules from 1260 patients. Several suspicious malignant US features were evaluated to create the prediction model using a scoring tool. The scores for such US features were estimated by calculating odds ratios, and the risk score of malignancy for each thyroid nodule was defined as the sum of these individual scores. Later, we verified the usefulness of developed scoring system by applying into the remaining 598 nodules from 536 patients. RESULTS: Among 2000 tumors, 1268 were benign and 732 were malignant. In our multiple regression analysis models, the following US features were statistically significant for malignant nodules when using the training data set: hypoechogenicity, marked hypoechogenicity, non-parallel orientation, microlobulated or spiculated margin, ill-defined margins, and microcalcifications. The malignancy rate was 7.3% in thyroid nodules that did not have suspicious-malignant features on US. Area under the receiver operating characteristic (ROC) curve was 0.867, which shows that the US risk score help predict thyroid malignancy well. In the test data set, the malignancy rates were 6.2% in thyroid nodules without malignant features on US. Area under the ROC curve of the test set was 0.872 when using the prediction model. CONCLUSION: The predictor model using suspicious malignant US features may be helpful in risk stratification of thyroid nodules.
Female ; Humans ; *Image Interpretation, Computer-Assisted ; Korea ; Male ; Middle Aged ; Predictive Value of Tests ; ROC Curve ; Regression Analysis ; Retrospective Studies ; Risk ; Thyroid Nodule/*ultrasonography

In order to investigate the effects of a fermented soybean product (Chungkookjang, CKJ) on nerve growth factor (NGF) metabolism, NGF secretion ability and its related signaling pathway were analyzed in B35 neuronal cells and the Tg2576 mouse model of Alzheimer's disease (AD). In B35 cells, the concentration of NGF significantly increased upon treatment with Taegwang (TG)-CKJ and Shinhwa (SH)-CKJ extracts compared with vehicle. Further, a significant increase in PC12 cell length as well as the phsophorylation levels of TrkA and Akt, which are members of a high affinity NGF receptor signaling pathway, were observed after treatment with TG-CKJ and SH-CKJ conditional medium (CM). On the other hand, there was no difference in activation of the NGF receptor p75NTR signaling pathway between vehicle and all CKJ treated groups. In Tg2576 mice showing early stage of AD, the concentrations of NGF in the serum and brain were reduced compared with those in Non-Tg mice. Treatment of Tg2576 mice with SH-CKJ, which contains high concentrations of total flavonoids and phenolic compounds, for 8 weeks dramatically recovered the NGF level to that of Non-Tg mice. Furthermore, the low phosphorylation levels of TrkA and Erk in the NGF receptor TrkA signaling pathway were rapidly recovered to those of Non-Tg mice after SH-CKJ treatment in vehicle treated Tg2576 mice, whereas the phosphorylation level of Akt was maintained at a constant level. These results suggest that CKJ may stimulate NGF secretion ability as well as the NGF receptor TrkA signaling pathway in PC12 cells and Tg2576 mice.
Alzheimer Disease ; Animals ; Brain ; Flavonoids ; Hand ; Isoflavones ; Mice ; Nerve Growth Factor ; Neurons ; PC12 Cells ; Phenol ; Phosphorylation ; Receptor, Nerve Growth Factor ; Soybean Proteins ; Soybeans