Neuroinflammation is an important process underlying a wide variety of neurodegenerative diseases. Carvacrol (CAR) is a phenolic monoterpene commonly used as a food additive due to its antibacterial properties, but it has also been shown to exhibit strong antioxidative, anti-inflammatory, and neuroprotective effects. Here, we sought to investigate the effects of CAR on inflammation in the hippocampus and prefrontal cortex, as well as the molecular mechanisms underlying these effects. In our study, lipopolysaccharide was injected into the lateral ventricle of rats to induce memory impairment and neuroinflammation. Daily administration of CAR (25, 50, and 100 mg/kg) for 21 days improved recognition, discrimination, and memory impairments relative to untreated controls. CAR administration significantly attenuated expression of several inflammatory factors in the brain, including interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2. In addition, CAR significantly increased expression of brain-derived neurotrophic factor (BDNF) mRNA, and decreased expression of Toll-like receptor 4 (TLR4) mRNA. Taken together, these results show that CAR can improve memory impairment caused by neuroinflammation. This cognitive enhancement is due to the anti-inflammatory effects of CAR medicated by its regulation of BDNF and TLR4. Thus, CAR has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases.
Animals ; Brain ; Brain-Derived Neurotrophic Factor ; Cyclooxygenase 2 ; Cytokines ; Discrimination (Psychology) ; Food Additives ; Hippocampus ; Inflammation ; Lateral Ventricles ; Lipopolysaccharides ; Memory ; Necrosis ; Neurodegenerative Diseases ; Neuroprotective Agents ; Phenol ; Prefrontal Cortex ; Rats ; RNA, Messenger ; Toll-Like Receptor 4

0.05). The area under the receiver operating characteristics curve (AUC) was 0.922 [95% confidence interval (CI) 0.89–0.95]. In external validation, the discrimination was good, with an AUC value of 0.833 (95% CI 0.70–0.92) for this model. Nomogram calibration plots indicated good agreement between the predicted and observed outcomes, exhibiting close approximation between the predicted and observed probability.CONCLUSION: We constructed a scoring model for predicting massive transfusion during cesarean section in women with placenta previa. This model may help in determining the need to prepare an appropriate amount of blood products and the optimal timing of blood transfusion.]]>
Area Under Curve ; Blood Transfusion ; Calibration ; Cesarean Section ; Cohort Studies ; Discrimination (Psychology) ; Early Intervention (Education) ; Erythrocytes ; Female ; Humans ; Logistic Models ; Maternal Age ; Nomograms ; Placenta Previa ; Placenta ; Placentation ; Postpartum Hemorrhage ; Pregnancy ; ROC Curve ; Ultrasonography

PURPOSE: To validate and update a nomogram for predicting ductal carcinoma in situ (DCIS) upstaging in preoperative biopsy. MATERIALS AND METHODS: Medical records of 444 preoperative DCIS patients were evaluated and used to validate a previous version of the Severance nomogram for predicting DCIS upstaging in preoperative biopsy. Patients were divided into two groups according to the final postoperative pathology. Univariate and multivariate analyses with the chi-square test, Student's t-test, and binary logistic regression method identified new significant variables. The updated nomogram was evaluated with the C-index and Hosmer—Lemeshow goodness of fit test. RESULTS: The area under a receiver operating characteristic curve for comparison with the previous nomogram was 0.48. In postoperative pathology, the pure DCIS and invasive cancer groups comprised 345 and 99 cases, respectively. Approximately 22.3% of patients preoperatively diagnosed with DCIS were upstaged to invasive cancer. Significant variables in the univariate analysis were operation type, human epidermal growth factor receptor 2 overexpression, comedo necrosis, sonographic mass, mammographic mass, preoperative biopsy method, and suspicious microinvasion in preoperative biopsy. In multivariate analysis, operation type, sonographic mass, mammographic mass, and suspicious microinvasion were risk factors for upstaging. The updated model with these variables showed moderate discrimination and was appropriate in the calibration test. CONCLUSION: The previous nomogram did not effectively discriminate upstaging of preoperative DCIS in an independent cohort. An updated version of the nomogram appears to provide more accurate information for predicting preoperative DCIS upstaging.
Biopsy ; Breast Neoplasms ; Breast ; Calibration ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Cohort Studies ; Discrimination (Psychology) ; Humans ; Logistic Models ; Medical Records ; Methods ; Multivariate Analysis ; Necrosis ; Nomograms ; Pathology ; Receptor, Epidermal Growth Factor ; Risk Factors ; ROC Curve ; Ultrasonography

PURPOSE: Identification of lymph node (LN) metastasis in non-small cell lung cancer (NSCLC) is critical for disease staging and selection of therapeutic modalities. Sometimes it is not possible to obtain LN core tissue by endobronchial ultrasound-guided transbronchial needle aspirate (EBUS-TBNA), resulting in low diagnostic yield. MATERIALS AND METHODS: In this study, 138 specimens were collected from 108 patients who underwent EBUS-TBNA under the suspicion of LN metastasis of NSCLC. Diagnostic yields of anti-CD45 and anti-methionyl-tRNA synthetase (MRS), immunofluorescent (IF) staining on cytology specimens were compared with those of conventional cytology and positron emission tomography-computed tomography (PET-CT). RESULTS: MRS was strongly expressed in NSCLC cells metastasized to LNs, but weakly expressed in cells at the periphery of the LN germinal center. The majority of cells were CD20 positive, although a few cells were either CD3 or CD14 positive, indicating that CD45 staining is required for discrimination of non-malignant LN constituent cells from NSCLC cells. When the diagnostic efficacy of MRS/CD45 IF staining was evaluated using 138 LN cellular aspirates from 108 patients through EBUS-TBNA, the sensitivity was 76.7% and specificity was 90.8%, whereas those of conventional cytology test were 71.8% and 100.0%, respectively. Combining the results of conventional cytology testing and those of PET-CT showed a sensitivity and specificity of 71.6% and 100%, and the addition of MRS/CD45 dual IF data to this combination increased sensitivity and specificity to 85.1% and 97.8%, respectively. CONCLUSION: MRS/CD45 dual IF staining showed good diagnostic performance and may be a good tool complementing conventional cytology test for determining LN metastasis of NSCLC.
Amino Acyl-tRNA Synthetases ; Carcinoma, Non-Small-Cell Lung ; Complement System Proteins ; Discrimination (Psychology) ; Electrons ; Germinal Center ; Humans ; Ligases ; Lymph Nodes ; Methionine-tRNA Ligase ; Needles ; Neoplasm Metastasis ; Sensitivity and Specificity

PURPOSE: To evaluate predictors of severe or moderate coronary artery disease (CAD) in individuals with zero or very low (<10) coronary artery calcium (CAC) scores. MATERIALS AND METHODS: The 1175 asymptomatic persons with zero or very low (<10) CAC scores were analyzed for CAD stenosis using coronary computed tomography angiography. Moderate and severe CADs were defined as having more than 50% and more than 70% stenosis in any of the major coronary arteries, respectively. Age, gender, body mass index, hypertension, type II diabetes, dyslipidemia, lipid profile, creatinine, and smoking status were evaluated as predictors for moderate and severe CAD. RESULTS: In the study population, moderate and severe CADs were found in 7.5% and 3.3%, respectively. Among evaluated risk factors, age [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.02−1.07, p<0.001], current smoking status (OR 3.12, 95% CI 1.82−5.34, p<0.001), and CAC 1−9 (OR 1.80, 95% CI 1.08−3.00, p=0.024) were significantly associated with moderate CAD. Meanwhile, age (OR 1.05, 95% CI 1.02−1.08, p=0.003), low high density lipoprotein (HDL) (OR 0.96, 95% CI 0.93−0.99, p=0.003), and current smoking status (OR 2.34, 95% CI 1.14−5.30, p=0.022) were found to be significantly associated with severe CAD. Improvement of discrimination power for predicting severe CAD was observed when smoking and HDL cholesterol were serially added into the age model. CONCLUSION: Smoking showed significant correlations with moderate or severe CAD, and low HDL cholesterol also proved to be a predictor of severe CAD in asymptomatic individuals with extremely low CAC scores.
Angiography ; Asymptomatic Diseases ; Body Mass Index ; Calcium ; Cholesterol, HDL ; Constriction, Pathologic ; Coronary Artery Disease ; Coronary Vessels ; Creatinine ; Discrimination (Psychology) ; Dyslipidemias ; Humans ; Hypertension ; Lipoproteins ; Risk Factors ; Smoke ; Smoking

BACKGROUND: Discrimination is a representative social determinant of health. Presenteeism is defined as presenting to work despite of illness and is an indicator of group health. We investigated the association of discrimination and presenteeism with cardiovascular disease using Korean data. METHODS: This study used the fourth Korea Working Conditions Survey (2014) data of 27,662 wage workers (employees). Presenteeism and discrimination related to age, sex, education, birth region, and employment type were ascertained. Self-reported cardiovascular disease was also assessed using the survey questionnaire. General and occupational characteristics found to be significant in univariate analyses were entered into a multivariate logistic regression analysis of the association of discrimination and presenteeism with cardiovascular disease. We also calculated the odds ratios of multiple discriminations and/or presenteeism for cardiovascular disease. RESULTS: In the univariate analyses, sex, age, education, monthly income, employment type, occupation, hours worked per week, workplace scale, and shift work were significantly associated with cardiovascular disease. A multivariate logistic regression analysis adjusted for general and occupational characteristics showed that discrimination and presenteeism were significantly associated with cardiovascular disease. Finally, the association with cardiovascular disease was strongest when both multiple discriminations and presenteeism were present. CONCLUSIONS: Discrimination and presenteeism are associated with cardiovascular disease, and this association was stronger in the presence of multiple types of discrimination and presenteeism.
Cardiovascular Diseases ; Discrimination (Psychology) ; Education ; Employment ; Korea ; Logistic Models ; Occupations ; Odds Ratio ; Parturition ; Presenteeism ; Salaries and Fringe Benefits

BACKGROUND: The objective of this study is to evaluate the risk of exposure to second hand smoke (SHS) during working hours by job status and occupation. METHODS: Using the 4th Korean Working Conditions Survey (KWCS), 49,674 respondents who answered the question about SHS were studied. A chi-square test was carried out to determine whether there is a significant different in SHS exposure frequency by general and occupational characteristics and experience of discrimination at work and logistic regression analysis was carried out to identify the risk level of SHS exposure by variables. RESULTS: In this study, we found that male workers in their 40s and 50s, workers employed in workplaces with fewer than 50 employees, daily workers, and people working outdoors had a higher rate of exposure to SHS than the others. The top five occupations with the highest SHS exposure were construction and mining-related occupations, metal core-makers-related trade occupations, wood and furniture, musical instrument, and signboard-related trade occupations, transport and machine-related trade occupations, transport and leisure services occupations. The least five exposed occupations were public and enterprise senior officers, legal and administrative professions, education professionals, and health, social welfare, and religion-related occupations. CONCLUSION: Tobacco smoke is a significant occupational hazard. Smoking ban policy in the workplace can be a very effective way to reduce the SHS exposure rate in the workplace and can be more effective if specifically designed by the job status and various occupations.
Discrimination (Psychology) ; Education ; Humans ; Interior Design and Furnishings ; Leisure Activities ; Logistic Models ; Male ; Music ; Occupations ; Smoke ; Smoking ; Social Welfare ; Surveys and Questionnaires ; Tobacco ; Tobacco Smoke Pollution ; Wood

BACKGROUND: Cell-free DNA (cfDNA) has the potential to serve as a non-invasive prognostic biomarker in some types of neoplasia. The investigation of plasma concentration of cfDNA may reveal its use as a valuable biomarker for risk stratification of diffuse large B-cell lymphoma (DLBCL). The present prognostic value of plasma cfDNA has not been widely confirmed in DLBCL subjects. Here, we evaluated cfDNA plasma concentration and assessed its potential prognostic value as an early DLBCL diagnostic tool. METHODS: cfDNA concentrations in plasma samples from 40 patients with DLBCL during diagnosis and of 38 normal controls were determined with quantitative polymerase chain reaction (qPCR) for the multi-locus L1PA2 gene. RESULTS: Statistically significant elevation in plasma cfDNA concentrations was observed in patients with DLBCL as compared to that in normal controls (P<0.05). A cutoff point of 2.071 ng/mL provided 82.5% sensitivity and 62.8% specificity and allowed successful discrimination of patients with DLBCL from normal controls (area under the curve=0.777; P=0.00003). Furthermore, patients with DLBCL showing higher concentrations of cfDNA had shorter overall survival (median, 9 mo; P=0.022) than those with lower cfDNA levels. In addition, elevated cfDNA concentration was significantly associated with age, B-symptoms, International Prognostic Index (IPI) score, and different stages of disease (all P<0.05). CONCLUSION: Quantification of cfDNA with qPCR at the time of diagnosis may allow identification of patients with high cfDNA concentration, which correlates with aggressive clinical outcomes and adverse prognosis.
B-Lymphocytes ; Diagnosis ; Discrimination (Psychology) ; DNA ; Humans ; Lymphoma, B-Cell ; Plasma ; Polymerase Chain Reaction ; Prognosis ; Sensitivity and Specificity

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system. MATERIALS AND METHODS: We used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included. RESULTS: Poor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS. CONCLUSION: This is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.
Classification ; Discrimination (Psychology) ; Disease-Free Survival ; Humans ; Joints ; Neoplasm Staging ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors ; Pancreas ; Survival Rate

PURPOSE: Hepatocellular carcinoma (HCC) is an aggressive disease with high recurrence rate. However, current staging systems were lack of predictive capacity for HCC recurrence. We aimed to develop prognostic nomograms based on inflammation-related markers for HCC patients underwent hepatectomy. MATERIALS AND METHODS: We recruited 889 surgically treated patients from two medical centers. Independent prognostic factors were identified by cox regression analyses. Nomograms for recurrence-free survival (RFS) and overall survival (OS) were established, and validated internally and externally. The performance, discrimination, and calibration of nomograms were assessed, and compared with existed staging systems. RESULTS: Neutrophil to lymphocyte ratio (NLR) and gamma-glutamyl transpeptidase to platelet ratio (GPR) were the two inflammation-related factor that independently correlated with survival. NLR, GPR, international normalized ratio (INR), microvascular invasion, satellite lesions, tumour number, tumour diameter, and macrovascular invasion were used to construct nomogram for RFS while GPR, total bilirubin, INR, α-fetoprotein, microvascular invasion, satellite lesions, tumour diameter, and macrovascular invasion were for OS. In the training cohort, the C-index of nomogram was 0.701 (95% confidence interval [CI], 0.669 to 0.732) for RFS and 0.761 (95% CI, 0.728 to 0.795) for OS. These results received both internal and external validation with C-index of 0.701 (95% CI, 0.647 to 0.755) and 0.707 (95% CI, 0.657 to 0.756) for RFS, and 0.706 (95% CI, 0.640 to 0.772) and 0.708 (95% CI, 0.646 to 0.771) for OS, respectively. The nomograms showed superior accuracy to conventional staging systems (p<0.001). CONCLUSION: The nomograms based on inflammation-related markers are of high efficacy in predicting survival of HCC patients after hepatectomy, which will be valuable in guiding postoperative interventions and follow-ups.
Bilirubin ; Blood Platelets ; Calibration ; Carcinoma, Hepatocellular ; Cohort Studies ; Discrimination (Psychology) ; Follow-Up Studies ; gamma-Glutamyltransferase ; Hepatectomy ; Humans ; Inflammation ; International Normalized Ratio ; Lymphocytes ; Neutrophils ; Nomograms ; Recurrence