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This study investigated the role of BRAF mutation analysis in thyroid fine-needle aspiration (FNA) samples compared to ultrasonographic and cytological diagnoses. A total 316 patients underwent ultrasonography (US)-guided FNA with BRAFV600E mutation analysis to diagnose thyroid nodules. One hundred sixteen patients with insufficient US images (n = 6), follow-up loss (n = 43), or unknown final diagnosis (n = 67) were excluded from the study. Comparisons between US diagnoses, cytological diagnoses, and BRAF mutation analysis were performed. Of 200 thyroid nodules, there was US diagnosis with 1 false negative and 11 false positive cases, cytological diagnosis with 10 false negative and 2 false positive cases, and BRAFV600E mutation analysis with 19 false negative and 2 false positive cases. The sensitivity, specificity, positive and negative predictive values, and accuracy of BRAFV600E mutation analysis were 83.2%, 98.1%, 97.5%, 86.6%, and 91%, respectively. Of the 18 nodules with Bethesda category III, 9 were true positive, 6 were true negative, 3 was a false negative, and none were false positive on BRAF mutation analysis. In conclusion, we recommend that BRAFV600E mutation analysis only be performed for evaluating thyroid nodules with Bethesda category III, regardless of US diagnosis. [ABSTRACT FROM AUTHOR]

Stress-related cardiomyopathy can develop during the postoperative period due to surgery-related stress factors. However, the prevalence and risk factors for this condition are not yet known. During a retrospective, observational study, patients older than 19 years who underwent procedures from January 2011 to December 2015 at a tertiary hospital were included. The main aim was to identify the prevalence and related risk factors for postoperative stress-related cardiomyopathy. To estimate the incidence per risk factor, univariate and multivariate Poisson regression analyses were performed. During the 5-year period, 95,840 patients older than 19 years underwent 125,314 procedures, and the prevalence of postoperative stress-related cardiomyopathy was 17.74 per 100,000 (95% confidence interval, 9.31–26.17), with an in-hospital mortality of 23.5%. As a result, three risk factors were significantly associated: preoperative American Society of Anesthesiologists classification (incidence rate ratio, 5.901 for American Society of Anesthesiologists class 1–2 [ref] versus 3–6; 95% confidence interval,1.289–27.002; P = 0.022); preoperative body mass index (incidence rate ratio, 1.247 for increases of 18.5 [ref] to 30; 95% confidence interval, 1.067–1.458; P = 0.006); and preoperative serum sodium (incidence rate ratio, 0.830 for each increase of 10 mmol/L from 130; 95% confidence interval, 0.731–0.942; P = 0.004). The incidence rate ratio for age for each increase of 10 years from 50 years was 1.057, but it was not statistically significant (P = 0.064). Our study found that the prevalence of postoperative stress-related cardiomyopathy was 17.74 patients per 100,000 adult patients over the course of 5 years, with four cases of in-hospital mortality. Factors that increased the risk of postoperative stress-related cardiomyopathy included higher American Society of Anesthesiologists class (≥3), preoperative hyponatremia, and higher preoperative body mass index. [ABSTRACT FROM AUTHOR]

Consumption of a typical Western diet is a risk factor for several disorders. Metabolic syndrome is the most common disease associated with intake of excess fat. However, the incidence of inflammatory bowel disease is also greater in subjects consuming a Western diet, although the mechanism of this phenomenon is not clearly understood. We examined the morphological and functional changes of the intestine, the first site contacting dietary fat, in mice fed a high-fat diet (HFD) inducing obesity. Paneth cell area and production of antimicrobial peptides by Paneth cells were decreased in HFD-fed mice. Goblet cell number and secretion of mucin by goblet cells were also decreased, while intestinal permeability was increased in HFD-fed mice. HFD-fed mice were more susceptible to experimental colitis, and exhibited severe colonic inflammation, accompanied by the expansion of selected pathobionts such as Atopobium sp. and Proteobacteria. Fecal microbiota transplantation transferred the susceptibility to DSS-colitis, and antibiotic treatment abrogated colitis progression. These data suggest that an experimental HFD-induced Paneth cell dysfunction and subsequent intestinal dysbiosis characterized by pathobiont expansion can be predisposing factors to the development of inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Atherosclerosis, the major pathology of cardiovascular disease, is caused by multiple factors involving psychological stress. Corticotropin-releasing hormone (CRH), which is released by neurosecretory cells in the hypothalamus, peripheral nerve terminals and epithelial cells, regulates various stress-related responses. Our current study aimed to verify the role of CRH in macrophage foam cell formation, the initial critical stage of atherosclerosis. Our quantitative real-time reverse transcriptase PCR (qRT-PCR), semi-quantitative reverse transcriptase PCR, and Western blot results indicate that CRH down-regulates ATP-binding cassette transporter-1 (ABCA1) and liver X receptor (LXR)-α, a transcription factor for ABCA1, in murine peritoneal macrophages and human monocyte-derived macrophages. Oil-red O (ORO) staining and intracellular cholesterol measurement of macrophages treated with or without oxidized LDL (oxLDL) and with or without CRH (10 nM) in the presence of apolipoprotein A1 (apoA1) revealed that CRH treatment promotes macrophage foam cell formation. The boron-dipyrromethene (BODIPY)-conjugated cholesterol efflux assay showed that CRH treatment reduces macrophage cholesterol efflux. Western blot analysis showed that CRH-induced down-regulation of ABCA1 is dependent on phosphorylation of Akt (Ser473) induced by interaction between CRH and CRH receptor 1(CRHR1). We conclude that activation of this pathway by CRH accelerates macrophage foam cell formation and may promote stress-related atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Although the proportion of the elderly patients with incident end-stage renal disease (ESRD) patients has been increasing in Korea, there has been a lack of information on outcomes of dialysis treatment. This study aimed to assess the survival rate and to elucidate predictors for all-cause mortality among elderly Korean patients initiating dialysis. Methods: We analyzed 11,301 patients (6,138 men) aged 65 years or older who had initiated dialysis from 2005 to 2008 and had followed up (median, 37.8 months; range, 3–84 months). Baseline demographics, comorbidities and mortality data were obtained using the database from the Health Insurance Review & Assessment Service. Results: The unadjusted 5-year survival rate was 37.6% for all elderly dialysis patients, and the rate decreased with increasing age categories; 45.9% (65∼69), 37.5% (70∼74), 28.4% (75∼79), 24.1% (80∼84), and 13.7% (≥85 years). The multivariate Cox proportional hazard model revealed that age, sex, dialysis modality, the type of insurance, and comorbidities such as diabetes mellitus, myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, hemiparesis, liver disease, and any malignancy were independent predictors for mortality. In addition, survival rate was significantly higher in patients on hemodialysis compared to patients on peritoneal dialysis during the whole follow-up period in the intention-to-treat analysis. Conclusions: Survival rate was significantly associated with age, sex, and various comorbidities in Korean elderly patients initiating dialysis. The results of our study can help to provide relevant guidance on the individualization strategy in elderly ESRD patients requiring dialysis. [ABSTRACT FROM AUTHOR]

Genomic changes frequently occur in cancer cells during tumorigenesis from normal cells. Using the Illumina Human NS-12 single-nucleotide polymorphism (SNP) chip to screen for gene copy number changes in primary hepatocellular carcinomas (HCCs), we initially detected amplification of 35 genes from four genomic regions (1q21-41, 6p21.2-24.1, 7p13 and 8q13-23). By integrated screening of these genes for both DNA copy number and gene expression in HCC and colorectal cancer, we selected CENPF (centromere protein F/mitosin), GMNN (geminin, DNA replication inhibitor), CDK13 (cyclin-dependent kinase 13), and FAM82B (family with sequence similarity 82, member B) as common cancer genes. Each gene exhibited an amplification frequency of ~30% (range, 20-50%) in primary HCC (n = 57) and colorectal cancer (n = 12), as well as in a panel of human cancer cell lines (n = 70). Clonogenic and invasion assays of NIH3T3 cells transfected with each of the four amplified genes showed that CENPF, GMNN, and CDK13 were highly oncogenic whereas FAM82B was not. Interestingly, the oncogenic activity of these genes (excluding FAM82B) was highly correlated with gene-copy numbers in tumor samples (correlation coefficient, r>0.423), indicating that amplifications of CENPF, GMNN, and CDK13 genes are tightly linked and coincident in tumors. Furthermore, we confirmed that CDK13 gene copy number was significantly associated with clinical onset age in patients with HCC (P = 0.0037). Taken together, our results suggest that coincidently amplified CDK13, GMNN, and CENPF genes can play a role as common cancer-driver genes in human cancers.