Association of the miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms with ischemic stroke and silent brain infarction risk.

OBJECTIVE: MicroRNAs play a role in atherosclerosis-related diseases, such as cerebrovascular or cardiovascular disease. However, the effect of miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms on stroke and silent brain infarction (SBI) susceptibility has not been reported. METHODS AND RESULTS: Using polymerase chain reaction-amplified DNA, microRNA polymorphisms were analyzed in 678 patients with ischemic stroke, 373 patients with SBI, and 553 control subjects. The miR-146aC>G polymorphism and miR-146aG/-149T/-196a2C/-499G allele combination was significantly associated with ischemic stroke prevalence. For SBI prevalence, there were no statistically significant genetic markers. However, some allele combinations were associated with increased SBI incidence (C-T-C-G and G-T-T-A of miR-146a/-149/-196a2/-499). In subgroup analyses, miR-146aC>G increased stroke risk in female, normotensive, and nondiabetic groups. There were significant combined effects between microRNA polymorphisms and homocysteine/folate levels on ischemic stroke and SBI prevalence. CONCLUSIONS: The miR-146aG allele and miR-146aG/-149T/-196a2C/-499G allele combination were associated with ischemic stroke pathogenesis. The combined effects between microRNA polymorphisms and homocysteine/folate levels may contribute to stroke and SBI prevalence.

Induction of a shorter compression phase is correlated with a deeper chest compression during metronome-guided cardiopulmonary resuscitation: a manikin study.

OBJECTIVES: Recent studies have shown that there may be an interaction between duty cycle and other factors related to the quality of chest compression. Duty cycle represents the fraction of compression phase. We aimed to investigate the effect of shorter compression phase on average chest compression depth during metronome-guided cardiopulmonary resuscitation. METHODS: Senior medical students performed 12 sets of chest compressions following the guiding sounds, with three down-stroke patterns (normal, fast and very fast) and four rates (80, 100, 120 and 140 compressions/min) in random sequence. Repeated-measures analysis of variance was used to compare the average chest compression depth and duty cycle among the trials. RESULTS: The average chest compression depth increased and the duty cycle decreased in a linear fashion as the down-stroke pattern shifted from normal to very fast (p<0.001 for both). Linear increase of average chest compression depth following the increase of the rate of chest compression was observed only with normal down-stroke pattern (p=0.004). CONCLUSIONS: Induction of a shorter compression phase is correlated with a deeper chest compression during metronome-guided cardiopulmonary resuscitation.

50% duty cycle may be inappropriate to achieve a sufficient chest compression depth when cardiopulmonary resuscitation is performed by female or light rescuers.

OBJECTIVE: Current guidelines for cardiopulmonary resuscitation recommend chest compressions (CC) during 50% of the duty cycle (DC) in part because of the ease with which individuals may learn to achieve it with practice. However, no consideration has been given to a possible interaction between DC and depth of CC, which has been the subject of recent study. Our aim was to determine if 50% DC is inappropriate to achieve sufficient chest compression depth for female and light rescuers. METHODS: Previously collected CC data, performed by senior medical students guided by metronome sounds with various down-stroke patterns and rates, were included in the analysis. Multiple linear regression analysis was performed to determine the association between average compression depth (ACD) with average compression rate (ACR), DC, and physical characteristics of the performers. Expected ACD was calculated for various settings. RESULTS: DC, ACR, body weight, male sex, and self-assessed physical strength were significantly associated with ACD in multivariate analysis. Based on our calculations, with 50% of DC, only men with ACR of 140/min or faster or body weight over 74 kg with ACR of 120/min can achieve sufficient ACD. CONCLUSION: A shorter DC is independently correlated with deeper CC during simulated cardiopulmonary resuscitation. The optimal DC recommended in current guidelines may be inappropriate for achieving sufficient CD, especially for female or lighter-weight rescuers.

Stent-graft placement in a traumatic internal carotid-internal jugular fistula and pseudoaneurysm.

Traumatic arteriovenous fistulas following carotid artery injuries are rare. Treatment of carotid artery-to-jugular vein fistula requires direct closure of the fistula or occlusion of the carotid artery above and below the level of the fistula, by a surgical or endovascular approach. A 32-year-old man presented with a right-sided pulsatile neck swelling 2 days following a stab wound. Neck computed tomography demonstrated a vascular mass protruding into the anterior neck. Digital subtraction arteriography demonstrated a bilobular large internal carotid artery pseudoaneurysm just distal to its bifurcation. There was simultaneous opacification of a dilated left internal jugular vein indicating a high-flow internal carotid-internal jugular fistula. A balloon-expandable stent-graft was delivered and successfully positioned across the fistula. The arteriovenous fistula and pseudoaneurysm completely disappeared and the right internal carotid artery was well preserved. The stent-graft is a promising technology to obliterate fistulae and preserve the parent artery with relative safety.

Overexpression of goosecoid homeobox is associated with chemoresistance and poor prognosis in ovarian carcinoma.

Ovarian carcinoma is the most lethal cancer among all gynecological malignancies due to recurrence through chemoresistance. The aim of the present study was to identify new biomarkers to predict chemoresistance and prognosis in ovarian carcinomas. The mRNA expression by qRT-PCR was examined in 60 ovarian serous carcinomas for selected genes from the screening by PCR array focusing on apoptosis, epithelial-to-mesenchymal transition and cancer pathways. The clinical impact was assessed by analyzing the correlation between gene expression and clinicopathological variables. Further validation with immunohistochemistry was performed with 75 cases of serous carcinomas. The chemoresistance was significantly associated with high expression of FOS, GSC, SNAI1, TERT and TNFRSF10D, and low expression of CDKN1A, TNFRSF10A, TNFRSF10C and TRAF1 (p<0.05, t-test). Low expression of TRAF1 and high expression of E2F1, FOS, TERT and GSC were significantly associated with advanced clinical stage (p<0.05, χ2-test). Lymph node metastasis was significantly associated with high expression of GSC. The upregulation group of TERT, GSC, NOTCH1 and SNAI1, and downregulation group of TRAF1 were significantly associated with poor overall survival (p<0.05, log-rank test). On further validation with immunohistochemistry, overexpression of goosecoid homeobox (GSC) was associated with poor overall survival. The results suggest that GSC is the most potential biomarker of drug response and poor prognosis in ovarian serous carcinomas.

MicroRNAs overexpressed in ovarian ALDH1-positive cells are associated with chemoresistance.

BACKGROUND: Ovarian carcinoma is the leading cause of cancer death worldwide among gynecological malignancies, and the majority of cases are related with recurrence and chemoresistance. Cancer stem cells (CSCs) are believed to be one of the causes of recurrent or chemoresistant ovarian cancer, and microRNAs are regulatory molecules newly implicated to control a variety of cellular processes, including CSCs. Therefore, we identified ovarian CSC-specific microRNAs and investigated their clinicopathological implication in ovarian carcinomas. METHODS: We isolated ALDH1 (+) cell population using the Aldefluor assay, and examined the differential expression pattern of miRNAs between ALDH1 (+) and ALDH1 (-) cells using a high-throughput microRNA microarray. We further investigated the expression patterns of differentially expressed miRNAs in human ovarian cancer samples using the real-time reverse transcription-polymerase chain reaction and analyzed their clinical impact in patients with ovarian cancer. RESULTS: We found that high ALDH1 expression was associated with chemoresistance in in vitro and ex vivo samples (p = 0.024). We identified six miRNAs, including miR-23b, miR-27a, miR-27b, miR-346, miR-424, and miR-503, overexpressed in ALDH1 (+) cells, and they were significantly upregulated in chemoresistant ovarian cancer cells (1.4 ~ 3.5-fold) and tumor samples (2.8 ~ 5.5-fold) compared with chemosensitive group. Upregulation of ALDH1 (p = 0.019) and miR-503 (p = 0.033) correlated with high clinical stage, and upregulation of miR-27a was related with distant metastasis (p = 0.046) in patients with ovarian cancer. CONCLUSION: Our findings indicate that ALDH1 is a useful marker for enriching ovarian CSCs, and high expression of ALDH1 and its related miRNAs, particularly miR-23b, miR-27b, miR-424, and miR-503, are significantly implicated in chemoresistance and tumor progression in ovarian cancer.

Quantitative analysis of periodontal pathogens present in the saliva of geriatric subjects.

PURPOSE: At present, information regarding periodontal disease in geriatric patients is scarce. The purpose of this study was to quantify the periodontal pathogens present in the saliva of Korean geriatric patients and assess the relationship between the bacterial levels and the periodontal condition. METHODS: Six putative periodontal pathogens were quantified by using a real-time polymerase chain reaction assay in geriatric patient groups (>60 years) with mild chronic periodontitis (MCP), moderate chronic periodontitis (MoCP), and severe chronic periodontitis (SCP). The copy numbers of Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, and Prevotella intermedia were measured. RESULTS: It was found that the bacterial copy numbers increased as the severity of the disease increased from MCP to SCP, except for P. intermedia. For P. intermedia, it was found that samples in the MCP group yielded the largest amount. It was also found that the quantities of P. gingivalis, T. forsythia, and T. denticola, the so-called "red complex" bacteria, were lower than those of F. nucleatum, A. actinomycetemcomitans, and P. intermedia in all of the samples. CONCLUSIONS: Collectively, the results of this study suggest that the levels of P. gingivalis, T. forsythia, F. nucleatum, and T. denticola present in saliva are associated with the severity of periodontal disease in geriatric patients.

P2Y receptors regulate proliferation of human pancreatic duct epithelial cells.

OBJECTIVES: The aim of this study was to investigate the effect of P2Y receptor activation on proliferation of human pancreatic duct epithelial cells. METHODS: Proliferation was measured by immunoassay for bromodeoxyuridine incorporation into a pancreatic duct epithelial cell line, PANC-1. Expression of P2Y receptors was examined using quantitative reverse transcription-polymerase chain reaction and Western blot. RESULTS: Extracellular nucleotides, adenosine diphosphate (ADP) and uridine diphosphate (UDP), stimulated proliferation of pancreatic duct cells in a concentration-dependent manner. The nucleotide efficacy order was ADP > UDP > uridine triphosphate (UTP) > adenosine triphosphate. P2Y(1) and P2Y(6) receptor blockers, MRS2500 and MRS2578, blocked the effect of ADP and UDP. The signal that transmitted the proliferative activity of ADP and UDP was transducted to phospholipase C, inositol 1,4,5-triphosphate receptor, and protein kinase C. These results indicate involvement of P2Y(1) and P2Y(6) receptors in ADP- and UDP-stimulated proliferation. Pancreatic duct cells expressed the messenger RNA transcripts of P2Y receptors, P2Y(1) , P2Y(2), and P2Y(6), and P2Y(1) and P2Y(6) receptor protein. CONCLUSIONS: Extracellular nucleotides increase proliferation of human pancreatic duct epithelial cells by activation of P2Y(1) and P2Y(6) receptors. This provides the basic model for the effect of P2Y receptors on the proliferation of pancreatic duct epithelial cells.

Adenomatoid odontogenic tumor associated with unerupted first primary molar.

Adenomatoid odontogenic tumors (AOTs) are an uncommon benign odontogenic tumor. Both central and peripheral forms occur. Radiographically, the central variants are comprised of a follicular type (those associated with the crown of an embedded tooth) and an extrafollicular type (those with no embedded tooth). A review of the literature showed that only 3 cases of an association between AOT and unerupted primary teeth have been published. The purpose of this paper was to report a rare case of adenomatoid odontogenic tumor associated with an unerupted primary first molar in a 7-year-old boy.

Polymorphisms of thymidylate synthase gene 5'- and 3'-untranslated region and risk of gastric cancer in Koreans.

BACKGROUND: Thymidylate synthase (TS) plays an important role in the conversion of dUMP to dTMP. Polymorphisms of the TS gene affect the expression of the gene, which in turn may result in differences in the outcome of cancer chemotherapy and the progression of gastric cancer. PATIENTS AND METHODS: These types of TS polymorphism were investigated in 318 gastric cancer patients and 280 controls. A variable number of tandem repeats (VNTR; 2R or 3R) in the thymidylate synthase enhancer region (TSER), a G/C single nucleotide polymorphism within the second repeat sequence of 3R (3G or 3C), and a 6 bp insertion/deletion polymorphism (6 bp or 0 bp) in the TS 3'-untranslated region (3'-UTR) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Patients were sub-grouped by the Lauren classification. RESULTS: The TSER 2R/2R genotype had a high odds ratio in gastric cancer and for the intestinal type, but was not statistically significant (adjusted odds ratio, AOR=2.31, 95% confidence interval, CI=0.94-5.65; and AOR=2.53, 95% CI=0.98-6.54, respectively). Among the combined genotypes of TSER VNTR-3'-UTR 6 bp ins/del, 2R2R-6 bp/6 bp having 4 risk alleles conferred a significantly high risk of gastric cancer, particularly of the intestinal type (AOR=8.70, 95% CI=1.09-68.93; and AOR=10.86, 95% CI=1.32-89.09, respectively). CONCLUSION: Our results indicate that the 2R/2R-6 bp/6 bp combined genotype may be related to high gastric cancer susceptibility.