Ventricular divergence correlates with epicardial wavebreaks and predicts ventricular arrhythmia in isolated rabbit hearts during therapeutic hypothermia

INTRODUCTION: High beat-to-beat morphological variation (divergence) on the ventricular electrogram during programmed ventricular stimulation (PVS) is associated with increased risk of ventricular fibrillation (VF), with unclear mechanisms. We hypothesized that ventricular divergence is associated with epicardial wavebreaks during PVS, and that it predicts VF occurrence. METHOD AND RESULTS: Langendorff-perfused rabbit hearts (n = 10) underwent 30-min therapeutic hypothermia (TH, 30°C), followed by a 20-min treatment with rotigaptide (300 nM), a gap junction modifier. VF inducibility was tested using burst ventricular pacing at the shortest pacing cycle length achieving 1:1 ventricular capture. Pseudo-ECG (p-ECG) and epicardial activation maps were simultaneously recorded for divergence and wavebreaks analysis, respectively. A total of 112 optical and p-ECG recordings (62 at TH, 50 at TH treated with rotigaptide) were analyzed. Adding rotigaptide reduced ventricular divergence, from 0.13±0.10 at TH to 0.09±0.07 (p = 0.018). Similarly, rotigaptide reduced the number of epicardial wavebreaks, from 0.59±0.73 at TH to 0.30±0.49 (p = 0.036). VF inducibility decreased, from 48±31% at TH to 22±32% after rotigaptide infusion (p = 0.032). Linear regression models showed that ventricular divergence correlated with epicardial wavebreaks during TH (p<0.001). CONCLUSION: Ventricular divergence correlated with, and might be predictive of epicardial wavebreaks during PVS at TH. Rotigaptide decreased both the ventricular divergence and epicardial wavebreaks, and reduced the probability of pacing-induced VF during TH

The relationship between gallbladder status and recurrent biliary complications in patients with choledocholithiasis following endoscopic treatment

AbstractBackgroundEndoscopic methods are currently the treatment of choice for patients with common bile duct (CBD) stones, but subsequent management of the intact gallbladder for patients following endoscopic treatment is still controversial. The primary aim of this study was to discover the association between gallbladder status and recurrent biliary complications for patients with CBD stones after endoscopic treatment. Additionally, we also sought to determine risk factors for recurrent biliary complications in these patients.MethodsThe records of 1625 patients with CBD stones following endoscopic treatment were reviewed. A total of 681 patients were enrolled and subsequently categorized into four groups: Group 1 (n = 201), calculous gallbladder; Group 2 (n = 140), acalculous gallbladder; Group 3 (n = 175), elective cholecystectomy after endoscopic treatment; and Group 4 (n = 165), prior cholecystectomy. The basic demographics and recurrent biliary complications during follow-up among these four groups were analyzed by Chi-square test, ANOVA, Kaplan-Meier analysis, and log-rank test.ResultsDuring the median follow-up period of 34 months, 133 patients (20%) with recurrent biliary complications were identified. The recurrence rates of Groups 1, 2, 3, and 4 were 29%, 11%, 15%, and 19%, respectively. Kaplan-Meier analysis showed that patients with calculous gallbladder had a significantly higher rate of recurrent biliary complication. In multivariate analysis, patients with a history of cirrhosis, juxta-papillary diverticulum, calculous gallbladder, CBD size ≥1.5 cm, and endoscopic management with endoscopic sphincterotomy were at a higher risk for developing biliary complications (p = 0.029, p = 0.039, p < 0.001, p = 0.002, p = 0.021, respectively.)ConclusionPatients with cholecystolithiasis and CBD stones had a higher incidence of recurrent biliary complications. For some of these patients, elective cholecystectomy following endoscopic treatment may be considered. However, routine elective cholecystectomy in patients with normal gallbladder is not appropriate because of the low recurrence of biliary complications. Whether gallbladder function affects the biliary clearance and biliary complications requires further research

The Efficacy of Endoscopic Papillary Balloon Dilation for Patients with Acute Biliary Pancreatitis

Background. No study investigated the efficacy and safety of endoscopic papillary balloon dilation (EPBD) for the treatment of acute biliary pancreatitis (ABP). Method. We retrospectively reviewed the effects of EPBD on patients with ABP from February 2003 to December 2012. The general data, findings of image studies, details of the procedure, and outcomes after EPBD were analyzed. Result. Total 183 patients (male/female: 110/73) were enrolled. The mean age was 65.9 years. Among them, 155 patients had mild pancreatitis. The meantime from admission to EPBD was 3.3 days. Cholangiogram revealed filling defects inside the common bile duct (CBD) in 149 patients. The mean dilating balloon size was 10.5 mm and mean duration of the dilating procedure was 4.3 minutes. Overall, 124 patients had gross stones retrieved from CBD. Four (2.2%) adverse events and 2 (1.1%) intraprocedure bleeding incidents but no procedure-related mortality were noted. Bilirubin and amylase levels significantly decreased after EPBD. On average, patients resumed oral intake within 1.4 days. The clinical parameters and outcomes were similar in patients with different severity of pancreatitis. Conclusion. EPBD can be effective and safe for the treatment of ABP, even in patients presenting with severe disease

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Nanopyramid surface plasmon resonance sensors

We report the achievement of sensitive chemical and biological sensing using periodic gold nanopyramids with nanoscale sharp tips created by a simple and scalable colloidal templating approach. The sharp tips and the long-range periodic structure of the nanopyramid arrays enable the excitement of both localized and propagating surface plasmons. The optical reflection and the detection sensitivity of the templated nanopyramid surface plasmon resonance sensors agree reasonably well with the theoretical predictions using a finite-difference time-domain model. We have also demonstrated that specific antigen-antibody binding can be detected by using nanopyramid arrays in a real-time and label-free manner

Bile aspiration enhances the diagnostic accuracy of Clonorchis sinensis : A case report

Clonorchis sinensis is endemic to Southeast Asia, Japan, China, and Taiwan. Those infected often have a history of consumption of raw fresh fish. Its manifestations can be asymptomatic of cholangitis, biliary stones, or cholangiocarcinoma. A 69-year-old male living in Chishan, Taiwan visited our hospital with obstructive jaundice. Noninvasive analyses, such as stool examination, abdominal ultrasound, and an abdominal computed tomography scan did not reveal clues of clonorchiasis. As the obstructive jaundice was unexplained, endoscopic retrograde cholangiopancreatography (ERCP) was then performed and a hepatic fluke was seen via aspiration of bile. Subsequently, the ova of C. sinensis were detected via microscopic examination of bile samples. Bile aspiration is not routine during an ERCP procedure, however, we suggest the bile aspiration can be diagnostically accurate for clonorchiasis, especially for patients with a suspicious infection