Diagnostic performance of 320-slice multidetector computed tomography coronary angiography in patients after coronary artery bypass grafting

Cardiovascular Aspects of Radiolog

Disturbed Expression of Splicing Factors in Renal Cancer Affects Alternative Splicing of Apoptosis Regulators, Oncogenes, and Tumor Suppressors

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer. One of the processes disturbed in this cancer type is alternative splicing, although phenomena underlying these disturbances remain unknown. Alternative splicing consists of selective removal of introns and joining of residual exons of the primary transcript, to produce mRNA molecules of different sequence. Splicing aberrations may lead to tumoral transformation due to synthesis of impaired splice variants with oncogenic potential. In this paper we hypothesized that disturbed alternative splicing in ccRCC may result from improper expression of splicing factors, mediators of splicing reactions. METHODOLOGY/PRINCIPAL FINDINGS: Using real-time PCR and Western-blot analysis we analyzed expression of seven splicing factors belonging to SR proteins family (SF2/ASF, SC35, SRp20, SRp75, SRp40, SRp55 and 9G8), and one non-SR factor, hnRNP A1 (heterogeneous nuclear ribonucleoprotein A1) in 38 pairs of tumor-control ccRCC samples. Moreover, we analyzed splicing patterns of five genes involved in carcinogenesis and partially regulated by analyzed splicing factors: RON, CEACAM1, Rac1, Caspase-9, and GLI1. CONCLUSIONS/SIGNIFICANCE: We found that the mRNA expression of splicing factors was disturbed in tumors when compared to paired controls, similarly as levels of SF2/ASF and hnRNP A1 proteins. The correlation coefficients between expression levels of specific splicing factors were increased in tumor samples. Moreover, alternative splicing of five analyzed genes was also disturbed in ccRCC samples and splicing pattern of two of them, Caspase-9 and CEACAM1 correlated with expression of SF2/ASF in tumors. We conclude that disturbed expression of splicing factors in ccRCC may possibly lead to impaired alternative splicing of genes regulating tumor growth and this way contribute to the process of carcinogenesis

10Kin1day: A Bottom-Up Neuroimaging Initiative.

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Structural modelling of amorphous vanadium pentoxide

Amorphous vanadium pentoxide (a -V2O5) is a component of many technically important semiconducting glasses. The transport properties are related directly to the material structure, and so in order to understand the transport mechanism the atom arrangement should be known. Much experimental work has been done to determine the short-range order in a -V2O5, but in view of contradicting conclusions the structure of the glass is still an open question. Thus, computer simulation techniques have been applied to get some insight into the structure of a -V2O5. In particular, the classical molecular dynamics (MD) simulations have been performed, using the original parametrisation of the interatomic interactions. Our effective interaction potential is derived from ab initio calculations of small hydrogen-saturated clusters VO„H„. The results of the MD simulations are discussed and compared to the available experimental data

Diagnostic yield is dependent on monitoring duration. Insights from a full-disclosure mobile cardiac telemetry system

Background: Despite the advancement of electrocardiogram (ECG) monitoring methods, the most important factor influencing diagnostic yield (DY) may still be monitoring duration. Ambulatory ECG monitoring, typically with 24–48 hours duration, is widely used but may result in underdiagnosis of rare arrhythmias. Aims: This study aimed to examine the relationship between the DY and monitoring duration in a large patient cohort and investigate sex and age differences in the presentation of arrhythmias. Methods: The study population consisted of 25 151 patients (57.8% women; median [interquartile range, IQR], 71 [64–78] years), who were examined with mobile cardiac telemetry during 2017 in the United States, using the PocketECGTM that continuously transmits a signal on a beat-to-beat basis. We investigated the occurrence of atrial fibrillation at a burden of both ≤1% (atrial fibrillation [AF], ≤1%) and ≤10% (AF ≤10%), premature ventricular contractions (PVC; >10 000 per 24 hours), non-sustained ventricular tachycardias (nsVT), sustained ventricular tachycardias (VT ≥30 seconds), atrioventricular blocks (AVB), pauses of >3 seconds duration, and bradycardia (heart rate <40 beats per minute for ≥60 seconds). Results: The median (IQR) recording duration was 15.4, 8.2–28.2) days. The DY increased gradually with monitoring duration for all types of investigated arrhythmias. Compared to DY after up to 30 days of monitoring, a standard 24 hours monitoring resulted in DY for males/females of 20%/18% for AF ≤1%, 29%/28% for AF ≤10%, 45%/40% for PVCs, 17%/11% for nsVT, 17%/11% for VT ≥30 seconds, 49%/42 for AVB, 27%/20% for pauses, 36%/29% for bradycardia. Conclusion: A substantial number of patients suffering from arrhythmias may remain undiagnosed due to insufficient ECG monitoring time

Iron deficiency: an ominous sign in patients with systolic chronic heart failure

Beyond erythropoiesis, iron is involved in numerous biological processes crucial for maintenance of homeostasis. Patients with chronic heart failure (CHF) are prone to develop iron deficiency (ID), and iron supplementation improves their functional status and quality of life. We sought to examine the relationship between ID and survival in patients with systolic CHF. In a prospective observational study, we evaluated 546 patients with stable systolic CHF [age: 55 +/- 11 (mean +/- standard deviation) years, males: 88%, left ventricular ejection fraction: 26 +/- 7%, New York Heart Association (NYHA) class (I/II/III/IV): 57/221/226/42]. Iron deficiency was defined as: ferritin &lt; 100 mu g/L, or 100-300 mu g/L with transferrin saturation &lt; 20%. The prevalence of ID was 37 +/- 4% [+/- 95% confidence intervals (CI)] in the entire CHF population (32 +/- 4 vs. 57 +/- 10%-in subjects without vs. with anaemia defined as haemoglobin level &lt; 12 g/dL in women and &lt; 13 g/dL in men, P &lt; 0.001). In a multiple logistic model, ID was more prevalent in women, those in the advanced NYHA class, with higher plasma N-terminal pro-type B natriuretic peptide and higher serum high-sensitivity C-reactive protein (all P &lt; 0.05). At the end of follow-up (mean duration: 731 +/- 350 days), there were 153 (28%) deaths and 30 (6%) heart transplantations (HTX). In multivariable models, ID (but not anaemia) was related to an increased risk of death or HTX (adjusted hazard ratio 1.58, 95% CI 1.14-2.17, P &lt; 0.01). In patients with systolic CHF, ID is common and constitutes a strong, independent predictor of unfavourable outcome. Iron supplementation may be considered as a therapeutic approach in these patients to improve prognosis

Local Ordering Changes in Pt–Co Nanocatalyst Induced by Fuel Cell Working Conditions

We present a detailed investigation of the changes in the local structure and chemical disorder induced by controlled potential cycling in Pt3 +/-delta Co nanoparticles used as a catalyst in the proton exchange membrane fuel cell (PEMFC) technology. Various state-of-the art material science techniques were used to study the microscopic properties of those nanomaterials including ex-situ and in-situ X-ray absorption spectroscopy (XAS), X-ray diffraction (XRD), and transmission electron microscopy (TEM). XAS double-edge multiple-scattering structural refinements of the Pt-CAM_PartnerCost.pdfCo spectra were performed taking into account the reduction of coordination numbers and degeneracy of three-atom configurations resulting from the measured size distribution obtained by TEM and XRD. The effect of chemical disorder in the considered nanoalloy was also taken into consideration. The PEMFC performance appears to be related to specific changes of the microscopic structural properties of the nanocatalyst during the first operation hours, especially during a cell activation period. In operating PEMFCs a small amount of Co oxide, initially present in the nanoalloy (on the surface of particles), disappeared gradually. At the same time, interatomic Pt-Pt and Pt-Co distances were slightly longer for higher current densities, while distance variances (sigma(2)) tended to decrease. Co-Co distribution remained unchanged. By combining XRD and XAS data, we also found that after controlled potential cycling in PEMFC the stoichiometry of the considered alloy changed from the initial Pt3 +/-delta Co to Pt4 +/-delta Co. Comparison of XAS and XRD-extracted values of the Co atomic fraction indicated that mainly cobalt not fully alloyed with platinum dissolved, and this process occurred in the first degradation period. At the same time, no substantial aggregation processes and no change in the mean size of nanoparticles were observed for this alloy. Accelerated degradation test, lasting up to 150 h, showed structural and electrochemical catalyst stability. The observed increase of chemical and local structural order of the particle core alloy did not affect the ORR kinetics