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Our method's robustness to noise is expected to not only improve the accuracy of the estimates, but also enable a meaningful interpretation of contrast in the derived scalar maps. The technique's performance on shorter acquisitions could make it feasible in routine clinical practice.Quality assurance (QA) is crucial in longitudinal and/or multi-site studies, which involve the collection of data from a group of subjects over time and/or at different locations. It is important to regularly monitor the performance of the scanners over time and at different locations to detect and control for intrinsic differences (e.g., due to manufacturers) and changes in scanner performance (e.g., due to gradual component aging, software and/or hardware upgrades, etc.). selleck chemical As part of the Ontario Neurodegenerative Disease Research Initiative (ONDRI) and the Canadian Biomarker Integration Network in Depression (CAN-BIND), QA phantom scans were conducted approximately monthly for three to four years at 13 sites across Canada with 3T research MRI scanners. QA parameters were calculated for each scan using the functional Biomarker Imaging Research Network's (fBIRN) QA phantom and pipeline to capture between- and within-scanner variability. We also describe a QA protocol to measure the full-width-at-half-maximum (FWHM) of slice-wise point spread functions (PSF), used in conjunction with the fBIRN QA parameters. Variations in image resolution measured by the FWHM are a primary source of variance over time for many sites, as well as between sites and between manufacturers. We also identify an unexpected range of instabilities affecting individual slices in a number of scanners, which may amount to a substantial contribution of unexplained signal variance to their data. Finally, we identify a preliminary preprocessing approach to reduce this variance and/or alleviate the slice anomalies, and in a small human data set show that this change in preprocessing can have a significant impact on seed-based connectivity measurements for some individual subjects. We expect that other fMRI centres will find this approach to identifying and controlling scanner instabilities useful in similar studies.

Mortality in cohorts with a single ventricle remains high with multiple associated factors. The effect of heart block during stage I palliation remains unclear.

The purpose of this study was to study patient and surgical risks of heart block and its effect on 12-month transplant-free survival in patients with a single ventricle.

Patient, surgical, outcome data and heart block status (transient and permanent) were obtained from the National Pediatric Cardiology Quality Improvement Collaborative single ventricle database. Bivariate analysis was performed comparing patients with and without heart block, and multivariate modeling was used to identify variables associated with block. One-year outcomes were analyzed to identify variables associated with lower 12-month transplant-free survival.

In total, 1423 patients were identified, of whom 28 (2%) developed heart block (second degree or complete) during their surgical admission. Associated risk factors for block included heterotaxy syndrome (odds ratio [Oblock after stage I palliation. The role of transient block in outcomes and potential rescue with long-term pacing remains unknown and requires additional study.

Pacemapping (PM) is a useful maneuver for aiding premature ventricular complex (PVC) ablation. Its standalone clinical value is still to be defined.

The purpose of this study was to analyze the efficacy of a predefined PM protocol for low-burden PVC ablation, regardless of their site of origin (SOO) and the presence of structural heart disease.

This was a prospective, nonrandomized, multicenter study. The PM protocol was performed when <1 PVC/min was found. The "target area" was delimited by the 3 best matching points >94% correlation, and 3 radiofreqency (RF) applications were delivered.

Of 185 patients, 105 (57%) underwent activation mapping, 60 (32%) were PM-guided, and 20 (11%) were canceled due to absence of PVCs. Baseline QRS, PVC burden, and outflow tract origin were independent predictors of PM-guided ablation. A higher proportion of right ventricular outflow tract SOO in the PM group (52% vs 40%; P = .03) was observed. Mean target area was 0.6± 0.9 cm

. Mean 10-ms isochronal area in local activation time (LAT)-guided procedures was higher (1.7 ± 2.3 cm

 ; P<.001). link2 Mean number of PM matching points acquired was 39± 21 (range 6-98). Mean mapping and RF times were similar in both groups. However, significantly shorter procedural (53 ± 24 vs 61 ± 26 minutes; P = .04) as well as RF times (111 ± 51 vs 149 ± 149 seconds; P = .05) were needed in the PM group using the proposed protocol. link3 Global clinical success reached 87% for the PM group and 90% (P = .58) the for LAT mapping group.

When LAT mapping is precluded, application of a PM-guided ablation protocol directed to >94% matching correlation target area is a more efficient alternative with comparable clinical results.

94% matching correlation target area is a more efficient alternative with comparable clinical results.The PBD (Permuted Block Design) is the most widely used randomization method in clinical trials due to its comparatively simplicity. However, greater selection bias may appear, especially in open-labeled trials, because the PBD requires absolute balance at the end of each block . The BSD(Big Stick Design) method is one of the MTI(Maximum Tolerated Imbalance) procedures, which can make the allocation process more unpredictable while maintaining the advantages the PBD. So it is theoretically superior to the PBD method. However, some practical problems in stratified randomization hinder the application of the BSD method such as the risk of serious imbalance for entire trials with the increasing of strata, the uncertainty of the reproducibility of randomization schedule, and the danger of greater selection bias in extreme cases. We propose solutions to the above three implementation problems, and explores the feasibility and effects of the solutions through simulations.In recent years, the occurrence of organic UV-filters (UVFs) and bisphenol derivatives (BPs) in the marine environment has raised high concerns all over the world, due to the potentially adverse impacts on marine organism and, indirectly on human health. This paper reports, for the first time in Romania, the occurrence, distribution pattern and environmental risk assessment of UVFs, BPs and their metabolites in seawater, sediment and algae collected from the Romania Black Sea coastal region. BP-3 (2-hydroxy-4-methoxy-benzophenone) was the most abundant contaminant in seawater samples, with detection frequency of 100 %. Sediment samples were dominated by ES (Ethylhexyl salicylate), with concentration values up to 5823 ng/g d.w., while for algae, concentrations of several hundreds of ng/g d.w. were determined for BP-3, BS (Benzyl salicylate) and BPE (Bisphenol E). Environmental risk assessment revealed that some UVFs and BPs detected in seawater samples were hazardous to the marine organism of the Black Sea.Copper (Cu) is an essential element for organism's metabolism, being controversially listed as a priority pollutant. Importantly, the toxicity of Cu has been linked to several cell death pathways. Thus, this study aimed to assess if macroautophagic pathways are triggered by Cu in zebrafish gill, the main target of waterborne pollutants. The electron microscopy findings indicated that Cu induced profound impacts on zebrafish gill structure and functions, being this tissue a biomarker sensitive enough to indicate early toxic effects. The findings also support a clear impairment of autophagy, througth the absence of phagossomes and the significant down-regulation mRNA transcript levels of microtubule-associated protein light chain 3 (LC3). The reduction of LC3 levels was often associated to an increase of apoptotic activation, indicating that the inhibition of macroautophagy triggers apoptosis in zebrafish gills. This study highlighted that the autophagic down-regulation might be affected through the activation of other cell death signaling pathway.Host immune response and viral factors are involved in disease progression in patients with chronic hepatitis B virus (HBV) infection. However, the relationship between HBV quasispecies and liver fibrosis progression remains unclear. In this study, 447 patients with chronic HBV infection, including 239 with chronic hepatitis B (CHB), 104 with liver cirrhosis (LC) and 104 with hepatocellular carcinoma (HCC) were enrolled. The 239 CHB patients were divided into groups F1, F2, and F3 according to liver fibrosis score. Four fragments of the HBV genome were determined and analyzed using next-generation sequencing. Specific mutations, such as A1762T, G1764A and G1896A, in the BCP/PC region were more common in patients with advanced liver disease and formed the majority of the viral quasispecies pool in patients with LC and HCC. The viral complexity and diversity increased as the fibrosis progressed, especially in patients with CHB who were comparable in age but at different stages of fibrosis. Patients with early-stage fibrosis experienced higher purifying selection pressure in the four sequenced regions, whereas different protein-coding region experienced different negative selection with disease progression. HBV quasispecies diversity may increase fibrosis progression in CHB patients with aging under immune selection.The rise in human adenovirus (HAdV) infections poses a serious challenge to public health in China. Real-time (RT) sequencing provides solutions for achieving rapid pathogen identification during outbreaks, whereas high-throughput sequencing yields higher sequence accuracy. In the present study, we report the outcomes of applying nanopore and BGI platforms in the identification and genomic analysis of an HAdV outbreak in Hubei province, China in May of 2019. A mixed sample of nine nasopharyngeal swabs and one single sample were submitted to direct nanopore sequencing (MinION device), generating their first HAdV-55 reads within 13 and 20 min, respectively. The sequences were confirmed by RT-polymerase chain reaction (PCR). Ten HAdV-positive samples were further sequenced using next-generation high-throughput sequencing (BGISEQ-500 device). Phylogenetic analysis revealed that the outbreak strain had a close genetic relation to strains isolated in Sichuan province. Metagenomic analysis showed that HAdV-55 was not a dominant species in samples from which the whole HAdV-55 genome could not be assembled. The present results highlight the value of combining sequencing platforms and using mixed samples for nucleic acid enrichment in pathogen detection of infectious disease outbreaks.

A frequent emergence of drug resistance has been observed and posed great threat to global public health recently. This work aimed to investigate the potential synergistic effect and the underlying mechanisms of AgNPs-fluconazole combination more extensively through 2 clinically isolated fluconazole-resistant Candida albicans (C. albicans) strains.

Antifungal properties of AgNPs and fluconazole alone or together against planktonic cells and biofilms were tested. Cellular and molecular targets associated with fluconazole resistance were monitored after AgNPs treatment. Antifungal potential of AgNPs-fluconazole combination was also explored in vivo using a mouse model of disseminated candidiasis. Tissue burden and survival rate were analyzed.

The results indicated that AgNPs worked synergistically with fluconazole against both planktonic cells of fluconazole-resistant C. albicans and biofilms formed <12h. AgNPs treatment down-regulated ERG1, ERG11, ERG25, and CDR2, decreased membrane ergosterol levels and membrane fluidity, reduced membrane content of Cdr1p, Cdr2p, and thus efflux bump activity.