Summary
Background
Hepatitis C virus (HCV) infection in patients undergoing haemodialysis is prevalent and aggressive. The treatment of chronic hepatitis C has been revolutionised by the advent of ...direct‐acting antivirals (DAAs). However, the safety, efficacy, and tolerance of DAAs in the treatment of acute HCV infection in patients with end‐stage renal disease who are on haemodialysis are unknown.
Aim
To evaluate the safety and efficacy of sofosbuvir plus daclatasvir in this specific, difficult‐to‐treat population.
Methods
We conducted a prospective and observational study of end‐stage renal disease patients who were undergoing haemodialysis and were acutely infected with HCV. Patients received a half dose of sofosbuvir (200 mg) and a full dose of daclatasvir (60 mg) daily. The primary endpoint was the proportion of patients with sustained virological responses (SVRs); the other primary outcomes were safety and tolerability.
Results
Thirty‐three patients were enrolled in the study. The median HCV RNA viral load at baseline was 6.8 log10IU/mL. Twenty‐four patients were infected with HCV genotype 2a, seven patients with 1b, and two patients with 2a+1b. All patients achieved a SVR at 12 weeks after the end of treatment. The treatment was well tolerated, and there were no drug‐related serious adverse events.
Conclusion
A half dose of sofosbuvir (200 mg once daily) plus a full dose of daclatasvir (60 mg once daily) were suitable for the treatment of acute HCV‐infected patients who were undergoing end‐stage renal disease and were on haemodialysis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Hepatocellular carcinoma (HCC) is one of the leading malignancies worldwide. Myocyte enhancer factor 2C (MEF2C) was traditionally regarded as a development-associated factor and was recently reported ...to be an oncogene candidate. We have previously reported overexpression of MEF2C in HCC; however, the roles of MEF2C in HCC remain to be clarified. In this study, HCC cell lines and a xenograft mouse model were used to determine the functions of MEF2C in vitro and in vivo, respectively. Specific plasmids and small interfering RNA were used to upregulate and downregulate MEF2C expression, respectively. Functional assays were performed to assess the influence of MEF2C on cell proliferation, and VEGF-induced vasculogenic mimicry, migration/invasion as well as angiogenesis. Co-immunoprecipitation was conducted to identify the interaction of MEF2C and β-catenin. Human HCC tissue microarrays were used to investigate correlations among MEF2C, β-catenin and involved biomarkers. MEF2C was found to mediate VEGF-induced vasculogenic mimicry, angiogenesis and migration/invasion, with involvement of the p38 MAPK and PKC signaling pathways. However, MEF2C itself inhibited tumor growth in vitro and in vivo. MEF2C was upregulated by and directly interacted with β-catenin. The nuclear translocation of β-catenin blocked by MEF2C was responsible for MEF2C-mediated growth inhibition. The nuclear translocation of MEF2C was associated with intracellular calcium signaling induced by β-catenin. HCC microarrays showed correlations of nuclear MEF2C with the angiogenesis-associated biomarker, CD31, and cytosolic MEF2C with the proliferation-associated biomarker, Ki-67. MEF2C showed double-edged activities in HCC, namely mediating VEGF-induced malignancy enhancement while inhibiting cancer proliferation via blockade of Wnt/β-catenin signaling. The overall effect of MEF2C in HCC progression regulation was dictated by its subcellular distribution. This should be determined prior to any MEF2C-associated intervention in HCC.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We present 24 is a subset of m and 70 is a subset of m Multiband Imaging Photometer for Spitzer (MIPS) observations of 70 A through M-type dwarfs with estimated ages from 8 Myr to 1.1 Gyr, as part of ...a Spitzer guaranteed time program, including a re-analysis of some previously published source photometry. Our sample is selected from stars with common youth indicators such as lithium abundance, X-ray activity, chromospheric activity, and rapid rotation. We compare our MIPS observations to empirically derived Ks -24 colors as a function of the stellar effective temperature to identify 24 is a subset of m and 70 is a subset of m excesses. We place constraints or upper limits on dust temperatures and fractional infrared luminosities with a simple blackbody dust model. We confirm the previously published 70 is a subset of m excesses for HD 92945, HD 112429, and AU Mic, and provide updated flux density measurements for these sources. We present the discovery of 70 is a subset of m excesses for five stars: HD 7590, HD 10008, HD 59967, HD 73350, and HD 135599. HD 135599 is also a known Spitzer IRS (InfraRed Spectrograph) excess source, and we confirm the excess at 24 is a subset of m. We also present the detection of 24 is a subset of m excesses for 10 stars: HD 10008, GJ 3400A, HD 73350, HD 112429, HD 123998, HD 175742, AT Mic, BO Mic, HD 358623 and Gl 907.1. We find that large 70 is a subset of m excesses are less common around stars with effective temperatures of less than 5000 K (3.7+7.6 -1.1%) than around stars with effective temperatures between 5000 K and 6000 K (21.4+9.5 -5.7%), despite the cooler stars having a younger median age in our sample (12 Myr vs. 340 Myr). We find that the previously reported excess for TWA 13A at 70 is a subset of m is due to a nearby background galaxy, and the previously reported excess for HD 177724 is due to saturation of the near-infrared photometry used to predict the mid-infrared stellar flux contribution. In the Appendix, we present an updated analysis of dust grain removal timescales due to grain-grain collisions and radiation pressure, Poynting-Robertson (P-R) drag, stellar wind drag, and planet-dust dynamical interaction. We find that drag forces can be important for disk dynamics relative to grain-grain collisions for L IR/L * < 10-4, and that stellar wind drag is more important than P-R drag for K and M dwarfs, and possibly for young (<1 Gyr) G dwarfs as well.
Organic superconductors have π-molecular orbitals, from which electrons can become delocalized, giving rise to metallic conductivity due to orbital overlap between adjacent molecules. Here we report ...the discovery of superconductivity at a transition temperature (T(c)) of ~5 K in alkali-metal-doped phenanthrene. A 1-GPa pressure leads to a 20% increase of T(c), suggesting that alkali-metal-doped phenanthrene shows unconventional superconductivity. Raman spectra indicate that alkali-metal doping injects charge into the system to realize the superconductivity. The discovery of superconductivity in A(3)phenanthrene (where A can be either K or Rb) produces a novel broad class of superconductors consisting of fused hydrocarbon benzene rings with π-electron networks. An increase of T(c) with increasing number of benzene rings from three to five suggests that organic hydrocarbons with long chains of benzene rings are potential superconductors with high T(c).
Fusarium crown rot (FCR) is a serious cereal disease in semi-arid regions worldwide. In assisting the effort of breeding cultivars with enhanced resistance, we identified several barley genotypes ...with high levels of FCR resistance. One of these genotypes, AWCS079 which is a barley landrace originating from Japan, was investigated by developing and assessing three populations of recombinant inbred lines. Two QTL, one located on the long arm of chromosome 1H (designated as Qcrs.cpi-1H) and the other on 3HL (designated as Qcrs.cpi-3H), were found to be responsible for the FCR resistance of this genotype. Qcrs.cpi-1H is novel as no other FCR loci have been reported on this chromosome arm. Qcrs.cpi-3H co-located with a reduced height (Rht) locus and the effectiveness of the former was significantly affected by the latter. The total phenotypic variance explained by these two QTL was over 60 %. Significant effects were detected for each of the QTL in each of the three populations assessed. The existence of these loci with major effects should not only facilitate breeding and exploitation of FCR-resistant barley cultivars but also their further characterization based on fine mapping and map-based gene cloning.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The structural and electronic properties of bilayer (AA- and AB-stacked) and tri-layer (AAA-, ABA- and AAB-stacked) penta-graphene (PG) have been investigated in the framework of density functional ...theory. The present results demonstrate that the ground state energy in AB stacking is lower than that in AA stacking, whereas ABA stacking is found to be the most energetically favorable, followed by AAB and AAA stackings. All considered model configurations are found to be semiconducting, independent of the stacking sequence. In the presence of a perpendicular electric field, their band gaps can be significantly reduced and completely closed at a specific critical electric field strength, demonstrating a Stark effect. These findings show that few-layer PG will have tremendous opportunities to be applied in nanoscale electronic and optoelectronic devices owing to its tunable band gap.
Our calculations show that the electronic properties of few-layer penta-graphene can obviously be modulated through an external electric field.
The purpose of this study was to investigate the role of microRNA-770-5p (miR-770-5p) in gestational diabetes mellitus (GDM).
In the present study, the expression levels of miR-770-5p in the ...peripheral blood from GDM women and healthy women were investigated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The relationship between TP53 regulated inhibitor of apoptosis 1 (TRIAP1) and miR-770-5p was determined using dual-luciferase reporter assay. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry were used to detect pancreatic β-cell proliferation and apoptosis. Enzyme-linked immunosorbent assay (ELISA) was used to measure total insulin content and insulin secretion.
Our data indicated that miR-770-5p was up-regulated in GDM patients. TRIAP1 was a direct target of miR-770-5p and it was down-regulated in GDM patients. Besides, miR-770-5p negatively regulated the expression of TRIAP1 in INS-1 cells. Then, we explored the effects of miR-770-5p down-regulation on the insulin secretion of pancreatic β-cells, and the results showed that miR-770-5p inhibitor promoted the generation of insulin secretion or total insulin content in INS-1 cells, while these effects were significantly inhibited by TRIAP1-siRNA. Moreover, we found that miR-770-5p inhibitor enhanced INS-1 cell proliferation and suppressed cell apoptosis, whereas these effects were eliminated by TRIAP1-siRNA. Accordingly, miR-770-5p inhibitor decreased the expression of Bax, apoptotic peptidase activating factor 1 (APAF1) and increased Bcl-2 level in INS1 cells. These results were all reversed by TRIAP1-siRNA.
The data demonstrated that miR-770-5p was a vital regulator in pancreatic β-cell proliferation, apoptosis and insulin secretion by targeting TRIAP1, and dysregulation of miR-770-5p resulted in the development of GDM via APAF1 signaling pathway.
A scarlet fever outbreak occurred in Hong Kong in 2011. The majority of cases resulted in the isolation of Streptococcus pyogenes emm12 with multiple antibiotic resistances. Phylogenetic analysis of ...22 emm12 scarlet fever outbreak isolates, 7 temporally and geographically matched emm12 non-scarlet fever isolates, and 18 emm12 strains isolated during 2005-2010 indicated the outbreak was multiclonal. Genome sequencing of 2 nonclonal scarlet fever isolates (HKU16 and HKU30), coupled with diagnostic polymerase chain reaction assays, identified 2 mobile genetic elements distributed across the major lineages: a 64.9-kb integrative and conjugative element encoding tetracycline and macrolide resistance and a 46.4-kb prophage encoding superantigens SSA and SpeC and the DNase Spd1. Phenotypic comparison of HKU16 and HKU30 with the S. pyogenes M1T1 strain 5448 revealed that HKU16 displays increased adherence to HEp-2 human epithelial cells, whereas HKU16, HKU30, and 5448 exhibit equivalent resistance to neutrophils and virulence in a humanized plasminogen murine model. However, in contrast to M1T1, the virulence of HKU16 and HKU30 was not associated with covRS mutation. The multiclonal nature of the emm12 scarlet fever isolates suggests that factors such as mobile genetic elements, environmental factors, and host immune status may have contributed to the 2011 scarlet fever outbreak.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
It is well established that preterm infants have altered brain development compared with full-term (FT; ≥37 weeks' gestational age GA) infants, however the perinatal factors associated with brain ...development in preterm infants have not been fully elucidated. In particular, perinatal predictors of brain development may differ between very preterm infants (VP; <32 weeks' GA) and infants born moderate (MP; 32–33 weeks' GA) and late (LP; 34–36 weeks' GA) preterm, but this has not been studied. This study aimed to investigate the effects of early life predictors on brain volume and microstructure at term-equivalent age (TEA; 38–44 weeks), and whether these effects differ for GA groups (VP, MP, LP or FT).
Structural images from 328 infants (91 VP, 63 MP, 104 LP and 70 FT) were segmented into white matter, cortical grey matter, cerebrospinal fluid, subcortical grey matter, brainstem and cerebellum. Cortical grey matter and white matter images were analysed using voxel-based morphometry. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) images from 361 infants (92 VP, 69 MP, 120 LP and 80 FT) were analysed using Tract-Based Spatial Statistics. Relationships between early life predictors (birthweight standard deviation score BWSDS, multiple birth, sex, postnatal growth and social risk) and global brain volumes were analysed using linear regressions. Relationships between early life predictors and regional brain volumes and diffusion measures were analysed using voxelwise non-parametric permutation testing.
Male sex was associated with higher global volumes of all tissues and higher regional volumes throughout much of the cortical grey matter and white matter, particularly in the FT group. Male sex was also associated with lower FA and higher AD, RD and MD in the optic radiation, external and internal capsules and corona radiata, and these associations were generally similar between GA groups. Higher BWSDS was associated with higher global volumes of all tissues and higher regional volumes in much of the cortical grey matter and white matter in all GA groups, as well as higher FA and lower RD and MD in many major tracts (corpus callosum, optic radiation, internal and external capsules and corona radiata), particularly in the MP and LP groups. Multiple birth and social risk also showed associations with global and regional volumes and regional diffusion values which varied by GA group, but these associations were not independent of the other early life predictors. Postnatal growth was not associated with brain volumes or diffusion values.
Early life predictors of brain volumes and microstructure at TEA include sex, BWSDS, multiple birth and social risk, which have different effects based on GA group at birth. This study improves knowledge of the perinatal factors associated with brain abnormalities in infants born across the prematurity spectrum.
•Early life factors affect regional brain volume and microstructural development.•Effects of early life factors on brain development differ by gestational age.•Males have higher brain volumes but less organised microstructure than females.•Poor prenatal growth is associated with lower volume and less mature white matter.•Multiple birth and social risk may also affect brain development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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