Background Diagnosis of chronic Hepatitis C Virus (HCV) infection requires both a positive HCV antibody screen and confirmatory nucleic acid test (NAT). HCV core antigen (HCVcAg) is a potential alternative to NAT. Purpose This systematic review evaluated the accuracy of diagnosis of active HCV infection among adults and children for five HCVcAg tests compared to NAT. Data Sources EMBASE, PubMed, Web of Science, Scopus, and Cochrane from 1990 through March 31, 2016. Study Selection Cohort, cross-sectional, and randomized controlled trials were included without language restriction Data Extraction Two independent reviewers extracted data and assessed quality using an adapted Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Data Synthesis 44 studies evaluated 5 index tests. Studies for the ARCHITECT had the highest quality, while those for Ortho ELISA were the lowest. From bivariate analyses, the sensitivity and specificity with 95% CI were: ARCHITECT 93.4% (90.1, 96.4) and 98.8% (97.4, 99.5), Ortho ELISA 93.2% (81.6, 97.7) and 99.2% (87.9, 100), and Hunan Jynda 59.5% (46.0, 71.7) and 82.9% (58.6, 94.3). Insufficient data were available for a meta-analysis for Lumipulse and Lumispot. In three quantitative studies using ARCHITECT, HCVcAg correlated closely with HCV RNA above 3000 IU/mL. Limitations There was insufficient data on covariates such as HIV or HBV status for sub-group analyses. Few studies reported genotypes of isolates and there were scant data for genotypes 4, 5, and 6. Most studies were conducted in high resource settings within reference laboratories. Conclusions HCVcAg assays with signal amplification have high sensitivity, high specificity, and good correlation with HCV RNA above 3000 IU/mL. HCVcAg assays have the potential to replace NAT in high HCV prevalence settings.

Graphical abstract

p53 colocalization with LGD at index LGD diagnosis is a risk factor for progression of LGD. This can potentially be used to risk stratify BE LGD patients in terms of surveillance intervals or enrollment into secondary prevention studies.

BackgroundReactive oxygen species are associated with inflammation implicated in cancer, atherosclerosis and autoimmune diseases. The complex nature of inflammation and of oxidative stress suggests that dual-target agents may be effective in combating diseases involving reactive oxygen species.ResultsA novel series of N-substituted 2,4-diaminopteridines has been synthesized and evaluated as antioxidants in several assays. Many exhibited potent lipid antioxidant properties, and some are inhibitors of soybean lipoxygenase, IC50 values extending down to 100 nM for both targets. Several pteridine derivatives showed efficacy at 0.01 mmol/kg with little tissue damage in a rat model of colitis. 2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)pteridin-4-amine (18f) at 0.01 mmol/kg exhibited potent anti-inflammatory activity (reduction by 41%).ConclusionThe 2,4-diaminopteridine core represents a new scaffold for lipoxygenase inhibition as well as sustaining anti-inflammatory properties.

The Aurora kinases are a family of highly homologous serine/threonine kinases, 1,2,3 which have welldocumented roles in the control of meiosis, mitosis and cell division. 4 There are three distinct subfamilies, Aurora A, Aurora B and Aurora C, which vary in their function and subcellular location.Since the first observation of the overexpression of Aurora kinases in cancer cell lines by Bischoff et al., 5 they have been regarded as promising drug targets for cancer chemotherapy. Aurora A overexpression is frequently detected in leukemia, breast, prostate and colon cancers, 2,5,6 with a lower overall survival rate seen in colorectal cancer patients with increased Aurora A levels. 7 This has seen a number of Aurora kinase inhibitors progressing through different stages of clinical trials. 3,8,9,10,11 The Aurora kinases are highly homologous, with a highly conserved C-terminal catalytic domain, a short N-terminal domain which varies in size, and an activation loop (Asp274-Glu299) which is conserved between the three family members. 3 The kinase activity of Aurora A is dependent on autophosphorylation of Thr288 (and possibly Thr287), found in the activation loop. In addition, binding of Aurora A to microtubule-associated proteins, in particular TPX2, alters the structure of Aurora A by stabilisation of the activation loop, allowing ATP to bind and driving the kinase into the optimal conformation for catalysis. 1,3,12 Inhibition of Aurora A results in inhibition of this phosphorylation, giving delayed entry into mitosis and the failure of the centrosomes to assemble bipolar spindles, resulting in aneuploidy and mitotic arrest. 13 Different conformational states of Aurora A can be induced or stabilised by different small molecule inhibitors, 14,15,16,17 and in particular the conformation of the activation loop modulates the interaction of Aurora A with its binding partners. 18 Coenzyme A (CoA) is an essential and ubiquitous cofactor made from vitamin B5 (pantothenate), ATP, and cysteine. CoA and its thioester derivatives (Acetyl CoA, Malonyl CoA, HMG CoA among others) are involved in diverse anabolic and catabolic pathways, biosynthesis of neurotransmitters and the regulation of gene expression. 19,20 Dysregulation of CoA biosynthesis or CoA thioester homoeostasis is associated with various human pathologies, including neurodegeneration, cancer and metabolic disorders. [21][22][23][24] Recent studies have uncovered a novel function of CoA in redox regulation, involving covalent modification of cellular proteins by disulphide bond formation, termed CoAlation, in cellular response to oxidative and metabolic stress. 25,26 Protein CoAlation is a widespread and reversible posttranslational modification, which occurs in single-cell and multicellular organisms, and modulates catalytic activity, regulatory interactions, subcellular localization and the stability of modified proteins. [27][28][29][30] Recently, we have reported that CoA is a specific ATP-competitive Aurora A inhibitor in vitro. 31 Using a combination of bioc...

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