Diagnostic accuracy of the aspartate aminotransferase-to-platelet ratio index for the prediction of hepatitis B-related fibrosis: a leading meta-analysis

<p>Abstract</p> <p>Background</p> <p>The aspartate aminotransferase-to-platelet ratio index (APRI), a tool with limited expense and widespread availability, is a promising noninvasive alternative to liver biopsy for detecting hepatic fibrosis. The objective of this study was to systematically review the performance of the APRI in predicting significant fibrosis and cirrhosis in hepatitis B-related fibrosis.</p> <p>Methods</p> <p>Areas under summary receiver operating characteristic curves (AUROC), sensitivity and specificity were used to examine the accuracy of the APRI for the diagnosis of hepatitis B-related significant fibrosis and cirrhosis. Heterogeneity was explored using meta-regression.</p> <p>Results</p> <p>Nine studies were included in this meta-analysis (n = 1,798). Prevalence of significant fibrosis and cirrhosis were 53.1% and 13.5%, respectively. The summary AUCs of the APRI for significant fibrosis and cirrhosis were 0.79 and 0.75, respectively. For significant fibrosis, an APRI threshold of 0.5 was 84% sensitive and 41% specific. At the cutoff of 1.5, the summary sensitivity and specificity were 49% and 84%, respectively. For cirrhosis, an APRI threshold of 1.0-1.5 was 54% sensitive and 78% specific. At the cutoff of 2.0, the summary sensitivity and specificity were 28% and 87%, respectively. Meta-regression analysis indicated that the APRI accuracy for both significant fibrosis and cirrhosis was affected by histological classification systems, but not influenced by the interval between Biopsy & APRI or blind biopsy.</p> <p>Conclusion</p> <p>Our meta-analysis suggests that APRI show limited value in identifying hepatitis B-related significant fibrosis and cirrhosis.</p

Antibody stabilization for thermally accelerated deep immunostaining

Antibodies have diverse applications due to their high reaction specificities but are sensitive to denaturation when a higher working temperature is required. We have developed a simple, highly scalable and generalizable chemical approach for stabilizing off-the-shelf antibodies against thermal and chemical denaturation. We demonstrate that the stabilized antibodies (termed SPEARs) can withstand up to 4 weeks of continuous heating at 55 °C and harsh denaturants, and apply our method to 33 tested antibodies. SPEARs enable flexible applications of thermocycling and denaturants to dynamically modulate their binding kinetics, reaction equilibrium, macromolecular diffusivity and aggregation propensity. In particular, we show that SPEARs permit the use of a thermally facilitated three-dimensional immunolabeling strategy (termed ThICK staining), achieving whole mouse brain immunolabeling within 72 h, as well as nearly fourfold deeper penetration with threefold less antibodies in human brain tissue. With faster deep-tissue immunolabeling and broad compatibility with tissue processing and clearing methods without the need for any specialized equipment, we anticipate the wide applicability of ThICK staining with SPEARs for deep immunostaining

A randomised controlled trial of a lengthened and multi-disciplinary consultation model in a socially deprived community: a study protocol

<p>Abstract</p> <p>Background</p> <p>There has been little development of the general practice consultation over the years, and many aspects of the present consultation do not serve communities with multiple health and social problems well. Many of the problems presenting to general practitioners in socio-economically disadvantaged areas are not amenable to a purely medical solution, and would particularly benefit from a multidisciplinary approach. Socio-economic deprivation is also associated with those very factors (more psychosocial problems, greater need for health promotion, more chronic diseases, more need for patient enablement) that longer consultations have been shown to address. This paper describes our study protocol, which aims to evaluate whether a lengthened multidisciplinary primary care team consultation with families in a socially deprived area can improve the psychological health of mothers in the families.</p> <p>Methods/Design</p> <p>In a randomised controlled trial, families with a history of social problems, substance misuse or depression are randomly allocated to an intervention or control group. The study is based in three general practices in a highly deprived area of North Dublin. Primary health care teams will be trained in conducting a multidisciplinary lengthened consultation. Families in the intervention group will participate in the new style multidisciplinary consultation. Outcomes of families receiving the intervention will be compared to the control group who will receive only usual general practitioner care. The primary outcome is the psychological health of mothers of the families and secondary outcomes include general health status, quality of life measures and health service usage.</p> <p>Discussion</p> <p>The main aim of this study is to evaluate the effectiveness of a lengthened multidisciplinary team consultation in primary care. The embedded nature of this study in general practices in a highly deprived area ensures generalisability to other deprived communities, but more particularly it promises relevance to primary care.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN70578736</p

A Large Population Histology Study Showing the Lack of Association between ALT Elevation and Significant Fibrosis in Chronic Hepatitis B

OBJECTIVE: We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. METHODS: From 1994 to 2008, liver biopsy was performed on 319 treatment-naive CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis. RESULTS: 211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%) HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading >/= 7 or fibrosis score >/= 3). There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively). An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no significant difference in fibrosis staging among ALT 1-2 x upper limit of normal (ULN) and > x 2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838) disease. CONCLUSION: An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.published_or_final_versio

The Long March: A Sample Preparation Technique that Enhances Contig Length and Coverage by High-Throughput Short-Read Sequencing

High-throughput short-read technologies have revolutionized DNA sequencing by drastically reducing the cost per base of sequencing information. Despite producing gigabases of sequence per run, these technologies still present obstacles in resequencing and de novo assembly applications due to biased or insufficient target sequence coverage. We present here a simple sample preparation method termed the “long march” that increases both contig lengths and target sequence coverage using high-throughput short-read technologies. By incorporating a Type IIS restriction enzyme recognition motif into the sequencing primer adapter, successive rounds of restriction enzyme cleavage and adapter ligation produce a set of nested sub-libraries from the initial amplicon library. Sequence reads from these sub-libraries are offset from each other with enough overlap to aid assembly and contig extension. We demonstrate the utility of the long march in resequencing of the Plasmodium falciparum transcriptome, where the number of genomic bases covered was increased by 39%, as well as in metagenomic analysis of a serum sample from a patient with hepatitis B virus (HBV)-related acute liver failure, where the number of HBV bases covered was increased by 42%. We also offer a theoretical optimization of the long march for de novo sequence assembly

Identification of the risk for liver fibrosis on CHB patients using an artificial neural network based on routine and serum markers

<p>Abstract</p> <p>Background</p> <p>Liver fibrosis progression is commonly found in patients with CHB. Liver biopsy is a gold standard for identifying the extent of liver fibrosis, but has many draw-backs. It is essential to construct a noninvasive model to predict the levels of risk for liver fibrosis. It would provide very useful information to help reduce the number of liver biopsies of CHB patients.</p> <p>Methods</p> <p>339 chronic hepatitis B patients with HBsAg-positive were investigated retrospectively, and divided at random into 2 subsets with twice as many patients in the training set as in the validation set; 116 additional patients were consequently enrolled in the study as the testing set. A three-layer artificial neural network was developed using a Bayesian learning algorithm. Sensitivity and ROC analysis were performed to explain the importance of input variables and the performance of the neural network.</p> <p>Results</p> <p>There were 329 patients without significant fibrosis and 126 with significant fibrosis in the study. All markers except gender, HB, ALP and TP were found to be statistically significant factors associated with significant fibrosis. The sensitivity analysis showed that the most important factors in the predictive model were age, AST, platelet, and GGT, and the influence on the output variable among coal miners were 22.3-24.6%. The AUROC in 3 sets was 0.883, 0.884, and 0.920. In the testing set, for a decision threshold of 0.33, sensitivity and negative predictive values were 100% and all CHB patients with significant fibrosis would be identified.</p> <p>Conclusions</p> <p>The artificial neural network model based on routine and serum markers would predict the risk for liver fibrosis with a high accuracy. 47.4% of CHB patients at a decision threshold of 0.33 would be free of liver biopsy and wouldn't be missed.</p

SDS-PAGE-Based Quantitative Assay for Screening of Kidney Stone Disease

Kidney stone disease is a common health problem in industrialised nations. We developed a SDS-PAGE-based method to quantify Tamm Horsfall glycoprotein (THP) for screening of kidney stone disease. Urinary proteins were extracted by using ammonium sulphate precipitation at 0.27 g salt/mL urine. The resulted pellet was dissolved in TSE buffer. Ten microliters of the urinary proteins extract was loaded and separated on 10% SDS-PAGE under reducing condition. THP migrated as single band in SDS-PAGE. The assay reproducibility and repeatability were 4.8% CV and 2.6% CV, respectively. A total of 117 healthy subjects and 58 stone patients were tested using this assay, and a distinct cut-off (P < 0.05) at 5.6 μg/mL THP concentration was used to distinguish stone patients from healthy subjects. The sensitivity and specificity of the method were 92.3% and 83.3%, respectively