Role of liver biopsy in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the “gold standard” for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease

Use of Finite Point Method for Wave Propagation in Nonhomogeneous Unbounded Domains

Wave propagation in an unbounded domain surrounding the stimulation resource is one of the important issues for engineers. Past literature is mainly concentrated on the modelling and estimation of the wave propagation in partially layered, homogeneous, and unbounded domains with harmonic properties. In this study, a new approach based on the Finite Point Method (FPM) has been introduced to analyze and solve the problems of wave propagation in any nonhomogeneous unbounded domain. The proposed method has the ability to use the domain properties by coordinate as an input. Therefore, there is no restriction in the form of the domain properties, such as being periodical as in the case of existing similar numerical methods. The proposed method can model the boundary points between phases with trace of errors and the results of this method satisfy both conditions of decay and radiation

Apobec1 complementation factor overexpression promotes hepatic steatosis, fibrosis, and hepatocellular cancer

The RNA-binding protein Apobec1 complementation factor (A1CF) regulates posttranscriptional ApoB mRNA editing, but the range of RNA targets and the long-term effect of altered A1CF expression on liver function are unknown. Here we studied hepatocyte-specific A1cf-transgenic (A1cf+/Tg), A1cf+/Tg Apobec1-/-, and A1cf-/- mice fed chow or high-fat/high-fructose diets using RNA-Seq, RNA CLIP-Seq, and tissue microarrays from human hepatocellular cancer (HCC). A1cf+/Tg mice exhibited increased hepatic proliferation and steatosis, with increased lipogenic gene expression (Mogat1, Mogat2, Cidea, Cd36) associated with shifts in polysomal RNA distribution. Aged A1cf+/Tg mice developed spontaneous fibrosis, dysplasia, and HCC, and this development was accelerated on a high-fat/high-fructose diet and was independent of Apobec1. RNA-Seq revealed increased expression of mRNAs involved in oxidative stress (Gstm3, Gpx3, Cbr3), inflammatory response (Il19, Cxcl14, Tnfα, Ly6c), extracellular matrix organization (Mmp2, Col1a1, Col4a1), and proliferation (Kif20a, Mcm2, Mcm4, Mcm6), and a subset of mRNAs (including Sox4, Sox9, Cdh1) were identified in RNA CLIP-Seq. Increased A1CF expression in human HCC correlated with advanced fibrosis and with reduced survival in a subset with nonalcoholic fatty liver disease. In conclusion, we show that hepatic A1CF overexpression selectively alters polysomal distribution and mRNA expression, promoting lipogenic, proliferative, and inflammatory pathways leading to HCC

Magnetic resonance imaging findings in 46 elbows with a radial head fracture

Radial head fractures are common, and may be associated with other injuries of clinical importance. We present the results of a standard additional MRI scan for patients with a radial head fracture. PATIENTS AND METhods: 44 patients (mean age 47 years) with 46 radial head fractures underwent MRI. 17 elbows had a Mason type-I fracture, 23 a Mason type-II fracture, and 6 elbows had a Mason type-III fracture. Associated injuries were found in 35 elbows: 28 elbows had a lateral collateral ligament lesion, 18 had capitellar injury, 1 had a coronoid fracture, and 1 elbow had medial collateral ligament injury. The incidence of associated injuries with radial head fractures found with MRI was high. The clinical relevance should be investigate

RAIphy: Phylogenetic classification of metagenomics samples using iterative refinement of relative abundance index profiles

Background: Computational analysis of metagenomes requires the taxonomical assignment of the genome contigs assembled from DNA reads of environmental samples. Because of the diverse nature of microbiomes, the length of the assemblies obtained can vary between a few hundred bp to a few hundred Kbp. Current taxonomic classification algorithms provide accurate classification for long contigs or for short fragments from organisms that have close relatives with annotated genomes. These are significant limitations for metagenome analysis because of the complexity of microbiomes and the paucity of existing annotated genomes. Results: We propose a robust taxonomic classification method, RAIphy, that uses a novel sequence similarity metric with iterative refinement of taxonomic models and functions effectively without these limitations. We have tested RAIphy with synthetic metagenomics data ranging between 100 bp to 50 Kbp. Within a sequence read range of 100 bp-1000 bp, the sensitivity of RAIphy ranges between 38%-81% outperforming the currently popular composition-based methods for reads in this range. Comparison with computationally more intensive sequence similarity methods shows that RAIphy performs competitively while being significantly faster. The sensitivityspecificity characteristics for relatively longer contigs were compared with the PhyloPythia and TACOA algorithms. RAIphy performs better than these algorithms at varying clade-levels. For an acid mine drainage (AMD) metagenome, RAIphy was able to taxonomically bin the sequence read set more accurately than the currently available methods, Phymm and MEGAN, and more accurately in two out of three tests than the much more computationally intensive method, PhymmBL. Conclusions: With the introduction of the relative abundance index metric and an iterative classification method, we propose a taxonomic classification algorithm that performs competitively for a large range of DNA contig lengths assembled from metagenome data. Because of its speed, simplicity, and accuracy RAIphy can be successfully used in the binning process for a broad range of metagenomic data obtained from environmental samples

Multiple Phenotypes in Adult Mice following Inactivation of the Coxsackievirus and Adenovirus Receptor (Car) Gene

To determine the normal function of the Coxsackievirus and Adenovirus Receptor (CAR), a protein found in tight junctions and other intercellular complexes, we constructed a mouse line in which the CAR gene could be disrupted at any chosen time point in a broad spectrum of cell types and tissues. All knockouts examined displayed a dilated intestinal tract and atrophy of the exocrine pancreas with appearance of tubular complexes characteristic of acinar-to-ductal metaplasia. The mice also exhibited a complete atrio-ventricular block and abnormal thymopoiesis. These results demonstrate that CAR exerts important functions in the physiology of several organs in vivo