A review of the clinical utility of the Enhanced Liver Fibrosis test in multiple aetiologies of chronic liver disease

The rising incidence of chronic liver disease continues to be an increasing health burden. The morbidity and mortality associated with chronic liver disease typically occur in patients with advanced fibrosis. Hence, early identification of those at-risk is of vital importance to ensure appropriate ongoing management. Currently, tools for appropriate risk stratification remain limited. Increasing awareness of the limitations of liver biopsy has driven research into alternative non-invasive methods of fibrosis assessment including serological markers assessing functional changes. One such biomarker, the Enhanced Liver Fibrosis test, was initially validated in a cohort of 1021 patients with mixed aetiology chronic liver disease and shown to perform well. Since this pathfinder study, it has been independently validated in cohorts of hepatitis C, non-alcoholic fatty liver disease, alcoholic liver disease, primary biliary cirrhosis and primary sclerosing cholangitis. In addition to performing well as a diagnostic tool, the Enhanced Liver Fibrosis test has been shown to outperform liver biopsy in prognostic studies and is the only non-invasive marker to do so. However, questions remain regarding the use of this test, particularly regarding the possible effect age and alcohol may have on test scores. This review examines the current literature published in relation to the Enhanced Liver Fibrosis test and its clinical utility and highlights areas requiring further study

Expulsion of Symbiotic Algae during Feeding by the Green Hydra – a Mechanism for Regulating Symbiont Density?

Background: Algal-cnidarian symbiosis is one of the main factors contributing to the success of cnidarians, and is crucial for the maintenance of coral reefs. While loss of the symbionts (such as in coral bleaching) may cause the death of the cnidarian host, over-proliferation of the algae may also harm the host. Thus, there is a need for the host to regulate the population density of its symbionts. In the green hydra, Chlorohydra viridissima, the density of symbiotic algae may be controlled through host modulation of the algal cell cycle. Alternatively, Chlorohydra may actively expel their endosymbionts, although this phenomenon has only been observed under experimentally contrived stress conditions. Principal Findings: We show, using light and electron microscopy, that Chlorohydra actively expel endosymbiotic algal cells during predatory feeding on Artemia. This expulsion occurs as part of the apocrine mode of secretion from the endodermal digestive cells, but may also occur via an independent exocytotic mechanism. Significance: Our results demonstrate, for the first time, active expulsion of endosymbiotic algae from cnidarians under natural conditions. We suggest this phenomenon may represent a mechanism whereby cnidarians can expel excess symbiotic algae when an alternative form of nutrition is available in the form of prey

The Enhanced Liver Fibrosis test maintains its diagnostic and prognostic performance in alcohol-related liver disease: a cohort study

BACKGROUND: Alcohol is the main cause of chronic liver disease. The Enhanced Liver Fibrosis (ELF) test is a serological biomarker for fibrosis staging in chronic liver disease, however its utility in alcohol-related liver disease warrants further validation. We assessed the diagnostic and prognostic performance of ELF in alcohol-related liver disease. METHODS: Observational cohort study assessing paired ELF and histology from 786 tertiary care patients with chronic liver disease due to alcohol (n = 81) and non-alcohol aetiologies (n = 705). Prognostic data were available for 64 alcohol patients for a median of 6.4 years. Multiple ELF cut-offs were assessed to determine diagnostic utility in moderate fibrosis and cirrhosis. Survival data were assessed to determine the ability of ELF to predict liver related events and all-cause mortality. RESULTS: ELF identified cirrhosis and moderate fibrosis in alcohol-related liver disease independently of aminotransferase levels with areas under receiver operating characteristic curves of 0.895 (95% CI 0.823-0.968) and 0.923 (95% CI 0.866-0.981) respectively, which were non-inferior to non-alcohol aetiologies. The overall performance of ELF was assessed using the Obuchowski method: in alcohol = 0.934 (95% CI 0.908-0.960); non-alcohol = 0.907 (95% CI 0.895-0.919). Using ELF < 9.8 to exclude and ≧ 10.5 to diagnose cirrhosis, 87.7% of alcohol cases could have avoided biopsy, with sensitivity of 91% and specificity of 85%. A one-unit increase in ELF was associated with a 2.6 (95% CI 1.55-4.31, p < 0.001) fold greater odds of cirrhosis at baseline and 2.0-fold greater risk of a liver related event within 6 years (95% CI 1.39-2.99, p < 0.001). CONCLUSIONS: ELF accurately stages liver fibrosis independently of transaminase elevations as a marker of inflammation and has superior prognostic performance to biopsy in alcohol-related liver disease

Avulsion fracture of the anterior superior iliac spine: misdiagnosis of a bone tumour

Avulsion fractures of the anterior superior iliac spine are rare. This injury is usually seen in adolescents, as an avulsion fracture of the apophyses, a result of sudden vigorous contraction or repetitive contraction of the sartorius and tensor fasciae latae muscles. Treatment for this injury is usually conservative; however, surgical management has been reported in those with significant displacement. We present a 14 year old male patient who was referred to our unit for biopsy of a possible pathological fracture of his right ilium. The authors feel it is essential to understand the importance of ruling out a bone tumour, if the possibility has been raised, before managing a suspected fracture. If there is any doubt, the case should be referred to an appropriate sarcoma unit for review prior to any intervention

Multicenter data acquisition made easy

<p>Abstract</p> <p>Background</p> <p>The process for data collection in multicenter trials may be troublesome and expensive. We report our experience with the spreadsheet function in Googledocs for this purpose.</p> <p>Methods</p> <p>In Googledocs the data manager creates a form similar to the paper case record form, which will function as a decentral data entry module. When the forms are submitted, they are presented in a spreadsheet in Googledocs, which can be exported to different standard spreadsheet formats.</p> <p>Results</p> <p>For a multicenter randomized clinical trial with five different participating hospitals we created a decentral data entry module using the spreadsheet function in Googledocs. The study comprised 332 patients (clinicaltrials.gov identifier: NCT00815698) with five visits per patient. One person at each study site entered data from the original paper based case report forms which were kept at the study sites as originals. We did not experience any technical problems using the system.</p> <p>Conclusions</p> <p>The system allowed for decentral data entry, and it was easy to use, safe, and free of charge. The spreadsheet function in Googledocs may potentially replace current expensive solutions for data acquisition in multicenter trials.</p> <p>Trial registration</p> <p>clinicaltrials.gov NCT00815698</p

Rapid generation of chromosome-specific alphoid DNA probes using the polymerase chain reaction

Non-isotopic in situ hybridization of chromosome-specific alphoid DNA probes has become a potent tool in the study of numerical aberrations of specific human chromosomes at all stages of the cell cycle. In this paper, we describe approaches for the rapid generation of such probes using the polymerase chain reaction (PCR), and demonstrate their chromosome specificity by fluorescence in situ hybridization to normal human metaphase spreads and interphase nuclei. Oligonucleotide primers for conserved regions of the alpha satellite monomer were used to generate chromosome-specific DNA probes from somatic hybrid cells containing various human chromosomes, and from DNA libraries from sorted human chromosomes. Oligonucleotide primers for chromosome-specific regions of the alpha satellite monomer were used to generate specific DNA probes for the pericentromeric heterochromatin of human chromosomes 1, 6, 7, 17 and X directly from human genomic DNA

Effective connectivity reveals strategy differences in an expert calculator

Mathematical reasoning is a core component of cognition and the study of experts defines the upper limits of human cognitive abilities, which is why we are fascinated by peak performers, such as chess masters and mental calculators. Here, we investigated the neural bases of calendrical skills, i.e. the ability to rapidly identify the weekday of a particular date, in a gifted mental calculator who does not fall in the autistic spectrum, using functional MRI. Graph-based mapping of effective connectivity, but not univariate analysis, revealed distinct anatomical location of “cortical hubs” supporting the processing of well-practiced close dates and less-practiced remote dates: the former engaged predominantly occipital and medial temporal areas, whereas the latter were associated mainly with prefrontal, orbitofrontal and anterior cingulate connectivity. These results point to the effect of extensive practice on the development of expertise and long term working memory, and demonstrate the role of frontal networks in supporting performance on less practiced calculations, which incur additional processing demands. Through the example of calendrical skills, our results demonstrate that the ability to perform complex calculations is initially supported by extensive attentional and strategic resources, which, as expertise develops, are gradually replaced by access to long term working memory for familiar material

A patient with glycogen storage disease type Ib presenting with acute myeloid leukemia (AML) bearing monosomy 7 and translocation t(3;8)(q26;q24) after 14 years of treatment with granulocyte colony-stimulating factor (G-CSF): A case report

<p>Abstract</p> <p>Introduction</p> <p>Glycogen storage disease type Ib is an autosomal recessive transmitted disorder of glycogen metabolism caused by mutations in the glucose-6-phosphate translocase gene on chromosome 11q23 and leads to disturbed glycogenolysis as well as gluconeogenesis. Besides hepatomegaly, growth retardation, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia, patients suffer from neutropenia associated with functional defects predisposing for severe infections. In order to attenuate these complications, long-term treatment with granulocyte colony-stimulating factor is common but this is associated with an increased risk for acute myeloid leukemia or myelodysplastic syndromes in patients with inherited bone marrow failures such as severe congenital neutropenia. Onset of these myeloid malignancies is linked to cytogenetic aberrations involving chromosome 7. In addition, granulocyte colony-stimulating factor is known to stimulate proliferation of monosomy 7 cells <it>in vitro</it>. To our knowledge, we report for the first time a case report of a patient with glycogen storage disease type Ib, who developed acute myeloid leukemia with a classical monosomy 7 and acute myeloid leukemia-associated translocation t(3;8)(q26;q24) after 14 years of continuous treatment with granulocyte colony-stimulating factor.</p> <p>Case presentation</p> <p>A 28-year-old Turkish man with glycogen storage disease type Ib was admitted to our department because of dyspnea and increasing fatigue. He also presented with gum bleeding, bone pain in his legs, night sweats, recurrent episodes of fever with temperatures up to 39°C and hepatosplenomegaly.</p> <p>A blood count taken on the day of admission showed pancytopenia and a differential count displayed 30% blasts. A bone marrow biopsy was taken which showed a hypercellular marrow with dysplastic features of all three cell lines, while blast count was 20%. Classical cytogenetic analyses as well as fluorescence in situ hybridization showed a monosomy 7 with a translocation t(3;8)(q26;q24). Based on these findings, the diagnosis of acute myeloid leukemia was made.</p> <p>Conclusion</p> <p>Our observations suggest that bone marrow examinations including cytogenetic analysis should be carried out on a regular basis in patients with glycogen storage disease type Ib who are on long-term treatment with granulocyte colony-stimulating factor for severe neutropenia, since this treatment might also contribute to an increased risk for acute myeloid leukemia or myelodysplastic syndromes.</p

Anthropogenic Impacts on Aquatic Insects in Six Streams of South Western Ghats

Diversity patterns of aquatic insects among sampling sites lying with!ç the unprotected and protected areas of Western Ghats were studied. This study primarily emphasizes whether anthropogenic influence is the prime cause for the presence of aquatic insects especialIy of pollution-sensitive organisms belonging to the orders Ephemeroptera, Plecoptera and Trichoptera, or to factors such as the physico-chemical features of the water, or sampling methods. Six streams were sampled quantitatively, of which three streams (Abbifalls, Monkey falls and SiIver Cascade) were within protected areas and the remaining three streams (Kumbakarai, Shenbagadevi and Manimutharu falls) were in unprotected areas. A total of 3,209 individual aquatic insects belonging to 25 genera, 18 families and 7 orders were collected. The highest species richness and abundance was observed in Monkey falls followed by Kumbakkarai falls. Large çumbers of more habitat-sensitive organisms such as Ecdyonurus sp., Epeorus sp., Thalerosphyrus sp., Euthraulus sp., and Nathanella sp., were found in Monkey falls. Though the species assemblage was somewhat different, pollution-sensitive taxa were also observed in Kumbakkarai falls. Shenbagadevi and Manimutharu falls had a lower diversity of aquatic insects. The likely causes of these differences are discussed