Genetic determinants in a critical domain of ns5a correlate with hepatocellular carcinoma in cirrhotic patients infected with hcv genotype 1b

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain‐1 interacts with cellular proteins inducing pro‐oncogenic pathways. Thus, we explore genetic variations in NS5A domain‐1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype‐1b infected DAA‐naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p < 0.001). Focusing on HCC‐group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell‐cycle regulation (p53, p85‐PIK3, and β‐ catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV‐mediated oncogenesis. The role of these NS5A domain‐1 mutations in triggering pro‐oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation

Reliability assessment of ultrasound muscle echogenicity in patients with rheumatic diseases: Results of a multicenter international web-based study

ObjectivesTo investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases.MethodsForty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0–3) and a continuous quantitative measurement (“VAS echogenicity,” 0–100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall’s Tau and Pearson’s Rho coefficients.ResultsThe semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57–0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68–0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. “VAS echogenicity” showed a high reliability both in the inter-observer [ICC = 0.80 (0.75–0.85)] and intra-observer [ICC = 0.88 (0.88–0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and “VAS echogenicity” [ICC = 0.52 (0.50–0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively).ConclusionThe results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases

GOAL: automated Gene Ontology analysis of expression profiles

One of the most common problems encountered while deciphering results from expression profiling experiments is in relating differential expression of genes to molecular functions and cellular processes. A second important problem is that of comparing experiments performed by different labs using different microarray platforms, or even unrelated techniques. Gene Ontology (GO) is now used to describe biological features, since GO terms are associated with genes, to overcome the apparent distance between expression profiles and biological comprehension. Here we describe the development, implementation and use of GOAL (Gene Ontology Automated Lexicon), a web-based application for the identification of functions and processes regulated in microarray and SAGE (serial analysis of gene expression) experiments. We applied GOAL to a range of experimental datasets related to different biological problems, including cancer and the cell cycle. By using GOAL, reported and novel relevant processes were identified in a number of experiments by our collaborators and by us. Different datasets could also be compared with each other to define conserved functional modules. GOAL allows a seamless and high-level analysis of expression profiles and is implemented as a free WWW resource (http://microarrays.unife.it)

Correlation of expression between different IMAGE clones from the same UniGene cluster

Through the use of DNA microarray it is now possible to obtain quantitative measurements of the expression of thousands of genes present in a biological sample. DNA arrays yield a global view of gene expression and they can be used in a number of interesting ways. In this paper we are investigating an approach for studying the correlations between different clones from the same UniGene cluster. We will explore all possible couples of clones valuing the linear relations between the expression of these sequences. In this way, we can obtain several results: for example we can estimate measurement errors, or we can highlight genetic mutations. The experiments were done using a real dataset, build from 161 microarray experiments about Hepatocellular Carcinoma. © Springer-Verlag Berlin Heidelberg 2004

Fetal MRI of the cardiovascular system: role of steady-state free precession sequences for the evaluation of normal and pathological appearances

Purpose. This study aimed to evaluate the feasibility of fetal magnetic resonance imaging (MRI) with steady-state free precession (SSFP) sequences to visualise the normal and pathological appearances of the cardiovascular system. Materials and methods. This is a prospective observational study of 83 pregnant women who underwent fetal cardiac MRI: 43 patients (cases) had echocardiographic suspicion of congenital heart disease; 40 patients (controls) did not. Fetal cardiac MRI consisted of a static phase with multiplanar SSFP sequences and a dynamic phase with real-time SSFP sequences. Two radiologists evaluated the diagnostic quality of the SSFP images in both the controls and cases, the MRI morphological and functional features in the controls and the MRI signs of congenital heart disease in the cases. Results. In both groups, SSFP sequences produced good-quality MR images and good visualisation of morphological features. Functional data appeared to be unavailable due to the current small temporal resolution and the technical impossibility of fetal cardiac triggering. MRI detected direct signs of congenital heart disease in 21 fetuses, indirect signs in six and both signs in 15. Conclusions. SSFP sequences are effective in demonstrating the morphological features of the cardiovascular system, whereas dynamic SSFP cine-MRI sequences may provide adjunctive albeit suboptimal functional information

Fetal mid-muscular ventricular septal defect: Role of fetal cardio-vascular evaluation with magnetic resonance (MR) imaging and MR-angiography

We report our experience with fetal cardiac MR imaging and fetal MR-angiography in a 35 + 5-week fetus with a ventricular septal defect (VSD). Case: A fetus with an abnormal four-chamber view at obstetric US and a VSD of the medio-muscular portion of the ventricular septum at echocardiography underwent MRI to assess possible associated anomalies. Gradient Echo (GE) sequences with steady-state free precession (TrueFISP) and cine-MR sequences demonstrated a 4 mm VSD involving the medio-muscular portion of the septum in a morphologically and volumetrically normal fetal heart with a correct origin of the great arteries. T1-weighted 3D spoiled sequences permitted to obtain angiographic images and MIP reconstructions that proved a normal size and position of the aorta disconfirming a suspected coartaction of the aorta. Conventional T2-weighted sequences excluded the presence of extracardiac abnormalities. A postnatal echocardiography, considered as standard of reference confirmed the VSD in an otherwise normal male newborn. © 2008 Elsevier Ireland Ltd. All rights reserved

Hyaluronan-cholesterol nanohydrogels: characterisation and effectiveness in carrying alginate lyase

Although in recent years several methods have been studied and developed to obtain different types of nanosized drug delivery systems, the set up of suitable procedures and materials remains highly expensive, their preparation is time consuming and often not feasible for a scale-up process. Furthermore, the sterilisation and storage of nanocarrier formulations represents a complicated but mandatory step for their effective use. In our previous work we assessed the use of an autoclaving process to achieve, in one simple step, sterile self-assembled hyaluronan-cholesterol (HA-CH) and hyaluronan-riboflavin (HA-Rfv) nanohydrogels (NHs). In the present work, the effect of the high temperature on HA-CH has been studied in detail. HA-CH suspensions were characterised in terms of size and polydispersity by Dynamic Light Scattering at different temperatures and conditions; the HA-CH chemical structure and its molecular weight were assessed via FT-IR and GPC analysis after the sterilising cycle in an autoclave at 121°C for 20min. The obtained NHs were then observed with TEM and AFM microscopy, in both dry and liquid conditions. The Young's modulus of the NHs was determined, evidencing the soft nature of these nanosystems; the critical aggregation concentration (c.a.c) of the nanosuspension was also assessed. Thereafter, alginate lyase (AL) was conjugated to NHs, with the aim of developing a useful system for therapies against bacterial infections producing alginate biofilms. The conjugation efficiency and the enzymatic activity of AL were determined after immobilisation. The AL-NHs system showed the ability to depolymerise alginate, offering an opportunity to be a useful nanosystem for the treatment of biofilm-associated infections

Diffusion-weighted MR imaging and apparent diffusion coefficient of the normal fetal lung: preliminary experience

OBJECTIVE: To assess if a correlation is present between apparent diffusion coefficient (ADC) values and normal lung maturation during gestation to define potential reference values as indicators of the lung development. METHODS: Our study included 50 pregnant women (gestational age, GA: 18-36 weeks), with normal fetal development of lungs assessed by a previous obstetric ultrasound (US), and then confirmed by our magnetic resonance (MR) examination. We used T2-weighted sequences, diffusion-weighted imaging sequences (DWI) and ADC maps for studying pulmonary tissue. In all cases the resulting ADC values were related to GA using Pearson correlation. RESULTS: ADC values ranged from 1,2 microm(2)/ms at 18 weeks' gestation to 3,9 microm(2)/ms at 36 weeks' gestation with a mean value, regardless for the gestational age, of 2, 352 +/- 0,623106 microm(2)/ms. We found a significant correlation between ADC and gestational age (Pearson correlation = 0,816). CONCLUSION: The ADC values correlate with gestational age since alveolar fluid secretion and angiogenesis increase gradually. Therefore, ADC can be considered as a new parameter for studying lung maturity

Role of fetal MRI in the diagnosis of cerebral ventriculomegaly assessed by ultrasonography. Radiol Med. 2009 Sep 5.

Purpose. To evaluate the additional diagnostic value of fetal MRI to evaluate cerebral ventriculomegaly assessed by ultrasonography (US) for the possibility to change the diagnosis, the counseling and the management of pregnancy. Materials and Methods. From february 2006 to october 2008, we studied 55 pregnant women by fetal MRI (mean age 28 years), 4 with twin pregnancy, for a total of 59 fetuses with mean gestational age of 27 weeks. The number of fetuses affected by ventriculomegaly assessed by US was 55. All fetuses had a US diagnosis of ventriculomegaly: 29 fetuses with isolated ventriculomegaly and 26 fetuses with ventriculomegaly associated with CNS (central nervous system) abnormalities (18) and with no CNS abnormalities (8). Results. The findings showed that the two techniques are substantially in agreement in defining the degree of VM, with the exception of some cases in which the disagreement could be attributed to the possible progression of the dilatation between the US and MRI examinations, which sway between two days and two weeks. We proved a low correlation between US and MRI in the evaluation of ventriculomegaly associated either with CNS or non-CNS anomalies: in fact while fetal MRI detected 26/55 (47,3%) VM associated with CNS anomalies, US demonstrated only 18/55(32,7%). Referring to VM associated with non-CNS anomalies, MRI diagnosed 10/55 cases (18,2%) compared to 8/55 fetuses (14,5%) showed by US. Conclusions. Our experience demonstrated that fetal MRI has an important role as adjunctive tool to sonography in the evaluation of cerebral ventriculomegaly for the additional informations given to parents and for the possibility to change the diagnosis, the counseling and the management of pregnancy