IL28B Gene Polymorphisms and US Liver Fatty Changes in Patients Who Spontaneously Cleared Hepatitis C Virus Infection

Background

Recent clinical studies have shown that the presence of CC genotype in the rs12979860 region of IL28B gene is associated with an increase in the probability of spontaneous clearance of hepatitis C virus (HCV). Moreover, IL28B polymorphism seems to influence the probability of developing liver steatosis in chronic HCV patients.

Aims

The aims of our clinical study were 1) to verify the distribution of IL28B genotypes (CC, CT or TT) among subjects with spontaneous clearance of HCV infection and 2) to examine the correlation between IL28B polymorphism and hepatic steatosis among these subjects.

Methods and patients

We enrolled 41 subjects with spontaneous resolution of HCV infection (detectable serum anti-HCV but undetectable HCV-RNA) and 134 healthy controls from the same geographical area. The IL28B single-nucleotide polymorphism (SNP) rs12979860 was genotyped by using a Pyrosequencing™ technique. The presence of steatosis was assessed by liver biopsy or ultrasound examination in the 41 study subjects.

Results

CC, CT and TT-genotypes of the SNP rs1979860 were found in 66%, 24% and 10% of the subjects who spontaneously cleared HCV and in 31%, 54% and 15% of controls, respectively (p = 0.0003). Among the study subjects, females with CC-genotype were significantly more represented (p = 0.02). Hepatic steatosis did not correlate with IL28B genotype (p = 0,14) but only with a high body mass index (BMI) value (p = 0.03).

Conclusions

Female subjects carrying IL28B CC-genotype are significantly more represented among Italian patients who spontaneously cleared HCV infection. In addition, among these subjects, the presence of liver steatosis does not correlate with IL28B genotype but is solely related to the occurrence of high BMI. Thus, the association between IL28B polymorphism and steatosis in chronic HCV patients requires the presence of active HCV replication to occur, while in subjects who have cleared the infection, the mechanism(s) inducing liver steatosis are independent from IL28B profile.     

Somatic Mutations in Exocrine Pancreatic Tumors: Association with Patient Survival

KRAS mutations are major factors involved in initiation and maintenance of pancreatic tumors. The impact of different mutations on patient survival has not been clearly defined. We screened tumors from 171 pancreatic cancer patients for mutations in KRAS and CDKN2A genes. Mutations in KRAS were detected in 134 tumors, with 131 in codon 12 and only 3 in codon 61. The GGT>GAT (G12D) was the most frequent mutation and was present in 60% (80/134). Deletions and mutations in CDKN2A were detected in 43 tumors. Analysis showed that KRAS mutations were associated with reduced patient survival in both malignant exocrine and ductal adenocarcinomas (PDAC). Patients with PDACs that had KRAS mutations showed a median survival of 17 months compared to 30 months for those without mutations (log-rank P = 0.07) with a multivariate hazard ratio (HR) of 2.19 (95%CI 1.09–4.42). The patients with G12D mutation showed a median survival of 16 months (log-rank-test P = 0.03) and an associated multivariate HR 2.42 (95%CI 1.14–2.67). Although, the association of survival in PDAC patients with CDKN2A aberrations in tumors was not statistically significant, the sub-group of patients with concomitant KRAS mutations and CDKN2A alterations in tumors were associated with a median survival of 13.5 months compared to 22 months without mutation (log-rank-test P = 0.02) and a corresponding HR of 3.07 (95%CI 1.33–7.10). Our results are indicative of an association between mutational status and survival in PDAC patients, which if confirmed in subsequent studies can have potential clinical application.     

Equilibrium-Phase High Spatial Resolution Contrast-Enhanced MR Angiography at 1.5T in Preoperative Imaging for Perforator Flap Breast Reconstruction

Objectives

The aim was (i) to evaluate the accuracy of equilibrium-phase high spatial resolution (EP) contrast-enhanced magnetic resonance angiography (CE-MRA) at 1.5T using a blood pool contrast agent for the preoperative evaluation of deep inferior epigastric artery perforator branches (DIEP), and (ii) to compare image quality with conventional first-pass CE-MRA.

Methods

Twenty-three consecutive patients were included. All patients underwent preoperative CE-MRA to determine quality and location of DIEP. First-pass imaging after a single bolus injection of 10 mL gadofosveset trisodium was followed by EP imaging. MRA data were compared to intra-operative findings, which served as the reference standard.

Results

There was 100% agreement between EP CE-MRA and surgical findings in identifying the single best perforator branch. All EP acquisitions were of diagnostic quality, whereas in 10 patients the quality of the first-pass acquisition was qualified as non-diagnostic. Both signal- and contrast-to-noise ratios were significantly higher for EP imaging in comparison with first-pass acquisitions (p<0.01).

Conclusions

EP CE-MRA of DIEP in the preoperative evaluation of patients undergoing a breast reconstruction procedure is highly accurate in identifying the single best perforator branch at 1.5Tesla (T). Besides accuracy, image quality of EP imaging proved superior to conventional first-pass CE-MRA.     

Psychiatric disorders and SLC6A4 gene variants: possible effects on alcohol dependence and alzheimer’s disease

Molecular Biology Reports - Serotoninergic system is one of the most important neurotransmission systems investigated in the field of psychiatry. Extensive evidence reveals how alterations of this...     

Application of CO2 carbon stable isotope analysis to ant trophic ecology

Stable isotope analysis of animal tissues is commonly used to infer diet and trophic position. However, it requires destructive sampling. The analysis of carbon isotopes from exhaled CO₂ is non-invasive and can provide useful ecological information because isotopic CO₂ signatures can reflect the diet and metabolism of an animal. However, this methodology has rarely been used on invertebrates and never on social insects. Here, we first tested whether this method reflects differences in δ¹³C-CO₂ between workers of the Mediterranean ant Crematogaster scutellaris (Olivier) (Hymenoptera: Formicidae, Crematogastrini) fed with sugar from beet (C3; Beta vulgaris L., Amaranthaceae) or cane (C4; Saccharum officinarum L., Poaceae). We found that a significant difference can be obtained after 24 h. Consequently, we used this technique on wild co-occurring ant species with different feeding preferences to assess their reliance on C3 or C4 sources. For this purpose, we sampled workers of C. scutellaris, the invasive garden ant Lasius neglectus (van Loon et al.) (Lasiini), and the harvester ant Messor capitatus (Latreille) (Stenammini). No significant differences in their carbon isotopic signatures were recorded, suggesting that in our study site no niche partitioning occurs based on the carbon pathway, with all species sharing similar resources. However, further analysis revealed that M. capitatus, a seed-eating ant, can be regarded as a C3 specialist, whereas L. neglectus and C. scutellaris are generalists that rely on both C3 and C4 pathways, though with a preference for the former. Our results show that this methodology can be applied even to small animals such as ants and can provide useful information on the diets of generalist omnivores.     

Characterization of the first eukaryotic cold-adapted patatin-like phospholipase from the psychrophilic Euplotes focardii: Identification of putative determinants of thermal-adaptation by comparison with the homologous protein from the mesophilic Euplotes crassus

The ciliated protozoon Euplotes focardii, originally isolated from the coastal seawaters of Terra Nova Bay in Antarctica, shows a strictly psychrophilic phenotype, including optimal survival and multiplication rates at 4–5 °C. This characteristic makes E. focardii an ideal model species for identifying the molecular bases of cold adaptation in psychrophilic organisms, as well as a suitable source of novel cold-active enzymes for industrial applications. In the current study, we characterized the patatin-like phospholipase from E. focardii (EfPLP), and its enzymatic activity was compared to that of the homologous protein from the mesophilic congeneric species Euplotes crassus (EcPLP). Both EfPLP and EcPLP have consensus motifs conserved in other patatin-like phospholipases.     

Obscurin is required for ankyrinB-dependent dystrophin localization and sarcolemma integrity

Obscurin is a large myofibrillar protein that contains several interacting modules, one of which mediates binding to muscle-specific ankyrins. Interaction between obscurin and the muscle-specific ankyrin sAnk1.5 regulates the organization of the sarcoplasmic reticulum in striated muscles. Additional muscle-specific ankyrin isoforms, ankB and ankG, are localized at the subsarcolemma level, at which they contribute to the organization of dystrophin and β-dystroglycan at costameres. In this paper, we report that in mice deficient for obscurin, ankB was displaced from its localization at the M band, whereas localization of ankG at the Z disk was not affected. In obscurin KO mice, localization at costameres of dystrophin, but not of β-dystroglycan, was altered, and the subsarcolemma microtubule cytoskeleton was disrupted. In addition, these mutant mice displayed marked sarcolemmal fragility and reduced muscle exercise tolerance. Altogether, the results support a model in which obscurin, by targeting ankB at the M band, contributes to the organization of subsarcolemma microtubules, localization of dystrophin at costameres, and maintenance of sarcolemmal integrity.