miR-155 in the progression of lung fibrosis in systemic sclerosis

Background: MicroRNA (miRNA) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from patients with SSc-ILD. A chronic lung fibrotic murine model was used. Methods: RNA was isolated from lung tissue of 12 patients with SSc-ILD and 5 controls. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and peripheral blood mononuclear cells (PBMC) were isolated from healthy controls and patients with SSc-ILD. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DNA Intelligent Analysis (DIANA)-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Results: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q < 0.25). DIANA-miRPath revealed 57 Kyoto Encyclopedia of Genes and Genomes pathways related to the most dysregulated miRNA. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts only mildly expressed miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. Conclusions: miRNA are dysregulated in the lungs and PBMC of patients with SSc-ILD. Based on mRNA-miRNA interaction analysis and pathway tools, miRNA may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD

Characterization of Fusarium verticillioides strains isolated from maize in Italy: Fumonisin production, pathogenicity and genetic variability

Fusarium verticillioides (teleomorph Gibberella moniliformis) is the main fungal agent of ear and kernel rot of maize (Zea mays L.) worldwide, including Italy. F.verticillioides is a highly toxigenic species since it is able to produce the carcinogenic mycotoxins fumonisins. In this study, 25 F. verticillioides strains, isolated from maize in different regions of Italy were analyzed for their ability to produce fumonisins, their pathogenicity and their genetic variability. A further referenced strain of G. moniliformis isolated from maize in USA was also used as outgroup. The fumonisins B 1 , B 2 , and B 3 were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pathogenicity tests were carried out by symptom observation and determination of growth parameters after inoculation of maize seeds, seedlings and wounded detached leaves. Total genomic DNA was used for Amplified Fragment Length Polymorphism (AFLP) analysis. About 20% of the analyzed strains were unable to produce fumonisins in in vitro experiments on inoculated maize flour, while, among fumonisin producers, a great variability was observed, with values ranging from 1 to 115 mg kg -1 . The different analyzed strains showed a wide range of pathogenicity in terms of effect on seed germination, seedling development and of symptoms produced on detached leaves, which were not correlated with the different in vitro fumonisin production. AFLP analysis indicated the presence of genetic diversity not only between the Italian strains and the American reference but also among the Italian isolates. © 2012 Elsevier Ltd

Management of residual subdural hematoma after burr-hole evacuation. The role of fluid therapy and review of the literature

A vast amount of literature has been published investigating the factors associated to the recurrence of a chronic subdural hematoma (SDH). However, little exists in the literature about the best medical management of the residual SDH in order to prevent the recurrence. Moreover only few studies quantitatively assess clinical and radiological outcomes of residual post-operative SDH. In this study, to our knowledge, we report the first series of chronic SDH with a quantitative outcomes analysis of the effects of fluid therapy on residual post-operative SDH. Moreover we discuss the pertinent literature. We reviewed clinical and outcome data of 39 patients (44 SDH; 12 F, 27 M) submitted to a burr-hole evacuation of a SDH. The mean age was 76.97 \ub1 7.77 years. All patients had a minimum 3-month follow-up (FU). Post-operatively, an intravenous saline solution was started in all cases (2000 ml in 24 h) and administered for 3 days. Then an oral hydration with 2 l per day of water was started and continued as outpatients. Glasgow Coma Scale (GCS), Karnofsky Performance Status (KPS), SDH volume and midline shift were evaluated pre-operatively, post-operatively and at FU. We found a statistically significant improvement of post-operative and at FU GCS and KPS compared to the pre-operative. SDH volume and midline shift were also statistically significant reduced in the post-operative and at FU. No complication occurred. Only 1 patient required a reoperation at 3 months FU for neurological worsening. Oral fluid therapy is a safe and effective treatment for residual SDH

Unrecognized failed back surgery syndrome: a paradigmatic case in a very young patient

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