145 research outputs found

    FMECA methodology applied to two pathways in an orthopaedic hospital in Milan.

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    INTRODUCTION: Adverse events pose a challenge to medical management: they can produce mild or transient disabilities or lead to permanent disabilities or even death; preventable adverse events result from error or equipment failure. METHODS: IRCCS Istituto Ortopedico Galeazzi implemented a clinical risk management program in order to study the epidemiology of adverse events and to improve new pathways for preventing clinical errors: a risk management FMECA-FMEA pro-active analysis was applied either to an existing clinical support pathway or to a new process before its implementation. RESULTS: The application of FMEA-FMECA allowed the clinical risk unit of our hospital to undertake corrective actions in order to reduce the adverse events and errors on high-risk procedure used inside the hospitals

    Prognostic Value of Viremia in Patients with Long-Standing Human Immunodeficiency Virus Infection

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    Human immunodeficiency virus (HIV) viremia was evaluated in 73 patients with long-standing infection to investigate its relationship with clinical or biologic parameters and to assess its use as a predictor of clinical progression and death. After adjustment for other parameters, baseline HIV RNA level was significantly associated with baseline clinical stage and CD4 cell count. During follow-up (mean, 14.6 months), 16 patients died; 34 others had clinical progression of disease. In multivariate analysis, mortality was better predicted by baseline CD4 cell count (relative hazard [RH] for 100-cell decrease, 3.5; 95% confidence interval [CI], 1.5-8.2; P = .003) than by HIV RNA (P = .28) or clinical stage. HIV RNA level was the best predictor of clinical progression (RH for 1 log increase, 2.8; 95% CI, 1.6-4.9; P < .001). Monitoring of HIV RNA level may help to identify patients who might benefit from antiretroviral or prophylactic therap

    PTEN deficiency and mutant p53 confer glucose-addiction to thyroid cancer cells: impact of glucose depletion on cell proliferation, cell survival, autophagy and cell migration.

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    Proliferating cancer cells oxidize glucose through the glycolytic pathway. Since this metabolism is less profitable in terms of ATP production, cancer cells consume large quantity of glucose, and those that experience insufficient blood supply become glucose-addicted. We have analyzed the response to glucose depletion in WRO and FTC133 follicular thyroid cancer cells, which differ in the expression of two key regulators of the glucose metabolism. WRO cells, which express wild type p53 and PTEN, showed a higher rate of cell proliferation and were much less sensitive to glucose-depletion than FTC133 cells, which are PTEN null and express mutant p53. Glucose depletion slowed-down the autophagy flux in FTC133 cells, not in WRO cells. In a wound-healing assay, WRO cells were shown to migrate faster than FTC133 cells. Glucose depletion slowed down the cell migration rate, and these effects were more evident in FTC133 cells. Genetic silencing of either wild-type PTEN or p53 in WRO cells resulted in increased uptake of glucose, whereas the ectopic expression of PTEN in FTC133 cells resulted in diminished glucose uptake. In conclusion, compared to WRO, FTC133 cells were higher glucose up-taker and consumer. These data do not support the general contention that cancer cells lacking PTEN or expressing the mutant p53R273H are more aggressive and prone to better face glucose depletion. We propose that concurrent PTEN deficiency and mutant p53 leads to a glucose-addiction state that renders the cancer cell more sensitive to glucose restriction. The present observation substantiates the view that glucose-restriction may be an adjuvant strategy to combat these tumours

    The Major Antigenic Membrane Protein of “Candidatus Phytoplasma asteris” Selectively Interacts with ATP Synthase and Actin of Leafhopper Vectors

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    Phytoplasmas, uncultivable phloem-limited phytopathogenic wall-less bacteria, represent a major threat to agriculture worldwide. They are transmitted in a persistent, propagative manner by phloem-sucking Hemipteran insects. Phytoplasma membrane proteins are in direct contact with hosts and are presumably involved in determining vector specificity. Such a role has been proposed for phytoplasma transmembrane proteins encoded by circular extrachromosomal elements, at least one of which is a plasmid. Little is known about the interactions between major phytoplasma antigenic membrane protein (Amp) and insect vector proteins. The aims of our work were to identify vector proteins interacting with Amp and to investigate their role in transmission specificity. In controlled transmission experiments, four Hemipteran species were identified as vectors of “Candidatus Phytoplasma asteris”, the chrysanthemum yellows phytoplasmas (CYP) strain, and three others as non-vectors. Interactions between a labelled (recombinant) CYP Amp and insect proteins were analysed by far Western blots and affinity chromatography. Amp interacted specifically with a few proteins from vector species only. Among Amp-binding vector proteins, actin and both the α and β subunits of ATP synthase were identified by mass spectrometry and Western blots. Immunofluorescence confocal microscopy and Western blots of plasma membrane and mitochondrial fractions confirmed the localisation of ATP synthase, generally known as a mitochondrial protein, in plasma membranes of midgut and salivary gland cells in the vector Euscelidius variegatus. The vector-specific interaction between phytoplasma Amp and insect ATP synthase is demonstrated for the first time, and this work also supports the hypothesis that host actin is involved in the internalization and intracellular motility of phytoplasmas within their vectors. Phytoplasma Amp is hypothesized to play a crucial role in insect transmission specificity
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