45 research outputs found

    Interpretazione dell'ECG: un momento fondamentale nella gestione clinica del paziente cardiologico

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    Il caso clinico proposto si riferisce a un paziente che presenta diverse manifestazioni elettrocardiografiche riferibili a doppia via nodale. Tale reperto, di riscontro non raro, deve essere opportunamente riconosciuto in quanto potrebbe condurre all'erronea diagnosi di blocco atrio-ventricolare, con conseguenti ripercussioni terapeutiche. Parole chiave: Tachicardia da rientro nodale; Blocco atrio-ventricolare; Elettrocardiogramma; Doppia via nodale

    Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens

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    Background: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. Study design: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization. Results: HCV-RNA kinetics was biphasic, reflecting a mean effectiveness in blocking viral production >99.8%. The first-phase of viral-decline was faster in patients receiving NS5A-inhibitors compared to TVR+PR or sofosbuvir+simeprevir (p<0.001), reflecting higher efficacy in blocking assembly/secretion. The second-phase, noted \u3b4 and attributed to infected-cell loss, was faster in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.27 vs 0.21 d-1, respectively, p = 0.0012). In contrast the rate of ALT-normalization, noted \u3bb, was slower in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.17 vs 0.27 d-1, respectively, p<0.001). There was no significant association between the second-phase of viral-decline and ALT normalization rate and, for a given level of viral reduction, ALT-normalization was more profound in patients receiving DAA, and NS5A in particular, than TVR+PR. Conclusions: Our data support a process of HCV-clearance by all-DAA regimens potentiated by NS5A-inhibitor, and less relying upon hepatocyte death than IFN-containing regimens. This may underline a process of "cell-cure" by DAAs, leading to a fast improvement of liver homeostasis

    Improving benchmarking by using an explicit framework for the development of composite indicators: an example using pediatric quality of care

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    <p>Abstract</p> <p>Background</p> <p>The measurement of healthcare provider performance is becoming more widespread. Physicians have been guarded about performance measurement, in part because the methodology for comparative measurement of care quality is underdeveloped. Comprehensive quality improvement will require comprehensive measurement, implying the aggregation of multiple quality metrics into composite indicators.</p> <p>Objective</p> <p>To present a conceptual framework to develop comprehensive, robust, and transparent composite indicators of pediatric care quality, and to highlight aspects specific to quality measurement in children.</p> <p>Methods</p> <p>We reviewed the scientific literature on composite indicator development, health systems, and quality measurement in the pediatric healthcare setting. Frameworks were selected for explicitness and applicability to a hospital-based measurement system.</p> <p>Results</p> <p>We synthesized various frameworks into a comprehensive model for the development of composite indicators of quality of care. Among its key premises, the model proposes identifying structural, process, and outcome metrics for each of the Institute of Medicine's six domains of quality (safety, effectiveness, efficiency, patient-centeredness, timeliness, and equity) and presents a step-by-step framework for embedding the quality of care measurement model into composite indicator development.</p> <p>Conclusions</p> <p>The framework presented offers researchers an explicit path to composite indicator development. Without a scientifically robust and comprehensive approach to measurement of the quality of healthcare, performance measurement will ultimately fail to achieve its quality improvement goals.</p

    E-Learning Cooperative Environments: Simulations and Virtual Labs as the New Frontiers of Inclusiveness and Immersiveness for Organizations

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    Virtual environments developed thanks to the use of advanced technologies, allow students to experience in a full and total way his/her learning and knowledge, from a subjective perspective, where multisensory interaction is provided. The social context of learning can be created from the content itself. If we can create social spaces on-line than in so far as disciplines connected with the social sciences are concerned, that content can be created as an interactive learning environments with unique, though simulated, social contexts for learning. The aim of this study was to investigate students' perceptions of simulations and role plays and how these tools, if well managed, offer a variety of powerful information sharing and collaboration features. Understanding students' perceptions and usage behavior of these systems is a very important goal, because the success of them depends on several social and psychological factors. In addition, the benefits of 3D graphics for education have been explored. 3D models are very useful to familiarize students with features of different shapes and objects, and can be particularly useful in teaching activities. Some courses have been developed using 3D images that the user must interact with in order to learn a certain lesson

    Accumulation of Fra-1 in ras-Transformed Cells Depends on Both Transcriptional Autoregulation and MEK-Dependent Posttranslational Stabilization

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    The AP-1 transcription factor plays an essential role in cell proliferation and tumorigenesis. It was previously shown that the fra-1 gene product is upregulated by various oncogenes and is involved in the in vitro and in vivo transformation of thyroid cells. Here we show that the ras oncogene-dependent accumulation of Fra-1 is mediated by a positive feedback mechanism which requires both transcriptional autoregulation and posttranslational stabilization of the protein. The oncogene-dependent transcriptional activation involves the cooperation between both Raf-dependent and Raf-independent pathways and is mediated by an AP-1 site within the fra-1 first intron, which becomes stably occupied by a transcriptionally active Fra-1-containing complex in ras-transformed cells. The posttranslational stabilization results in a drastic increase in the Fra-1 half-life in ras-transformed cells and is totally dependent on the activity of the MEK/ERK phosphorylation pathway. The analysis of the Fra-1 transactivation potential shows that the protein is able to stimulate a heterologous promoter in a ras-dependent manner, but the transactivating activity requires the recruitment of a heterodimeric partner. These data show that the alteration of multiple regulatory mechanisms is required for the constitutive activation of Fra-1 as a nuclear target of ras transformation
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