1,721,022 research outputs found

    Control of mitochondria dynamics and oxidative metabolism by cAMP, AKAPs and the proteasome.

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    Mitochondria are highly specialized organelles and major players in fundamental aspects of cell physiology. In yeast, energy metabolism and coupling of mitochondrial activity to growth and survival is controlled by the protein kinase A pathway. In higher eukaryotes, modulation of the so-called A-kinase anchor protein (AKAP) complex regulates mitochondrial dynamics and activity, adapting the oxidative machinery and the metabolic pathway to changes in physiological demand. Protein kinases and phosphatases are assembled by AKAPs within transduction units, providing a mechanism to control signaling events at mitochondria and other target organelles. Ubiquitin-mediated proteolysis of signal transducers and effectors provides an additional layer of complexity in the regulation of mitochondria homeostasis. Genetic evidence indicates that alteration of one or more components of these biochemical pathways leads to mitochondrial dysfunction and human diseases. In this review, we focus on the emerging role of AKAP scaffolds and the proteasome pathway in the control of oxidative metabolism, organelle dynamics and the mitochondrial signaling network. These aspects are crucial elements for maintaining a proper energy balance and cellular lifespan

    Prognostic value of soluble major histocompatibility complex class I polypeptide-related sequence A in non-small-cell lung cancer – significance and development

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    Soluble major histocompatibility complex class I polypeptide-related sequence A (sMICA) is a useful marker in surveillance of lung cancer. High serum sMICA level in patients with non-small-cell lung cancer (NSCLC) seems to be a poor prognostic factor being correlated with poor differentiation and advanced stage. However, the low specificity limits its role as a single prognostic marker of NSCLC, but its evaluation, in addition to standard serum markers, could improve the staging of NSCLC. Despite promising, all current studies are insufficient to assess the real efficiency of sMICA as a prognostic marker of NSCLC, and hence, future studies are required to validate it

    Noninvasive ventilation for weaning and post extubation failure

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    Invasive Mechanical Ventilation (IMV) is a life-saving procedure not lacking from complications that enhances morbidity and mortality for intubated patients; therefore, it is important to minimize the duration of IMV. When the weaning fails, it is associated with an increased risk of death and prolonged intensive care unit (ICU) stay. Many investigators examined the possibility to wean patients ventilated invasively by Noninvasive ventilation (NIV). Several studies, tested, in patients affected by chronic respiratory disorders (ie, chronic obstructive pulmonary disease), the use of NIV as a weaning strategy after a failure of a spontaneous breathing trial; as a result, NIV reduced mortality, minimized ventilator-associated pneumonia, and shortened length of hospital stay. Further studies will be needed to assess the real impact of NIV on other form of respiratory failure.\Another major clinical problem in ICU is the post extubation failure. In fact, more than 15% of patients need to be reintubated within the first 72 hours. After a successful weaning trial,their prognosis is poor with an hospital mortality that exceeds 30%_40%. Randomized controlled studies have demonstrated that when NIV is applied to treat an overt episode of post extubation respiratory failure, it can be indeed harmful perhaps due to the delay of reintubation. Conversely, promising results were obtained using NIV to prevent the development of a post extubation failure in patients considered at high risk, particularly in those affected by hypercapnia at the time of a successful T-piece trial

    Hemoptysis due to a large endobronchial mass successful regression after the use of high flow nasal cannula

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    In recent years, high flow nasal cannula is being increasingly used. Most studies showed positive results when used in hypoxaemic respiratory failure. Its use in a patient with a large endobronchial mass has not yet being described. We report a patient who presented with hemoptysis and hypoxaemic respiratory failure second to a large mass obstructing the right main bronchus. High flow oxygen via nasal cannula was initiated with a quick improvement of the hemoptysis and the oxygen saturation. Thus, allowing the patient to be rapidly stabilized

    Long-term home noninvasive ventilation (LTHNIV) in restrictive thoracic diseases: The Italian snapshot

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    Long-term home noninvasive ventilation (LTHNIV) in restrictive thoracic diseases was explored via the recently published international REINVENT ERS survey. The Italian subset of respondents (ITA-r), the highest above all participating nations, was analyzed and compared to non-Italian respondents (NO-ITA-r). The ITA-r represented 20% of the total answers examined. Ninety-four percent were physicians, whose half worked in a respiratory ICU (RICU). ITA-r mainly worked in community hospitals vs NO-ITA-r who are largely affiliated with university hospitals (p<0.0001). Amyotrophic lateral sclerosis (ALS) was considered the most common medical condition leading to NIV indication by both ITA-r and NO-ITA-r (93% vs 78%, p>0.5). A greater proportion of ITA-r considered MIP/MEP the most important test for NIV initiation as compared to NO-IRA-r (p<0.05). There was no significant difference for both ITA-r and NO-ITA-r as regards the other questions. This study illustrates Italian LTHNIV practices in patients with NMD and it shows some important differences with the other countries' practices but agreement in terms of goals to achieve, reasons to initiate NIV, and practices among the two communities

    Non-invasive ventilation in chronic obstructive pulmonary disease patients: Helmet versus facial mask

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    RATIONALE: The helmet is a new interface with the potential of increasing the success rate of non-invasive ventilation by improving tolerance. OBJECTIVES: To perform a physiological comparison between the helmet and the conventional facial mask in delivering non-invasive ventilation in hypercapnic patients with chronic obstructive pulmonary disease. METHODS: Prospective, controlled, randomized study with cross-over design. In 10 patients we evaluated gas exchange, inspiratory effort, patient-ventilator synchrony and patient tolerance after 30 min of non-invasive ventilation delivered either by helmet or facial mask; both trials were preceded by periods of spontaneous unassisted breathing. MEASUREMENTS: Arterial blood gases, inspiratory effort, duration of diaphragm contraction and ventilator assistance, effort-to-support delays (at the beginning and at the end of inspiration), number of ineffective efforts, and patient comfort. MAIN RESULTS: Non-invasive ventilation improved gas exchange (p<0.05) and inspiratory effort (p<0.01) with both interfaces. The helmet, however, was less efficient than the mask in reducing inspiratory effort (p<0.05) and worsened the patient-ventilator synchrony, as indicated by the longer delays to trigger on (p<0.05) and cycle off (p<0.05) the mechanical assistance and by the number of ineffective efforts (p<0.005). Patient comfort was no different with the two interfaces. CONCLUSIONS: Helmet and facial mask were equally tolerated and both were effective in ameliorating gas exchange and decreasing inspiratory effort. The helmet, however, was less efficient in decreasing inspiratory effort and worsened the patient-ventilator interaction

    Noninvasive ventilation to prevent respiratory failure after extubation in high-risk patients

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    Compared with standard medical therapy (SMT), noninvasive ventilation (NIV) does not reduce the need for reintubation in unselected patients who develop respiratory failure after extubation. The goal of this study was to assess whether early application of NIV, immediately after extubation, is effective in preventing postextubation respiratory failure in an at-risk population
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