Ventricular pacemaker lead in the left hemithorax: Mechanisms and evidence-based management of a late-onset hazardous complication

Late-onset migration of pacing leads in the left hemithorax is a rare but potentially life-threatening complication. Radiological examinations are required to detect any involvement of either left ventricle or lung parenchyma, prompting immediate surgical extraction in this setting. Identification of high-risk patients is mandatory to prevent this complex iatrogenic complication

XIPE: the x-ray imaging polarimetry explorer

XIPE, the X-ray Imaging Polarimetry Explorer, is a mission dedicated to X-ray Astronomy. At the time of writing XIPE is in a competitive phase A as fourth medium size mission of ESA (M4). It promises to reopen the polarimetry window in high energy Astrophysics after more than 4 decades thanks to a detector that efficiently exploits the photoelectric effect and to X-ray optics with large effective area. XIPE uniqueness is time-spectrally-spatially- resolved X-ray polarimetry as a breakthrough in high energy astrophysics and fundamental physics. Indeed the payload consists of three Gas Pixel Detectors at the focus of three X-ray optics with a total effective area larger than one XMM mirror but with a low weight. The payload is compatible with the fairing of the Vega launcher. XIPE is designed as an observatory for X-ray astronomers with 75 % of the time dedicated to a Guest Observer competitive program and it is organized as a consortium across Europe with main contributions from Italy, Germany, Spain, United Kingdom, Poland, Sweden

Urging Europe to put non-adherence to inhaled respiratory medication higher on the policy agenda:A report from the First European Congress on Adherence to Therapy

Huge impact, but little attention: time to put respiratory non-adherence higher on Europe's policy agenda

HIV-1 Myristoylated Nef Treatment of Murine Microglial Cells Activates Inducible Nitric Oxide Synthase, NO₂ Production and Neurotoxic Activity

<div><p>Background</p><p>The potential role of the human immunodeficiency virus-1 (HIV-1) accessory protein Nef in the pathogenesis of neuroAIDS is still poorly understood. Nef is a molecular adapter that influences several cellular signal transduction events and membrane trafficking. In human macrophages, Nef expression induces the production of extracellular factors (<i>e</i>.<i>g</i>. pro-inflammatory chemokines and cytokines) and the recruitment of T cells, thus favoring their infection and its own transfer to uninfected cells via exosomes, cellular protrusions or cell-to-cell contacts. Murine cells are normally not permissive for HIV-1 but, in transgenic mice, Nef is a major disease determinant. Both in human and murine macrophages, myristoylated Nef (myr⁺Nef) treatment has been shown to activate NF-κB, MAP kinases and interferon responsive factor 3 (IRF-3), thereby inducing tyrosine phosphorylation of signal transducers and activator of transcription (STAT)-1, STAT-2 and STAT-3 through the production of proinflammatory factors.</p><p>Methodology/Principal Findings</p><p>We report that treatment of BV-2 murine microglial cells with myr⁺Nef leads to STAT-1, -2 and -3 tyrosine phosphorylation and upregulates the expression of inducible nitric oxide synthase (iNOS) with production of nitric oxide. We provide evidence that extracellular Nef regulates iNOS expression through NF-κB activation and, at least in part, interferon-β (IFNβ) release that acts in concert with Nef. All of these effects require both myristoylation and a highly conserved acidic cluster in the viral protein. Finally, we report that Nef induces the release of neurotoxic factors in the supernatants of microglial cells.</p><p>Conclusions</p><p>These results suggest a potential role of extracellular Nef in promoting neuronal injury in the murine model. They also indicate a possible interplay between Nef and host factors in the pathogenesis of neuroAIDS through the production of reactive nitrogen species in microglial cells.</p></div

Endovascular treatment for acute ischemic stroke

BACKGROUND: In patients with ischemic stroke, endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy. However, comparison of the clinical efficacy of the two approaches is needed. METHODS: We randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours after onset, to endovascular therapy (intraarterial thrombolysis with recombinant tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a combination of these approaches) or intravenous t-PA. Treatments were to be given as soon as possible after randomization. The primary outcome was survival free of disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability despite symptoms, and 6 death) at 3 months. RESULTS: A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous t-PA. The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P<0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence interval, 0.44 to 1.14; P=0.16). Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6% of the patients in each group, and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate. CONCLUSIONS: The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to standard treatment with intravenous t-PA. (Funded by the Italian Medicines Agency, ClinicalTrials.gov number, NCT00640367.)