Churg-Strauss syndrome: outcome and long-term follow-up of 38 patients from a single Italian centre

Objective: This study was aimed at verifying any potential correlation between anti-myeloperoxidase antineutrophil cytoplasmic antibodies (ANCA-MPO) and clinical features and outcome indices in Churg-Strauss Syndrome (CSS). Methods: Thirhty-eight Churg-Strauss syndrome patients were selected from the medical records of all vasculitis patients attending the Rheumatology and Immunology Unit at the Department of Internal Medicine of the University of Pisa in the decades between 1989 and 2008. Data were analysed retrospectively. Statistical analyses of the results were carried out using the Mann-Whitney test to determine the correlations between the clinical and serological parameters. Qualitative variables were compared using contingency table analysis and Fisher's exact test. Results: ANCA-MPO were detected in15/38 (39%) patients. Positive ANCA status was associated with peripheral neuropathy (p=0.0006), whereas negative ANCA status was associated with lung involvement (p=0.002). Relapses were strongly associated with positive ANCA status (p=0.01) and with an increase in- or a reappearence of ANCA-MPO levels (p=0.006). Finally, ANCA-MPO were significantly associated with neurological damage (p=0.003). Conclusions: The presence or absence of ANCA-MPO identify different clinical subsets in CSS. Overall, ANCA-MPO appears as a useful tool in the monitoring of CSS and in particular a good predictor of CSS relapse

Arachidonic acid-evoked Ca^{2+} signals promote nitric oxide release and proliferation in human endothelial colony forming cells

Arachidonic acid (AA) stimulates endothelial cell (EC) proliferation through an increase in intracellular Ca^{2+} concentration ([Ca^{2+}]_{i}), that, in turn, promotes nitric oxide (NO) release. AA-evoked Ca^{2+} signals are mainly mediated by Transient Receptor Potential Vanilloid 4 (TRPV4) channels. Circulating endothelial colony forming cells (ECFCs) represent the only established precursors of ECs. In the present study, we, therefore, sought to elucidate whether AA promotes human ECFC (hECFC) proliferation through an increase in [Ca^{2+}]_{i} and the following activation of the endothelial NO synthase (eNOS). AA induced a dose-dependent [Ca^{2+}]_{i} raise that was mimicked by its non-metabolizable analogue eicosatetraynoic acid. AA-evoked Ca^{2+} signals required both intracellular Ca^{2+} release and external Ca^{2+} inflow. AA-induced Ca^{2+} release was mediated by inositol-1,4,5-trisphosphate receptors from the endoplasmic reticulum and by two pore channel 1 from the acidic stores of the endolysosomal system. AA-evoked Ca^{2+} entry was, in turn, mediated by TRPV4, while it did not involve store-operated Ca^{2+} entry. Moreover, AA caused an increase in NO levels which was blocked by preventing the concomitant increase in [Ca^{2+}]_{i} and by inhibiting eNOS activity with NG-nitro-l-arginine methyl ester (l-NAME). Finally, AA per se did not stimulate hECFC growth, but potentiated growth factors-induced hECFC proliferation in a Ca^{2+} - and NO-dependent manner. Therefore, AA-evoked Ca^{2+} signals emerge as an additional target to prevent cancer vascularisation, which may be sustained by ECFC recruitment

Upgraded Pulsating Heat Pipe Only For Space (U-Phos): Results of the 22nd Rexus Sounding Rocket Campaign

A large tube may still behave, to a certain extent, as a capillary in a micro-gravity environment. This very basic concept is here applied to a two-phase passive heat transfer devices in order to obtain a new family of hybrid wickless heat pipes. Indeed, a Loop Thermosyphon, which usually consists of a large tube, closed end to end in a loop, evacuated and partially filled with a working fluid and intrinsically gravity assisted, may become a capillary tube in space condition and turn its thermo-fluidic behavior into a so called Pulsating Heat Pipe (PHP), or better, a Space Pulsating Heat Pipe (SPHP). Since the objective of the present work is to experimentally demonstrate the feasibility of such a hybrid device, a SPHP has been designed, built, instrumented and tested both on ground and microgravity conditions on the 22nd ESA REXUS Sounding Rocket Campaign. Ground tests demonstrate that the device effectively work as a gravity assisted loop thermosyphon, whether the sounding rocket data clearly reveal a change in the thermal hydraulic behavior very similar to the PHP. Since a microgravity period of approximately 120s is not sufficient to reach a pseudo steady state regime, further investigation on a longer term weightless condition is mandatory

U-PHOS Project: Development of a Large Diameter Pulsating Heat Pipe Experiment on board REXUS 22

U-PHOS Project aims to analyse and characterise the behaviour of a large diameter Pulsating Heat Pipe (PHP) on board REXUS 22 sounding rocket. A PHP is a passive thermal control device consisting of a serpentine capillary tube, evacuated, partially filled with a working fluid and finally sealed. In this configuration, the liquid and vapour phases are randomly distributed in the form of liquid slugs and vapour plugs. The heat is efficiently transported by means of the self-sustained oscillatory fluid motion driven by the phase change phenomena. On ground conditions, a small diameter is required in order to obtain a confined slug flow regime. In milli-gravity conditions, buoyancy forces become less intense and the PHP diameter may be increased still maintaining the slug/plug flow configuration typical of the PHP operation. Consequently, the PHP heat power capability may be increased too. U-PHOS aims at proving that a Large Diameter PHP effectively works in milli-g conditions by characterizing its thermal response during a sounding rocket flight. The actual PHP tube is made of aluminum (3 mm inner diameter, filled with FC-72), heated at the evaporator by a compact electrical resistance, cooled at the condenser by a Phase Change Material (PCM) embedded in a metallic foam. The tube wall temperatures are recorded by means of Fibre Bragg Grating (FBG) sensors; the local fluid pressure is acquired by means of a pressure transducer. The present work intends to report the actual status of the project, focusing in particular on the experiment improvements with respect to the previous campaign

Early childhood pedagogies: spaces for young children to flourish

This paper introduces the Special Issue of Early Child Development and Care focused on Early Childhood Pedagogy. It opens by considering past and present discourses concerning early childhood pedagogy, and focus is given to established philosophical underpinnings in the field and their translation to contemporary guidance, alongside research and policy. It is argued that early childhood pedagogy is a contested, complex and diverse space, yet these factors are entirely appropriate for supporting young children to flourish as valued individuals in different contexts. Building on this argument, it is posited that it may be more appropriate to discuss early childhood pedagogies rather than early childhood pedagogy. The paper goes on to critique a range of established early childhood pedagogies, before introducing 18 papers from across the world that make exciting new contributions to the discourse. It is intended that this collection will inspire new debates and fresh endeavours concerning early childhood pedagogies

Serotonin depresses the after-hyperpolarization through the inhibition of the Na+/K+ electrogenic pump in T sensory neurones of the leech

In T sensory neurones of the leech, a train of impulses elicited by intracellular electrical stimulation leads to an after-hyperpolarization of up to 30 mV, mainly due to the activation of the electrogenic Na+/K+-ATPase but partly to a Ca2+-activated K+ conductance. It was found that serotonin reversibly reduced the amplitude of this after-hyperpolarization. We investigated the mechanism of action of serotonin and found: (1) after inhibition of the Ca2+-activated K+ conductance with BaCl2 or CdCl2, serotonin was still able to reduce the after-hyperpolarization; (2) when penetration of T cells with microelectrodes leaking sodium was preceded by serotonin perfusion of the ganglia, the normal hyper-polarization due to the activation of the electrogenic pump was converted to a depolarization; (3) after long-lasting perfusion with K+-free saline solution (which inhibits the Na+/K+ pump), the application of CsCl caused repolarization by reactivating the electrogenic ATPase; serotonin slowed and reduced this repolariz-ation; (4) serotonin potentiated the depolarization of T neurones caused by the inhibition of the Na + /K + pump following cooling of ganglia and depressed the hyperpolarization after rewarming to room temperature. These data taken together suggest that serotonin directly inhibits the Na+/K+ electrogenic pump