Un client web EPP per la Regione Toscana

L\u27Istituto di Informatica e Telematica del CNR di Pisa (IIT-CNR) gestisce il Registro del country code Top Level Domain .it (Registro .it). Nel corso del 2009, il Registro .it ha attivato un nuovo sistema di registrazione, denominato "sistema sincrono", basato sul protocollo di comunicazione EPP (Extensible Provisioning Protocol). Al fine di supportare la Regione Toscana nell\u27evoluzione dei propri sistemi di gestione dei domini, conseguentemente al passaggio dal vecchio sistema asincrono al nuovo sistema sincrono, lo IIT-CNR, sulla base di una convenzione tra i due enti, ha fornito il supporto tecnico per la progettazione e realizzazione di un\u27interfaccia client web EPP che disponesse delle funzionalit? necessarie alla registrazione e al mantenimento dei nomi a dominio nel .it in modalit? sincrona. Il client web ? stato implementato con un\u27applicazione J2EE da deployare su un\u27opportuna istanza dell\u27application server JBoss

Neurologic and Psychiatric Manifestations of Bradykinin-Mediated Angioedema: Old and New Challenges

Neurologic manifestations have been occasionally described in patients with bradykinin-mediated angioedema. The existing literature is currently limited to case series and case reports mainly described in the hereditary forms (HAE) concerning central nervous system (CNS) involvement. On the contrary, very little is known about peripheral and autonomic nervous system manifestations. CNS involvement in HAE may present with symptoms including severe headaches, visual disturbance, seizures, and various focal and generalized deficits. In addition, a stroke-like clinical picture may present in HAE patients. In turn, some drugs used in patients with cardiovascular and neurologic disorders, such as recombinant tissue plasminogen activator (r-tPA) and angiotensin-converting enzyme inhibitors (ACEI), may produce medication-induced angioedema, resulting in a diagnostic challenge. Finally, most patients with HAE have higher levels of psychological distress, anxiety, and depression. With this review, we aimed to provide an organized and detailed analysis of the existing literature on neurologic and psychiatric manifestations of HAE to shed light on these potentially invalidating symptoms and lay the foundation for further personalized diagnostic pathways for patients affected by this protean disease

Chromosome anomalies in bone marrow as primarycause of aplastic or hypoplastic conditions andperipheral cytopenia: disorders due to secondaryimpairment of RUNX1 and MPL genes

Background Chromosome changes in the bone marrow (BM) of patients with persistent cytopenia are often considered diagnostic for a myelodysplastic syndrome (MDS). Comprehensive cytogenetic evaluations may give evidence of the real pathogenetic role of these changes in cases with cytopenia without morphological signs of MDS. Results Chromosome anomalies were found in the BM of three patients, without any morphological evidence of MDS: 1) an acquired complex rearrangement of chromosome 21 in a boy with severe aplastic anaemia (SAA); the rearrangement caused the loss of exons 2-8 of the RUNX1 gene with subsequent hypoexpression. 2) a constitutional complex rearrangement of chromosome 21 in a girl with congenital thrombocytopenia; the rearrangement led to RUNX1 disruption and hypoexpression. 3) an acquired paracentric inversion of chromosome 1, in which two regions at the breakpoints were shown to be lost, in a boy with aplastic anaemia; the MPL gene, localized in chromosome 1 short arms was not mutated neither disrupted, but its expression was severely reduced: we postulate that the aplastic anaemia was due to position effects acting both in cis and in trans, and causing Congenital Amegakaryocytic Thrombocytopenia (CAMT). Conclusions A clonal anomaly in BM does not imply per se a diagnosis of MDS: a subgroup of BM hypoplastic disorders is directly due to chromosome structural anomalies with effects on specific genes, as was the case of RUNX1 and MPL in the patients here reported with diagnosis of SAA, thrombocytopenia, and CAMT. The anomaly may be either acquired or constitutional, and it may act by deletion/disruption of the gene, or by position effects. Full cytogenetic investigations, including a-CGH, should always be part of the diagnostic evaluation of patients with BM aplasia/hypoplasia and peripheral cytopenias

Cytokine dysregulation despite immunoglobulin replacement therapy in common variable immunodeficiency (CVID)

IntroductionCommon variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency. CVID is a heterogeneous disorder with a presumed multifactorial etiology. Intravenous or subcutaneous immunoglobulin replacement therapy (IgRT) can prevent severe infections but not underlying immune dysregulation.MethodsIn this study, we evaluated the serum concentrations of proinflammatory (TNF-α, IL-1β, IL-6) and immunoregulatory cytokines (IL-10), as well as lipopolysaccharide (LPS) and soluble CD14 (sCD14) in CVID individuals with infectious only (INF-CVID), and those with additional systemic autoimmune and inflammatory disorders (NIC-CVID), and healthy donors (HD).ResultsOur results showed increased serum concentrations of TNF-α, IL-1β, IL-6, and IL-10 in both INF-CVID and NIC-CVID subjects compared to HD. However, elevations of TNF-α, IL-1β, IL-6, and IL-10 were significantly more marked in NIC-CVID than INF-CVID. Additionally, LPS concentrations were increased only in NIC-CVID but not in INF-CVID compared to HD. Circulating levels of sCD14 were significantly increased in NIC-CVID compared to both INF-CVID and HD.DiscussionThese findings indicate persistent cytokine dysregulation despite IgRT in individuals with CVID. Moreover, the circulating cytokine profile reveals the heterogeneity of immune dysregulation in different subgroups of CVID subjects

Oxidized Low-Density Lipoproteins Induce Tissue Factor Expression in T-Lymphocytes via activation of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1

T-lymphocytes plays an important role in the pathophysiology of acute coronary syndromes (ACS). T-cell activation in vitro by pro-inflammatory cytokines may lead to functional Tissue Factor (TF) expression, indicating a possible contribution of immunity to thrombosis. Oxidized low-density lipoproteins (oxLDLs) are found abundantly in atherosclerotic plaques. We aimed at evaluating the effects of oxLDLs on TF expression in T-cells and the role of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)

Size-based effects of anthropogenic ultrafine particles on activation of human lung macrophages

The anthropogenic particulate matter (PM), suspended air dust that can be inhaled by humans and deposited in the lungs, is one of the main pollutants in the industrialized cities atmosphere. Recent studies have shown that PM has adverse effects on respiratory diseases. These effects are mainly due to the ultrafine particles (PM0.1, PM < 100 nm), which, thanks to their PM size, are efficiently deposited in nasal, tracheobronchial, and alveolar regions. Pulmonary macrophages are a heterogeneous cell population distributed in different lung compartments, whose role in inflammatory response to injury is of particular relevance. In this study, we investigated the effect of PM0.1 on Human Lung Macrophages (HLMs) activation evaluated as proinflammatory cytokines and chemokine release, Reactive Oxygen Species (ROS) production and intracellular Ca2+concentration ([Ca2+]i). Furthermore, PM0.1, after removal of organic fraction, was fractionated in nanoparticles both smaller (NP20) and bigger (NP100) than 20 nm by a properlydeveloped analytical protocol, allowed isolating their individual contribution. Interestingly, while PM0.1 and NP20 induced stimulatory effects on HLM cytokines release, NP100 had not effect. In particular, PM0.1 induced IL-6, IL-1β, TNF-α, but not CXCL8, release from HLMs. Moreover, PM0.1, NP20 and NP100 did not induce β-glucuronidase release, a preformed mediator contained in HLMs. The long time necessary for cytokines release (18 h) suggested that PM0.1 and NP20 could induce ex-novo production of the tested mediators. Accordingly, after 6 h of incubation, PM0.1 and NP20 induced mRNA expression of IL-6, TNF-α and IL-1β. Moreover, NP20 induced ROS production and [Ca2+]i increase in a time-dependent manner, without producing cytotoxicity. Collectively, the present data highlight the main proinflammatory role of NP20 among PM fractions. This is particularly of concern because this fraction is not currently covered by legal limits as it is not easily measured at the exhausts by the available technical methodologies, suggesting that it is mandatory to search for new monitoring techniques and strategies for limiting NP20 formation

Epigenetics: an Opportunity to Shape Innate and Adaptive Immune Responses

Epigenetics connects genetic and environmental factors: it includes DNA methylation, histone post-translational modifications and the regulation of chromatin accessibility by non-coding RNAs, all of which control constitutive or inducible gene transcription. This plays a key role in harnessing the transcriptional programs of both innate and adaptive immune cells due to its plasticity and environmental-driven nature, piloting myeloid and lymphoid cell fate decision with no change in their genomic sequence. In particular, epigenetic marks at the site of lineage specific transcription factors and maintenance of cell type-specific epigenetic modifications, referred to as "epigenetic memory", dictate cell differentiation, cytokine production and functional capacity following repeated antigenic exposure in memory T cells. Moreover, metabolic and epigenetic reprogramming occurring during a primary innate immune response leads to enhanced responses to secondary challenges, a phenomenon known as "trained immunity". Here we discuss how stable and dynamic epigenetic states control immune cell identity and plasticity in physiological and pathological conditions. Dissecting the regulatory circuits of cell fate determination and maintenance is of paramount importance for understanding the delicate balance between immune cell activation and tolerance, in healthy conditions and in autoimmune diseases. This article is protected by copyright. All rights reserved

In-flight calibration system of imaging x-ray polarimetry explorer

The NASA/ASI Imaging X-ray Polarimetry Explorer, which will be launched in 2021, will be the first instrument to perform spatially resolved X-ray polarimetry on several astronomical sources in the 2-8 keV energy band. These measurements are made possible owing to the use of a gas pixel detector (GPD) at the focus of three X-ray telescopes. The GPD allows simultaneous measurements of the interaction point, energy, arrival time, and polarization angle of detected X-ray photons. The increase in sensitivity, achieved 40 years ago, for imaging and spectroscopy with the Einstein satellite will thus be extended to X-ray polarimetry for the first time. The characteristics of gas multiplication detectors are subject to changes over time. Because the GPD is a novel instrument, it is particularly important to verify its performance and stability during its mission lifetime. For this purpose, the spacecraft hosts a filter and calibration set (FCS), which includes both polarized and unpolarized calibration sources for performing in-flight calibration of the instruments. In this study, we present the design of the flight models of the FCS and the first measurements obtained using silicon drift detectors and CCD cameras, as well as those obtained in thermal vacuum with the flight units of the GPD. We show that the calibration sources successfully assess and verify the functionality of the GPD and validate its scientific results in orbit; this improves our knowledge of the behavior of these detectors in X-ray polarimetry

PixDD: a multi-pixel silicon drift detector for high-throughput spectral-timing studies

The Pixelated silicon Drift Detector (PixDD) is a two-dimensional multi-pixel X-ray sensor based on the technology of Silicon Drift Detectors, designed to solve the dead time and pile-up issues of photon-integrating imaging detectors. Read out by a two-dimensional self-triggering Application-Specific Integrated Circuit named RIGEL, to which the sensor is bump-bonded, it operates in the 0:5 — 15 keV energy range and is designed to achieve single-photon sensitivity and good spectroscopic capabilities even at room temperature or with mild cooling (< 150 eV resolution at 6 keV at 0 °C). The paper reports on the design and performance tests of the 128-pixel prototype of the fully integrated system

Complete atrioventricular canal

Complete atrioventricular canal (CAVC), also referred to as complete atrioventricular septal defect, is characterised by an ostium primum atrial septal defect, a common atrioventricular valve and a variable deficiency of the ventricular septum inflow. CAVC is an uncommon congenital heart disease, accounting for about 3% of cardiac malformations. Atrioventricular canal occurs in two out of every 10,000 live births. Both sexes are equally affected and a striking association with Down syndrome was found. Depending on the morphology of the superior leaflet of the common atrioventricular valve, 3 types of CAVC have been delineated (type A, B and C, according to Rastelli's classification). CAVC results in a significant interatrial and interventricular systemic-to-pulmonary shunt, thus inducing right ventricular pressure and volume overload and pulmonary hypertension. It becomes symptomatic in infancy due to congestive heart failure and failure to thrive. Diagnosis of CAVC might be suspected from electrocardiographic and chest X-ray findings. Echocardiography confirms it and gives anatomical details. Over time, pulmonary hypertension becomes irreversible, thus precluding the surgical therapy. This is the reason why cardiac catheterisation is not mandatory in infants (less than 6 months) but is indicated in older patients if irreversible pulmonary hypertension is suspected. Medical treatment (digitalis, diuretics, vasodilators) plays a role only as a bridge toward surgery, usually performed between the 3rd and 6th month of life