Management of synchronous operations on domain names of the ccTLD .it

This document details the operations needed for registering and maintaining domain names in accordance with synchronous registration. The synchronous system for registering and maintaining a domain name is provided by organizations (henceforth Registrars) that have an active contract with the Registry (henceforth .it Registry or Registry of the ccTLD.it), which is subordinate to an accreditation procedure. The Registrar will always be an intermediary with the Registry for all domain name registering and maintenance and also for correctly updating the Database of Assigned Names (DBNA) by using the synchronous registration system. The synchronous registration system allows Registrars to register and maintain domain names in realtime within the limits set out in the "Rules for assigning and managing domain names in the ccTLD.it" (hereafter, "Rules"). The synchronous system for registering and maintaining domain names of the .it Registry uses the protocol EPP (Extensible Provisioning Protocol) to comply with internationally accepted standards and to comply with decisions already made by other ccTLDs and gTLDs. EPP is a synchronous client-server protocol based on XML

Malocclusion and rhinitis in children: an easy-going relationship or a yet to be resolved paradox? A systematic literature revision

Objective: The relation between nasal flow and malocclusion represents a practical concern to pediatricians, otorhinolaryngologists, orthodontists, allergists and speech therapists. If naso-respiratory function may influence craniofacial growth is still debated. Chronic mouth-breathing is reported to be associated also with a characteristic pattern of dental occlusion. On the other hand, also malocclusion may reduce nasal air flows promoting nasal obstruction. Hereby, the aim of this review was to describe the relationship between rhinitis and malocclusion in children. Methods: An electronic search was conducted using online database including Pubmed, Web of Science, Google Scholar and Embase. All studies published through to January 30, 2017 investigating the prevalence of malocclusion in children and adolescents (aged 0-20 years) affected by rhinitis and the prevalence of rhinitis in children with malocclusion were included. The protocol was registered at PROSPERO - International prospective register of systematic reviews under CRD42016053619. Results: Ten studies with 2733 patients were included in the analysis. The prevalence of malocclusion in children with rhinitis was specified in four of the studies ranging from as high as 78.2% to as low as 3%. Two out of the studies reported the prevalence of rhinitis in children with malocclusion with a rate ranging from 59.2 to 76.4%. Conclusion: The results of this review underline the importance of the diagnosis and treatment of the nasal obstruction at an early age to prevent an altered facial growth, but the data currently available on this topic do not allow to establish a possible causal relationship between rhinitis and malocclusion

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

Effect of tungsten disulfide (WS_2) nanotubes on structural, morphological and mechanical properties of poly(L-lactide) (PLLA) films

Poly(L-lactide) (PLLA) is a semicrystalline, biocompatible and biodegradable polymer widely employed in many applications (food packaging, biomedical devices, drug delivery systems). This work deals with nanocomposites of PLLA and tungsten disulfide (WS_2) nanotubes (NTs) as a novel material to obtain thinner and stronger bioresorbable vascular scaffolds. We studied the influence of WS_2 NTs on the mechanical properties of PLLA-WS_2 films. Polarized optical microscopy reveals a high degree of orientation of the polymer molecules in stretched films that further increases with a post-stretching annealing treatment. At the same time, X-ray diffraction (XRD) and Raman spectroscopy confirm enhancement of the crystallinity induced by the WS_2 NTs

Effect of tungsten disulfide (WS_2) nanotubes on structural, morphological and mechanical properties of poly(L-lactide) (PLLA) films

Poly(L-lactide) (PLLA) is a semicrystalline, biocompatible and biodegradable polymer widely employed in many applications (food packaging, biomedical devices, drug delivery systems). This work deals with nanocomposites of PLLA and tungsten disulfide (WS_2) nanotubes (NTs) as a novel material to obtain thinner and stronger bioresorbable vascular scaffolds. We studied the influence of WS_2 NTs on the mechanical properties of PLLA-WS_2 films. Polarized optical microscopy reveals a high degree of orientation of the polymer molecules in stretched films that further increases with a post-stretching annealing treatment. At the same time, X-ray diffraction (XRD) and Raman spectroscopy confirm enhancement of the crystallinity induced by the WS_2 NTs

Oral Manifestations in Children and Young Adults with Down Syndrome: A Systematic Review of the Literature

Down syndrome (DS) is an autosomal disorder associated with mental and physical involvement. The typical craniofacial phenotype and the dental anomalies in DS subjects have been widely described, but a systematic report on the manifestations affecting the oral mucosae in children with DS is still lacking. This systematic review aimed to establish the prevalence of oral mucosal manifestations in children/young adults with DS. Pubmed, Web of Science, and Scopus were investigated in September 2020. Documents in English on DS children/young adults (up to 25 years) reporting oral mucosal findings were considered. Study quality was assessed with ROBIN-I. Of the 150 references retrieved, 14 studies were considered eligible. The risk of bias ranged from low to unclear. Fissured tongue appeared to increase with age and was more prevalent in DS children than in the general population. Lip fissures and cheilitis were heterogeneously reported. Candida spp. carriage with and without active candidiasis was more frequent in DS children/young adults than in controls. C. albicans was the most prevalent species. Few other oral mucosal conditions have been reported sporadically. The heterogeneity of the works revealed the need for more appropriate oral examination to intercept the oral manifestations of oral mucosa and prevent recurrent candidiasis

Pulmonary Safety Profile of Esc Peptides and Esc-Peptide-Loaded Poly(lactide-co-glycolide) Nanoparticles: A Promising Therapeutic Approach for Local Treatment of Lung Infectious Diseases

In recent years, we have discovered Esc(1-21) and its diastereomer (Esc peptides) as valuable candidates for the treatment of Pseudomonas lung infection, especially in patients with cystic fibrosis (CF). Furthermore, engineered poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) were revealed to be a promising pulmonary delivery system of antimicrobial peptides. However, the "ad hoc" development of novel therapeutics requires consideration of their stability, tolerability, and safety. Hence, by means of electrophysiology experiments and preclinical studies on healthy mice, we demonstrated that neither Esc peptides or Esc-peptide-loaded PLGA NPs significantly affect the integrity of the lung epithelium, nor change the global gene expression profile of lungs of treated animals compared to those of vehicle-treated animals. Noteworthy, the Esc diastereomer endowed with the highest antimicrobial activity did not provoke any pulmonary pro-inflammatory response, even at a concentration 15-fold higher than the efficacy dosage 24 h after administration in the free or encapsulated form. The therapeutic index was ≥70, and the peptide was found to remain available in the bronchoalveolar lavage of mice, after two days of incubation. Overall, these studies should open an avenue for a new up-and-coming pharmacological approach, likely based on inhalable peptide-loaded NPs, to address CF lung disease

Oxidative stress and gut-derived lipopolysaccharides in children affected by paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections

BACKGROUND: Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) identifies patients with acute onset of obsessive-compulsive and tic disorders. The objective of this study was to evaluate serum NOX2 levels, as well as 8-iso-prostaglandin F2α (8-iso-PGF2α) and lipopolysaccharide (LPS) of PANDAS patients. METHODS: In this study we wanted to compare serum levels of soluble NOX2-dp (sNOX-2-dp), iso-PGF2α and LPS in 60 consecutive subjects, including 30 children affected by PANDAS and 30 controls (CT) matched for age and gender. Serum zonulin was used as intestinal permeability assay. RESULTS: Compared with CT, PANDAS children had increased serum levels of sNOX-2-dp, 8-iso-PGF2α and LPS. Bivariate analysis showed that serum sNOX2-dp was significantly correlated with LPS (Rs = 0.359; p = 0.005), zonulin (Rs = 0.444; p < 0.001) and 8-iso-PGF2α (Rs = 0.704; p < 0.001). Serum LPS significantly correlated with zonulin (Rs = 0.610; p < 0.001), and 8-iso-PGF2α (Rs = 0.591; p = 0.001). Finally, a multiple linear regression analysis showed that serum 8-iso-PGF2α and zonulin were the only independent variables associated with sNOX2-dp (R2 = 68%). CONCLUSION: This study shows that children affected by PANDAS have high circulating levels of sNOX2-dp, isoprostanes and of LPS that could be involved in the process of neuroinflammation

Low grade endotoxemia and oxidative stress in offspring of patients with early myocardial infarction

Background and aims: Offspring of patients with early myocardial infarction are at higher cardiovascular risk, but the underlying physio-pathological mechanism is unclear. NADPH oxidase-type 2 (NOX-2) plays a pivotal role as mediator of oxidative stress and could be involved in activating platelets in these patients. Furthermore, altered intestinal permeability and serum lipopolysaccharide (LPS) could be a trigger to promote NOX-2 activation and platelet aggregation. This study aims to evaluate the behavior of low grade endotoxemia, oxidative stress and platelet activation in offspring of patients with early myocardial infarction. Methods: We enrolled, in a cross-sectional study, 46 offspring of patients with early myocardial infarction and 86 healthy subjects (HS). LPS levels and gut permeability (assessed by zonulin), oxidative stress (assessed by serum NOX-2-derived peptide (sNOX2-dp) release, hydrogen peroxide (H2O2) production and isoprostanes), serum nitric oxide (NO) bioavailability and platelet activation (by serum thromboxane B2 (TXB2) and soluble P-Selectin (sP-Selectin)) were analyzed. Results: Compared to HS, offspring of patients with early myocardial infarction had higher values of LPS, zonulin, serum isoprostanes, sNOX2-dp H2O2, TXB2, p-selectin and lower NO bioavailability. Logistic regression analysis showed that the variables associated with offspring of patients with early myocardial infarction were LPS, TXB2 and isoprostanes. The multiple linear regression analysis confirmed that serum NOX-2, isoprostanes, p-selectin and H2O2 levels were significantly associated to LPS. Furthermore, serum LPS, isoprostanes and TXB2 levels were significantly associated with sNOX-2-dp. Conclusions: Offspring of patients with early myocardial infarction have a low grade endotoxemia that could generate oxidative stress and platelet activation increasing their cardiovascular risk. Future studies are needed to understand the role of dysbiosis in this population

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