Nanovectors Design for Theranostic Applications in Colorectal Cancer

Colorectal cancer (CRC) is a diffused disease with limited therapeutic options, none of which are often curative. Based on the molecular markers and targets expressed by the affected tissues, numerous novel approaches have been developed to study and treat this disease. In particular, the field of nanotechnology offers an astonishingly wide array of innovative nanovectors with high versatility and adaptability for both diagnosis and therapy (the so called \u201ctheranostic platforms\u201d). However, such complexity can make the selection of a specific nanocarrier model to study a perplexing endeavour for the biomedical scientist or clinician not familiar with this field of inquiry. This review offers a comprehensive overview of this wide body of knowledge, in order to outline the essential requirements for the clinical viability evaluation of a nanovector model in CRC. In particular, the differences among the foremost designs, their specific advantages, and technological caveats will be treated, never forgetting the ultimate endpoint for these systems development: the clinical practice

Regio- and stereoselective behavior of l-arabinal-derived vinyl epoxide in nucleophilic addition reactions. Comparison with conformationally restricted d-galactal-derived analogs

Abstract The regio- and stereoselectivity of the addition reactions of O-, C-, N-, and S-nucleophiles to l-arabinal-derived vinyl epoxide 2, the simplest non-conformationally restricted glycal-derived vinyl epoxide, has been examined and compared with the corresponding, conformationally restricted d-galactal-derived analogs 1β and 1β-Me. Results indicated that the 1,4-/1,2-regioselectivity ratio and the related syn-1,4-/anti-1,2-stereoselectivity observed in glycal-derived vinyl oxiranes is independent of the presence of substituents on the six-membered unsaturated ring, and the absence of conformational freedom: it depends only on the ability of the nucleophile to give a coordination process with the oxirane oxygen in the form of a hydrogen bond or through a coordinating cation

Delayed larval development in Anopheles mosquitoes deprived of Asaia bacterial symbionts

<p>Abstract</p> <p>Background</p> <p>In recent years, acetic acid bacteria have been shown to be frequently associated with insects, but knowledge on their biological role in the arthropod host is limited. The discovery that acetic acid bacteria of the genus <it>Asaia</it> are a main component of the microbiota of <it>Anopheles stephensi</it> makes this mosquito a useful model for studies on this novel group of symbionts. Here we present experimental results that provide a first evidence for a beneficial role of <it>Asaia</it> in <it>An. stephensi</it>.</p> <p>Results</p> <p>Larvae of <it>An. stephensi</it> at different stages were treated with rifampicin, an antibiotic effective on wild-type <it>Asaia</it> spp., and the effects on the larval development were evaluated. Larvae treated with the antibiotic showed a delay in the development and an asynchrony in the appearance of later instars. In larvae treated with rifampicin, but supplemented with a rifampicin-resistant mutant strain of <it>Asaia</it>, larval development was comparable to that of control larvae not exposed to the antibiotic. Analysis of the bacterial diversity of the three mosquito populations confirmed that the level of <it>Asaia</it> was strongly decreased in the antibiotic-treated larvae, since the symbiont was not detectable by PCR-DGGE (denaturing gradient gel electrophoresis), while <it>Asaia</it> was consistently found in insects supplemented with rifampicin plus the antibiotic-resistant mutant in the diet, and in those not exposed to the antibiotic.</p> <p>Conclusions</p> <p>The results here reported indicate that <it>Asaia</it> symbionts play a beneficial role in the normal development of <it>An. stephensi</it> larvae.</p

D'Annunzio, "il ferro di Erme e lo specchio di Atena"

A useful track to read "Il fuoco" is the one provided years later and implicitly by d'Annunzio himself in "Il compagno dagli occhi senza cigli". Following that trace and the epiphanic value of an object, the mirror, the essay proposes to outline, at least in one of its aspects, the path from reality to myth

Chimeric symbionts expressing a Wolbachia protein stimulate mosquito immunity and inhibit filarial parasite development

Wolbachia can reduce the capability of mosquitoes to transmit infectious diseases to humans and is currently exploited in campaigns for the control of arboviruses, like dengue and Zika. Under the assumption that Wolbachia-mediated activation of insect immunity plays a role in the reduction of mosquito vectorial capacity, we focused our attention on the Wolbachia surface protein (WSP), a potential inductor of innate immunity. We hypothesized that the heterologous expression of this protein in gut- and tissue-associated symbionts may reduce parasite transmission. We thus engineered the mosquito bacterial symbiont Asaia to express WSP (AsaiaWSP). AsaiaWSP induced activation of the host immune response in Aedes aegypti and Anopheles stephensi mosquitoes, and inhibited the development of the heartworm parasite Dirofilaria immitis in Ae. aegypti. These results consolidate previous evidence on the immune-stimulating property of WSP and make AsaiaWSP worth of further investigations as a potential tool for the control of mosquito-borne diseases

Performance Evaluation of Instrument Transformers in Power Quality Measurements: Activities and Results from 19NRM05 IT4PQ Project

The accuracy of power quality measurements relies on the use of common measurement procedures and traceable measurement systems, which necessarily include instrument transformers. The paper provides an overview of the progress achieved within the EU project 19NRM05 IT4PQ in developing the needed metrological framework, in terms of performance indexes to qualify the instrument transformers for PQ measurements, simplified testing procedures and set-ups, and quantification of their behaviour under multiple influence factor

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Next-Generation Sequencing in Post-mortem Genetic Testing of Young Sudden Cardiac Death Cases.

Sudden cardiac death (SCD) in the young (<40 years) occurs in the setting of a variety of rare inherited cardiac disorders and is a disastrous event for family members. Establishing the cause of SCD is important as it permits the pre-symptomatic identification of relatives at risk of SCD. Sudden arrhythmic death syndrome (SADS) is defined as SCD in the setting of negative autopsy findings and toxicological analysis. In such cases, reaching a diagnosis is even more challenging and post-mortem genetic testing can crucially contribute to the identification of the underlying cause of death. In this review, we will discuss the current achievements of "the molecular autopsy" in young SADS cases and provide an overview of key challenges in assessing pathogenicity (i.e., causality) of genetic variants identified through next-generation sequencing

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19)

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients