A review of the main genetic factors influencing the course of COVID-19 in Sardinia: the role of human leukocyte antigen-G

Introduction: A large number of risk and protective factors have been identified during the SARS-CoV-2 pandemic which may influence the outcome of COVID-19. Among these, recent studies have explored the role of HLA-G molecules and their immunomodulatory effects in COVID-19, but there are very few reports exploring the genetic basis of these manifestations. The present study aims to investigate how host genetic factors, including HLA-G gene polymorphisms and sHLA-G, can affect SARS-CoV-2 infection. Materials and Methods: We compared the immune-genetic and phenotypic characteristics between COVID-19 patients (n = 381) with varying degrees of severity of the disease and 420 healthy controls from Sardinia (Italy). Results: HLA-G locus analysis showed that the extended haplotype HLA-G*01:01:01:01/UTR-1 was more prevalent in both COVID-19 patients and controls. In particular, this extended haplotype was more common among patients with mild symptoms than those with severe symptoms [22.7% vs 15.7%, OR = 0.634 (95% CI 0.440 – 0.913); P = 0.016]. Furthermore, the most significant HLA-G 3’UTR polymorphism (rs371194629) shows that the HLA-G 3’UTR Del/Del genotype frequency decreases gradually from 27.6% in paucisymptomatic patients to 15.9% in patients with severe symptoms (X2 = 7.095, P = 0.029), reaching the lowest frequency (7.0%) in ICU patients (X2 = 11.257, P = 0.004). However, no significant differences were observed for the soluble HLA-G levels in patients and controls. Finally, we showed that SARS-CoV-2 infection in the Sardinian population is also influenced by other genetic factors such as β-thalassemia trait (rs11549407C>T in the HBB gene), KIR2DS2/HLA-C C1+ group combination and the HLA-B*58:01, C*07:01, DRB1*03:01 haplotype which exert a protective effect [P = 0.005, P = 0.001 and P = 0.026 respectively]. Conversely, the Neanderthal LZTFL1 gene variant (rs35044562A>G) shows a detrimental consequence on the disease course [P = 0.001]. However, by using a logistic regression model, HLA-G 3’UTR Del/Del genotype was independent from the other significant variables [ORM = 0.4 (95% CI 0.2 – 0.7), PM = 6.5 x 10-4]. Conclusion: Our results reveal novel genetic variants which could potentially serve as biomarkers for disease prognosis and treatment, highlighting the importance of considering genetic factors in the management of COVID-19 patients

Natural killer-cell immunoglobulin-like receptors trigger differences in immune response to SARS-CoV-2 infection

Background: The diversity in the clinical course of COVID-19 has been related to differences in innate and adaptative immune response mechanisms. Natural killer (NK) lymphocytes are critical protagonists of human host defense against viral infections. It would seem that reduced circulating levels of these cells have an impact on COVID-19 progression and severity. Their activity is strongly regulated by killer-cell immuno-globulin-like receptors (KIRs) expressed on the NK cell surface. The present study's focus was to investigate the impact of KIRs and their HLA Class I ligands on SARS-CoV-2 infection. Methods: KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 396 Sardinian patients with SARS-CoV-2 infection. Comparisons were made between 2 groups of patients divided according to disease severity: 240 patients were symptomatic or paucisymptomatic (Group A), 156 hospitalized patients had severe disease (Group S). The immunogenetic characteristics of patients were also compared to a population group of 400 individuals from the same geographical areas. Results: Substantial differences were obtained for KIR genes, KIR haplotypes and KIR-HLA ligand combinations when comparing patients of Group S to those of Group A. Patients in Group S had a statistically significant higher frequency of the KIR A/A haplotype compared to patients in Group A [34.6% vs 23.8%, OR = 1.7 (95% CI 1.1-2.6); P = 0.02, Pc = 0.04]. Moreover, the KIR2DS2/HLA C1 combination was poorly represented in the group of patients with severe symptoms compared to those of the asymptomatic-paucisymptomatic group [33.3% vs 50.0%, OR = 0.5 (95% CI 0.3-0.8), P = 0.001, Pc = 0.002]. Multivariate analysis confirmed that, regardless of the sex and age of the patients, the latter genetic variable correlated with a less severe disease course [ORM = 0.4 (95% CI 0.3-0.7), PM = 0.0005, PMC = 0.005]. Conclusions: The KIR2DS2/HLA C1 functional unit resulted to have a strong protective effect against the adverse outcomes of COVID-19. Combined to other well known factors such as advanced age, male sex and concomitant autoimmune diseases, this marker could prove to be highly informative of the disease course and thus enable the timely intervention needed to reduce the mortality associated with the severe forms of SARS-CoV-2 infection. However, larger studies in other populations as well as experimental functional studies will be needed to confirm our findings and further pursue the effect of KIR receptors on NK cell immune-mediated response to SARS-Cov-2 infection

Status of the High-Frequency Upgrade of the Sardinia Radio Telescope

The Sardinia Radio Telescope is going through a major upgrade aimed at observing the universe at up to 116 GHz. A budget of 18.700.000 E has been awarded to the Italian National Institute of Astrophysics to acquire new state-of-the-art receivers, back-end, and high-performance computing, to develop a sophisticated metrology system and to upgrade the infrastructure and laboratories. This contribution draws the status of the whole project at eight months from the end of the funding scheme planned for August 2022

The high-frequency upgrade of the Sardinia Radio Telescope

We present the status of the Sardinia Radio Telescope (SRT) and its forthcoming update planned in the next few years. The post-process scenario of the upgraded infrastructure will allow the national and international scientific community to use the SRT for the study of the Universe at high radio frequencies (up to 116 GHz), both in single dish and in interferometric mode. A telescope like SRT, operating at high frequencies, represents a unique resource for the scientific community. The telescope will be ideal for mapping quickly and with relatively high angular resolution extended radio emissions characterized by low surface brightness. It will also be essential for spectroscopic and polarimetric studies of both Galactic and extragalactic radio sources. With the use of the interferometric technique, SRT and the other Italian antennas (Medicina and Noto) will operate within the national and international radiotelescope network, allowing astronomers to obtain images of radio sources at very high angular resolution

I materiali costruttivi storici nel trattato di Vincenzo Scamozzi: dalle fonti al trattato: un itinerario di ricerca

Si è cercato di capire che cosa stava realmente dietro il lavoro dello Scamozzi, in che maniera questo fosse strutturato. Capire il tipo di sapere contenuto nella sua opera, da dove arrivi questo sapere e se il suo modo di trasmetterlo sia un modo efficace. Infine capire in che maniera organizza il suo sapere, che cosa mette di suo nelle notizie che ci fornisce e quali sono gli apporti delle fonti. Concludendo, se la maniera di trasmettere questo sapere arrivasse realmente al lettore

I materiali costruttivi storici nel trattato di Vincenzo Scamozzi: dalle fonti al trattato: un itinerario di ricerca

Si è cercato di capire che cosa stava realmente dietro il lavoro dello Scamozzi, in che maniera questo fosse strutturato. Capire il tipo di sapere contenuto nella sua opera, da dove arrivi questo sapere e se il suo modo di trasmetterlo sia un modo efficace. Infine capire in che maniera organizza il suo sapere, che cosa mette di suo nelle notizie che ci fornisce e quali sono gli apporti delle fonti. Concludendo, se la maniera di trasmettere questo sapere arrivasse realmente al lettore

I materiali costruttivi storici nel trattato di Vincenzo Scamozzi: dalle fonti al trattato: un itinerario di ricerca

Si è cercato di capire che cosa stava realmente dietro il lavoro dello Scamozzi, in che maniera questo fosse strutturato. Capire il tipo di sapere contenuto nella sua opera, da dove arrivi questo sapere e se il suo modo di trasmetterlo sia un modo efficace. Infine capire in che maniera organizza il suo sapere, che cosa mette di suo nelle notizie che ci fornisce e quali sono gli apporti delle fonti. Concludendo, se la maniera di trasmettere questo sapere arrivasse realmente al lettore

Linguistica generale

General Linguistics The aim of this handbook is to provide a general introduction to linguistics. Whilst aimed mainly at college students, it will also be of interest to anyone else approaching this complex subject for the first time. Designed primarily for training purposes, it sets out to provide a precise but comprehensible description of the concepts and methods used in analyzing verbal language and languages. The phenomena examined are presented using examples drawn both from Italian as well as from a wide variety of other languages, with each chapter looking at particular concepts or phenomena in some depth. The book opens with two introductory chapters: the first provides an overview of world languages and the criteria for their classification, while the second aims to classify linguistics in the context of semiotics (explaining basic concepts such as language, sign, communication, etc.). The following six chapters deal in detail with the traditional levels of linguistic analysis: phonetics, phonology, morphology, lexicon, semantics, syntax. The volume closes with two chapters devoted to pragmatics and sociolinguistics

Deep Infiltrating Endometriosis: Comparison Between 2-Dimensional Ultrasonography (US), 3-Dimensional US, and Magnetic Resonance Imaging

Objectives—To evaluate the diagnostic accuracy of 2-dimensional (2D) and 3dimensional (3D) transvaginal ultrasonography (US) in comparison with magnetic resonance imaging (MRI) for identification of deep infiltrating endometriosis. Methods—In this prospective observational study, 159 premenopausal women who underwent surgery for a clinical suspicion of deep infiltrating endometriosis were prospectively enrolled. All women underwent 2DUS, 3DUS, and MRI. The following 3 locations of deep endometriosis were considered: (1) intestinal; (2) other posterior lesions (retrocervical septum, rectovaginal septum, uterosacral ligaments, and vaginal fornix); and (3) anterior. The sensitivity, specificity, positive predictive value, and negative predictive value of 2D and 3D transvaginal US in comparison with MRI were determined. Results—Intestinal deep infiltrating endometriosis was identified by 2DUS in 56 of 66 patients, by 3DUS in 59 of 66, and by MRI in 61 of 66. A receiver operating characteristic curve analysis showed optimal results for 2DUS, 3DUS, and MRI (areas under the curve, 0.86, 0.915, and 0.935, respectively) with a statistically significant difference between 2DUS and MRI (P=.0103), even when the 95% confidence interval showed an overlap. Other posterior deep infiltrating endometriosis was identified by 2DUS in 55 of 75 patients, by 3DUS in 65 of 75, and by MRI in 66 of 75. A receiver operating characteristic curve analysis showed very good results for 2DUS, 3DUS, and MRI (areas under the curve, 0.801, 0.838, and 0.857) with no statistically significant differences. In the 12 women with deep infiltrating endometriosis in the anterior location, the nodules were correctly identified by 2DUS in 3 of 12 patients, by 3DUS in 5 of 12, and by MRI in 6 of 12. Conclusions—Our results seem to suggest that there is a statistically significant difference between 2DUS and MRI for the intestinal location of deep infiltrating endometriosis, whereas no differences were found among the techniques for the other locations