What do we learn from a Genome Wide Association Study performed on HIV-1 infected Long Term Non Progressors individuals?

International audiencePrevious Genome Wide Association Studies performed on Elite Controllers and control HIV-1 infected individuals have shown that the MHC locus is predominantly responsible for containing plasma viremia below a threshold of detection. Here we performed a GWAS on a cohort of 160 HIV-1 infected Caucasian Long Term Non Progressors (LTNP) from the EC-funded European-African ''GISHEAL'' Consortium in order to explore whether novel genetic factors could account for the LTNP phenotype (i.e. maintenance of CD4 T cell counts >500 cells/μl and good health conditions without therapy)

B-cell subset alterations and correlated factors in HIV-1 infection

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Definition of the Immune Parameters Related to COVID-19 Severity

A relevant portion of patients with disease caused by the severe acute respiratory syndrome coronavirus 2 (COVID-19) experience negative outcome, and several laboratory tests have been proposed to predict disease severity. Among others, dramatic changes in peripheral blood cells have been described. We developed and validated a laboratory score solely based on blood cell parameters to predict survival in hospitalized COVID-19 patients. We retrospectively analyzed 1,619 blood cell count from 226 consecutively hospitalized COVID-19 patients to select parameters for inclusion in a laboratory score predicting severity of disease and survival. The score was derived from lymphocyte- and granulocyte-associated parameters and validated on a separate cohort of 140 consecutive COVID-19 patients. Using ROC curve analysis, a best cutoff for score of 30.6 was derived, which was associated to an overall 82.0% sensitivity (95% CI: 78–84) and 82.5% specificity (95% CI: 80–84) for detecting outcome. The scoring trend effectively separated survivor and non-survivor groups, starting 2 weeks before the end of the hospitalization period. Patients’ score time points were also classified into mild, moderate, severe, and critical according to the symptomatic oxygen therapy administered. Fluctuations of the score should be recorded to highlight a favorable or unfortunate trend of the disease. The predictive score was found to reflect and anticipate the disease gravity, defined by the type of the oxygen support used, giving a proof of its clinical relevance. It offers a fast and reliable tool for supporting clinical decisions and, most important, triage in terms of not only prioritization but also allocation of limited medical resources, especially in the period when therapies are still symptomatic and many are under development. In fact, a prolonged and progressive increase of the score can suggest impaired chances of survival and/or an urgent need for intensive care unit admission

The Rheumatology drugs for COVID-19 management: Which and when?

Introduction: While waiting for the development of specific antiviral therapies and vaccines to effectively neutralize the SARS-CoV2, a relevant therapeutic strategy is to counteract the hyperinflammatory status, characterized by an increase mainly of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor (TNF)-α, which hallmarks the most severe clinical cases. 'Repurposing' immunomodulatory drugs and applying clinical management approved for rheumatic diseases represents a game-changer option. In this article, we will review the drugs that have indication in patients with COVID-19, including corticosteroids, antimalarials, anti-TNF, anti-IL-1, anti-IL-6, baricitinib, intravenous immunoglobulins, and colchicine. The PubMed, Medline, and Cochrane Library databases were searched for English-language papers concerning COVID-19 treatment published between January 2020 and October 2020. Results were summarized as a narrative review due to large heterogeneity among studies. In the absence of specific treatments, the use of immunomodulatory drugs could be advisable in severe COVID-19 patients, but clinical outcomes are still suboptimal. An early detection and treatment of the complications combined with a multidisciplinary approach could allow a better recovery of these patient

Astro MBSE: overview on requirement management approaches for astronomical instrumentation

Systems Engineering requires the involvement of different engineering disciplines: Software, Electronics, Mechanics (often nowadays together as Mechatronics), Optics etc. Astronomical Instrumentation is no exception to this. A critical point is the handling of the requirements, their tracing, flow down and the interaction with stakeholders (flow up) and subsystems (flow down) in order to have traceable and methodical evolution and management. In the Italian Astronomical Community, we are developing methodologies and tools to share the expertise in this field among the different projects. In this paper we will focus on the requirement management approach among different projects (ground and space based, …). The target and synthesis of tis work will be a support framework for the Requirement management of the Italian Astronomical Community (INAF) projects

Astro MBSE: model based system engineering synthesized for the Italian astronomical community

Systems Engineering requires the involvement of different engineering disciplines: Software, Electronics, Mechanics (often nowadays together as Mechatronics), Optics etc. Systems Engineering of Astronomical Instrumentation is no exception to this. A critical point is the handling of the different point of view introduced by these disciplines often related to different tools and cultures. Model Based Systems Engineering (MBSE) approach can help the Systems Engineer to always have a complete view of the full system. Moreover, in an ideal situation, all of the information resides in the model thus allowing different views of the System without having to resort to different sources of information, often outdated. In the real world, however, this does not happen because the different actors (Optical Designers, Mechanical Engineers, Astronomers etc.) should adopt the same language and this is clearly, at least nowadays and for the immediate future, close to impossible. In the Italian Astronomical Community, we are developing methodologies and tools to share the expertise in this field among the different projects. In this paper we present the status of this activity that aims to deliver to the community proper tools and template to enable a uniformed use of MBSE (friendly name Astro MBSE) among different projects (ground and space based, …). We will analyze here different software and different approaches. The target and synthesis of this work will be a support framework for the MBSE based system Engineering activity to the Italian Astronomical Community (INAF)

GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease—study protocol and preliminary results

Background: GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results. Methods: Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies. Results: Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed. Conclusion: An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy

Elderly HIV-positive women: A gender-based analysis from the Multicenter Italian \u201cGEPPO\u201d Cohort

BACKGROUND: HIV-positive patients are facing age-and disease-related comorbidities. Since gender differences in viro-immunological, clinical and therapeutic features have been described, aim of this analysis was to explore such differences in elderly HIV-positive females compared to males coming from the same cohort. DESIGN: Cross-sectional study. SETTING: Ten Infectious Diseases Center participating to a new multicenter Italian geriatric Cohort aiming at describing health transition over time in HIV-positive individuals. PARTICIPANTS: HIV-positive patients aged 6565 years old. MEASUREMENTS: We recorded clinical, viro-immunological and therapeutical data. RESULTS: We included 210 women (17%) out of 1237 patients. Compared to males, elderly females were less likely to present a HIV-RNA <50 copies/mL (74.3% vs. 81.8%, OR 0.64, 95%CI 0.44-0.93); they showed higher CD4+/CD8+ ratio (p = 0.016). Combined antiretroviral therapy (cART) strategies were similar between genders (p>0.05), although women were less likely to be treated with protease Inhibitors (PIs) (p = 0.05); specifically, in triple-drug regimens females received less PIs (28% vs 38% p = 0.022) and more integrase inhibitors (30% vs. 20% p = 0.012). Bone disease was more common in females (p<0.001) while males presented more frequently cardiovascular disease (CVD) (p<0.001). In females with bone disease, PIs and boosted regimens (38% vs. 53.7% p = 0.026 and 30.4 vs 44.0% p = 0.048 respectively) were prescribed less frequently. Polypharmacy was common and similar in both genders (20% vs. 22.8%, p = >0.05). A higher use of lipid-lowering drugs (20.5% vs. 14.8%, p = 0.04) was observed in females and yet they were less likely to receive anti-thrombotic agents (18.6% vs. 26.3%, p = 0.019) even when CVD was recorded (57.1% vs. 83.1%, p = 0.018). In multivariate analysis, we found that female gender was independently associated with a higher CD4+/CD8+ ratio but not with virological suppression. CONCLUSIONS: Elderly HIV-positive women display a worse virologic response despite a better immune reconstitution compared to males. The burden of comorbidities as well as the medications received (including cART) may slightly differ according to gender. Our data suggest that more efforts and focused interventions are needed in this population

Can You Activate Me? From Robots to Human Brain

L'efficacia dei robot sociali \ue8 stata ampiamente riconosciuta in diversi contesti della vita quotidiana degli umani, ma ancora poco si sa sulle aree cerebrali attivate osservando o interagendo con un robot. La ricerca che combina neuroscienze, scienze cognitive e robotica pu\uf2 fornire nuove intuizioni sia sul funzionamento del nostro cervello che sull'implementazione dei robot. Studi comportamentali sui robot sociali hanno dimostrato che la percezione sociale dei robot \ue8 influenzata da almeno due fattori: aspetto fisico e comportamento (Marchetti et al., 2018). Come possono le neuroscienze spiegare tali risultati? Ad oggi sono stati condotti studi attraverso l'utilizzo di tecniche sia EEG che fMRI per indagare le aree cerebrali coinvolte nell'interazione uomo-robot. Questi studi hanno affrontato principalmente le attivazioni cerebrali in risposta a paradigmi che coinvolgono o la performance di un'azione o la carica di una componente emotiva.The effectiveness of social robots has been widely recognized in different contexts of humans\u2019 daily life, but still little is known about the brain areas activated by observing or interacting with a robot. Research combining neuroscience, cognitive science and robotics can provide new insights into both the functioning of our brain and the implementation of robots. Behavioural studies on social robots have shown that the social perception of robots is influenced by at least two factors: physical appearance and behavior (Marchetti et al., 2018). How can neuroscience explain such findings? To date, studies have been conducted through the use of both EEG and fMRI techniques to investigate the brain areas involved in human-robot interaction. These studies have mainly addressed brain activations in response to paradigms involving either action performance or charged of an emotional component