Emerging insights into atypical B cells in pediatric chronic infectious diseases and immune system disorders: T(o)-bet on control of B-cell immune activation

: repetitive or persistent cellular stimulation in vivo has been associated with the development of a heterogeneous B-cell population that exhibits a distinctive phenotype and, in addition to classical B-cell markers, often expresses the transcription factor T-bet and myeloid marker CD11c. research suggests that this atypical population consists of B cells with distinct B-cell receptor specificities capable of binding the antigens responsible for their development. the expansion of this population occurs in the presence of chronic inflammatory conditions and autoimmune diseases where different nomenclatures have been used to describe them. however, as a result of the diverse contexts in which they have been investigated, these cells have remained largely enigmatic, with much ambiguity remaining regarding their phenotype and function in humoral immune response as well as their role in autoimmunity. atypical B cells have garnered considerable interest because of their ability to produce specific antibodies and/or autoantibodies and because of their association with key disease manifestations. although they have been widely described in the context of adults, little information is present for children. Therefore, the aim of this narrative review is to describe the characteristics of this population, suggest their function in pediatric immune-related diseases and chronic infections, and explore their potential therapeutic avenues

Cybersecurity Impacts of the Covid-19 Pandemic in Italy

The Covid-19 pandemic has pushed companies to the extensive use of digital services, to implement home working and provide online services to people in lockdown. As a consequence, it is interesting to study how this has affected the number, kind and distribution of cybersecurity attacks. This paper gives an empirical evaluation of the cybersecurity attacks at the beginning of the Covid-19 pandemic in Italy, based on data collected from the questionnaires of the annual Digital Attacks Observatory. It shows that the overall number of attacks has not increased, but attacks have affected smaller companies than before. This can be explained with the fact that the Italian industrial scenario is mostly populated by small and medium enterprises, that have been obliged to a quick reconversion of their IT systems and typically lack the necessary cybersecurity culture

Modelling complex bimolecular reactions in a condensed phase: the case of phosphodiester hydrolysis

Background: the theoretical modelling of reactions occurring in liquid phase is a research line of primary importance both in theoretical-computational chemistry and in the context of organic and biological chemistry. Here we present the modelling of the kinetics of the hydroxide-promoted hydrolysis of phosphoric diesters. Method: the theoretical-computational procedure involves a hybrid quantum/classical approach based on the perturbed matrix method (PMM) in conjunction with molecular mechanics. Results: the presented study reproduces the experimental data both in the rate constants and in the mechanistic aspects (C-O bond vs. O-P bond reactivity). The study suggests that the basic hydrolysis of phosphodiesters occurs through a concerted ANDN mechanism, with no formation of penta-coordinated species as reaction intermediates. Conclusions: the presented approach, despite the approximations, is potentially applicable to a large number of bimolecular transformations in solution and therefore leads the way to a fast and general method to predict the rate constants and reactivities/selectivities in complex environments

Synthesis and anti-picornavirus activity of homo-isoflavonoids

Substituted homo-isoflavonoids were synthesized in order to study their in vitro anti-picornavirus activity. The maximum non-toxic concentration of the compounds for susceptible cells (HeLa) was determined, and the ability of non-cytotoxic concentrations to interfere with plaque formation by human rhinovirus (HRV) 1B and 14 and poliovirus (PV) 2 was examined. All the tested compounds were weakly effective against PV-2, while they exhibited a variable degree of activity against HRV-1B and -14 infection. Serotype 1B was much more sensitive than 14 to the action of the compounds, and the presence of one or more chlorine atoms increased the antiviral effect in all homo-isoflavonoids tested, confirming the positive influence of this substituent on activity

Novel protein-truncating variant in the APOB gene may protect from coronary artery disease and adverse cardiovascular events

Background and aims: Genetic testing is still rarely used for the diagnosis of dyslipidemia, even though gene variants determining plasma lipids levels are not uncommon.Methods: Starting from a a pilot-analysis of targeted Next Generation Sequencing (NGS) of 5 genes related to familial hypercholesterolemia (LDLR, APOB, PCSK9, HMGCR, APOE) within a cardiovascular cohort in subjects with extreme plasma concentrations of low-density lipoprotein (LDL) cholesterol, we discovered and characterized a novel point mutation in the APOB gene, which was associated with very low levels of apolipoprotein B (ApoB) and LDL cholesterol.Results: APOB c.6943 G > T induces a premature stop codon at the level of exon 26 in the APOB gene and generates a protein which has the 51% of the mass of the wild type ApoB-10 0 (ApoB-51), with a trun-cation at the level of residue 2315. The premature stop codon occurs after the one needed for the synthesis of ApoB-4 8, allowing chylomicron production at intestinal level and thus avoiding potential nutritional impairments. The heterozygous carrier of APOB c.6943G > T, despite a very high-risk profile encompassing all the traditional risk factors except for dyslipidemia, had normal coronary arteries by angiography and did not report any major adverse cardiovascular event during a 20-years follow-up, thereby obtaining advantage from the gene variant as regards protection against atherosclerosis, apparently without any metabolic retaliation.Conclusions: Our data support the use of targeted NGS in well-characterized clinical settings, as well as they indicate that.a partial block of ApoB production may be well tolerated and improve cardiovascular outcomes. (C) 2022 The Authors. Published by Elsevier B.V

Confronto fra sistemi foraggero-zootecnici per ovini da latte in ambiente asciutto: nota II: risultati zootecnici del triennio 1990-93

Three 5 ha dairy sheep systems with different input levels were compared during three years. The percentage oftotal system area conventionally cultivated each year was equal to 80%, 20% and 30% in systems C, EPM and EPMP respectively. Each system was rotationally grazed by 30 dairy ewes. Milk yield was significantly higher in EPM group, the total annual yield for each system being equal to 1.10 (C), 1.33 (EPM) and 1.17 (EPMP) t ha-1 of milk. Hay consumption tended to be lower in the system EPM in comparison with system C and EPMP averaging to 0.30 (EPM), 0.34 (C) and 0.36 t ha-1 of DM (EPMP). On the basis of overall results, the EPM system showed the best performances. Nel triennio 1990-93 sono stati confrontati tre sistemi foraggero zootecnici C (Cereali), EPM (Erbaio Pascolo Migliorato) e EPMP (Erbaio Pascolo Migliorato Prati), caratterizzati da una percentuale di SAU coltivata rispettivamente pari all'80, 20 e 30%. Ciascun sistema è stato pascolato da 30 pecore da latte di razza Sarda. La produzione di latte è stata significativamente più elevata nel sistema EPM e la produzione totale media annua è stata di 1,10 (C), 1,33 (EPM) e 1,17 (EPMP) t ha-1. Il consumo di fieno è stato in media 0,30 (EPM), 0,34 (C) e 0,36 (EPMP) t ha-1 di sostanza secca. In conclusione il sistema EPM, fra quelli a confronto, ha mostrato i migliori risultati sia in termini di produzione di latte e di carne e nel contempo di un minore consumo di supplementi

Not Just Arterial Damage: Increased Incidence of Venous Thromboembolic Events in Cardiovascular Patients With Elevated Plasma Levels of Apolipoprotein CIII

Background Apolipoprotein CIII (apo CIII ) is a crucial player in triglyceride-rich lipoprotein metabolism, but may also act pleiotropically, provoking inflammatory responses and stimulating coagulation. Elevated apo CIII plasma levels have been associated with increased activity of coagulation factors. Since these features of prothrombotic diathesis are linked with venous thromboembolism ( VTE ), we hypothesized that apo CIII plays a role in VTE . Methods and Results We recorded nonfatal VTE events in 1020 patients (age 63.3\ub111.4 years; 29.1% women) with or without coronary artery disease (79.1% with coronary artery disease and 20.9% without coronary artery disease) during a long follow-up. Complete plasma lipid and apolipoproteins were available for all patients. Forty-five patients (4.4%) experienced nonfatal VTE events during a median follow-up period of 144 months. Apo CIII plasma concentration at enrollment was higher in patients with VTE compared with patients without VTE (12.2 [95% CI, 11.10-13.5] mg/dL vs 10.6 [95% CI, 10.4-10.9] mg/dL, respectively; P=0.011). Patients with apo CIII levels above the median value (10.6 mg/dL) exhibited an increased risk of VTE (incidence rate, 6.0 [95% CI , 4.0-8.0] vs 1.8 [95% CI, 0.7-2.9] VTE events/1000 person-years; unadjusted hazard ratio [ HR ], 3.42 [95% CI , 1.73-6.75]; P<0.001). This association was confirmed after adjustment for sex, age, coronary artery disease diagnosis, body mass index, hypertension, and anticoagulant treatment at enrollment ( HR , 2.66; 95% CI , 1.31-5.37 [ P=0.007]), with inclusion of lipid parameters in the Cox model (HR, 3.74; 95% CI , 1.24-11.33 [ P=0.019]), and even with exclusion of patients who died at follow-up ( HR, 3.92; 95% CI , 1.68-9.14 [ P=0.002]) or patients taking anticoagulants ( HR , 3.39; 95% CI , 1.72-6.69 [ P<0.001]). Conclusions Our results suggest that high plasma apo CIII concentrations may predict an increased risk of VTE in patients with cardiovascular disease

Hidden Comorbidities in Asthma: A Perspective for a Personalized Approach

: Bronchial asthma is the most frequent inflammatory non-communicable condition affecting the airways worldwide. It is commonly associated with concomitant conditions, which substantially contribute to its burden, whether they involve the lung or other districts. The present review aims at providing an overview of the recent acquisitions in terms of asthma concomitant systemic conditions, besides the commonly known respiratory comorbidities. The most recent research has highlighted a number of pathobiological interactions between asthma and other organs in the view of a shared immunological background underling different diseases. A bi-univocal relationship between asthma and common conditions, including cardiovascular, metabolic or neurodegenerative diseases, as well as rare disorders such as sickle cell disease, α1-Antitrypsin deficiency and immunologic conditions with hyper-eosinophilia, should be considered and explored, in terms of diagnostic work-up and long-term assessment of asthma patients. The relevance of that acquisition is of utmost importance in the management of asthma patients and paves the way to a new approach in the light of a personalized medicine perspective, besides targeted therapies

ERMES: Design and preliminary simulations for an autonomous docking manoeuvre

In the last decades, small satellites have played an important role in space missions. Due to their reduced dimension and costs, they became affordable to smaller companies and research laboratories to conduct scientific experiments and technological demonstrations in space. In addition, the number of these satellites has considerably increased due to their wide use in technological, scientific and commercial domains. In this scenario, autonomous architectures, as well as miniaturized mechanical subsystems for small satellites, are continuously investigated. Experimental Rendezvous in Microgravity Environment Study (ERMES) is a student project that focuses on the simulation of an autonomous docking manoeuvres between two CubeSats mock-ups equipped with miniaturized Guidance Navigation and Control systems and mechanical docking interfaces. ERMES aims to integrate different subsystems for autonomous docking, to increase the Technology Readiness Level and to study possible applications for in-orbit servicing. This paper deals with the design and development of the tests for autonomous docking manoeuvres between two CubeSats mock-ups to be performed in a reduced-gravity environment during a parabolic flight. A Target-Chaser configuration has been selected, where the Chaser is fully active and the Target is cooperative. The Chaser is equipped with a miniaturized cold gas propulsion system with eight thrusters to control its attitude and position; in contrast, the Target has a set of three reaction wheels to control only its attitude. The tested miniaturized mechanical docking interfaces employs a probe-drogue configuration. The most demanding aspect of the development phase will be the dedicated software for the proximity navigation. The reduced-gravity conditions will be achieved during a campaign of parabolic flights thanks to the participation to the European Space Agency “Fly Your Thesis!” programme 2022

Case Report: Microangiopathic Hemolytic Anemia With Normal ADAMTS13 Activity

Thrombotic microangiopathies (TMAs) include a heterogeneous group of diseases characterized by abnormalities in the vessel walls of arterioles and capillaries resulting in microvascular thrombosis that typically presents with a microangiopathic hemolytic anemia (MAHA) and severe thrombocytopenia. We describe here the case of an 82-year-old woman, who came to our attention for a clinical condition consistent with thrombotic microangiopathy. Even if initially highly suggestive for a thrombotic thrombocytopenic purpura (TTP), the elevated ADAMTS13 activity together with the alteration of the main coagulation parameters (D-dimer elevation, fibrinogen consumption, slightly prolonged prothrombin time), induced us to consider several other diseases in the differential diagnostic process. The case evolved toward a suspected overlapped secondary hemophagocytic syndrome, though the hyperferritinemia was finally interpreted within the frame of a cytokine storm. After a complex diagnostic workup, the clinical and biochemical parameters guided us toward the diagnosis of a cancer-related microangiopathic hemolytic anemia (CR-MAHA) secondary to a relapsing breast cancer with multiple metastatic localizations. Prednisone 1 mg/kg body weight was started, and several units of fresh frozen plasma were infused, obtaining a good control of the hemolysis. No specific oncological therapies were, however, possible, due to the older age and the critically compromised general condition of the patient; therefore, after clinical stabilization, the patient was discharged for treatment in a palliative care Hospital