The metabolic fingerprints of HCV and HBV infections studied by Nuclear Magnetic Resonance Spectroscopy

Abstract Few studies are available on metabolic changes in liver injuries and this is the first metabolomic study evaluating a group of HCV-positive patients, before and after viral eradication via DAA IFN-free regimens, using 1H-NMR to characterize and compare their serum fingerprints to naïve HBV-patients and healthy donors. The investigation clearly shows differences in the metabolomic profile of HCV patients before and after effective DAA treatment. Significant changes in metabolites levels in patients undergoing therapy suggest alterations in several metabolic pathways. It has been shown that 1H-NMR fingerprinting approach is an optimal technique in predicting the specific infection and the healthy status of studied subjects (Monte-Carlo cross validated accuracies: 86% in the HCV vs HBV model, 98.7% in the HCV vs HC model). Metabolite data collected support the hypothesis that the HCV virus induces glycolysis over oxidative phosphorylation in a similar manner to the Warburg effect in cancer, moreover our results have demonstrated a different action of the two viruses on cellular metabolism, corroborating the hypothesis that the metabolic perturbation on patients could be attributed to a direct role in viral infection. This metabolomic study has revealed some alteration in metabolites for the first time (2-oxoglutarate and 3-hydroxybutrate) concerning the HCV-infection model that could explain several extrahepatic manifestations associated with such an infection

COVID-19 vaccine immunogenicity in 16 patients with autoimmune systemic diseases. Lack of both humoral and cellular response to booster dose and ongoing disease modifying therapies

Patients with autoimmune systemic diseases (ASDs) represent a frail population during the ongoing COVID-19 pandemic. The vaccination is the major preventive measure; however, a significant number of ASD patients show an impaired production of anti-COVID-19 neutralizing antibodies (NAb), possibly counterbalanced by adequate T-cell response. The present study aimed at evaluating both humoral and cellular response to COVID-19 vaccine booster dose in this particular setting

Course and Lethality of SARS-CoV2 Epidemic in Nursing Homes after Vaccination in Florence, Italy

Evidence on the effectiveness of SARS-CoV-2 vaccines in nursing home (NHs) residents is limited. We examined the impact of the BNT162b2 mRNA SARS-CoV-2 vaccine on the course of the epidemic in NHs in the Florence Health District, Italy, before and after vaccination. Moreover, we assessed survival and hospitalization by vaccination status in SARS-CoV-2-positive cases occurring during the post-vaccination period. We calculated the weekly infection rates during the pre-vaccination (1 October–26 December 2020) and post-vaccination period (27 December 2020–31 March 2021). Cox analysis was used to analyze survival by vaccination status. The study involved 3730 residents (mean age 84, 69% female). Weekly infection rates fluctuated during the pre-vaccination period (1.8%–6.5%) and dropped to zero during the post-vaccination period. Nine unvaccinated (UN), 56 partially vaccinated (PV) and 35 fully vaccinated (FV) residents tested SARS-CoV-2+ during the post-vaccination period. FV showed significantly lower hospitalization and mortality rates than PV and UV (hospitalization: FV 3%, PV 14%, UV 33%; mortality: FV 6%, PV 18%, UV 56%). The death risk was 84% and 96% lower in PV (HR 0.157, 95%CI 0.049–0.491) and FV (HR 0.037, 95%CI 0.006–0.223) versus UV. SARS-CoV-2 vaccination was followed by a marked decline in infection rates and was associated with lower morbidity and mortality among infected NH residents

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

The Relevance of MicroRNAs in the Pathogenesis and Prognosis of HCV-Disease: The Emergent Role of miR-17-92 in Cryoglobulinemic Vasculitis

Hepatitis C virus (HCV) is a major public health problem. HCV is a hepatotropic and lymphotropic virus that leads to hepatocellular carcinoma (HCC) and lymphoproliferative disorders such as cryoglobulinemic vasculitis (CV) and non-Hodgkin’s lymphoma (NHL). The molecular mechanisms by which HCV induces these diseases are not fully understood. MicroRNAs (miRNAs) are small non-coding molecules that negatively regulate post-transcriptional gene expression by decreasing their target gene expression. We will attempt to summarize the current knowledge on the role of miRNAs in the HCV life cycle, HCV-related HCC, and lymphoproliferative disorders, focusing on both the functional effects of their deregulation as well as on their putative role as biomarkers, based on association analyses. We will also provide original new data regarding the miR 17-92 cluster in chronically infected HCV patients with and without lymphoproliferative disorders who underwent antiviral therapy. All of the cluster members were significantly upregulated in CV patients compared to patients without CV and significantly decreased in those who achieved vasculitis clinical remission after viral eradication. To conclude, miRNAs play an important role in HCV infection and related oncogenic processes, but their molecular pathways are not completely clear. In some cases, they may be potential therapeutic targets or non-invasive biomarkers of tumor progression

Role of Notch Receptors in Hematologic Malignancies

Notch receptors are single-pass transmembrane proteins that play a critical role in cell fate decisions and have been implicated in the regulation of many developmental processes. The human Notch family comprises of four receptors (Notch 1 to 4) and five ligands. Their signaling can regulate extremely basic cellular processes such as differentiation, proliferation and death. Notch is also involved in hematopoiesis and angiogenesis, and increasing evidence suggests that these genes are involved and frequently deregulated in several human malignancies, contributing to cell autonomous activities that may be either oncogenic or tumor suppressive. It was recently proposed that Notch signaling could play an active role in promoting and sustaining a broad spectrum of lymphoid malignancies as well as mutations in Notch family members that are present in several disorders of T- and B-cells, which could be responsible for altering the related signaling. Therefore, different Notch pathway molecules could be considered as potential therapeutic targets for hematological cancers. In this review, we will summarize and discuss compelling evidence pointing to Notch receptors as pleiotropic regulators of hematologic malignancies biology, first describing the physiological role of their signaling in T- and B-cell development and homeostasis, in order to fully understand the pathological alterations reported

Norms in MAS: Definitions and Related Concepts

In this chapter we provide an introductory presentation of normative multi-agent systems (nMAS). The key idea of the chapter is that any definition of nMAS should preliminarily clarify meaning, scope, and function of the concept of norm. On account of this idea, we focus on three definitions and some related requirements for nMAS. For each of such definitions we propose some guidelines for developing nMAS. Second, we suggest how to relate the concept of nMAS to different conceptions of norms and how norms can be used within the systems. Finally, we identify some specific issues that open research questions or that exhibit interesting overlaps with other disciplines

Vaccination with an innovative pressure-adjustable needle-free injection device

The Valery® is an innovative pressure-adjustable needle-free injection device (NFID). The objective of this study was to determine appropriate operation of this NFID for vaccination by evaluating the location of a vaccine in pigs after application. In a first trial, 4 groups of 12 pigs weighing respectively 4-5 kg, 6-7 kg, 8-10 kg and 15-20 kg were injected with a dye-labeled vaccine (Circovac, Merial), 0.5 mL in the neck using the NFID. Per group 3 pressure settings of the device were tested (A:low, B:medium or C:high), 4 pigs each. The pigs were immediately euthanized and frozen in vertical position (48 h; -20°C). Cross-sectional slices (3 per pig, 1 cm thick) at the injection sites were collected and digitalized by photography. The slices were checked on the penetration and dispersion of the vaccine by image analysis. In a second trial, 2 groups of 4 pigs weighing respectively 6-7 kg or 8-10 kg were used. Following cleaning and drying of the skin surface, the vaccine was injected using the NFID, in the neck. Before injection a piece of blotting paper in an empty screw cap tube had been weighed. Just after injection, the piece of paper was applied on the skin surface at the injection site for 2 secs , then stored in the screw cap container. The tube was weighed. The percentage of vaccine dose on the skin surface (SkQ) was calculated by difference. The depth of penetration of the vaccine whatever the weight group or pressure settings was 2.33±0.76 cm (n=48) with no difference observed between the pressure settings (A, n. 16, 2.14±0.77; B n. 16, 2.61±0.72; C, n. 16, 2.23±0.75 cm) or the weight group (4-5Kg, n.12, 2.18±0.4; 6-7Kg, n. 12, 2.40±0.24; 8-10Kg, n. 12, 1.89±0.56; 15-20Kg, n. 12, 2.83±1.18 cm) . The percentage of the vaccine present at the muscular level was varying between 70% (pressure A, 4-5kg) to 100% (pressure C, 6-7 Kg). In the different weight groups on average 87.0%. Setting B and C had the highest amount IM, resp.92.5 and 89.2%. The area of muscular distribution is the highest with pressure C compared to A and B (p=0.04). In trial 2,the SkQ was low whatever the operating pressure (A: 3.5±2.2%; B: 2.9±1.9%; C:1.5±0.4%) and the weight groups with a significant inverse relation between operating pressure and SkQ as well as a remarkable uniformity at the highest pressure setting. Under the conditions of the study, the Valery NFID was shown to deliver a 0.5 mL vaccine recommended for IM vaccination satisfactorily. It is advised to use pressure settings medium to high. The volume of vaccine spread on the skin was considered as acceptable. Vaccination compliance was thought not to be impacted by the NFID