The Hepatitis C Virus Nonstructural Protein 2 (NS2): An Up-and-Coming Antiviral Drug Target

Infection with Hepatitis C Virus (HCV) continues to be a major global health problem. To overcome the limitations of current therapies using interferon-α in combination with ribavirin, there is a need to develop drugs that specifically block viral proteins. Highly efficient protease and polymerase inhibitors are currently undergoing clinical testing and will become available in the next few years. However, with resistance mutations emerging quickly, additional enzymatic activities or functions of HCV have to be targeted by novel compounds. One candidate molecule is the nonstructural protein 2 (NS2), which contains a proteolytic activity that is essential for viral RNA replication. In addition, NS2 is crucial for the assembly of progeny virions and modulates various cellular processes that interfere with viral replication. This review describes the functions of NS2 in the life cycle of HCV and highlights potential antiviral strategies involving NS2

Unstable pelvic fractures in women: implications on obstetric outcome

Purpose Obstetric outcomes in women following pelvic injuries requiring surgical fixation is not thoroughly known. We aimed to evaluate if radiographic measurements (RMs) can be used to provide information on delivery methods outcome after these injuries, and to evaluate if metal work removal is required prior to delivery. Method A retrospective study in a level 1 trauma centre of female patients with pelvic fractures treated operatively, aged 16–45 at the time of injury. Participants completed a questionnaire regarding their obstetric history. RM evaluating pelvic symmetry, displacement, and pelvimetry were conducted on postoperative radiographs and CT scans. Patients who gave birth after the injury were divided to two groups according to the delivery method: vaginal delivery (VD) and caesarean section (CS). These two groups RM were compared. Results Forty-four patients were included, comparison of the RM of patients who delivered by CS (9) and patients who had only VD (11) showed no significant difference between the groups. Two patients underwent a trial of VD who subsequently underwent urgent CS due to prolonged labour, their RM were below the average and their pelvimetry measurements were above the cut-off for CS recommendation. Eleven patients had uncomplicated VD, all had retained sacroiliac screws at the time of delivery and one patient had an anterior pubic plate. Conclusion Postoperative RM did not show an effect on delivery method of women after pelvic fracture fixation. A relatively high number of patients who underwent normal vaginal delivery had retained sacroiliac screws. These findings can form the foundation for larger cohort studies

A Meta-Analysis of the Existing Knowledge of Immunoreactivity against Hepatitis C Virus (HCV)

Approximately 3% of the world population is infected by HCV, which represents a major global health challenge. Almost 400 different scientific reports present immunological data related to T cell and antibody epitopes derived from HCV literature. Analysis of all HCV-related epitope hosted in the Immune Epitope Database (IEDB), a repository of freely accessible immune epitope data, revealed more than 1500 and 1900 distinct T cell and antibody epitopes, respectively. The inventory of all data revealed specific trends in terms of the host and the HCV genotypes from which sequences were derived. Upon further analysis we found that this large number of epitopes reflects overlapping structures, and homologous sequences derived from different HCV isolates. To access and visualize this information we developed a novel strategy that assembles large sets of epitope data, maps them onto reference genomes and displays the frequency of positive responses. Compilation of the HCV immune reactivity from hundreds of different studies, revealed a complex and thorough picture of HCV immune epitope data to date. The results pinpoint areas of more intense reactivity or research activities at the level of antibody, CD4 and CD8 responses for each of the individual HCV proteins. In general, the areas targeted by the different effector immune functions were distinct and antibody reactivity was positively correlated with hydrophilicity, while T cell reactivity correlated with hydrophobicity. At the sequence level, epitopes frequently recognized by both T cell and B cell correlated with low variability, and our analysis thus highlighted areas of potential interest for practical applications. The human reactivity was further analyzed to pinpoint differential patterns of reactivity associated with acute versus chronic infection, to reveal the apparent impact of glycosylation on T cell, but not antibody responses, and to highlight a paucity of studies involved antibody epitopes associated with virus neutralization

Biochemical aspects of nitric oxide synthase feedback regulation by nitric oxide

Nitric oxide (NO) is a small gas molecule derived from at least three isoforms of the enzyme termed nitric oxide synthase (NOS). More than 15 years ago, the question of feedback regulation of NOS activity and expression by its own product was raised. Since then, a number of trials have verified the existence of negative feedback loop both in vitro and in vivo. NO, whether released from exogenous donors or applied in authentic NO solution, is able to inhibit NOS activity and also intervenes in NOS expression processes by its effect on transcriptional nuclear factor NF-κB. The existence of negative feedback regulation of NOS may provide a powerful tool for experimental and clinical use, especially in inflammation, when massive NOS expression may be detrimental

Health Technology Assessment: a value-based tool for the evaluation of healthcare technologies. Reassessment of the cell-culture-derived quadrivalent influenza vaccine: Flucelvax Tetra® 2.0

1. Health Technology Assessment: strumento value‑based per la valutazione delle tecnologie sanitarie 2. Il burden dell'influenza stagionale in Italia 3. Epidemiologia dell’influenza stagionale in Italia 4. Vaccini antinfluenzali attualmente disponibili in Italia 5. Flucelvax Tetra®, il vaccino quadrivalente su coltura cellulare: una revisione sistematica e meta-analisi di immunogenicità, efficacia e sicurezza 6. Valutazione economica dell’introduzione del nuovo vaccino antinfluenzale quadrivalente da coltura cellulare nel contesto di cura italiano (update da nuova indicazione) 7. Aspetti organizzativi della vaccinazione antinfluenzale in Italia 8. Valutazione etica dell'introduzione del vaccino antinfluenzale quadrivalente da coltura cellulare 9. Il valore della vaccinazione antinfluenzale nel quadro più complesso della Value-Based Healthcare 10. Elelemnti chiave per il processo decisional

Harnessing collective intelligence for the future of learning – a co-constructed research and development agenda

Learning, defined as the process of constructing meaning and developing competencies to act on it, is instrumental in helping individuals, communities, and organizations tackle challenges. When these challenges increase in complexity and require domain knowledge from diverse areas of expertise, it becomes difficult for single individuals to address them. In this context, collective intelligence, a capacity of groups of people to act together and solve problems using their collective knowledge, becomes of great importance. Technologies are instrumental both to support and understand learning and collective intelligence, hence the need for innovations in the area of technologies that can support user needs to learn and tackle collective challenges. Use-inspired research is a fitting paradigm that spans applied solutions and scientific explanations of the processes of learning and collective intelligence, and that can improve the technologies that may support them. Although some conceptual and theoretical work explaining and linking learning with collective intelligence is emerging, technological infrastructures as well as methodologies that employ and evidence that support them are nascent. We convened a group of experts to create a middleground and engage with the priorities for use-inspired research. Here we detail directions and methods they put forward as most promising for advancing a scientific agenda around learning and collective intelligence