101,956 research outputs found
Mitochondrial interactome: a focus on antiviral signaling pathways
No full textIn the last years, proteomics has represented a valuable approach to elucidate key aspects in the regulation of type I/III interferons (IFNs) and autophagy, two main processes involved in the response to viral infection, to unveil the molecular strategies that viruses have evolved to counteract these processes. Besides their main metabolic roles, mitochondria are well recognized as pivotal organelles in controlling signaling pathways essential to restrain viral infections. In particular, a major role in antiviral defense is played by mitochondrial antiviral signaling (MAVS) protein, an adaptor protein that coordinates the activation of IFN inducing pathways and autophagy at the mitochondrial level. Here, we provide an overview of how mass spectrometry-based studies of protein–protein interactions and post-translational modifications (PTMs) have fostered our understanding of the molecular mechanisms that control the mitochondria-mediated antiviral immunity. © Copyright © 2020 Refolo, Vescovo, Piacentini, Fimia and Ciccosanti
The concept of the mask and the doctor-patient relationship: insights from a (re)reading of Luigi Pirandello’s Six Characters in Search of an Author
No full textThe concept of the mask and the doctor-patient relationship: insights from a (re)reading of Luigi Pirandello's Six Characters in Search of an Author. The aim of this article is to explore the concept of the "mask" and its relevance within the doctor-patient relationship, as well as within the broader medical-scientific context. The primary reference for this analysis is Luigi Pirandello's work Six Characters in Search of an Author (1921), which embodies universal themes, supplemented by examples from figurative art. What emerges is the patient's necessity, utilizing artistic expression, to narrate their own experiences through a mask that serves as the vessel for their innermost emotions
Procedura per l'analisi della trasformazione territoriale
No full textDepositata domanda di brevetto nazionale presso l’Ufficio Italiano Brevetti e Marchi il 16.06.200
The impact of mevastatin on HCV replication and autophagy of non-transformed HCV replicon hepatocytes is influenced by the extracellular lipid uptake
No full textStatins efficiently inhibit cholesterol synthesis by blocking 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase in the mevalonate pathway. However, the effect of statins on intracellular cholesterol is partially counterbalanced by a consequent increased uptake of extracellular lipid sources. Hepatitis C virus (HCV) infection induces intracellular accumulation of cholesterol by promoting both new synthesis and uptake of circulating lipoproteins, which is required for HCV replication and release. Hepatocytes respond to the increase in intracellular cholesterol levels by inducing lipophagy, a selective type of autophagy mediating the degradation of lipid deposits within lysosomes. In a cellular system of HCV replication based on HuH7 hepatoma cells, statin treatment was shown to be sufficient to decrease intracellular cholesterol, which is accompanied by reduced HCV replication and decreased lipophagy, and has no apparent impact on endocytosis-mediated cholesterol uptake. To understand whether these results were influenced by an altered response of cholesterol influx in hepatoma cells, we analyzed the effect of statins in non-transformed murine hepatocytes (MMHD3) harboring subgenomic HCV replicons. Notably, we found that total amount of cholesterol is increased in MMHD3 cells upon mevastatin treatment, which is associated with increased HCV replication and lipophagy. Conversely, mevastatin is able to reduce cholesterol amounts only when cells are grown in the presence of delipidated serum to prevent extracellular lipid uptake. Under this condition, HCV replication is reduced and autophagy flux is severely impaired. Altogether, these results indicate that both de novo synthesis and extracellular uptake have to be targeted in non-transformed hepatocytes in order to decrease intracellular cholesterol levels and consequently limit HCV replication. Copyright © 2019 Vescovo, Refolo, Manuelli, Tisone, Piacentini and Fimia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
Lo sviluppo della consulenza etica nei processi di HTA: i dati preliminari dell'esperienza dell'Istituto di Bioetica dell'Università Cattolica del Sacro Cuore (Roma)
No full textTitolo: Lo sviluppo della consulenza etica nei processi di HTA: i dati preliminari dell'esperienza dell'Istituto di Bioetica dell'Università Cattolica del Sacro Cuore, Roma.
Autori: SACCHINI D*, REFOLO P*, MINACORI R*, DI PIETRO ML*, RICCIARDI G**, LA TORRE G***, CICCHETTI A§, MARCHETTI M§§, AND SPAGNOLO AG*
Affiliazioni: * Istituto di Bioetica, Università Cattolica del Sacro Cuore (UCSC), Roma; ** Istituto di Igiene, UCSC, Roma; *** Dipartimento di Medicina Sperimentale, Sezione di Igiene, Università di Roma "Sapienza" ; § Facoltà di Economia, UCSC, Roma; §§ Unità di Valutazione delle Tecnologie sanitarie, Policlinico Universitario "A. Gemelli", Roma
Testo
La valutazione etica in un rapporto di Health Technology Assessment (HTA) concerne sia le questioni etiche sollevate dalla stessa tecnologia sia le questioni etiche che riguardano il processo di HTA. Anche se elencata come uno degli obiettivi dell’HTA, in pratica l'integrazione di questa dimensione in un report di HTA è stata, in passato, limitata.
Nel contesto italiano, già caratterizzato da un certo ritardo nella diffusione della HTA in generale, l'Istituto di Bioetica dell'Università Cattolica del Sacro Cuore (UCSC), Roma, Italia, dal 2007 ha cercato di colmare - dal rispettivo punto di vista disciplinare - questa lacuna, cominciando a integrare le analisi etiche in report di HTA in una attività consulenziale, sulla scia di esperienze internazionali : in particolare nel Progetto EunetHTA (2006-2008) ed ,attualmente, nell’EUnetHTA Joint Action (2010-2012).
Il contributo intende mostrare i risultati preliminari dell’applicazione dell’expertise etico in diversi rapporti di HTA nel periodo 2007-2010. I seguenti elementi saranno presentati: 1. per descrivere le metodologie / procedure utilizzate per incorporare le analisi etiche in report di HTA; 2. per rivedere l'insieme delle questioni etiche trattate; 3. per visualizzare tutte le risorse coinvolte, 4. Analizzare, infine, le difficoltà sorte nella valutazione.
In conclusione, la prospettiva è quella di strutturare e consolidare procedure operative standard (SOPs) per la consulenza etica in un processo di HTA all’interno di un servizio consulenziale facente capo all’Istituto di Bioetica dell'UCSC
Characterization of HCV NS5A cellular interactors: role of MOB1B and LRPPRC in viral replication and assembly
No full textHepatitis C virus (HCV) is a hepatotropic positive-strand RNA virus which belongs to the Flaviviridae family. With almost 170 million people infected worldwide, HCV is a leading cause of chronic hepatitis, liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC) (Poynard, T., et al., 2003). Major improvements in patient treatment were achieved by the approval of the first direct acting antivirals (DAAs) in 2011 (Welsch, C., et al., 2012). Nonetheless, HCV variants resistant to DAAs may arise during treatment as well as a heavy burden of side effects, thus affecting therapy outcome. Cellular models of HCV replication and infection have recently allowed the characterization of molecular details of HCV life cycle. HCV RNA replication occurs in association with ER-like cellular membranes and requires several viral non-structural (NS) proteins including; NS3, NS4A, NS4B, NS5A, and NS5B, as well as host cell factors (Moriishi, K., and Matsuura, Y., 2003; Gosert R., et al., 2003). The site of virus assembly is yet unknown, but recent data haves proposed the recruitment of HCV RNA from the replicase complex to lipid droplets mediated by the HCV core and the non-structural proteins as an early event in virion assembly (Miyanari, Y., et al., 2007). Since HCV is a relative small virus, in order to accomplish genome replication and formation of new viral particle, it needs to interact with and subvert cellular machineries for its own purpose. A large number proteinprotein interaction has been described between HCV and host cells. However to date, most of them are only descriptive and their functions in HCV life cycle remain to be characterized (Tellinghuisen and Rice, 2002). NS5A is an important component of the viral replication complex and also participates to HCV particle assembly (Kim, S., et al., 2010). While no known enzymatic function has been ascribed to NS5A, it is known to interact with host cell proteins to affect a variety of processes, including innate immunity, host cell growth and proliferation (He, Y., et al., 2006). The molecular mechanism by which NS5A contributes to HCV life cycles remains largely uncharacterized. To get insights on NS5A function, we performed a screening to search for cellular proteins interacting with NS5A in HCV replicon cells, by means of a tandem affinity purification approach coupled to mass spectrometry (TAPMS/MS). NS5A protein complexes were isolated from HCV replicon cells, resolved by monodimensional gel (SDS-PAGE) and revealed by SYPRORuby staining. Protein bands were submitted to trypsin digestion and identified by MALDI-TOF/TOF mass spectrometry. 24 proteins were identified as NS5A binding proteins, including 14 factors not previously reported. Among them, we functionally characterized the interaction of NS5A with the kinase protein Mob1b, an important regulator of the Hippo pathway, and the mitochondrial protein LRPPRC. Here we show that individually knockdown of Mob1b and LRPPRC significantly reduces new HCV particle production and, to lesser extent, intracellular HCV RNA replication. We also found that Mob1b relocalizes to NS5A-positive structures and Mob1b downregulation results in a decrease in NS5A phosphorylation. Finally, we show that the Hippo signaling pathway is perturbed in HCV replicon cells, as indicated by the increased nuclear localization of the Mob1b target transcription factor Yap. Furthermore we observed that NS5A interaction with LRPPRC occurs at mitochondria-ER synapses (MAM) and that LRPPRC downregulation causes a significant increase in different the inflammation-related genes: IFNβ, Mx1, IL 6 and TNFα. Altogether, our results indicate that, through NS5A interactions, HCV hijacks the cellular functions of Mob1b and LRPPRC to ensure its life cycle
Storia di una scelta difficile: il valore della consulenza etica in cure palliative
No full textIl contributo tenta di far emergere il valore della consulenza etica a partire dalla discussione di un caso clinic
Reading as a rite for the training of future doctors: Some reflections from Sir William Osler's bedside library
No full textOn the basis of some inputs both of the Iranian writer Azar Nafisi (The Republic of the Imagination 2015), according to which imaginative knowledge is pragmatic and of the great physician William Osler (1849-1919), who, being an avid reader and bibliophile, listed a number of classics - the so-called bedside library - which every future doctor should have read, the Authors highlight the importance of classics for improving personal growth of physicians as well as their clinical competence. Another input is from Italo Calvino, who argued that there are things that only literature can reach by its specific means. Literature is a sort of bridge that enables dialogue regardless of the worlds we live in (universality); it is a place of identification (empathy); it brings to light the archetypes of human behaviour (ethical resonance). On this basis is founded the idea of stimulating the reading of the classics starting from the first year of medical student training in the context of Medical Humanities
Towards an integrated assessment of complex health interventions. Results of the European INTEGRATE-HTA project
No full textINTEGRATE-HTA, an innovative research project was co-funded by the European Union (EU) under the Seventh Frame¬work Programme from January 2013 until December 2015. This project developed concepts and methods that enable a patient-centred, comprehensive, and integrated assessment of complex health technologies which were applied in a palliative care case study. The practical guidances are available through the project website www.integrate-hta.eu.
Introduction: background and objectives:
In recent years there have been major advances in the development of health technology assessment (HTA). However, HTA still has certain limitations when assessing technologies which:
- are context-dependent, as current HTA focusses on the health technology, not on the (socio-cultural, healthcare) system within it is used;
- perform differently depending on the way they are implemented;
- may have different effects on different patients/consumers.
Furthermore, HTA usually assesses and appraises aspects side-by-side while decision-making needs an integrated perspective on the value of a health technology. In the EU-funded INTEGRATE-HTA project, we (a Consortium of seven partners from five different European countries: Germany, Italy, The Netherlands, Norway, United Kingdom) developed concepts and methods to deal with these challenges. As the rise in chronic diseases in ageing populations has led to the development of increasingly complex technologies, we used palliative care as a case study to test the concepts and methods.
Methods:Different approaches were used to develop guidances on how to conduct an integrated assessment of a complex health technology. These include building on existing concepts and methods for single assessment aspects, i.e. effectiveness, ethical, socio-cultural, economic, and legal issues; Logic models were used to conceptualize the intervention in its context; Feedback from stakeholder advisory panels in seven different European countries to ensure public and patient involvement; and Application in a case study on palliative care. The applicability and relevance of the draft guidances were reviewed by an external panel of 31 experts, representing 14 nationalities and a variety of professional backgrounds.
Results: INTEGRATE-HTA resulted in six guidances: “Assessing effectiveness, economic, ethical, socio-cultural and legal aspects in complex health technologies”; “Guidance on moderators, predictors and patient preferences for treatment outcomes, and their integration”; “Assessment of context and implementation in systematic reviews and HTAs of complex interventions”; “Use of logic models in systematic reviews and HTAs of complex interventions”; “Integrated assessment of complex health technologies – The INTEGRATE-HTA model”; and a case study report: “Integrated assessment of home based palliative care with and without reinforced caregiver support: ‘A Demonstration HTA”. At the meeting, we will present the added value of the guidances to HTA-doers and users.
Conclusion: The INTEGRATE-HTA guidances can help to unlock the value of health technology. It is not a matter of collecting the facts, but a matter of collecting facts that are considered relevant, plausible to stakeholders and which are amenable to scientific inquiry. The guidances therefore contribute to a transparent HTA process and a deeper understanding of complex health technologies. As already stated by Farrell et al.: “Assessment processes are embedded in different sorts of institutional settings, within which scientists, decision-makers, and advocates communicate to define relevant questions for analysis, mobilize certain kinds of experts and expertise, and interpret findings in particular ways.
The dream anatomy between prohibitions and prejudices
No full textA large body of international literature agrees that anatomical dissection is irreplaceable for the education of both medical and surgical students. However, as it happened several times in the past, the problem of supplying cadavers persists. Recently, Italy has filled a legal vacuum, and it has passed a law (Law no. 10 of 10 February 2020) on the disposal of one's own body and post-mortem tissues for study purposes. The aim of this contribution is to provide a brief historical overview of the practice of anatomical dissection in its gradual development around a closely related theme, namely the way of conceiving the human body. The ultimate aim is to underline the importance it has always had for medical education
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