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| 2. |
- Guimond, S. E., et al.
(författare)
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Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction
- 2022
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Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 8:5, s. 527 - 545
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein receptor binding domain and directly inhibits its binding to ACE2, consistent with molecular modeling identification of multiple molecular contacts and overlapping pixatimod and ACE2 binding sites. Assays with multiple clinical isolates of SARS-CoV-2 virus show that pixatimod potently inhibits the infection of monkey Vero E6 cells and physiologically relevant human bronchial epithelial cells at safe therapeutic concentrations. Pixatimod also retained broad potency against variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, in a K18-hACE2 mouse model, pixatimod significantly reduced SARS-CoV-2 viral titers in the upper respiratory tract and virus-induced weight loss. This demonstration of potent anti-SARS-CoV-2 activity tolerant to emerging mutations establishes proof-of-concept for targeting the HS-Spike protein-ACE2 axis with synthetic HS mimetics and provides a strong rationale for clinical investigation of pixatimod as a potential multimodal therapeutic for COVID-19.
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- Santi, I., et al.
(författare)
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European marine omics biodiversity observation network: a strategic outline for the implementation of omics approaches in ocean observation
- 2023
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Ingår i: Frontiers in Marine Science. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Marine ecosystems, ranging from coastal seas and wetlands to the open ocean, accommodate a wealth of biological diversity from small microorganisms to large mammals. This biodiversity and its associated ecosystem function occurs across complex spatial and temporal scales and is not yet fully understood. Given the wide range of external pressures on the marine environment, this knowledge is crucial for enabling effective conservation measures and defining the limits of sustainable use. The development and application of omics-based approaches to biodiversity research has helped overcome hurdles, such as allowing the previously hidden community of microbial life to be identified, thereby enabling a holistic view of an entire ecosystem's biodiversity and functioning. The potential of omics-based approaches for marine ecosystems observation is enormous and their added value to ecosystem monitoring, management, and conservation is widely acknowledged. Despite these encouraging prospects, most omics-based studies are short-termed and typically cover only small spatial scales which therefore fail to include the full spatio-temporal complexity and dynamics of the system. To date, few attempts have been made to establish standardised, coordinated, broad scaled, and long-term omics observation networks. Here we outline the creation of an omics-based marine observation network at the European scale, the European Marine Omics Biodiversity Observation Network (EMO BON). We illustrate how linking multiple existing individual observation efforts increases the observational power in large-scale assessments of status and change in biodiversity in the oceans. Such large-scale observation efforts have the added value of cross-border cooperation, are characterised by shared costs through economies of scale, and produce structured, comparable data. The key components required to compile reference environmental datasets and how these should be linked are major challenges that we address.
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| 4. |
- Buttigieg, Sandra C., et al.
(författare)
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Researching Ageism in Health-Care and Long Term Care
- 2018
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Ingår i: Contemporary Perspectives on Ageism. - Cham : Springer. - 9783319738192 - 9783319738208 ; , s. 493-515
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Bokkapitel (refereegranskat)abstract
- The literature across different fields defines ageism ambiguously and widely covers a span of intolerant knowledge, values, attitudes and behaviors towards older adults or more generally toward people of a certain age. In this chapter we provide an overview of how ageism is defined, measured, and assessed in health care and long-term care. In so doing, we aim to bridge the gap between the concept and measurement of ageism in these two contexts and to provide some general insights into the approaches, which researchers can apply to assess ageism in these settings. In this chapter, we therefore aim to answer the following questions namely (i) Why is it important to know how ageism in healthcare and long-term care has been empirically studied? (ii) What evidence for the existence of ageism among key stakeholders (e.g. health care professionals and long-term care workers, family members and older adults) is reported in empirical research covering these two contexts? and (iii) Which are the conceptual and methodological approaches used to measure and assess ageism involving these key stakeholders in the two contexts?
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| 5. |
- Lloyd, H. M., et al.
(författare)
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Supporting Innovative Person-Centred Care in Financially Constrained Environments: The WE CARE Exploratory Health Laboratory Evaluation Strategy
- 2020
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 17:9
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Tidskriftsartikel (refereegranskat)abstract
- The COST CARES project aims to support healthcare cost containment and improve healthcare quality across Europe by developing the research and development necessary for person-centred care (PCC) and health promotion. This paper presents an overview evaluation strategy for testing 'Exploratory Health Laboratories' to deliver these aims. Our strategy is theory driven and evidence based, and developed through a multi-disciplinary and European-wide team. Specifically, we define the key approach and essential criteria necessary to evaluate initial testing, and on-going large-scale implementation with a core set of accompanying methods (metrics, models, and measurements). This paper also outlines the enabling mechanisms that support the development of the "Health Labs" towards innovative models of ethically grounded and evidenced-based PCC.
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| 6. |
- Swedberg, Karl, 1944, et al.
(författare)
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Testing cost containment of future healthcare with maintained or improved quality—The COSTCARES project
- 2021
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Ingår i: Health Science Reports. - : Wiley. - 2398-8835. ; 4:2
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Forskningsöversikt (refereegranskat)abstract
- Background: Increasing healthcare costs need to be contained in order to maintain equality of access to care for all EU citizens. A cross-disciplinary consortium of experts was supported by the EU FP7 research programme, to produce a roadmap on cost containment, while maintaining or improving the quality of healthcare. The roadmap comprises two drivers: person-centred care and health promotion; five critical enablers also need to be addressed: information technology, quality measures, infrastructure, incentive systems, and contracting strategies. Method: In order to develop and test the roadmap, a COST Action project was initiated: COST−CARES, with 28 participating countries. This paper provides an overview of evidence about the effects of each of the identified enablers. Intersections between the drivers and the enablers are identified as critical for the success of future cost containment, in tandem with maintained or improved quality in healthcare. This will require further exploration through testing. Conclusion: Cost containment of future healthcare, with maintained or improved quality, needs to be addressed through a concerted approach of testing key factors. We propose a framework for test lab design based on these drivers and enablers in different European countries.
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