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- 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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| 3. |
- Berbakov, Maria E, et al.
(författare)
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Adapting a community pharmacy intervention to improve medication safety.
- 2024
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Ingår i: Journal of the American Pharmacists Association : JAPhA. - 1544-3450. ; 64:1, s. 159-168
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Community pharmacies are an ideal location to address challenges of over-the-counter medication safety, yet many successful interventions are only tested in a few pharmacies without expansion, creating unrealized opportunities to improve patient care on a larger scale. Scaling up to numerous pharmacies can be challenging because each community pharmacy has unique needs and layouts and requires individualized adaptation.OBJECTIVES: This paper reports techniques for (a) adapting a community pharmacy intervention to fit the unique physical layout and patient needs of health system pharmacy sites without increasing staff workload, (b) identifying strategies to gather feedback on adaptations from stakeholders, and (c) developing materials to share with pharmacy champions for them to independently implement and sustain the intervention in their organization.PRACTICE DESCRIPTION: The study team collaborated with Aurora Pharmacy, Inc to develop an intervention designed to increase awareness of safe over-the-counter medication use for older adults.PRACTICE INNOVATION: Senior Safe, a community pharmacy-based intervention, was designed, implemented, and tested using the Exploration, Preparation, Implementation, and Sustainment implementation framework.EVALUATION METHODS: Senior Safe was adapted through pilot testing and a randomized control trial. Feedback was collected from key stakeholders, including pharmacy staff, older adults, and a research advisory group.RESULTS: A finalized version of Senior Safe, as well as an implementation package, was provided to Aurora Pharmacy to integrate into all 63 sites.CONCLUSION: This multiphase study illustrated that refining an intervention is possible and welcomed by pharmacy staff, but it requires time, resources, and funds to create an impactful, sustainable community pharmacy intervention.
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| 5. |
- Watterson, Taylor L., et al.
(författare)
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Linking Inner Context and Innovation Factors : Examining a pharmacy-based intervention through the eyes of pharmacy staff
- 2024
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Ingår i: Exploratory Research in Clinical and Social Pharmacy. - : Elsevier. - 2667-2766. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Community pharmacies, as unique and accessible healthcare venues, are ideal locations to implement interventions aiming to improve patient care. However, these interventions may increase workload or disrupt workflow for community pharmacists, technicians, and other staff members, threatening long-term sustainment. There are growing calls from the field of implementation science to design for intervention sustainment and maintenance by maximizing innovation fit. Senior SafeTM, an intervention to facilitate safer overthe-counter (OTC) product selection by older adults, serves as a case study to examine the congruence between Innovation Factors and community pharmacy Inner Context constructs and their implications for workload and sustainment.Methods: Using the Exploration, Preparation, Implementation, Sustainment (EPIS) framework, this qualitative study identified factors surrounding Senior Safe implementation. Semi-structured interviews were conducted with staff from pharmacies where Senior Safe was implemented. Two coders independently analyzed interview transcripts using deductive analysis based on EPIS constructs. Thematic analysis was used to generate three themes that encapsulated innovation fit.Results: Nineteen pharmacy staff members participated, with the majority reporting no significant change in their workload or workflow due to Senior Safe. Interview feedback supported a pre-existing culture of the healthcare system to engage patients, of leadership commitment to patient safety initiatives, and of an amplified role of pharmacy technicians.Discussion and Conclusion: Pharmacy staff interviews revealed congruence between Innovation Factors and Inner Context that likely yielded intervention workload neutrality. This study highlighted the importance for researchers to consider maintenance and sustainability when designing and implementing an intervention and the critical influence of culture and leadership support during this process.
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| 7. |
- Moslehi, S., et al.
(författare)
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Fractal Electronics for Stimulating and Sensing Neural Networks : Enhanced Electrical, Optical, and Cell Interaction Properties
- 2024
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Ingår i: The Fractal Geometry of the Brain. - 2190-5215 .- 2190-5223. - 9783031476051 - 9783031476068 ; 36, s. 849-875
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Bokkapitel (refereegranskat)abstract
- Imagine a world in which damaged parts of the body – an arm, an eye, and ultimately a region of the brain – can be replaced by artificial implants capable of restoring or even enhancing human performance. The associated improvements in the quality of human life would revolutionize the medical world and produce sweeping changes across society. In this chapter, we discuss several approaches to the fabrication of fractal electronics designed to interface with neural networks. We consider two fundamental functions – stimulating electrical signals in the neural networks and sensing the location of the signals as they pass through the network. Using experiments and simulations, we discuss the favorable electrical performances that arise from adopting fractal rather than traditional Euclidean architectures. We also demonstrate how the fractal architecture induces favorable physical interactions with the cells they interact with, including the ability to direct the growth of neurons and glia to specific regions of the neural–electronic interface.
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