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Model-based evaluation of policy impacts and the continued COVID-19 risk at long term care facilities

Infectious Disease Modelling 2022年第3期7卷 463-472页

作者： Bailey K.Fosdick Jude Bayham Jake Dilliott Gregory D.Ebel nicole ehrhart Department of Statistics Colorado State UniversityFt.CollinsCO80523USA Department of Agricultural and Resource Economics Colorado State UniversityFt.CollinsCO80523USA Arthropod-Borne and Infectious Diseases Laboratory Department of MicrobiologyImmunology and PathologyColorado State UniversityFt.CollinsCO80526USA Columbine Health Systems Center for Healthy Aging and Department of Clinical Sciences Colorado State UniversityFt.CollinsCO80523USA

The COVID-19 pandemic severely impacted long-term care facilities resulting in the death of approximately 8%of residents nationwide as of March *** COVID-19 case rates declined and state and county restrictions were lifted in spring 2021,facility managers,local and state health agencies were challenged with defining their own policies moving forward to appropriately mitigate disease *** continued emergence of variants of concern and variable vaccineuptake across facilitieshighlighted the need for a readily available tool that can beemployed at the facility-level to determine best practices for mitigation and ensure resident and staff *** assist leadership in determining the impact of various infection surveillance and response strategies,we developed an agent-based model and an online dashboard interface that simulates COVID-19 infection within congregate care settings under various mitigation *** dashboard quantifies the continued risk for COVID-19 infections within a facility given a designated testing schedule and vaccine *** findings were that choice of COVID-19 diagnostic(*** swab qRT-PCR vs rapid antigen)and testing cadence has less impact on attack rate and staff workdays missed than does vaccination rates among staff and ***,low vaccine uptake among staff at long-term care facilities puts staff and residents at risk of ongoing COVID-19 *** we present our model and dashboard as an exemplar of a tool for state public health officials and facility directors to gain insights from an infectious disease model that can directly inform policy decisions in the midst of a pandemic.

关键词： Agent-based model Nonpharmaceutical interventions Vaccine uptake COVID-19

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β-catenin mRNA encapsulated in SM-102 lipid nanoparticles enhances bone formation in a murine tibia fracture repair model

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Bioactive Materials 2024年第9期39卷 273-286页

作者： Anna Laura Nelson Chiara Mancino Xueqin Gao Joshua AChoe Laura Chubb Katherine Williams Molly Czachor Ralph Marcucio Francesca Taraballi John P.Cooke Johnny Huard Chelsea Bahney nicole ehrhart Steadman Philippon Research Institute(SPRI) Center for Regenerative and Personalized MedicineVailCOUSA Houston Methodist Research Institute Center for Musculoskeletal RegenerationHouston TXUSA University of Wisconsin-Madison Department of Orthopedics and RehabilitationDepartment of Biomedical EngineeringMedical Scientist Training ProgramMadisonWIUSA Colorado State University School of Biomedical EngineeringFort Collins COUSA Colorado State University Department of Clinical SciencesFort Collins COUSA Colorado State University Department of MicrobiologyImmunologyand PathologyFort CollinsCOUSA Houston Methodist Research Institute Center for RNA TherapeuticsDepartment of Cardiovascular SciencesHoustonTXUSA University of Californi1 San Francisco(UCSF)Orthopaedic Trauma InstituteSan FranciscoCAUSA

Fractures continue to be a global economic burden as there are currently no osteoanabolic drugs approved to accelerate fracture *** this study,we aimed to develop an osteoanabolic therapy which activates the Wnt/β-catenin pathway,a molecular driver of endochondral *** hypothesize that using an mRNAbased therapeutic encodingβ-catenin could promote cartilage to bone transformation formation by activating the canonical Wnt signaling pathway in *** optimize a delivery platform built on recent advancements in liposomal technologies,two FDA-approved ionizable phospholipids,DLin-MC3-DMA(MC3)and SM-102,were used to fabricate unique ionizable lipid nanoparticle(LNP)formulations and then tested for transfection efficacy both in vitro and in a murine tibia fracture *** firefly luciferase mRNA as a reporter gene to track and quantify transfection,SM-102 LNPs showed enhanced transfection efficacy in vitro and prolonged transfection,minimal fracture interference and no localized inflammatory response in vivo over MC3 *** generatedβ-cateninGOF mRNA encapsulated in SM-102 LNPs(SM-102-β-cateninGOF mRNA)showed bioactivity in vitro through upregulation of downstream canonical Wnt genes,axin2 and *** testing SM-102-β-cateninGOF mRNA therapeutic in a murine tibia fracture model,histomorphometric analysis showed increased bone and decreased cartilage composition with the 45μg concentration at 2 weeks post-fracture.μCT testing confirmed that SM-102-β-cateninGOF mRNA promoted bone formation in vivo,revealing significantly more bone volume over total volume in the 45μg ***,we generated a novel mRNA-based therapeutic encoding aβ-catenin mRNA and optimized an SM-102-based LNP to maximize transfection efficacy with a localized delivery.

关键词： Gene therapy Fracture healing Lipid nanoparticles mRNA Canonical Wnt

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