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1.
Social Sciences ; 11(12):557, 2022.
Статья в английский | MDPI | ID: covidwho-2143496

Реферат

There is a well-established body of evidence that intergenerational bonding programs (IGPs) can improve the overall well-being of older adults and strengthen relationships and understanding between generations. There is limited literature on the experience of IGPs in an Asian context, despite many of these countries facing faster rates of population ageing than other Western countries. In Singapore, intergenerational bonding is a priority in national efforts to encourage successful ageing. This paper presents a case study of the development and implementation of a co-located (shared site) model IGP in Singapore. Drawing on interviews with key stakeholders, the aim of this case study is to present the realities of the evolution of an IGP from conceptualisation through to implementation, and used the nursing home's COVID-19 experience to illustrate issues of sustainability affecting IGPs with vulnerable populations. The findings will inform the development and implementation of similar future programs.

2.
Sci Rep ; 12(1): 17058, 2022 Oct 12.
Статья в английский | MEDLINE | ID: covidwho-2062275

Реферат

The emergence of Omicron variant raises great concerns because of its rapid transmissibility and its numerous mutations in spike protein (S-protein). S-protein can act as a pathogen-associated molecular pattern and complement activator as well as antigen. We compared some immune characteristics of trimer S-proteins for wild type (WT-S) and B.1.1.529 Omicron (Omicron-S) to investigate whether the mutations have affected its pathogenicity and antigenic shift. The results indicated that WT-S and Omicron-S directly activated nuclear factor-κB (NF-κB) and induced the release of pro-inflammatory cytokines in macrophages, but the actions of Omicron-S were weaker. These inflammatory reactions could be abrogated by a Toll-like receptor 4 antagonist TAK-242. Two S-proteins failed to induce the production of antiviral molecular interferon-ß. In contrast to pro-inflammatory effects, the ability of two S-proteins to activate complement was comparable. We also compared the binding ability of two S-proteins to a high-titer anti-WT-receptor-binding domain antibody. The data showed that WT-S strongly bound to this antibody, while Omicron-S was completely off-target. Collectively, the mutations of Omicron have a great impact on the pro-inflammatory ability and epitopes of S-protein, but little effect on its ability to activate complement. Addressing these issues can be helpful for more adequate understanding of the pathogenicity of Omicron and the vaccine breakthrough infection.


Тема - темы
COVID-19 , Vaccines , Antiviral Agents , Cytokines , Epitopes , Humans , Interferon-beta/genetics , Membrane Glycoproteins/genetics , NF-kappa B , Pathogen-Associated Molecular Pattern Molecules , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Toll-Like Receptor 4/genetics , Viral Envelope Proteins/genetics
3.
Proc Natl Acad Sci U S A ; 117(34): 20803-20813, 2020 08 25.
Статья в английский | MEDLINE | ID: covidwho-695945

Реферат

Virus entry is a multistep process. It initiates when the virus attaches to the host cell and ends when the viral contents reach the cytosol. Genetically unrelated viruses can subvert analogous subcellular mechanisms and use similar trafficking pathways for successful entry. Antiviral strategies targeting early steps of infection are therefore appealing, particularly when the probability for successful interference through a common step is highest. We describe here potent inhibitory effects on content release and infection by chimeric vesicular stomatitis virus (VSV) containing the envelope proteins of Zaire ebolavirus (VSV-ZEBOV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (VSV-SARS-CoV-2) elicited by Apilimod and Vacuolin-1, small-molecule inhibitors of the main endosomal phosphatidylinositol-3-phosphate/phosphatidylinositol 5-kinase, PIKfyve. We also describe potent inhibition of SARS-CoV-2 strain 2019-nCoV/USA-WA1/2020 by Apilimod. These results define tools for studying the intracellular trafficking of pathogens elicited by inhibition of PIKfyve kinase and suggest the potential for targeting this kinase in developing small-molecule antivirals against SARS-CoV-2.


Тема - темы
Betacoronavirus/drug effects , Ebolavirus/drug effects , Heterocyclic Compounds, 4 or More Rings/pharmacology , Morpholines/pharmacology , Phosphatidylinositol 3-Kinases , Triazines/pharmacology , Virus Internalization/drug effects , Animals , Betacoronavirus/physiology , COVID-19 , Cells, Cultured , Coronavirus Infections , Ebolavirus/physiology , Gene Editing , Humans , Hydrazones , Pandemics , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Pneumonia, Viral , Pyrimidines , SARS-CoV-2 , Viral Envelope Proteins/genetics
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