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MeSH Disease

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SARS-CoV-2 proteins

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SARS-CoV-2 Proteins
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    Characterizing the incidence of adverse events of special interest for COVID-19 MESHD vaccines across eight countries: a multinational network cohort study

    Authors: Xintong Li; Anna Ostropolets; Rupa Makadia; Azza Shoaibi; Gowtham Rao; Anthony G. Sena; Eugenia Martinez-Hernandez; Antonella Delmestri; Katia Verhamme; Peter Rijnbeek; Talita Duarte-Salles; Marc A Suchard; Patrick B Ryan; George Hripcsak; DANIEL PRIETO-ALHAMBRA

    doi:10.1101/2021.03.25.21254315 Date: 2021-03-26 Source: medRxiv

    As large-scale immunization programs against COVID-19 MESHD proceed around the world, safety signals will emerge that need rapid evaluation.1,2 We report population-based, age- and sex-specific background incidence rates of potential adverse events of special interest (AESI) in eight countries using thirteen databases. This multi-national network cohort study included eight electronic medical record and five administrative claims databases from Australia, France, Germany, Japan, Netherlands, Spain, the United Kingdom and the United States, mapped to a common data model. People observed for at least 365 days before 1 January 2017, 2018, or 2019 were included. We based study outcomes on lists published by regulators: acute myocardial infarction MESHD, anaphylaxis MESHD, appendicitis MESHD, Bell s palsy MESHD, deep vein thrombosis MESHD, disseminated intravascular coagulation MESHD, encephalomyelitis MESHD, Guillain-Barre syndrome MESHD, hemorrhagic MESHD and non-hemorrhagic stroke MESHD, immune thrombocytopenia MESHD, myocarditis/pericarditis MESHD, narcolepsy, pulmonary embolism MESHD, and transverse myelitis MESHD.3 We calculated incidence rates stratified by age, sex, and database. We pooled rates across databases using random effects meta-analyses. We classified meta-analytic estimates into Council of International Organizations of Medical Sciences categories: very common, common, uncommon, rare, or very rare.4 We analyzed 126,661,070 people. Rates varied greatly between databases and by age and sex. Some AESI (e.g., myocardial infarction MESHD, Guillain-Barre syndrome MESHD) increased with age, while others (e.g., anaphylaxis MESHD, appendicitis MESHD) were more common in young people. As a result, AESI were classified differently according to age. For example, myocardial infarction MESHD was very rare in children, rare in women aged 35-54 years, uncommon in men and women aged 55-84 years, and common in those aged [≥]85 years. We report robust baseline rates of prioritized AESI across 13 databases. Age, sex, and variation between databases should be considered if background AESI rates are compared to event rates observed with COVID-19 MESHD vaccines.

    Efficacy of vafidemstat in experimental autoimmune encephalomyelitis MESHD highlights the KDM1A/RCOR1/HDAC epigenetic axis in multiple sclerosis MESHD

    Authors: Fernando Cavalcanti; Elena Gonzalez-Rey; Mario Delgado; Leyre Mestre; Carmen Guaza; Michele MP Lufino; Jordi Xaus; Cristina Mascaró; Serena Lunardi; Natalia Sacilotto; Paola Dessanti; David Rotllant; Xavier Navarro; Mireia Herrando-Grabulosa; Carlos Buesa; Tamara Maes

    doi:10.21203/ Date: 2020-11-23 Source: ResearchSquare

    Background Vafidemstat (ORY-2001) is a clinical stage inhibitor of the Lysine Specific Demethylase KDM1A in development for treatment of neurodegenerative and psychiatric diseases MESHD. KDM1A demethylates H3K4me1/2 and together with the histone deacetylases HDAC1/2, it forms part of co-repressor complexes recruited by zinc finger factors to control transcription. The exact role of KDM1A in neuroinflammation remained to be explored.  Methods Compounds were administered p.o. gavage to mice with MOG35-55 induced experimental autoimmune encephalomyelitis MESHD or mice infected with Theiler’s murine encephalomyelitis MESHD virus. Immune cell infiltration was analyzed by immunohistochemistry. Cytokine and chemokine levels were analyzed by ELISA. Genome wide gene expression in spinal cord and brain were analyzed by two-color microarray analysis and qRT-PCR. Results ORY-2001 improved the clinical score in mouse experimental autoimmune encephalomyelitis MESHD and in mice infected with the Theiler’s murine encephalomyelitis MESHD virus. The compound reduced lymphocyte egress and infiltration of immune cells in the spinal cord and prevented demyelination MESHD. ORY-2001 was more effective and/or faster acting than a sphingosine 1-phosphate receptor antagonist in the effector phase of the disease and reduced the induction of the inflammatory gene expression signature in the central nervous system more potently. Gene expression changes and axonal protection in animals, and protection against glutamate excitoxicity in spinal cord explants support that ORY-2001 has neuroprotective qualities.  Conclusions ORY-2001 exerts therapeutic activity in two mouse models of multiple sclerosis MESHD. The anti-inflammatory properties of ORY-2001 are being tested in a Phase IIa clinical trial in patients with relapse remitting and secondary progressive multiple sclerosis MESHD, and in severely ill COVID-19 MESHD patients at risk for acute respiratory distress syndrome MESHD

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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