Studies On the Reactivity of Acyl Glucuronides .8. Generation of An Antiserum for the Detection of Diflunisal-Modified Proteins in Diflunisal-Dosed Rats

Acyl glucuronide metabolites of carboxylic drugs such as the salicylate derivative diflunisal (DF) have been shown to react with proteins to produce covalent adducts. To aid in the study of the formation and distribution of these adducts in both humans and rats, we raised an antiserum against human serum albumin modified by covalent attachment of DF via an amide bond, using a carbodiimide reagent. This antiserum had wide reactivity, reacting with all types of DF-modified proteins tested and with free DF (albeit at a lower affinity). It did not cross-react with other salicylates or other nonsteroidal anti-inflammatory drugs. The antiserum has been used in immunoblotting to detect proteins covalently modified by DF in the plasma and livers of rats treated with the drug for 7 days. Although some cross-reactivity was apparent on the blots, a series of DF-modified proteins was found in cytosolic, mitochondrial and mixed membrane fractions of hepatocytes, with molecular weights ranging from 28 to 130 kDa

Early Introduction and Community Transmission of SARS-CoV-2 Omicron Variant, New York, New York, USA

The Omicron variant of SARS-CoV-2 has become dominant in most countries and has raised significant global health concerns. As a global commerce center, New York, New York, USA, constantly faces the risk for multiple variant introductions of SARS-CoV-2. To elucidate the introduction and transmission of the Omicron variant in the city of New York, we created a comprehensive genomic and epidemiologic analysis of 392 Omicron virus specimens collected during November 25–December 11, 2021. We found evidence of 4 independent introductions of Omicron subclades, including the Omicron subclade BA.1.1 with defining substitution of R346K in the spike protein. The continuous genetic divergence within each Omicron subclade revealed their local community transmission and co-circulation in New York, including both household and workplace transmissions supported by epidemiologic evidence. Our study highlights the urgent need for enhanced genomic surveillance and effective response planning for better prevention and management of emerging SARS-CoV-2 variants