Clinical Experiences With the Nitazene Class of Synthetic Opioids: A Cohort Study.

Objectives: Nitazenes are illicit novel opioid agonists, and data describing the clinical course, management, and outcome of nitazene opioid poisoning are limited. The aim of this study is to describe our clinical experiences with analytically confirmed nitazene opioid exposures.

Methods: We extracted data on analytically confirmed nitazene opioid exposures in a cohort of prospectively identified cases in a state-based comprehensive surveillance program in New South Wales, Australia.

Surveillance of Viral Respiratory Infections within Maximum-Security Prison, Australia.

Limited surveillance data have hindered understanding of SARS-CoV-2 transmission within prisons. We integrated routine surveillance data with viral sequencing to investigate transmission dynamics and associated factors during a Delta variant outbreak in a maximum-security prison in Sydney, New South Wales, Australia. Infection incidence and associated factors were determined by using person-time and Cox regression.

A quantitative analysis of MDMA seized at New South Wales music festivals over the 2019/2020 season: Form, purity, dose and adulterants.

Introduction: This research aims to understand the content and nature, and to explore the harm potential, of suspected 3,4-methylenedioxymethamphetamine (MDMA) substances circulating at music festivals in New South Wales.

Methods: Across 19 music festivals held between October 2019 and March 2020, 302 substances detected and suspected by police to contain MDMA were selected for quantitative analysis.

Results: Five percent of substances contained a drug other than MDMA (n = 13) or no drug (n = 2).

Structural Analysis of Binding Determinants of Trehalose-6-phosphate Phosphatase Using Ground-State Complexes.

Trehalose-6-phosphate phosphatase (T6PP) catalyzes the dephosphorylation of trehalose 6-phosphate (T6P) to the disaccharide trehalose. The enzyme is not present in mammals but is essential to the viability of multiple lower organisms as trehalose is a critical metabolite, and T6P accumulation is toxic. Hence, T6PP is a target for therapeutics of human pathologies caused by bacteria, fungi, and parasitic nematodes.

Interaction Energetics and Druggability of the Protein-Protein Interaction between Kelch-like ECH-Associated Protein 1 (KEAP1) and Nuclear Factor Erythroid 2 Like 2 (Nrf2).

Development of small molecule inhibitors of protein-protein interactions (PPIs) is hampered by our poor understanding of the druggability of PPI target sites. Here, we describe the combined application of alanine-scanning mutagenesis, fragment screening, and FTMap computational hot spot mapping to evaluate the energetics and druggability of the highly charged PPI interface between Kelch-like ECH-associated protein 1 (KEAP1) and nuclear factor erythroid 2 like 2 (Nrf2), an important drug target. FTMap identifies four binding energy hot spots at the active site.

Crystallization of Liganded Phosphatases in the HAD Superfamily.

Phosphotransferases catalyze reactions on chemically diverse molecules in organisms from all domains of life. The haloalkanoate dehalogenase superfamily (HADSF) is a model system for phosphoryl transfer enzymes as members catalyze phosphoester hydrolase, phosphonate hydrolase, and phosphomutase reactions on sugars, lipids, nucleotides, and peptides. Because these reactions are fundamental to essential metabolic transformations, understanding the mechanism and determinants of substrate specificity in the HADSF is critical.