While postmortem (PM) toxicology results provide valuable information towards ascertaining both the cause and manner of death in coronial cases, there are also significant difficulties associated with the interpretation of PM drug levels. Such difficulties are influenced by several pharmacokinetic and pharmacodynamic factors including PM redistribution, diffusion, site-to-site variability in drug levels, different drug properties and metabolism, bacterial activity, genetic polymorphisms, tolerance, resuscitation efforts, underlying conditions, and the toxicity profile of cases (i.e. single- or mixed-drug toxicity). A large body of research has been dedicated for better understanding and even quantifying the influence of these factors on PM drug levels. For example, several investigative matrices have been developed as potential indicators of PM redistribution, but they have limited practical value. Reference tables of clinically relevant therapeutic, toxic, and potentially fatal drug concentrations have also been compiled, but these unfortunately do not provide reliable reference values for PM toxicology. More recent research has focused on developing databases of peripheral PM drug levels for a variety of case-types to increase transferability to real-life cases and improve interpretations. Changes to drug levels after death are inevitable and unavoidable. As such, guidelines and practices will continue to evolve as we further our understanding of such phenomena.
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http://dx.doi.org/10.1093/jat/bkae052 | DOI Listing |
Sci Rep
December 2024
Department of Chemical and Biological Engineering, Gachon University, Seongnam, 13120, Republic of Korea.
The Crimean Congo virus has been reported to be a part of the spherical RNA-enveloped viruses from the Bunyaviridae family. Crimean Congo fever (CCHF) is a fatal disease with having fatality rate of up to 40%. It is declared endemic by the World Health Organization.
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December 2024
Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul, 02447, Korea.
To understand the action mechanism of probiotics against postmenopausal symptoms, we examined the effects of Lactococcus lactis P32 (P) and Bifidobacterium bifidum P45 (P), which suppressed interleukin (IL)-6 and receptor activator of nuclear factor-κB (RANK) ligand (RNAKL) expression in Gardnerella vaginalis (Gv)-stimulated macrophages, on vaginitis, osteoporosis, and depression/cognitive impairment (DC) in mice with vaginally infected Gv, ovariectomy (Ov), or Ov/Gv (oG). Oral administration of P or P decreased Gv-induced DC-like behavior and tumor necrosis factor (TNF)-α, IL-6, RANK, and/or RANKL expression in the vagina, bone, hypothalamus, hippocampus, and colon, while Gv-suppressed bone osteoprotegerin and brain serotonin and brain-derived neurotrophic factor (BDNF) levels increased. They partially shifted vaginal and gut dysbiosis in Gv-infected mice to the gut microbiota composition in normal control mice.
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December 2024
Department of Drug Prohibition and Public Security, Criminal Investigation Police University of China, Shenyang, 110035, China.
Methamphetamine use disorder has emerged as a significant public health concern globally. This study endeavors to elucidate the alterations in expression changes of miRNAs in the plasma of methamphetamine use disorder and elucidate the alterations in miRNA expression in the plasma of individuals with methamphetamine use disorder and investigate the relationship between these differentially expressed miRNAs and the disorder itself, cravings for methamphetamine, and associated mental disorders. Furthermore, the study seeks to clarify the expression of downstream target molecules of specific miRNAs in the plasma of methamphetamine use disorder, assess the diagnostic utility of these miRNAs and their target molecules, explore their potential as biomarkers, and identify potential targets for the diagnosis and treatment of methamphetamine use disorder.
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December 2024
Laboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
The immune escape capacities of XBB variants necessitate the authorization of vaccines with these antigens. In this study, we produce three recombinant trimeric proteins from the RBD sequences of Delta, BA.5, and XBB.
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December 2024
Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology.
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