Search bioRxiv⌕ Search

Biology subjects

Pfeiffer, J.

Publications and source records attributed to Pfeiffer, J..

2 recordsLinked to original sources

Comparative Evaluation of Commercial Gradient Diffusion and Disk Diffusion Tests for Aztreonam-Avibactam Susceptibility Testing

BackgroundAztreonam-avibactam (AZA) is a recently approved agent active against metallo-{beta}-lactamase-producing Enterobacterales. However, independent evaluations of commercially available antimicrobial susceptibility testing (AST) products remain limited. MethodsWe evaluated 56 carbapenem-resistant Enterobacterales isolates using four newly available AZA AST products, including two gradient diffusion (bioMerieux Etest; Liofilchem MIC Test Strip) and two disk diffusion (Hardy, Liofilchem) tests across three Mueller-Hinton agar manufacturers at two independent clinical laboratories. A diverse isolate collection enriched for nonsusceptible and breakpoint-adjacent MICs was used to rigorously assess categorical agreement. Broth microdilution (BMD) was used as the reference method. Essential agreement (EA), categorical agreement (CA), error rates, and reproducibility were analyzed. ResultsAll four commercial AST products demonstrated acceptable analytical performance compared with reference BMD. Gradient diffusion demonstrated high EA (bioMerieux 94.3%, Liofilchem 90.5%), whereas CA ranged from 83.3% to 89.0% across all four products. Minor errors accounted for all categorical discrepancies, and occurred almost exclusively among breakpoint-adjacent isolates. Media-related variability was modest, and quality control performance was generally high, with strong within-site precision and consistent performance across laboratories. ConclusionsThis study provides the first comprehensive head-to-head comparison of commercial AZA susceptibility testing products and supports their implementation in clinical microbiology laboratories.

microbiology↗

Associations between childhood family emotional health, fronto-limbic grey matter volume, and saliva 5mC in young adulthood

BackgroundPoor family emotional health (FEH) during childhood is prevalent and impactful, and likely confers similar neurodevelopmental risks as other adverse social environments. Pointed FEH study efforts are underdeveloped, and the mechanisms by which poor FEH are biologically embedded are unclear. The current exploratory study examined whether variability in DNA methylation (DNAm) and fronto-limbic grey matter volume may represent pathways through which FEH may become biologically embedded. ResultsSelf-reported childhood FEH was nominally associated with right hemisphere hippocampus (b=10.4, p=0.005), left hemisphere amygdala (b=5.3, p=0.009), and right hemisphere amygdala (b=5.8, p=0.016) volumes. Childhood FEH was also nominally associated with 49 DNAm MEs (prange=3x10-6 to 0.047). After limiting analyses to probes correlated between saliva and brain, saliva-derived DNAm MEs partially mediated the association between FEH and right hippocampal volume (Burlywood ME indirect effect b=-111, p=0.014), and fully mediated the FEH and right amygdala volume relationship (Pink4 ME indirect effect b=-48, p=0.026). Modules were enriched with probes falling in genes with immune, CNS, and metabolic functions. ConclusionsFindings extend work highlighting neurodevelopmental variability associated with adverse social environment exposure during childhood by specifically implicating poor FEH, while informing a mechanism of biological embedding. FEH-associated epigenetic signatures could function as proxies of altered fronto-limbic grey matter volume associated with poor childhood FEH and inform further investigation into primarily affected tissues such as endocrine, immune, and CNS cell types.

genomics↗