Acinetobacter baumannii is a high-priority pathogen due to its extensive antimicrobial resistance and persistence in clinical environments. Quorum sensing (QS) and toxin-antitoxin (TA) systems regulate virulence and stress tolerance, yet their interconnection remains unclear. We analyzed transcriptomic data (GSE87009) from A. baumannii treated with 3-oxo-C12-HSL using WGCNA, differential expression, and machine learning (LASSO and Random Forest). To identify potential inhibitors of the HigBA TA system, we performed molecular docking of 202 chemically diverse compounds - comprising approved drugs, natural products, and synthetic molecules - against the four HigBA proteins using AutoDock Vina, followed by Protein-Ligand Interaction Profiler (PLIP)-based interaction profiling to validate binding modes. WGCNA identified Module 1 (10 genes) as the primary QS-responsive module (r = -0.996, p = 0.0041), containing two complete HigBA systems (chromosomal and plasmid-borne), proteases, transposases, and a catalase. LASSO and Random Forest converged on the four TA genes as robust QS predictors. Docking identified Ligand 17 as the best binder for HigB2 (-7.65 kcal/mol), followed by Ligand 147 for HigA2 (-6.61 kcal/mol), Ligand 198 for HigB1 (-6.79 kcal/mol), and Ligand 178 for HigA1 (-4.51 kcal/mol). PLIP validation confirmed that all ligands occupy the ATP-binding cleft; Deslanoside (147) forms 23 hydrogen bonds, Meclizine (198) anchors via CYS83, while Promazine (178) and Estradiol (17) rely on hydrophobic contacts. These findings provide a mechanistic link between QS and TA systems, thus providing new therapeutic targets for tackling virulence and persistence.

Occasional doses of meclizine are probably acceptable during breastfeeding. Large doses or more prolonged use may cause effects in the infant or decrease the milk supply, particularly in combination with a sympathomimetic such as pseudoephedrine or before lactation is well established.

The Interventions Testing Program (ITP) evaluated eleven compounds in genetically heterogeneous UM-HET3 mice to assess their potential to extend lifespan. These interventions included both novel agents and previously tested compounds administered at novel doses or starting ages. Despite prior evidence suggesting lifespan benefits of these proposed interventions in other models or under different conditions, none of the tested compounds significantly increased lifespan in male or female mice. Notably, astaxanthin, mitoglitazone, and meclizine-previously associated with lifespan extension in the ITP-showed no benefit when administered at different doses or starting at later ages. In females, astaxanthin, late-start mitoglitazone, and pioglitazone were associated with significantly reduced lifespan when pooling the data from all three sites. However, site-specific analysis revealed unusually long lifespans in control females at The Jackson Laboratory, prompting reanalysis using data from the other two sites and only showed a negative effect for mitoglitazone and pioglitazone. This study underscores the importance of rigorous, multi-site testing and highlights the challenges of translating promising initial findings into consistent lifespan benefits at other doses or with alternate starting ages. These results suggest that timing and dosage are critical variables in aging intervention studies and reinforce the need for cautious interpretation of single-site or single-cohort findings.

Vertebrobasilar dolichoectasia (VBD) is a rare condition characterized by dilated and tortuous basilar and/or vertebral arteries. It can be asymptomatic or present as an ischemic stroke, hemorrhage, brainstem/cranial nerve compression, or hydrocephalus. We present a case of a 51-year old woman with a history of transient ischemic attack who presented with persistent vertigo and left-sided weakness and numbness for multiple days. Physical exam was remarkable for the findings of central vertigo and left-sided impairment in sensation and strength. While computed tomography (CT) and magnetic resonance imaging were unremarkable, CT angiography showed a tortuous and dilated basilar artery to 4.9 mm, likely the underlying cause of her symptoms. She was continued on her home aspirin, clopidogrel, and high-intensity atorvastatin and started on meclizine for symptomatic management of vertigo. Although rare, VBD should remain on the differential diagnosis for a variety of patient presentations, especially given its poor prognosis in symptomatic patients.