Lipid-Functionalized Single-Walled Carbon Nanotubes as Probes for Screening Cell Wall Disruptors.

Membrane-active molecules are of great importance to drug delivery and antimicrobials applications. While the ability to prototype new membrane-active molecules has improved greatly with the advent of automated chemistries and rapid biomolecule expression techniques, testing methods are still limited by throughput, cost, and modularity. Existing methods suffer from feasibility constraints of working with pathogenic living cells and by intrinsic limitations of model systems. Herein, we demonstrate an abiotic sensor that uses semiconducting single-walled carbon nanotubes (SWCNTs) as near-infrared fluorescent transducers to report membrane interactions. This sensor is composed of SWCNTs aqueously suspended in lipid, creating a cylindrical, bilayer corona; these SWCNT probes are very sensitive to solvent access (changes in permittivity) and thus report morphological changes to the lipid corona by modulation of fluorescent signals, where binding and disruption are reported as brightening and attenuation, respectively. This mechanism is first demonstrated with chemical and physical membrane-disruptive agents, including ethanol and sodium dodecyl sulfate, and application of electrical pulses. Known cell-penetrating and antimicrobial peptides are then used to demonstrate how the dynamic response of these sensors can be deconvoluted to evaluate different parallel mechanisms of interaction. Last, SWCNTs functionalized in several different bacterial lipopolysaccharides (Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli) are used to evaluate a panel of known membrane-disrupting antimicrobials to demonstrate that drug selectivity can be assessed by suspension of SWCNTs with different membrane materials.

Characteristics and retention of emergency department patients who left without being seen (LWBS).

A retrospective observational study was conducted for patients 18 years or older presenting to a Midwestern emergency department (ED) in the United States during February 2019-January 2020 to characterize associated subsequent care utilization in patients who left the ED without being seen. Patients were classified as left without being seen (LWBS) based on documented ED disposition. The healthcare system's records were reviewed for any associated utilizations within 3 weeks following the initial ED encounter. During the study period, 45,456 patients presented to the ED, with 2269 (5.0%) classified as LWBS. The median documented time until patients left the ED was 112 min. Of these patients, 1257 (55.4%) had a subsequent encounter within the health system within 3 weeks and 920 (73.2%) of these visits were determined to be related to the LWBS chief complaint. These visits included 67.5% of patients returning to ED or hospital, 27.5% to primary care or an urgent care clinic, and 5.0% to a specialty or other provider appointment. Of patients returning to ED, 78.1% did so within 72 h. Patients without a subsequent health system associated encounter tended to be younger, female, non-White, and present with possible lower-acuity chief complaints. At least one-half of LWBS patients sought care related to the concerns by a health system provider within 3 weeks of the initial encounter within the same system. The high prevalence of ED returns within a narrow turnaround window highlights a missed opportunity to provide services to these patients during their initial encounter.