Multicompartment Theranostic Nanoemulsions Stabilized by a Triphilic Semifluorinated Block Copolymer.

The presence of a perfluorocarbon block in a multiblock polymer has been shown to be an additional driving force toward nanoparticle assembly. In the preparation of nanoemulsions, this perfluorocarbon block also provides enhanced particle stability. Herein, the synthesis of a new triphilic, semifluorinated copolymer, M2F8H18, is introduced. This ABC type block copolymer can be used to formulate extremely stable nanoemulsions, assembled around a lipophilic droplet, with lifetimes of one year or more. The central oil droplet can stably solubilize high concentrations of hydrophobic drugs, making this system an ideal drug delivery vehicle. The incorporation of the perfluorocarbon block modulates drug release from the lipophilic core via the surrounding fluorous shell. Fluorous imaging agents incorporated into the fluorous shell prolong drug release even further as well as provide potent 19F-MRI contrast ability. In vitro studies show that these nanoemulsions efficiently inhibit cancer cell growth, thus providing a theranostic drug delivery system.

Diagnostic testing and antibiotic utilization among inpatients evaluated for coronavirus disease 2019 (COVID-19) pneumonia.

We evaluated diagnostic test and antibiotic utilization among 252 patients from 11 US hospitals who were evaluated for coronavirus disease 2019 (COVID-19) pneumonia during the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) omicron variant pandemic wave. In our cohort, antibiotic use remained high (62%) among SARS-CoV-2-positive patients and even higher among those who underwent procalcitonin testing (68%).

The impact of coronavirus disease 2019 (COVID-19) on the antimicrobial stewardship pharmacist workforce: A multicenter survey.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has required healthcare systems and hospitals to rapidly modify standard practice, including antimicrobial stewardship services. Our study examines the impact of COVID-19 on the antimicrobial stewardship pharmacist. Design: A survey was distributed nationally to all healthcare improvement company members. Participants: Pharmacist participants were mostly leaders of antimicrobial stewardship programs distributed evenly across the United States and representing urban, suburban, and rural health-system practice sites. Results: Participants reported relative increases in time spent completing tasks related to medication access and preauthorization (300%; P = .018) and administrative meeting time (34%; P = .067) during the COVID-19 pandemic compared to before the pandemic. Time spent rounding, making interventions, performing pharmacokinetic services, and medication reconciliation decreased. Conclusion: A shift away from clinical activities may negatively affect the utilization of antimicrobials.

Sequential unfolding of the hemolysin two-partner secretion domain from Proteus mirabilis.

Protein secretion is a major contributor to Gram-negative bacterial virulence. Type Vb or two-partner secretion (TPS) pathways utilize a membrane bound ß-barrel B component (TpsB) to translocate large and predominantly virulent exoproteins (TpsA) through a nucleotide independent mechanism. We focused our studies on a truncated TpsA member termed hemolysin A (HpmA265), a structurally and functionally characterized TPS domain from Proteus mirabilis. Contrary to the expectation that the TPS domain of HpmA265 would denature in a single cooperative transition, we found that the unfolding follows a sequential model with three distinct transitions linking four states. The solvent inaccessible core of HpmA265 can be divided into two different regions. The C-proximal region contains nonpolar residues and forms a prototypical hydrophobic core as found in globular proteins. The N-proximal region of the solvent inaccessible core, however, contains polar residues. To understand the contributions of the hydrophobic and polar interiors to overall TPS domain stability, we conducted unfolding studies on HpmA265 and site-specific mutants of HpmA265. By correlating the effect of individual site-specific mutations with the sequential unfolding results we were able to divide the HpmA265 TPS domain into polar core, nonpolar core, and C-terminal subdomains. Moreover, the unfolding studies provide quantitative evidence that the folding free energy for the polar core subdomain is more favorable than for the nonpolar core and C-terminal subdomains. This study implicates the hydrogen bonds shared among these conserved internal residues as a primary means for stabilizing the N-proximal polar core subdomain.