Nanoaerosols reduce required effective dose of liposomal levofloxacin against pulmonary murine Francisella tularensis subsp. novicida infection.

BACKGROUND: The Institute of Theoretical and Experimental Biophysics in Moscow recently developed a new nanoaerosol generator. This study evaluated this novel technology, which has the potential to enhance therapeutic delivery, with the goal of using the generator to treat pulmonary Francisella tularensis subsp. novicida (F. novicida) infections in BALB/c mice. RESULTS: First, the analysis of quantum dots distribution in cryosections of murine lungs demonstrated that nanoaerosols penetrate the alveoli and spread more homogenously in the lungs than upon intranasal delivery. Second, the generator was used to aerosolize the antibiotic levofloxacin to determine the effectiveness of nanoaerosolized levofloxacin as treatment against F. novicida. The generator was capable of delivering a sufficient dose of nanoaerosolized liposome-encapsulated levofloxacin to rescue mice against 100LD50 of F. novicida. CONCLUSIONS: The nanoaerosol-delivered dosage of liposome-encapsulated levofloxacin required to rescue mice is approximately 94× lower than the oral required dose and approximately 8× lower than the intraperitoneal dose required for rescue. In addition, treatment with nanoaerosols consumes less total volume of therapeutic solutions and is gentler on sprayed material than the aerosolization by a conventional three-jet Collison nebulizer as seen by the preservation of liposomes. This could represent a significant advance for the use of expensive therapeutics and lung directed therapies.

Sex and race visual representation in emergency medicine textbooks and the hidden curriculum.

Introduction: In addition to formal training, informal training often occurs through a hidden curriculum. As the hidden curriculum shapes the knowledge and values held by learners, we must consider its role in implicit bias. One example is through the selection of images used in formal instruction. This study aimed to examine the representation of sex and race among images in two textbooks in emergency medicine (EM). Methods: We performed a cross-sectional study of the sex and race representation of figures in Rosen's Emergency Medicine: Concepts and Clinical Practice 9th Edition and Tintinalli's Emergency Medicine: A Comprehensive Study Guide 9th Edition. Two reviewers screened all images for inclusion, with disagreements resolved by a third reviewer. Images were excluded if they did not include visualized skin. Two reviewers independently reviewed each image and assessed the sex, race, and roles in the image. A third reviewer resolved any disagreements. Results: A total of 959 images (Rosen's n = 377; Tintinalli's n = 582) met inclusion criteria. Race was estimated in 877 cases (91.3%). Of those, White individuals comprised 77.6% (95% confidence interval [CI] 75.0%-80.2%). Sex was estimated in 362 cases (37.7%). Of those images, males comprised 70.2% (95% CI 65.4%-74.9%), and females comprised 29.8% (95% CI 25.1%-34.6%). Conclusion: There is a male sex and White race predominance in visual representation among two EM textbooks. We propose a call to action for the mindful selection of images in formal education to represent diversity, equity, and inclusion and close the gap between the formal and hidden curriculum.

Chitinases are negative regulators of Francisella novicida biofilms.

Biofilms, multicellular communities of bacteria, may be an environmental survival and transmission mechanism of Francisella tularensis. Chitinases of F. tularensis ssp. novicida (Fn) have been suggested to regulate biofilm formation on chitin surfaces. However, the underlying mechanisms of how chitinases may regulate biofilm formation are not fully determined. We hypothesized that Fn chitinase modulates bacterial surface properties resulting in the alteration of biofilm formation. We analyzed biofilm formation under diverse conditions using chitinase mutants and their counterpart parental strain. Substratum surface charges affected biofilm formation and initial attachments. Biophysical analysis of bacterial surfaces confirmed that the chi mutants had a net negative-charge. Lectin binding assays suggest that chitinase cleavage of its substrates could have exposed the concanavalin A-binding epitope. Fn biofilm was sensitive to chitinase, proteinase and DNase, suggesting that Fn biofilm contains exopolysaccharides, proteins and extracellular DNA. Exogenous chitinase increased the drug susceptibility of Fn biofilms to gentamicin while decreasing the amount of biofilm. In addition, chitinase modulated bacterial adhesion and invasion of A549 and J774A.1 cells as well as intracellular bacterial replication. Our results support a key role of the chitinase(s) in biofilm formation through modulation of the bacterial surface properties. Our findings position chitinase as a potential anti-biofilm enzyme in Francisella species.