Polymer-Based Bioorthogonal Nanocatalysts for the Treatment of Bacterial Biofilms.

Bioorthogonal catalysis offers a unique strategy to modulate biological processes through the in situ generation of therapeutic agents. However, the direct application of bioorthogonal transition metal catalysts (TMCs) in complex media poses numerous challenges due to issues of limited biocompatibility, poor water solubility, and catalyst deactivation in biological environments. We report here the creation of catalytic "polyzymes", comprised of self-assembled polymer nanoparticles engineered to encapsulate lipophilic TMCs. The incorporation of catalysts into these nanoparticle scaffolds creates water-soluble constructs that provide a protective environment for the catalyst. The potential therapeutic utility of these nanozymes was demonstrated through antimicrobial studies in which a cationic nanozyme was able to penetrate into biofilms and eradicate embedded bacteria through the bioorthogonal activation of a pro-antibiotic.

Trends in Orthopedic Management of Distal Radius Fractures Among Medicare Beneficiaries From 2019 to 2020: A Claims Analysis.

Purpose: Radius and ulna fractures are among the most common fractures. These fractures are managed through operative or nonsurgical treatment, with varying implications in terms of cost and functional outcome. There are few studies that robustly characterize the management of distal radius fractures (DRFs) in the United States during the COVID-19 pandemic. Furthermore, this has not been studied among the Medicare patient population, who are particularly vulnerable to fragility fractures and COVID-19. The purpose of this study is to analyze the services provided to Medicare beneficiaries both before and during the COVID-19 pandemic to determine how procedure volume was affected in this patient population. Methods: We retrospectively analyzed services using the physician or supplier procedure summary data from the Centers for Medicare and Medicaid Services. All services provided by physicians between January 1, 2019, and December 31, 2020, were included. The data were stratified by US census region using insurance carrier number and pricing locality codes. We also compared data between states that maintained governors affiliated with the Democratic or Republican parties for the duration of the study. Results: There was an overall decrease in claims regarding DRFs management from 2019 to 2020. There was a dramatic decline in procedure volume (-6.3% vs -12.9%). Of all distal radius related claims there was a relative increase in the proportion of operatively managed DRFs in 2020, from 50.2% to 52.0%. The Midwest saw the greatest decline in operatively managed DRFs, whereas the West experienced the smallest per-capita decline across all procedures. After separating the data by party affiliation, it was also found that operative and nonsurgical procedure volumes fell more sharply in states with Democratic governors. Conclusions: This study shows a decrease in DRF procedural volume among Medicare beneficiaries. This data suggests that the operative and nonsurgical management of DRFs may have been affected by pandemic factors such as quarantine guidelines and supply chain or resource limitations. This may assist surgeons and health care systems in predicting how similar crises may affect operative volume. Type of study/level of evidence: Therapeutic IV.

Modulating the Catalytic Activity of Enzyme-like Nanoparticles Through their Surface Functionalization.

The inclusion of transition metal catalysts into nanoparticle scaffolds permits the creation of catalytic nanosystems (nanozymes) able to imitate the behaviour of natural enzymes. Here we report the fabrication of a family of nanozymes comprised of bioorthogonal ruthenium catalysts inserted in the protective monolayer of gold nanoparticles. By introducing simple modifications to the functional groups at the surface of the nanozymes, we have demonstrated control over the kinetic mechanism of our system. Cationic nanozymes with hydrophobic surface functionalities tend to replicate the classical Michaelis Menten model, while those with polar groups display substrate inhibition behaviour, a key mechanism present in 20 % of natural enzymes. The structural parameters described herein can be used for creating artificial nanosystems that mimic the complexity observed in cell machinery.