A Role for Cross-linking Proteins in Actin Filament Network Organization and Force Generation.

The high turgor pressure across the plasma membrane of yeasts creates a requirement for substantial force production by actin polymerization and myosin motor activity for clathrin-mediated endocytosis (CME). Endocytic internalization is severely impeded in the absence of fimbrin, an actin filament crosslinking protein called Sac6 in budding yeast. Here, we combine live-cell imaging and mathematical modeling to gain new insights into the role of actin filament crosslinking proteins in force generation. Genetic manipulation showed that CME sites with more crosslinking proteins are more effective at internalization under high load. Simulations of an experimentally constrained, agent-based mathematical model recapitulate the result that endocytic networks with more double-bound fimbrin molecules internalize the plasma membrane against elevated turgor pressure more effectively. Networks with large numbers of crosslinks also have more growing actin filament barbed ends at the plasma membrane, where the addition of new actin monomers contributes to force generation and vesicle internalization. Our results provide a richer understanding of the crucial role played by actin filament crosslinking proteins during actin network force generation, highlighting the contribution of these proteins to the self-organization of the actin filament network and force generation under increased load.

Pharmacist-Driven MRSA Nasal PCR Screening and the Duration of Empirical Vancomycin Therapy for Suspected MRSA Respiratory Tract Infections.

OBJECTIVE: To assess the effect of a pharmacist-driven, polymerase chain reaction (PCR)-based nasal screening protocol for methicillin-resistant Staphylococcus aureus (MRSA) on vancomycin therapy duration and on rates of adverse drug events and 30-day hospital readmission. PATIENTS AND METHODS: From July 8, 2017, through January 31, 2019, we performed a retrospective, multicenter, preimplementation-postimplementation study. Patients with a vancomycin order to treat lower respiratory tract infection (LRTI) underwent MRSA PCR screening; tests were ordered by health care providers, including physicians, physician assistants, and advanced practice registered nurses. During the preimplementation period (July 8, 2017, through September 30, 2018), pharmacists could order MRSA PCR screening only after receiving a verbal order from a health care provider. During the postimplementation period (October 1, 2018, through January 31, 2019), a collaborative practice agreement allowed pharmacists to order MRSA PCR screening tests. RESULTS: The preimplementation group included 241 patients, and the postimplementation group included 74 patients. Of these patients, 124 in the preimplementation group and 62 in the postimplementation group received MRSA PCR screening. Twenty patients (16.1%) in the preimplementation group and 9 (14.5%) in the postimplementation group had a positive MRSA PCR screening test result (between-group difference, 1.6%; P=.80). Duration of therapy was significantly shorter in the postimplementation group (median [interquartile range], 14.3 [5.0-28.6] hours vs 24.0 [12.4-47.0] hours; P<.001). CONCLUSION: Vancomycin therapy carries a risk of adverse events and may increase health care costs. A pharmacist-driven protocol for MRSA nasal swab PCR screening effectively reduces the duration of vancomycin therapy for patients with lower respiratory tract infection.

5 drug interactions you don't want to miss.

These interactions can affect contraceptive efficacy, increase bleeding risk, or lead to rhabdomyolysis. This practical guide can help you avoid trouble.