Supercharged coiled-coil protein with N-terminal decahistidine tag boosts siRNA complexation and delivery efficiency of a lipoproteoplex.

Short interfering RNA (siRNA) therapeutics have soared in popularity due to their highly selective and potent targeting of faulty genes, providing a non-palliative approach to address diseases. Despite their potential, effective transfection of siRNA into cells requires the assistance of an accompanying vector. Vectors constructed from non-viral materials, while offering safer and non-cytotoxic profiles, often grapple with lackluster loading and delivery efficiencies, necessitating substantial milligram quantities of expensive siRNA to confer the desired downstream effects. We detail the recombinant synthesis of a diverse series of coiled-coil supercharged protein (CSP) biomaterials systematically designed to investigate the impact of two arginine point mutations (Q39R and N61R) and decahistidine tags on liposomal siRNA delivery. The most efficacious variant, N8, exhibits a twofold increase in its affinity to siRNA and achieves a twofold enhancement in transfection activity with minimal cytotoxicity in vitro. Subsequent analysis unveils the destabilizing effect of the Q39R and N61R supercharging mutations and the incorporation of C-terminal decahistidine tags on α-helical secondary structure. Cross-correlational regression analyses reveal that the amount of helical character in these mutants is key in N8's enhanced siRNA complexation and downstream delivery efficiency.

Point-of-Care Ultrasound Reduces Visit Time and Cost of Care for Infants with Developmental Dysplasia of the Hip.

Background: Healthcare institutions and policymakers are searching for system-wide approaches to reduce costs while maintaining quality and improving patient outcomes. In most healthcare systems infants referred for the detecting or treating developmental dysplasia of the hip (DDH) are sent to a radiology department for sonographic evaluation. The total duration of visit and cost of visit are essential variables in any healthcare setting and affect both efficiency and "the bottom line". By having the treating clinician perform point-of-care ultrasound (POCUS) for the detection and follow-up of patients with DDH, we hypothesize that there would be a significant reduction in the time spent on the visit and the cost incurred without compromising quality or patient satisfaction. To our knowledge, no prior study has examined the effect of incorporating POCUS on the duration and cost of the visit in patients with DDH. Purpose: To determine if there was a difference in the duration of the visit for patients with DDH when POCUS was performed compared to when traditional "formal" sonography was performed. To determine if there was a difference in the cost of the visit for patients with DDH when POCUS was performed compared to when traditional "formal" sonography was performed. Methods: Data for visits to a specialized outpatient office were collected over two years at a single-specialty orthopedic hospital, comparing the duration and cost of the visit between patient encounters for infants who had "formal" sonograms performed in the radiology suite to infants who underwent POCUS of the hip. In all, we included 532 patient encounters, 326 patients had POCUS performed, and 206 had a "formal" ultrasonographic evaluation performed. Of these, 140 were new evaluations and 392 were follow-up evaluations for treatment. Of the 140 new patients, 80 were in the POCUS group, and 60 were in the "formal" US group. Of the 392 follow-ups, 246 were in the POCUS group, and 146 were in the "formal" US group. Results: The mean duration of the encounter for the POCUS group was 42 min (range 16-75 min), and for the "formal" US group, it was 92 min (range 36-163 min). This difference was statistically significant (p = 0.002). The mean cost of the encounter for the POCUS group was $121.13, and for the "formal" US group, it was $339.38. This difference was statistically significant (p = 0.002). Conclusion: Ultimately, our study demonstrated a statistically significant reduction in the duration and cost of a patient encounter for infants with DDH when they undergo POCUS rather than "formal" sonographic evaluation.