Delivering medication to the lungs via nebulization of pharmaceuticals is a noninvasive and efficient therapy route, particularly for respiratory diseases. The recent worldwide severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic urges the development of such therapies as an effective alternative to vaccines. The main difficulties in using inhalation therapy are the development of effective medicine and methods to stabilize the biological molecules and transfer them to the lungs efficiently following nebulization. We have developed a high-affinity angiotensin-converting enzyme 2 (ACE2) receptor-binding domain (RBD-62) that can be used as a medication to inhibit infection with SARS-CoV-2 and its variants. In this study, we established a nebulization protocol for drug delivery by inhalation using two commercial vibrating mesh (VM) nebulizers (Aerogen Solo and PARI eFlow) that generate similar mist size distribution in a size range that allows efficient deposition in the small respiratory airway. In a series of experiments, we show the high activity of RBD-62, interferon-α2 (IFN-α2), and other proteins following nebulization. The addition of gelatin significantly stabilizes the proteins and enhances the fractions of active proteins after nebulization, minimizing the medication dosage. Furthermore, hamster inhalation experiments verified the feasibility of the protocol in pulmonary drug delivery. In short, the gelatin-modified RBD-62 formulation in coordination with VM nebulizer can be used as a therapy to cure SARS-CoV-2.

Objective To quantify the relative volumetric flows in stent and ureter lumina, as a function of stent size and configuration, in both unobstructed and externally obstructed stented ureters. Methods Magnetic resonance imaging was used to measure flow in stented ureters using a phantom kidney model. Volumetric flow in the stent and ureter lumina were determined along the stented ureters, for each of four single stent sizes (4.8F, 6F, 7F, and 8F), and for tandem (6F and 7F) configurations. Measurements were made in the presence of a fully encircling extrinsic ureteral obstruction as well as in benchmark cases with no extrinsic ureteral obstruction. Results Under no obstruction, the relative contribution of urine flow in single stents is 1–10%, while the relative contributions to flow are ~6 and ~28% for tandem 6F and 7F, respectively. In the presence of an extrinsic ureteral obstruction and single stents, all urine passes within the stent lumen near the extrinsic ureteral obstruction. For tandem 6F and 7F stents under extrinsic ureteral obstruction, relative volumetric flows in the two stent lumina are ~73% and ~81%, respectively, with the remainder passing through the ureter lumen. Conclusions Magnetic resonance imaging demonstrates that with no extrinsic ureteral obstruction, minimal urine flow occurs within a stent. Stent lumen flow is significant in the presence of extrinsic ureteral obstruction, in the vicinity of the extrinsic ureteral obstruction. For tandem stents subjected to extrinsic ureteral obstruction, urine flow also occurs in the ureter lumen between the stents, which can reduce the likelihood of kidney failure even in the case of both stent lumina being occluded.

In current work, the influence of static structural inclusions in heterogeneous highly scattering media such as biotissue on the results of laser speckle contrast imaging using both temporal and spatial processing algorithms has been investigated. The applicability of laser speckle contrast imaging technique has been studied in case of non-ergodic conditions. It was shown using the phantom model that increment of amount of static scatterers comparing to the dynamic ones in tissue causes significant error in results of temporal and spatial speckle contrast processing for the given camera exposure time. At the same time, the analysis of the spatial and temporal speckle contrast values, values of coefficient of speckle dynamics as well as results of Monte Carlo simulation of sampling volumes showed that presence of relatively thin static layer (up to 30% of all volume) cannot cause significant changes in results of laser speckle contrast imaging. The camera exposure time, as well as amount of frames for image processing can vary depending on the experiment goals. Finally, the proposed spatial and temporal algorisms of laser speckle contrast imaging were verified during transcranial visualization of the mouse brain vasculature.

No abstract