Microfluidic Platform Enables Shearless Aerosolization of Lipid Nanoparticles for mRNA Inhalation.

Leveraging the extensive surface area of the lungs for gene therapy, the inhalation route offers distinct advantages for delivery. Clinical nebulizers that employ vibrating mesh technology are the standard choice for converting liquid medicines into aerosols. However, they have limitations when it comes to delivering mRNA through inhalation, including severe damage to nanoparticles due to shearing forces. Here, we introduce a microfluidic aerosolization platform (MAP) that preserves the structural and physicochemical integrity of lipid nanoparticles, enabling safe and efficient delivery of mRNA to the respiratory system. Our results demonstrated the superiority of the MAP over the conventional vibrating mesh nebulizer, as it avoided problems such as particle aggregation, loss of mRNA encapsulation, and deformation of the nanoparticle morphology. Notably, aerosolized nanoparticles generated by the microfluidic device led to enhanced transfection efficiency across various cell lines. In vivo experiments with mice that inhaled these aerosolized nanoparticles revealed successful lung-specific mRNA transfection without observable signs of toxicity. This MAP may represent an advancement for the pulmonary gene therapy, enabling precise and effective delivery of aerosolized nanoparticles.

Microfluidic platform enables shear-less aerosolization of lipid nanoparticles for messenger RNA inhalation.

Leveraging the extensive surface area of the lungs for gene therapy, inhalation route offers distinct advantages for delivery. Clinical nebulizers that employ vibrating mesh technology are the standard choice for converting liquid medicines into aerosols. However, they have limitations when it comes to delivering mRNA through inhalation, including severe damage to nanoparticles due to shearing forces. Here, we introduce a novel microfluidic aerosolization platform (MAP) that preserves the structural and physicochemical integrity of lipid nanoparticles, enabling safe and efficient mRNA delivery to the respiratory system. Our results demonstrated the superiority of the novel MAP over the conventional vibrating mesh nebulizer, as it avoided problems such as particle aggregation, loss of mRNA encapsulation, and deformation of nanoparticle morphology. Notably, aerosolized nanoparticles generated by the microfluidic device led to enhanced transfection efficiency across various cell lines. In vivo experiments with mice that inhaled these aerosolized nanoparticles revealed successful, lung-specific mRNA transfection without observable signs of toxicity. This pioneering MAP represents a significant advancement for the pulmonary gene therapy, enabling precise and effective delivery of aerosolized nanoparticles.

Remote Patient Monitoring Improves Patient Falls and Reduces Harm.

BACKGROUND: Minimizing patient falls and fall-related injuries within organizational constraints is a high priority for nurse leaders. The Centers for Medicare & Medicaid Services do not reimburse hospitals for fall-related expenditures. In-person sitters are used to prevent falls but are resource intensive and costly. Remote patient monitoring (RPM) may offer alternatives to in-person sitters to reduce fall-related harm. PURPOSE: The efficacy of RPM to reduce patient falls and fall-related injuries was explored. METHODS: Electronic health record data were extracted from a 13-hospital integrated health care system. Incidence rate ratios were used to analyze the impact of RPM technology on falls and fall-related injuries. RESULTS: When used in conjunction with standard fall precautions, RPM reduced falls 33.7% and fall-related injuries 47.4%. Fall-related expenditures decreased $304 400 with a combined estimated savings systemwide of $2 089 600 annually. CONCLUSIONS: RPM technology minimized falls and associated harm and improved patient safety, positively impacting hospital expenditures.

Switchgrass yield on reclaimed surface mines for bioenergy production.

The high cost of transportation fuels and the environmental risks associated with acquiring and using nonrenewable energy sources have created a demand for developing renewable bioenergy crops. Switchgrass ( L.), a warm-season perennial grass, is a promising feedstock due to its high biomass production under a wide range of growing conditions and its satisfactory forage quality and chemical composition. West Virginia contains vast expanses of reclaimed surface mine lands that could be used to produce switchgrass as a bioenergy feedstock. This study determined dry matter yields of three switchgrass varieties (Cave-In-Rock, Shawnee, and Carthage) during the second to fourth years of production. Two research sites were established on reclaimed surface mines in southern West Virginia: Hobet and Hampshire. The Hobet site was prepared using crushed, unweathered sandstone as the soil material, and yields were significantly lower at 803 kg ha averaged across varieties and years than annual yields at Hampshire. The highest yield at Hobet, with Shawnee in the third year, was 1964 kg ha. The Hamphire site, which was reclaimed in the late 1990s using topsoil and treated municipal sludge, averaged 5760 kg ha of switchgrass across varieties and years. The highest yield, obtained with Cave-in-Rock during the third year, was 9222 kg ha. Switchgrass yields on agricultural lands in this region averaged 12,000 kg ha. Although average switchgrass yields at Hampshire were about 50% lower than agricultural lands, they were greater than a target yield of 5000 kg ha, a threshold for economically feasible production. Yields during the fourth year from a two-harvest per year system were not significantly different from a single, end-of-year harvest at both sites. Reclaimed lands show promise for growing bioenergy crops such as switchgrass on areas where topsoil materials are replaced and amended like that at the Hampshire site.

Clinical evaluation of single-shot and readout-segmented diffusion-weighted imaging in stroke patients at 3 T.

BACKGROUND: Diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) is most commonly performed utilizing a single-shot echo-planar imaging technique (ss-EPI). Susceptibility artifact and image blur are severe when this sequence is utilized at 3 T. PURPOSE: To evaluate a readout-segmented approach to DWI MR in comparison with single-shot echo planar imaging for brain MRI. MATERIAL AND METHODS: Eleven healthy volunteers and 14 patients with acute and early subacute infarctions underwent DWI MR examinations at 1.5 and 3T with ss-EPI and readout-segmented echo-planar (rs-EPI) DWI at equal nominal spatial resolutions. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) calculations were made, and two blinded readers ranked the scans in terms of high signal intensity bulk susceptibility artifact, spatial distortions, image blur, overall preference, and motion artifact. RESULTS: SNR and CNR were greatest with rs-EPI (8.1 ± 0.2 SNR vs. 6.0 ± 0.2; P <10(-4) at 3T). Spatial distortions were greater with single-shot (0.23 ± 0.03 at 3T; P <0.001) than with rs-EPI (0.12 ± 0.02 at 3T). Combined with blur and artifact reduction, this resulted in a qualitative preference for the readout-segmented scans overall. CONCLUSION: Substantial image quality improvements are possible with readout-segmented vs. single-shot EPI - the current clinical standard for DWI - regardless of field strength (1.5 or 3 T). This results in improved image quality secondary to greater real spatial resolution and reduced artifacts from susceptibility in MR imaging of the brain.

Contrast-enhanced 3-dimensional SPACE versus MP-RAGE for the detection of brain metastases: considerations with a 32-channel head coil.

PURPOSE: The aim of this study was to compare the detection of brain metastases at 3 T using a 32-channel head coil with 2 different 3-dimensional (3D) contrast-enhanced sequences, a T1-weighted fast spin-echo-based (SPACE; sampling perfection with application-optimized contrasts using different flip angle evolutions) sequence and a conventional magnetization-prepared rapid gradient-echo (MP-RAGE) sequence. MATERIALS AND METHODS: Seventeen patients with 161 brain metastases were examined prospectively using both SPACE and MP-RAGE sequences on a 3-T magnetic resonance system. Eight healthy volunteers were similarly examined for determination of signal-to-noise ratio (SNR) values. Parameters were adjusted to equalize acquisition times between the sequences (3 minutes and 30 seconds). The order in which sequences were performed was randomized. Two blinded board-certified neuroradiologists evaluated the number of detectable metastatic lesions with each sequence relative to a criterion standard reading conducted at the Gamma Knife facility by a neuroradiologist with access to all clinical and imaging data. RESULTS: In the volunteer assessment with SPACE and MP-RAGE, SNR (10.3 ± 0.8 vs 7.7 ± 0.7) and contrast-to-noise ratio (0.8 ± 0.2 vs 0.5 ± 0.1) were statistically significantly greater with the SPACE sequence (P < 0.05). Overall, lesion detection was markedly improved with the SPACE sequence (99.1% of lesions for reader 1 and 96.3% of lesions for reader 2) compared with the MP-RAGE sequence (73.6% of lesions for reader 1 and 68.5% of lesions for reader 2; P < 0.01). CONCLUSIONS: A 3D T1-weighted fast spin echo sequence (SPACE) improves detection of metastatic lesions relative to 3D T1-weighted gradient-echo-based scan (MP-RAGE) imaging when implemented with a 32-channel head coil at identical scan acquisition times (3 minutes and 30 seconds).