Radiofrequency-Triggered Drug Release from Nanoliposomes with Millimeter-Scale Resolution Using a Superimposed Static Gating Field.

Drug delivery to a specific site in the body typically relies on the use of targeting agents that recognize a unique biomarker. Unfortunately, it is often difficult to identify unique molecular signatures that exist only at the site of interest. An alternative strategy is to deliver energy (e.g., light) to locally trigger release from a drug carrier; however, the use of this approach is limited because energy delivery to deep tissues is often impractical or invasive. In this work, radiofrequency-responsive superparamagnetic iron oxide nanoparticles (SPIONs) are used to trigger drug release from nanoscale vesicles. Because the body is inherently nonmagnetic, this approach allows for deep tissue targeting. To overcome the unfavorable meter-scale diffraction limit of SPION-compatible radiofrequency (RF) fields, a strong static gating field containing a sharp zero point is superimposed on the RF field. Only drug carriers that are at or near the zero point are susceptible to RF-triggered drug release, thereby localizing drug delivery with millimeter-scale resolution. This approach induces >40% drug release from thermally responsive doxorubicin-loaded liposomes within a 3.2 mm radius of the zero point with <10% release in the surrounding area, leading to a >2.5 therapeutic index in Huh 7 hepatocellular carcinoma cells.

MicroRNAs control intestinal epithelial differentiation, architecture, and barrier function.

BACKGROUND & AIMS: Whereas the importance of microRNA (miRNA) for the development of several tissues is well established, its role in the intestine is unknown. We aimed to quantify the complete miRNA expression profile of the mammalian intestinal mucosa and to determine the contribution of miRNAs to intestinal homeostasis using genetic means. METHODS: We determined the miRNA transcriptome of the mouse intestinal mucosa using ultrahigh throughput sequencing. Using high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP), we identified miRNA-messenger RNA target relationships in the jejunum. We employed gene ablation of the obligatory miRNA-processing enzyme Dicer1 to derive mice deficient for all miRNAs in intestinal epithelia. RESULTS: miRNA abundance varies dramatically in the intestinal mucosa, from 1 read per million to 250,000. Of the 453 miRNA families identified, mmu-miR-192 is the most highly expressed in both the small and large intestinal mucosa, and there is a 53% overlap in the top 15 expressed miRNAs between the 2 tissues. The intestinal epithelium of Dicer1(loxP/loxP);Villin-Cre mutant mice is disorganized, with a decrease in goblet cells, a dramatic increase in apoptosis in crypts of both jejunum and colon, and accelerated jejunal cell migration. Furthermore, intestinal barrier function is impaired in Dicer1-deficient mice, resulting in intestinal inflammation with lymphocyte and neutrophil infiltration. Our list of miRNA-messenger RNA targeting relationships in the small intestinal mucosa provides insight into the molecular mechanisms behind the phenotype of Dicer1 mutant mice. CONCLUSIONS: We have identified all intestinal miRNAs and shown using gene ablation of Dicer1 that miRNAs play a vital role in the differentiation and function of the intestinal epithelium.

The academic experience in distance (virtual) rounding and education of emergency surgery during COVID-19 pandemic.

BACKGROUND: To cope with COVID-19 pandemic control precautions, many surgical residency programs have adopted a Declared Health Emergency rotation to minimize exposure to the COVID-19. We evaluated the experience and educational value of virtual education activities by reviewing the perceptions of the Declared Health Emergency rotation participants through survey questionnaire analysis. METHODS: Participants of the Declared Health Emergency rotation virtual educational activities were asked to complete a survey questionnaire describing their perception and experience. RESULTS: The survey response rate was 100% (faculty, n = 13; residents, n = 8; nurse practitioners/physician assistants, n = 4). The majority reported that virtual activities required minimal technical skills (n = 17, 68%). Compared to the traditional in-person conferences before the pandemic, the majority reported that they participated in virtual rounds more often or the same (n = 22, 88%), that the overall level and quality of interactions were the same or better (n = 19, 76%), and that the knowledge gained was the same or more (n = 22, 88%). All respondents reported that virtual conferences educational objectives were met. CONCLUSION: The quality of education and the knowledge gain during the virtual educational activities are equivalent or better than in the traditional face-to-face activities. The use of technology in virtual educational activities is a practical and convenient approach to achieve the desired educational objectives during and potentially after the COVID-19 pandemic.