Background During the COVID-19 pandemic, in-person cadaveric dissection laboratories for teaching anatomy were omitted by many schools around the world. While knowledge domains can be easily evaluated via remote exams, non-traditional discipline-independent skills such as those encouraged through reflection on the topic of death are often overlooked. This study investigated how different anatomy course formats played a role in initiating students’ reflections on death during the COVID-19 pandemic. Method In fall 2020, 217 medical, dental, premedical, and health sciences students from 13 international universities discussed differences in their anatomy courses online. Formats of anatomy courses ranged from dissection-based, prosection-based, hybrid (combination of dissection and prosection) to no laboratory exposure at all. Students’ responses to the question, “Did/does your anatomy course initiate your thinking about life's passing?” were collected, and they self-reported themes that were present in their reflections on death using a multiple-choice prompt. Statistical analyses to detect differences between students with and without exposure to cadavers were performed using the chi-squared test. Results When comparing students who had exposure to human anatomical specimens to those who had no exposure, the majority of students with exposure thought that the course did initiate thoughts about life’s passing, compared to students without exposure ( P < 0.05). Reflection themes were consistent across groups. Discussion These findings indicate that anatomy dissection courses are important for the initiation of students’ feelings about the topic of death. Omission of cadaveric dissection- or prosection-based laboratories will decrease the likelihood that students initiate reflection on this topic and gain important transferable skills.
microRNAs (miRs) are small regulatory RNAs that are frequently deregulated in liver disease. Liver fibrosis is characterized by excessive scarring caused by chronic inflammatory processes. In this study, we determined the functional role of miR-132 using a locked nucleic acid (LNA)-anti-miR approach in liver fibrosis. A significant induction in miR-132 levels was found in mice treated with CCl 4 and in patients with fibrosis/ cirrhosis. Inhibition of miR-132 in mice with LNA-anti-miR-132 caused decreases in CCl 4 -induced fibrogenesis and inflammatory phenotype. An attenuation in collagen fibers, a SMA, MCP1, IL-1b, and Cox2 was found in LNA-anti-miR-132treated mice. CCl 4 treatment increased caspase 3 activity and extracellular vesicles (EVs) in control but not in anti-miR-132-treated mice. Inhibition of miR-132 was associated with augmentation of MMP12 in the liver and Kupffer cells. In vivo and in vitro studies suggest miR-132 targets SIRT1 and inflammatory genes. Using tumor cancer genome atlas data, an increase in miR-132 was found in hepatocellular carcinoma (HCC). Increased miR-132 levels were associated with fibrogenic genes, higher tumor grade and stage, and unfavorable survival in HCC patients. Therapeutic inhibition of miR-132 might be a new approach to alleviate liver fibrosis, and treatment efficacy can be monitored by observing EV shedding.
Historically, Anatomy education is an in‐person discipline involving exposure to human body donors that facilitates personal and professional growth through, in part, the initiation of reflection on the topic of death. However, during the COVID‐19 pandemic the decreased exposure to cadaveric anatomy for many health professions students may have influenced the depth of their individual reflections on this topic. Accordingly, this study aimed to investigate the effect of an alternate approach—focus group discussions between peers with varying degrees of exposure to cadaveric material—that may offer one strategy to stimulate deep reflection on the topic of death. A programmatic intervention was introduced, wherein students (n = 221) from 13 international universities discussed differences in their anatomy courses during small focus group sessions as part of an online exchange program. An inductive semantic thematic analysis was conducted on responses to an open‐ended text–response question on how the activity influenced students' reflections about death. Resulting themes were organized into categories that described the content and topics of the students' discussions as they grappled with this sensitive topic. The students reportedly engaged in deep reflection and expressed an increased sense of connectedness with their peers, despite their disparate exposure levels to cadaveric anatomy and being physically distanced. This demonstrates that focus groups with students experiencing different laboratory contexts can be used to help all students reflect on the topic of death and that interchanges between dissecting and non‐dissecting students can initiate thoughts about death and body donation among non‐dissecting students.
Exosomes are naturally occurring vesicles that have the potential to be manipulated to become promising drug delivery vehicles for on-demand in vitro and in vivo gene editing. Here, we developed the modular safeEXO platform, a prototype exosome delivery vehicle that is mostly devoid of endogenous RNA and can efficaciously deliver RNA and ribonucleoprotein (RNP) complexes to their intended intracellular targets manifested by downstream biologic activity. We also successfully engineered producer cells to produce safeEXO vehicles that contain endogenous Cas9 (safeEXO-CAS) to effectively deliver efficient ribonucleoprotein (RNP)-mediated CRISPR genome editing machinery to organs or diseased cells in vitro and in vivo. We confirmed that safeEXO-CAS exosomes could co-deliver ssDNA, sgRNA and siRNA, and efficaciously mediate gene insertion in a dose-dependent manner. We demonstrated the potential to target safeEXO-CAS exosomes by engineering exosomes to express a tissue-specific moiety, integrin alpha-6 (safeEXO-CAS-ITGA6), which increased their uptake to lung epithelial cells in vitro and in vivo. We tested the ability of safeEXO-CAS-ITGA6 loaded with EMX1 sgRNAs to induce lung-targeted editing in mice, which demonstrated significant gene editing in the lungs with no signs of morbidity or detectable changes in immune cell populations. Our results demonstrate that our modular safeEXO platform represents a targetable, safe and efficacious vehicle to deliver nucleic acid-based therapeutics that successfully reach their intracellular targets. Furthermore, safeEXO producer cells can be genetically manipulated to produce safeEXO vehicles containing CRISPR machinery for more efficient RNP-mediated genome editing. This platform has the potential to improve current therapies and increase the landscape of treatment for various human diseases using RNAi and CRISPR approaches.
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