Does an instructional video as a stand-alone tool promote the acquisition of practical clinical skills? A randomised simulation research trial of skills acquisition and short-term retention.

BACKGROUND: The effectiveness of instructional videos as a stand-alone tool for the acquisition of practical skills is yet unknown because instructional videos are usually didactically embedded. Therefore, we evaluated the acquisition of the skill of a humeral intraosseous access via video in comparison to that of a self-study with an additional retention test. METHODS: After ethical approval, we conducted two consecutive studies. Both were designed as randomised controlled two-armed trials with last-year medical students as independent samples at our institutional simulation centre of a tertiary university hospital centre. In Study 1, we randomly assigned 78 participants to two groups: Vid-Self participants watched an instructional video as an intervention, followed by a test, and after seven days did a self-study as a control, followed by a test. Self-Vid ran through the trial in reverse order. In Study 2, we investigated the influence of the sequence of the two teaching methods on learning success in a new sample of 60 participants: Vid-Self watched an instructional video and directly afterward did the self-study followed by a test, whereas Self-Vid ran through that trial in reverse order. In Studies 1 and 2, the primary outcome was the score (worst score = 0, best score = 20) of the test after intervention and control. The secondary outcome in Study 1 was the change in score after seven days. RESULTS: Study 1: The Vid-Self (Participants n = 42) was superior to the Self-Vid (n = 36) (mean score 14.8 vs. 7.7, p < 0.001). After seven days, Self-vid outperformed Vid-Self (mean score 15.9 vs. 12.5, p < 0.001). Study 2: The Vid-Self (n = 30) and Self-Vid (n = 30) scores did not significantly differ (mean 16.5 vs. mean 16.5, p = 0.97). CONCLUSION: An instructional video as a stand-alone tool effectively promotes the acquisition of practical skills. The best results are yielded by a combination of an instructional video and self-study right after each other, irrespective of sequence. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT05066204 (13/04/2021) (Study 1) and NCT04842357 (04/10/2021) (Study 2).

Bionic Nanocoating of Prosthetic Grafts Significantly Reduces Bacterial Growth.

Prosthetic materials are a source of bacterial infections, with significant morbidity and mortality. Utilizing the bionic "Lotus effect," we generated superhydrophobic vascular prostheses by nanocoating and investigated their resistance to bacterial colonization. Nanoparticles were generated from silicon dioxide (SiO2), and coated vascular prostheses developed a nanoscale roughness with superhydrophobic characteristics. Coated grafts and untreated controls were incubated with different bacterial solutions including heparinized blood under mechanical stress and during artificial perfusion and were analyzed. Bioviability- and toxicity analyses of SiO2 nanoparticles were performed. Diameters of SiO2 nanoparticles ranged between 20 and 180 nm. Coated prostheses showed a water contact angle of > 150° (mean 154 ± 3°) and a mean water roll-off angle of 9° ± 2°. Toxicity and viability experiments demonstrated no toxic effects of SiO2 nanoparticles on human induced pluripotent stem cell-derived cardiomyocytes endothelial cells, fibroblasts, and HEK239T cells. After artificial perfusion with a bacterial solution (Luciferase+ Escherichia coli), bioluminescence imaging measurements showed a significant reduction of bacterial colonization of superhydrophobic material-coated prostheses compared to that of untreated controls. At the final measurement (t = 60 min), a 97% reduction of bacterial colonization was observed with superhydrophobic material-coated prostheses. Superhydrophobic vascular prostheses tremendously reduced bacterial growth. During artificial perfusion, the protective superhydrophobic effects of the vascular grafts could be confirmed using bioluminescence imaging.

Capsid protein structure, self-assembly, and processing reveal morphogenesis of the marine virophage mavirus.

Virophages have the unique property of parasitizing giant viruses within unicellular hosts. Little is understood about how they form infectious virions in this tripartite interplay. We provide mechanistic insights into assembly and maturation of mavirus, a marine virophage, by combining structural and stability studies on capsomers, virus-like particles (VLPs), and native virions. We found that the mavirus protease processes the double jelly-roll (DJR) major capsid protein (MCP) at multiple C-terminal sites and that these sites are conserved among virophages. Mavirus MCP assembled in Escherichia coli in the absence and presence of penton protein, forming VLPs with defined size and shape. While quantifying VLPs in E. coli lysates, we found that full-length rather than processed MCP is the competent state for capsid assembly. Full-length MCP was thermally more labile than truncated MCP, and crystal structures of both states indicate that full-length MCP has an expanded DJR core. Thus, we propose that the MCP C-terminal domain serves as a scaffolding domain by adding strain on MCP to confer assembly competence. Mavirus protease processed MCP more efficiently after capsid assembly, which provides a regulation mechanism for timing capsid maturation. By analogy to Sputnik and adenovirus, we propose that MCP processing renders mavirus particles infection competent by loosening interactions between genome and capsid shell and destabilizing pentons for genome release into host cells. The high structural similarity of mavirus and Sputnik capsid proteins together with conservation of protease and MCP processing suggest that assembly and maturation mechanisms described here are universal for virophages.

Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells.

Oncogenic KRas reprograms pancreatic ductal adenocarcinoma (PDAC) cells to states which are highly resistant to apoptosis. Thus, a major preclinical goal is to identify effective strategies for killing PDAC cells. Artesunate (ART) is an anti-malarial that specifically induces programmed cell death in different cancer cell types, in a manner initiated by reactive oxygen species (ROS)-generation. In this study we demonstrate that ART specifically induced ROS- and lysosomal iron-dependent cell death in PDAC cell lines. Highest cytotoxicity was obtained in PDAC cell lines with constitutively-active KRas, and ART did not affect non-neoplastic human pancreatic ductal epithelial (HPDE) cells. We determined that ART did not induce apoptosis or necroptosis. Instead, ART induced ferroptosis, a recently described mode of ROS- and iron-dependent programmed necrosis which can be activated in Ras-transformed cells. Co-treatment with the ferroptosis inhibitor ferrostatin-1 blocked ART-induced lipid peroxidation and cell death, and increased long-term cell survival and proliferation. Importantly, analysis of PDAC patient mRNA expression indicates a dependency on antioxidant homeostasis and increased sensitivity to free intracellular iron, both of which correlate with Ras-driven sensitivity to ferroptosis. Overall, our findings suggest that ART activation of ferroptosis is an effective, novel pathway for killing PDAC cells.