Does high school health education class satisfaction influence student perceptions of public health and pandemic response?

BACKGROUND: The COVID-19 pandemic significantly affected high school students. Little is known about the mediators of student perceptions of infection prevention and public health entities. We piloted a survey to evaluate the relationship between student perceptions of COVID-19 topics and satisfaction with their most recent health class. METHODS: Students from one private high school in southeast Michigan completed a survey in early 2022. The primary outcomes were 4 domains: vaccination knowledge, intervention effectiveness, intervention impact, and willingness to readopt an intervention. We assessed the associations between health class satisfaction and these outcomes using multiple linear regression. RESULTS: One-hundred ninety students reported their health class satisfaction and were eligible for analysis. Students reported high confidence in vaccines (93%) but limited knowledge of COVID-19 vaccination (45%). Students perceived COVID-19 interventions as highly effective (range, 72% [hand hygiene]-93% [vaccination]) and reported a willingness to readopt them (range, 73% [stay-at-home orders]-96% [vaccination]). Health class satisfaction (54%) was positively associated with composite scores on vaccination knowledge and intervention effectiveness. DISCUSSION: Assessing students' intrapandemic perspectives on infection prevention illuminated areas of strength (ie, intervention confidence) and areas for improvement (ie, intervention knowledge and institutional confidence). CONCLUSIONS: Students reported favorable perceptions regarding common infection prevention interventions. Future work should investigate the role of educational satisfaction in mediating confidence in public health interventions and institutions.

Argonaute 2 modulates EGFR-RAS signaling to promote mutant HRAS and NRAS-driven malignancies.

Activating mutations in RAS GTPases drive nearly 30% of all human cancers. Our prior work described an essential role for Argonaute 2 (AGO2), of the RNA-induced silencing complex, in mutant KRAS-driven cancers. Here, we identified a novel endogenous interaction between AGO2 and RAS in both wild-type (WT) and mutant HRAS/NRAS cells. This interaction was regulated through EGFR-mediated phosphorylation of Y393-AGO2, and utilizing molecular dynamic simulation, we identified a conformational change in pY393-AGO2 protein structure leading to disruption of the RAS binding site. Knockdown of AGO2 led to a profound decrease in proliferation of mutant HRAS/NRAS-driven cell lines but not WT RAS cells. These cells demonstrated oncogene-induced senescence (OIS) as evidenced by ß-galactosidase staining and induction of multiple downstream senescence effectors. Mechanistically, we discovered that the senescent phenotype was mediated via induction of reactive oxygen species. Intriguingly, we further identified that loss of AGO2 promoted a novel feed forward pathway leading to inhibition of the PTP1B phosphatase and activation of EGFR-MAPK signaling, consequently resulting in OIS. Taken together, our study demonstrates that the EGFR-AGO2-RAS signaling axis is essential for maintaining mutant HRAS and NRAS-driven malignancies.

An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development.

Both KRAS and EGFR are essential mediators of pancreatic cancer development and interact with Argonaute 2 (AGO2) to perturb its function. Here, in a mouse model of mutant KRAS-driven pancreatic cancer, loss of AGO2 allows precursor lesion (PanIN) formation yet prevents progression to pancreatic ductal adenocarcinoma (PDAC). Precursor lesions with AGO2 ablation undergo oncogene-induced senescence with altered microRNA expression and EGFR/RAS signaling, bypassed by loss of p53. In mouse and human pancreatic tissues, PDAC progression is associated with increased plasma membrane localization of RAS/AGO2. Furthermore, phosphorylation of AGO2Y393 disrupts both the wild-type and oncogenic KRAS-AGO2 interaction, albeit under different conditions. ARS-1620 (G12C-specific inhibitor) disrupts the KRASG12C-AGO2 interaction, suggesting that the interaction is targetable. Altogether, our study supports a biphasic model of pancreatic cancer development: an AGO2-independent early phase of PanIN formation reliant on EGFR-RAS signaling, and an AGO2-dependent phase wherein the mutant KRAS-AGO2 interaction is critical for PDAC progression.

Novel method used to test pullout parameters of different nephrostomy catheters.

PURPOSE: To present a novel in-vitro pig model for testing the design and function of different internal catheter constructs, along with the resulting exit wound resulting from removal. MATERIALS AND METHODS: We compared the pullout parameters of two nephrostomy catheters that differ only in their internal loop design. RESULTS: Greater force, work, and displacement are necessary to extricate catheters with a double loop without increasing exit-wound size. CONCLUSION: Although the differences were not statistically significant, results from this model have potential clinical implications that may prompt further design modifications and prototype development to improve the retention of catheters in the kidney, thus reducing patient discomfort and costs associated with repeated catheter placement.