Biomedical Engineering

Introduction: Traditional Advanced Cardiac Life Support (ACLS) courses are evaluated using written multiple-choice tests. High-fidelity simulation is a widely used adjunct to didactic content, and has been used in many specialties as a training resource as well as an evaluative tool. There are no data to our knowledge that compare simulation examination scores with written test scores for ACLS courses. Objective: To compare and correlate a novel high-fidelity simulation-based evaluation with traditional written testing for senior medical students in an ACLS course.

Methods: We performed a prospective cohort study to determine the correlation between simulation-based evaluation and traditional written testing in a medical school simulation center. Students were tested on a standard acute coronary syndrome/ventricular fibrillation cardiac arrest scenario. Our primary outcome measure was correlation of exam results for 19 volunteer fourth-year medical students after a 32-hour ACLS-based Resuscitation Boot Camp course. Our secondary outcome was comparison of simulation-based vs. written outcome scores.

Results: The composite average score on the written evaluation was substantially higher (93.6%) than the simulation performance score (81.3%, absolute difference 12.3%, 95% CI [10.6-14.0%], p<0.00005). We found a statistically significant moderate correlation between simulation scenario test performance and traditional written testing (Pearson r=0.48, p=0.04), validating the new evaluation method.

Conclusion: Simulation-based ACLS evaluation methods correlate with traditional written testing and demonstrate resuscitation knowledge and skills. Simulation may be a more discriminating and challenging testing method, as students scored higher on written evaluation methods compared to simulation.

Cardiovascular disease affects nearly 50% of adults in the United States, with many requiring right heart catheterization as part of their diagnosis or treatment. A common approach for this procedure is the groin-to-right heart catheterization, which involves inserting a catheter through the femoral vein into the right atrium, allowing access to the interatrial septum. While transradial access (via the arm or wrist) has become increasingly popular due to a lower risk of complications such as major bleeding or stroke, femoral access (via the groin) remains necessary in cases requiring larger catheters or more complex procedures. However, the femoral access approach carries a higher risk of bleeding and vascular injury due to its deeper access site and the potential for excessive insertion force. Therefore, there is a critical need to develop realistic, high-fidelity testing models that simulate the femoral access procedure to enhance procedural safety and outcomes. These models are designed to accurately assess catheter insertion forces and allow early detection of potential device failures before animal or clinical testing. Contemporary simulation models are costly, use hard-to-source materials, and are intended for training purposes rather than research and development (R&D). To address these gaps, we developed a cost-effective, accessible, and easy-to-manufacture groin puncture model that simulates femoral access. Our model features viscoelastic components with anatomically relevant thickness that mimic the mechanical properties (i.e. Young’s modulus and Ultimate Tensile Strength (UTS)) of skin, fat, and the femoral vein. These layers are supported by a 3D-printed, Instron-compatible fixture that securely holds the model during catheter puncture force testing. The model is also made from cheap and easily-accessible materials, including: Dragon Skin™ 10 Fast, Ecoflex™ Gel, FlexFoam-iT!™ III, and F-116 REV 1. Our preliminary tensile tests yielded Young’s modulus values (in MPa) within an order of magnitude for the skin, fat, and vein layers. To approach higher values for the Young’s modulus, we plan to explore curing agent ratios, additional thickening agents, and alternative biomaterial additions. The improvement of this fundamental mechanical property and assessment of UTS ensures that catheter testing is evaluated at realistic, physiologically-accurate stiffnesses to prevent catheter failure. In the future, we aim to expand our platform to develop patient-specific models and simulate the entire right heart catheterization pathway, including the tortuous vascular anatomy and transseptal puncture to the left atrium, with the ultimate goal of enabling more comprehensive testing of catheter performance.

The 3xTg-AD transgenic mouse model develops Aβ plaque and tau pathology and is purported to closely resemble pathological development in the human Alzheimer's disease (AD) brain. Nicotinic acetylcholine receptors (nAChRs) α4β2* subtype, was studied in this mouse model using [¹⁸F]nifene PET/CT and compared with non-transgenic B6129SF2/J mice (male and female). Young 2-month old B6129SF2/J exhibited normal [¹⁸F]nifene distribution (measured as standard uptake volume ratios, SUVR with cerebellum as reference) thalamus (TH) 3.12> medial prefrontal cortex (mPFC) 2.33> frontal cortex (FC) 2.06> hippocampus-subiculum (HP-SUB) 1.6. At 11-months of age, B6129SF2/J exhibited high, irreversible and non-saturable [¹⁸F]nifene binding in mPFC higher than in TH (mPFC 3.8> TH 2.82> FC 1.79> HP-SUB 1.73). The 3xTg-AD also exhibited high mPFC binding, although the region of highest binding within the mPFC was different compared to B6129SF2/J mice (mPFC 2.44> TH 2.27> FC 1.61> HP-SUB 1.48). [¹²⁵I]IBETA and immunohistochemistry in 3xTg-AD brain slices confirmed Aβ plaques. The TH of 3xTg-AD mice had lower [¹⁸F]nifene binding (reduced by approximately 20 %) compared to both, young and old B6129SF2/J, and was significant. The mPFC [¹⁸F]nifene binding was significantly higher in the old B6129SF2/J compared to both the young B6129SF2/J and the 3xTg-AD mice (>150 %). Overall, 3xTg-AD transgenic mice had reduced [¹⁸F]nifene binding compared to B6129SF2/J controls, suggesting possible effects of Aβ plaques and Tau on α4β2* nAChRs.

The nasal valves are not simple, 2-dimensional cross-sections but rather a complex, 3-dimensional, collapsible, and heterogeneous structure. Historically, the internal nasal valve (INV) is defined by the septum medially, the caudal margin of the upper lateral cartilage laterally, and the inferior turbinate inferiorly. Typically located 1.3 cm deep into the nasal cavity, the INV angle delineated by the upper lateral cartilage and septum typically measures 10° to 15° in the Caucasian population. As computational methods reveal new insights into nasal valve function, a new conceptual framework is needed to guide rhinoplasty surgical decision-making.

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Use of one addictive drug typically influences the behavioral response to other drugs, either administered at the same time or a subsequent time point. The nature of the drugs being used, as well as the timing and dosing, also influence how these drugs interact. Here, we tested the effects of adolescent THC exposure on the development of morphine-induced behavioral adaptations following repeated morphine exposure during adulthood. We found that adolescent THC administration paradoxically prevented the development of anxiety-related behaviors that emerge during a forced abstinence period following morphine administration but facilitated reinstatement of morphine CPP. Following forced abstinence, we then mapped the whole-brain response to a moderate dose of morphine and found that adolescent THC administration led to an overall increase in brain-wide neuronal activity and increased the functional connectivity between frontal cortical regions and the ventral tegmental area. Last, we show using rabies virus-based circuit mapping that adolescent THC exposure triggers a long-lasting elevation in connectivity from the frontal cortex regions onto ventral tegmental dopamine cells. Our study adds to the rich literature on the interaction between drugs, including THC and opioids, and provides potential neural substates by which adolescent THC exposure influences responses to morphine later in life.

In epithelial tissues, juxtaposition of cells of different phenotypes can trigger cell competition, a process whereby one type of cell drives death and extrusion of another. During growth and homeostasis, cell competition is thought to serve a quality control function, eliminating cells that are "less fit". Tissues may also attack and eliminate newly arising tumor cells, exploiting mechanisms shared with other instances of cell competition, but that differ, reportedly, in the involvement of the immune system. Whereas immune cells have been shown to play a direct role in killing tumor cells, this has not been observed in other cases of cell competition, suggesting that tissues recognize and handle cancer cells differently. Here, we challenge this view, showing that, in the fruit fly Drosophila, innate immune cells play similar roles in cell killing during classical cell competition as in eliminating tumors. These findings suggest that immune suppression of cancer may exploit the same mechanisms as are involved in promoting phenotypic uniformity among epithelial cells.

Morphogenesis requires highly coordinated, complex interactions between cellular processes: proliferation, migration and apoptosis, along with physical tissue interactions. How these cellular and tissue dynamics drive morphogenesis remains elusive. Three dimensional (3D) microscopic imaging holds great promise, and generates elegant images, but generating even moderate throughput for quantified images is challenging for many reasons. As a result, the association between morphogenesis and cellular processes in 3D developing tissues has not been fully explored. To address this gap, we have developed an imaging and image analysis pipeline to enable 3D quantification of cellular dynamics along with 3D morphology for the same individual embryo. Specifically, we focus on how 3D distribution of proliferation relates to morphogenesis during mouse facial development. Our method involves imaging with light-sheet microscopy, automated segmentation of cells and tissues using machine learning-based tools, and quantification of external morphology by geometric morphometrics. Applying this framework, we show that changes in proliferation are tightly correlated with changes in morphology over the course of facial morphogenesis. These analyses illustrate the potential of this pipeline to investigate mechanistic relationships between cellular dynamics and morphogenesis during embryonic development.