An Innovative Curriculum For Teaching Transesophageal Echocardiography (TEE) to Emergency Medicine Residents.

BACKGROUND: Focused transesophageal echocardiogram (TEE) can be a valuable tool for emergency physicians (EP) during cardiac arrest. OBJECTIVES: We sought to demonstrate the ability of emergency medicine (EM) residents without prior TEE experience to perform a simulated four-view TEE following a short, flipped conference curriculum. METHODS: This was a prospective, simulation-based study where EM residents participated in the following four-view TEE curriculum: 1 h of online content reviewed prior to a 20-min in-person lecture and 30-min hands-on practice using a TEE trainer. Each resident attended four testing sessions over an 8-week period and performed a total of 25 TEE scans. Each TEE scan was graded in real time using a 10-point checklist by a TEE-credentialed EP. Interrater reliability of the checklist was calculated using the kappa coefficient (κ). A random sample of 10% of the TEE scans were reviewed by a TEE expert using a standard ultrasound 1-5 scale for image acquisition quality, with a "3" considered to be satisfactory. Residents completed an online pretest and posttest. RESULTS: Twenty-four residents participated. Mean pre- and posttest scores were 52% (SD 16) and 92% (SD 12), respectively. Mean TEE scores using the 10-point checklist after sessions one and four were 9.4 (SD 0.4) and 9.7 (SD 0.3), respectively. Mean time to complete each TEE scan after sessions one and four were 118.1 (SD 28.3) and 57.1 (SD 17.0) s, respectively. The κ for the checklist was 1. The median score for the image acquisition review was 3 (interquartile range 3-4). CONCLUSIONS: This simplified flipped conference curriculum can train EM residents to competently perform TEE in a simulated environment.

Cross-inhibition of pathogenic agents and the host proteins they exploit.

The major limitations of pathogen-directed therapies are the emergence of drug-resistance and their narrow spectrum of coverage. A recently applied approach directs therapies against host proteins exploited by pathogens in order to circumvent these limitations. However, host-oriented drugs leave the pathogens unaffected and may result in continued pathogen dissemination. In this study we aimed to discover drugs that could simultaneously cross-inhibit pathogenic agents, as well as the host proteins that mediate their lethality. We observed that many pathogenic and host-assisting proteins belong to the same functional class. In doing so we targeted a protease component of anthrax toxin as well as host proteases exploited by this toxin. We identified two approved drugs, ascorbic acid 6-palmitate and salmon sperm protamine, that effectively inhibited anthrax cytotoxic protease and demonstrated that they also block proteolytic activities of host furin, cathepsin B, and caspases that mediate toxin's lethality in cells. We demonstrated that these drugs are broad-spectrum and reduce cellular sensitivity to other bacterial toxins that require the same host proteases. This approach should be generally applicable to the discovery of simultaneous pathogen and host-targeting inhibitors of many additional pathogenic agents.

Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus.

Diverse pathogenic agents often utilize overlapping host networks, and hub proteins within these networks represent attractive targets for broad-spectrum drugs. Using bacterial toxins, we describe a new approach for discovering broad-spectrum therapies capable of inhibiting host proteins that mediate multiple pathogenic pathways. This approach can be widely used, as it combines genetic-based target identification with cell survival-based and protein function-based multiplex drug screens, and concurrently discovers therapeutic compounds and their protein targets. Using B-lymphoblastoid cells derived from the HapMap Project cohort of persons of African, European, and Asian ancestry we identified host caspases as hub proteins that mediate the lethality of multiple pathogenic agents. We discovered that an approved drug, Bithionol, inhibits host caspases and also reduces the detrimental effects of anthrax lethal toxin, diphtheria toxin, cholera toxin, Pseudomonas aeruginosa exotoxin A, Botulinum neurotoxin, ricin, and Zika virus. Our study reveals the practicality of identifying host proteins that mediate multiple disease pathways and discovering broad-spectrum therapies that target these hub proteins.