FLECS technology for high-throughput screening of hypercontractile cellular phenotypes in fibrosis: A function-first approach to anti-fibrotic drug discovery.

The pivotal role of myofibroblast contractility in the pathophysiology of fibrosis is widely recognized, yet HTS approaches are not available to quantify this critically important function in drug discovery. We developed, validated, and scaled-up a HTS platform that quantifies contractile function of primary human lung myofibroblasts upon treatment with pro-fibrotic TGF-ß1. With the fully automated assay we screened a library of 40,000 novel small molecules in under 80 h of total assay run-time. We identified 42 hit compounds that inhibited the TGF-ß1-induced contractile phenotype of myofibroblasts, and enriched for 19 that specifically target myofibroblasts but not phenotypically related smooth muscle cells. Selected hits were validated in an ex vivo lung tissue models for their inhibitory effects on fibrotic gene upregulation by TGF-ß1. Our results demonstrate that integrating a functional contraction test into the drug screening process is key to identify compounds with targeted and diverse activity as potential anti-fibrotic agents.

Simplified, High-throughput Analysis of Single-cell Contractility using Micropatterned Elastomers.

Cellular contractile force generation is a fundamental trait shared by virtually all cells. These contractile forces are crucial to proper development, function at both the cellular and tissue levels,and regulate the mechanical systems in the body. Numerous biological processes are force-dependent, including motility, adhesion, and division of single-cells, as well as contraction and relaxation of organs such as the heart, bladder, lungs, intestines, and uterus. Given its importance in maintaining proper physiological function, cellular contractility can also drive disease processes when exaggerated or disrupted. Asthma, hypertension, preterm labor, fibrotic scarring, and underactive bladder are all examples of mechanically driven disease processes that could potentially be alleviated with proper control of cellular contractile force. Here, we present a comprehensive protocol for utilizing a novel microplate-based contractility assay technology known as fluorescently labeled elastomeric contractible surfaces (FLECS), that provides simplified and intuitive analysis of single-cell contractility in a massively scaled manner. Herein, we provide a step-wise protocol for obtaining two six-point dose-response curves describing the effects of two contractile inhibitors on the contraction of primary human bladder smooth muscle cells in a simple procedure utilizing just a single FLECS assay microplate, to demonstrate proper technique to users of the method. Using FLECS Technology, all researchers with basic biological laboratories and fluorescent microscopy systems gain access to studying this fundamental but difficult-to-quantify functional cell phenotype, effectively lowering the entry barrier into the field of force biology and phenotypic screening of contractile cell force.

Characteristics of Takotsubo cardiomyopathy in patients with COVID-19: Systematic scoping review.

BACKGROUND: COVID-19 has recently been associated with the development of Takotsubo cardiomyopathy (TCM). This scoping review aims to summarize the existing evidence regarding TCM in COVID-19 and offer future direction for study. METHODS: Following the PRISMA Extension for Scoping Reviews, MEDLINE and EMBASE were searched for all peer-reviewed articles with relevant keywords including "Takotsubo", "Stress-induced cardiomyopathy" and "COVID-19" from their inception to September 25, 2021. RESULTS: A total of 40 articles with 52 cases were included. Patients with TCM and COVID-19 showed only slight female predominance (59.6%), median age of 68.5 years, and were mostly of the apical subtype (88.6%). All-cause mortality was 36.5%. The median LVEF was 30%. Compared to those without TCM, those with TCM in COVID-19 had more critical illness, higher mortality, lower LVEF, and higher cardiac and inflammatory biomarkers. Notably, the diagnostic criteria of TCM were considerably different between case reports and observational studies. CONCLUSION: This scoping review identifies that TCM in COVID-19 may have distinct features that distinguish this condition from TCM without COVID-19. Future studies are warranted to help describe risk factors, determine the utility of inflammatory biomarkers and serum catecholamine levels, and establish disease-specific diagnostic criteria.

Characteristics of bradyarrhythmia in patients with COVID-19: Systematic scoping review.

COVID-19 has recently been associated with the development of bradyarrhythmias, although its mechanism is still unclear. We aim to summarize the existing evidence regarding bradyarrhythmia in COVID-19 and provide future directions for research. Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including"Bradycardia," "atrioventricular block," and "COVID-19″ from their inception to October 13, 2021. Forty-three articles, including 11 observational studies and 59 cases from case reports and series, were included in the systematic review. Although some observational studies reported increased mortality in those with bradyarrhythmia and COVID-19, the lack of comparative groups and small sample sizes hinder the ability to draw definitive conclusions. Among 59 COVID-19 patients with bradycardia from case reports and series, bradycardia most often occurred in those with severe or critical COVID-19, and complete heart block occurred in the majority of cases despite preserved LVEF (55.9%). Pacemaker insertion was required in 76.3% of the patients, most of which were permanent implants (45.8%). This systematic review summarizes the current evidence and characteristics of bradyarrhythmia in patients with COVID-19. Further studies are critical to assess the reversibility of bradyarrhythmia in COVID-19 patients and to clarify potential therapeutic targets including the need for permanent pacing.

vTrain: a novel curriculum for patient surge training in a multi-user virtual environment (MUVE).

INTRODUCTION: During a pandemic influenza, emergency departments will be overwhelmed with a large influx of patients seeking care. Although all hospitals should have a written plan for dealing with this surge of health care utilization, most hospitals struggle with ways to educate the staff and practice for potentially catastrophic events. Hypothesis/Problem To better prepare hospital staff for a patient surge, a novel educational curriculum was developed utilizing an emergency department for a patient surge functional drill. METHODS: A multidisciplinary team of medical educators, evaluators, emergency preparedness experts, and technology specialists developed a curriculum to: (1) train novice users to function in their job class in a multi-user virtual environment (MUVE); (2) obtain appropriate pre-drill disaster preparedness training; (3) perform functional team exercises in a MUVE; and (4) reflect on their performance after the drill. RESULTS: A total of 14 students participated in one of two iterations of the pilot training program; seven nurses completed the emergency department triage course, and seven hospital administrators completed the Command Post (CP) course. All participants reported positive experiences in written course evaluations and structured verbal debriefings, and self-reported increase in disaster preparedness knowledge. Students also reported improved team communication, planning, team decision making, and the ability to visualize and reflect on their performance. CONCLUSION: Data from this pilot program suggest that the immersive, virtual teaching method is well suited to team-based, reflective practice and learning of disaster management skills.

Achieving reliable communication in dynamic emergency responses.

Emergency responses require the coordination of first responders to assess the condition of victims, stabilize their condition, and transport them to hospitals based on the severity of their injuries. WIISARD is a system designed to facilitate the collection of medical information and its reliable dissemination during emergency responses. A key challenge in WIISARD is to deliver data with high reliability as first responders move and operate in a dynamic radio environment fraught with frequent network disconnections. The initial WIISARD system employed a client-server architecture and an ad-hoc routing protocol was used to exchange data. The system had low reliability when deployed during emergency drills. In this paper, we identify the underlying causes of unreliability and propose a novel peer-to-peer architecture that in combination with a gossip-based communication protocol achieves high reliability. Empirical studies show that compared to the initial WIISARD system, the redesigned system improves reliability by as much as 37% while reducing the number of transmitted packets by 23%.

Comparison of the effectiveness of wireless electronic tracking devices versus traditional paper systems to track victims in a large scale disaster.

We conducted an unblinded experimental comparative trial during a disaster drill involving DMATs using the WIISARD system and traditional paper tracking of casualties. We shadowed the paper work flow to collect data on 40 victims tracked by both systems. WIISARD captured patients as well as the paper system. However, WIISARDwas superior at tracking patient destinations and transporting units. WIISARD proved to be an effective victim tracking system.

Field provider position tracking at mass gathering events.

WIISARD (Wireless Internet Information System for Medical Response to Disasters) utilizes wireless technology to improve medical care at mass casualty disasters. An important component of WIISARD is geolocation tracking of field personnel at the disaster site. Accurate, real-time information on personnel has the potential to improve resource utilization at the disaster site, as well as increase the safety of first responders caring for victims at a hazardous scene.

Role-tailored software systems for coordinating care at disaster sites: enhancing collaboration between the base hospitals with the field.

The WIISARD disaster response patient tracking program that allows for improved process flow, communication, and patient care using sophisticated wireless technology to coordinate and enhance the care of mass casualties in terrorist attacks or natural disasters. The MICN device has been developed as the link between the Base Station Mobile Intensive Care Nurse and Incident Command in the field. This tool allows the MICN coordinating the incident from the hospital side to more effectively and efficiently communicate with the Incident Command for the accurate and rapid distribution of patients from the scene to the hospitals.

Tablet computing for disaster scene managers.

WIISARD utilizes wireless technology to improve the care of victims following a mass casualty disaster. The WIISARD Scene Manager device (WSM) is designed to enhance the collection and accessibility of real-time data on victims, ambulances and hospitals for disaster supervisors and managers. We recently deployed WSM during a large-scale disaster exercise. The WSM performed well logging and tracking victims and ambulances. Scene managers had access to data and utilized the WSM to coordinate patient care and disposition.