60 Years of the 3Rs symposium: Lessons learned and the road ahead.

When The Principles of Humane Experimental Technique was published in 1959, authors William Russell and Rex Burch had a modest goal: to make researchers think about what they were doing in the laboratory – and to do it more humanely. Sixty years later, their groundbreaking book was celebrated for inspiring a revolution in science and launching a new field: The 3Rs of alternatives to animal experimentation. On November 22, 2019, some pioneering and leading scientists and researchers in the field gathered at the Johns Hopkins Bloomberg School of Public Health in Bal­timore for the 60 Years of the 3Rs Symposium: Lessons Learned and the Road Ahead.

The 35th annual advances in contrast ultrasound international bubble conference, Chicago 2021: synopsis and take-home messages.

The 35th Annual Advances in Contrast Ultrasound International Bubble Conference convened in Chicago, IL, USA, on September 30th to October 1st, 2021. It featured a range of novel research from animal studies to clinical applications in multiple organ systems, demonstrating the utility of contrast enhanced ultrasound (CEUS). A multidisciplinary group of experts on the use of CEUS, including physicians, basic scientists, engineers, and industry partners, convened to discuss cutting edge research and new applications for CEUS.

Echocardiographic predictors of mortality and morbidity in COVID-19 disease using focused cardiovascular ultrasound.

Background: Focused transthoracic echocardiography (fTTE) has emerged as a critical diagnostic tool during the COVID-19 pandemic, allowing for efficient cardiac imaging while minimizing staff exposure. The utility of fTTE in predicting clinical outcomes in COVID-19 remains under investigation.

Methods: We conducted a retrospective study of 2,266 hospitalized patients at Rush University Medical Center with COVID-19 infection between March and November 2020 who received a fTTE.

Contrast-enhanced ultrasound in pediatric echocardiography.

The safety and benefits of cardiac contrast-enhanced ultrasound (CEUS) have been demonstrated in children and adolescents for a variety of clinical indications, including congenital heart disease. Cardiac CEUS is performed with US and the intravenous administration of ultrasound contrast agents (UCAs). It improves transthoracic echocardiography, which can be challenging in children and adults with acoustic window limitations (e.

Benzocaine-related methaemoglobinemia after transoesophageal echocardiography: a rare, life-threatening complication.

Methaemoglobinemia is an uncommon but potentially life-threatening complication of topical benzocaine use that requires prompt identification in patients who undergo transoesophageal echocardiography (TEE). In this case, a 21-year-old patient who had sustained a stroke with residual right-sided weakness a few days prior to presentation underwent TEE to evaluate for intracardiac shunt. She required intubation as part of her poststroke care with some instrumentation to the posterior oropharynx.

Expecting the unexpected: Echo laboratory preparedness in the time of COVID-19.

COVID-19 poses a unique set of challenges to the healthcare system due to its rapid spread, intensive resource utilization, and relatively high morbidity and mortality. Healthcare workers are at especially high risk of exposure given the viruses spread through close contact. Reported cardiac complications of COVID-19 include myocarditis, acute coronary syndrome, cardiomyopathy, pericardial effusion, arrhythmia, and shock.

The 34th Annual Advances in Contrast Ultrasound International Bubble Conference, Chicago 2019: synopsis and take-home messages.

The 34th annual Advances in Contrast Ultrasound (ACU) International Bubble Conference convened in Chicago, IL, USA, on September 5-6, 2019 to feature new directions of research, preclinical and first-in-man clinical trials, and novel clinical applications highlighting the diversity and utility of contrast enhanced ultrasound (CEUS). An expert group comprising clinicians, engineers, basic scientists, government officials, attorneys, and industry partners convened to collaborate on cutting-edge ultrasound enhancement technology. Utilizing this information, the International Contrast Ultrasound Society (ICUS) continues to have cause to advocate for the safe and appropriate use of CEUS with expanding indications and applications.

Hypertension in older adults: Assessment, management, and challenges.

Hypertension in older adults is related to adverse cardiovascular outcomes, such as heart failure, stroke, myocardial infarction, and death. The global burden of hypertension is increasing due to an aging population and increasing prevalence of obesity, and is estimated to affect one third of the world's population by 2025. Adverse outcomes in older adults are compounded by mechanical hemodynamic changes, arterial stiffness, neurohormonal and autonomic dysregulation, and declining renal function.

An Unusual Cardiac Metastasis: Right Atrial Chondrosarcoma Diagnosed With Multimodality Cardiac Imaging.

• Metastatic cardiac tumors are about 20 times more common than primary cardiac tumors. • Metastatic CS to the myocardium has only rarely been described in case reports. • Cardiac masses are differentiated by clinical context, location, and imaging appearance.

Small Cell Lung Cancer Invading the Left Atrium With Subsequent Malignant Embolic Stroke: A Case Report and Review of Literature.

Cardiac tumors are uncommon, and the vast majority of them are metastases from extracardiac sources. Metastatic spread to the heart causes symptoms by mechanical obstruction of circulation, direct myocardial invasion, or distal embolization. We herein report a case of a 58-year-old male who presented to the hospital with multilobar intracranial embolic infarcts who was found to have small cell lung cancer (SCLC) with invasion of the left atrium and pulmonary artery resulting in malignant embolic stroke.

Consensus statement on the need for innovation, transition and implementation of developmental neurotoxicity (DNT) testing for regulatory purposes.

This consensus statement voices the agreement of scientific stakeholders from regulatory agencies, academia and industry that a new framework needs adopting for assessment of chemicals with the potential to disrupt brain development. An increased prevalence of neurodevelopmental disorders in children has been observed that cannot solely be explained by genetics and recently pre- and postnatal exposure to environmental chemicals has been suspected as a causal factor. There is only very limited information on neurodevelopmental toxicity, leaving thousands of chemicals, that are present in the environment, with high uncertainty concerning their developmental neurotoxicity (DNT) potential.

Pulmonary hypertension: diagnosis, imaging techniques, and novel therapies.

Pulmonary hypertension (PH), defined as the elevation of mean pulmonary arterial pressure (mPAP) above 25 mmHg, has numerous causes, which the World Health Organization (WHO) has divided into five distinct categories based upon the underlying mechanism of action. This review will explore the pathophysiology, diagnostic testing, and treatment of PH. Identification of PH depends on a strong clinical suspicion, a detailed history, and a thorough physical exam.

From in vivo to in vitro: The medical device testing paradigm shift.

Amid growing efforts to advance the replacement, reduction, and refinement of the use of animals in research, there is a growing recognition that in vitro testing of medical devices can be more effective, both in terms of cost and time, and also more reliable than in vivo testing. Although the technological landscape has evolved rapidly in support of these concepts, regulatory acceptance of alternative testing methods has not kept pace. Despite the acceptance by regulators of some in vitro tests (cytotoxicity, gene toxicity, and some hemocompatibility assays), many toxicity tests still rely on animals (irritation, sensitization, acute toxicity, reproductive/developmental toxicity), even where other industrial sectors have already abandoned them.

Multiple Cardioembolic Strokes Caused by Caseous Calcification of the Mitral Annulus.

• Mitral annular calcification (MAC) is a common echocardiographic finding, estimated at around 14%, and occurs especially in elderly women. • Caseous calcification of the mitral annulus (CCMA) is a rare subvariant of MAC, with an echocardiographic prevalence of 0.6% and necropsy prevalence of about 2.

Farm Animal Welfare and Human Health.

The paper examines the relationship between farm animal welfare, industrial farm animal production, and human health consequences. The data suggest that when the animal welfare of land-based farm animals is compromised, there are resulting significant negative human health consequences due to environmental degradation, the use of non-therapeutic levels of antibiotics for growth promotion, and the consequences of intensification. This paper accepts that even if meat and fish consumption is reduced, meat and fish will be part of the diet of the future.

Consensus report on the future of animal-free systemic toxicity testing.

Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing.

Green toxicology.

Historically, early identification and characterization of adverse effects of industrial chemicals was difficult because conventional toxicological test methods did not meet R&D needs for rapid, relatively inexpensive methods amenable to small amounts of test material. The pharmaceutical industry now front-loads toxicity testing, using in silico, in vitro, and less demanding animal tests at earlier stages of product development to identify and anticipate undesirable toxicological effects and optimize product development. The Green Chemistry movement embraces similar ideas for development of less toxic products, safer processes, and less waste and exposure.

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology.

Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.

The use of biomarkers of toxicity for integrating in vitro hazard estimates into risk assessment for humans.

The role that in vitro systems can play in toxicological risk assessment is determined by the appropriateness of the chosen methods, with respect to the way in which in vitro data can be extrapolated to the in vivo situation. This report presents the results of a workshop aimed at better defining the use of in vitro-derived biomarkers of toxicity (BoT) and determining the place these data can have in human risk assessment. As a result, a conceptual framework is presented for the incorporation of in vitro-derived toxicity data into the risk assessment process.

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing.

Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds especially true in the context of the scheduled 2013 marketing ban on cosmetic ingredients tested for systemic toxicity.

A framework program for the teaching of alternative methods (replacement, reduction, refinement) to animal experimentation.

Development of improved communication and education strategies is important to make alternatives to the use of animals, and the broad range of applications of the 3Rs concept better known and understood by different audiences. For this purpose, the Center for Alternatives to Animal Testing in Europe (CAAT-Europe) together with the Transatlantic Think Tank for Toxicology (t(4)) hosted a three-day workshop on "Teaching Alternative Methods to Animal Experimentation". A compilation of the recommendations by a group of international specialists in the field is summarized in this report.