Comparing Cardiac Dynamics between Neonatal and Adult Rats

Background: Cardiovascular physiology studies have been largely limited to adult models; yet, significant developmental differences exist between the immature and adult heart. The field of pediatric research has largely been limited to immortalized cardiomyocyte cell lines, which lack physiologically relevant action potentials, and primary neonatal myocytes that have a limited life span and lack physiologically relevant automaticity. As a result, our understanding of developmental changes in ion channel expression, t-tubule development, and excitation-contraction coupling have been deduced from 2D simplified cell models. To fully understand cardiac development from neonate to adult, a physiologically-relevant 3D whole heart model is needed to monitor dynamic changes in electrical activity and excitation-contraction coupling. Objective: This study aimed to establish a pediatric research model to monitor developmental changes in electrical activity and excitation-contraction coupling, using both imaging tools and electrocardiograms. Methods/Design: Sprague-Dawley rat hearts (3 days – adult) were excised, the aorta was cannulated, and then the heart was transferred to a temperature-controlled constant pressure Langendorff-perfusion system. The perfusate was supplemented with 10 mM blebbistatin to reduce motion artifacts by mechanically uncoupling electrical and mechanical activity. Calcium (50 mg Rhod2-AM) and voltage (62 mg RH237) sensitive dyes were used to stain the heart, signals were acquired using a sCMOS camera (Andor, Zyla 4.2 Plus; \u3e500fps). Electrocardiograms were monitored continuously (lead II configuration) and analyzed using ecgAUTO. Results/Discussion: Initial results showed that compared to adult cohorts, neonatal rats displayed a longer action potential duration (APD80: adult= 85.9ms, neonatal=95.5ms, p=0.026), and a steeper Tau Fall (adults: 33.8ms, neonatal 69.9ms, p=.012) which are likely associated with delayed Ito expression. Calcium handling was also slower in the neonatal hearts (Cad80: Adults: 128.9ms, neonatal=138.8, p=.004), likely due to immature calcium handling and less robust calcium-induced calcium release. The developing excitation-contraction coupling machinery will be further probed using pharmacological tools to elucidate underlying mechanisms; and the newly developed pediatric model will be used for toxicological screening. Acknowledgements: The authors gratefully acknowledge Daniel McInerney for technical assistance. This work was supported by the National Institutes of Health (R00ES023477, R01HL139472), Children’s Research Institute and Children’s National Heart Institute

Atividades digitais através do Edilim no 1º ciclo do ensino básico : resultados de uma investigação na prática de ensino supervisionada

As TIC fazem parte fundamental da nossa vida sendo indispensáveis para as atividades diárias de cada cidadão. Naturalmente, no sistema educativo as TIC também transformam o dia a dia na comunidade educativa. Neste sentido, a formação dos jovens em TIC para adquirirem competências digitais é um aspeto fundamental para os preparar para a sociedade atual e que deve ser inicializada através da sua utilização em contexto de sala de aula. O Relatório de Estágio pretendeu averiguar as potencialidades da utilização das TIC e o impacto, em particular, da implementação de um software de autor «EdiLim» através dos seguintes objetivos: promover a utilização de recursos digitais nas aprendizagens do 1.° Ciclo; identificar qual a utilização das TIC que os professores fazem no contexto de sala de aula; implementar atividades pedagógicas com atividades através do EdiLim; avaliar o contributo para as aprendizagens através da utilização do EdiLim. Esta investigação foi desenvolvida no âmbito da Prática de Ensino Supervisionada no 1º Ciclo do Ensino Básico (PES1CEB), no 2º ano do Mestrado em Educação Pré-Escolar e Ensino do 1º Ciclo do Ensino Básico. A turma era constituída por 22 alunos com idades compreendidas entre os 9 e os 10 anos. A investigação assumiu um caráter qualitativo no qual se realizou uma abordagem de estudo de caso e de investigação-ação. O principal instrumento de recolha de dados consistiu na observação participada com recurso a registo fotográfico e notas de campo, tendo como participantes, para além da investigadora e dos alunos, a «Orientadora Cooperante» e o «Par Pedagógico». Houve ainda necessidade de realizar inquéritos por questionários aos alunos e entrevistas semiestruturadas à «Orientadora Cooperante» e a um professor do 1º CEB da Instituição, como forma de conhecer a opinião dos inquiridos e entrevistados face à utilização das TIC e de softwares educativos como recurso no Ensino Básico. Em suma, os resultados da investigação, através da triangulação de dados possibilitaram a perceção de que a utilização do EdiLim veio promover maiores e melhores níveis de motivação dos alunos, favorecendo o processo de ensino e de aprendizagem.info:eu-repo/semantics/publishedVersio

Stop the beat to see the rhythm: excitation-contraction uncoupling in cardiac research.

Optical mapping is an imaging technique that is extensively used in cardiovascular research, wherein parameter-sensitive fluorescent indicators are used to study the electrophysiology and excitation-contraction coupling of cardiac tissues. Despite many benefits of optical mapping, eliminating motion artifacts within the optical signals is a major challenge, as myocardial contraction interferes with the faithful acquisition of action potentials and intracellular calcium transients. As such, excitation-contraction uncoupling agents are frequently used to reduce signal distortion by suppressing contraction. When compared with other uncoupling agents, blebbistatin is the most frequently used, as it offers increased potency with minimal direct effects on cardiac electrophysiology. Nevertheless, blebbistatin may exert secondary effects on electrical activity, metabolism, and coronary flow, and the incorrect administration of blebbistatin to cardiac tissue can prove detrimental, resulting in erroneous interpretation of optical mapping results. In this “Getting It Right” perspective, we briefly review the literature regarding the use of blebbistatin in cardiac optical mapping experiments, highlight potential secondary effects of blebbistatin on cardiac electrical activity and metabolic demand, and conclude with the consensus of the authors on best practices for effectively using blebbistatin in optical mapping studies of cardiac tissue

Bisphenol A exposure and cardiac electrical conduction in excised rat hearts

BACKGROUND: Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased BPA urinary concentrations and cardiovascular disease; yet the direct effects of BPA on the heart are unknown. OBJECTIVES: The goal of our studies was to measure BPA\u27s effect (0.1-100 μM) on cardiac impulse propagation ex vivo, using excised whole hearts from adult rats. METHODS: We measured atrial and ventricular activation times during sinus and paced rhythms using epicardial electrodes and optical mapping of transmembrane potential. Atrioventricular activation intervals and epicardial conduction velocities were computed using recorded activation times. RESULTS: Cardiac BPA exposure resulted in prolonged PR segment and decreased epicardial conduction velocity (0.1 - 100 μM), prolonged action potential duration (1 - 100 μM) and delayed atrioventricular conduction (10 - 100 μM). Importantly, these effects were observed after acute exposure (≤ 15 min), underscoring the potential detrimental effects of continuous BPA exposure. The highest BPA concentration used (100 μM) resulted in prolonged QRS intervals, dropped ventricular beats and eventually resulted in complete heart block. CONCLUSIONS: Our results show that acute BPA exposure slows electrical conduction in excised hearts from female rats. These findings emphasize the importance of examining BPA\u27s effect on heart electrophysiology and determining whether chronic in vivo exposure can cause/exacerbate conduction abnormalities in patients with pre-existing heart conditions and other high-risk populations

Mathematics and biology: a Kantian view on the history of pattern formation theory

Driesch’s statement, made around 1900, that the physics and chemistry of his day were unable to explain self-regulation during embryogenesis was correct and could be extended until the year 1972. The emergence of theories of self-organisation required progress in several areas including chemistry, physics, computing and cybernetics. Two parallel lines of development can be distinguished which both culminated in the early 1970s. Firstly, physicochemical theories of self-organisation arose from theoretical (Lotka 1910–1920) and experimental work (Bray 1920; Belousov 1951) on chemical oscillations. However, this research area gained broader acceptance only after thermodynamics was extended to systems far from equilibrium (1922–1967) and the mechanism of the prime example for a chemical oscillator, the Belousov–Zhabotinski reaction, was deciphered in the early 1970s. Secondly, biological theories of self-organisation were rooted in the intellectual environment of artificial intelligence and cybernetics. Turing wrote his The chemical basis of morphogenesis (1952) after working on the construction of one of the first electronic computers. Likewise, Gierer and Meinhardt’s theory of local activation and lateral inhibition (1972) was influenced by ideas from cybernetics. The Gierer–Meinhardt theory provided an explanation for the first time of both spontaneous formation of spatial order and of self-regulation that proved to be extremely successful in elucidating a wide range of patterning processes. With the advent of developmental genetics in the 1980s, detailed molecular and functional data became available for complex developmental processes, allowing a new generation of data-driven theoretical approaches. Three examples of such approaches will be discussed. The successes and limitations of mathematical pattern formation theory throughout its history suggest a picture of the organism, which has structural similarity to views of the organic world held by the philosopher Immanuel Kant at the end of the eighteenth century

Cross Cultural Experiential Simulation in the Global Marketing Classroom: Bafa-Bafa and Its Variants

This paper reviews the use of the Bafa-Bafa Cross-Cultural Simulation in the Global Marketing classroom. Bafa-Bafa is a powerful experiential cultural simulation designed to encourage exploration of cross-cultural interaction. Its primary strength is its ability, in an artificially manipulated safe and fun environment, to engender the strong feelings associated with being part of one culture and then being forced to interact with another. Variants of the simulation are presented that reduce the time requirements, simplify the simulation, and accommodate large classes

Cheating Goes High Tech: Online Term Paper Mills

As part of the explosive growth in usage of the Internet, an increasing number of vendors are using this medium to make term papers available for students to purchase. This article provides information for management and organizational behavior faculty with regard to the availability of term papers for sale to students over the Internet. A sampling of term paper providers, along with the services they offer and their price structures, are given. Examples of paper titles that are specifically targeted toward management and organizational behavior are also provided. The article concludes with suggestions for ways in which instructors can deal with the proliferation of term paper providers