Relación entre conductancias de sodio y potasio al estilo Hodgkin y Huxley y su efeto en la propagación del potencial de acción a 40ºC

ResumenIntroducción. En un axón de Jibia, se forman potenciales de acción debido a dos tipos de canales de sodio y potasio voltaje dependientes y con una cinética adecuada para funcionar a 6.3ºC de temperatura. Estos canales con los mismos valores de conductancias máximas no podrían dar paso a la formación de potenciales de acción en neuronas a 40ºC. Objetivo. Determinar, a partir de simulación computacional, la respuesta de un axón no mielinado a un estimulo de corriente para diferentes valores de conductancias máximas de sodio (GNa) y potasio (GK) al estilo HH en el espacio GNa vs. GK tal que 0S/cm

Data Exporter: A complementary tool to export data simulation from NEURON

ResumenObjetivos: Desarrollar una herramienta computacional en ambiente lenguaje de programación hoc de NEURON y de fácil uso, que permita el rápido almacenamiento de los resultados obtenidos para su posterior análisis en otros software tales como Matlab or IgorPro.Materiales y métodos: Para el desarrollo de Data Exporter se escribió un algoritmo en lenguaje de programación hoc de NEURON. El algoritmo, escrito en un único archivo de texto, esta dividido en 13 bloques, de los cuales solo el primero debe ser modificado para adaptarlo a una geometría y biofísica neuronal particular y para determinar la ruta de almacenamiento de los datos.Resultados: Se desarrollo un software que simula la propagación de potenciales de acción a través de geometrías neuronales complejas. El uso de esta herramienta permite el almacenamiento de los resultados obtenidos, como potenciales y corrientes de membrana en diferentes puntos de toda la neurona, sin incremento significativo en el tiempo para el desarrollo de los procesos.Conclusiones: Data Exporter es un software que le da mayor flexibilidad a NEURON facilitando el acceso a nuevos neurocientíficos, los cuales pueden usarlo con solo conocer los códigos necesarios para el desarrollo de los archivos relacionados con las propiedades geométricas y biofísicas neuronales.AbstractObjectives: To develop a computational simulation tool in NEURON’s programming language hoc to be easily usable, in order to save the results generated by the software and later be analyzed with other tools such as Matlab and IgorPRo.Materials and Methods: To develop Data Exporter an algorithm was implemented in the programming language hoc used in NEURON. This algorithm was written in a text file and divided in 13 segments or program blocks, in which only the first one can be modified in order to be adapted to a particular geometry and neural biophysics and to determine the necessary path for saving the data.Results: Software that simulates the propagation of potential actions by using neuronal complex geometries was developed. The use of this tool allows the storage of the obtained results, as potential and membrane currents in different points of the whole neuron, without significant increase in the time for the development of the processes.Conclusions: Data Exporter is software that offers greater flexibility to NEURON and facilitates access to new neuroscientists who can use it by only knowing the codes related to geometry and biophysical properties of the neuron.Objectives: To develop a computational tool for NEURON simulation environment, user friendly, to store the results generated during simulation and to make subsequent analysis with other tools such as Matlab and IgorPRo Materials and Methods: Data Exporter was implemented in the programming lan- guage hoc. This algorithm is divided in 13 sections or blocks. The first section is necessary to edit in a new simulation. These new configuration determine the geometry, biophysic properties the neurons to simulate and path to save data. Results: To check the efficiency of the algorithm, we simulated the propagation of action potential in TRN(thalamic reticular nucleus) neuron in different large of simulation. We determine that the time of simulation is linear respect to time of simulation. Conclusions: Data Exporter makes easier to start to neural simulation in NEURON re- ducing the steps of programming to geometry and biophysical properties of the neuron and to allow save data to next steps of analysis

Efecto de la temperature en las descargas en ráfaga de la células del núcleo reticular del tálamo

Objective: To show the relation between the four parameters associated to bursting discharges of the thalamic reticular cells (TRNn): the maximum firing frequency (fmax) and the temperature at which it occurs (Tfmax), the range of temperatures defined as the full width at half maximum (∆Th ) and the maximum specific low threshold calcium conductance (GT). Materials and Methods: In order to simulate the TRNn bursting activity, a computational simulation model was implemented using the NEURON software, which incorporates morphological and electrophysiological data, and stimuli properties closely related to reality. Results: It was found that there are nonlinear relations between the parameters. The fmax frequency follows a quadratic growth with temperature and tends asymptotically towards a limit value with the maximum calcium conductance. In the same manner, ∆Th increases until reaching a limit value as function of fmax and GT . However, the increment per frequency unit is bigger than the increment per conductance unit. Conclusions: Four equations were obtained that model the relations between the parameters associated to bursting discharges of the TRNn in rats and other neurons with similar characteristics in different animal species

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Relación entre conductancias de sodio y potasio al estilo Hodgkin y Huxley y su efeto en la propagación del potencial de acción a 40ºC

ResumenIntroducción. En un axón de Jibia, se forman potenciales de acción debido a dos tipos de canales de sodio y potasio voltaje dependientes y con una cinética adecuada para funcionar a 6.3ºC de temperatura. Estos canales con los mismos valores de conductancias máximas no podrían dar paso a la formación de potenciales de acción en neuronas a 40ºC. Objetivo. Determinar, a partir de simulación computacional, la respuesta de un axón no mielinado a un estimulo de corriente para diferentes valores de conductancias máximas de sodio (GNa) y potasio (GK) al estilo HH en el espacio GNa vs. GK tal que 0S/cm

Efecto de la conductancia de potasio Kv3.1 en la tasa y frecuencia de disparo de un axón no mielinado

ResumenObjetivo: Determinar la relación entre la conductancia de potasio Kv3.1 y la tasa dedisparo (Td) de un modelo neuronal llamado neurona1 formado por un soma, un cuelloy un axón no mielinado durante un estímulo de corriente de 10 ms de duración y a 40°C.Materiales y métodos: A partir del software libre NEURON se simuló la propagación deráfagas de potenciales de acción a través de neurona1, variando la conductancia específicamáxima de potasio Kv3.1 (GKv3.1) relativa a la conductancia específica máxima de potasio(GK) estudiada por A.L. Hodgkin y A.F. Huxley en 1952, de tal forma que GKv3.1+GK=1.6S/cm2.Resultados: En una estructura neuronal con las características biofísicas de neurona1,Td varía en forma sigmoidea para 0 &le; GKv3.1/GK &le; 0.455 y decae exponencialmente para0.455 < GKv3.1/GK &le; 15, respectivamente. Para el primer caso, Td aumenta 11 veces másque la frecuencia (f) respecto del número de espigas en cada ráfaga.Conclusión: La observación de la conductancia de potasio del tipo Kv3.1 en algún tipode neurona no implica necesariamente la propagación de ráfagas de alta tasa de disparo.Su efecto es más pronunciado (11 veces) en la modulación de Td que en el aumento de f.Palabras clave: Frecuencia de disparo, tasa de disparo, conductancia de potasio Kv3.1,axón no mielinado.AbstractObjective: To determine the relationship between the Kv3.1 potassium conductance andthe firing rate (Td) in a neuronal model called neuron1, consisting of a soma, a hillock andan unmyelinated axon, during a constant current stimulus 10ms long and at 40°C.Methodology: Using the free software NEURON, the propagation of action potentialsalong a neuronal structure called neurona1 was simulated. The maximum Kv3.1 conductance (GKv3.1) relative to the maximum potassium conductance (Gk) studied in 1952 byA.L. Hodgkin and A.F. Huxley and in this paper called HH conductance, was varied suchthat Gk +GKv3.1 = 1.6s/cm2.Results: In a neuronal structure with the biophysical characteristics of neuron1, Td variesin a sigmoid way for all GKv3.1 such that 0&le;GKv3.1/Gk&le; 0.455 and drops exponentiallyfor all GKv3.1 such that 0.45

Reduction of cardiac imaging tests during the COVID-19 pandemic: The case of Italy. Findings from the IAEA Non-invasive Cardiology Protocol Survey on COVID-19 (INCAPS COVID)

Background: In early 2020, COVID-19 massively hit Italy, earlier and harder than any other European country. This caused a series of strict containment measures, aimed at blocking the spread of the pandemic. Healthcare delivery was also affected when resources were diverted towards care of COVID-19 patients, including intensive care wards. Aim of the study: The aim is assessing the impact of COVID-19 on cardiac imaging in Italy, compare to the Rest of Europe (RoE) and the World (RoW). Methods: A global survey was conducted in May–June 2020 worldwide, through a questionnaire distributed online. The survey covered three periods: March and April 2020, and March 2019. Data from 52 Italian centres, a subset of the 909 participating centres from 108 countries, were analyzed. Results: In Italy, volumes decreased by 67% in March 2020, compared to March 2019, as opposed to a significantly lower decrease (p &lt; 0.001) in RoE and RoW (41% and 40%, respectively). A further decrease from March 2020 to April 2020 summed up to 76% for the North, 77% for the Centre and 86% for the South. When compared to the RoE and RoW, this further decrease from March 2020 to April 2020 in Italy was significantly less (p = 0.005), most likely reflecting the earlier effects of the containment measures in Italy, taken earlier than anywhere else in the West. Conclusions: The COVID-19 pandemic massively hit Italy and caused a disruption of healthcare services, including cardiac imaging studies. This raises concern about the medium- and long-term consequences for the high number of patients who were denied timely diagnoses and the subsequent lifesaving therapies and procedures

International Impact of COVID-19 on the Diagnosis of Heart Disease

Background: The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified. Objectives: The study sought to assess COVID-19's impact on global cardiovascular diagnostic procedural volumes and safety practices. Methods: The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained. Results: Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoracic echocardiography decreased by 59%, transesophageal echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p &lt; 0.001 for each procedure). In multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower–middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and telehealth. Conclusions: COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world's economically challenged. Further study of cardiovascular outcomes and COVID-19–related changes in care delivery is warranted

Impact of COVID-19 on Diagnostic Cardiac Procedural Volume in Oceania: The IAEA Non-Invasive Cardiology Protocol Survey on COVID-19 (INCAPS COVID)

Objectives: The INCAPS COVID Oceania study aimed to assess the impact caused by the COVID-19 pandemic on cardiac procedure volume provided in the Oceania region. Methods: A retrospective survey was performed comparing procedure volumes within March 2019 (pre-COVID-19) with April 2020 (during first wave of COVID-19 pandemic). Sixty-three (63) health care facilities within Oceania that perform cardiac diagnostic procedures were surveyed, including a mixture of metropolitan and regional, hospital and outpatient, public and private sites, and 846 facilities outside of Oceania. The percentage change in procedure volume was measured between March 2019 and April 2020, compared by test type and by facility. Results: In Oceania, the total cardiac diagnostic procedure volume was reduced by 52.2% from March 2019 to April 2020, compared to a reduction of 75.9% seen in the rest of the world (p&lt;0.001). Within Oceania sites, this reduction varied significantly between procedure types, but not between types of health care facility. All procedure types (other than stress cardiac magnetic resonance [CMR] and positron emission tomography [PET]) saw significant reductions in volume over this time period (p&lt;0.001). In Oceania, transthoracic echocardiography (TTE) decreased by 51.6%, transoesophageal echocardiography (TOE) by 74.0%, and stress tests by 65% overall, which was more pronounced for stress electrocardiograph (ECG) (81.8%) and stress echocardiography (76.7%) compared to stress single-photon emission computerised tomography (SPECT) (44.3%). Invasive coronary angiography decreased by 36.7% in Oceania. Conclusion: A significant reduction in cardiac diagnostic procedure volume was seen across all facility types in Oceania and was likely a function of recommendations from cardiac societies and directives from government to minimise spread of COVID-19 amongst patients and staff. Longer term evaluation is important to assess for negative patient outcomes which may relate to deferral of usual models of care within cardiology

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field