Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegenerative diseases

Copyright © 2020 Armada-Moreira, Gomes, Pina, Savchak, Gonçalves-Ribeiro, Rei, Pinto, Morais, Martins, Ribeiro, Sebastião, Crunelli and Vaz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Excitotoxicity is a phenomenon that describes the toxic actions of excitatory neurotransmitters, primarily glutamate, where the exacerbated or prolonged activation of glutamate receptors starts a cascade of neurotoxicity that ultimately leads to the loss of neuronal function and cell death. In this process, the shift between normal physiological function and excitotoxicity is largely controlled by astrocytes since they can control the levels of glutamate on the synaptic cleft. This control is achieved through glutamate clearance from the synaptic cleft and its underlying recycling through the glutamate-glutamine cycle. The molecular mechanism that triggers excitotoxicity involves alterations in glutamate and calcium metabolism, dysfunction of glutamate transporters, and malfunction of glutamate receptors, particularly N-methyl-D-aspartic acid receptors (NMDAR). On the other hand, excitotoxicity can be regarded as a consequence of other cellular phenomena, such as mitochondrial dysfunction, physical neuronal damage, and oxidative stress. Regardless, it is known that the excessive activation of NMDAR results in the sustained influx of calcium into neurons and leads to several deleterious consequences, including mitochondrial dysfunction, reactive oxygen species (ROS) overproduction, impairment of calcium buffering, the release of pro-apoptotic factors, among others, that inevitably contribute to neuronal loss. A large body of evidence implicates NMDAR-mediated excitotoxicity as a central mechanism in the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and epilepsy. In this review article, we explore different causes and consequences of excitotoxicity, discuss the involvement of NMDAR-mediated excitotoxicity and its downstream effects on several neurodegenerative disorders, and identify possible strategies to study new aspects of these diseases that may lead to the discovery of new therapeutic approaches. With the understanding that excitotoxicity is a common denominator in neurodegenerative diseases and other disorders, a new perspective on therapy can be considered, where the targets are not specific symptoms, but the underlying cellular phenomena of the disease.This work was funded by Fundação para a Ciência e Tecnologia (FCT), Portugal (PTDC/BTM-SAL/32147/2017, PD/BD/114278/2016, IMM/BI/2-2020), and by FCT/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado (UID/BIM/50005/2019). TM was funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska/Curie grant agreement No. 722053.info:eu-repo/semantics/publishedVersio

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Estima e satisfação com a imagem corporal em estudantes de Medicina

Introduction: The term body image is an illustration of a person's feelings, perceptions, and thoughts about their own body. The most common eating disorders today are characterized by excessive preoccupation with the image and its appearance is related to a complex range of factors. Objective: The objective of the study was to investigate the esteem and satisfaction with body image verified in students of both sexes, of medical students. Method: a cross-sectional study composed of a sample of 109 students was used to investigate the estimation and corporal satisfaction using the scale of figures of silhouettes (EFS), an instrument developed for the Brazilian population by Kakeshita. Results: 109 students were analyzed and 74 (64.88%) were female and 35 (32.11%) were male. Regarding nutritional status, female prevailed eutrophy, whereas in males the mean BMI corresponded to overweight. Body estimation and satisfaction were assessed by comparisons between the Real BMI, the Current BMI and the BMI Desired. The female group demonstrated inactivity of body perception and body dissatisfaction. Already in the male group, accuracy. Conclusion: It was concluded that the female sex presented with body dissatisfaction, inaccuracy and desire for lower BMI as age increased. On the other hand, the male showed a desire for BMI lower than the Real and the Current, without influence of age.Introdução: O termo imagem corporal é uma ilustração dos sentimentos, percepções e pensamentos de uma pessoa a respeito do seu próprio corpo. Os distúrbios alimentares mais comuns na atualidade são caracterizados pela excessiva preocupação com a imagem e o seu aparecimento está relacionado com uma complexa gama de fatores. Objetivo: O objetivo do estudo foi investigar a estima e satisfação com a imagem corporal verificadas em alunos de ambos os sexos, estudantes de medicina. Método: tratou-se de um estudo transversal composto por uma amostra de 109 estudantes, para investigar a estima e satisfação corporais, foi utilizado a Escala de Figuras de Silhuetas (EFS), instrumento desenvolvido para a população brasileira por Kakeshita. Resultados: Foram analisados 109 alunos e destes, 74 (64,88%) eram mulheres e 35 (32,11%) homens. Em relação ao estado nutricional, no sexo feminino prevaleceu eutrofia, enquanto no sexo masculino a média de IMC correspondeu ao sobrepeso. A estima e satisfação corporais foram avaliadas por comparações entre o IMC Real, o IMC Atual e o IMC Desejado. O grupo feminino demonstrou inacurácia da percepção corporal e insatisfação corporal. Já no grupo masculino, acurácia. Conclusão: Pôde-se concluir que o sexo feminino apresentou insatisfação corporal, inacurácia e desejo de IMC menor, com o passar da idade. Já o sexo masculino, demonstrou desejo de IMC menor do que o Real e o Atual, sem influência da idade. ABSTRACT Estimation and satisfaction of the body image in students of the medicineIntroduction: The term body image is an illustration of a person's feelings, perceptions, and thoughts about their own body. The most common eating disorders today are characterized by excessive preoccupation with the image and its appearance is related to a complex range of factors. Objective: The objective of the study was to investigate the esteem and satisfaction with body image verified in students of both sexes, of medical students. Method: a cross-sectional study composed of a sample of 109 students was used to investigate the estimation and corporal satisfaction using the scale of figures of silhouettes (EFS), an instrument developed for the Brazilian population by Kakeshita. Results: 109 students were analyzed and 74 (64.88%) were female and 35 (32.11%) were male. Regarding nutritional status, female prevailed eutrophy, whereas in males the mean BMI corresponded to overweight. Body estimation and satisfaction were assessed by comparisons between the Real BMI, the Current BMI and the BMI Desired. The female group demonstrated inactivity of body perception and body dissatisfaction. Already in the male group, accuracy. Conclusion: It was concluded that the female sex presented with body dissatisfaction, inaccuracy and desire for lower BMI as age increased. On the other hand, the male showed a desire for BMI lower than the Real and the Current, without influence of age

In situ and in vitro degradation kinetics and prediction of the digestible neutral detergent fiber of agricultural and agro-industrial byproducts

The objective of this study was to evaluate the in situ and in vitro degradation kinetics and to predict the digestible neutral detergent fiber (dNDF) from the incubation times; in situ and in vitro degradation kinetic parameters; and equations fitted for agricultural and agro-industrial byproducts. Byproducts from pineapple, cocoa, palm kernel, corn gluten meal, common bean, sunflower, guava, cassava bark, cassava stems, cassava foliage, papaya, mango, passion fruit and turnips were evaluated. There were differences between the byproducts as for the potentially neutral detergent fiber (NDF) fraction and the in situ NDF degradation rate in the final volume of the gases generated by fibrous carbohydrates (FC), for the lag time and for the in vitro fractional degradation rate of the FC. There was equivalence between the dNDF values predicted in situ and those observed in vivo; however, there was low precision of estimates. The degradability in the in vitro incubation times of 30 and 48 hours presented equivalence with the values observed, but also did not present precision in the estimates. The equations fitted without lignin were not precise and accurate to estimate the dNDF of agricultural and agro-industrial byproducts. The equation with lignin and with the digestion rate obtained by the in vitro method presented more precise estimates. Byproducts from common bean, cassava bark and papaya presented greater NDF availability, whereas those of guava had the lowest NDF availability. The digestible NDF fraction was best predicted with the in situ incubation time of 72 hours. The equation fitted utilizing in vitro or in situ digestion rates enables the prediction of the NDF availability of agricultural and agroindustrial byproducts