Electrophysiological studies in healthy subjects involving caffeine

Copyright ©2012 IOS Press All rights reserved.We review the electrophysiological studies concerning the effects of caffeine on muscle, lower and upper motor neuron excitability and cognition. Several different methods have been used, such as electromyography, recruitment analysis, H-reflex, transcranial magnetic stimulation (TMS), electroencephalography and event-related potentials. The positive effect of caffeine on vigilance, attention, speed of reaction, information processing and arousal is supported by a number of electrophysiological studies. The evidence in favor of an increased muscle fiber resistance is not definitive, but higher or lower motor neuron excitability can occur as a consequence of a greater excitation of the descending input from the brainstem and upper motor neurons. TMS can address the influence of caffeine on the upper motor neuron. Previous studies showed that cortico-motor threshold and intracortical excitatory and inhibitory pathways are not influenced by caffeine. Nonetheless, our results indicate that cortical silent period (CSP) is reduced in resting muscles after caffeine consumption, when stimulating the motor cortex with intensities slightly above threshold. We present new data demonstrating that this effect is also observed in fatigued muscle. We conclude that CSP can be considered a surrogate marker of the effect of caffeine in the brain, in particular of its central ergogenic effect

Levosimendan for amyotrophic lateral sclerosis

© 2021 Elsevier Ltd. All rights reserved.Levosimendan is a drug developed and approved in the EU to treat severe heart failure by intravenous administration. Its principal pharmacological effect is to increase cardiac contractility by calcium sensitisation of troponin C. Because of the positive action of the drug on the neuromechanical efficiency and contractile function of the diaphragm in healthy controls, levosimendan was considered potentially useful for treating amyotrophic lateral sclerosis, a disease characterised by progressive upper and lower motor neuron deficits. This hypothesis was tested in the phase LEVALS 2 trial, in which the drug was given orally.info:eu-repo/semantics/publishedVersio

Exploring children’s ideas of discrete variables using graphs, tables and isolated cases

A survey was conducted to analyse the effect of different representation of information on 6th graders mathematical reasoning (N=120), when discrete variables are involved. It addresses two questions: 1) Are there differences on children’s performance when the information is represented by bar graphs, tables and isolated cases? 2) Are there differences on children’s reasoning in each of these conditions? And 3) What difficulties do children present when solving problems with information presented using bar graphs, tables and isolates cases? The children were randomly assigned to work in one of the three groups: Graphs, Tables and Isolated Cases. The same problems were presented to all children using the representation of information of the group condition. The problems comprised simple and double proportions. Results show that the type of representation used to present discrete variables does not have an effect on students’ performance.info:eu-repo/semantics/acceptedVersio

Representações e interpretações de gráficos de barras, tabelas e casos isolados por alunos do 6.º ano de escolaridade

Ser capaz de organizar um conjunto de dados e representá-los em tabela ou gráfico de barras é uma das ambições da aprendizagem matemática já no 1º ciclo. Contudo, diferentes representações parecem afetar de modo distinto a interpretação de informação pelos alunos. Carvalho (2008) destaca os gráficos de barras como mais facilitadores de interpretação de informação do que tabelas ou casos isolados, com alunos do 8.º ano no Brasil. Em Portugal, os alunos iniciam o trabalho com gráficos variados e tabelas a partir de conjuntos de dados não organizados (aqui referidos como casos isolados) desde o 1º ciclo. No entanto, pouco se sabe sobre o efeito do tipo de representação de informação na interpretação que os alunos fazem da mesma. Os casos isolados, os gráficos de barras e as tabelas são das primeiras representações de informação que os alunos aprendem no 1.º ciclo. Procura-se aqui conhecer o efeito destes diferentes tipos de representação de informação no desempenho dos alunos, tentando conhecer: 1) Que desempenhos apresentam os alunos quando a informação é representada por gráficos de barras, tabelas e casos isolados? 2) Que justificações apresentam na interpretação de informação nas várias representações?CIEC - Centro de Investigação em Estudos da Criança, IE, UMinho (UI 317 da FCT), PortugalFundos Nacionais através da FCT (Fundação para a Ciência e a Tecnologia) e cofinanciado pelo Fundo Europeu de Desenvolvimento Regional (FEDER) através do COMPETE 2020 – Programa Operacional Competitividade e Internacionalização (POCI) com a referência POCI-01-0145-FEDER-007562info:eu-repo/semantics/publishedVersio

Phrenic nerve study as outcome in clinical trials for amyotrophic lateral sclerosis

© 2021 The Author(s). Published by Informa UK Limited trading as Taylor & Francis Group on behalf of the Montreal Neurological Institute-Hospital This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Respiratory tests are fundamental for monitoring respiratory function in ALS, and essential in clinical trials. Slow vital capacity (SVC) was canceled in some countries to prevent COVID-19 transmission. We aimed to test phrenic nerve motor responses as an option to SVC in clinical trials. Methodology: Patients followed-up in our unit were selected respecting inclusion criteria used elsewhere: possible/probable/definite disease; onset-age 18-80years; disease duration from disease duration ≤24months; body mass index (BMI)>20kg/m2; respiratory subscore of the revised ALS functional rating scale (ALSFRS-R)≥11; upright SVC ≥ 70%. We added normal phrenic responses (meanPhrenAmpl, ≥0.4mV). All patients were on riluzole. SVC and meanPhrenAmpl were recorded at study entry (T0) and 24 weeks later (T1). Decays were determined. Sample size was calculated for a treatment effect of 30% on the decay rate. Results: We included 317 ALS patients (191 males, 225 spinal-onset), mean onset-age 59.9 ± 10.7 (31-80)years, mean onset BMI 25.48 ± 3.2 (20.1-35)kg/m2, mean disease duration 10.5 ± 5.6 (1-24)months, mean ALSFRS-R 41.54 ± 4.3 (22-47) and respiratory subscore 11.83 ± 0.38 (11-12). MeanPhrenAmpl and SVC were weakly but significantly correlated at T0 and T1. At T1, MeanPhrenAmpl decayed 16.94 ± 16.45% and SVC 13.5 ± 16.86%. For the proposed drug effect, 174 and 272 patients would be needed to recruit using respectively meanPhrenAmpl and SVC decline as the primary outcome measurement (accepting no dropouts). Discussion: Contrary to SVC, meanPhrenAmpl is non-volitional and not associated with aerosolization risk. Lower recruitment number (98 patients less) would be needed, translating shorter inclusion period, trial length and costs, and probable lower missed data rate. MeanPhrenAmp is an alternative test in ALS clinical trials.This work was funded by Comprehensive evaluation of circulating MicroRNA as diagnostic and prognostic biomarkers in Amyotrophic Lateral Sclerosis (PTDC/MEC-NEU/31195/2017).info:eu-repo/semantics/publishedVersio

The cutaneous silent period as a measure of upper motor neuron dysfunction in amyotrophic lateral sclerosis

© 2022 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Objectives: We investigated the cutaneous silent period (CutSP) as a measure of upper motor neuron (UMN) dysfunction in amyotrophic lateral sclerosis. Methods: The onset latency, duration, and amount of EMG suppression of the CutSP were compared with clinical UMN signs in 24 patients with amyotrophic lateral sclerosis (ALS). UMN signs were quantified using a clinical index and transcranial magnetic stimulation (TMS). Central motor conduction time (CMCT), cortical motor threshold and motor evoked potential amplitudes were assessed as measures of UMN dysfunction. CutSP was studied in abductor digit minimi (ADM) and tibialis anterior (TA) EMG recordings following stimulation of the 5th finger and sural nerves respectively. Non-parametric tests and binomial logistic regression were applied to evaluate the data. Results: CutSP onset latency was increased in ALS patients, compared to healthy controls, both for ADM and TA muscles. In limbs with clinical UMN signs or abnormal TMS findings, the CutSP onset latency was particularly increased. There was a significant positive correlation between CutSP onset latency and the UMN score in both upper and lower limbs. In TA muscles there was also a negative correlation between CutSP onset latency and EMG suppression. The logistic regression model based on CutSP parameters correctly classified more than 70% of the cases regarding the presence of clinical signs of UMN lesion, in both upper and lower limbs. The results were not significant for TMS. Conclusion: We conclude that upper limb CutSP changes associates with UMN lesion in ALS. This neurophysiological measurement merits further investigation in ALS.This work was funded by the project “Spinal circuitry in Motor Neuron Disease: Changes in Spinal and Corticospinal Mechanisms in Amyotrophic Lateral Sclerosis and its variants” (sponsored by Biogen Inc)info:eu-repo/semantics/publishedVersio

Health-related quality of life in hereditary transthyretin amyloidosis polyneuropathy: a prospective, observational study

Background Hereditary Transthyretin Amyloidosis Polyneuropathy is a rare life-threatening neurologic disease that imposes considerable mortality and it is associated with progressive related disabilities. In this study, we aimed to assess the effect of the disease across health-related quality of life dimensions, in both carriers of the mutation and patients, to compare health-related quality of life with general population, as well as to explore health-related quality of life prognostic factors among patients, including disease progression and treatment. Methods This study was a multi-institutional, longitudinal, prospective, observational study of hereditary Transthyretin Amyloidosis Polyneuropathy Portuguese adult subjects (621 asymptomatic carriers and 733 symptomatic patients) enrolled in the Transthyretin Amyloidosis Outcomes Survey. Health-related quality of life was captured with the preference-based instrument EQ-5D-3 L. For general population the dataset included all subjects enrolled in a representative national study (n = 1500). Different econometric models were specified; multivariate probit, generalized linear model and generalized estimating equations model; including demographic and clinical covariates. Results Hereditary Transthyretin Amyloidosis Polyneuropathy patients have their health status severely impaired in all quality of life dimensions and more anxiety/depression problems were found among asymptomatic carriers. No differences on utility were found between carriers and general population (p = 0.209). Among patients, the utility value is estimated to be 0.51 (0.021), a decrement of 0.27 as compared with general population utility. Higher disease duration, advanced disease stage and not receiving treatment are associated with impaired health-related quality of life. No differences were found between genders (p = 0.910) or between late (≥50 years) and early-onset patients (p = 0.254). The utility estimate ranged from 0.63 (0.009) in stage I to 0.01 (0.005) in stage IV. Conclusions Hereditary Transthyretin Amyloidosis Polyneuropathy symptoms and progressive associated disabilities substantially decrease patient’s health-related quality of life. Clinical strategies focused on health-related quality of life preservation such as close follow-up of asymptomatic carriers, prompt diagnosis and adequate, early treatment would benefit patient’s long-term outcomes, slowing the progressive decline in health-related quality of life.info:eu-repo/semantics/publishedVersio

Exploring the split hand phenomenon with the neurophysiological index

© 2023 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).In 164 subjects of different age groups, we studied the neurophysiological index (NI) ([CMAP amplitude/Distal motor latency] *[F-wave frequency]; CMAP=compound muscle action potential) for three hand muscles (APB= abductor pollicis brevis; FDI= first dorsal interosseous; ADM= abductor digiti minimi). A split hand index based on CMAP amplitude (SHI_CMAP) and NI (SHI_NI) were calculated ([APB CMAP amplitude or NI * FDI CMAP amplitude or NI]/[ADM CMAP amplitude or NI]). All these neurophysiological measurements differed between age groups (p<0.001). Hand muscle NIs, as well as SHI_NI and SHI_CMAP were age dependent. This may be relevant for diagnostic purposes in motor neuron diseases.info:eu-repo/semantics/publishedVersio

As mulheres e a economia : a discriminação de gênero no consumo e no trabalho

Trabalho de Conclusão de Curso (graduação)—Universidade de Brasília, Faculdade de Economia, Administração e Contabilidade, Departamento de Economia, 2021.Costuma-se dividir a microeconomia tradicional em duas áreas: Teoria do Consumidor e Teoria da Firma. A contingência do estudo microeconômico são justamente as escolhas do Homo Economicus. Este trabalho tem como escopo discutir os percalços da mulher enquanto consumidora (Capítulo 1) e a mulher no contexto da firma e sua participação no mercado de trabalho, explorando o conceito de Divisão Sexual do Trabalho (Capítulo 2). A partir de uma revisão bibliográfica discutiremos sobre como o fato de ser mulher, e apenas por isso, pode gerar mecanismos discriminatórios de preço tendo como base conceitos microeconômicos para diferenciar a elasticidade-preço da demanda entre os sexos fornecendo uma explicação via Teoria dos Jogos no Capítulo 1. No segundo capítulo, discutiremos sobre a influência do sexo do indivíduo na escolha profissional utilizando a metodologia bibliográfica e documental para explorar as relações de gênero no mercado de trabalho.It is customary to divide traditional microeconomics into two areas: Consumer Theory and Firm Theory. The contingency of the microeconomic study is precisely the choices of Homo Economicus. This work aims to discuss the misfortunes of women as consumers (Chapter 1) and their participation in the firm context and, beyond that, in the labor market, exploring the concept of the Sexual Division of Labor (Chapter 2). Starting from a bibliographic review, we will discuss how the fact of being a woman, and just for that reason, can generate discriminatory price mechanisms based on microeconomic concepts to differentiate the price elasticity of demand between the sexes providing an explanation via Game Theory in Chapter 1. In the second chapter, we will discuss the influence of the individual's gender on professional choice using bibliographic and documentary methodology to explore gender relations in the labor market

Therapeutic targeting of ALS pathways: refocusing an incomplete picture

© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Numerous potential amyotrophic lateral sclerosis (ALS)-relevant pathways have been hypothesized and studied preclinically, with subsequent translation to clinical trial. However, few successes have been observed with only modest effects. Along with an improved but incomplete understanding of ALS as a neurodegenerative disease is the evolution of more sophisticated and diverse in vitro and in vivo preclinical modeling platforms, as well as clinical trial designs. We highlight proposed pathological pathways that have been major therapeutic targets for investigational compounds. It is likely that the failures of so many of these therapeutic compounds may not have occurred because of lack of efficacy but rather because of a lack of preclinical modeling that would help define an appropriate disease pathway, as well as a failure to establish target engagement. These challenges are compounded by shortcomings in clinical trial design, including lack of biomarkers that could predict clinical success and studies that are underpowered. Although research investments have provided abundant insights into new ALS-relevant pathways, most have not yet been developed more fully to result in clinical study. In this review, we detail some of the important, well-established pathways, the therapeutics targeting them, and the subsequent clinical design. With an understanding of some of the shortcomings in translational efforts over the last three decades of ALS investigation, we propose that scientists and clinicians may choose to revisit some of these therapeutic pathways reviewed here with an eye toward improving preclinical modeling, biomarker development, and the investment in more sophisticated clinical trial designs.Research funding: Cytokinetics National Institutes of Health, USA. Grant Number: 5R01NS117604-03info:eu-repo/semantics/publishedVersio