Increased soluble TNF receptor 2 in antidepressant-free patients with late-life depression

Increased pro-inflammatory state has been implicated in the pathophysiology of major depressive disorder. The aim of this study was to determine serum levels of INF-alpha and soluble TNF-alpha receptors 1 and 2 (sTNFR1 and sTNFR2) in anti-depressant free depressed elderly patients as compared to healthy controls. Sixty-seven older adults (28 with major depression and 39 controls) were enrolled to this study. Participants were assessed by the SCID and diagnosis of major depressive episode was made according to the DSM-IV criteria. Serum INF-alpha, 5TNFR1 and sTNFR2 were determined by ELISA. Anti-depressant free patients with late-life depression showed an increased level of the sTNFR2 as compared to controls (p = 0.03). No significant differences were found in serum INF-alpha and sTNFR1 levels (p = 0.1 and p = 0.4, respectively). There was no correlation between serum levels of these inflammatory markers and the severity of depression. Our findings provide additional evidence of the involvement of abnormal pro-inflammatory state in late-life depression. (c) 2010 Elsevier Ltd. All rights reserved.

Serum brain-derived neurotrophic factor level is reduced in antidepressant-free patients with late-life depression

Objectives. The aim of the present study is to investigate serum BDNF levels in older depressed patients as compared to healthy elderly controls. Methods. Twenty-nine elderly subjects with major depression and 42 healthy older adults were enrolled to this study. All depressed patients were antidepressant-free for at least 1 month prior clinical and laboratorial assessments. Serum BDNF levels were determined by sandwich ELISA. Results. BDNF levels were lower in elderly depressed patients as compared to controls (P = 0.034). Patients with late-onset depression had the lowest BDNF level (median 478.5, interquartile range 373.5-740.9 pg/l) when compared to early-onset depression (median 620.7, interquartile range 366.1-971.9 pg/l) and healthy controls (median 711.3, interquartile range 534.7-1181.0 pg/l) (P < 0.03). Conclusions. Reduced serum BDNF level may be a state marker of late-life depression in non-medicated elderly patients. Our findings provide further evidences that reduced neurotrophic support may have an important role in the physiopathology of late-life depression.

Higher Serum sTNFR1 Level Predicts Conversion from Mild Cognitive Impairment to Alzheimer`s Disease

The activation of inflammatory cascades has been consistently demonstrated in the pathophysiology of Alzheimer`s disease (AD). Among several putative neuroinflammatory mechanisms, the tumor necrosis factor alpha (TNF-alpha) signaling system has a central role in this process. Recent evidence indicates that the abnormal production of inflammatory factors may accompany the progression from mild cognitive impairment (MCI) to dementia. We aimed to examine serum levels of TNF-alpha and its soluble receptors (sTNFR1 and sTNFR2) in patients with MCI and AD as compared to cognitively unimpaired elderly subjects. We further aimed to investigate whether abnormal levels of these cytokines predict the progression from MCI to AD upon follow-up. We utilized cross-sectional determination of serum levels of TNF-alpha, sTNFR1, and sTNFR2 (ELISA method) in a test group comprising 167 older adults (31 AD, 72 MCI, and 64 healthy controls), and longitudinal reassessment of clinical status after 18.9 +/- 10.0 months. At baseline, there were no statistically significant differences in serum TNF-alpha, sTNFR1, and sTNFR2 between patients with MCI and AD as compared to controls. Nevertheless, patients with MCI who progressed to AD had significantly higher serum sTNFR1 levels as opposed to patients who retained the diagnosis of MCI upon follow-up (p = 0.03). Cox regression analysis showed that high serum sTNFR1 levels predicted the conversion from MCI to AD (p = 0.003), whereas no significant differences were found with respect to serum levels of TNF-alpha and sTNFR2. Abnormal activation of TNF-alpha signaling system, represented by increased expression of sTNFR1, is associated with a higher risk of progression from MCI to AD.

Effect of brain-derived neurotrophic factor Val66Met polymorphism and serum levels on the progression of mild cognitive impairment

Objectives. Abnormalities in neurotrophic systems have been reported in Alzheimer`s disease (AD), as shown by decreased serum brain-derived neurotrophic factor (BDNF) levels and association with BDNF genetic polymorphisms. In this study, we investigate whether these findings can be detected in patients with mild cognitive impairment (MCI), which is recognized as a high risk condition for AD. We also address the impact of these variables on the progression of cognitive deficits within the MCI-AD continuum. Methods. One hundred and sixty older adults with varying degrees of cognitive impairment (30 patients with AD, 71 with MCI, and 59 healthy controls) were longitudinally assessed for up to 60 months. Baseline serum BDNF levels were determined by sandwich ELISA, and the presence of polymorphisms of BDNF and apolipoprotein E (Val66Met and APOE*E4, respectively) was determined by allelic discrimination analysis on real time PCR. Modifications of cognitive state were ascertained for non-demented subjects. Results. Mean serum BDNF levels were reduced in patients with MCI and AD, as compared to controls (509.2 +/- 210.5; 581.9 +/- 379.4; and 777.5 +/- 467.8 pg/l respectively; P < 0.001). Baseline serum BDNF levels were not associated with the progression of cognitive impairment upon follow-up in patients with MCI (progressive MCI, 750.8 +/- 463.0; stable MCI, 724.0 +/- 343.4; P = 0.8), nor with the conversion to AD. Although Val66Met polymorphisms were not associated with the cross-sectional diagnoses of MCI or AD, the presence of Met-BDNF allele was associated with a higher risk of disease-progression in patients with MCI (OR = 3.0 CI(95%) [1.2-7.8], P = 0.02). We also found a significant interaction between the APOE*E4 and Met-BDNF allele increasing the risk of progression of cognitive impairment in MCI patients (OR = 4.4 CI(95%) [1.6-12.1], P = 0.004). Conclusion. Decreased neurotrophic support, as indicated by a reduced systemic availability of BDNF, may play role in the neurodegenerative processes that underlie the continuum from MCI to AD. The presence of Met-BDNF allele, particularly in association with APOE*E4, may predict a worse cognitive outcome in patients with MCI.

Increased Serum IL-1 beta Level in Alzheimer`s Disease and Mild Cognitive Impairment

Background/Aims: Abnormal inflammatory response has been associated to the pathogenesis of Alzheimer`s disease (AD) and may be a marker of an ongoing neurodegenerative process. The aim of this study was to evaluate the serum levels of interleukin-1 beta (IL-1 beta) in patients with mild cognitive impairment (MCI) and AD. Methods: One hundred and sixty-three older adults ( 58 with mild to moderate AD, 74 with MCI and 31 healthy controls) were recruited for this study. Serum IL-1 beta levels were measured by ELISA. Patients with MCI were subcategorized in single-domain amnestic (aMCI), nonamnestic (naMCI), and multiple-domain (mdMCI) subtypes. Results: Patients with AD and MCI ( all subtypes) had a significant increase in serum IL-1 beta levels as compared to controls (p = 0.03). Patients with mdMCI had serum IL-1 beta levels comparable to those with AD, and significantly higher than those observed in aMCI and naMCI ( p = 0.02). Discussion: The present study provides evidence that inflammatory mechanisms, represented by elevated IL-1 beta, are observed in patients with MCI, specifically in those with impairment in multiple cognitive domains. As these patients are at higher risk of conversion to dementia, we propose that an increased serum IL-1 beta level is a stage marker of the ongoing brain neurodegeneration in the continuum between normal ageing and AD. Copyright (C) 2009 S. Karger AG, Basel

Sexual differentiation of cortical spreading depression propagation after acute and kindled audiogenic seizures in the Wistar audiogenic rat (WAR)

Brain excitability diseases like epilepsy constitute one factor that influences brain electrophysiological features. Cortical spreading depression (CSD) is a phenomenon that can be altered by changes in brain excitability. CSD propagation was presently characterized in adult mate and female rats from a normal Wistar strain and from a genetically audiogenic seizure-prone strain, the Wistar audiogenic rat (WAR), both previously submitted (RAS(+)), or not (RAS(-)), to repetitive acoustic stimulation, to provoke audiogenic kindling in the WAR-strain. A gender-specific change in CSD-propagation was found. Compared to seizure-resistant animals, in the RAS- condition, mate and female WARs, respectively, presented CSD-propagation impairment and facilitation, characterized, respectively, by lower and higher propagation velocities (P<0.05). In contraposition, in the RAS(+) condition, mate and female WARs displayed, respectively, higher and tower CSD-propagation rates, as compared to the corresponding controls. In some Wistar and WAR females, we determined estrous cycle status on the day of the CSD-recording as being either estrous or diestrous; no cycle-phase-related differences in CSD-propagation velocities were detected. In contrast to other epilepsy models, such as Status Epilepticus induced by pilocarpine, despite the CSD-velocity reduction, in no case was CSD propagation blocked in WARs. The results suggest a gender-related, estrous cycle-phase-independent modification in the CSD-susceptibility of WAR rats, both in the RAS(+) and RAS(-) situation. (C) 2008 Elsevier B.V. All rights reserved.

Increased plasma levels of brain derived neurotrophic factor (BDNF) after multiple sclerosis relapse

Brain derived neurotrophic factor (BDNF) has been related to neuroprotection in a series of central nervous system diseases, although its role in multiple sclerosis (MS) was only partially investigated. In this work, we aimed to evaluate the plasma levels of BDNF from 29 MS patients and 24 control subjects. MS patients had decreased levels of BDNF in comparison with healthy controls. BDNF levels increased significantly after MS relapse. Our results provide some evidence for the involvement of BDNF in the pathogenesis of MS and suggest a role for this neurotrophin during the recovery of acute demyelinating inflammatory lesion. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Variabilidade espacial do estado nutricional do cafeeiro conilon utilizando índice DRIS

A combinação da agricultura de precisão e do Sistema Integrado de Recomendação Foliar (DRIS) possibilita monitorar espacialmente o balanço nutricional dos cafezais para fornecer recomendações de adubação mais equilibradas e mais ajustadas economicamente. O objetivo deste trabalho foi avaliar a variabilidade espacial do estado nutricional do cafeeiro conilon, utilizando o Índice de Balanço Nutricional (IBN) e sua relação com a produtividade. A produtividade das plantas em cada ponto amostral foi determinada e construiu-se o seu mapa considerando a variabilidade espacial; determinou-se o Índice de Equilíbrio Nutricional (IBN) das plantas em cada ponto amostral e construiu-se o seu mapa; e utilizou-se a análise de componentes principais (ACP) para estimar o IBN do cafeeiro por cokrigagem. Os dados do cafeeiro conilon foram coletados em fazenda experimental, no município de Cachoeiro de Itapemirim-ES. O IBN do cafeeiro e a sua produtividade foram analisados por meio de geoestatística, com base nos modelos e parâmetros dos semivariogramas, utilizando o método de interpolação krigagem ordinária para estimar valores para locais não amostrados. O índice de Balanço Nutricional da lavoura do cafeeiro conilon apresentou dependência espacial, porém não apresentou correlação linear e nem espacial com a produtividade. A lavoura em estudo se encontra em desequilíbrio nutricional, sendo que entre os macronutrientes, o Potássio foi o que apresentou maior desequilíbrio na área, entre os micronutrientes, o Zinco e o Ferro foram os que apresentaram menores concentrações nas folhas. A confecção dos mapas possibilitou a distinção de regiões com maior e menor desequilíbrio nutricional e produtividade, o que possibilita adotar o manejo de forma diferenciada e localizada. A análise multivariada baseada em componentes principais fornece componentes com alta correlação com as variáveis originais P, Ca, Zn , Cu, K e B. A cokrigagem utilizando as componentes principais permite estimar o IBN e a produtividade da área.

Adjihâd no extremo Sudoeste Peninsular. O recém- identificado Ribat da Arrifana (Século XII)

A concepção de djihâd, ou de Guerra Santa, e a sua prática, estiveram sempre presentes durante a permanência da administração muçulmana na Península Ibérica e, principalmente, tanto no início daquela como na sua fase final. A djihâd foi, e é ainda hoje, o combate religioso, considerando-se inimigos todos aqueles que professam outros credos, como os que enveredam por heresias dentro do islamismo. Ela aufere de dimensão individual, enquanto incute e faz desenvolver a fé em cada um dos crentes mas é, também, dever colectivo, na medida em que deve propagar o Islão, entre terras e populações consideradas inimigas, legitimando a guerra. Segundo Ibn al-Talla, o profeta Maomé terá incitado os seus seguidores à Guerra Santa na Península Ibérica dizendo: "O ribat terminará em todo o lado menos na ilha do al-Andalus, no Magreb Extremo, onde será o mais meritório de toda a face da terra" (Molina, 1983, p. 34). Os militares do Islão mortos em combate tomam-se mártires em nome de Alá, encontrando-se registada, durante a Idade Média, a presença, entre as tropas regulares, de voluntários, designados "gentes do ribaf ou muridún, que se ofereciam tendo em vista cumprirem obrigação canônica conforme à Guerra Santa.

A aprendizagem da escrita no ensino das línguas

Relatório de estágio apresentado para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Ensino do Português e das e de Língua Estrangeira no 3º Ciclo do Ensino Básico e no Ensino Secundário – Português / Francês.

O funcionalismo e o socioconstrutivismo no ensino da História e da Geografia: dois modelos em análise

Relatório de Estágio apresentado para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Ensino da História e da Geografia no 3º Ciclo do Ensino Básico e Ensino Secundário

A exploração de webrecursos e os debates no ensino da História e da Geografia: reflexão sobre a aplicação destas metodologias em sala de aula

Relatório da Prática de Ensino Supervisionada para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Ensino da História e da Geografia no 3º Ciclo do Ensino Básico e Ensino Secundário

A componente lúdica na sala de aula como elemento facilitador da aprendizagem

O presente relatório visa, num primeiro capítulo, descrever em que medida a componente lúdica, utilizada em ambiente de sala de aula, pode ser considerada como elemento facilitador da aprendizagem. Para tal, parte-se, para uma abordagem à evolução das metodologias de ensino, sobre qual a importância da comunicação e da aprendizagem por tarefas, bem como à definição de lúdico, analisando-se a sua importância na aquisição e consolidação de conhecimentos. Refere-se ainda o papel do docente e discente na abordagem e aplicação da ludicidade e motivação na realização de atividades. No segundo capítulo, faz-se uma apresentação do Agrupamento de Escolas Ibn Mucana, onde foi realizada a Prática de Ensino Supervisionada e num terceiro capítulo faz-se referência à observação e caracterização da turma em que foram lecionadas as aulas práticas. Por fim, no quarto capítulo, apresenta-se e reflete-se sobre as atividades lúdicas que foram desenvolvidas durante o período de lecionação.

O projeto eTwinning e a motivação dos alunos: o impacto da sua implementação nas aulas de Português Língua Materna e de Espanhol Língua Estrangeira

Este relatório assume como finalidade analisar e avaliar as potencialidades das tecnologias da informação e comunicação (TIC), com especial enfoque nas ferramentas da Web 2.0, para a criação de ambientes de aprendizagem colaborativa e construtiva. Para isso, parte-se da implementação de um projeto eTwinning levado a cabo com mais sete escolas europeias e desenvolvido, em Portugal, no Agrupamento de escolas Ibn Mucana, com alunos do 9º ano, no âmbito da disciplina de Espanhol Língua Estrangeira (ELE). O projeto implementado intitula-se Europa estudia español e encontra-se centrado na vida escolar dos alunos e nas obras literárias, teatrais e cinematográficas que integram o currículo dos diversos participantes. Pretende-se, com este relatório, alcançar um melhor conhecimento do processo de ensino e aprendizagem, no que se refere ao impacto da implementação de um projeto colaborativo eTwinning e do seu potencial na promoção da motivação e na melhoria dos resultados escolares. No primeiro capítulo, dá-se conta da pesquisa bibliográfica relativa a campos de conhecimento que possam oferecer contributos válidos para fundamentar e orientar a análise e avaliação das potencialidades das TIC. No segundo capítulo apresenta-se e descreve-se o programa de intervenção, o espaço escolar onde foi realizada a Prática de Ensino Supervisionada (PES) e faz-se uma caracterização das turmas em que foram lecionadas as aulas práticas e, finalmente, reflete-se sobre o impacto da sua implementação.

Development of Anatomophysiologic Knowledge Regarding the Cardiovascular System: From Egyptians to Harvey

Our knowledge regarding the anatomophysiology of the cardiovascular system (CVS) has progressed since the fourth millennium BC. In Egypt (3500 BC), it was believed that a set of channels are interconnected to the heart, transporting air, urine, air, blood, and the soul. One thousand years later, the heart was established as the center of the CVS by the Hippocratic Corpus in the medical school of Kos, and some of the CVS anatomical characteristics were defined. The CVS was known to transport blood via the right ventricle through veins and the pneuma via the left ventricle through arteries. Two hundred years later, in Alexandria, following the development of human anatomical dissection, Herophilus discovered that arteries were 6 times thicker than veins, and Erasistratus described the semilunar valves, emphasizing that arteries were filled with blood when ventricles were empty. Further, 200 years later, Galen demonstrated that arteries contained blood and not air. With the decline of the Roman Empire, Greco-Roman medical knowledge about the CVS was preserved in Persia, and later in Islam where, Ibn Nafis inaccurately described pulmonary circulation. The resurgence of dissection of the human body in Europe in the 14th century was associated with the revival of the knowledge pertaining to the CVS. The main findings were the description of pulmonary circulation by Servetus, the anatomical discoveries of Vesalius, the demonstration of pulmonary circulation by Colombo, and the discovery of valves in veins by Fabricius. Following these developments, Harvey described blood circulation.