The development of the N1 and N2 components in auditory oddball paradigms: a systematic review with narrative analysis and suggested normative values

Auditory event-related potentials (AERPs) are widely used in diverse fields of today’s neuroscience, concerning auditory processing, speech perception, language acquisition, neurodevelopment, attention and cognition in normal aging, gender, developmental, neurologic and psychiatric disorders. However, its transposition to clinical practice has remained minimal. Mainly due to scarce literature on normative data across age, wide spectrumof results, variety of auditory stimuli used and to different neuropsychological meanings of AERPs components between authors. One of the most prominent AERP components studied in last decades was N1, which reflects auditory detection and discrimination. Subsequently, N2 indicates attention allocation and phonological analysis. The simultaneous analysis of N1 and N2 elicited by feasible novelty experimental paradigms, such as auditory oddball, seems an objective method to assess central auditory processing. The aim of this systematic review was to bring forward normative values for auditory oddball N1 and N2 components across age. EBSCO, PubMed, Web of Knowledge and Google Scholarwere systematically searched for studies that elicited N1 and/or N2 by auditory oddball paradigm. A total of 2,764 papers were initially identified in the database, of which 19 resulted from hand search and additional references, between 1988 and 2013, last 25 years. A final total of 68 studiesmet the eligibility criteria with a total of 2,406 participants from control groups for N1 (age range 6.6–85 years; mean 34.42) and 1,507 for N2 (age range 9–85 years; mean 36.13). Polynomial regression analysis revealed thatN1latency decreases with aging at Fz and Cz,N1 amplitude at Cz decreases from childhood to adolescence and stabilizes after 30–40 years and at Fz the decrement finishes by 60 years and highly increases after this age. Regarding N2, latency did not covary with age but amplitude showed a significant decrement for both Cz and Fz. Results suggested reliable normative values for Cz and Fz electrode locations; however, changes in brain development and components topography over age should be considered in clinical practice.

Neural mechanisms of stimulus generalization in auditory fear conditioning

Dissertation presented to obtain the Ph.D degree in Neuroscience Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa

Avaliação funcional e farmacológica do corpo carotídeo do rato no envelhecimento

Resumo: O corpo carotídeo gera o quimiorreflexo à hipoxia, tendo por objectivo principal a homeostase dos gases do sangue. Esta tese testou a hipótese da função destes quimiossensores não se deteriorar ao longo da idade. In vivo, em ratos anestesiados, foram estudados os efeitos da idade nas respostas cardiorespiratórias a dois tipos de estímulos diferentes: a isquemia carotídea e a manipulação farmacológica de dois neurotransmissores com efeitos opostos nos quimiorreceptores, a adenosina e a dopamina. O modelo de isquemia carotídea corresponde à oclusão bilateral da artéria carótida comum, durante períodos de 5 a 15 s, o que determina um efeito excitatório na ventilação que é abolido pela secção bilateral dos nervos do seio carotídeo. No estudo farmacológico foram analisadas as respostas cardio-respiratórias à adenosina e à dopamina exógenas na presença e na ausência de antagonistas selectivos para os receptores A2A e D2, respectivamente. In vitro, no corpo carotídeo, foi quantificado o efeito de diferentes concentrações de oxigénio no conteúdo do segundo mensageiro comum à activação dos receptores A2A e D2, o cAMP. Em conjunto, estes resultados demonstraram que no rato o controlo da ventilação pelo corpo carotídeo se mantém inalterado ao longo da idade.--------------------- ABSTRACT: The carotid body initiates reflexes aimed principally at the homeostatic maintenance of blood gas tensions. This thesis tested the hypothesis of the function of these quimiossensores not deteriorate through age. In vivo, in anesthetized rats, we studied the effects of age on cardiorespiratory responses to two different types of stimuli: carotid ischemia and pharmacological manipulation of neurotransmitters with two opposite effects on chemoreceptors, adenosine and dopamine. The model of carotid ischemia corresponded to bilateral occlusion of common carotid artery, during periods of 5 to 15 s, which determines an excitatory effect on ventilation that is abolished by bilateral section of carotid sinus nerve. The pharmacological study analyzed the cardiorespiratory responses to exogenous adenosine and dopamine in the presence and absence of selective antagonists for the A2A and D2 receptors, respectively. In vitro, at the carotid body, it was quantified the effect of different concentrations of oxygen in the content of the common second messenger for the activation of A2A and D2 receptors, the cAMP. Together, these results showed that in rats the control of ventilation by carotid body remains unchanged through age.

Functional and therapeutical implications of ligand recognition by the scavenger-like lymphocyte receptors CD5 and CD6

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Marketing experiencial, emoções, satisfação e lealdade

O marketing transacional apresenta-se nos dias de hoje insuficiente para fazer face às exigências de um consumidor mais participativo, seletivo e crítico. No mercado global, industrializado e em constante evolução tecnológica, é, cada vez mais, difícil obter um grau de diferenciação assente apenas nos benefícios funcionais e racionais. O marketing transacional evoluiu para o marketing relacional, constituindo o cliente o centro do processo de trocas. A economia das experiências alterou a forma como as marcas trabalham o mercado, introduzindo o conceito de experiências, o que por sua vez conceptualizou o marketing experiencial, orientado para a gestão da experiência do cliente, transformando o ato de consumo em algo memorável, cheio de estímulos sensoriais e emocionais, convertendo-se, por vezes, no próprio produto, seja ele de âmbito industrial, desportivo ou mesmo cultural. Este grau de envolvimento do cliente com a marca é elemento gerador de emoção, de satisfação, de lealdade e de valor. Este trabalho pretendeu analisar a importância e os componentes estimuladores do marketing experiencial e a sua relação com as emoções, satisfação e a lealdade dos consumidores no evento cultural “Serralves em festa 2013”. Para tal, utilizamos uma metodologia de investigação quantitativa, com recurso a análise de equações estruturais, suportada por uma pesquisa teórica. O estudo empírico realizado, baseado num inquérito por questionário, possibilitou obter uma amostra de 264 respostas válidas. Após a validação e melhoria das escalas de medida dos conceitos, os resultados destas e do modelo estrutural demonstraram valores adequados. Estudaram-se e comprovaram-se as relações previstas nas hipóteses, nomeadamente, a relação positiva do impacto das experiências no comportamento do consumidor, designadamente, na sua emoção e satisfação e o impacto destas na sua lealdade. Entre as variáveis estudadas foram obtidos interessantes níveis de correlação e capacidades preditivas.

Microglial clearance function: dependence on phenotypes

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Cold Urticaria and Infectious Mononucleosis in Children

Physical urticaria includes a heterogeneous group of disorders characterized by the development of urticarial lesions and/or angioedema after exposure to certain physical stimuli. The authors present the case of a child with severe acquired cold urticaria secondary to infectious mononucleosis. Avoidance of exposure to cold was recommended; prophylactic treatment with ketotifen and cetirizine was begun and a self-administered epinephrine kit was prescribed. The results of ice cube test and symptoms significantly improved. Physical urticaria, which involves complex pathogenesis, clinical course and therapy, may be potentially life threatening. Evaluation and diagnosis are especially important in children. To our knowledge this is the first description of persistent severe cold-induced urticaria associated with infectious mononucleosis in a child.

Role of oxidative stress-induced systemic and cavernosal molecular alterations in the progression of diabetic erectile dysfunction

Background Erectile dysfunction (ED) is a prevalent complication of diabetes, and oxidative stress is an important feature of diabetic ED. Oxidative stress-induced damage plays a pivotal role in the development of tissue alterations. However, the deleterious effects of oxidative stress in the corpus cavernosum with the progression of diabetes remain unclear. The aim of this study was to evaluate systemic and penile oxidative stress status in the early and late stages of diabetes. Methods Male Wistar streptozotocin-diabetic rats (and age-matched controls) were examined 2 (early) and 8 weeks (late) after the induction of diabetes. Systemic oxidative stress was evaluated by urinary H2O2 and the ratio of circulating reduced/oxidized glutathione (GSH/GSSG). Penile oxidative status was assessed by H2O2 production and 3-nitrotyrosine (3-NT) formation. Cavernosal endothelial nitric oxide synthase (eNOS) was analyzed by quantitative immunohistochemistry. Dual immunofluorescence was also performed for 3-NT and α-smooth muscle actin (α-SMA) and eNOS–α-SMA. Results There was a significant increase in urinary H2O2 levels in both diabetic groups. The plasma GSH/GSSG ratio was significantly augmented in late diabetes. In cavernosal tissue, H2O2 production was significantly increased in late diabetes. Reactivity for 3-NT was located predominantly in cavernosal smooth muscle (SM) and was significantly reduced in late diabetes. Quantitative immunohistochemistry revealed a significant decrease in eNOS levels in cavernosal SM and endothelium in late diabetes. Conclusions The findings indicate that the noxious effects of oxidative stress are more prominent in late diabetes. Increased penile protein oxidative modifications and decreased eNOS expression may be responsible for structural and/or functional deregulation, contributing to the progression of diabetes-associated ED.

Transgenerational Inheritance of Paternal Neurobehavioral Phenotypes: Stress, Addiction, Ageing and Metabolism

Epigenetic modulation is found to get involved in multiple neurobehavioral processes. It is believed that different types of environmental stimuli could alter the epigenome of the whole brain or related neural circuits, subsequently contributing to the long-lasting neural plasticity of certain behavioral phenotypes. While the maternal influence on the health of offsprings has been long recognized, recent findings highlight an alternative way for neurobehavioral phenotypes to be passed on to the next generation, i.e., through the male germ line. In this review, we focus specifically on the transgenerational modulation induced by environmental stress, drugs of abuse, and other physical or mental changes (e.g., ageing, metabolism, fear) in fathers, and recapitulate the underlying mechanisms potentially mediating the alterations in epigenome or gene expression of offsprings. Together, these findings suggest that the inheritance of phenotypic traits through male germ-line epigenome may represent the unique manner of adaptation during evolution. Hence, more attention should be paid to the paternal health, given its equivalently important role in affecting neurobehaviors of descendants.

Detrimental role of prolonged sleep deprivation on adult neurogenesis

Adult mammalian brains continuously generate new neurons, a phenomenon called adult neurogenesis. Both environmental stimuli and endogenous factors are important regulators of adult neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and adult neurogenesis in brain function, such as learning, memory, and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on adult neurogenesis.

Neural Mechanisms of Exercise: Effects on Gut Miccrobiota and Depression

Microbiota is a set of microorganisms resident in gut ecosystem that reacts to psychological stressful stimuli, and is involved in depressed or anxious status in both animals and human being. Interestingly, a series of studies have shown the effects of physical exercise on gut microbiota dynamics, suggesting that gut microbiota regulation might act as one mediator for the effects of exercise on the brain. Recent studies found that gut microbiota dynamics are also regulated by metabolism changes, such as through physical exercise or diet change. Interestingly, physical exercise modulates different population of gut bacteria in compared to food restriction or rich diet, and alleviates gut syndromes to toxin intake. Gut microbiota could as well contribute to the beneficial effects of exercise on cognition and emotion, either directly through serotonin signaling or indirectly by modulating metabolism and exercise performance.

Effects of Aerobic Exercise on Anxiety Disorders: A Systematic Review

Anxiety disorders are the most common psychiatric disorders observed currently. It is a normal adaptive response to stress that allows coping with adverse situations. Nevertheless, when anxiety becomes excessive or disproportional in relation to the situation that evokes it or when there is not any special object directed at it, such as an irrational dread of routine stimuli, it becomes a disabling disorder and is considered to be pathological. The traditional treatment used is medication and cognitive behavioral psychotherapy, however, last years the practice of physical exercise, specifically aerobic exercise, has been investigated as a new non-pharmacological therapy for anxiety disorders. Thus, the aim of this article was to provide information on research results and key chains related to the therapeutic effects of aerobic exercise compared with other types of interventions to treat anxiety, which may become a useful clinical application in a near future. Researches have shown the effectiveness of alternative treatments, such as physical exercise, minimizing high financial costs and minimizing side effects. The sample analyzed, 66.8% was composed of women and 80% with severity of symptoms anxiety as moderate to severe. The data analyzed in this review allows us to claim that alternative therapies like exercise are effective in controlling and reducing symptoms, as 91% of anxiety disorders surveys have shown effective results in treating. However, there is still disagreement regarding the effect of exercise compared to the use of antidepressant symptoms and cognitive function in anxiety, this suggests that there is no consensus on the correct intensity of aerobic exercise as to achieve the best dose-response, with intensities high to moderate or moderate to mild.

A Publicidade no Ensino do Inglês no 1.º Ciclo: uma abordagem didática

Numa era de globalização, de desenvolvimento tecnológico exponencial e de consumismo exacerbado, a publicidade conquistou o quotidiano das sociedades modernas e seduziu, também, as nossas crianças. Subjacente ao paradigma de que o comportamento humano dá respostas favoráveis a estímulos adequados e apresentados com oportunidade e habilidade (Caetano et al., 2011), colocamos a hipótese de utilização didática de anúncios publicitários na aula de Inglês para o desenvolvimento de competências comunicativas. Este projeto assentou no aproveitamento do potencial que a publicidade oferece, tendo em conta, por um lado, a envolvência sedutora que a torna um meio privilegiado para captar a atenção e veicular informação e, por outro, a prevalência de palavras em Inglês que nela se observa. O estudo, de natureza qualitativa, é o resultado de uma investigação-ação, na qual adotamos uma metodologia baseada num modelo descritivo e interpretativo, através de métodos qualitativos de recolha de dados e análise de informação, que teve como participantes crianças do 4.º ano de escolaridade. Desenvolvemos questionários, como instrumentos de recolha de dados, aplicados a professores e alunos. Construímos, igualmente, guiões de atividades com sugestões de exploração da publicidade no ensino da língua. Comprovamos que a publicidade, aliada ao Inglês, pode ser um valioso recurso no desenvolvimento e aprendizagem das crianças, pois é um material autêntico, motivador, atrai a atenção, possibilita o contacto com situações reais, envolve linguagem verbal e não-verbal e permite a exploração de diferentes temas, o que contribui, certamente, para a compreensão intercultural, a mobilização de saberes e o desenvolvimento do espírito crítico.

Bioactive beads for local sensing of proteases in 3D engineered tissues

Dissertação para obtenção do Grau de Doutor em Bioengenharia (MIT)

Management of Childhood Urticaria: Current Knowledge and Practical Recommendations

Urticaria, defined by the presence of wheals and/or angioedema,is a common condition in children, prompting parents to consult physicians. For its successful management, paediatric-specific features must be taken into account, regarding the identification of eliciting triggers and pharmacological therapy. This review systematically discusses the current best-available evidence on spontaneous acute and chronic urticaria as well as physical and other urticaria types in children. Potential underlying causes, namely infections, food and drug hypersensitivity, autoreactivity and autoimmune or other conditions, and eliciting stimuli are considered, with practical recommendations for specific diagnostic approaches. Second-generation antihistamines are the mainstay of pharmacological treatment aimed at relief of symptoms, which require dose adjustment for paediatric use. Other therapeutic interventions are also discussed. In addition, unmet needs are highlighted, aiming to promote research into the paediatric population, ultimately aiming at the effective management of childhood urticaria.