914 resultados para Cognition disorders.


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In this work we explored the role of the 3'UTR of the MECP2 gene in patients with clinical diagnosis of RTT and mental retardation; focusing on regions of the 3'UTR with almost 100% conservation at the nucleotide level among mouse and human. By mutation scanning (DOVAM-S technique) the MECP2 3'UTR of a total of 66 affected females were studied. Five3'UTR variants in the MECP2 were found (c.1461+9G>A, c.1461+98insA, c.2595G>A, c.9961C>G and c.9964delC) in our group of patients. None of the variants found is located in putative protein-binding sites nor predicted to have a pathogenic role. Our data suggest that mutations in this region do not account for a large proportion of the RTT cases without a genetic explanation.

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RESUMO: A cognição social encontra-se frequentemente alterada na esquizofrenia. Esta alteração relaciona-se com a diminuição do funcionamento social,caracterizando-se quer por défices quer por vieses cognitivos sociais. No entanto, existem poucos instrumentos fiáveis e válidos para avaliar a cognição social na esquizofrenia, nomeadamente capazes de medir os vieses cognitivos sociais e a cognição social auto-relevante. Adicionalmente, as bases biológicas da disfunção social não estão totalmente esclarecidas. Evidências recentes sugerem que o peptídeo oxitocina (OXT) influencia o funcionamento social, e que esta relação poderá ser mediada pela cognição social. Este Trabalho de Projecto descreve a contribuição do autor para o desenvolvimento e avaliação psicométrica inicial de um novo instrumento de avaliação da cognição social, e a utilidade desta escala na investigação das associações entre a OXT e a capacidade e vieses cognitivos sociais. A Waiting Room Task (WRT), uma escala constituída por 26 vídeos sequenciais que simulam a experiência de observar outra pessoa numa sala de espera, foi administrada num estudo transversal com 61 doentes com esquizofrenia e 20 controlos saudáveis. Observou-se uma menor capacidade cognitiva social e um aumento dos vieses cognitivos sociais nos doentes com esquizofrenia, comparativamente aos controlos. Nos controlos e doentes com delírios, o desempenho na WRT correlacionou-se significativamente com os níveis de OXT. Esta correlação não se observou nos doentes sem delírios, sugerindo que o papel da OXT na cognição social poderá encontrar-se atenuado neste grupo. Estes achados fornecem suporte inicial para a adequação da WRT como instrumento de avaliação da cognição social na esquizofrenia, podendo ainda ser útil na investigação da sua base biológica. ------------ ABSTRACT: Social cognition is often impaired in schizophrenia. This impairment is related to poor social functioning and is characterized by both social cognitive deficits and biases. However, there are few reliable and valid measures of social cognition in schizophrenia, particularly measures of social cognitive bias and of self-relevant social cognition. Also, the biological bases of social dysfunction are not well understood. Emerging evidence suggests that the peptide oxytocin (OXT) influences social functioning, and that this relationship may be mediated by social cognition. This Research Project describes the author’s contribution to the development and initial psychometric testing of a new measure of social cognition, and the utility of this instrument to examine associations between OXT and social cognitive capacity and bias. The Waiting Room Task WRT), a video-based test comprising 26 sequential videos simulating the experience of facing another person in a waiting room, was administered in a cross-sectional study involving 61 patients with schizophrenia and 20 healthy controls. Social cognitive capacity was lower and social cognitive bias was increased in patients with schizophrenia compared with controls. Among controls and patients with delusions, performance on the WRT was significantly correlated with OXT level. This correlation was not found in patients without delusions suggesting that OXT’s role in social cognition may be blunted in this group. These findings provide initial support for the adequacy of the WRT as a measure for assessing social cognition in schizophrenia that may also be useful in understanding its biological underpinnings.

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ABSTRACT: Background: Sleep is integral to biological function and sleep disruption can result in both physiological and psychological dysfunction. The acute cognitive consequences of sleep loss has been an active field of recent investigation, evidence suggests that sleep disruption in critically ill older adults can result in acute decrements in cognitive functioning. Surgery activates the innate immune system, inducing neuroinflammatory changes that interfere with cognition. The fact that patients with sleep disorders have an increased likelihood of exhibiting postoperative delirium encourages us to investigate the contribution of perioperative SF to the neuroinflammatory and cognitive responses of surgery. Methods: The effects of 24h sleep fragmentation (SF) and surgery were explored on adult C57BL/6J male mice. SF procedure started at 7 am with the home-cages being placed on a large platform orbital shaker cycled every 120 seconds (30 sec on/90 sec off). This procedure lasted for 24h. Stabilized tibia fracture was performed either before or after the 24h SF procedure. Separate cohorts of mice were tested for systemic and hippocampal inflammation and cognition. Results: Twenty-four hours of SF induced non-hippocampal memory dysfunction and increase in systemic IL-6. SF and surgery caused hippocampal-dependent memory impairment, although memory impairment was not exacerbated by combining SF with surgery. One day after either SF or surgery there was a significant increase in IL6 mRNA and TNF-alpha mRNA. These increments were more pronounced when either pre or post operative SF was combined with surgery. Conclusions: We show that while SF and surgery can independently produce significant memory impairment, perioperative SF significantly increased hippocampal inflammation without further cognitive impairment. The dissociation between neuroinflammation and cognitive decline may relate to our use of a sole memory paradigm that does not capture other aspects of cognition, especially learning.

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RESUMO: A reprogramação celular permite que uma célula somática seja reprogramada para outra célula diferente através da expressão forçada de factores de transcrição (FTs) específicos de determinada linhagem celular, e constitui uma área de investigação emergente nos últimos anos. As células somáticas podem ser experimentalmente manipuladas de modo a obter células estaminais pluripotentes induzidas (CEPi), ou convertidas directamente noutro tipo de célula somática. Estas descobertas inovadoras oferecem oportunidades promissoras para o desenvolvimento de novas terapias de substituição celular e modelos de doença, funcionando também como ferramentas valiosas para o estudo dos mecanismos moleculares que estabelecem a identidade celular e regulam os processos de desenvolvimento. Existem várias doenças degenerativas hereditárias e adquiridas da retina que causam deficiência visual devido a uma disfunção no tecido de suporte da retina, o epitélio pigmentar da retina (EPR). Uma destas doenças é a Coroideremia (CHM), uma doença hereditária monogénica ligada ao cromossoma X causada por mutações que implicam a perda de função duma proteína com funções importantes na regulação do tráfico intracelular. A CHM é caracterizada pela degenerescência progressiva do EPR, assim como dos foto-receptores e da coróide. Resultados experimentais sugerem que o EPR desempenha um papel importante na patogénese da CHM, o que parece indicar uma possível vantagem terapêutica na substituição do EPR nos doentes com CHM. Por outro lado, existe uma lacuna em termos de modelos in vitro de EPR para estudar a CHM, o que pode explicar o ainda desconhecimento dos mecanismos moleculares que explicam a patogénese desta doença. Assim, este trabalho focou-se principalmente na exploração das potencialidades das técnicas de reprogramação celular no contexto das doenças de degenerescência da retina, em particular no caso da CHM. Células de murganho de estirpe selvagem, bem como células derivadas de um ratinho modelo de knockout condicional de Chm, foram convertidos com sucesso em CEPi recorrendo a um sistema lentiviral induzido que permite a expressão forçada dos 4 factores clássicos de reprogramação, a saber Oct4, Sox2, Klf4 e c-Myc. Estas células mostraram ter equivalência morfológica, molecular e funcional a células estaminais embrionárias (CES). As CEPi obtidas foram seguidamente submetidas a protocolos de diferenciação com o objectivo final de obter células do EPR. Os resultados promissores obtidos revelam a possibilidade de gerar um valioso modelo de EPR-CHM para estudos in vitro. Em alternativa, a conversão directa de linhagens partindo de fibroblastos para obter células do EPR foi também abordada. Uma vasta gama de ferramentas moleculares foi gerada de modo a implementar uma estratégia mediada por FTs-chave, seleccionados devido ao seu papel fundamental no desenvolvimento embrionário e especificação do EPR. Conjuntos de 10 ou menos FTs foram usados para transduzir fibroblastos, que adquiriram morfologia pigmentada e expressão de alguns marcadores específicos do EPR. Adicionalmente, observou-se a activação de regiões promotoras de genes específicos de EPR, indicando que a identidade transcricional das células foi alterada no sentido pretendido. Em conclusão, avanços significativos foram atingidos no sentido da implementação de tecnologias de reprogramação celular já estabelecidas, bem como na concepção de novas estratégias inovadoras. Metodologias de reprogramação, quer para pluripotência, quer via conversão directa, foram aplicadas com o objectivo final de gerar células do EPR. O trabalho aqui descrito abre novos caminhos para o estabelecimento de terapias de substituição celular e, de uma maneira mais directa, levanta a possibilidade de modelar doenças degenerativas da retina com disfunção do EPR numa placa de petri, em particular no caso da CHM.---------------ABSTRACT: Cellular reprogramming is an emerging research field in which a somatic cell is reprogrammed into a different cell type by forcing the expression of lineage-specific transcription factors (TFs). Cellular identities can be manipulated using experimental techniques with the attainment of pluripotency properties and the generation of induced Pluripotent Stem (iPS) cells, or the direct conversion of one somatic cell into another somatic cell type. These pioneering discoveries offer new unprecedented opportunities for the establishment of novel cell-based therapies and disease models, as well as serving as valuable tools for the study of molecular mechanisms governing cell fate establishment and developmental processes. Several retinal degenerative disorders, inherited and acquired, lead to visual impairment due to an underlying dysfunction of the support cells of the retina, the retinal pigment epithelium (RPE). Choroideremia (CHM), an X-linked monogenic disease caused by a loss of function mutation in a key regulator of intracellular trafficking, is characterized by a progressive degeneration of the RPE and other components of the retina, such as the photoreceptors and the choroid. Evidence suggest that RPE plays an important role in CHM pathogenesis, thus implying that regenerative approaches aiming at rescuing RPE function may be of great benefit for CHM patients. Additionally, lack of appropriate in vitro models has contributed to the still poorly-characterized molecular events in the base of CHM degenerative process. Therefore, the main focus of this work was to explore the potential applications of cellular reprogramming technology in the context of RPE-related retinal degenerations. The generation of mouse iPS cells was established and optimized using an inducible lentiviral system to force the expression of the classic set of TFs, namely Oct4, Sox2, Klf4 and c-Myc. Wild-type cells, as well as cells derived from a conditional knockout (KO) mouse model of Chm, were successfully converted into a pluripotent state, that displayed morphology, molecular and functional equivalence to Embryonic Stem (ES) cells. Generated iPS cells were then subjected to differentiation protocols towards the attainment of a RPE cell fate, with promising results highlighting the possibility of generating a valuable Chm-RPE in vitro model. In alternative, direct lineage conversion of fibroblasts into RPE-like cells was also tackled. A TF-mediated approach was implemented after the generation of a panoply of molecular tools needed for such studies. After transduction with pools of 10 or less TFs, selected for their key role on RPE developmental process and specification, fibroblasts acquired a pigmented morphology and expression of some RPE-specific markers. Additionally, promoter regions of RPE-specific genes were activated indicating that the transcriptional identity of the cells was being altered into the pursued cell fate. In conclusion, highly significant progress was made towards the implementation of already established cellular reprogramming technologies, as well as the designing of new innovative ones. Reprogramming into pluripotency and lineage conversion methodologies were applied to ultimately generate RPE cells. These studies open new avenues for the establishment of cell replacement therapies and, more straightforwardly,raise the possibility of modelling retinal degenerations with underlying RPE defects in apetri dish, particularly CHM.

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INTRODUCTION: Toxoplasma gondii and Neospora caninum are related Apicomplexa parasites responsible for systemic diseases in many species of animals, including dogs. METHODS: This study aimed to determine the occurrence of T. gondii and N. caninum infections in 50 dogs with neurological signs that were admitted to the Veterinary Hospital of Universidade Estadual Paulista, City of Botucatu, Brazil. All animals were screened for antibodies using an immunofluorescent antibody test for both parasites. Tissues of positive animals were bioassayed in mice (T. gondii) and gerbils (N. caninum), and DNA was analyzed using the polymerase chain reaction (PCR). Positive samples for T. gondii by PCR were typed using restriction fragment length polymorphism-PCR for 11 markers: SAG1, SAG2 (5′-3′-SAG2 and alt.SAG2), SAG3, Btub, GRA6, L358, c22-8, c29-6, PK1 and Apico, and CS3 marker for virulence analysis. RESULTS: Specific antibodies were detected in 11/50 (22%; 95% confidence interval (CI95%), 12.8-35.3%) animals for T. gondii and 7/50 (14%; CI95%, 7.02-26.3%) for N. caninum. In the bioassay and PCR, 7/11 (63.6%; CI95%, 34.9-84.8%) samples were positive for T. gondii and 3/7 (42.9%; CI95%I, 15.7-75.5%) samples were positive for N. caninum. Three different genotypes were identified, but only 1 was unique. CONCLUSIONS: These data confirm the presence of T. gondii and N. caninum in dogs from Brazil, indicating the importance of this host as a sentinel of T. gondii for human beings, and the genotypic variation of this parasite in Brazil.

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Este trabalho aborda a conceito de desordem psíquica na obra de Galeno (129-216). A primeira parte enquadra o pensamento de Galeno na visão da Filosofia e Medicina em vigor no início do séc. II d.C. De seguida descrevo a concepção Hipocrática de epilepsia, e a abordagem que Platão desenvolve no Timeu e Fedro acerca da loucura, para de seguida abordar a concepção de doença em Galeno, onde são analisados os conceitos de nosêma, diathesis, pathos e energeia. Após este excurso descrevo o ponto de vista de Galeno acerca da controvérsia sobre a localização da parte dirigente da alma (hêgemonikon) que se dividia entre defensores do encefalocentrismo (Platão, Hipócrates e Herófilo) e do cardiocentrismo (Aristóteles e os Estóicos). De modo a aprofundar a compreensão de Galeno acerca deste tema descrevo o trabalho anatómico-fisiológico desenvolvido pelos médicos Alexandrinos Erasistrato e Herófilo, activos no sec. III a. C., que descobriram, através de dissecação de animais e muito provavelmente de humanos, o papel dos nervos e tendões nas atividades cognitivas e sensório-motoras. Esta foi uma descoberta central para a argumentação de Galeno acerca da interacção mente-corpo assim como para a descrição das desordens psíquicas. Posteriormente apresento a metodologia de Galeno no que concerne ao processo de diagnóstico e etiologia, essencial para se compreender como é possível aceder a ‘entidades’ não visíveis, como o hêgemonikon e as suas diferentes faculdades: ‘imaginação’, memória e raciocínio. Por fim, analiso alguns casos clínicos de pacientes afectados por desordens do hêgemonikon, a saber: phrenitis, mania e melancolia. Os principais textos objecto de análise são: Acerca dos Lugares Afectados, Acerca das Teses de Hipócrates e Platão e Que as Faculdades da Alma Seguem as Disposições do Corpo. Todavia, outros textos de Galeno serão convocados consoante a necessidade de analisar os conceitos que me proponho compreender, entre eles Acerca do Método Terapêutico e Acerca da Utilidade das Partes.

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The Free and Cued Selective Reminding Test (FCSRT) is a memory test that controls attention and acquisition, by providing category cues in the learning process. Because it enables an assessment of memory not confounded by normal age-related changes in cognition and a high accuracy on Alzheimer's disease (AD) evaluation, it has been suggested by the International Working Group on AD. Our aim was to assess the construct related validity of the FCSRT in the AD spectrum disorders.

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AbstractINTRODUCTION:Combined antiretroviral therapy has enabled human immunodeficiency virus (HIV) carriers to live longer. This increased life expectancy is associated with the occurrence of degenerative diseases, including HIV-associated neurocognitive disorders (HAND), which are diagnosed via a complex neuropsychological assessment. The International HIV Dementia Scale (IHDS) is a screening instrument validated in Brazil for use in the absence of neuropsychological evaluation. HIV patients are frequently diagnosed with depression. We aimed to determine the prevalence of neurocognitive impairment using the IHDS and depressive disorders using the Hamilton Rating Scale for Depression (HAM-D17), compare the IHDS performance with the performances on the Timed Gait Test (TGT), the Digit Symbol Coding Test (DS) and the Brazilian version of the Scale of Instrumental Activities of Daily Living (IADL), and evaluate the association between the IHDS performance and clinical-demographic variables.METHODS:One hundred fourteen patients were evaluated in a cross-sectional study conducted in a public outpatient clinic for infectious diseases in Marília City, State of São Paulo, Brazil. Data were collected following consultation. Statistical analysis was performed in accordance with the nature and distribution of the data and hypotheses.RESULTS:According to the IHDS, 53.2% of the sampled patients were neuropsychologically impaired. According to the HAM-D17, 26.3% had depressive disorders. There were significant associations between the IHDS and the TGT and DS. Multiple regression analysis indicated that female gender, educational level, and cluster of differentiation 4 (CD4) levels were significantly and independently associated with neurocognitive impairment.CONCLUSIONS:The prevalence of neurocognitive impairment according to the IHDS is high and associated with female gender, education level, and low CD4 levels.

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Abstract INTRODUCTION : The human T-lymphotropic virus-1 (HTLV-1) is associated with chronic inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic inflammatory disease. Disturbances in lipid metabolism are involved in inflammatory and demyelinating diseases. METHODS : Plasma levels of triglycerides, total cholesterol, and fractions of HTLV-1-infected individuals of both sexes with different clinical progressions were determined. RESULTS : Elevated levels of triglyceride and very low-density lipoproteins (VLDL) were exclusively detected in HTLV-1-infected women from asymptomatic and HAM/TSP groups compared with uninfected individuals (p = 0.02). CONCLUSIONS : Elevated triglyceride and VLDL levels in HTLV-1-infected women may be related to the predominance of HAM/TSP in women.

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Obsessive-compulsive disorder (OCD) has been reported in association with some neurological diseases that affect the basal ganglia such as Tourette's syndrome, Sydenham's chorea, Parkinson's disease, and Huntington's disease. Furthermore, studies such as neuroimaging, suggest a role of the basal ganglia in the pathophysiology of OCD. The aim of this paper is to describe the association of OCD and several neurologic disorders affecting the basal ganglia, report the existing evidences of the role of the basal ganglia in the pathophysiology of OCD, and analyze the mechanisms probably involved in this pathophysiology.

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Youngsters are increasingly using 3,4 methylenedioxymethamphetamine, known as ecstasy, because it is wrongly believed that it does not induce harm. However, there are many reports of adverse effects, including acute intoxication, abuse potential, and possible neurotoxic effects. Therefore, health care providers need to promptly recognize the symptoms of systemic intoxication in order to initiate early treatment. The drug is used by the oral route for long hours during crowded dance parties. Acutely, ecstasy increases the release of serotonin and decreases its reuptake, leading to hypertension, hyperthermia, trismus, and vomiting. There is debate on whether recreational doses of ecstasy cause permanent damage to human serotonergic neurons. Ecstasy users showed a high risk of developing psychopathological disturbances. The prolonged use of ecstasy might induce dependence, characterized by tolerance and hangover. Acute ecstasy intoxication needs emergency-type treatment to avoid the dose-dependent increase in adverse reactions and in severity of complications. There are no specific antidotes to be used during acute intoxication. Supportive measures and medical treatment for each one of the complications should be implemented, keeping in mind that symptoms originate mainly from the central nervous system and the cardiovascular system.

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RESUMO: Resumo Uma prestação de serviços de saúde mental para crianças e adolescentes (CAMHS) oportuna, eficaz e baseada na evidência pode evitar incapacidade a longo prazo. No entanto, estes serviços são criticamente sub-financiados em todo o mundo. É um imperativo garantir que este precioso recurso não seja desperdiçado. Os governos e outras partes interessadas relevantes na área da saúde mental precisam de conhecer o estado de saúde mental da população, quais os recursos disponíveis e como melhor utilizar os recursos disponíveis para orientar uma política e decisões efectivas sobre os níveis de serviços. Objetivo: O objetivo deste artigo é explorar o papel da acuidade, gravidade e complexidade na determinação dos cuidados em saúde mental especializados recebidos por crianças e adolescentes que sofrem perturbações mentais. Métodos: Este estudo é exploratório envolvendo uma revisão sistemática da literatura. Foi realizada uma pesquisa com palavras-chave utilizando bases de dados PsychINFO, EMBASE, PubMed e MEDLINE. A literatura cinzenta também foi investigada com um enfoque nas abordagens sistémicas, organizacionais e políticas para a organização e comissionamento de CAMHS. Foram selecionados apenas documentos escritos em Inglês. Três países, Bélgica, Reino Unido e Estados Unidos, todos eles com modelos muito diferentes de organização de CAMHS, foram revistos para investigar de que forma os conceitos de acuidade, gravidade e complexidade foram utilizados na sua concepção de serviços para determinar o nível da assistência prestada. Resultados: Nem a Bélgica, nem o modelo norte-americano de CAMHS organização de serviço parecem estar alinhados com os principais conceitos na determinação do nível de prestação de serviços. O sistema de serviços do Reino Unido de CAMHS está mais estreitamente alinhado com esses conceitos e tem uma alocação de recursos mais equilibrada entre o hospital e a comunidade. O seu ponto fraco está na falta de flexibilidade entre os níveis de serviço e na falta de apoio para com o sector dos cuidados de saúde primários. Conclusões: A variabilidade na alocação de recursos a diferentes níveis especializados de CAMHS (em regime de internamento, ambulatório, e na comunidade) e o modelo diferente de estrutura de serviços entre os países estudados indica uma inconsistência na forma como as crianças e adolescentes que apresentam aos CAMHS são referenciados para os cuidados que recebem. Isto põe em questão se as crianças e adolescentes com perturbações mentais estão a receber o nível e tipo de cuidados concordantes com as suas necessidades. A concepção e o comissionamento de sistemas de CAMHS levam-nos à discussão de uma série de princípios fundamentais que devem ser considerados. O sistema perfeito no entanto, ainda está para ser encontrado. -------------------------------- ABSTRACT: Provision of timely, effective, evidence based mental health services to children and adolescents can prevent long term impairment, but they are critically underfunded across the globe. There is an imperative to ensure this precious resource is not wasted. Governments and other relevant mental health stakeholders need to know the mental health status of the population, what resources are available and how best to use the resources available to guide effective policy and decisions about service levels. Aim: The aim of this paper is to explore the role of acuity, severity and complexity in determining the specialist mental health care that children and adolescents experiencing mental disorders receive. Methods: This study is exploratory involving a systematic scan of the literature. A key word search was conducted using databases PSYCHINFO, EMBASE, PUBMED and MEDLINE. Grey literature was also searched to focus on systemic, organisational and policy approaches to the organisation and commissioning of CAMHS. Only documents written in English were selected. Three countries Belgium, UK and the US all with very different models of service organisation for CAMHS were reviewed to investigate how well the concepts of acuity, severity and complexity were used to determine the level of care delivered in their service design. Findings: Neither the Belgium nor the US model of CAMHS service organisation appear to align with the key concepts driving intensity of level of service provision. The UK CAMHS service system most closely aligns with the concepts. It has a more balanced resource allocation between hospital and community. Its downfall is in its lack of flexibility between service levels and its lack of support for the primary care sector. Conclusions: The variability in resource allocation to different service levels (inpatient, outpatient, community) within specialist CAMHS and the differing model of service structure across countries indicates an inconsistency in how children and adolescents presenting to CAMHS are allocated to the care they receive. This puts into question whether children and adolescent with mental disorders are receiving a level and type of care commensurate with their needs. In commissioning and designing CAMHS systems a number of key principles that should be considered are discussed. The perfect system however, is yet to be found.

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Dissertação de mestrado em Educação Especial (área de especialização em Dificuldades de Aprendizagem Específicas)

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Graphics based systems of Augmented and Alternative Communication are widely used to promote communication in people with Autism Spectrum Disorders. This study discusses an integration of Augmented Reality in communication interventions, by relating elements of Augmented and Alternative Communication and Applied Behaviour Analysis strategies. An architecture for an Augmented Reality based interactive system to assist interventions is proposed. STAR provides an Augmented Reality tool to assist interventions performed by therapists and support for parents to join in and participate in the child’s intervention. Finally we report on the usage of the Augmented Reality tool in interventions with children with Autism Spectrum Disorders.