Role of the cotransporter KCC2 in cortical excitatory synapse development and febrile seizure susceptibility

Le co-transporteur KCC2 spécifique au potassium et chlore a pour rôle principal de réduire la concentration intracellulaire de chlore, entraînant l’hyperpolarisation des courants GABAergic l’autorisant ainsi à devenir inhibiteur dans le cerveau mature. De plus, il est aussi impliqué dans le développement des synapses excitatrices, nommées aussi les épines dendritiques. Le but de notre projet est d’étudier l’effet des modifications concernant l'expression et la fonction de KCC2 dans le cortex du cerveau en développement dans un contexte de convulsions précoces. Les convulsions fébriles affectent environ 5% des enfants, et ce dès la première année de vie. Les enfants atteints de convulsions fébriles prolongées et atypiques sont plus susceptibles à développer l’épilepsie. De plus, la présence d’une malformation cérébrale prédispose au développement de convulsions fébriles atypiques, et d’épilepsie du lobe temporal. Ceci suggère que ces pathologies néonatales peuvent altérer le développement des circuits neuronaux irréversiblement. Cependant, les mécanismes qui sous-tendent ces effets ne sont pas encore compris. Nous avons pour but de comprendre l'impact des altérations de KCC2 sur la survenue des convulsions et dans la formation des épines dendritiques. Nous avons étudié KCC2 dans un modèle animal de convulsions précédemment validé, qui combine une lésion corticale à P1 (premier jour de vie postnatale), suivie d'une convulsion induite par hyperthermie à P10 (nommés rats LHS). À la suite de ces insultes, 86% des rats mâles LHS développent l’épilepsie à l’âge adulte, au même titre que des troubles d’apprentissage. À P20, ces animaux presentent une augmentation de l'expression de KCC2 associée à une hyperpolarisation du potentiel de réversion de GABA. De plus, nous avons observé des réductions dans la taille des épines dendritiques et l'amplitude des courants post-synaptiques excitateurs miniatures, ainsi qu’un déficit de mémoire spatial, et ce avant le développement des convulsions spontanées. Dans le but de rétablir les déficits observés chez les rats LHS, nous avons alors réalisé un knock-down de KCC2 par shARN spécifique par électroporation in utero. Nos résultats ont montré une diminution de la susceptibilité aux convulsions due à la lésion corticale, ainsi qu'une restauration de la taille des épines. Ainsi, l’augmentation de KCC2 à la suite d'une convulsion précoce, augmente la susceptibilité aux convulsions modifiant la morphologie des épines dendritiques, probable facteur contribuant à l’atrophie de l’hippocampe et l’occurrence des déficits cognitifs. Le deuxième objectif a été d'inspecter l’effet de la surexpression précoce de KCC2 dans le développement des épines dendritiques de l’hippocampe. Nous avons ainsi surexprimé KCC2 aussi bien in vitro dans des cultures organotypiques d’hippocampe, qu' in vivo par électroporation in utero. À l'inverse des résultats publiés dans le cortex, nous avons observé une diminution de la densité d’épines dendritiques et une augmentation de la taille des épines. Afin de confirmer la spécificité du rôle de KCC2 face à la région néocorticale étudiée, nous avons surexprimé KCC2 dans le cortex par électroporation in utero. Cette manipulation a eu pour conséquences d’augmenter la densité et la longueur des épines synaptiques de l’arbre dendritique des cellules glutamatergiques. En conséquent, ces résultats ont démontré pour la première fois, que les modifications de l’expression de KCC2 sont spécifiques à la région affectée. Ceci souligne les obstacles auxquels nous faisons face dans le développement de thérapie adéquat pour l’épilepsie ayant pour but de moduler l’expression de KCC2 de façon spécifique.

The role of mechanistic target of rapamycin (mTOR) pathway and synaptic protein GABAA-R in cortical GABAergic cell connectivity

Quelque 30 % de la population neuronale du cortex mammalien est composée d’une population très hétérogène d’interneurones GABAergiques. Ces interneurones diffèrent quant à leur morphologie, leur expression génique, leurs propriétés électrophysiologiques et leurs cibles subcellulaires, formant une riche diversité. Après leur naissance dans les éminences ganglioniques, ces cellules migrent vers les différentes couches corticales. Les interneurones GABAergiques corticaux exprimant la parvalbumin (PV), lesquels constituent le sous-type majeur des interneurones GABAergiques, ciblent spécifiquement le soma et les dendrites proximales des neurones principaux et des neurones PV+. Ces interneurones sont nommés cellules à panier (Basket Cells –BCs) en raison de la complexité morphologique de leur axone. La maturation de la connectivité distincte des BCs PV+, caractérisée par une augmentation de la complexité de l’axone et de la densité synaptique, se déroule graduellement chez la souris juvénile. Des travaux précédents ont commencé à élucider les mécanismes contrôlant ce processus de maturation, identifiant des facteurs génétiques, l’activité neuronale ainsi que l’expérience sensorielle. Cette augmentation marquante de la complexité axonale et de la synaptogénèse durant cette phase de maturation suggère la nécessité d’une synthèse de protéines élevée. La voie de signalisation de la cible mécanistique de la rapamycine (Mechanistic Target Of Rapamycin -mTOR) a été impliquée dans le contrôle de plusieurs aspects neurodéveloppementaux en régulant la synthèse de protéines. Des mutations des régulateurs Tsc1 et Tsc2 du complexe mTOR1 causent la sclérose tubéreuse (TSC) chez l’humain. La majorité des patients TSC développent des problèmes neurologiques incluant des crises épileptiques, des retards mentaux et l’autisme. D’études récentes ont investigué le rôle de la dérégulation de la voie de signalisation de mTOR dans les neurones corticaux excitateurs. Toutefois, son rôle dans le développement des interneurones GABAergiques corticaux et la contribution spécifique de ces interneurones GABAergiques altérés dans les manifestations de la maladie demeurent largement inconnus. Ici, nous avons investigué si et comment l’ablation du gène Tsc1 perturbe le développement de la connectivité GABAergique, autant in vitro que in vivo. Pour investiguer le rôle de l’activation de mTORC1 dans le développement d’une BC unique, nous avons délété le gène Tsc1 en transfectant CRE-GFP dirigé par un promoteur spécifique aux BCs dans des cultures organotypiques provenant de souris Tsc1lox. Le knockdown in vitro de Tsc1 a causé une augmentation précoce de la densité des boutons et des embranchements terminaux formés par les BCs mutantes, augmentation renversée par le traitement à la rapamycine. Ces données suggèrent que l’hyperactivation de la voie de signalisation de mTOR affecte le rythme de la maturation des synapses des BCs. Pour investiguer le rôle de mTORC1 dans les interneurones GABAergiques in vivo, nous avons croisé les souris Tsc1lox avec les souris Nkx2.1-Cre et PV-Cre. À P18, les souris Tg(Nkx2.1-Cre);Tsc1flox/flox ont montré une hyperactivation de mTORC1 et une hypertrophie somatique des BCs de même qu’une augmentation de l’expression de PV dans la région périsomatique des neurones pyramidaux. Au contraire, à P45 nous avons découvert une réduction de la densité des punctas périsomatiques PV-gephyrin (un marqueur post-synaptique GABAergique). L’étude de la morphologie des BCs en cultures organotypiques provenant du knock-out conditionnel Nkx2.1-Cre a confirmé l’augmentation initiale du rythme de maturation, lequel s’effondre ensuite aux étapes développementales tardives. De plus, les souris Tg(Nkx2.1Cre);Tsc1flox/flox montrent des déficits dans la mémoire de travail et le comportement social et ce d’une façon dose-dépendante. En somme, ces résultats suggèrent que l’activation contrôlée de mTOR régule le déroulement de la maturation et la maintenance des synapses des BCs. Des dysfonctions de la neurotransmission GABAergique ont été impliquées dans des maladies telles que l’épilepsie et chez certains patients, elles sont associées avec des mutations du récepteur GABAA. De quelle façon ces mutations affectent le processus de maturation des BCs demeuret toutefois inconnu. Pour adresser cette question, nous avons utilisé la stratégie Cre-lox pour déléter le gène GABRA1, codant pour la sous-unité alpha-1 du récepteur GABAA dans une unique BC en culture organotypique. La perte de GABRA1 réduit l’étendue du champ d’innervation des BCs, suggérant que des variations dans les entrées inhibitrices en raison de l’absence de la sous-unité GABAAR α1 peuvent affecter le développement des BCs. La surexpression des sous-unités GABAAR α1 contenant des mutations identifiées chez des patients épileptiques ont montré des effets similaires en termes d’étendue du champ d’innervation des BCs. Pour approfondir, nous avons investigué les effets de ces mutations identifiées chez l’humain dans le développement des épines des neurones pyramidaux, lesquelles sont l’endroit privilégié pour la formation des synapses excitatrices. Somme toute, ces données montrent pour la première fois que différentes mutations de GABRA1 associées à des syndromes épileptiques peuvent affecter les épines dendritiques et la formation des boutons GABAergiques d’une façon mutation-spécifique.

Évaluation électrophysiologique auditive et examen du langage et de l’attention chez l’enfant né prématurément et l’enfant né à terme

L’objectif de cette thèse est l’étude du développement de l’attention auditive et des capacités de discrimination langagière chez l’enfant né prématurément ou à terme. Les derniers mois de grossesse sont particulièrement importants pour le développement cérébral de l’enfant et les conséquences d’une naissance prématurée sur le développement peuvent être considérables. Les enfants nés prématurément sont plus à risque de développer une variété de troubles neurodéveloppementaux que les enfants nés à terme. Même en l’absence de dommages cérébraux visibles, de nombreux enfants nés avant terme sont à risque de présenter des troubles tels que des retards langagiers ou des difficultés attentionnelles. Dans cette thèse, nous proposons donc une méthode d’investigation des processus préattentionnels auditifs et de discrimination langagière, à l’aide de l’électrophysiologie à haute densité et des potentiels évoqués auditifs (PEAs). Deux études ont été réalisées. La première visait à mettre sur pied un protocole d’évaluation de l’attention auditive et de la discrimination langagière chez l’enfant en santé, couvrant différents stades de développement (3 à 7 ans, 8 à 13 ans, adultes ; N = 40). Pour ce faire, nous avons analysé la composante de Mismatch Negativity (MMN) évoquée par la présentation de sons verbaux (syllabes /Ba/ et /Da/) et non verbaux (tons synthétisés, Ba : 1578 Hz/2800 Hz ; Da : 1788 Hz/2932 Hz). Les résultats ont révélé des patrons d’activation distincts en fonction de l’âge et du type de stimulus présenté. Chez tous les groupes d’âge, la présentation des stimuli non verbaux a évoqué une MMN de plus grande amplitude et de latence plus rapide que la présentation des stimuli verbaux. De plus, en réponse aux stimuli verbaux, les deux groupes d’enfants (3 à 7 ans, 8 à 13 ans) ont démontré une MMN de latence plus tardive que celle mesurée dans le groupe d’adultes. En revanche, en réponse aux stimuli non verbaux, seulement le groupe d’enfants de 3 à 7 ans a démontré une MMN de latence plus tardive que le groupe d’adulte. Les processus de discrimination verbaux semblent donc se développer plus tardivement dans l’enfance que les processus de discrimination non verbaux. Dans la deuxième étude, nous visions à d’identifier les marqueurs prédictifs de déficits attentionnels et langagiers pouvant découler d’une naissance prématurée à l’aide des PEAs et de la MMN. Nous avons utilisé le même protocole auprès de 74 enfants âgés de 3, 12 et 36 mois, nés prématurément (avant 34 semaines de gestation) ou nés à terme (au moins 37 semaines de gestation). Les résultats ont révélé que les enfants nés prématurément de tous les âges démontraient un délai significatif dans la latence de la réponse MMN et de la P150 par rapport aux enfants nés à terme lors de la présentation des sons verbaux. De plus, les latences plus tardives de la MMN et de la P150 étaient également corrélées à des performances langagières plus faibles lors d’une évaluation neurodéveloppementale. Toutefois, aucune différence n’a été observée entre les enfants nés à terme ou prématurément lors de la discrimination des stimuli non verbaux, suggérant des capacités préattentionnelles auditives préservées chez les enfants prématurés. Dans l’ensemble, les résultats de cette thèse indiquent que les processus préattentionnels auditifs se développent plus tôt dans l'enfance que ceux associés à la discrimination langagière. Les réseaux neuronaux impliqués dans la discrimination verbale sont encore immatures à la fin de l'enfance. De plus, ceux-ci semblent être particulièrement vulnérables aux impacts physiologiques liés à la prématurité. L’utilisation des PEAs et de la MMN en réponse aux stimuli verbaux en bas âge peut fournir des marqueurs prédictifs des difficultés langagières fréquemment observées chez l’enfant prématuré.

Abordando o sono no ensino médio: proposta de unidade didática contextualizada com o tema saúde

Biological rhythms are part of the life from the simplest to the most complex living beings. In humans, one of the most important biological rhythms is the sleep-wake cycle (SWC), which represents an indispensable behavior for health, since sleep deprivation can lead to deficits in attention and memory, mood and daytime sleepiness which may affect school performance. Nevertheless, the SWC is a content rarely discussed in schools. Thus, the aim of this research was to address contents of the sleep-wake cycle, related to the content of Health to encourage healthy sleep habits. This study was conducted in a public school with 33 students of the 3rd year of high school and is divided into four stages: 1st) Study and analysis of the content of the textbook adopted by the school to subsidize the activities covered in the teaching unit (TU) and approximation with the biology teacher from the class to evaluated the feasibility of schedules for the development of TU; 2nd) Survey of students' prior knowledge, through a questionnaire, to guide the development of the TU; 3rd) Development and implementation of a TU based on meaningful learning and characterization of the students sleep habits, 4th) Evaluation of the TU as a viable proposal to teach biological rhythms concepts. Previous knowledge of students about the SWC are scarce and this content is not covered in the books adopted by the school. Alternative conceptions were observed, particularly with regard to individual differences in sleep, which may contribute to the occurrence of inadequate sleep habits, as reported by the adolescents in this study. The activities developed during UD were well received by the students who showed participative, motivated and evaluated positively the procedures used by the researcher. After the TU, students' knowledge about the concept of biological rhythms has been increased and they started to identify that the SWC changes throughout life and occur due biological and socio-cultural factors. Thus, the UD elaborated in this study represents a viable proposal to teach the concepts of biological rhythms contextualized to the content of Health, in high school

A cafeína como agente modulador do ciclo atividade-repouso e memória em saguis (Callithrix jacchus)

Caffeine is the most consumed psychostimulant, with effects on attention, memory, and arousal. But when this substance is ingested near to bedtime there is a decrease on sleep, interfering on mnemonic processes. So, our ain was to investigate how the caffeine ingested near to sleep onset acts on sleep and memory in marmosets. We used 16 adult marmosets, single housed, in a 12:12h light-dark cycle. For registering locomotor activity were used two kinds of sensors. The gyroscope sensor registers activity each 30 sec and detects motion with good accuracy. Because of this we used this sensor for detecting nocturnal activity. The second sensor was based on infrared and accumulates activity each 5 min and it’s not able to detect nocturnal activity, just diurnal activity. We also used camera for registering Rest phase of one marmoset. For the cognitive task, the animals needed to learn a rewarded context (CR) when compared to a non-rewarded context CNR). This experiment comprises 5 phases: 1) Two days of habituation to apparatus; 2)Training for 8 days; 3) oral administration of caffeine (10 mg/kg) or placebo administration ±1h before sleep onset, for 8 days, with marmosets receiving placebo or caffeine; 4) retraining to apparatus and after that, placebo administration (placebo group-GP), or caffeine administration (with continuous group-GC and acute groupGA); 5) Test, for evaluating learning to CR. The sessions were filmed and each one had 8 min of duration. At 7 am started the habituation, training and test sessions, and at 3:15 pm started retraining. The results for gyroscope sensor showed that there was coincidence of 68,57% with nocturnal register of the cameras. Then, the gyroscope sensors detected nocturnal activity for all experimental groups Moreover, when compared sensor gyroscope with sensor based on infrared, was observed that both sensor presented similarity on patterns of activity curve. When we observed the effects of caffeine on Activity-Rest Cycle in GP, GA and GC, is possible to see that that gyroscope sensors and based on infrared presented only intra group differences. As behavioral results, the marmosets learned to discriminate CR when compared to CNR. Moreover, GP presented deficits on memory recall during the test, and GA increased the memory recall, when both were compared to GP. We concluded that the marmosets were able to learning the cognitive task and that the caffeine ingested near to sleep onset acts modulating memory in these animals. Moreover the gyroscope sensor can be used as alternative tool for investigating nocturnal activity. Then, the utilization of this non-invasive device allows marmosets exhibit their behavior within the laboratory conditions as natural as possible.

Efeitos da senescência no folheto intergeniculado do tálamo de ratos: análises morfológicas e neuroquímicas

The circadian timing system (CTS), in rodents, consists of interconnected neural structures such as the suprachiasmatic nucleus (SCN) of the hypothalamus, Intergeniculate Leaflet (IGL) of the thalamus, synchronous pathways and behavioral effectors. The SCN has been described as the major circadian pacemaker in several species of mammals, while the IGL appears to be involved in integration of photic and non-photic clues relaying them to SCN. The CTS allows an ordered internal temporal organization to the organism, providing the proper execution of physiological and behavioral mechanisms, which brings homeostasis. However, this stability is disrupted with aging process causing numerous pathological disorders, ranging from simple loss of physiological functions to decreases in cognitive performance. Therefore, is fundamental understanding the effects of senescence in this system. In this context, is proposed in this study to check if there are changes in IGL cytoarchitecture, neurochemical and retinal afferent markers with aging and their possible morpho-functional implications. To achieve this goal wistar rats were divided into 3 groups: young (3 months); Middle Age (13 months); Old (23 months). They were submitted to paraformaldhyde (4%) transcardiac perfusion to tissue fixation. Then, they had their brain removed and sectioned in 30 µm slices, which every sixth section were collected. This sections were processed by nissl method and immunostaining for GFAP, GAD, ENK, NPY and CTb in order to analyze the IGL features. It was observed a cell loss in middle age and old animals at Nissl, NPY and CTb stains. In addition, it was shown a increase in GFAP in middle aged animals compared to young and old ones. No differences were found in other neurochemichal stains. These data suggests IGL loss retinal afferents and neurons, in special the NPY-IR ones, likely having a compensatory gliogenesis. This supports the correlations between the CTS functional deficits and an anatomical deterioration of its components with the aging process.

Avaliação dos efeitos do extrato de Passiflora cincinnata Masters em camundongos: efeito na ansiedade e potencial neuroprotetor

Anxiety disorders and Parkinson’s disease (PD) affect a large portion of the world population. Indeed, therapeutic alternatives available do not contribute to improve most clinical conditions and/or are linked with undesirable side effects. Thus, there is a great demand for the development of new drugs to treatment of these diseases. Passiflora cincinnata Mast. is a native species present in several Brazilian states, popularly known as “maracujá do mato”, “maracujá tubarão” or “maracujá mochila”. Additionally, species of Passiflora genus are traditionally known for their exotic flowers, edible fruits with pronounced flavor and for their sedative, tranquilizer and anxiolytic properties reported by folk medicine. These plants possess important organic compounds such as phenols, cyanogenic glycosides, flavonoids and alkaloids, which are responsible for the anxiolytic, antioxidant, anti-inflammatory, antihyperglycemic, among others activities when tested in mammals. Despite this fact, only a few studies have been conducted to investigate the possible in vivo biological effects of Passiflora cincinnata Mast extracts. Thereby, in this study we evaluated the effects of the alcoholic extract of this plant in anxiety and PD animal model. Mice acutely or chronically administered with ethanolic extract of P. cincinnata do not showed any anxiogenic- or anxyolitic-like effect in elevated plus maze (EPM). In order to reproduce PD symptom’s in mice, we administered repeated injections of reserpine which progressively induced motor impairments such as increase in catalepsy, oral movements, and reduction of the average speed of the animals in the open field, as well as depleted dopamine prodution in SNpc cells. Furthermore, this treatment resulted in the loss of aversive memory recall in mice when undergoing PMDAT. Yet, passiflora group also show this amnesic profile. However, animals treated concomitantly with the alcoholic extract of Passiflora cincinnata Mast. showed higher latency for the onset of motor impairment evaluated by catalepsy. Thus, our results shows that the alcoholic extract of the plant P. cincinnata was able to delay the onset of the catalepsy induced by reserpine administration, plus reverted the depletion of dopamine production in SNpc cells.

Impacts of the Madden-Julian oscillation on intraseasonal precipitation over northeast Brazil

Este estudo tem como objetivo investigar os impactos da oscilação de Madden-Julian (OMJ) na precipitação da região Nordeste do Brasil (NEB). Para tanto foram utilizados dados diários de precipitação baseados em 492 pluviômetros distribuídos na região e cobrindo um período de 30 anos (1981 − 2010). As análises através de composições de anomalias de precipitação, radiação de onda longa e fluxo de umidade, foram obtidas com base no índice da OMJ desenvolvido por Jones-Carvalho. Para distinguir o sinal da OMJ de outros padrões de variabilidade climática, todos os dados diários foram filtrados na escala de 20 − 90 dias; portanto somente dias classificados como eventos da OMJ foram considerados nas composições. Uma análise preliminar baseada apenas nos dados de precipitação foi feita para uma pequena área localizada no interior semiárido do NEB, conhecida como Seridó. Essa microrregião é uma das áreas mais secas do NEB e foi reconhecida pela Convenção das Nações Unidas para o Combate à Desertificação e Mitigação dos Efeitos das Secas como particularmente vulnerável à desertificação. Composições de anomalias de precipitação foram feitas para cada uma das oito fases da OMJ durante Fevereiro-Maio (principal período chuvoso da microrregião). Os resultados mostraram a existência de variações significativas nos padrões de precipitação (de precipitação excessiva à deficiente) associados à propagação da OMJ. A combinação dos sinais de precipitação obtidos durantes as fases úmidas e secas da OMJ mostrou que a diferença corresponde cerca de 50 − 150% de modulação das chuvas na microrregião. Em seguida, uma investigação abrangente sobre o papel da OMJ sobre toda a região Nordeste foi feita considerando-se as quatro estações do ano. Os resultados mostraram que os impactos da OMJ na precipitação intrassazonal do NEB apresentam forte sazonalidade. A maior coerência espacial dos sinais de precipitação ocorreram durante o verão austral, quando cerca de 80% das estações pluviométricas apresentaram anomalias positivas de precipitação durante as fases 1 − 2 da OMJ e anomalias negativas de precipitação nas fases 5 − 6 da oscilação. Embora impactos da OMJ na precipitação intrassazonal tenham sido encontrados na maioria das localidades e em todas as estações do ano, eles apresentaram variações na magnitude dos sinais e dependem da fase da oscilação. As anomalias de precipitação do NEB observadas são explicadas através da interação existente entre as ondas de Kelvin-Rossby acopladas convectivamente e as características climáticas predominantes sobre a região em cada estação do ano. O aumento de precipitação observado sobre a maior parte do NEB durante o verão e primavera austrais encontra-se associado com o fluxo de umidade de oeste (regime de oeste), o qual favorece a atividade convectiva em amplas áreas da América do Sul tropical. Por outro lado, as anomalias de precipitação durante o inverno e outono austrais apresentaram uma variabilidade espacial mais complexa. Durante estas estações, as anomalias de precipitação observadas nas estações localizadas na costa leste do NEB dependem da intensidade do anticiclone do Atlântico Sul, o qual é modulado em grande parte por ondas de Rossby. As características topográficas do NEB parecem desempenhar um papel importante na variabilidade observada na precipitação, principalmente nestas áreas costeiras. A intensificação do anticiclone aumenta a convergência dos ventos alísios na costa contribuindo para a ocorrência de precipitação observada à barlavento do planalto da Borborema. Por outro lado, o aumento da subsidência parece ser responsável pelos déficits de precipitação observados à sotavento. Tais condições mostraram-se típicas durante o predomínio do regime de leste sobre a região tropical da América do Sul e o NEB, durante o qual ocorre uma diminuição no fluxo de umidade proveniente da Amazônia.

Diagnóstico e tratamento do TDA/H: investigação dos critérios utilizados por diferentes categorias profissionais da cidade de Natal-RN

TDA/H is usually considered among the most frequent psychological malfunctions in both childhood and adolescence. It covers a complex combination of neurocognitive deficits leading to developmental troubles linked to attention failure, hyperactivity and impulsivity. On the other hand, diagnosis of TDA/H is frequently a hard task, since sociocultural aspects concerning the evaluation of symptoms lead to some etiologic vagueness. Additionally, the large extent of evaluation tools, together with the diversity of therapeutic approaches referred by specialized literature justify the interest of investigating the diverse ways of diagnosing and treating TDA/H by medical doctors, psychologists and psycho-pedagogues developing professional activities in Natal-RN (Brazil) in the assistance of children and teenagers with TDA/H diagnosis hypothesis. A sample of thirty-four professionals participated in this study in a convenience-basis, and submitted to a semi-directed interview. Information from this procedure was analyzed, categorized and submitted to a multidimensional descriptive analysis (cluster analysis procedure), allowing to verify the partition of the sample in two groups: Group 1, basically composed by medical professionals, and Group 2, composed by psychologists and psycho-pedagogues. The categorized variable “Number of sessions” – average time used for arriving to a diagnosis – was the partition-variable showing the larger amount of statistical contribution for the partition, followed by the variables “Professional formation” and “Use of diagnostic tools”. Variables such “Comorbidity”, “TDA/H Definition” and Modalities of Intervention” also showed contribution to the partition obtained, even though their lesser amount of statistical contribution. Despite some similarity between these two groups, data allowed to demonstrate specific association between academic source-formation of the professional concerned and diagnosis and intervention modalities shown by these professionals when dealing with TDA/H. These data confirm relevant heterogeneity in dealing with TDA/H due to professional formation of professionals involved in diagnosis and treatment tasks.

Diagnóstico e tratamento do TDA/H: investigação dos critérios utilizados por diferentes categorias profissionais da cidade de Natal-RN

TDA/H is usually considered among the most frequent psychological malfunctions in both childhood and adolescence. It covers a complex combination of neurocognitive deficits leading to developmental troubles linked to attention failure, hyperactivity and impulsivity. On the other hand, diagnosis of TDA/H is frequently a hard task, since sociocultural aspects concerning the evaluation of symptoms lead to some etiologic vagueness. Additionally, the large extent of evaluation tools, together with the diversity of therapeutic approaches referred by specialized literature justify the interest of investigating the diverse ways of diagnosing and treating TDA/H by medical doctors, psychologists and psycho-pedagogues developing professional activities in Natal-RN (Brazil) in the assistance of children and teenagers with TDA/H diagnosis hypothesis. A sample of thirty-four professionals participated in this study in a convenience-basis, and submitted to a semi-directed interview. Information from this procedure was analyzed, categorized and submitted to a multidimensional descriptive analysis (cluster analysis procedure), allowing to verify the partition of the sample in two groups: Group 1, basically composed by medical professionals, and Group 2, composed by psychologists and psycho-pedagogues. The categorized variable “Number of sessions” – average time used for arriving to a diagnosis – was the partition-variable showing the larger amount of statistical contribution for the partition, followed by the variables “Professional formation” and “Use of diagnostic tools”. Variables such “Comorbidity”, “TDA/H Definition” and Modalities of Intervention” also showed contribution to the partition obtained, even though their lesser amount of statistical contribution. Despite some similarity between these two groups, data allowed to demonstrate specific association between academic source-formation of the professional concerned and diagnosis and intervention modalities shown by these professionals when dealing with TDA/H. These data confirm relevant heterogeneity in dealing with TDA/H due to professional formation of professionals involved in diagnosis and treatment tasks.

A relação entre memória de trabalho e competência leitora em crianças em risco de transtorno de aprendizagem do Projeto Acerta: um estudo exploratório

Reading and writing are essential rights, which involve individual and social aspects; in addition, these skills are important when it comes to socio economic and political development, critical thinking and an active participation in society (UNESCO 2005). From a neurobiological standpoint, our brain is not prepared for reading, and this practice must be deliberately acquired via instructional guidance (DEHAENE 2009). However, reading disorders and deficits within executive functions, such as low working memory capacity, can make reading arduous. The aim of this study is to investigate the development of reading skills within 45 third grade students from public schools in the city of Natal – RN and its connection to working memory capacity, through information gathered from the Provinha Brasil, data generated from working memory tasks (Portuguese version of AWMA - Automated Working Memory Assessment) and fluid intelligence measures RAVEN. Based on this main objective, we attempted to answer the following research questions: (a) What are the correlations between working memory and reading scores?; (b) What characterizes the relationship between working memory capacity and the risk of reading disabilities amongst the participants in this study?; Following a quantitative research methodology, the Provinhas Brasil from 3rd grade students belonging to the six public schools members of Project ACERTA - Avaliação de Crianças em Risco de Transtornos de Aprendizagem (CAPES/OBEDUC)- were analyzed and compared to the scores from the working memory tests and the fluid intelligence ones. Results indicate that reading skills within children at risk of reading disabilities are directly linked to working memory capacity, especially with regards to the phonological component. It is also evident that the participants with less working memory capacity show more difficulties in the reading abilities that demand interpretation skills. Thus, we intend to contribute to the discussion regarding the diagnosis of reading disabilities and possible intervention strategies.

A relação entre memória de trabalho e competência leitora em crianças em risco de transtorno de aprendizagem do Projeto Acerta: um estudo exploratório

Reading and writing are essential rights, which involve individual and social aspects; in addition, these skills are important when it comes to socio economic and political development, critical thinking and an active participation in society (UNESCO 2005). From a neurobiological standpoint, our brain is not prepared for reading, and this practice must be deliberately acquired via instructional guidance (DEHAENE 2009). However, reading disorders and deficits within executive functions, such as low working memory capacity, can make reading arduous. The aim of this study is to investigate the development of reading skills within 45 third grade students from public schools in the city of Natal – RN and its connection to working memory capacity, through information gathered from the Provinha Brasil, data generated from working memory tasks (Portuguese version of AWMA - Automated Working Memory Assessment) and fluid intelligence measures RAVEN. Based on this main objective, we attempted to answer the following research questions: (a) What are the correlations between working memory and reading scores?; (b) What characterizes the relationship between working memory capacity and the risk of reading disabilities amongst the participants in this study?; Following a quantitative research methodology, the Provinhas Brasil from 3rd grade students belonging to the six public schools members of Project ACERTA - Avaliação de Crianças em Risco de Transtornos de Aprendizagem (CAPES/OBEDUC)- were analyzed and compared to the scores from the working memory tests and the fluid intelligence ones. Results indicate that reading skills within children at risk of reading disabilities are directly linked to working memory capacity, especially with regards to the phonological component. It is also evident that the participants with less working memory capacity show more difficulties in the reading abilities that demand interpretation skills. Thus, we intend to contribute to the discussion regarding the diagnosis of reading disabilities and possible intervention strategies.

Cidades saudáveis e qualidade de vida em Uberlândia (MG): aportes metodológicos para um processo em construção

The current study includes theoretical and methodological reflections on the quality of life in the city of Uberlândia, Minas Gerais. It started from the thought that the quality of life is multifactorial and is permanently under construction and the main objective of analyzing it as one of the componets of Healthy Cities's moviment. The theoretical research focused on the concepts of healthy cities, quality of life, health, sustainability, well-being, happiness, indexes and indicators. From the use of multiple search strategies, documentary and on field of quantitative and qualitative character, this research of exploratory descriptive nature can offers a contribution to the studies on the quality of life in cities. It is proposed that the studies startes to work with some concept, like some notions os life quality adequated for some paticular reality, whose notions can approach concepts already established as health. This step is important on the exploratory researches. The studies may include aspects of objective analysis, subjective or both. The objective dimension, which is most common approach, are traditionally considered variables and indicators related to: the urban infrastructure (health, education, leisure, security, mobility), dwelling (quantitative and qualitative dwlling deficit), the urban structure (density and mix uses), socioeconomic characteristics (age, income, education), urban infrastructure (sanitation, communication), governance (social mobilization and participation). To focus on the subjective dimension, most recent and unusual, it is proposed to consider the (dis)satisfaction, the personal assessment in relation to the objective aspects. In conclusion, being intrinsically related to the health, the quality of life also has a number of determinants, and the ideal of the reach of quality of life depends on the action of all citizens based on the recognition of networks and territories, in a interescalar perspective and intersectoral. Therefore, emphasis in given on the potential of tools, such as the observatories, to monitor and intervent in reality, aiming in a building process of healthy cities.

Entorno de realidad virtual controlado en tiempo real por señales motoras para la rehabilitación del miembro superior en pacientes con daño cerebral

Este trabajo tiene como meta el desarrollo de un sistema de neurorrehabilitación mediante realidad virtual para pacientes con problemas motores en las extremidades superiores provocados por un daño cerebral. Para entender y enfrentarse de manera correcta al problema, se han revisado todos los aspectos concernientes al daño cerebral y déficits motores derivados así como las terapias empleadas para su rehabilitación, como las que utilizan tecnologías asistidas como la realidad virtual. Se han expuesto las ventajas que han llevado a utilizar esta terapia en el proyecto y se han mencionado algunos estudios de investigación previos y con resultados favorables. Por último, se ha hecho hincapié en las novedades (embodiment y neuronas espejo) que aporta este proyecto con las que se podría acelerar la rehabilitación de los pacientes incidiendo en la plasticidad cerebral. En lo que se refiere al desarrollo del entorno, se ha utilizado el motor de videojuegos Unity 3D, con el que se ha integrado el dispositivo Myo Armband, para capturar el movimiento, y las gafas de realidad virtual Oculus Rift DK2. Durante la terapia, el paciente tiene que superar una serie de niveles definidos por el terapeuta y, para ello, debe realizar un alcance y tocar un botón un número de veces por cada nivel. En cada nivel, el esfuerzo que tiene que realizar el paciente es distinto, dependiendo de la distancia a la que se encuentre el botón (relativa al calibrado previo del paciente) e igualmente, está definido por el terapeuta. También se lleva a cabo un registro de las aceleraciones y del porcentaje de acierto del paciente en un fichero, para llevar un control de su progreso. Como conclusión, cabe mencionar que el entorno desarrollado es adaptable a las posibilidades de cada paciente, permitiendo una recuperación óptima. Se trata de un sistema de bajo coste, intuitivo y que lleva a cabo un registro de datos de la actividad del paciente, lo que posibilita, como trabajo futuro, el control de forma remota por parte del terapeuta. Todos estos aspectos dejan abierta la posibilidad de que el paciente lo utilice a domicilio, con las ventajas que conlleva. Del mismo modo, el sistema se podría adaptar fácilmente para la rehabilitación de las extremidades inferiores. Tras su análisis, los investigadores expertos en la materia del Consejo Superior de Investigaciones Científicas afirman que el sistema satisface con creces su propósito. Con todo esto, se concluye que este entorno tiene un excelente presente y un futuro muy prometedor.

Estudio longitudinal del rendimiento neuropsicológico, neuropsiquiátrico y motor en la enfermedad de Parkinson

La enfermedad de Parkinson (EP) es una enfermedad progresiva, crónica e incapacitante cuyos síntomas principales son el temblor de reposo, la rigidez y la bradicinesia, apareciendo en el transcurso del tiempo la inestabilidad postural. Las alteraciones cognitivas y del estado de ánimo son otra de las características de esta enfermedad, pudiendo constituir una de sus complicaciones más incapacitantes. Ni el deterioro cognitivo leve (DCL) ni la demencia (D-EP) son fáciles de definir ni de evaluar. Algunos autores describen el DCL como una fase premórbida de la demencia (Pigott et al, 2015) aunque no todos los pacientes evolucionan a D-EP. La prevalencia de la D-EP es de 20-40% (Aarsland, Anderson et al, 2001), siendo algunos de los factores de riesgo la edad avanzada al diagnóstico, los síntomas motores más graves, sobre todo los relacionados con el trastorno de la marcha y la inestabilidad postural, el deterioro cognitivo leve, la depresión, el déficit temprano en fluidez verbal, la aparición de alucinaciones o la escasa respuesta al tratamiento con levodopa (Emre, 2003). El perfil de demencia en la EP es de tipo frontosubcortical, con déficits en las funciones atencionales y ejecutivas, mnésicas, visoespaciales, la fluidez verbal y las praxias...