Avaliação ecotoxicológica de fármacos psicotrópicos e suas possíveis interações com nanomateriais usando embriões de peixe-zebra

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Biologia Animal, 2016.

Effects of elevated calcium on motor and exploratory activities of rats

The effects of serum and brain calcium concentration on rat behavior were tested by maintaining animals on either distilled water (N = 60) or water containing 1% calcium gluconate (N = 60) for 3 days. Animals that were maintained on high calcium drinking water presented increased serum calcium levels (control = 10.12 ± 0.46 vs calcium treated = 11.62 ± 0.51 µg/dl). Increase of brain calcium levels was not statistically significant. In the behavioral experiments each rat was used for only one test. Rats that were maintained on high calcium drinking water showed increased open-field behavior of ambulation (20.68%) and rearing (64.57%). on the hole-board, calcium-supplemented animals showed increased head-dip (67%) and head-dipping (126%), suggesting increased ambulatory and exploratory behavior. The time of social interaction was normal in animals maintained on drinking water containing added calcium. Rats supplemented with calcium and submitted to elevated plus-maze tests showed a normal status of anxiety and elevated locomotor activity. We conclude that elevated levels of calcium enhance motor and exploratory behavior of rats without inducing other behavioral alterations. These data suggest the need for a more detailed analysis of several current proposals for the use of calcium therapy in humans, for example in altered blood pressure states, bone mineral metabolism disorders in the elderly, hypocalcemic states, and athletic activities.

Improvements in fundamental movement skill competency mediate the effect of the SCORES intervention on physical activity and cardiorespiratory fitness in children

Numerous studies have identified a positive association between fundamental movement skill (FMS) competency and physical activity in children; however, the causal pathways have not been established. The aim of this study is to determine if changes in FMS competency mediated the effect of the Supporting Children's Outcomes using Rewards, Exercise and Skills (SCORES) intervention on physical activity and cardiorespiratory fitness in children. Eight primary schools (25 classes) and 460 children (aged 8.5 ± 0.6, 54% girls) were randomised to the SCORES intervention or control group for the 12-month study. The outcomes were accelerometer-determined moderate-to-vigorous physical activity (MVPA) and cardiorespiratory fitness. The hypothesised mediators were actual FMS competency and perceived sport competence. Mediation analyses were conducted using multilevel linear analysis in MPlus. From the original sample, 138 (30.0%) and 370 (80.4%) children provided useable physical activity and cardiorespiratory fitness data at post-test assessments. There were significant treatment effects for locomotor skills and overall FMSs. Changes in MVPA were associated with changes in object-control skills, overall FMSs and perceived competence. The overall FMSs had a significant mediating effect on MVPA (AB = 2.09, CI = 0.01-4.55). Overall FMSs (AB = 1.19, CI = 0.002-2.79) and locomotor skills (AB = 0.74, CI = 0.01-1.69) had a significant mediating effect on cardiorespiratory fitness. The results of this study conclude that actual but not perceived movement skill competency mediated the effect of the SCORES intervention on physical activity and cardiorespiratory fitness.

Mood regulatory actions of nucleus accumbens deep brain stimulation

The mood regulatory mechanisms of deep brain stimulation (DBS)therapy are yet to be fully understood. DBS is shown to have antidepressant actions in severe, treatment-resistant depression (TRD).Interestingly, DBS of mesoaccumbens neurologic targets, includingthe nucleus accumbens (NAc), have also been shown to induce mania in vulnerable individuals. The nucleus accumbens (NAc) is a critical node in the mesocorticolimbic system and plays a major role in mediating antidepressant behavioral responses in the forced swim test (FST), a preclinical screen for antidepressant efficacy. This study investigates the antidepressant effects of NAc DBS in an established animal model of TRD. Wistar rats were divided into 4 groups: TRD-DBS (n = 9), TRD-Sham (n = 8), TRD (n = 10), and Control (n = 10). Bilateral stimulating electrodes were implanted into the NAc of TRD-Sham and TRD-DBS animals. Antidepressant-resistance and depression behaviors were induced through adrenocorticotropic-hormone (ACTH-(1–24); 100 lg/day; 2nd and 3rd weeks) administration and concurrent social isolation (all 3 weeks) respectively. DBS was administered throughout the 2nd week of ACTH treatment via a back mounted rodent DBS system. 24-hour locomotor activity counts were obtained using infrareddetectors and weekly sucrose preference tests were performedthroughout the 3 week protocol. Open field and FST were completedat the end of the 3 weeks. Brains were then removed and stored at 80°C. NAc tissue levels of brain-derived and glialderived neurotrophic factors (BDNF and GDNF, respectively) were quantified using western blot. Results demonstrate significant increases in locomotor activity for TRD-DBS animals (DBS-Vs-Sham: p = 0.0248). Lowered immobility was observed during FST for TRD-DBS animals (DBS-Vs-Sham: p = 0.0188). ACTHinduced BDNF expression increased in the outer region substructure NAc-shell (p = 0.0487) and decreased in the inner region substructure NAc-core (p = 0.0275) compared to controls. These datasupport antidepressant actions of NAc DBS in TRD. Local changes in neurotrophic factors may contribute to these mechanisms. Importantly, observed increases in locomotor activity over the 3 weeks highlight the potential for mesoaccumbens DBS to impact behaviors such as locomotor activity which may contribute to risk for induction of mania. Preliminary analysis of concurrent effects of daily dopamine reuptake inhibitor GBR12909 (16 mg/kg) administration coupled with NAc DBS demonstrates dopamine-mediated augmentation of these mania-like behaviors.

Correlates of gross motor competence in children and adolescents: a systematic review and meta-analysis

BACKGROUND: Gross motor competence confers health benefits, but levels in children and adolescents are low. While interventions can improve gross motor competence, it remains unclear which correlates should be targeted to ensure interventions are most effective, and for whom targeted and tailored interventions should be developed.

OBJECTIVE: The aim of this systematic review was to identify the potential correlates of gross motor competence in typically developing children and adolescents (aged 3-18 years) using an ecological approach.

METHODS: Motor competence was defined as gross motor skill competency, encompassing fundamental movement skills and motor coordination, but excluding motor fitness. Studies needed to assess a summary score of at least one aspect of motor competence (i.e., object control, locomotor, stability, or motor coordination). A structured electronic literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Six electronic databases (CINAHL Complete, ERIC, MEDLINE Complete, PsycINFO(®), Scopus and SPORTDiscus with Full Text) were searched from 1994 to 5 August 2014. Meta-analyses were conducted to determine the relationship between potential correlates and motor competency if at least three individual studies investigated the same correlate and also reported standardized regression coefficients.

RESULTS: A total of 59 studies were identified from 22 different countries, published between 1995 and 2014. Studies reflected the full range of age groups. The most examined correlates were biological and demographic factors. Age (increasing) was a correlate of children's motor competence. Weight status (healthy), sex (male) and socioeconomic background (higher) were consistent correlates for certain aspects of motor competence only. Physical activity and sport participation constituted the majority of investigations in the behavioral attributes and skills category. Whilst we found physical activity to be a positive correlate of skill composite and motor coordination, we also found indeterminate evidence for physical activity being a correlate of object control or locomotor skill competence. Few studies investigated cognitive, emotional and psychological factors, cultural and social factors or physical environment factors as correlates of motor competence.

CONCLUSION: This systematic review is the first that has investigated correlates of gross motor competence in children and adolescents. A strength is that we categorized correlates according to the specific ways motor competence has been defined and operationalized (object control, motor coordination, etc.), which enables us to have an understanding of what correlates assist what types of motor competence. Indeed our findings do suggest that evidence for some correlates differs according to how motor competence is operationalized.

The effect of structural parameters on air permeability of bifacial fabrics

In our recent study, a bifacial fabric with a knitted structure on one side and a woven structure on the other side of the fabric was designed and manufactured for apparel applications. The physical properties of the bifacial fabrics were previously reported. In this study, bifacial fabrics with two different weft densities of 18 and 22 picks per cm in the woven structure and loop lengths of 10 and 11 mm in the knitted structure were prepared, then the air permeability of the fabrics was analyzed. The extension of the analysis of variance techniques was applied to the data. It was found that there were highly significant differences in the air permeability of bifacial fabrics with different weft densities and loop lengths, while the interaction between these two factors was not statistically significant in their effects on the air permeability. Briefly, increasing loop length increased air permeability, while air permeability decreased with an increase in weft density. This finding shows that fabric’s parameters can be manipulated to affect air permeability of the bifacial fabrics, and further to influence comfort properties of such novel fabrics.

Integrating network analysis, sensor tags, and observation to understand shark ecology and behavior

Group living in animals is a well-studied phenomenon, having been documented extensively in a wide range of terrestrial, freshwater, and marine species. Although social dynamics are complex across space and time, recent technological and analytical advances enable deeper understanding of their nature and ecological implications. While for some taxa, a great deal of information is known regarding the mechanistic underpinnings of these social processes, knowledge of these mechanisms in elasmobranchs is lacking. Here, we used an integrative and novel combination of direct observation, accelerometer biologgers, and recent advances in network analysis to better understand the mechanistic bases of individual-level differences in sociality (leadership, network attributes) and diel patterns of locomotor activity in a widespread marine predator, the lemon shark (Negaprion brevirostris). We found that dynamic models of interaction based on Markov chains can accurately predict juvenile lemon shark social behavior and that lemon sharks did not occupy consistent positions within their network. Lemon sharks did however preferentially associate with specific group members, by sex as well as by similarity or nonsimilarity for a number of behavioral (nonsimilarity: leadership) and locomotor traits (similarity: proportion of time swimming "fast," mean swim duration; nonsimilarity: proportion of swimming bursts/transitions between activity states). Our study provides some of the first information on the mechanistic bases of group living and personality in sharks and further, a potential experimental approach for studying fine-scale differences in behavior and locomotor patterns in difficult-to-study organisms.

Validity and reliability of a pictorial instrument for assessing perceived motor competence in Portuguese children

BACKGROUND: It is important to assess young children's perceived Fundamental Movement Skill (FMS) competence in order to examine the role of perceived FMS competence in motivation toward physical activity. Children's perceptions of motor competence may vary according to the culture/country of origin; therefore, it is also important to measure perceptions in different cultural contexts. The purpose was to assess the face validity, internal consistency, test-retest reliability and construct validity of the 12 FMS items in the Pictorial Scale for Perceived Movement Skill Competence for Young Children (PMSC) in a Portuguese sample.

METHODS: Two hundred one Portuguese children (girls, n = 112), 5 to 10 years of age (7.6 ± 1.4), participated. All children completed the PMSC once. Ordinal alpha assessed internal consistency. A random subsamples (n = 47) were reassessed one week later to determine test-retest reliability with Bland-Altman method. Children were asked questions after the second administration to determine face validity. Construct validity was assessed on the whole sample with a Bayesian Structural Equation Modelling (BSEM) approach. The hypothesized theoretical model used the 12 items and two hypothesized factors: object control and locomotor skills.

RESULTS: The majority of children correctly identified the skills and could understand most of the pictures. Test-retest reliability analysis was good, with an agreement ration between 0.99 and 1.02. Ordinal alpha values ranged from acceptable (object control 0.73, locomotor 0.68) to good (all FMS 0.81). The hypothesized BSEM model had an adequate fit.

CONCLUSIONS: The PMSC can be used to investigate perceptions of children's FMS competence. This instrument can also be satisfactorily used among Portuguese children.

Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects

Mitochondrial dysfunction has a critical role in the pathophysiology of mood disorders and treatment response. To investigate this, we established an animal model exhibiting a state of antidepressant treatment resistance in male Wistar rats using 21 days of adrenocorticotropic hormone (ACTH) administration (100 μg per day). First, the effect of ACTH treatment on the efficacy of imipramine (10 mg kg(-1)) was investigated alongside its effect on the prefrontal cortex (PFC) mitochondrial function. Second, we examined the mood-regulatory actions of chronic (7 day) high-frequency nucleus accumbens (NAc) deep-brain stimulation (DBS; 130 Hz, 100 μA, 90 μS) and concomitant PFC mitochondrial function. Antidepressant-like responses were assessed in the open field test (OFT) and forced swim test (FST) for both conditions. ACTH pretreatment prevented imipramine-mediated improvement in mobility during the FST (P<0.05). NAc DBS effectively improved FST mobility in ACTH-treated animals (P<0.05). No improvement in mobility was observed for sham control animals (P>0.05). Analyses of PFC mitochondrial function revealed that ACTH-treated animals had decreased capacity for adenosine triphosphate production compared with controls. In contrast, ACTH animals following NAc DBS demonstrated greater mitochondrial function relative to controls. Interestingly, a proportion (30%) of the ACTH-treated animals exhibited heightened locomotor activity in the OFT and exaggerated escape behaviors during the FST, together with general hyperactivity in their home-cage settings. More importantly, the induction of this mania-like phenotype was accompanied by overcompensative increased mitochondrial respiration. Manifestation of a DBS-induced mania-like phenotype in imipramine-resistant animals highlights the potential use of this model in elucidating mechanisms of mood dysregulation.

Estimation de cartes d'énergie de hautes fréquences ou d'irrégularité de périodicité de la marche humaine par caméra de profondeur pour la détection de pathologies

Ce travail présente deux nouveaux systèmes simples d'analyse de la marche humaine grâce à une caméra de profondeur (Microsoft Kinect) placée devant un sujet marchant sur un tapis roulant conventionnel, capables de détecter une marche saine et celle déficiente. Le premier système repose sur le fait qu'une marche normale présente typiquement un signal de profondeur lisse au niveau de chaque pixel avec moins de hautes fréquences, ce qui permet d'estimer une carte indiquant l'emplacement et l'amplitude de l'énergie de haute fréquence (HFSE). Le second système analyse les parties du corps qui ont un motif de mouvement irrégulier, en termes de périodicité, lors de la marche. Nous supposons que la marche d'un sujet sain présente partout dans le corps, pendant les cycles de marche, un signal de profondeur avec un motif périodique sans bruit. Nous estimons, à partir de la séquence vidéo de chaque sujet, une carte montrant les zones d'irrégularités de la marche (également appelées énergie de bruit apériodique). La carte avec HFSE ou celle visualisant l'énergie de bruit apériodique peut être utilisée comme un bon indicateur d'une éventuelle pathologie, dans un outil de diagnostic précoce, rapide et fiable, ou permettre de fournir des informations sur la présence et l'étendue de la maladie ou des problèmes (orthopédiques, musculaires ou neurologiques) du patient. Même si les cartes obtenues sont informatives et très discriminantes pour une classification visuelle directe, même pour un non-spécialiste, les systèmes proposés permettent de détecter automatiquement les individus en bonne santé et ceux avec des problèmes locomoteurs.

Activité physique et récompense : impact de la leptine et de la signalisation STAT3 dans les neurones dopaminergiques

La course d’endurance active le système de récompense (SR) et est reliée aux comportements de recherche alimentaire. L’influence de la leptine sur l’activité physique (AP) volontaire est bien documentée d’un point de vue physiologique, mais très peu en termes d’impact hédonique. La leptine inhibe l’effet récompensant lié à la consommation de nourriture et joue un rôle semblable pour d’autres types de stimuli. La leptine s’arrime à la forme longue du récepteur à la leptine (Leprb) situé sur les neurones à dopamine (DA) et GABA de l’aire tegmentale ventrale (ATV) dans le mésencéphale. Signal transducer and Activator of Transcription 3 (STAT3) est un facteur de transcription important de la cascade de signalisation de la leptine. La phosphorylation de STAT3 n’est détectée que dans une parcelle des neurones DA positifs pour le Leprb, conférant aux neurones DA STAT3-spécifiques des caractéristiques uniques. Nous avons généré un modèle murin invalidé pour STAT3 sélectivement dans les neurones DA (STAT3DAT-KO). La première expérience consistait à évaluer les paramètres métaboliques de base de notre modèle en utilisant les chambres métaboliques Comprehensive Lab Animal Monitoring System (CLAMS), incluant l’activité ambulatoire, le ratio d’échanges respiratoires (RER) et la production de chaleur. Les STAT3DAT-KO sont hyperactives, démontré par une activité locomotrice augmentée, mais aucune variation entre les deux groupes n’est observée pour le RER et la production de chaleur, en plus d’un gain de poids identique. Une stratégie de récupération ciblant la réinsertion de STAT3 dans les neurones DA du système mésolimbique normalise l’AP anciennement plus élevée des STAT3DAT-KO à celle des contrôles, suivant l’accès libre à une roue d’exercice (RE) pour une durée de 4 semaines, suivant l’accès libre à une roue d’exercice (RE) pour une durée de 4 semaines. L’injection d’un psychostimulant (agoniste du récepteur DA de type 1 (D1R), le Chloro-APB-Hydrobromide (SKF 82958)) reflète une fonction dopaminergique réduite chez les STAT3DAT-KO. Un test de recherche compulsive de nourriture révèle une suppression de la prise alimentaire chez les deux groupes expérimentaux. Nous démontrons pour la première fois que la motivation alliée à la course d’endurance, indépendamment de la régulation de la prise alimentaire par la leptine, est dépendant d’une signalisation leptine-STAT3 amoindrie dans les neurones DA du système mésolimbique, révélant STAT3 comme élément clé dans la régulation du tonus dopaminergique et des propriétés récompensantes de l’AP.

Estimation de cartes d'énergie de hautes fréquences ou d'irrégularité de périodicité de la marche humaine par caméra de profondeur pour la détection de pathologies

Ce travail présente deux nouveaux systèmes simples d'analyse de la marche humaine grâce à une caméra de profondeur (Microsoft Kinect) placée devant un sujet marchant sur un tapis roulant conventionnel, capables de détecter une marche saine et celle déficiente. Le premier système repose sur le fait qu'une marche normale présente typiquement un signal de profondeur lisse au niveau de chaque pixel avec moins de hautes fréquences, ce qui permet d'estimer une carte indiquant l'emplacement et l'amplitude de l'énergie de haute fréquence (HFSE). Le second système analyse les parties du corps qui ont un motif de mouvement irrégulier, en termes de périodicité, lors de la marche. Nous supposons que la marche d'un sujet sain présente partout dans le corps, pendant les cycles de marche, un signal de profondeur avec un motif périodique sans bruit. Nous estimons, à partir de la séquence vidéo de chaque sujet, une carte montrant les zones d'irrégularités de la marche (également appelées énergie de bruit apériodique). La carte avec HFSE ou celle visualisant l'énergie de bruit apériodique peut être utilisée comme un bon indicateur d'une éventuelle pathologie, dans un outil de diagnostic précoce, rapide et fiable, ou permettre de fournir des informations sur la présence et l'étendue de la maladie ou des problèmes (orthopédiques, musculaires ou neurologiques) du patient. Même si les cartes obtenues sont informatives et très discriminantes pour une classification visuelle directe, même pour un non-spécialiste, les systèmes proposés permettent de détecter automatiquement les individus en bonne santé et ceux avec des problèmes locomoteurs.

Activité physique et récompense : impact de la leptine et de la signalisation STAT3 dans les neurones dopaminergiques

La course d’endurance active le système de récompense (SR) et est reliée aux comportements de recherche alimentaire. L’influence de la leptine sur l’activité physique (AP) volontaire est bien documentée d’un point de vue physiologique, mais très peu en termes d’impact hédonique. La leptine inhibe l’effet récompensant lié à la consommation de nourriture et joue un rôle semblable pour d’autres types de stimuli. La leptine s’arrime à la forme longue du récepteur à la leptine (Leprb) situé sur les neurones à dopamine (DA) et GABA de l’aire tegmentale ventrale (ATV) dans le mésencéphale. Signal transducer and Activator of Transcription 3 (STAT3) est un facteur de transcription important de la cascade de signalisation de la leptine. La phosphorylation de STAT3 n’est détectée que dans une parcelle des neurones DA positifs pour le Leprb, conférant aux neurones DA STAT3-spécifiques des caractéristiques uniques. Nous avons généré un modèle murin invalidé pour STAT3 sélectivement dans les neurones DA (STAT3DAT-KO). La première expérience consistait à évaluer les paramètres métaboliques de base de notre modèle en utilisant les chambres métaboliques Comprehensive Lab Animal Monitoring System (CLAMS), incluant l’activité ambulatoire, le ratio d’échanges respiratoires (RER) et la production de chaleur. Les STAT3DAT-KO sont hyperactives, démontré par une activité locomotrice augmentée, mais aucune variation entre les deux groupes n’est observée pour le RER et la production de chaleur, en plus d’un gain de poids identique. Une stratégie de récupération ciblant la réinsertion de STAT3 dans les neurones DA du système mésolimbique normalise l’AP anciennement plus élevée des STAT3DAT-KO à celle des contrôles, suivant l’accès libre à une roue d’exercice (RE) pour une durée de 4 semaines, suivant l’accès libre à une roue d’exercice (RE) pour une durée de 4 semaines. L’injection d’un psychostimulant (agoniste du récepteur DA de type 1 (D1R), le Chloro-APB-Hydrobromide (SKF 82958)) reflète une fonction dopaminergique réduite chez les STAT3DAT-KO. Un test de recherche compulsive de nourriture révèle une suppression de la prise alimentaire chez les deux groupes expérimentaux. Nous démontrons pour la première fois que la motivation alliée à la course d’endurance, indépendamment de la régulation de la prise alimentaire par la leptine, est dépendant d’une signalisation leptine-STAT3 amoindrie dans les neurones DA du système mésolimbique, révélant STAT3 comme élément clé dans la régulation du tonus dopaminergique et des propriétés récompensantes de l’AP.

Estudio del impacto de las dismetrías leves en las presiones plantares y variables oscilométricas en niños y adolescentes de la Comunidad de Madrid

La diferencia de longitud de las extremidades, o anisomelia, se define como una condición en la que alguno de los miembros, bien superior o inferior, es notablemente desigual frente al otro. Cuando esta diferencia se detecta en las extremidades inferiores, se conoce como discrepancia en la longitud de las extremidades inferiores (DLEEII, en inglés: LLD, “Leg Length Discrepancy” o LLI, “Leg Length Inequality”) o también dismetría de piernas o del miembro inferior (DM). Las DLEEII son bastante frecuentes en la población adulta, con una prevalencia que se encuentra entre el 40% y el 70% y una magnitud media de desigualdad anatómica mayor de 2 cm en aproximadamente un 0,1% de la misma. Si bien diversas teorías establecen que una DLEEII altera la postura corporal de una persona afectando a determinadas actividades de la vida diaria y pueden ser causa de trastornos del aparato locomotor, no existe un criterio unánime sobre la magnitud de DLEEII necesaria para inducir una respuesta en la postura, así como suponer un impacto clínico. Por otro lado existen estudios que sugieren que la edad de inicio puede ser un factor determinante y que los niños pueden compensar una DLEEII más fácilmente que los adultos que han experimentado su repentina aparición...

Literature review and update of lower limb neural mobilization

Summarize the available literature descriptions of neural mobilization (NM) techniques and neural provocation tests (NPT) for the Lower Limb (LL). Compilation of data was performed in May 2016 using MEDLINE data base, Google Scholar and the library of the European University of Madrid. After application of inclusion/exclusion criterions 5 books and 14 journal publications where found to be of interest and used during data extraction.Results: a list of 8 different LLNM techniques are applied in a rhythmic alternating oscillatory cycle fashion, starting in the initial position from where the therapist proceeds to move the limb in order to achieve a final position. LL NPTs are useful tools for differential diagnose and selecting the proper LLNM procedure. There is no consensus about the time frame of repetition intervals or amount of tensile strength during NPT never the less it is found to normally be performed at a rate of 2-4 seconds per complete cycle of movement, during 1-5 minutes, 3-5 times a week. LLNM treatment techniques all thou increasingly popular in clinical practice are found to be frugally described and lack proper standardization in regards to therapeutic dosification.