Ultrasonic vocalizations during male–female interaction in the mouse model of Down syndrome Ts65Dn

AbstractDown syndrome (DS) is the leading cause of genetically defined intellectual disability. Although speech and language impairments are salient features of this disorder, the nature of these phenotypes and the degree to which they are exacerbated by concomitant oromotor dysfunction and/or hearing deficit are poorly understood. Mouse models like Ts65Dn, the most extensively used DS animal model, have been critical to understanding the genetic and developmental mechanisms that contribute to intellectual disability. In the present study, we characterized the properties of the ultrasonic vocalizations (USVs) emitted by Ts65Dn males during courtship episodes with female partners. USVs emitted by mice in this setting have been proposed to have some basic correlation to human speech. Data were collected and analyzed from 22 Ts65Dn mice and 22 of their euploid littermates. We found that both the minimum and maximum peak frequencies of Ts65Dn calls were lower than those produced by euploid mice, whereas the mean individual duration of “down” and “complex” syllable types was significantly longer. Peak, minimal and maximal, and the fundamental frequencies of short syllables generated by Ts65Dn mice were lower compared to those by euploid mice. Finally, Ts65Dn males made fewer multiple jumps calls during courtship and the mean total duration of their “arc”, “u”, and “complex” syllables was longer. We discuss the human correlates to these findings, their translational potential, and the limitations of this approach. To our knowledge, this is the first characterization of differences between adult Ts65Dn and euploid control mice with respect to USVs

Evidence of Energy Metabolism Alterations in Cultured Neonatal Astrocytes Derived from the Ts65Dn Mouse Model of Down Syndrome

For many decades, neurons have been the central focus of studies on the mechanisms underlying the neurodevelopmental and neurodegenerative aspects of Down syndrome (DS). Astrocytes, which were once thought to have only a passive role, are now recognized as active participants of a variety of essential physiological processes in the brain. Alterations in their physiological function have, thus, been increasingly acknowledged as likely initiators of or contributors to the pathogenesis of many nervous system disorders and diseases. In this study, we carried out a series of real-time measurements of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in hippocampal astrocytes derived from neonatal Ts65Dn and euploid control mice using a Seahorse XFp Flux Analyzer. Our results revealed a significant basal OCR increase in neonatal Ts65Dn astrocytes compared with those from control mice, indicating increased oxidative phosphorylation. ECAR did not differ between the groups. Given the importance of astrocytes in brain metabolic function and the linkage between astrocytic and neuronal energy metabolism, these data provide evidence against a pure “neurocentric” vision of DS pathophysiology and support further investigations on the potential contribution of disturbances in astrocytic energy metabolism to cognitive deficits and neurodegeneration associated with DS

The new urbanism in brazilian territory: configurational analysis of the subdivision Cidade Criativa Pedra Branca/SC

A partir da demanda por cidades mais ordenadas e sustentáveis, verifica-se uma ascensão da aplicação de preceitos do Novo Urbanismo no planejamento de novos loteamentos em territórios brasileiros. Seus princípios visam o desenvolvimento de malhas urbanas compactas, facilmente acessíveis a pé, de modo a resgatar o conceito de vizinhança das ruas e ocupação dos espaços públicos. Neste âmbito, questiona-se se a configuração espacial de tais loteamentos estão em conformidade com os princípios deste movimento. Para tanto, a metodologia faz uso da teoria da Sintaxe Espacial e sua exploração a partir de mapas axiais. Como objeto de estudo elege-se o bairro Cidade Criativa Pedra Branca, localizado no município de Palhoça, que compõe a região conturbada de Florianópolis. Os resultados evidenciam que, em escala local, o loteamento tende a atender parcialmente os objetivos do modelo, todavia, apresenta uma baixa articulação configuracional junto a cidade e a região em que se insere.From the demand for more orderly and sustainable cities, check if there is a rise in the application of New Urbanism precepts in the planning of new lots in Brazilian territories. Its principles aim at or develop compact urban suitcases, easily accessible on foot, in order to rescue the concept of neighborhood streets and occupation of public spaces. In this scope, questions and answers about the spatial configuration of these lots are in accordance with the principles of this movement. For this, the methodology makes use of the Spatial Syntax theory and its exploration from axial maps. As an eligible study object in the Cidade Criativa Pedra Branca neighborhood, located in the municipality of Palhoça, which makes up a region adjacent to Florianópolis. The results that show, on a local scale, or fill below, following the objectives of the model, however, present a low configurable articulation with the city and region in which it is located.Peer Reviewe

Implementation of a Brazilian Cardioprotective Nutritional (BALANCE) Program for improvement on quality of diet and secondary prevention of cardiovascular events: A randomized, multicenter trial

Background: Appropriate dietary recommendations represent a key part of secondary prevention in cardiovascular disease (CVD). We evaluated the effectiveness of the implementation of a nutritional program on quality of diet, cardiovascular events, and death in patients with established CVD. Methods: In this open-label, multicenter trial conducted in 35 sites in Brazil, we randomly assigned (1:1) patients aged 45 years or older to receive either the BALANCE Program (experimental group) or conventional nutrition advice (control group). The BALANCE Program included a unique nutritional education strategy to implement recommendations from guidelines, adapted to the use of affordable and regional foods. Adherence to diet was evaluated by the modified Alternative Healthy Eating Index. The primary end point was a composite of all-cause mortality, cardiovascular death, cardiac arrest, myocardial infarction, stroke, myocardial revascularization, amputation, or hospitalization for unstable angina. Secondary end points included biochemical and anthropometric data, and blood pressure levels. Results: From March 5, 2013, to Abril 7, 2015, a total of 2534 eligible patients were randomly assigned to either the BALANCE Program group (n = 1,266) or the control group (n = 1,268) and were followed up for a median of 3.5 years. In total, 235 (9.3%) participants had been lost to follow-up. After 3 years of follow-up, mean modified Alternative Healthy Eating Index (scale 0-70) was only slightly higher in the BALANCE group versus the control group (26.2 ± 8.4 vs 24.7 ± 8.6, P <.01), mainly due to a 0.5-serving/d greater intake of fruits and of vegetables in the BALANCE group. Primary end point events occurred in 236 participants (18.8%) in the BALANCE group and in 207 participants (16.4%) in the control group (hazard ratio, 1.15; 95% CI 0.95-1.38; P =.15). Secondary end points did not differ between groups after follow-up. Conclusions: The BALANCE Program only slightly improved adherence to a healthy diet in patients with established CVD and had no significant effect on the incidence of cardiovascular events or death. © 2019 The Author