Specific targeting of the GABA-A receptor α5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice

An imbalance between inhibitory and excitatory neurotransmission has been proposed to contribute to altered brain function in individuals with Down syndrome (DS). Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system and accordingly treatment with GABA-A antagonists can efficiently restore cognitive functions of Ts65Dn mice, a genetic model for DS. However, GABA-A antagonists are also convulsant which preclude their use for therapeutic intervention in DS individuals. Here, we have evaluated safer strategies to release GABAergic inhibition using a GABA-A-benzodiazepine receptor inverse agonist selective for the α5-subtype (α5IA). We demonstrate that α5IA restores learning and memory functions of Ts65Dn mice in the novel-object recognition and in the Morris water maze tasks. Furthermore, we show that following behavioural stimulation, α5IA enhances learning-evoked immediate early gene products in specific brain regions involved in cognition. Importantly, acute and chronic treatments with α5IA do not induce any convulsant or anxiogenic effects that are associated with GABA-A antagonists or non-selective inverse agonists of the GABA-A-benzodiazepine receptors. Finally, chronic treatment with α5IA did not induce histological alterations in the brain, liver and kidney of mice. Our results suggest that non-convulsant α5-selective GABA-A inverse agonists could improve learning and memory deficits in DS individuals

Self‐medication and pain catastrophizing in patients with myofascial pain : are they related?

Evidence shows that acute symptoms of temporomandibular dysfunction (TMD) would eventually lead to chronicity and self‐medication would play a significant interfering role on such dynamics (Dias, Bastos, Alves, & Leite, 2019; Pastore, Goulart, Pastore, Prati, & de Moraes, 2018). Furthermore, some authors concluded that both propensity to catastrophize and depression contribute to the progression of chronic temporomandibular muscle and joint disorders (Velly et al., 2011). Hence, the aim of this study was to assess the relationship between the habit of self‐medicating and the propensity to catastrophize pain in a clinical population with myofascial pain (MP).© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reservedinfo:eu-repo/semantics/publishedVersio

Energy end-use flexibility of the next generation of decision-makers in a smart grid setting: an exploratory study

Demand Response (DR) mechanisms have been developed to reshape consumption patterns in face of price signals, enabling to deal with the increasing penetration of intermittent renewable resources and balance electricity demand and supply. Although DR mechanisms have been in place for some time, it is still unclear to what extent end-users are ready, or willing, to embrace DR programs that can be complex and imply adjustments of daily routines. This work aims to understand how the next generation of Portuguese decision makers, namely young adults in higher education, are prepared to deal with energy decisions in the context of the challenges brought by the smart grids. Results demonstrate that cost savings and the contribution to environmental protection are found to be important motivating factors to enroll into DR programs, which should be further exploited in future actions for the promotion of end-user engagement. Moreover, DR solutions are well-accepted by higher education students, although with limited flexibility levels. In addition, there is room to exploit the willingness to adopt time-differentiated tariffs, yet savings should be clearer and more attractive to end-users. Also, the framing effect should be considered when promoting this type of time-differentiated tariffs.This work was partially supported by project grants UID/MULTI/00308/2013 and UID/CEC/00319/2013 and by the European Regional Development Fund through the COMPETE 2020 Programme, FCT—Portuguese Foundation for Science and Technology with in projects ESGRIDS (POCI-01-0145-FEDER-016434), Learn2Behave (02/SAICT/2016-023651), MAnAGER (POCI-01-0145-FEDER-028040), and POCI-01-0145-FEDER-007043, as well as by the Energy for Sustainability Initiative of the University of Coimbra

Saturn satellites as seen by Cassini Mission

In this paper we will summarize some of the most important results of the Cassini mission concerning the satellites of Saturn. Given the long duration of the mission, the complexity of the payload onboard the Cassini Orbiter and the amount of data gathered on the satellites of Saturn, it would be impossible to describe all the new discoveries made, therefore we will describe only some selected, paramount examples showing how Cassini's data confirmed and extended ground-based observations. In particular we will describe the achievements obtained for the satellites Phoebe, Enceladus and Titan. We will also put these examples in the perspective of the overall evolution of the system, stressing out why the selected satellites are representative of the overall evolution of the Saturn system.Comment: 34 pages, 10 figures, to appear on the special issue of Earth, Moon and Planets for the Elba worksho

Discrimination of water quality monitoring sites in River Vouga using a mixed-effect state space model

The surface water quality monitoring is an important concern of public organizations due to its relevance to the public health. Statistical methods are taken as consistent and essential tools in the monitoring procedures in order to prevent and identify environmental problems. This work presents the study case of the hydrological basin of the river Vouga, in Portugal. The main goal is discriminate the water monitoring sites using the monthly dissolved oxygen concentration dataset between January 2002 and May 2013. This is achieved through the extraction of trend and seasonal components in a linear mixed-effect state space model. The parameters estimation is performed with both maximum likelihood method and distribution-free estimators in a two-step procedure. The application of the Kalman smoother algorithm allows to obtain predictions of the structural components as trend and seasonality. The water monitoring sites are discriminated through the structural components by a hierarchical agglomerative clustering procedure. This procedure identified different homogenous groups relatively to the trend and seasonality components and some characteristics of the hydrological basin are presented in order to support the results

Factors associated with post-traumatic stress disorder and depression amongst internally displaced persons in northern Uganda

BACKGROUND: The 20 year war in northern Uganda between the Lord's Resistance Army and the Ugandan government has resulted in the displacement of up to 2 million people within Uganda. The purpose of the study was to measure rates of post-traumatic stress disorder (PTSD) and depression amongst these internally displaced persons (IDPs), and investigate associated demographic and trauma exposure risk factors. METHODS: A cross-sectional multi-staged, random cluster survey with 1210 adult IDPs was conducted in November 2006 in Gulu and Amuru districts of northern Uganda. Levels of exposure to traumatic events and PTSD were measured using the Harvard Trauma Questionnaire (original version), and levels of depression were measured using the Hopkins Symptom Checklist-25. Multivariate logistic regression was used to analyse the association of demographic and trauma exposure variables on the outcomes of PTSD and depression. RESULTS: Over half (54%) of the respondents met symptom criteria for PTSD, and over two thirds (67%) of respondents met symptom criteria for depression. Over half (58%) of respondents had experienced 8 or more of the 16 trauma events covered in the questionnaire. Factors strongly linked with PTSD and depression included gender, marital status, distance of displacement, experiencing ill health without medical care, experiencing rape or sexual abuse, experiencing lack of food or water, and experiencing higher rates of trauma exposure. CONCLUSION: This study provides evidence of exposure to traumatic events and deprivation of essential goods and services suffered by IDPs, and the resultant effect this has upon their mental health. Protection and social and psychological assistance are urgently required to help IDPs in northern Uganda re-build their lives