491 research outputs found
MDMA and brain activity during neurocognitive performance: An overview of neuroimaging studies with abstinent 'Ecstasy' users.
MDMA/Ecstasy has had a resurgence in popularity, with recent supplies comprising higher strength MDMA, potentially leading to increased drug-related harm. Neurocognitive problems have been widely reported in ecstasy users, equally some studies report null findings, and it remains unclear which factors underlie the development of neurocognitive impairments. This review covers the empirical research into brain activity during neurocognitive performance, using fMRI, fNIRS, and EEG. Our main conclusion is that chronic repeated use of recreational ecstasy can result in haemodynamic and electrophysiological changes that reflect recruitment of additional resources to perform cognitive tasks. Findings are consistent with serotonergic system changes, although whether this reflects neurotoxicity or neuroadaptation, cannot be answered from these data. There is a degree of heterogeneity in the methodologies and findings, limiting the strengths of current conclusions. Future research with functional neuroimaging paired with molecular imaging, genetics or pharmacological challenges of the serotonin system may help to decipher the link between serotonergic and cognitive changes in ecstasy users
Modelling spatio-temporal data with multiple seasonalities: the NO2 portuguese case
This study aims at characterizing the spatial and temporal dynamics of spatio-temporal data sets, characterized by high resolution in the temporal dimension which are becoming the norm rather than the exception in many application areas, namely environmental modelling. In particular, air pollution data, such as NO2 concentration levels, often incorporate also multiple recurring patterns in time imposed by social habits, anthropogenic activities and meteorological conditions. A two-stage modelling approach is proposed which combined with a block bootstrap procedure correctly assesses uncertainty in parameters estimates and produces reliable confidence regions for the space-time phenomenon under study. The methodology provides a model that is satisfactory in terms of goodness of fit, interpretability, parsimony, prediction and forecasting capability and computational costs. The proposed framework is potentially useful for scenario drawing in many areas, including assessment of environmental impact and environmental policies, and in a myriad applications to other research fields. (C) 2017 Elsevier B.V. All rights reserved.- The authors acknowledge Foundation FCT (Fundacao para a Ciencia e Tecnologia) for funding through Individual Scholarship Ph.D. PD/BD/105743/2014, Centre of Mathematics of Minho University within project UID/MAT/00013/2013 and Center for Research & Development in Mathematics and Applications of Aveiro University within project UID/MAT/04106/2013.info:eu-repo/semantics/publishedVersio
Mechanistic insights revealed by lipid profiling in monogenic insulin resistance syndromes.
BACKGROUND: Evidence from several recent metabolomic studies suggests that increased concentrations of triacylglycerols with shorter (14-16 carbon atoms), saturated fatty acids are associated with insulin resistance and the risk of type 2 diabetes. Although causality cannot be inferred from association studies, patients in whom the primary cause of insulin resistance can be genetically defined offer unique opportunities to address this challenge. METHODS: We compared metabolite profiles in patients with congenital lipodystrophy or loss-of-function insulin resistance (INSR gene) mutations with healthy controls. RESULTS: The absence of significant differences in triacylglycerol species in the INSR group suggest that changes previously observed in epidemiological studies are not purely a consequence of insulin resistance. The presence of triacylglycerols with lower carbon numbers and high saturation in patients with lipodystrophy suggests that these metabolite changes may be associated with primary adipose tissue dysfunction. The observed pattern of triacylglycerol species is indicative of increased de novo lipogenesis in the liver. To test this we investigated the distribution of these triacylglycerols in lipoprotein fractions using size exclusion chromatography prior to mass spectrometry. This associated these triacylglycerols with very low-density lipoprotein particles, and hence release of triacylglycerols into the blood from the liver. To test further the hepatic origin of these triacylglycerols we induced de novo lipogenesis in the mouse, comparing ob/ob and wild-type mice on a chow or high fat diet, confirming that de novo lipogenesis induced an increase in relatively shorter, more saturated fatty acids. CONCLUSIONS: Overall, these studies highlight hepatic de novo lipogenesis in the pathogenesis of metabolic dyslipidaemia in states where energy intake exceeds the capacity of adipose tissue
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