Pharmacogenetic: screening relevant polymorphisms on antiretroviral therapy in a HIV Portuguese population

Poster presented at the 15th European AIDS Conference. Barcelona, 21-24 October 2015"Several factors cause heterogeneity of response to antiretroviral therapy. Genetic polymorphisms, particularly in metabolizing enzyme, cytochrome P450 isoenzymes and transport proteins MDR, MRP and SLC, may cause pharmacokinetic variability in some ARVs, leading to viral failure, drug toxicity and may explain the interpatient variability for drug absorption pathways.

Searching for the G516T Polymorphism on the CYP2B6 gene in HIV-1Patients

Poster presented at the International Young Researchers in Life Sciences Conference. Pasteur Institute, Paris, France, 26-28 May 2014

Adenosine A(2A) receptor blockade reverts hippocampal stress-induced deficits and restores corticosterone circadian oscillation

Maternal separation (MS) is an early life stress model that induces permanent changes in the central nervous system, impairing hippocampal long-term potentiation (LTP) and spatial working memory. There are compelling evidences for a role of hippocampal adenosine A(2A) receptors in stress-induced modifications related to cognition, thus opening a potential window for therapeutic intervention. Here, we submitted rats to MS and evaluated the long-lasting molecular, electrophysiological and behavioral impairments in adulthood. We then assessed the therapeutic potential of KW6002, a blocker of A(2A) receptors, in stress-impaired animals. We report that the blockade of A(2A) receptors was efficient in reverting the behavior, electrophysiological and morphological impairments induced by MS. In addition, this effect is associated with restoration of the hypothalamic-pituitary-adrenal axis (HPA-axis) activity, as both the plasma corticosterone levels and hippocampal glucocorticoid receptor expression pattern returned to physiological-like status after the treatment. These results reveal the involvement of A(2A) receptors in the stress-associated impairments and directly in the stress response system by showing that the dysfunction of the HPA-axis as well as the long-lasting synaptic and behavioral effects of MS can be reverted by targeting adenosine A(2A) receptors. These findings provide a novel evidence for the use of adenosine A(2A) receptor antagonists as potential therapy against psychopathologiesWe acknowledge Alexandre de Mendonca, David Blum and Rodrigo Cunha for helpful discussions. VLB is thankful to Joao Baiao and Carla Batalha for technical assistance. VLB has been awarded a PhD fellowship from Fundacao para a Ciencia e Tecnologia (BD/63041/2009). LVL is funded by Fundacao para a Ciencia e Tecnologia (PTDC/SAU-NEU/099853/2008) and by EU programme Egide-Pessoa. YB and CEM were funded by the Ministry for Education and Research (BMBF, Grant number 01EW0911) in the frame of ERA-NET NEURON

A distinct neuromelanin magnetic resonance imaging pattern in parkinsonian multiple system atrophy

© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background: Parkinsonian variant of multiple system atrophy is a neurodegenerative disorder frequently misdiagnosed as Parkinson's disease. No early imaging biomarkers currently differentiate these disorders. Methods: Simple visual imaging analysis of the substantia nigra and locus coeruleus in neuromelanin-sensitive magnetic resonance imaging and nigrosome 1 in susceptibility-weighted sequences was performed in thirty patients with parkinsonian variant of multiple system atrophy fulfilling possible/probable second consensus diagnostic criteria. The neuromelanin visual pattern was compared to patients with Parkinson's disease with the same disease duration (n = 10) and healthy controls (n = 10). Substantia nigra semi-automated neuromelanin area/signal intensity was compared to the visual data. Results: Groups were similar in age, sex, disease duration, and levodopa equivalent dose. Hoehn & Yahr stage was higher in parkinsonian multiple system atrophy patients, 69% of whom had normal neuromelanin size/signal, significantly different from Parkinson's disease patients, and similar to controls. Nigrosome 1 signal was lost in 74% of parkinsonian multiple system atrophy patients. Semi-automated neuromelanin substantia nigra signal, but not area, measurements were able to differentiate groups. Conclusions: In patients with parkinsonism, simple visual magnetic resonance imaging analysis showing normal neuromelanin substantia nigra and locus coeruleus, combined with nigrosome 1 loss, allowed the distinction of the parkinsonian variant of multiple system atrophy from Parkinson's disease and healthy controls. This easy and widely available method was superior to semi-automated measurements in identifying specific imaging changes in substantia nigra and locus coeruleus.info:eu-repo/semantics/publishedVersio

Patients and health professional's perspective of functional mobility in Parkinson's Disease

Copyright © 2020 Bouça-Machado, Gonçalves, Lousada, Patriarca, Costa, Nunes, Dias, Caldas, Valadas, Lobo, Guedes, Rosa, Coelho and Ferreira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Background: Functional mobility (FM) is the person's ability to move to accomplish daily living tasks and activities. FM limitations are common in Parkinson's disease, increase with disease progression, and can be highly disabling. Although several studies in Parkinson's disease (PD) field use this concept, only recently, a formal definition has been proposed. Objective: We aimed to explore patient's and health professional's perspectives of FM in PD. Methods: A focus group methodology has been used. Four focus groups, with a total of 10 patients and 10 health professionals, were performed. Six patients were early stage and four advanced stage. The health professional's group was composed of five neurologists and five physiotherapists. The suitability of the new concept, the impact of FM limitations in PD patient's daily routine, and the potential benefit of walking aids have been discussed. Results: All participants were able to provide a spontaneous definition of FM, matching with the proposed concept. All agreed that PD affects patient's FM, increasing the limitations with disease progression, and with the existence of a serious prejudice with walking aids that hinders its use. Early-stage patient's perspective seems to be more in line with neurologist's perspective, while the views of advanced-stage patients were closer to physiotherapist's views. Conclusion: FM concept was considered as intuitive and useful. FM limitations have an important physical and social impact in the advanced stage of the disease. Although patients and health professionals acknowledge walking aid's benefit improving patient's FM, the prejudice associated with this type of tools limits its recommendation and use.The authors would like to thank to the Fundação para a Ciência e a Tecnologia (FCT) (SFRH/BD/120773/2016 to RB-M).info:eu-repo/semantics/publishedVersio

An analysis of survival and disability milestones

Funding Information: This work was supported by Fundação para a Ciência e Tecnologia (FCT) through a Ph.D. Scholarship ( SFRH/BD/143797/2019 ) and Prémio João Lobo Antunes by Santa Casa da Misericórdia de Lisboa. Funding Information: This work was supported by Fundação para a Ciência e Tecnologia (FCT) through a Ph.D. Scholarship (SFRH/BD/143797/2019) and Prémio João Lobo Antunes by Santa Casa da Misericórdia de Lisboa. Publisher Copyright: © 2023Background: Data on the long-term survival and incidence of disability milestones after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) is limited. Objectives: To estimate mortality and assess the frequency/time-to-development of disability milestones (falls, freezing, hallucinations, dementia, and institutionalization) among PD patients post STN-DBS. Methods: A longitudinal retrospective study of patients undergoing STN-DBS. For mortality, Cox proportional hazards regression analysis was performed. For disease milestones, competing risk analyses were performed and cumulative incidence functions reported. The strength of association between baselines features and event occurrence was calculated based on adjusted hazard ratios. Results: The overall mortality for the 109 patients was 16 % (62.1 ± 21.3 months after surgery). Falls (73 %) and freezing (47 %) were both the earliest (40.4 ± 25.4 and 39.6 ± 28.4 months, respectively) and most frequent milestones. Dementia (34 %) and hallucinations (32 %) soon followed (56.2 ± 21.2 and mean 60.0 ± 20.7 months after surgery, respectively). Higher ADL scores in the OFF state and higher age at surgery were associated with falls, freezing, dementia and institutionalization. Conclusions: Long-term mortality rate is low after STN-DBS. Disease milestones occur later during the disease course, with motor milestones appearing first and at a higher frequency than cognitive ones.publishersversionpublishe

Diagnóstico da biodeterioração por fungos e bactérias nas pinturas murais da Casa de Fresco de Sanches Baena (Vila Viçosa, Portugal)

A Casa de Fresco de Sanches Baena, situada em Vila Viçosa (Sudeste de Portugal), é uma pequena construção semi-subterrânea, de planta quadrangular,anexa à nora do antigo Palácio dos Sanches Baena. Os frescos que cobrem a sua abóbada e paredes apresentam cenas mitológicas ricas conjugadas com anjos musicais, conchas, porcelana e outros elementos decorativos, os quais fazem dela um exemplar especialmente rico e invulgar.As pinturas apresentam uma policromia intensa que sugere o uso de uma paleta rica composta por diferentes pigmentos. Infelizmente, devido ao abandono parcial e à falta de preservação, as pinturas estão num estado avançado de degradação sendo visível o destacamento de camadas pictóricas e argamassas, eflorescências salinas e uma abundante colonização microbiológica. Com este trabalho pretende-se identificar as diferentes populações microbianas presentes e avaliar a sua importância na deterioração destas pinturas. O estudo microbiológico foi efectuado em amostras recolhidas de zonas visivelmente contaminadas, utilizando zaragatoas e bisturis estéreis, por cultura em meios selectivos e observação por microscopia óptica e electrónica. Este estudo permitiu isolar 32 estirpes bacterianas e 34 fúngicas nos quatro painéis de frescos.As estirpes bacterianas predominantes foram as estirpes Gram+ do género Bacillus existindo também um elevado número de estirpes Gramdo género Pseudomonas. Entre as estirpes fúngicas predominantes destacam-se as estirpes de Cladosporium spp. e Penicillium spp. Para avaliação da biodeterioração procedeu-se também à quantificação da actividade da desidrogenase em zonas de reboco degradadas, como biomarcador da presença de microrganismos vivos. Paralelamente, para caracterização da actividade da desidrogenase, procedeu-se à sua quantificação em culturas de uma das estirpes predominantes isolada de um dos painéis com deterioração. Nas zonas degradadas analisadas foi detectada uma forte actividade desidrogenase, pelo que esta enzima parece ser um bom marcador da biodeterioração