The Demise of Multidrug-Resistant HIV-1: the National Time Trend in Portugal

OBJECTIVES: Despite a decreasing mortality and morbidity in treated HIV-1 patients, highly active antiretroviral treatment (HAART) can still fail due to the development of drug resistance. Especially, multidrug-resistant viruses pose a threat to efficient therapy. We studied the changing prevalence of multidrug resistance (MDR) over time in a cohort of HIV-1-infected patients in Portugal. PATIENTS AND METHODS: We used data of 8065 HIV-1-infected patients followed from July 2001 up to April 2012 in 22 hospitals located in Portugal. MDR at a specific date of sampling was defined as no more than one fully active drug (excluding integrase and entry inhibitors) at that time authorized by the Portuguese National Authority of Medicines and Health Products (INFARMED), as interpreted with the Rega algorithm version 8.0.2. A generalized linear mixed model was used to study the time trend of the prevalence of MDR. RESULTS: We observed a statistically significant decrease in the prevalence of MDR over the last decade, from 6.9% (95% CI: 5.7-8.4) in 2001-03, 6.0% (95% CI: 4.9-7.2) in 2003-05, 3.7% (95% CI: 2.8-4.8) in 2005-07 and 1.6% (95% CI: 1.1-2.2) in 2007-09 down to 0.6% (95% CI: 0.3-0.9) in 2009-12 [OR=0.80 (95% CI: 0.75-0.86); P<0.001]. In July 2011 the last new case of MDR was seen. CONCLUSIONS: The prevalence of multidrug-resistant HIV-1 is decreasing over time in Portugal, reflecting the increasing efficiency of HAART and the availability of new drugs. Therefore, in designing a new drug, safety and practical aspects, e.g. less toxicity and ease of use, may need more attention than focusing mainly on efficacy against resistant strains.info:eu-repo/semantics/publishedVersio

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

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

Approaches to study in higher education portuguese students: a portuguese version of the Approaches and Study Skills Inventory for Students (ASSIST)

This paper examines the validity of the Approaches and Study Skills Inventory for Students—short version (ASSIST; Tait et al. in Improving student learning: Improving students as learners, 1998), to be used with Portuguese undergraduate students. The ASSIST was administrated to 566 students, in order to analyse a Portuguese version of this inventory. Exploratory factor analysis (principal axis factor analysis followed by direct oblimin rotation) reproduced the three main factors that correspond to the original dimensions of the inventory (deep, surface apathetic and strategic approaches to learning). The results are consistent with the background theory on approaches to learning. Additionally, the reliability analysis revealed acceptable internal consistency indexes for the main scales and subscales. This inventory might represent a valuable research tool for the assessment of approaches to learning among Portuguese higher education students

Feasibility, acceptability, and effectiveness of non-pharmaceutical interventions against infectious diseases among crisis-affected populations: a scoping review

BACKGROUND: Colonization of large part of Europe by the Asian tiger mosquito Aedes albopictus is causing autochthonous transmission of chikungunya and dengue exotic arboviruses. While pyrethroids are recommended only to reduce/limit transmission, they are widely implemented to reduce biting nuisance and to control agricultural pests, increasing the risk of insurgence of resistance mechanisms. Worryingly, pyrethroid resistance (with mortality < 70%) was recently reported in Ae. albopictus populations from Italy and Spain and associated with the V1016G point mutation in the voltage-sensitive sodium channel gene conferring knockdown resistance (kdr). Genotyping pyrethroid resistance-associated kdr mutations in field mosquito samples represents a powerful approach to detect early signs of resistance without the need for carrying out phenotypic bioassays which require availability of live mosquitoes, dedicated facilities and appropriate expertise. METHODS: Here we report results on the PCR-genotyping of the V1016G mutation in 2530 Ae. albopictus specimens from 69 sampling sites in 19 European countries. RESULTS: The mutation was identified in 12 sites from nine countries (with allele frequencies ranging from 1 to 8%), mostly distributed in two geographical clusters. The western cluster includes Mediterranean coastal sites from Italy, France and Malta as well as single sites from both Spain and Switzerland. The eastern cluster includes sites on both sides of the Black Sea in Bulgaria, Turkey and Georgia as well as one site from Romania. These results are consistent with genomic data showing high connectivity and close genetic relationship among West European populations and a major barrier to gene flow between West European and Balkan populations. CONCLUSIONS: The results of this first effort to map kdr mutations in Ae. albopictus on a continental scale show a widespread presence of the V1016G allele in Europe, although at lower frequencies than those previously reported from Italy. This represents a wake-up call for mosquito surveillance programs in Europe to include PCR-genotyping of pyrethroid resistance alleles, as well as phenotypic resistance assessments, in their routine activities

Geographic distribution of the V1016G knockdown resistance mutation in aedes albopictus. A warning bell for Europe

Background: Colonization of large part of Europe by the Asian tiger mosquito Aedes albopictus is causing autochthonous transmission of chikungunya and dengue exotic arboviruses. While pyrethroids are recommended only to reduce/limit transmission, they are widely implemented to reduce biting nuisance and to control agricultural pests, increasing the risk of insurgence of resistance mechanisms. Worryingly, pyrethroid resistance (with mortality &lt; 70%) was recently reported in Ae. albopictus populations from Italy and Spain and associated with the V1016G point mutation in the voltage-sensitive sodium channel gene conferring knockdown resistance (kdr). Genotyping pyrethroid resistance-associated kdr mutations in field mosquito samples represents a powerful approach to detect early signs of resistance without the need for carrying out phenotypic bioassays which require availability of live mosquitoes, dedicated facilities and appropriate expertise.Methods: Here we report results on the PCR-genotyping of the V1016G mutation in 2530 Ae. albopictus specimens from 69 sampling sites in 19 European countries.Results: The mutation was identified in 12 sites from nine countries (with allele frequencies ranging from 1 to 8%), mostly distributed in two geographical clusters. The western cluster includes Mediterranean coastal sites from Italy, France and Malta as well as single sites from both Spain and Switzerland. The eastern cluster includes sites on both sides of the Black Sea in Bulgaria, Turkey and Georgia as well as one site from Romania. These results are consistent with genomic data showing high connectivity and close genetic relationship among West European populations and a major barrier to gene flow between West European and Balkan populations.Conclusions: The results of this first effort to map kdr mutations in Ae. albopictus on a continental scale show a widespread presence of the V1016G allele in Europe, although at lower frequencies than those previously reported from Italy. This represents a wake-up call for mosquito surveillance programs in Europe to include PCR-genotyping of pyrethroid resistance alleles, as well as phenotypic resistance assessments, in their routine activities