Antimalarial agents as therapeutic tools against toxoplasmosis: a short bridge between two distant illnesses

Toxoplasmosis is an infectious disease with paramount impact worldwide, affecting many vulnerable populations and representing a significant matter of concern. Current therapies used against toxoplasmosis are based essentially on old chemotypes, which fail in providing a definitive cure for the disease, placing the most sensitive populations at risk for irreversible damage in vital organs, culminating in death in the most serious cases. Antimalarial drugs have been shown to possess key features for drug repurposing, finding application in the treatment of other parasite-borne illnesses, including toxoplasmosis. Antimalarials provide the most effective therapeutic solutions against toxoplasmosis and make up for the majority of currently available antitoxoplasmic drugs. Additionally, other antiplasmodial drugs have been scrutinized and many promising candidates have emanated in recent developments. Available data demonstrate that it is worthwhile to explore the activity of classical and most recent antimalarial chemotypes, such as quinolines, endoperoxides, pyrazolo[1,5-a]pyrimidines, and nature-derived peptide-based parasiticidal agents, in the context of toxoplasmosis chemotherapy, in the quest for encountering more effective and safer tools for toxoplasmosis control or eradication.Fundação para a Ciência e Tecnologia (FCT): UID/MULTI/04326/2019 (CCMAR), UID/QUI/00313/2019 (CQC), PTDC/MAR-BIO/4132/2014, SFRH/BD/140249/2018 (AS).info:eu-repo/semantics/publishedVersio

Beyond width and density: stable carbon and oxygen isotopes in cork-rings provide insights of physiological responses to water stress in Quercus suber L

As climate change increasingly affects forest ecosystems, detailed understanding of major effects is important to anticipate their consequences under future climate scenarios. The Mediterranean region is a prominent climate change hotspot, and evergreen cork oak (Quercus suber L.) woodlands are particularly climatically sensitive due to cork (bark) harvesting. Cork oak’s drought avoidance strategy is well-known and includes structural and physiological adaptations that maximise soil water uptake and transport and limit water use, potentially leading to reduced stem and cork growth. Trees’ responses to cope with water-limited conditions have been extensively described based on cork-rings width and, more recently, on cork-rings density, in dendroecological studies. However, so far, tree functional attributes and physiological strategies, namely photosynthetic metabolism adjustments affecting cork formation, have never been addressed and/or integrated on these previous cork-rings-based studies. In this study, we address the relation between carbon and oxygen stable isotopes of cork rings and precipitation and temperature, in two distinct locations of southwestern Portugal–the (wetter) Tagus basin peneplain and the (drier) Grândola mountains. We aimed at assessing whether the two climatic factors affect cork-ring isotopic composition under contrasting conditions of water availability, and, therefore, if carbon and oxygen signatures in cork can reflect tree functional (physiological and structural) responses to stressful conditions, which might be aggravated by climate change. Our results indicate differences between the study areas. At the drier site, the stronger statistically significant negative cork δ13C correlations were found with mean temperature, whereas strong positive cork δ18O correlations were fewer and found only with precipitation. Moreover, at the wetter site, cork rings are enriched in 18O and depleted in 13C, indicating, respectively, shallow groundwater as the water source for physiological processes related with biosynthesis of non-photosynthetic secondary tissues, such as suberin, and a weak stomatal regulation under high water availability, consistent with non-existent water availability constrains. In contrast, at the drier site, trees use water from deeper ground layers, depleted in 18O, and strongly regulate stomatal conductance under water stress, thus reducing photosynthetic carbon uptake and probably relying on stored carbon reserves for cork ring formation. These results suggest that although stable isotopes signatures in cork rings are not proxies for net growth, they may be (fairly) robust indicators of trees’ physiological and structural adjustments to climate and environmental changes in Mediterranean environments.info:eu-repo/semantics/publishedVersio

Estudo Paramétrico do Efeito de Arco em Barragens de Terra

Esta dissertação tem por objetivo o estudo paramétrico do efeito de arco numa barragem de terra. O efeito de arco está intrinsecamente ligado à segurança das barragens de aterro contudo, embora seja objeto de estudo em barragens de enrocamento, o seu efeito não é muito estudado em barragens de terra. O fenómeno de efeito de arco surge associado à fase de construção da barragem, primeiro enchimento e exploração da mesma. Propõe-se o estudo deste fenómeno durante a fase de construção da barragem. pelo que se começa por uma breve descrição relativamente ao efeito de arco e qual a importância do seu estudo. A diferença entre os assentamentos ocorridos no núcleo da barragem e nos maciços durante a construção da barragem provoca uma variação de tensões no núcleo da barragem que podem levar à fraturação hidráulica. À diferença de tensões existente entre o núcleo e os maciços chamamos de efeito de arco. Neste trabalho, recorrendo ao software Plaxis2D, apresenta-se um primeiro caso base descrevendo o faseamento construtivo do mesmo. Procede-se a uma análise aos deslocamentos verticais, tensões verticais totais e tensões verticais efetivas considerando vários tempos de consolidação e diferentes estados de saturação dos materiais. É ainda feito um estudo relativamente à secção a considerar para analise do efeito neste caso base e de seguida analisa-se o efeito de arco. Por fim, efetua-se uma análise paramétrica onde se estuda a influência no efeito de arco da deformabilidade do maciço e do núcleo, da resistência ao corte no maciço e no núcleo, das inclinações dos taludes do núcleo e da altura da barragem. De onde se concluiu que o parâmetro com maior influência no efeito de arco é a deformabilidade dos maciços e do núcleo

Occurrence of Multidrug-Resistant Bacteria Resulting from the Selective Pressure of Antibiotics: A Comprehensive Analysis of ESBL K. pneumoniae and MRSP Isolated in a Dog with Rhinorrhea

(This article belongs to the Special Issue Antimicrobial Use in Companion Animals)Because of public health concerns, much greater scrutiny is now placed on antibiotic use in pets, especially for antimicrobial agents that have human analogs. Therefore, this study aimed to characterize the phenotypic and genotypic profiles of multidrug-resistant bacteria isolated from nasal swabs samples taken from a one-year-old male Serra da Estrela dog with rhinorrhea that was treated with amikacin. An extended-spectrum β-lactamases (ESBL) Klebsiella pneumoniae was isolated in the first sample taken from the left nasal cavity of the dog. Seven days later, methicillin-resistant (MRSP) Staphylococcus pseudintermedius was also isolated. Nevertheless, no alterations to the therapeutic protocol were performed. Once the inhibitory action of the antibiotic disappeared, the competitive advantage of the amikacin-resistant MRSP was lost, and only commensal flora was observed on both nasal cavities. The genotypic profile of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae revealed the same characteristics and close relation to other strains, mainly from Estonia, Slovakia and Romania. Regarding MRSP isolates, although resistance to aminoglycosides was present in the first MRSP, the second isolate carried aac(6')-aph(2″), which enhanced its resistance to amikacin. However, the veterinary action was focused on the treatment of the primary agent (ESBL K. pneumoniae), and the antibiotic applied was according to its phenotypic profile, which may have led to the resolution of the infectious process. Therefore, this study highlights the importance of targeted therapy, proper clinical practice and laboratory-hospital communication to safeguard animal, human and environmental health.Simple Summary: Antimicrobial resistance (AMR) poses a major threat to human and animal health. One of the causes underlying the emergence of increasingly resistant strains is antibiotic selective pressure. This study aimed to evaluate the impact of treatment with amikacin on an extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae isolated in a dog with rhinorrhea. In the middle of the treatment, methicillin-resistant Staphylococcus pseudintermedius (MRSP) was isolated from the left nasal cavity of the dog. At the end of the treatment, K. pneumoniae was not recovered from nasal swab samples, while MRSP displayed phenotypical and genotypical changes. Six weeks after the end of the treatment, only commensal flora was observed in both nasal cavities. These results warn of the effects of antibiotic pressure, which can lead to the emergence of multidrug-resistant strains either by directly promoting the enrichment of bacteria with resistance to multiple antimicrobial agents or via the subsequent acquisition of resistance genes. Therefore, adapting clinical practice to this new reality is crucial to limit the selection and spread of multi-resistant bacteria among pets, humans and the environment.info:eu-repo/semantics/publishedVersio

Synthesis, structure and antileishmanial evaluation of endoperoxide–pyrazole hybrids

Leishmaniases are among the most impacting neglected tropical diseases. In attempts to repurpose antimalarial drugs or candidates, it was found that selected 1,2,4-trioxanes, 1,2,4,5-tetraoxanes, and pyrazole-containing chemotypes demonstrated activity against Leishmania parasites. This study reports the synthesis and structure of trioxolane–pyrazole (OZ1, OZ2) and tetraoxane–pyrazole (T1, T2) hybrids obtained from the reaction of 3(5)-aminopyrazole with endoperoxide-containing building blocks. Interestingly, only the endocyclic amine of 3(5)-aminopyrazole was found to act as nucleophile for amide coupling. However, the fate of the reaction was influenced by prototropic tautomerism of the pyrazole heterocycle, yielding 3- and 5-aminopyrazole containing hybrids which were characterized by different techniques, including X-ray crystallography. The compounds were evaluated for in vitro antileishmanial activity against promastigotes of L. tropica and L. infantum, and for cytotoxicity against THP-1 cells. Selected compounds were also evaluated against intramacrophage amastigote forms of L. infantum. Trioxolane–pyrazole hybrids OZ1 and OZ2 exhibited some activity against Leishmania promastigotes, while tetraoxane–pyrazole hybrids proved inactive, most likely due to solubility issues. Eight salt forms, specifically tosylate, mesylate, and hydrochloride salts, were then prepared to improve the solubility of the corresponding peroxide hybrids and were uniformly tested. Biological evaluations in promastigotes showed that the compound OZ1•HCl was the most active against both strains of Leishmania. Such finding was corroborated by the results obtained in assessments of the L. infantum amastigote susceptibility. It is noteworthy that the salt forms of the endoperoxide–pyrazole hybrids displayed a broader spectrum of action, showing activity in both strains of Leishmania. Our preliminary biological findings encourage further optimization of peroxide–pyrazole hybrids to identify a promising antileishmanial lead.info:eu-repo/semantics/publishedVersio

Comparison of the co-amorphization ability of Olanzapine with amino, carboxylic and sulfonic acids

Abstract of the poster presented at the 3rd European Conference on Pharmaceutics. 25-26 March 2019, Bologne, ItalyN/

Práticas de pesquisa : como acontecem nas escolas de 2º. e 3º. graus?

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Representações da andropausa: um estudo de métodos mistos com mulheres portuguesas

Since psychosocial factors have some impact on andropause, and this phenomenon can affect conjugal relationships (and women tend to be health information seekers) it becomes important to study the representations of andropause using the Common-Sense Model – a model used to understand the representations of menopause. This research aimed to assess Portuguese women’s representations of andropause, the suitability of the Common-Sense Model in explaining those representations, and to explore differences among participants with different characteristics (e.g., level of education), regarding andropause representations. Interviews to 30 women were analysed (directed qualitative content analysis). A multiple correspondence analysis explored the association between the emergent categories. Mann-Whitney U tests were performed to test differences regarding the frequency of emergent categories. Undefined identity was the most frequently mentioned feature regarding andropause Identity, whereas Sexual Function was the most mentioned Negative Consequence; few Positive Consequences were mentioned, being the Absence of positives consequences and the Lack of information the most frequent ones. Two bidimensional models were found - one for Identity of andropause: (1) Aging related changes, and (2) Sexual changes/lack of information; the other for Negative Consequences: (1) Symptoms/health problems, and (2) Depression/lack of information. No differences were found in the frequency of andropause representations between women with different characteristics (e.g., with a romantic relationship vs. without a romantic relationship). The suitability of the Common-Sense Model to explain these women’s andropause representations did not differ among participants with distinctive characteristics. This research may help healthcare professionals to develop comprehensive interventions (based on this theoretical model) in order to help couples to better understand and cope with andropause.info:eu-repo/semantics/publishedVersio

Wired: impacts of increasing power line use by a growing bird population

Power lines are increasingly widespread across many regions of the planet. Although these linear infrastructures are known for their negative impacts on bird populations, through collision and electrocution, some species take advantage of electricity pylons for nesting. In this case, estimation of the net impact of these infrastructures at the population level requires an assessment of trade-offs between positive and negative impacts. We compiled historical information (1958–2014) of the Portuguese white stork Ciconia ciconia population to analyze long-term changes in numbers, distribution range and use of nesting structures. White stork population size increased 660% up to 12000 breeding pairs between 1984 and 2014. In the same period, the proportion of nests on electricity pylons increased from 1% to 25%, likely facilitated by the 60% increase in the length of the very high tension power line grid (holding the majority of the nests) in the stork's distribution range. No differences in breeding success were registered for storks nesting on electricity pylons versus other structures, but a high risk of mortality by collision and electrocution with power lines was estimated. We discuss the implications of this behavioral change, and of the management responses by power line companies, both for stork populations and for managers

Gulls in Porto Coastline as Reservoirs for Salmonella spp.: Findings from 2008 and 2023

(This article belongs to the Special Issue Water Microorganisms Associated with Human Health)Gulls act as intermediaries in the exchange of microorganisms between the environment and human settlements, including Salmonella spp. This study assessed the antimicrobial resistance and molecular profiles of Salmonella spp. isolates obtained from fecal samples of gulls in the city of Porto, Portugal, in 2008 and 2023 and from water samples in 2023. Antimicrobial susceptibility profiling revealed an improvement in the prevalence (71% to 17%) and antimicrobial resistance between the two collection dates. Two isolate collections from both 2008 and 2023 underwent serotyping and whole-genome sequencing, revealing genotypic changes, including an increased frequency in the monophasic variant of S. Typhimurium. qacE was identified in 2008 and 2023 in both water and fecal samples, with most isolates exhibiting an MDR profile. The most frequently observed plasmid types were IncF in 2008 (23%), while IncQ1 predominated in 2023 (43%). Findings suggest that Salmonella spp. circulate between humans, animals, and the environment. However, the genetic heterogeneity among the isolates from the gulls' feces and the surface water may indicate a complex ecological and evolutionary dynamic shaped by changing conditions. The observed improvements are likely due to measures to reduce biological contamination and antimicrobial resistance. Nevertheless, additional strategies must be implemented to reduce the public health risk modeled by the dissemination of pathogens by gulls.Funding: WGS was supported by funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No 773830: One Health European Joint Programme, as part of the DiSCoVeR project (Discovering the sources of Salmonella, Campylobacter, VTEC, and Antimicrobial Resistance).info:eu-repo/semantics/publishedVersio