5,152 research outputs found
Chiral Analysis of Pesticides and Drugs of Environmental Concern: Biodegradation and Enantiomeric Fraction
The importance of stereochemistry for medicinal chemistry and pharmacology is well recognized and the dissimilar behavior of enantiomers is fully documented. Regarding the environment, the significance is equivalent since enantiomers of chiral organic pollutants can also differ in biodegradation processes and fate, as well as in ecotoxicity. This review comprises designed biodegradation studies of several chiral drugs and pesticides followed by enantioselective analytical methodologies to accurately measure the enantiomeric fraction (EF). The enantioselective monitoring of microcosms and laboratory-scale experiments with different environmental matrices is herein reported. Thus, this review focuses on the importance of evaluating the EF variation during biodegradation studies of chiral pharmaceuticals, drugs of abuse, and agrochemicals and has implications for the understanding of the environmental fate of chiral pollutants.The authors wish to thank Fundação para a Ciência e Tecnologia—FCT for financial support under the project Fluoropharma PTDC/EBB-EBI/111699/2009, the PhD grant attributed to Alexandra S. Maia SFRH/BD/86939/2012, QREN-POPH, European Social Fund, MCTES, PEst FCOMP-01-0124-FEDER-022718; PEst-OE/EQB/LA0016/2011, PEst-OE/SAU/UI4040/2014. This research was partially supported by the Strategic Funding UID/Multi/04423/2013 through national funds provided by FCT—Fundação para a Ciência e Tecnologia
and European Regional Development Fund (ERDF), in the framework of the program PT2020 and by CESPU
(ChiralDrugs_CESPU_2017
Formate supplementation enhances folate-dependent nucleotide biosynthesis and prevents spina bifida in a mouse model of folic acid-resistant neural tube defects
The curly tail mouse provides a model for neural tube defects (spina bifida and exencephaly) that are resistant to prevention by folic acid. The major ct gene, responsible for spina bifida, corresponds to a hypomorphic allele of grainyhead-like 3 (Grhl3) but the frequency of NTDs is strongly influenced by modifiers in the genetic background. Moreover, exencephaly in the curly tail strain is not prevented by reinstatement of Grhl3 expression. In the current study we found that expression of Mthfd1L, encoding a key component of mitochondrial folate one-carbon metabolism (FOCM), is significantly reduced in ct/ct embryos compared to a partially congenic wild-type strain. This expression change is not attributable to regulation by Grhl3 or the genetic background at the Mthfd1L locus. Mitochondrial FOCM provides one-carbon units as formate for FOCM reactions in the cytosol. We found that maternal supplementation with formate prevented NTDs in curly tail embryos and also resulted in increased litter size. Analysis of the folate profile of neurulation-stage embryos showed that formate supplementation resulted in an increased proportion of formyl-THF and THF but a reduction in proportion of 5-methyl THF. In contrast, THF decreased and 5-methyl THF was relatively more abundant in the liver of supplemented dams than in controls. In embryos cultured through the period of spinal neurulation, incorporation of labelled thymidine and adenine into genomic DNA was suppressed by supplemental formate, suggesting that de novo folate-dependent biosynthesis of nucleotides (thymidylate and purines) was enhanced. We hypothesise that reduced Mthfd1L expression may contribute to susceptibility to NTDs in the curly tail strain and that formate acts as a one-carbon donor to prevent NTDs
A First Look at CQVID-19 Messages on WhatsApp in Pakistan
The worldwide spread of COVID-19 has prompted extensive online discussions,
creating an `infodemic' on social media platforms such as WhatsApp and Twitter.
However, the information shared on these platforms is prone to be unreliable
and/or misleading. In this paper, we present the first analysis of COVID-19
discourse on public WhatsApp groups from Pakistan. Building on a large scale
annotation of thousands of messages containing text and images, we identify the
main categories of discussion. We focus on COVID-19 messages and understand the
different types of images/text messages being propagated. By exploring user
behavior related to COVID messages, we inspect how misinformation is spread.
Finally, by quantifying the flow of information across WhatsApp and Twitter, we
show how information spreads across platforms and how WhatsApp acts as a source
for much of the information shared on Twitter
Giant Cell Arteritis Presenting as Simultaneous Bilateral Critical Upper Limb Ischemia - Clinical Case
Introdução: A arterite de células gigantes (ACG), de etiologia desconhecida, é a vasculite sistémica mais comum nos adultos e pode ter uma ampla variedade de apresentações clínicas.
Atinge mais frequentemente os ramos extracranianos da artéria carótida mas, em 10-15% dos
casos, pode ocorrer o envolvimento das artérias subclávia, axilar e braquial.
Caso clínico: Tratava-se de uma doente do sexo feminino, de 80 anos, com antecedentes de
HTA e doença cerebrovascular. Foi observada no serviço de urgência por arrefecimento e dor em
repouso nos membros superiores, com evidências de cianose digital distal bilateral. As queixas
tinham tido início 2 meses antes e agravamento progressivo desde então.
Realizou um angio-TC que mostrou a existência de oclusão de ambas as artérias axilares/braquiais proximais e imagens sugestivas de vasculite ao nível de ambas as artérias
subclávias, aorta e artérias femorais comuns. Foi medicada com corticoterapia; contudo,
por não apresentar melhoria significativa após 5 dias, optou-se por realizar um bypass
carotídeo-umeral bilateral. Após a cirurgia, ocorreu resolução completa das queixas e a
doente apresentava pulso radial palpável bilateralmente. Seis meses após a cirurgia, a doente
encontrava-se assintomática e os bypasses permeáveis.
Conclusão: O presente trabalho pretende expor o caso de uma doente com o diagnóstico inaugural e ACG,que se apresentou com isquemia crítica bilateral e simultânea. Este quadro clínico
exigiu a realização de um procedimento de revascularização raro
Impact of Community-Based Larviciding on the Prevalence of Malaria Infection in Dar es Salaam, Tanzania.
The use of larval source management is not prioritized by contemporary malaria control programs in sub-Saharan Africa despite historical success. Larviciding, in particular, could be effective in urban areas where transmission is focal and accessibility to Anopheles breeding habitats is generally easier than in rural settings. The objective of this study is to assess the effectiveness of a community-based microbial larviciding intervention to reduce the prevalence of malaria infection in Dar es Salaam, United Republic of Tanzania. Larviciding was implemented in 3 out of 15 targeted wards of Dar es Salaam in 2006 after two years of baseline data collection. This intervention was subsequently scaled up to 9 wards a year later, and to all 15 targeted wards in 2008. Continuous randomized cluster sampling of malaria prevalence and socio-demographic characteristics was carried out during 6 survey rounds (2004-2008), which included both cross-sectional and longitudinal data (N = 64,537). Bayesian random effects logistic regression models were used to quantify the effect of the intervention on malaria prevalence at the individual level. Effect size estimates suggest a significant protective effect of the larviciding intervention. After adjustment for confounders, the odds of individuals living in areas treated with larviciding being infected with malaria were 21% lower (Odds Ratio = 0.79; 95% Credible Intervals: 0.66-0.93) than those who lived in areas not treated. The larviciding intervention was most effective during dry seasons and had synergistic effects with other protective measures such as use of insecticide-treated bed nets and house proofing (i.e., complete ceiling or window screens). A large-scale community-based larviciding intervention significantly reduced the prevalence of malaria infection in urban Dar es Salaam
Evolution of Landau Levels into Edge States at an Atomically Sharp Edge in Graphene
The quantum-Hall-effect (QHE) occurs in topologically-ordered states of
two-dimensional (2d) electron-systems in which an insulating bulk-state
coexists with protected 1d conducting edge-states. Owing to a unique
topologically imposed edge-bulk correspondence these edge-states are endowed
with universal properties such as fractionally-charged quasiparticles and
interference-patterns, which make them indispensable components for QH-based
quantum-computation and other applications. The precise edge-bulk
correspondence, conjectured theoretically in the limit of sharp edges, is
difficult to realize in conventional semiconductor-based electron systems where
soft boundaries lead to edge-state reconstruction. Using scanning-tunneling
microscopy and spectroscopy to follow the spatial evolution of bulk
Landau-levels towards a zigzag edge of graphene supported above a graphite
substrate we demonstrate that in this system it is possible to realize
atomically sharp edges with no edge-state reconstruction. Our results single
out graphene as a system where the edge-state structure can be controlled and
the universal properties directly probed.Comment: 16 pages, 4 figure
Network 'small-world-ness': a quantitative method for determining canonical network equivalence
Background: Many technological, biological, social, and information networks fall into the broad class of 'small-world' networks: they have tightly interconnected clusters of nodes, and a shortest mean path length that is similar to a matched random graph (same number of nodes and edges). This semi-quantitative definition leads to a categorical distinction ('small/not-small') rather than a quantitative, continuous grading of networks, and can lead to uncertainty about a network's small-world status. Moreover, systems described by small-world networks are often studied using an equivalent canonical network model-the Watts-Strogatz (WS) model. However, the process of establishing an equivalent WS model is imprecise and there is a pressing need to discover ways in which this equivalence may be quantified.
Methodology/Principal Findings: We defined a precise measure of 'small-world-ness' S based on the trade off between high local clustering and short path length. A network is now deemed a 'small-world' if S. 1-an assertion which may be tested statistically. We then examined the behavior of S on a large data-set of real-world systems. We found that all these systems were linked by a linear relationship between their S values and the network size n. Moreover, we show a method for assigning a unique Watts-Strogatz (WS) model to any real-world network, and show analytically that the WS models associated with our sample of networks also show linearity between S and n. Linearity between S and n is not, however, inevitable, and neither is S maximal for an arbitrary network of given size. Linearity may, however, be explained by a common limiting growth process.
Conclusions/Significance: We have shown how the notion of a small-world network may be quantified. Several key properties of the metric are described and the use of WS canonical models is placed on a more secure footing
Time Delays on Carotid Endarterectomy: Institutional Experience and Improvement Strategies
Objetivos: Avaliar as vias de referenciação dos doentes com estenoses carotídeas sintomáticas
que foram operados na nossa instituição; estruturar os tempos de espera desde os primeiros
sintomas neurológicos à data da cirurgia; identificar os fatores responsáveis pelos atrasos e criar
estratégias que permitam reduzi-los.
Material e métodos: Realizou-se um estudo observacional retrospetivo de todos os doentes com
estenoses carotídeas sintomáticas submetidas a endarterectomia carotídea na nossa instituição
entre 2011-2013. Foram identificadas as etapas essenciais no processo de referenciação dos
doentes e foram colhidos dados referentes às datas do início dos sintomas, primeiro contacto
médico, exames de imagem vascular, referenciação ao cirurgião, consulta de cirurgia vascular
e da endarterectomia carotídea. O tempo decorrido entre o evento neurológico e a cirurgia foi
calculado em dias e todos os atrasos identificados foram analisados detalhadamente.
Resultados: A mediana do tempo de espera do evento neurológico à cirurgia foi de 27,5 dias
(intervalo 7-581).Os maiores atrasos verificaram-se entre a data em que é colocada a indicação
cirúrgica e a endarterectomia carotídea (mediana 9 dias; intervalo 1-349); na referenciação dos
doentes à consultadecirurgia vascular (mediana 6,5 dias; intervalo 0-97)e entre o primeiro contacto médico e a realização dos exames de imagem vascular (mediana 6 dias; intervalo 1-71).
Dos 60 doentes incluídos, apenas 21,7% foram operados nos primeiros 14 dias após o evento
neurológico. O atraso foi significativamente menor nos doentes admitidos de forma urgente
por transferência inter/intra-hospitalar (n=30; mediana 15 dias, intervalo 7-163) comparativamente aos doentes admitidos eletivamente pela consulta (n=30; mediana 86 dias, intervalo
13-581 dias) (p<0,0001).Discussão: Apesar da evidência atual, ainda existem atrasos significativos no processo de referenciação dos doentes com estenoses carotídeas sintomáticas. Estratégias direcionadas à
redução destes atrasos poderão aumentar substancialmente a proporção de doentes submetidos
a endarterectomia carotídea até 14 dias após o evento neurológico inicial
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Testing different CNN architectures for semantic segmentation for landscaping with forestry robotics
Increasingly mechanized, leading to the emergence of forestry robotics. In this article, we present the results of our evaluation of a set of state-of-the-art convolutional neural network-based solutions for semantic segmentation using the Bonnetal open-source training and deployment framework, together with a custom-made solution based on an adaptation of an alternative decoder and encoder for that framework, the Adapnet++–eASPP architecture, in the context of a robotic perception pipeline designed to perform landscaping in woodlands to reduce the amount of living flammable material (the Fuel class) for wildfire prevention. Results show that, overall, Adapnet++–eASPP was the most robust and comprehensive encoder for our application, demonstrating a consistently high average level of performance in comparison to the other architectures, and displaying the greatest robustness of the group. With this solution, we demonstrated to be able to satisfy our requirements of a low rate of false positives for the Fuel class and operational performance of 10fps
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