Building on surface-active ionic liquids for the rescuing of the antimalarial drug chloroquine

Ionic liquids derived from classical antimalarials are emerging as a new approach towards the cost-effective rescuing of those drugs. Herein, we disclose novel surface-active ionic liquids derived from chloroquine and natural fatty acids whose antimalarial activity in vitro was found to be superior to that of the parent drug. The most potent ionic liquid was the laurate salt of chloroquine, which presented IC50 values of 4 and 110 nM against a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodium falciparum, respectively, corresponding to an 11-and 6-fold increase in potency as compared to the reference chloroquine bisphosphate salt against the same strains. This unprecedented report opens new perspectives in both the fields of malaria chemotherapy and of surface-active ionic liquids derived from active pharmaceutical ingredients.publishersversionpublishe

Analysis of the immunological biomarker profile during acute zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage

BACKGROUND Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. OBJECTIVES To define the immunologic biomarkers that correlate with acute ZIKV infection. METHODS We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining. FINDINGS ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues. MAIN CONCLUSIONS Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application. © 2018, Fundacao Oswaldo Cruz. All rights reserved

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Abordagens para Prevenção Secundária do Tromboembolismo Pulmonar (TEP): Uma Revisão de Literatura

This literature review aims to investigate contemporary strategies for the secondary prevention of Pulmonary Embolism (PE). The research encompassed recent studies, focusing on anticoagulation, including novel oral anticoagulants, surgical interventions, and advanced diagnostic methods. Emphasizing the importance of personalized treatment considering individual factors, the review underscores the need for additional studies to validate conclusions and inform more robust clinical guidelines. This review contributes to an in-depth understanding of secondary prevention strategies for PE, highlighting the integrated and personalized approach as crucial for optimizing clinical outcomes and reducing PE recurrence.Esta revisão de literatura explora estratégias contemporâneas para a prevenção secundária do Tromboembolismo Pulmonar (TEP). A pesquisa abrangeu estudos recentes, enfocando anticoagulação, incluindo novos anticoagulantes orais, intervenções cirúrgicas, e métodos de diagnóstico avançados. Destaca-se a importância da personalização do tratamento, considerando fatores individuais, enquanto ressalta a necessidade de estudos adicionais para validar conclusões e informar diretrizes clínicas mais sólidas. Esta revisão contribui para uma compreensão aprofundada das estratégias de prevenção secundária do TEP, enfatizando a abordagem integrada e personalizada como crucial para otimizar desfechos clínicos e reduzir recorrências do TEP

Generalidades sobre o quadro clínico da Rinossinusite: uma revisão narrativa de literatura: Generalities about the clinical picture of Rhinosinusitis: a narrative literature reviewv

A rinossinusite é um processo inflamatório da mucosa dos seios paranasais e da cavidade nasal. O sistema nasossinusal é responsável pelo balanço adequado entre a fabricação e o clearence de muco nas cavidades paranasais. A fisiologia deste é de vital importância para a proteção das vias aéreas superiores. No advém, determinados fatores podem acarretar um desbalanço nesse complexo, consequentemente um processo inflamatório. Qualquer fator que altere a drenagem, seja por obstrução, maior produção ou espessamento do muco, como processo infecciosos ou alérgicos, haverá uma impactação de secreções e a facilitação de colonização bacteriana, dando início ao processo infeccioso. A identificação da inflamação do nariz e seios paranasais é basicamente clínica. A suspeição desta ocorre através da manifestação de dois ou mais sintomatologias. As quais são o bloqueio ou obstrução nasal, a descarga nasal, pressão ou dor facial e redução ou perda do olfato. De modo geral, é essencial à prevenção básica das rinossinusites agudas é barrar a infecção viral. O suporte inclui medidas gerais de higiene, alimentação e hidratação, imunização para o combate de vírus respiratórios , administração de fármacos para turbinar o sistema imune se necessário

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

O Uso de Redes Sociais na Engenharia de Requisitos

This paper describes a research which is being conducted in order to investigate the use of social networks tools in requirements engineering. We understand that social networks tools can minimize communication problems during the requirements definition process. A questionnaire was developed to be applied in software houses in order to know if this hypothesis is viable or not

Increased CSF levels of total Tau in patients with subcortical cerebrovascular pathology and cognitive impairment

ABSTRACT. Cognitive impairment includes mild cognitive decline and dementia, such as Alzheimer's disease (AD) and cerebrovascular-related pathologies. Objective: To investigate the profile of AD-related CSF biomarkers in a sample of cognitively impaired and unimpaired older adults with concomitant subcortical cerebrovascular burden. Methods: Seventy-eight older adults attending an outpatient psychogeriatric clinic were enrolled. Diagnoses were based on clinical, neuropsychological, laboratory, and neuroimaging data. Participants were classified into: cognitively normal (controls, n = 30), mild cognitive impairment (MCI, n = 34), and dementia (AD, n = 14). All subjects were submitted to CSF analyses for determination of amyloid-beta (Aβ1-42), total tau (t-tau), phosphorylated tau (p-tau) and Aβ1-42/p-tau ratio according to the Luminex method. MRI was performed in all individuals, and was scored independently by two experts according to Fazekas scale. Statistical analyses were conducted with the aid of general linear model procedures, and the Chi-squared test. Results: T-tau levels were significantly associated with subcortical lesion pattern when Fazekas was considered as a group factor. CSF biomarkers were not associated with MCI, AD, or controls when considered separately. There was a tendency for reduction in CSF Aβ1-42 together with increasing Fazekas scores, but without statistical significance. Comparisons of Aβ1-42 and t-tau with each clinical group or with each neuroimaging pattern did not reach statistical differences. Likewise, Fazekas scores had no impact on CAMCOG scores. Conclusion: We found a significant association between t-tau levels and subcortical lesions when all Fazekas classifications were considered as a single group; comparisons of Fazekas subgroups and CSF biomarkers did not reach significance