Efficacy of Pentavalent Antimony, Amphotericin B, and Miltefosine in Leishmania amazonensis-Infected Macrophages Under Normoxic and Hypoxic Conditions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Recently, our group demonstrated that mouse lesions infected with Leishmania. a amazonensis are hypoxic. Evidence indicates the negative impact of hypoxia on the efficacy of a variety of chemotherapeutic agents against tumors, fungi,. bacteria. and malaria parasites. In the present study, comparison of the effect of antileishmanial drug's oil L. amazonensis-infected macrophages under normoxic and hypoxic Conditions was performed. We compared the effect of 5% oxygen tension with a tension of 21% oxygen on peritoneal murine macrophage cultures infected with the parasite and treated with glucantime, amphotericin B. or miltefosine. Analysis of the infection index (percentage of infected macrophages X number of amastigotes per macrophage, dose-dependent efficacy of drugs, and IC(50) values demonstrated that hypoxia conferred it small, but significant resistance to all 3 antileishmanial drugs. The present finding suggest that in vitro assays under hypoxia should not be neglected ill drug studies.94614151417Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenacao Aperfeicoamento de Pessoal de Nivel Superior. Brazil.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Improving SNR and reducing training time of classifiers in large datasets via kernel averaging

Kernel methods are of growing importance in neuroscience research. As an elegant extension of linear methods, they are able to model complex non-linear relationships. However, since the kernel matrix grows with data size, the training of classifiers is computationally demanding in large datasets. Here, a technique developed for linear classifiers is extended to kernel methods: In linearly separable data, replacing sets of instances by their averages improves signal-to-noise ratio (SNR) and reduces data size. In kernel methods, data is linearly non-separable in input space, but linearly separable in the high-dimensional feature space that kernel methods implicitly operate in. It is shown that a classifier can be efficiently trained on instances averaged in feature space by averaging entries in the kernel matrix. Using artificial and publicly available data, it is shown that kernel averaging improves classification performance substantially and reduces training time, even in non-linearly separable data

An Evolutionary Upgrade of Cognitive Load Theory: Using the Human Motor System and Collaboration to Support the Learning of Complex Cognitive Tasks

Cognitive load theory is intended to provide instructional strategies derived from experimental, cognitive load effects. Each effect is based on our knowledge of human cognitive architecture, primarily the limited capacity and duration of a human working memory. These limitations are ameliorated by changes in long-term memory associated with learning. Initially, cognitive load theory's view of human cognitive architecture was assumed to apply to all categories of information. Based on Geary's (Educational Psychologist 43, 179-195 2008; 2011) evolutionary account of educational psychology, this interpretation of human cognitive architecture requires amendment. Working memory limitations may be critical only when acquiring novel information based on culturally important knowledge that we have not specifically evolved to acquire. Cultural knowledge is known as biologically secondary information. Working memory limitations may have reduced significance when acquiring novel

Human aging and somatic point mutations in mtDNA: A comparative study of generational differences (grandparents and grandchildren)

The accumulation of somatic mutations in mtDNA is correlated with aging. In this work, we sought to identify somatic mutations in the HVS-1 region (D-loop) of mtDNA that might be associated with aging. For this, we compared 31 grandmothers (mean age: 63 ± 2.3 years) and their 62 grandchildren (mean age: 15 ± 4.1 years), the offspring of their daughters. Direct DNA sequencing showed that mutations absent in the grandchildren were detected in a presumably homoplasmic state in three grandmothers and in a heteroplasmic state in an additional 13 grandmothers; no mutations were detected in the remaining 15 grandmothers. However, cloning followed by DNA sequencing in 12 grandmothers confirmed homoplasia in only one of the three mutations previously considered to be homoplasmic and did not confirm heteroplasmy in three out of nine grandmothers found to be heteroplasmic by direct sequencing. Thus, of 12 grandmothers in whom mtDNA was analyzed by cloning, eight were heteroplasmic for mutations not detected in their grandchildren. In this study, the use of genetically related subjects allowed us to demonstrate the occurrence of age-related (> 60 years old) mutations (homoplasia and heteroplasmy). It is possible that both of these situations (homoplasia and heteroplasmy) were a long-term consequence of mitochondrial oxidative phosphorylation that can lead to the accumulation of mtDNA mutations throughout life

CONSULTA DE ENFERMAGEM NO AMBULATÓRIO DE HIV/AIDS: A PERCEPÇÃO DOS USUÁRIOS

O estudo busca analisar como a consulta de enfermagem é percebida pelos usuários de um ambulatório especializado em Vírus da Imunodeficiência Humana/Síndrome da Imunodeficiência Adquirida (HIV/AIDS) no município de Fortaleza-CE. Trata-se de um estudo exploratório e descritivo, com abordagem qualitativa. Os dados foram coletados através de entrevista semiestruturada com quinze usuários da referida instituição e analisados com o suporte da análise de conteúdo. A consulta de enfermagem foi relatada pelos usuários como um momento de aprendizado, centrado no fornecimento de informações. A confiança e o apoio emocional estabelecido pelo profissional atuam como um suporte frente aos conflitos vivenciados pelo paciente, possibilitando a construção de um novo olhar frente à doença. Acreditamos que a realização da consulta de enfermagem em uma perspectiva dialogal poderá proporcionar aos sujeitos a ressignificação dos conflitos que permeiam o seu adoecimento

Soil water-holding capacity and monodominance in Southern Amazon tropical forests

Background and aims: We explored the hypothesis that low soil water-holding capacity is the main factor driving the monodominance of Brosimum rubescens in a monodominant forest in Southern Amazonia. Tropical monodominant forests are rare ecosystems with low diversity and high dominance of a single tree species. The causes of this atypical condition are still poorly understood. Some studies have shown a relationship between monodominance and waterlogging or soil attributes, while others have concluded that edaphic factors have little or no explanatory value, but none has accounted for soil-moisture variation other than waterlogging. This study is the first to explicitly explore how low soil water-holding capacity influences the monodominance of tropical forests. Methods: We conducted in situ measurements of vertical soil moisture using electrical resistance collected over 1 year at 0–5; 35–40 and 75–80 cm depths in a B. rubescens monodominant forest and in an adjacent mixed-species forest in the Amazon-Cerrado transition zone, Brazil. Minimum leaf water potential (Ψmin) of the seven most common species, including B. rubescens, and soil water-holding capacity for both forests were determined. Results: The vertical soil moisture decay pattern was similar in both forests for all depths. However, the slightly higher water availability in the monodominant forest and Ψmin similarity between B. rubescens and nearby mixed forest species indicate that low water-availability does not cause the monodominance. Conclusions: We reject the hypothesis that monodominance of B. rubescens is primarily determined by low soil water-holding capacity, reinforcing the idea that monodominance in tropical forests is not determined by a single factor