tackling malaria

Malaria is an infectious disease that affects over 216 million people worldwide, killing over 445,000 patients annually. Due to the constant emergence of parasitic resistance to the current antimalarial drugs, the discovery of new drug candidates is a major global health priority. Aiming to make the drug discovery processes faster and less expensive, we developed binary and continuous Quantitative Structure-Activity Relationships (QSAR) models implementing deep learning for predicting antiplasmodial activity and cytotoxicity of untested compounds. Then, we applied the best models for a virtual screening of a large database of chemical compounds. The top computational predictions were evaluated experimentally against asexual blood stages of both sensitive and multi-drug-resistant Plasmodium falciparum strains. Among them, two compounds, LabMol-149 and LabMol-152, showed potent antiplasmodial activity at low nanomolar concentrations (EC50 <500 nM) and low cytotoxicity in mammalian cells. Therefore, the computational approach employing deep learning developed here allowed us to discover two new families of potential next generation antimalarial agents, which are in compliance with the guidelines and criteria for antimalarial target candidates.publishersversionpublishe

Concepções alternativas dos Alunos de Ensino Médio sobre ácidos e bases

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Synaptic Homeostasis and Restructuring across the Sleep-Wake Cycle

Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK) showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS) followed by a rebound during rapid-eye-movement sleep (REM). The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes synaptic restructuring.: Support obtained from Financiadora de Estudos e Projetos (http://www.finep.gov.br/) Grant # 01.06.1092.00 to SR; Conselho Nacional de Desenvolvimento Científico e Tecnológico (http:// www.cnpq.br/): Grants 481506/2007-1, 481351/2011- 6 and 306604/2012-4 to SR, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (http://www.capes.gov.br/) and Ciencias sem Fronteiras (http://www.cienciasemfronteiras.gov.br/ web/csf/home) to AT and CRC; Fundação de Amparo à Pesquisa do Rio Grande do Norte (http://wwwfapern.rn.gov.br/): Grant Pronem 003/2011 to SR; Fundação de Amparo à Pesquisa do Estado de São Paulo (http://www.fapesp.br/): Grant #2013/ 07699-0 - Center for Neuromathematics to SR; CMP and VRC supported by post-doctoral fellowships from Fundação de Amparo à Pesquisa do Rio Grande do Norte /CNPq. Additional support obtained from the Federal University of Rio Grande do Norte (www.ufrn. br); Ministry of Science, Technology and Innovation (http://www.mcti.gov.br/); Associação Alberto Santos Dumont de Apoio à Pesquisa (http://natalneuro.com/ associacao/index.asp); Pew Latin American Fellows Program (http://www.pewtrusts.org/en/projects/pewlatin-american-fellows/) to SR; Informatics Department of the Instituto Federal de Educação, Ciência e Tecnologia do Rio Grande do Norte (http:// portal.ifrn.edu.br/) to WB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Petróleo: O ensino de Química Orgânica voltado para o cotidiano

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The concept of anorexia of aging in late life depression:A cross-sectional analysis of a cohort study.

INTRODUCTION: Anorexia of aging (AA) is classically associated with depression. However, robust evidence is lacking regarding general clinic populations. Our aim was to evaluate the association between AA and major depressive disorder (MDD) in geriatric outpatients from a middle-income country. METHODS: We conducted a cross-sectional analysis of a cohort study. MDD diagnosis was assessed with a psychiatric interview (SCID-5-CV) according to DSM-5 criteria. Depressive symptomatology was assessed by a 15-items Geriatric Depression Scale (GDS) and the PHQ-9 questionnaire. Appetite was measured with the Simple Nutrition Appetite Questionnaire (SNAQ), whereas AA was defined as a SNAQ score ≤13 points). Linear and logistic regression analysis adjusted for potential confounders were applied to assess the association between depressive symptomatology, MDD and AA. RESULTS: Of the total 339 participants, MDD was present in 65. AA was more frequent in patients with MDD compared to non-depressed patients (30.7 versus 7.7%; p<0.001). The SNAQ score was lower in depressed patients (14.5 vs. 16.6, p<0.001). Adjusted for confounding, linear and logistic regression showed a significant association between the GDS score, PHQ-9 score and MDD with the SNAQ score (p<0.001) and cut-off representing AA (p<0.001), respectively. Moreover, MDD and AA interacted significantly with their association with weight loss (p<0.001). CONCLUSIONS: Depression scales (even without somatic complaints) and MDD were associated with AA in geriatric outpatients. AA is associated with weight loss in MDD. Prospective studies should expand these findings

Ações lúdicas como ferramenta para prevenção da obesidade do pré- escolar: relato de experiência

Doi: 10.5902/2179769211338 Objective: To report the experience of a health education activity carried out with children using playful actions as tools for obesity prevention. Method: it is a descriptive study in the form of an experience report, focused on the health of school children. The study was held in a municipal educational institution in northeastern Brazil, in March 2013. Results: It was possible to perceive that playful actions arouse children's interest, which favors the involvement in activities, the interaction between them and the teacher, and thus a better understanding of the theme. Thus, it enables the integration of the actions of prevention in health care with the school context, sensitizing children about their reality, relevant premise to the promotion of health. Final Considerations: The experience leads to the understanding that playful tools are constructive mechanisms of understanding on any theme.Objetivo: Presentar la experiencia de una actividad de educación sanitaria realizada con niños, mediante acciones lúdicas como herramienta para la prevención de obesidad. Método: se trata de un estudio descriptivo, del tipo relato de experiencia, con enfoque en la salud del preeescolar, realizada en una institución municipal de educación, en el nordeste de Brasil, en marzo de 2013. Resultados: Se percibió que acciones lúdicas despiertan el interés de los niños, lo que favorece la participación en las actividades, la interacción entre ellos y con el profesor, y así, una mejor comprensión del tema tratado. De esta forma, permite la integración de las acciones de prevención en salud con el contexto escolar, sensibilizando al niño acerca de su realidad, premisa relevante para la promoción de la salud. Consideraciones finales: La experiencia lleva a entender que las herramientas lúdicas son mecanismos constructivos de entendimiento sobre cualquier tema.Doi: 10.5902/2179769211338Objetivo: relatar a experiência de uma atividade de educação em saúde realizada com crianças, utilizando-se ações lúdicas como ferramenta para prevenção da obesidade. Método: trata-se de um estudo descritivo, do tipo relato de experiência,com foco na saúde do escolar, realizado em uma instituição municipal de ensino, no Nordeste do Brasil, no mês de março de 2013. Resultados: foi possível perceber que as ações lúdicas despertam o interesse das crianças, o que favorece o envolvimento nas atividades, a interação entre elas e com o professor, e assim, uma melhor apreensão da temática abordada. Desta forma, possibilita uma integração das ações de prevenção em saúde com o contexto escolar, sensibilizando a criança acerca da sua realidade, premissa relevante para promoção à saúde. Considerações Finais: a vivência leva a entender que as ferramentas lúdicas são mecanismos construtivos de entendimento diante de qualquer temática abordada

Ações lúdicas como ferramenta para prevenção da obesidade do pré- escolar: relato de experiência

Doi: 10.5902/2179769211338 Objective: To report the experience of a health education activity carried out with children using playful actions as tools for obesity prevention. Method: it is a descriptive study in the form of an experience report, focused on the health of school children. The study was held in a municipal educational institution in northeastern Brazil, in March 2013. Results: It was possible to perceive that playful actions arouse children's interest, which favors the involvement in activities, the interaction between them and the teacher, and thus a better understanding of the theme. Thus, it enables the integration of the actions of prevention in health care with the school context, sensitizing children about their reality, relevant premise to the promotion of health. Final Considerations: The experience leads to the understanding that playful tools are constructive mechanisms of understanding on any theme.Objetivo: Presentar la experiencia de una actividad de educación sanitaria realizada con niños, mediante acciones lúdicas como herramienta para la prevención de obesidad. Método: se trata de un estudio descriptivo, del tipo relato de experiencia, con enfoque en la salud del preeescolar, realizada en una institución municipal de educación, en el nordeste de Brasil, en marzo de 2013. Resultados: Se percibió que acciones lúdicas despiertan el interés de los niños, lo que favorece la participación en las actividades, la interacción entre ellos y con el profesor, y así, una mejor comprensión del tema tratado. De esta forma, permite la integración de las acciones de prevención en salud con el contexto escolar, sensibilizando al niño acerca de su realidad, premisa relevante para la promoción de la salud. Consideraciones finales: La experiencia lleva a entender que las herramientas lúdicas son mecanismos constructivos de entendimiento sobre cualquier tema.Doi: 10.5902/2179769211338Objetivo: relatar a experiência de uma atividade de educação em saúde realizada com crianças, utilizando-se ações lúdicas como ferramenta para prevenção da obesidade. Método: trata-se de um estudo descritivo, do tipo relato de experiência,com foco na saúde do escolar, realizado em uma instituição municipal de ensino, no Nordeste do Brasil, no mês de março de 2013. Resultados: foi possível perceber que as ações lúdicas despertam o interesse das crianças, o que favorece o envolvimento nas atividades, a interação entre elas e com o professor, e assim, uma melhor apreensão da temática abordada. Desta forma, possibilita uma integração das ações de prevenção em saúde com o contexto escolar, sensibilizando a criança acerca da sua realidade, premissa relevante para promoção à saúde. Considerações Finais: a vivência leva a entender que as ferramentas lúdicas são mecanismos construtivos de entendimento diante de qualquer temática abordada

Silver nanoparticles-composing alginate/gelatine hydrogel improves wound healing in vivo

Polymer hydrogels have been suggested as dressing materials for the treatment of cutaneous wounds and tissue revitalization. In this work, we report the development of a hydrogel composed of natural polymers (sodium alginate and gelatin) and silver nanoparticles (AgNPs) with recognized antimicrobial activity for healing cutaneous lesions. For the development of the hydrogel, different ratios of sodium alginate and gelatin have been tested, while different concentrations of AgNO3 precursor (1.0, 2.0, and 4.0 mM) were assayed for the production of AgNPs. The obtained AgNPs exhibited a characteristic peak between 430450 nm in the ultraviolet-visible (UVVis) spectrum suggesting a spheroidal form, which was confirmed by Transmission Electron Microscopy (TEM). Fourier Transform Infra-red (FTIR) analysis suggested the formation of strong intermolecular interactions as hydrogen bonds and electrostatic attractions between polymers, showing bands at 2920, 2852, 1500, and 1640 cm1. Significant bactericidal activity was observed for the hydrogel, with a Minimum Inhibitory Concentration (MIC) of 0.50 µg/mL against Pseudomonas aeruginosa and 53.0 µg/mL against Staphylococcus aureus. AgNPs were shown to be non-cytotoxic against fibroblast cells. The in vivo studies in female Wister rats confirmed the capacity of the AgNP-loaded hydrogels to reduce the wound size compared to uncoated injuries promoting histological changes in the healing tissue over the time course of wound healing, as in earlier development and maturation of granulation tissue. The developed hydrogel with AgNPs has healing potential for clinical applications.This research received funding from the Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Sergipe (FAPITEC), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, #443238/2014-6, #470388/2014-5), and from the Portuguese Science and Technology Foundation (FCT) projects M-ERA-NET/0004/2015 (PAIRED) and UIDB/04469/2020 (strategic fund).info:eu-repo/semantics/publishedVersio

Correction: Diniz et al. Silver Nanoparticles-Composing Alginate/Gelatine Hydrogel Improves Wound Healing In Vivo. Nanomaterials 2020, 10, 390

In the original publication, there was a mistake in Figure 6 as published [...]info:eu-repo/semantics/publishedVersio