Neuronal network model of interictal and recurrent ictal activity

This is the final version of the article. Available from American Physical Society via the DOI in this record.We propose a neuronal network model which undergoes a saddle node on an invariant circle bifurcation as the mechanism of the transition from the interictal to the ictal (seizure) state. In the vicinity of this transition, the model captures important dynamical features of both interictal and ictal states. We study the nature of interictal spikes and early warnings of the transition predicted by this model. We further demonstrate that recurrent seizures emerge due to the interaction between two networks.This work was partially supported by FET IP Project MULTIPLEX 317532. A.V.G. is grateful to LA I3N for Grant No. PEST UID/CTM/50025/2013. M.A.L. acknowledges the financial support of the Medical Research Council (MRC) via Grant No. MR/K013998/01. K.E.L. was supported by the Department of Anesthesiology at the University of Michigan and the National Institutes of Health, Grant No. RO1 GM098578

OS CONCEITOS DE MORTE E MORRER NA ENFERMAGEM E AS RELAÇÕES COM O ETHOS DO CUIDADO

 In this study, we analyze the influence of the concepts of death and dying of the nursing staff on the practice of care given in some areas of hospitalization. The data was produced by from a questionnaire containing open ended questions. The subjects of the investigation nurses, technicians and nurses’ auxiliaries who act in the sectors of the medical clinic, the center of intensive care and emergency in public hospitals in the city of Rio de Janeiro, Brazil. After the analysis of the data, two categories emerged: the INFLUENCE and CONFLICT of the concepts about death in the CHOICE and DYNAMICS of ethos of care and death: BEGINNING a new life and END of everything. The results point that the concepts of do not change among the nursing professionals who work in the units studied, and also it seems not to have influenced them when they chose their ethos of care giving. It draws attention that professionals in these units relate a conflict when thinking of death and facing it in their daily care.En este estudio analizamos la influencia de los conceptos de muerte y morir del equipo de Enfermería sobre las prácticas de cuidados en algunos espacios de internación hospitalaria. Los datos se produjeron a partir de la aplicación de un formulario conteniendo preguntas abiertas, siendo los sujetos de la investigación Enfermeros, Técnicos y Auxiliares de Enfermería que actúan en los sectores de Clínica Médica, Unidad de Terapia Intensiva y Emergencia de hospitales de la red pública localizados en el municipio de Rio de Janeiro. Después del análisis de los datos, emergieron dos categorías: la INFLUENCIA y el CONFLICTO de los conceptos acerca de la muerte en la ELECCIÓN y en la DINÁMICA de del ethos del cuidado, y Muerte: INICIO de una nueva vida y FIN de todo.  Los resultados apuntan que los conceptos de muerte no se alteran entre los profesionales de enfermería que actúan en esas unidades investigadas y también parece no haberles influenciado cuando eligieron sus ethos para cuidar. Llama la atención que los profesionales entrevistados relataron conflicto en el pensar la muerte y en encararla en su cotidianidad de cuidar.Neste estudo, analisamos a influência dos conceitos de morte e morrer da equipe de Enfermagem sobre as práticas de cuidar em alguns espaços de internação hospitalar. Os dados foram produzidos a partir da aplicação de um formulário contendo perguntas abertas, sendo os sujeitos da pesquisa, Enfermeiros, Técnicos e Auxiliares de Enfermagem que atuam nos setores de Clínica Médica, Unidade de Terapia Intensiva e Emergência de hospitais da rede pública localizados no município do Rio de Janeiro. Após a análise dos dados, emergiram duas categorias: A INFLUÊNCIA e o CONFLITO dos conceitos acerca da morte na ESCOLHA e na DINAMICA do ethos do cuidado; e Morte: INICIO de uma nova vida e FIM de tudo. Os resultados apontam que os conceitos de morte não se alteram entre os profissionais de enfermagem que atuam nessas unidades pesquisadas e também parece não ter os influenciado quando escolheram os seus ethos para cuidar. Chama atenção que os profissionais entrevistados relataram conflito no pensar a morte, e de encará-la em seu cotidiano de cuidar.

Paradox of life among survivors of bladder cancer and treatments* Paradoxo da vida entre sobreviventes do câncer de bexiga e tratamentos Paradoja de la vida entre supervivientes del cáncer de vejiga y tratamientos

abstract Objective: To interpret the meanings attributed to the experience of bladder cancer among survivors in therapeutic follow-up. Method: Qualitative methodological approach, based on medical anthropology and narrative methodology. After approval by the research ethics committee of a public university hospital, data were collected from January 2014 to February 2015, by means of recorded semi-structured interviews, direct observation and field journal entries on daily immersion with a group of six men and six women, aged between 57 and 82 years, in therapeutic follow-up. Narratives were analyzed by means of inductive thematic analysis. Results: The meanings revealed difficulties with the processes of disease and treatment, such as breakdown of normal life, uncertainty about the future due to possible recurrence of the disease, difficulty with continuity of care and emotional control, relating it to conflicting ways of understanding the present life. Thus, the meaning of this narrative synthesis is paradox. Conclusion: Interpretation of the meaning of experience with bladder cancer among patients provides nurses with a comprehensive view of care, which encompasses biological, psychological and social dimensions, and thereby systematizes humanized care. descriPtOr

TERTp mutations and p53 expression in head and neck cutaneous basal cell carcinomas with different aggressive features

Cutaneous basal cell carcinoma (cBCC) is an economic burden to health services, due to its great morbidity and increasing incidence in old people. Infiltrative cBCCs and cBCCs with micronodular pattern are considered as more aggressive. The role of p53 expression and TERTp mutation on cBCC behavior remains to be clarified. We aimed to assess TERTp mutations and p53 expression in relation to the cBCC histological subtype in a cohort of patients referred to an ENT Department of a tertiary Hospital of Northern Portugal. We performed a retrospective clinicopathological and histological review of the head and neck cBCCs followed-up at the otorhinolaryngology department of Trás-os-Montes e Alto Douro hospital (January 2007–June 2018). We assessed TERTp mutations in 142 cBCCs and p53 protein expression, through immunohistochemistry, in 157 cBCCs. We detected TERTp mutations in 43.7% of cBCCs and p53 overexpression in 60.5% of cBCCs. We spotted association of p53 overexpression and TERTp mutation with necrosis. In the infitrative-growth pattern cBCCs, there was no significant association with the clinical and histological features evaluated, except for necrosis. In the indolent-growth cBCCs, we identified a significant association of TERTp mutation status with female sex, necrosis, multiple cBCCs, and p53 positive expression. Our results suggest that TERTp mutation may be useful to identify more aggressive features in the indolent-growth pattern cBCCs (nodular and superficial subtypes). Further studies with larger cohorts are warranted to clarify the relevance of TERTp mutation in cBCCs.This study was supported by FCT, the Portuguese Foundation for Science and Technology through a Ph.D. Grant to SM (SFRH/BD/137802/2018). This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnolo-gia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). Additional funding by the European Regional Development Fund (ERDF) through the Operational Programme for Competitiveness and Internationalization—COMPETE2020, and Portuguese national funds via FCT, under project POCI-01-0145-FEDER-016390: CANCEL STEM and from the FCT, under the project POCI-01-0145-FEDER-031438: The other faces of telomerase: Looking beyond tumour immortalization (PDTC/MED-ONC/31438/2017)

Using zeta-potential measurements to quantify peptide partition to lipid membranes

© The Author(s) 2011. This article is published with open access at Springerlink.com.Open Access: This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.Many cellular phenomena occur on the biomembranes. There are plenty of molecules (natural or xenobiotics) that interact directly or partially with the cell membrane. Biomolecules, such as several peptides (e.g., antimicrobial peptides) and proteins, exert their effects at the cell membrane level. This feature makes necessary investigating their interactions with lipids to clarify their mechanisms of action and side effects necessary. The determination of molecular lipid/water partition constants (Kp) is frequently used to quantify the extension of the interaction. The determination of this parameter has been achieved by using different methodologies, such as UV-Vis absorption spectrophotometry, fluorescence spectroscopy and ζ-potential measurements. In this work, we derived and tested a mathematical model to determine the Kp from ζ-potential data. The values obtained with this method were compared with those obtained by fluorescence spectroscopy, which is a regular technique used to quantify the interaction of intrinsically fluorescent peptides with selected biomembrane model systems. Two antimicrobial peptides (BP100 and pepR) were evaluated by this new method. The results obtained by this new methodology show that ζ-potential is a powerful technique to quantify peptide/lipid interactions of a wide variety of charged molecules, overcoming some of the limitations inherent to other techniques, such as the need for fluorescent labeling.This work was partially supported by project PTDC/QUI/ 69937/2006 from Fundação para a Ciência e Tecnologia-Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), and by Fundação Calouste Gulbenkian (Portugal). JMF and MMD also thank FCT-MCTES for grants IMM/BT/37-2010 and SFRH/BD/41750/2007, respectively

In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa

<p>Abstract</p> <p>Background</p> <p>To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. <it>Caesalpinia pluviosa</it>, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity.</p> <p>Methods</p> <p>Crude extract (CE) was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested <it>in vitro </it>against chloroquine-sensitive (3D7) and -resistant (S20) strains of <it>Plasmodium falciparum</it> and <it>in vivo </it>in <it>Plasmodium chabaudi</it>-infected mice. <it>In vitro </it>interaction with artesunate and the active <it>C. pluviosa </it>fractions was assessed, and mass spectrometry analyses were conducted.</p> <p>Results</p> <p>At non-toxic concentrations, the 100% ethanolic (F4) and 50% methanolic (F5) fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to <it>m/z </it>303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of <it>m/z </it>137 and 153.</p> <p>Conclusions</p> <p>The findings show that the F4 fraction of <it>C. pluviosa </it>exhibits anti-malarial activity <it>in vitro </it>at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained <it>in vivo </it>after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.</p

The Inviscid Limit and Boundary Layers for Navier-Stokes Flows

The validity of the vanishing viscosity limit, that is, whether solutions of the Navier-Stokes equations modeling viscous incompressible flows converge to solutions of the Euler equations modeling inviscid incompressible flows as viscosity approaches zero, is one of the most fundamental issues in mathematical fluid mechanics. The problem is classified into two categories: the case when the physical boundary is absent, and the case when the physical boundary is present and the effect of the boundary layer becomes significant. The aim of this article is to review recent progress on the mathematical analysis of this problem in each category.Comment: To appear in "Handbook of Mathematical Analysis in Mechanics of Viscous Fluids", Y. Giga and A. Novotn\'y Ed., Springer. The final publication is available at http://www.springerlink.co

Diets containing sea cucumber (Isostichopus badionotus) meals are hypocholesterolemic in young rats

Peer reviewedPublisher PD

Linking Proteins to Signaling Pathways for Experiment Design and Evaluation

Biomedical experimental work often focuses on altering the functions of selected proteins. These changes can hit signaling pathways, and can therefore unexpectedly and non-specifically affect cellular processes. We propose PathwayLinker, an online tool that can provide a first estimate of the possible signaling effects of such changes, e.g., drug or microRNA treatments. PathwayLinker minimizes the users' efforts by integrating protein-protein interaction and signaling pathway data from several sources with statistical significance tests and clear visualization. We demonstrate through three case studies that the developed tool can point out unexpected signaling bias in normal laboratory experiments and identify likely novel signaling proteins among the interactors of known drug targets. In our first case study we show that knockdown of the Caenorhabditis elegans gene cdc-25.1 (meant to avoid progeny) may globally affect the signaling system and unexpectedly bias experiments. In the second case study we evaluate the loss-of-function phenotypes of a less known C. elegans gene to predict its function. In the third case study we analyze GJA1, an anti-cancer drug target protein in human, and predict for this protein novel signaling pathway memberships, which may be sources of side effects. Compared to similar services, a major advantage of PathwayLinker is that it drastically reduces the necessary amount of manual literature searches and can be used without a computational background. PathwayLinker is available at http://PathwayLinker.org. Detailed documentation and source code are available at the website