Efeitos antiangiogênicos in vivo convalidam a atividade antineoplásica potencial do metiljasmonato

Molecular plant components have long been aimed at the angiogenesis and anti-angiogenesis pathways, and have been tested as sources for antineoplasic drugs with promising success. The present work deals with the anti-angiogenic effects of Methyl Jasmonate. Jasmonate derivatives were demonstrated to selectively damage the mitochondria of cancer cells. In vitro, 1-10 mM Methyl Jasmonate induced the cell death of the human umbilical vein endothelial cells (HUVEC) and the Murine melanoma cells (B16F10), while micromolar concentrations were ineffective. In vivo, comparable concentrations were toxic and reduced the vessel density of the Chorioallantoic Membrane of the Chicken Embryo (CAM). However, 1-10 µM concentrations produced a complex effect. There was increased capillary budding, but the new vessels were leakier and less organised than corresponding controls. It is suggested that not only direct toxicity, but also the drug effects upon angiogenesis are relevant to the antineoplasic effects of Methyl Jasmonate.Moléculas de origem vegetal são, há muito, conhecidas como substâncias ativas sobre as vias de angiogênese e antiangiogênese e foram testadas como fonte de drogas antineoplásicas com sucesso promissor. Este trabalho trata dos efeitos antiangiogênicos do Metiljasmonato, um protótipo da família dos derivados do ácido jasmônico, que danificam seletivamente a mitocôndria de células neoplásicas. In vitro, metiljasmonato 1-10 mM promoveu a morte celular de células endoteliais humanas de cordão umbilical (HUVEC) e de melanoma murino (B16F10); concentrações micromolares foram inócuas. In vivo, concentrações equivalentes foram tóxicas e reduziram a densidade de vasos em membranas corioalantoicas de embrião de galinha (CAM). Entretanto, concentrações entre 1-10 µM produziram um efeito complexo. Ocorreu aumento no brotamento capilar, mas os novos vasos apresentaram-se frágeis e menos organizados que os controles correspondentes. Sugere-se que, além da toxicidade direta contra as células tumorais, a ação do metiljasmonato sobre a angiogênese seja relevante para seu efeito antineoplásico

Development of Cork Biocomposites Enriched with Chitosan Targeting Antibacterial and Antifouling Properties

The demand for bio-based and safer composite materials is increasing due to the growth of the industry, human population, and environmental concerns. In this framework, sustainable and safer cork-polymer composites (CPC), based on green low-density polyethylene (LDPE) were developed using melt-based technologies. Chitosan and polyethylene-graft-maleic anhydride (PE-g-MA) were employed to enhance the CPC's properties. The morphology, wettability, mechanical, thermal, and antibacterial properties of the CPC against Pseudomonas putida (P. putida) and Staphylococcus aureus (S. aureus) were examined. The CPC showed improved stiffness when compared with that of the LDPE matrix, preferably when combined with chitosan and PE-g-MA (5 wt. %), reinforcing the stiffness (58.8%) and the strength (66.7%). Chitosan also increased the composite stiffness and strength, as well as reduced the surface hydrophilicity. The CPCs' antibacterial activity revealed that cork significantly reduces the biofilm on the polymer matrix. The highest biofilm reduction was found with CPC containing cork and 5 wt. % chitosan for both P. putida (54% reduction) and S. aureus (36% reduction), confirming their potential to extend the lifespan of products for packaging and healthcare, among other applications. This work leads to the understanding of the factors that influence biofilm formation in cork composites and provides a strategy to reinforce their behavior using chitosan

What is the impact of population ageing on the future provision of end-of-life care? Population-based projections of place of death.

BACKGROUND: Population ageing represents a global challenge for future end-of-life care. Given new trends in place of death, it is vital to examine where the rising number of deaths will occur in future years and implications for health and social care. AIM: To project where people will die from 2015 to 2040 across all care settings in England and Wales. DESIGN: Population-based trend analysis and projections using simple linear modelling. Age- and gender-specific proportions of deaths in hospital, care home, home, hospice and 'other' were applied to numbers of expected future deaths. Setting/population: All deaths (2004-2014) from death registration data and predicted deaths (2015-2040) from official population forecasts in England and Wales. RESULTS: Annual deaths are projected to increase from 501,424 in 2014 (38.8% aged 85 years and over) to 635,814 in 2040 (53.6% aged 85 years and over). Between 2004 and 2014, proportions of home and care home deaths increased (18.3%-22.9% and 16.7%- 21.2%) while hospital deaths declined (57.9%-48.1%). If current trends continue, numbers of deaths in care homes and homes will increase by 108.1% and 88.6%, with care home the most common place of death by 2040. If care home capacity does not expand and additional deaths occur in hospital, hospital deaths will start rising by 2023. CONCLUSION: To sustain current trends, end-of-life care provision in care homes and the community needs to double by 2040. An infrastructure across care settings that supports rising annual deaths is urgently needed; otherwise, hospital deaths will increase.The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work is independent research funded by Cicely Saunders International and The Atlantic Philanthropies (grant number 24610). This research was supported by the Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South London, which is part of the National Institute for Health Research (NIHR), and is a partnership between King’s Health Partners, St. George’s, University London and St George’s Healthcare NHS Trust. I.J.H. is an NIHR Senior Investigator. C.J.E. is funded by a Health Education England (HEE)/NIHR Senior Clinical Lectureship. B.G. is funded by the Calouste Gulbenkian Foundation. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health

Approximated stability analysis of bi-modal hybrid co-simulation scenarios

This is an accepted manuscript of an article published by Springer in: Cerone A., Roveri M. (eds) Software Engineering and Formal Methods. SEFM 2017. Lecture Notes in Computer Science, vol 10729, available online at: https://doi.org/10.1007/978-3-319-74781-1_24 The accepted version of the publication may differ from the final published version. For information on re-use, please refer to the publisher’s terms and conditions.Co-simulation is a technique to orchestrate multiple simulators in order to approximate the behavior of a coupled system as a whole. Simulators execute in a lockstep fashion, each exchanging inputs and output data points with the other simulators at pre-accorded times. In the context of systems with a physical and a cyber part, the communication frequency with which the simulators of each part communicate can have a negative impact in the accuracy of the global simulation results. In fact, the computed behavior can be qualitatively different, compared to the actual behavior of the original system, laying waste to potentially many hours of computation. It is therefore important to develop methods that answer whether a given communication frequency guarantees trustworthy co-simulation results. In this paper, we take a small step in that direction. We develop a technique to approximate the lowest frequency for which a particular set of simulation tools can exchange values in a co-simulation and obtain results that can be trusted.Published versio

Leishmania Parasites Drive PD-L1 Expression in Mice and Human Neutrophils With Suppressor Capacity

Neutrophils play an important role in the outcome of leishmaniasis, contributing either to exacerbating or controlling the progression of infection, a dual effect whose underlying mechanisms are not clear. We recently reported that CD4+ and CD8+ T cells, and dendritic cells of Leishmania amazonensis-infected mice present high expression of PD-1 and PD-L1, respectively. Given that the PD-1/PD-L1 interaction may promote cellular dysfunction, and that neutrophils could interact with T cells during infection, we investigated here the levels of PD-L1 in neutrophils exposed to Leishmania parasites. We found that both, promastigotes and amastigotes of L. amazonensis induced the expression of PD-L1 in the human and murine neutrophils that internalized these parasites in vitro. PD-L1-expressing neutrophils were also observed in the ear lesions and the draining lymph nodes of L. amazonensis-infected mice, assessed through cell cytometry and intravital microscopy. Moreover, expression of PD-L1 progressively increased in neutrophils from ear lesions as the disease evolved to the chronic phase. Co-culture of infected neutrophils with in vitro activated CD8+ T cells inhibits IFN-γ production by a mechanism dependent on PD-1 and PD-L1. Importantly, we demonstrated that in vitro infection of human neutrophils by L braziliensis induced PD-L1+ expression and also PD-L1+ neutrophils were detected in the lesions of patients with cutaneous leishmaniasis. Taken together, these findings suggest that the Leishmania parasite increases the expression of PD-L1 in neutrophils with suppressor capacity, which could favor the parasite survival through impairing the immune response

Reflexões sobre a maternidade : um estudo exploratório com mulheres acima de 40 anos

Este artigo apresenta um estudo exploratório-descritivo de caráter qualitativo que busca conhecer como o conceito de maternidade é compreendido e vivenciado pelas mulheres, destacando vivências de libertação e cativeiro, segundo a Teoria do Espaço Consciente de Krista K. Burlae (2004). Através da Entrevista Biográfica proposta por Connie J. G. Gersick & Kathy. E. Kram (2002), seis mulheres acima de 40 anos relataram sobre sua vida no passado, presente e futuro. A análise dos resultados deu-se a partir da Análise do Discurso, proposto por Rosalind Gill (2002), baseando-se nos pressupostos epistemológicos dos estudos de gênero, perspectiva feminista, teoria do Desenvolvimento de Daniel Levinson (1996) e visão sistêmica. Os resultados trazem que as concepções e as vivências de maternidade são diversas, complexas e apresentam diferentes implicações na vida das mulheres. Perspectivas mais conservadoras interagem com visões mais críticas sobre as relações mãe-mulher.En este artículo se presenta un estudio cualitativo, exploratorio-descriptivo que busca entender cómo entienden y experimentan las mujeres el concepto de la maternidad, destacando las experiencias de la liberación y de la esclavitud, de acuerdo con la Teoría del Espacio Consciente Burlae (2004). A través de entrevista biográfica propuesto por Gersick y Kram (2002), 6 mujeres de más de 40 informaron sobre su vida en el pasado, presente y futuro. El análisis se llevó a cabo del análisis del discurso, propuesto por Gill (2002), sobre la base de los supuestos epistemológicos de los estudios de género, perspectiva feminista y vista sistémico. Los resultados traen a las concepciones y experiencias de la maternidad son diversos, complejos y tienen diferentes implicaciones para la vida de las mujeres. Perspectivas más conservadores interactúan con puntos de vista más críticos en las relaciones madre-mujer.This article presents an exploratory descriptive study of qualitative character, who seeks to understand how the notion of maternity is perceived and experienced by women, emphasizing experiences of liberation and captivity, as per Krista K. Burlae's Theory of Mindful Space (2004). Via the biographical interview proposed by Connie J. G. Gersick & Kathy. E. Kram (2002), six women over the age of 40 described their lives in the past, present and future. The analysis of results was conducted using the Discourse Analysis proposed by Rosalind Gill (2002), basing itself on epistemological assumptions from studies of gender, feminine perspective, Daniel Lenvinson's Development Theory (1996) and systemic vision. The results show that the conceptions and experiences of maternity are diverse and complex, presenting different implications in the lives of women. More conservative perspectives interact with more critical views of the mother-woman relationships

Association of CD40 Gene Polymorphisms with Sporadic Breast Cancer in Chinese Han Women of Northeast China

BACKGROUND: Breast cancer is a polygenetic disorder with a complex inheritance pattern. Single nucleotide polymorphisms (SNPs), the most common genetic variations, influence not only phenotypic traits, but also interindividual predisposition to disease, treatment outcomes with drugs and disease prognosis. The co-stimulatory molecule CD40 plays a prominent role in immune regulation and homeostasis. Accumulating evidence suggests that CD40 contributes to the pathogenesis of cancer. Here, we set out to test the association between polymorphisms in the CD40 gene and breast carcinogenesis and tumor pathology. METHODOLOGY AND PRINCIPAL FINDINGS: Four SNPs (rs1800686, rs1883832, rs4810485 and rs3765459) were genotyped by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method in a case-control study including 591 breast cancer patients and 600 age-matched healthy controls. Differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed by the Chi-square test for trends. Our preliminary data showed a statistically significant association between the four CD40 gene SNPs and sporadic breast cancer risk (additive P = 0.0223, 0.0012, 0.0013 and 0.0279, respectively). A strong association was also found using the dominant, recessive and homozygote comparison genetic models. In the clinical features analysis, significant associations were observed between CD40 SNPs and lymph node metastasis, human epidermal growth factor receptor 2 (C-erbB2), estrogen receptor (ER), progesterone receptor (PR) and tumor protein 53 (P53) statuses. In addition, our haplotype analysis indicated that the haplotype C(rs1883832)G(rs4810485), which was located within the only linkage disequilibrium (LD) block identified, was a protective haplotype for breast cancer, whereas T(rs1883832)T(rs4810485) increased the risk in the studied population, even after correcting the P value for multiple testing (P = 0.0337 and 0.0430, respectively). CONCLUSIONS AND SIGNIFICANCE: Our findings primarily show that CD40 gene polymorphisms contribute to sporadic breast cancer risk and have a significant association with clinicopathological features among Chinese Han women from the Heilongjiang Province