A first new look into the interaction of Staphylococcus epidermidis biofilm-released cells with the host immune system

The widespread application of indwelling medical devices in the clinical setting, together with the remarkable ability of the commensal Staphylococcus epidermidis to adhere to these surfaces and form biofilms, has given to this bacterium the recognition of being a leading causative agent of nosocomial infections. Biofilms lifecycle is currently divided into 4 main steps: initial adhesion, accumulation, maturation and, disassembly. Biofilm disassembly, the release of the cells within the biofilm into the involving environment, is the less understood of all steps despite its involvement in the development of several serious acute infections such as endocarditis, bacteremia and pneumonia. Hence, due to its important consequences in human health and disease, the study of the cells released from S. epidermidis biofilms is crucial to create effective therapeutic strategies against these serious infections. For that reason, in order to better characterize S. epidermidis biofilm-released cells, we assessed their cell properties by determining 1) the expression of key genes involved in initial adhesion, biofilm regulation and disassembly, 2) the total protein profile, 3) the susceptibility to routinely used antibiotics for the treatment of staphylococcal infection, and 4) the adhesion ability to coated and uncoated surfaces. Additionally, 5) the interaction of these cells with the host immune system was also assessed using an intravenous mouse infection model. Planktonic and biofilm cells were also used for comparison purposes. Our results revealed that S. epidermidis biofilm-released cells share some particular features with planktonic cells, such as expression of psmβ, but at the same time share some features similar to biofilms, such as high antibiotic tolerance. Moreover, although these shared features, the cells released from the S. epidermidis biofilms produced a unique protein that is not detected in the other assessed phenotypes. Additionally, S. epidermidis biofilm-released cells elicit a different in vivo response than their planktonic counterparts, by stimulating a lower production of inflammatory chemokines KC and MCP-1, and interleukine-6 as well. Altogether, these results indicate that this particular phenotype may present some advantageous features allowing a more effective host colonization and infection spreading. Thus, the targeting of the particular properties of the biofilm-released cells could present new opportunities to more effectively prevent the pathologic events associated with dissemination of cells from a biofilm to more distant sites.This work was funded by Fundação para a Ciência e a Tecnologia (The Foundation for Science and Technology: FCT) and COMPETE (Programa Operacional Factores de Competitividade) grants PTDC/BIA-MIC/113450/2009 and FCOMP-01-0124-FEDER-014309. AF and VC were funded by FCT fellowship SFRH/BD/62359/2009 and SFRH/BD/78235/2011, respectively

Biomedical Cyber-Physical Systems in the Light of Database as a Service (DBaaS) Paradigm

Background: A database (DB) to store indexed information about drug delivery, test, and their temporal behavior is paramount in new Biomedical Cyber-Physical Systems (BCPSs). The term Database as a Service (DBaaS) means that a corporation delivers the hardware, software, and other infrastructure required by companies to operate their databases according to their demands instead of keeping an internal data warehouse. Methods: BCPSs attributes are presented and discussed.  One needs to retrieve detailed knowledge reliably to make adequate healthcare treatment decisions. Furthermore, these DBs store, organize, manipulate, and retrieve the necessary data from an ocean of Big Data (BD) associated processes. There are Search Query Language (SQL), and NoSQL DBs.  Results: This work investigates how to retrieve biomedical-related knowledge reliably to make adequate healthcare treatment decisions. Furthermore, Biomedical DBaaSs store, organize, manipulate, and retrieve the necessary data from an ocean of Big Data (BD) associated processes. Conclusion: A NoSQL DB allows more flexibility with changes while the BCPSs are running, which allows for queries and data handling according to the context and situation. A DBaaS must be adaptive and permit the DB management within an extensive variety of distinctive sources, modalities, dimensionalities, and data handling according to conventional ways

A Pyranoxanthone as a potent antimitotic and sensitizer of cancer cells to low doses of Paclitaxel

Microtubule-targeting agents (MTAs) remain a gold standard for the treatment of several cancer types. By interfering with microtubules dynamic, MTAs induce a mitotic arrest followed by cell death. This antimitotic activity of MTAs is dependent on the spindle assembly checkpoint (SAC), which monitors the integrity of the mitotic spindle and proper chromosome attachments to microtubules in order to ensure accurate chromosome segregation and timely anaphase onset. However, the cytotoxic activity of MTAs is restrained by drug resistance and/or toxicities, and had motivated the search for new compounds and/or alternative therapeutic strategies. Here, we describe the synthesis and mechanism of action of the xanthone derivative pyranoxanthone 2 that exhibits a potent anti-growth activity against cancer cells. We found that cancer cells treated with the pyranoxanthone 2 exhibited persistent defects in chromosome congression during mitosis that were not corrected over time, which induced a prolonged SAC-dependent mitotic arrest followed by massive apoptosis. Importantly, pyranoxanthone 2 was able to potentiate apoptosis of cancer cells treated with nanomolar concentrations of paclitaxel. Our data identified the potential of the pyranoxanthone 2 as a new potent antimitotic with promising antitumor potential, either alone or in combination regimens.Portugal 2020: PTDC/SAU-PUB/28736/2017 (POCI-01-0145-FEDER-028736; FCT: SFRH/BD/116167/2016/ SFRH/BD/140844/2018/ PD/00016/2012info:eu-repo/semantics/publishedVersio

SAÚDE E TRABALHO DOS PROFESSORES DE EDUCAÇÃO FÍSICA QUE ATUAM COM ATIVIDADES AQUÁTICAS

Objetivo: O objetivo do presente estudo foi identificar a relação entre o processo de trabalho e a saúde dos professores de educação física que atuam com atividades aquáticas, bem como, verificar as diferenças entre os gêneros. Método: Foram pesquisados 184 professores de educação física, através de um levantamento realizado com questionários anônimos. Resultados: Foi observada desigualdade entre os gêneros no que se refere à distribuição da remuneração, embora não significativa. O estudo também permitiu observar uma excessiva queixa de dores (n=97; 52,72%). A percepção sobre o desgaste revelou um valor médio de 14,18 para escala de Borg e o sofrimento psíquico, medido pelo SRQ-20, apresentou valores de 2,58; 2,04 e 3,03 para todos, homens e mulheres, respectivamente, com diferença significativa entre os gêneros (

Desenvolvimento Neuropsicomotor em Crianças Nascidas Prematuras e com Baixo Peso

O estudo objetivou analisar o desenvolvimento neuropsicomotor, segundo o Teste de Triagem do Desenvolvimento Denver II, em crianças nascidas prematuras e com baixo peso acompanhadas nas Unidades de Saúde da Família. Realizou-se um estudo do tipo transversal com delineamento do tipo caso controle numa amostra de 85 crianças, distribuídas em grupo caso (47) e controle (38). Para análise dos dados utilizou-se tabelas de distribuição de frequências, testes de Qui-quadrado e Teste Exato de Fisher e análise de regressão logística. A análise individual mostrou associação significativa entre os grupos e a idade gestacional, peso ao nascer, tipo de parto, internação, local da residência, renda do pai, idade e escolaridade da mãe. Ao interpretar os itens individuais nas quatro áreas do desenvolvimento (pessoal-social, motor-fino-adaptativo, linguagem e motor grosso), observou-se um maior percentual de alterações no grupo caso, porém sem diferença significativa entre os grupos. Já na interpretação do teste inteiro, 14,1% das crianças avaliadas apresentaram resultado questionável, sendo 21,3% das crianças do grupo caso e 5,3% do grupo controle. A análise de regressão logística múltipla evidenciou que apenas a internação da criança e a escolaridade da mãe apresentaram associação significativa com o desenvolvimento neuropsicomotor. Crianças que foram internadas e de mães com escolaridade mais baixa têm 18,52 e 8,57 vezes mais chance, respectivamente, de apresentar resultado questionável no Denver II. Palavras-chave: Teste de Denver II, Desenvolvimento infantil, Motricidade

Genetic diversity in natural populations of Jacaranda decurrens Cham. determined using RAPD and AFLP markers

Jacaranda decurrens (Bignoniaceae) is an endemic species of the Cerrado with validated antitumoral activity. The genetic diversity of six populations of J. decurrens located in the State of São Paulo was determined in this study by using molecular markers for randomly amplified polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP). Following optimization of the amplification reaction, 10 selected primers generated 78 reproducible RAPD fragments that were mostly (69.2%) polymorphic. Two hundred and five reproducible AFLP fragments were generated by using four selected primer combinations; 46.3% of these fragments were polymorphic, indicating a considerable level of genetic diversity. Analysis of molecular variance (AMOVA) using these two groups of markers indicated that variability was strongly structured amongst populations. The unweighted pair group method with arithmatic mean (UPGMA) and Pearson's correlation coefficient (RAPD -0.16, p = 0.2082; AFLP 0.37, p = 0.1006) between genetic matrices and geographic distances suggested that the population structure followed an island model in which a single population of infinite size gave rise to the current populations of J. decurrens, independently of their spatial position. The results of this study indicate that RAPD and AFLP markers were similarly efficient in measuring the genetic variability amongst natural populations of J. decurrens. These data may be useful for developing strategies for the preservation of this medicinal species in the Cerrado