Nódulo umbilical da Irmã Maria José: caso de uma religiosa do Norte de Portugal

O nódulo da “Irmã Maria José” é tumor metastático que acomete a cicatriz umbilical e pode ser a primeira evidência de neoplasia intraabdominal disseminada1. Os autores relatam o caso de uma paciente com o nódulo da “Irmã Maria José” internada numa Unidade de Cuidados Paliativos, e cujo modo de vida era a vida religiosa, “irmã”. O primeiro relato de tumoração umbilical por cancro foi feito em 1846 por Walshe e o epónimo “Nódulo de Irmã Maria José” foi utilizado posteriormente para lesão metastática na cicatriz umbilical por Bailey. A Irmã Maria José, assistente que trabalhava no Hospital St. Mary em Rochester, Minnesota, entre 1889 e 1939, observou a relação existente entre o nódulo umbilical e a presença de tumores maligno intra-abdominal1.info:eu-repo/semantics/publishedVersio

Garch models for drug effects on patient heart rate, during general anaesthesia

A model that can describe the effect of anaesthetic drugs on patient’s heart rate (HR) is of great importance when considering haemodynamic stability under surgery. A Generalized Autoregressive Conditional Heteroscedasticity (GARCH) model was used to model HR considering the effect concentrations of the anaesthetic propofol and the analgesic remifentanil, using the clinical data of 16 patients. The model was able to capture the HR trend in all 16 patients with very small errors throughout the surgical time. A correlation was found between the GARCH parameters and patient baseline characteristics, leading to the possibility a patient adjusted adaptive model.info:eu-repo/semantics/publishedVersio

Transcriptome mining to identify molecular markers for the diagnosis of Staphylococcus epidermidis bloodstream infections

Bloodstream infections caused by Staphylococcus epidermidis are often misdiagnosed since no diagnostic marker found so far can unequivocally discriminate true infection from sample contamination. While attempts have been made to find genomic and/or phenotypic differences between invasive and commensal isolates, possible changes in the transcriptome of these isolates under in vivo-mimicking conditions have not been investigated. Herein, we characterized the transcriptome, by RNA sequencing, of three clinical and three commensal isolates after 2 h of exposure to whole human blood. Bioinformatics analysis was used to rank the genes with the highest potential to distinguish invasive from commensal isolates and among the ten genes identified as candidates, the gene SERP2441 showed the highest potential. A collection of 56 clinical and commensal isolates was then used to validate, by quantitative PCR, the discriminative power of the selected genes. A significant variation was observed among isolates, and the discriminative power of the selected genes was lost, undermining their potential use as markers. Nevertheless, future studies should include an RNA sequencing characterization of a larger collection of isolates, as well as a wider range of conditions to increase the chances of finding further candidate markers for the diagnosis of bloodstream infections caused by S. epidermidis.This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of the unit [UIDB/04469/2020]. S.B. was supported by a fellowship granted by a Doctoral Advanced Training [NORTE-69-2015-15] funded by the European Social Fund under the scope of NORTE2020.info:eu-repo/semantics/publishedVersio

Hipertensão arterial e hiperinsulinismo de mãos dadas

As doenças cardiovasculares são uma importante causa de morte e incapacidade a nível mundial, sendo que a Hipertensão Arterial (HTA) contribui para 45% do total de mortes por doenças cardíacas e até 51% das mortes por Acidente Vascular Cerebral (AVC). Em Portugal, a HTA tem uma prevalência estimada de 24,5% (por inquérito) e de 42% com base em estudos sobre a medicação anti hipertensora1. A prevalência de HTA aumenta com a idade dos utentes1, aumentando também associada a diversos fatores como: hiperatividade simpática, alterações da fisiologia renal, excesso de ingestão de sódio, alterações da dinâmica vascular como: Disfunção endotelial e Alterações nas vias do Óxido Nítrico (NO); Alterações endócrinas: Sistema Renina-Angiotensina-Aldosterona (SRAA); Obesidade; Resistência periférica à insulina e Síndrome Metabólico (SM) e Diabetes Melitus (DM) tipo 2 e aumento da atividade simpática3info:eu-repo/semantics/publishedVersio

Developing an affordable but reliable human blood ex vivo model to analyse gene expression by Staphylococcus epidermidis

Microbiotec'17 - Congress of Microbiology and Biotechnology 2017Background: Staphylococcus epidermidis is a commensal inhabitant of healthy human skin and mucosae. However, when external barriers, such as the skin, are damaged, the bacterium gains accesses into the bloodstream and emerges as an opportunistic pathogen. S. epidermidis can originate important infections such as medical device-associated bloodstream infections. This is mainly due to its ability to attach and form biofilms on the surface of vascular catheters. Hence, due to the clinical relevance of S. epidermidis medical device-associated bloodstream infections, human blood is frequently used as an ex vivo model, to mimic the environment encountered by the bacterium and study its behavior. An important limitation in the use of human blood is the availability of donors and the considerable quantity of blood necessary. As any other biological resource, the use of blood shall be reduced to a minimum and, thus, our goal was to test the influence of different volumes of human blood on the stability of S. epidermidis gene expression and on bacterial culturability.This work was supported by national funds (FCT) by the strategic project of UID/BIO/04469/2013 and by BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by European Regional Development Fund under the scope of Norte2020. SB had an individual fellowship (UMINHO/BD/15/2016) supported by the Doctoral Program in Chemical and Biological Engineering (NORTE-08-5369-FSE-000052 Operation) by NORTE 2020 Program and co-funded by European Social Fund.NC is an Investigador FCT.info:eu-repo/semantics/publishedVersio

Transparência na disponiblização da avaliação do desempenho : o caso das Direções-Gerais

Dissertaçao de mestrado em Gestão, apresentada à Faculdade de Economia da Universidade de Coimbra, sob a orientação de Patrícia Moura e Sá e Rui dos Santos Lourenço.A avaliação do desempenho nos organismos da Administração Pública (AP) ganhou um enfoque particularmente relevante nos anos 80. Desde então as Administrações Públicas têm vindo a adotar modelos e ferramentas para medir o desempenho, alguns deles ancorados em princípios da Qualidade, como é em particular o caso da Common Assessment Framework (CAF), referencial especialmente desenvolvido para a AP lançado pela União Europeia em 2000. A nível nacional, a avaliação do desempenho dos organismos da AP foi operacionalizada através do Sistema Integrado de Gestão e Avaliação do Desempenho na Administração Pública (SIADAP), atualmente regulado pela Lei n.º 66-B/2007, de 28 de dezembro, a qual impôs a avaliação dos serviços, estabelecendo que esta assenta num Quadro de Avaliação e Responsabilização (QUAR), o qual deve ser objeto de publicação na página eletrónica do respetivo serviço. A publicação do QUAR com os respetivos objetivos e indicadores e os resultados da autoavaliação visa dar cumprimento ao desígnio de transparência que integra o objetivo mais amplo de Administração Aberta. Desta forma, no presente trabalho, procura-se avaliar se a AP utiliza a Internet para prestar contas relativamente ao seu desempenho e se o faz cobrindo as principais áreas da CAF. Para tal recorreu-se a uma pesquisa simultânea nas páginas das Direções-Gerais (DG) e no Portal GeADAP, analisando os QUAR e os Relatórios de Atividades e de Autoavaliação ai disponibilizados. A análise dos resultados evidência que as DG têm pouca aptidão para a disponibilização online dos dados relativos à avaliação do desempenho, tanto no que se refere aos objetivos e indicadores, como, em especial, aos resultados da autoavaliação. Em qualquer caso, a disponibilização é feita essencialmente através das páginas web dos organismos, sendo de questionar a utilidade do Portal GeADAP. Adicionalmente, nota-se que os indicadores escolhidos no âmbito do QUAR se centram em determinadas dimensões, não captando adequadamente vários critérios da CAF

On the old story of the accidental pathogen: can transcriptomics clarify how S. epidermidis becomes virulent?

Background: Staphylococcus epidermidis is a commensal inhabitant of healthy human skin and mucosae that can originate important infections such as medical device-associated bloodstream infections, often associated to patients with impaired or undeveloped immune systems. Of concern, the current inability to discriminate between true bacteraemia caused by S. epidermidis and contaminated blood cultures often leads to misdiagnosis, resulting in a significant increase in patient morbidity and in healthcare costs. Until now, several genetic and phenotypic approaches were not able to identify any specific marker that clearly distinguishes commensal from isolates that cause infection. Hence, our goal was to identify possible RNA-based molecular markers for the diagnosis of S. epidermidis infections, a strategy never reported before.The authors acknowledge the Doctoral Advanced Training [Norte 69-2015-15] funded by the European Social Fund under the scope of Norte2020, FCT project EXPL/BIA-MIC/0101/2013; strategic funding of unit UID/BIO/04469/2019; BioTecNorte operation (NORTE-01-0145-FEDER-000004).info:eu-repo/semantics/publishedVersio

Optimizing a reliable ex vivo human blood model to analyze expression of Staphylococcus epidermidis genes

Human blood is often used as an ex vivo model to mimic the environment encountered by pathogens inside the host. A significant variety of experimental conditions has been reported. However, optimization strategies are often not described. This study aimed to evaluate key parameters that are expected to influence Staphylococcus epidermidis gene expression when using human blood ex vivo models. Our data confirmed that blood antimicrobial activity was dependent on initial bacterial concentration. Furthermore, blood degradation over time resulted in lower antimicrobial activity, with a 2% loss of leukocytes viability correlating with a 5-fold loss of antimicrobial activity against S. epidermidis. We further demonstrated that the volume of human blood could be reduced to as little as 0.18 mL without affecting the stability of gene expression of the tested genes. Overall, the data described herein highlight experimental parameters that should be considered when using a human blood ex vivo model for S. epidermidis gene expression analysis.This work was supported by the Portuguese Foundation for Science and Technology (FCT) by the funded project PTDC/BIA-MOL/29553/2017, under the scope of COMPETE2020 [POCI-01-0145-FEDER-02955 and by the strategic funding of unit UIDB/04469/2020 and by European funds under BioTecNorte operation [NORTE-01-0145-FEDER-000004 funded by European Regional Development Fund under the scope of Norte2020. Susana Brás is supported by a fellowship granted by a Doctoral Advanced Training [Norte 69- 2015-15 funded by the European Social Fund under the scope of Norte2020. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptinfo:eu-repo/semantics/publishedVersio

Melanoma in the Eyes of Mechanobiology

Skin is the largest organ of the human body with several important functions that can be impaired by injury, genetic or chronic diseases. Among all skin diseases, melanoma is one of the most severe, which can lead to death, due to metastization. Mechanotransduction has a crucial role for motility, invasion, adhesion and metastization processes, since it deals with the response of cells to physical forces. Signaling pathways are important to understand how physical cues produced or mediated by the Extracellular Matrix (ECM), affect healthy and tumor cells. During these processes, several molecules in the nucleus and cytoplasm are activated. Melanocytes, keratinocytes, fibroblasts and the ECM, play a crucial role in melanoma formation. This manuscript will address the synergy among melanocytes, keratinocytes, fibroblasts cells and the ECM considering their mechanical contribution and relevance in this disease. Mechanical properties of melanoma cells can also be influenced by pigmentation, which can be associated with changes in stiffness. Mechanical changes can be related with the adhesion, migration, or invasiveness potential of melanoma cells promoting a high metastization capacity of this cancer. Mechanosensing, mechanotransduction, and mechanoresponse will be highlighted with respect to the motility, invasion, adhesion and metastization in melanoma cancer.The authors acknowledge to Ana Silva ([email protected]) for expert assistance with graphical design, and to Portuguese funds – FCT UID/BIM/04293/2019.info:eu-repo/semantics/publishedVersio