Conização, exame de congelação e histerectomia planejada no tratamento de neoplasia intra-epitelial de alto grau

PURPOSE: We tested the role of frozen section examination of the cone specimen in the evaluation of the resection margin status and to rule out invasion in patients with high-grade cervical intraepithelial neoplasia. METHODS: Twenty-five patients with cervical intraepithelial neoplasia underwent conization followed by frozen section examination and planned hysterectomy. The results of the definitive paraffin exam were compared with frozen section examination. RESULTS: In the evaluation of the margins by frozen section examination, 16 patients (64%) had positive cone margins and 9 (36%) had negative margins. The definitive paraffin examination of margin status was concordant in all the cases. Intraoperative diagnosis of invasion was made in 5 cases, and 1 of these was microinvasive. Among the remaining 20 cases, we detected 2 additional microinvasive carcinomas after paraffin study, so the diagnosis of the frozen section examination was concordant with the paraffin sections in 23/25 cases (92%). Two cases of microinvasive carcinoma were diagnosed as cervical intraepithelial neoplasia by frozen section examination and had less than 2 mm stromal invasion. CONCLUSIONS: In high-grade cervical intraepithelial neoplasia, frozen section examination can provide immediate and precise evaluation of the cone margin status in high-grade cervical intraepithelial neoplasia. It can identify frank invasion and permit adequate treatment in a one-stage procedure. In early microinvasive disease, frozen section examination fails to detect the area of invasion but reliably detects clear resection margins.OBJETIVOS: Foi avaliado o papel do exame intra-operatório de congelação no diagnóstico de invasão e no estado das margens cirúrgicas em pacientes com neoplasia intra-epitelial de alto grau. CASUÍSTICA E MÉTODO: Vinte e cinco pacientes com neoplasia intra-epitelial de alto grau foram submetidas a conização cervical seguida de histerectomia. O resultado do exame definitivo em parafina foi comparado com o exame de congelação. RESULTADOS: Dezesseis pacientes (64 %) tiveram margens comprometidas e 9 (36 %) livres. O diagnóstico definitivo na parafina foi concordante em todos os casos no diagnóstico do estado das margens. Em cinco casos foi diagnosticada invasão, sendo 1 caso de carcinoma microinvasivo. Entre os 20 casos restantes foram detectados 2 carcinomas microinvasivos adicionais após o exame em parafina. Desta forma o exame intra-operatório de congelação foi concordante com o exame definitivo em 23/25 casos (92 %). Dois casos de carcinoma microinvasivo foram diagnosticados como neoplasia intra-epitelial de alto grau no exame de congelação e apresentavam invasão estromal menor que 2 cm. CONCLUSÕES: O exame intra-operatório de congelação é capaz de predizer o estado das margens cirúrgicas em todos os casos de neoplasia intra-epitelial de alto grau assim como o diagnóstico de invasão franca. Nos casos de carcinoma microinvasivo este exame falha na detecção de invasão, entretanto é capaz de garantir margens livres de ressecção

Molecular biomarkers associated with respiratory insufficiency in amyotrophic lateral sclerosis

Abstract in proceedings of the Fourth International Congress of CiiEM: Health, Well-Being and Ageing in the 21st Century, held at Egas Moniz’ University Campus in Monte de Caparica, Almada, from 3–5 June 2019.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.info:eu-repo/semantics/publishedVersio

Protein-biomembrane interactions as therapeutic targets

Biological membranes are dynamic structures essential for several cellular phenomena. The scope of the work of the Institute of Molecular Medicine (IMM) Biomembranes Unit is the study of biochemical and biophysical processes occurring at the membrane level on human cells and on their viral and bacterial pathogens. On the viral context, we are primarily interested on HIV and dengue virus, and particularly on the two steps of their life cycle involving their interaction with host cell membranes: the viral entry into target cells and the assembly of new viral particles. A special focus will be given to the study of the role of biological membranes on the mechanism of action of the HIV entry (membrane fusion) inhibitors enfuvirtide and T-1249. We are also involved in assessing the molecular basis of the activity of microbicides, such as rBPI21, that bind to specific components of bacterial membranes. Additionally, our line of work on the binding of fibrinogen to erythrocytes, and its relevance as a cardiovascular risk factor will be presented. An approach to the latter problem by single-molecule force spectroscopy, using an atomic force microscope (AFM), allowed the molecular recognition, characterization and partial identification of the human erythrocyte receptor for fibrinogen.These lines of work were supported by Fundação para a Ciência e a Tecnologia – Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal; projects PTDC/SAU-OSM/73449/2006 and PTDC/ QUI-BIQ/104787/2008), by the FP7-PEOPLE IRSES (International Research Staff Exchange Scheme) project MEMPEPACROSS (EU), and by Fundação Calouste Gulbenkian (Portugal). MMD and PMM also thank FCT-MCTES for the PhD fellowships SFRH/BD/41750/2007 and SFRH/BD/42205/2007, respectively

Advancements in on-line monitoring and control of parameters in knitting and sewing processes

This paper presents a summary of the developments in process control in textile processes at the University of Minho, by a multidisciplinary research group involving three different departments (Textile, lectronic and Mechanical Engineering). The studies target the automatic process parameter monitoring and control in the areas of industrial sewing and knitting.Fundação para a Ciência e a Tecnologia (FCT)

Antioxidant potential of the bio-based fucose-rich polysaccharide fucopol supports its use in oxidative stress-inducing systems

UIDP/04378/2020 UIDB/04378/2020 SFRH/BD/144258/2019Reactive oxygen species (ROS) are dangerous sources of macromolecular damage. While most derive from mitochondrial oxidative phosphorylation, their production can be triggered by ex-ogenous stresses, surpassing the extinction capacity of intrinsic antioxidant defense systems of cells. Here, we report the antioxidant activity of FucoPol, a fucose-rich polyanionic polysaccharide produced by Enterobacter A47, containing ca. 17 wt% of negatively charged residues in its struc-ture. Ferric reducing antioxidant power (FRAP) assays coupled to Hill binding kinetics fitting have shown FucoPol can neutralize ferricyanide and Fe3+-TPTZ species at an EC50 of 896 and 602 µg/mL, respectively, with positive binding cooperativity (2.52 ≤ H ≤ 4.85). This reducing power is greater than most polysaccharides reported. Moreover, an optimal 0.25% w/v FucoPol concentration shown previously to be cryo-and photoprotective was also demonstrated to protect Vero cells against H2O2-induced acute exposure not only by attenuating metabolic viability decay, but also by accentuating post-stress proliferation capacity, whilst preserving cell morphology. These results on antioxidant activity provide evidence for the biopolymer’s ability to prevent positive feedback cascades of the radical-producing Fenton reaction. Ultimately, FucoPol provides a biotechnological alternative for implementation in cryopreservation, food supplementation, and photoprotective sunscreen formula design, as all fields benefit from an antioxidant functionality.publishersversionpublishe

2,3-Diphosphoglycerate and the Protective Effect of Pyruvate Kinase Deficiency against Malaria Infection—Exploring the Role of the Red Blood Cell Membrane

Malaria remains a major world public health problem, contributing to poverty and inequality. It is urgent to find new efficacious tools with few adverse effects. Malaria has selected red blood cell (RBC) alterations linked to resistance against infection, and understanding the protective mechanisms involved may be useful for developing host-directed tools to control Plasmodium infection. Pyruvate kinase deficiency has been associated with resistance to malaria. Pyruvate kinase-deficient RBCs display an increased concentration of 2,3-diphosphoglycerate (2,3-DPG).We recently showed that 2,3-DPG impacts in vitro intraerythrocytic parasite growth, induces a shift of the metabolic profile of infected cells (iRBCs), making it closer to that of noninfected ones (niRBCs), and decreases the number of parasite progenies that invade new RBCs. As an increase of 2,3-DPG content may also have an adverse effect on RBC membrane and, consequently, on the parasite invasion, in this study, we explored modifications of the RBC morphology, biomechanical properties, and RBC membrane on Plasmodium falciparum in vitro cultures treated with 2,3-DPG, using atomic force microscopy (AFM)-based force spectroscopy and other experimental approaches. The presence of infection by P. falciparum significantly increased the rigidity of parasitized cells and influenced the morphology of RBCs, as parasitized cells showed a decrease of the area-to-volume ratio. The extracellular addition of 2,3-DPG also slightly affected the stiffness of niRBCs, making it more similar to that of infected cells. It also changed the niRBC height, making the cells appear more elongated. Moreover, 2,3-DPG treatment influenced the cell surface charge, becoming more negative in treated RBCs than in untreated ones. The results indicate that treatment with 2,3-DPG has only a mild effect on RBCs in comparison with the effect of the presence of the parasite on the host cell. 2,3-DPG is an endogenous host metabolite, which may, in the future, originate a new antimalarial tool with few adverse effects on noninfected cells.publishersversionpublishe

Understanding dengue virus capsid protein interaction with key biological targets

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Supplementary information accompanies this paper at http://www.nature.com/srepDengue virus (DENV) causes over 500,000 hospitalizations and 20,000 deaths worldwide every year. Dengue epidemics now reach temperate regions due to globalization of trade and travel and climate changes. Currently, there are no successful therapeutic or preventive approaches. We previously developed a peptide drug lead, pep14-23, that inhibits the biologically relevant interaction of DENV capsid (C) protein with lipid droplets (LDs). Surprisingly, pep14-23 also inhibits DENV C interaction with very low-density lipoproteins (VLDL). We thus investigated the similarity between the proposed DENV C molecular targets in LDs and VLDL, respectively, the proteins perilipin 3 (PLIN3) and apolipoprotein E (APOE). APOE N-terminal and PLIN3 C-terminal regions are remarkably similar, namely APOE α -helix 4 (APOEα 4) and PLIN3 α -helix 5 (PLIN3α 5) sequences, which are also highly superimposable structurally. Interestingly, APOE α -helical N-terminal sequence and structure superimposes with DENV C α -helices α 1 and α 2. Moreover, the DENV C hydrophobic cleft can accommodate the structurally analogous APOEα 4 and PLIN3α 5 helical regions. Mirroring DENV C-LDs interaction (previously shown experimentally to require PLIN3), we experimentally demonstrated that DENV C-VLDL interaction requires APOE. Thus, the results fit well with previous data and suggest future drug development strategies targeting the above mentioned α –helical structures.We acknowledge the support of Fundação para a Ciência e Tecnologia – Ministério da Educação e Ciência (FCT-MEC, Portugal) project PTDC/SAU-ENB/117013/2010, and Calouste Gulbenkian Foundation (Portugal). AFF and ICM also acknowledge FCT-MEC fellowship SFRH/BD/77609/2011 and Investigador FCT Program research contract IF/00772/2013, respectively

Role of fibrinogen–erythrocyte and erythrocyte–erythrocyte adhesion on cardiovascular pathologies

Abstract in proceedings of the Fourth International Congress of CiiEM: Health, Well-Being and Ageing in the 21st Century, held at Egas Moniz’ University Campus in Monte de Caparica, Almada, from 3–5 June 2019.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.info:eu-repo/semantics/publishedVersio