810 research outputs found

    Anti-MuSK-positive myasthenia gravis diagnosed during pregnancy: New challenges for an old disease

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    Myasthenia gravis is an autoimmune disorder affecting predominantly women in their reproductive age. The course of the disease during pregnancy is unpredictable, although it is more difficult to manage earlier in the gestation. Myasthenia gravis with antibodies against the muscle-specific receptor tyrosine kinase (anti-MuSK) has been described as a subtype of disease with more localised clinical features and a poorer response to treatment than acetylcholine receptor antibody (anti-AChR)-positive patients. Few cases have been reported in pregnant women, with deliveries being performed mainly by caesarean section. We report a successful case of vaginal delivery and describe our experience providing the first review of the management of this subtype of disease during pregnancy

    Improved voltage control of the electric vehicle operating as UPS in smart homes

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    As a contribution for sustainability, electric vehicles (EVs) are seen as one of the most effective influences in the transport sector. As complement to the challenges that entails the EVs integration into the grid considering the bidirectional operation (grid-to-vehicle and vehicle-to-grid), there are new concepts associated with the EV operation integrating various benefits for smart homes. In this sense, this paper proposes an improved voltage control of the EV operating as uninterruptible power supply (UPS) in smart homes. With the EV plugged-in into the smart home, it can act as an off-line UPS protecting the electrical appliances from power grid outages. Throughout the paper, the foremost advantages of the proposed voltage control strategy are comprehensively emphasized, establishing a comparison with the classical approach. Aiming to offer a sinusoidal voltage for linear and nonlinear electrical appliances, a pulse-width modulation with a multi-loop control scheme is used. A Kalman filter is used for decreasing significantly the time of detecting power outages and, consequently, the transition for the UPS mode. The experimental validation was executed with a bidirectional charger containing a double stage power conversion (an ac-dc interfacing the grid-side and a dc-dc interfacing the batteries- side) and a digital stage. The computer simulations and the acquired experimental results validate the proposed strategy in different conditions of operation.This work has been supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT – Fundação para a Ciência e Tecnologia within the Project Scope: UID/CEC/00319/2013. This work is financed by the ERDF – European Regional Development Fund through the Operational Programme for Competitiveness and Internationalisation – COMPETE 2020 Programme, and by National Funds through the Portuguese funding agency, FCT – Fundação para a Ciência e a Tecnologia, within project SAICTPAC/0004/2015 – POCI – 01–0145–FEDER–016434. This work is part of the FCT project 0302836 NORTE-01-0145-FEDER-030283.info:eu-repo/semantics/publishedVersio

    Power electronics converters for an electric vehicle fast charging station with storage capability

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    Fast charging stations are a key element for the wide spreading of Electric Vehicles (EVs) by reducing the charging time to a range between 20 to 40 min. However, the integration of fast charging stations causes some adverse impacts on the Power Grid (PG), namely by the huge increase in the peak demand during short periods of time. This paper addresses the design of the power electronics converters for an EV DC fast charging station with local storage capability and easy interface of renewables. In the proposed topology, the energy storage capability is used to smooth the peak power demand, inherent to fast charging systems, and contributes to the stability of the PG. When integrated in a Smart Grid, the proposed topology may even return some of the stored energy back to the power grid, when necessary. The accomplishment of the aforementioned objectives requires a set of different power electronics converters that are described and discussed in this paper.This work has been supported by COMPETE: POCI-01-0145-FEDER-007043 and by FCT within the Project Scope: UID/CEC/00319/2013. This work is financed by the ERDF – COMPETE 2020 Programme, and FCT within project SAICTPAC/0004/2015‐POCI‐01‐0145–FEDER‐016434 and FCT within project PTDC/EEI-EEE/28813/2017. Mr. Luis A. M. Barros is supported by the doctoral scholarship PD/BD/143006/2018 granted by the Portuguese FCT agency. Mr. Tiago Sousa is supported by the doctoral scholarship SFRH/BD/134353/2017 granted by the Portuguese FCT agency

    SINGLE RADIAL IMMUNE HEMOLYSIS TEST FOR DETECTION OF ESCHERICHIA-COLI THERMOLABILE ENTERO-TOXIN

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    findings from a Portuguese study

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    A role for atorvastatin and insulin combination in protecting from liver injury in a model of type 2 diabetes with hyperlipidemia

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    Non-alcoholic fatty liver disease (NAFLD) is a major complication linked with the metabolic syndrome associated with dyslipidemia, inflammation, and oxidative stress. Impact of type 2 diabetes with hyperlipidemia in NAFLD has to be established, as well as the utility of commonly prescribed anti-diabetic and lipid-lowering agents in improving liver injury markers. Genetic type 2 diabetic Goto-Kakizaki rats were fed with a high-fat diet to test hepatic effects of type 2 diabetes with hyperlipidemia and the effect of atorvastatin and insulin, individually and in combination, in systemic and hepatic inflammatory and oxidative stress markers. High-fat diet aggravated fasting glycemia, systemic and liver lipids, and inflammatory and oxidative stress markers. Individual treatments improved glycemic and lipid profiles, but failed to improve inflammatory markers, whereas insulin was able to reduce liver oxidative stress parameters. Combination of insulin and atorvastatin further improved glycemic and lipid profiles and decreased circulating C-reactive protein levels and liver inflammatory and oxidative stress markers. Insulin and atorvastatin combination leads to better glycaemic and lipid profiles and to better protection against liver inflammation and oxidative stress, giving a superior level of liver protection in type 2 diabetic with hyperlipidemia

    Paclitaxel targets FOXM1 to regulate KIF20A in mitotic catastrophe and breast cancer paclitaxel resistance

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    FOXM1 has been implicated in taxane resistance, but the molecular mechanism involved remains elusive. In here, we show that FOXM1 depletion can sensitize breast cancer cells and mouse embryonic fibroblasts into entering paclitaxel-induced senescence, with the loss of clonogenic ability, and the induction of senescence-associated beta-galactosidase activity and flat cell morphology. We also demonstrate that FOXM1 regulates the expression of the microtubulin-associated kinesin KIF20A at the transcriptional level directly through a Forkhead response element (FHRE) in its promoter. Similar to FOXM1, KIF20A expression is downregulated by paclitaxel in the sensitive MCF-7 breast cancer cells and deregulated in the paclitaxel-resistant MCF-7TaxR cells. KIF20A depletion also renders MCF-7 and MCF-7TaxR cells more sensitive to paclitaxel-induced cellular senescence. Crucially, resembling paclitaxel treatment, silencing of FOXM1 and KIF20A similarly promotes abnormal mitotic spindle morphology and chromosome alignment, which have been shown to induce mitotic catastrophe-dependent senescence. The physiological relevance of the regulation of KIF20A by FOXM1 is further highlighted by the strong and significant correlations between FOXM1 and KIF20A expression in breast cancer patient samples. Statistical analysis reveals that both FOXM1 and KIF20A protein and mRNA expression significantly associates with poor survival, consistent with a role of FOXM1 and KIF20A in paclitaxel action and resistance. Collectively, our findings suggest that paclitaxel targets the FOXM1-KIF20A axis to drive abnormal mitotic spindle formation and mitotic catastrophe and that deregulated FOXM1 and KIF20A expression may confer paclitaxel resistance. These findings provide insights into the underlying mechanisms of paclitaxel resistance and have implications for the development of predictive biomarkers and novel chemotherapeutic strategies for paclitaxel resistance.Oncogene advance online publication, 11 May 2015; doi:10.1038/onc.2015.152.published_or_final_versio

    A fabric-based soft hand exoskeleton for assistance: the ExHand Exoskeleton

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    INTRODUCTION: The rise of soft robotics has driven the development of devices for assistance in activities of daily living (ADL). Likewise, different types of actuation have been developed for safer human interaction. Recently, textile-based pneumatic actuation has been introduced in hand exoskeletons for features such as biocompatibility, flexibility, and durability. These devices have demonstrated their potential use in assisting ADLs, such as the degrees of freedom assisted, the force exerted, or the inclusion of sensors. However, performing ADLs requires the use of different objects, so exoskeletons must provide the ability to grasp and maintain stable contact with a variety of objects to lead to the successful development of ADLs. Although textile-based exoskeletons have demonstrated significant advancements, the ability of these devices to maintain stable contact with a variety of objects commonly used in ADLs has yet to be fully evaluated. MATERIALS AND METHODS: This paper presents the development and experimental validation in healthy users of a fabric-based soft hand exoskeleton through a grasping performance test using The Anthropomorphic Hand Assessment Protocol (AHAP), which assesses eight types of grasping with 24 objects of different shapes, sizes, textures, weights, and rigidities, and two standardized tests used in the rehabilitation processes of post- stroke patients. RESULTS AND DISCUSSION: A total of 10 healthy users (45.50 ± 14.93 years old) participated in this study. The results indicate that the device can assist in developing ADLs by evaluating the eight types of grasps of the AHAP. A score of 95.76 ± 2.90% out of 100% was obtained for the Maintaining Score, indicating that the ExHand Exoskeleton can maintain stable contact with various daily living objects. In addition, the results of the user satisfaction questionnaire indicated a positive mean score of 4.27 ± 0.34 on a Likert scale ranging from 1 to 5

    SRC inhibition prevents P-cadherin mediated signaling and function in basal-like breast cancer cells

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    BACKGROUND: Basal-like breast cancer (BLBC) is a poor prognosis subgroup of triple-negative carcinomas that still lack specific target therapies and accurate biomarkers for treatment selection. P-cadherin is frequently overexpressed in these tumors, promoting cell invasion, stem cell activity and tumorigenesis by the activation of Src-Family kinase (SRC) signaling. Therefore, our aim was to evaluate if the treatment of BLBC cells with dasatinib, the FDA approved SRC inhibitor, would impact on P-cadherin induced tumor aggressive behavior. METHODS: P-cadherin and SRC expression was evaluated in a series of invasive Breast Cancer and contingency tables and chi-square tests were performed. Cell-cell adhesion measurements were performed by Atomic Force Microscopy, where frequency histograms and Gaussian curves were applied. 2D and 3D cell migration and invasion, proteases secretion and self-renew potential were evaluated in vitro. Student's t-tests were used to determine statistically significant differences. The cadherin/catenin complex interactions were evaluated by in situ proximity-ligation assay, and statistically significant results were determined by using Mann-Whitney test with a Bonferroni correction. In vivo xenograft mouse models were used to evaluate the impact of dasatinib on tumor growth and survival. ANOVA test was used to evaluate the differences in tumor size, considering a confidence interval of 95%. Survival curves were estimated by the Kaplan-Meier's method, using the log-rank test to assess significant differences for mice overall survival. RESULTS: Our data demonstrated that P-cadherin overexpression is significantly associated with SRC activation in breast cancer cells, which was also validated in a large series of primary tumor samples. SRC activity suppression with dasatinib significantly prevented the in vitro functional effects of P-cadherin overexpressing cells, as well as their in vivo tumorigenic and metastatic ability, by increasing mice overall survival. Mechanistically, SRC inhibition affects P-cadherin downstream signaling, rescues the E-cadherin/p120-catenin complex to the cell membrane, recovering cell-cell adhesion function. CONCLUSIONS: In conclusion our findings show that targeting P-cadherin/SRC signaling and functional activity may open novel therapeutic opportunities for highly aggressive and poor prognostic basal-like breast cancer.This work was funded by Laço Grant 2014, by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by FCT - Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Ensino Superior under the projects PTDC/SAU-GMG/120049/ 2010-FCOMP-01-0124-FEDER-021209, PEst-C/SAU/LA0003/2013, NORTE-01- 0145-FEDER-000029 and POCI-01-0145-FEDER-016390. FCT funded the research grants of ASR (SFRH/BPD/75705/2011), ARN (SFRH/BD/100380/2014), BS (SFRH/ BPD/104208/2014), AFV (SFRH/BPD/90303/2012), as well as JP with Programa IFCT 2013 (FCT Investigator). IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274)
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