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Costa A.M.,University of Minho | Costa A.M.,ICVS 3Bs PT Government Associate Laboratory | Pinto F.,University of Minho | Pinto F.,ICVS 3Bs PT Government Associate Laboratory | And 7 more authors.
Oncotarget | Year: 2015

Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade extracellular matrix (ECM), thus assisting invasion. Upregulation of MMPs, frequently reported in gliomas, is associated with aggressive behavior. WNK2 is a tumor suppressor gene expressed in normal brain, and silenced by promoter methylation in gliomas. Patients without WNK2 exhibited poor prognosis, and its downregulation was associated with increased glioma cell invasion. Here we showed that MMP2 expression and activity are increased in glioma cell lines that do not express WNK2. Also, WNK2 inhibited JNK, a process associated with decreasing levels of MMP2. Thus, WNK2 promoter methylation and silencing in gliomas is associated with increased JNK activation and MMP2 expression and activity, thus explaining in part tumor cell invasion potential.


Almeida R.,University of Porto | Almeida R.,CIBER ISCIII | Almeida R.,Aragon Institute of Engineering Research | Almeida R.,University of Zaragoza | And 5 more authors.
Physiological Measurement | Year: 2014

Fetal heart rate monitoring is used for pregnancy surveillance in obstetric units all over the world but in spite of recent advances in analysis methods, there are still inherent technical limitations that bound its contribution to the improvement of perinatal indicators. In this work, a previously published wavelet transform based QRS detector, validated over standard electrocardiogram (ECG) databases, is adapted to fetal QRS detection over abdominal fetal ECG. Maternal ECG waves were first located using the original detector and afterwards a version with parameters adapted for fetal physiology was applied to detect fetal QRS, excluding signal singularities associated with maternal heartbeats. Single lead (SL) based marks were combined in a single annotator with post processing rules (SLR) from which fetal RR and fetal heart rate (FHR) measures can be computed. Data from PhysioNet with reference fetal QRS locations was considered for validation, with SLR outperforming SL including ICA based detections. The error in estimated FHR using SLR was lower than 20bpm for more than 80% of the processed files. The median error in 1min based FHR estimation was 0.13bpm, with a correlation between reference and estimated FHR of 0.48, which increased to 0.73 when considering only records for which estimated FHR> 110bpm. This allows us to conclude that the proposed methodology is able to provide a clinically useful estimation of the FHR. © 2014 Institute of Physics and Engineering in Medicine.


Goncalves H.,University of Porto | Bernardes J.,University of Porto | Bernardes J.,Sao Joao Hospital | Bernardes J.,INEB Institute of Biomedical Engineering | And 3 more authors.
Early Human Development | Year: 2013

Background: Management of intrauterine growth restriction (IUGR) remains a major issue in perinatalogy. Aims: The objective of this paper was the assessment of gender-specific fetal heart rate (FHR) dynamics as a diagnostic tool in severe IUGR. Subjects: FHR was analyzed in the antepartum period in 15 severe IUGR fetuses and 18 controls, matched for gestational age, in relation to fetal gender. Outcome measures: Linear and entropy methods, such as mean FHR (mFHR), low (LF), high (HF) and movement frequency (MF), approximate, sample and multiscale entropy. Sensitivities and specificities were estimated using Fisher linear discriminant analysis and the leave-one-out method. Results: Overall, IUGR fetuses presented significantly lower mFHR and entropy compared with controls. However, gender-specific analysis showed that significantly lower mFHR was only evident in IUGR males and lower entropy in IUGR females. In addition, lower LF/(MF. +. HF) was patent in IUGR females compared with controls, but not in males. Rather high sensitivities and specificities were achieved in the detection of the FHR recordings related with IUGR male fetuses, when gender-specific analysis was performed at gestational ages less than 34. weeks. Conclusions: Severe IUGR fetuses present gender-specific linear and entropy FHR changes, compared with controls, characterized by a significantly lower entropy and sympathetic-vagal balance in females than in males. These findings need to be considered in order to achieve better diagnostic results. © 2013 Elsevier Ltd.


Pinto P.,Hospital Nelio Mendonca | Pinto P.,University of Porto | Costa-Santos C.,University of Porto | Ayres-De-Campos D.,University of Porto | And 5 more authors.
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2016

Objective: To assess combined maternal (MHR) and fetal heart rate (FHR) recordings during labor, in relation with maternal-fetal attachment and prediction of newborn acidemia.Study design: Fifty-nine simultaneous MHR and FHR recordings were acquired in the final minutes of labor. Computer analysis followed the FIGO guidelines with estimation of MHR and FHR baselines, accelerations, decelerations, short- (STV) and long-term variabilities. MHR and FHR characteristics, their differences and correlations were assessed in relation to labor progression and to newborn umbilical artery blood (UAB) pH lower than 7.15 and 7.20. To assess prediction of acidemia, areas under ROC curves (auROC) were calculated.Results: Progression of labor was associated with a significant increase in MHR accelerations and FHR decelerations both in the non-acidemic and acidemic fetuses (p < 0.01). At the same time there was an increase in MHR-FHR correlations and differences in accelerations and decelerations in acidemic fetuses. The auROC ranged between 0.50 for FHR accelerations and 0.77 for MHR baseline plus FHR STV.Conclusions: MHR and FHR respond differently during labor with signs of increased maternal-fetal attachment during labor progression in acidemic fetuses. Combined MHR-FHR analysis may help to improve prediction of newborn acidemia compared with FHR analysis alone. © 2015 Informa UK Ltd.


Reynolds A.,University of Porto | Ayres-de-Campos D.,University of Porto | Ayres-de-Campos D.,INEB Institute of Biomedical Engineering | Pereira-Cavaleiro A.,University of Porto | Ferreira-Bastos L.,INEB Institute of Biomedical Engineering
Education for Health: Change in Learning and Practice | Year: 2010

Introduction and objective: The cognitive impact of using simulation sessions in midwifery training has not been the subject of previous research. The aim of this study was to compare the effect on students' knowledge of a simulation session versus an image-based lecture, for teaching routine management of normal delivery and resolution of shoulder dystocia to midwives in training. Methods: Sixty students were enrolled three weeks after a "labour and delivery" class, and randomly assigned to two groups. Ten were subsequently excluded as they were not able to attend the whole session and/or did not complete the tests. In the simulation group (n=26), students were divided into pairs and attended a 30-minute hands-on session in the simulation centre. In the lecture group (n=24), students participated in a 30-minute image-based interactive lecture. A ten-question multiple-choice test was taken before (pre-test) and after (post-test) both sessions, to evaluate students' knowledge of labour and delivery and shoulder dystocia. Learner satisfaction was evaluated by adding a six question Likert scale questionnaire to the post-test. Independent t-test, paired samples t-test, and Mann-Whitney test were used for statistical analysis, setting significance at p<0.05. Results: The simulation group showed a significantly higher mean post-test score (6.38 vs. 5.16; p=0.003) and a significantly greater inter-test score progression (p<0.0001). Overall learner satisfaction was also higher in this group (p=0.0001). Conclusions: A significantly higher short-term reinforcement of knowledge and greater learner satisfaction was obtained using simulation sessions compared to image-based lectures when teaching routine management of normal delivery and resolution of shoulder dystocia to midwives in training. © A Reynolds, D Ayres-de-Campos, A Pereira-Cavaleiro, L Ferreira-Bastos, 2010.


Goncalves H.,University of Porto | Pinto P.,Hospital Dr Nelio Mendonca | Pinto P.,University of Porto | Ayres-de-Campos D.,University of Porto | And 5 more authors.
IFMBE Proceedings | Year: 2014

Labor dystocia is a major cause of operative delivery, which is associated with increased risks for both mother and fetus. We assessed linear and non-linear dynamics of external uterine contraction signals, in relation to labor progression and dystocia. Linear time domain, spectral and entropy methods were used to analyze external uterine contraction recordings obtained during the last two hours of labor, in 28 cases with normal and 27 cases with operative deliveries (forceps, vacuum or caesarean). Progression of labor was associated with a statistically significant increase in most linear time domain and spectral indices, both in normal and operative deliveries, whereas most entropy indices increased in normal deliveries, but did not change in operative deliveries. On the other hand, when compared with normal births, operative deliveries were associated with significantly increased entropy indices before the last hour of labor and significantly decreased (a probably associated) sympatho-vagal balance in the last hour of labor. Linear and non-linear analysis of external uterine contraction recordings may provide useful physiopathological and clinical information on the progression of labor and the diagnosis of dystocia. © Springer International Publishing Switzerland 2014.


Almeida R.,University of Porto | Almeida R.,Communications Technology Group GTC | Goncalves H.,University of Porto | Rocha A.P.,University of Porto | And 3 more authors.
Computing in Cardiology | Year: 2013

Fetal heart rate monitoring is widespread all over the world. However, despite recent advances in analysis methods, there are still inherent technical limitations. One of the main challenges is to extract accurate and useful information from the external fetal ECG, which may provide a better non-invasive characterization of the fetal cardiovascular system during the third trimester of pregnancy. In this work, maternal ECG waves were first located using a wavelet transform based system previously developed and validated. Then, a similar strategy with adapted parameters for fetal physiology was applied to detect fetal QRS, excluding signal singularities associated to maternal heartbeats. Single lead based annotations were combined in a single annotator from which RR and HRV fetal measures could be taken. Data provided from PhysioNet 2013 Challenge was considered. The average scores were: 521.43 / 401,50 for event 4 and 32.99 / 29,70 for event 5 on set B /A respectively. The median rate of true positives, false positives and false negatives, normalized by number of fetal beats, found in the (training) set A was, respectively 78%, 17% and 22%. Median FHR estimation error was 2.0 bpm. Correlation between reference and estimated median FHR was 0.65 for estimated FHR>120bpm. The proposed approach seems promising for assessing fetal cardiac rhythms from abdominal ECGs. © 2013 CCAL.


Felgueiras H.P.,University of Paris 13 | Murthy N.S.,New Jersey Center for Biomaterials | Sommerfeld S.D.,New Jersey Center for Biomaterials | Bras M.M.,University of Porto | And 3 more authors.
ACS Applied Materials and Interfaces | Year: 2016

Proteins that get adsorbed onto the surfaces of biomaterials immediately upon their implantation mediate the interactions between the material and the environment. This process, in which proteins in a complex mixture compete for adsorption sites on the surface, is determined by the physicochemical interactions at the interface. Competitive adsorption of bovine serum albumin (BSA), fibronectin (Fn), and collagen type I (Col I), sequentially and from mixtures, was investigated so as to understand the performances of different surfaces used in biomedical applications. A quartz crystal microbalance with dissipation was used to monitor the adsorption of these proteins onto two materials used in functional bone replacement, a titanium alloy (Ti6Al4V) and Ti6Al4V physisorbed with poly(sodium styrenesulfonate) [poly(NaSS)], and three controls, gold, poly(desaminotyrosyltyrosine ethyl ester carbonate) [poly(DTEc)], and polystyrene (PS). In experiments with individual proteins, the adsorption was the highest with Fn and Col I and the least with BSA. Also, protein adsorption was the highest on poly(NaSS) and Ti6Al4V and the least on poly(DTEc). In sequential adsorption experiments, protein exchange was observed in BSA + Fn, Fn + Col I, and BSA + Col I sequences but not in Fn + BSA and Col I + BSA because of the lower affinity of BSA to surfaces relative to Fn and Col I. Protein adsorption was the highest with Col I + Fn on hydrophobic surfaces. In experiments with protein mixtures, with BSA & Fn, Fn appears to be preferentially adsorbed; with Fn & Col I, both proteins were adsorbed, probably as multilayers; and with Col I & BSA, the total amount of protein was the highest, greater than that in sequential and individual adsorption of the two proteins, probably because of the formation of BSA and Col I complexes. Protein conformational changes induced by the adsorbing surfaces, protein-protein interactions, and affinities of proteins appear to be the important factors that govern competitive adsorption. The findings reported here will be useful in understanding the host response to surfaces used for implants. © 2016 American Chemical Society.


Goncalves H.,University of Porto | Pinto P.,University of Porto | Pinto P.,Hospital Dr Nelio Mendonca | Silva M.,Hospital Dr Nelio Mendonca | And 6 more authors.
Medical and Biological Engineering and Computing | Year: 2015

Fetal heart rate (FHR) monitoring is used routinely in labor, but conventional methods have a limited capacity to detect fetal hypoxia/acidosis. An exploratory study was performed on the simultaneous assessment of maternal heart rate (MHR) and FHR variability, to evaluate their evolution during labor and their capacity to detect newborn acidemia. MHR and FHR were simultaneously recorded in 51 singleton term pregnancies during the last two hours of labor and compared with newborn umbilical artery blood (UAB) pH. Linear/nonlinear indices were computed separately for MHR and FHR. Interaction between MHR and FHR was quantified through the same indices on FHR–MHR and through their correlation and cross-entropy. Univariate and bivariate statistical analysis included nonparametric confidence intervals and statistical tests, receiver operating characteristic curves and linear discriminant analysis. Progression of labor was associated with a significant increase in most MHR and FHR linear indices, whereas entropy indices decreased. FHR alone and in combination with MHR as FHR–MHR evidenced the highest auROC values for prediction of fetal acidemia, with 0.76 and 0.88 for the UAB pH thresholds 7.20 and 7.15, respectively. The inclusion of MHR on bivariate analysis achieved sensitivity and specificity values of nearly 100 and 89.1 %, respectively. These results suggest that simultaneous analysis of MHR and FHR may improve the identification of fetal acidemia compared with FHR alone, namely during the last hour of labor. © 2015 International Federation for Medical and Biological Engineering


Goncalves H.,University of Porto | Ayres-de-Campos D.,University of Porto | Ayres-de-Campos D.,Sao Joao Hospital | Ayres-de-Campos D.,INEB Institute of Biomedical Engineering | And 3 more authors.
Developmental Psychobiology | Year: 2014

Differences in fetal neurodevelopment can have important implications on future perceptual and learning capabilities. The aim of this study was to assess autonomic nervous system and complexity dynamics in fetal heart rate (FHR) tracings from 27 singleton fetuses in cephalic or breech presentations, matched for gestational age (37+3-40+4 weeks), weight, gender and outcome. Breeches exhibited significantly higher mean FHR and LF/(MF+HF) ratio, as well as lower entropy, denoting increased sympatho-vagal balance and decreased complexity, consistent with the occurrence of more active fetal behavioral states. These findings suggest that there are neurodevelopment differences between fetuses in cephalic and breech presentation. © 2014 Wiley Periodicals, Inc.

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