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Miguelote R.F.,University of Minho | Miguelote R.F.,Centro Hospitalar Do Alto Ave | Vides B.,Hospital de Sao Marcos | Santos R.F.,Centro Hospitalar Do Alto Ave | And 2 more authors.
Fetal Diagnosis and Therapy | Year: 2012

Objective: To compare the feasibility and reproducibility of transvaginal and transabdominal approaches, and 3D volume reconstruction sonography for measurement of corpus callosum (CC) length at different gestational ages. Methods: Forty-six normal fetuses were examined by 2D and 3D ultrasound at 23-25, 27-28 and 31-32 weeks of gestation. Direct mid-sagittal views were obtained by either a transabdominal and/or transvaginal approach. 3D reconstructed midsagittal views were obtained by 3D multiplanar manipulations and Volume Contrast Imaging in the C-plane technique (VCI-C) from volumes acquired in axial planes. Results: The CC could be measured in 91% of transvaginal acquisitions, in 52% of transabdominal acquisitions, in 92% of multiplanar reconstructions, and in 86% of VCI-C reconstructions. The success rate was independent of gestational age for transvaginal acquisition and slightly dependent on gestational age for 3D reconstruction techniques. Transabdominal acquisition was dependent on gestational age and fetal presentation. Inter- and intra-observer agreement was slightly better for measurements obtained from direct mid-sagittal views with either transvaginal or transabdominal acquisition than in views obtained by volume reconstruction. The reproducibility of measurements taken in reconstructed mid-sagittal views decreased with gestational age. Conclusion: 3D volume reconstruction techniques allow visualization and measurement of the CC in a high percentage of cases, with good reproducibility. Copyright © 2012 S. Karger AG, Basel.

Faustino A.,University of Porto | Couto J.P.,University of Porto | Populo H.,University of Porto | Rocha A.S.,University of Porto | And 5 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: There are several genetic and molecular evidences suggesting dysregulation of the mammalian target of rapamycin (mTOR) pathway in thyroid neoplasia. Activation of the phosphatidylinositol- 3-kinase/AKT pathway by RET/PTC and mutant RAS has already been demonstrated, but no data have been reported for the BRAFV600E mutation. Objective: The aim of this study was to evaluate the activation pattern of the mTOR pathway in malignant thyroid lesions and whether itmaybe correlated withknowngenetic alterations, as well as to explore the mechanisms underlying mTOR pathway activation in these neoplasias. Results: We observed, by immunohistochemical evaluation, an up-regulation/activation of the mTORpathway proteins in thyroid cancer, particularly in conventional papillary thyroid carcinoma (cPTC). Overactivation of the mTOR signaling was particularly evident in cPTC samples harboring the BRAFV600E mutation. Transfection assays with BRAF expression vectors as well as BRAF knockdownby small interfering RNA revealed a positive association between BRAF expression andmTOR pathway activation, which appears to be mediated by pLKB1 Ser428, and emerged as a possible mechanism contributing to the association between BRAF mutation and mTOR pathway up-regulation. When we evaluated the rapamycin in the growth of thyroid cancer cell lines, we detected that cell lines with activating mutations in the MAPK pathway show a higher sensitivity to this drug. Conclusions: We determined that the AKT/mTOR pathway is particularly overactivated in human cPTC harboring the BRAFV600E mutation. Moreover, our results suggest that the mTOR pathway could be a good target to enhance therapy effects in certain types of thyroid carcinoma, namely in those harboring the BRAFV600E mutation. Copyright © 2012 by The Endocrine Society.

Nour M.M.,University of Oxford | Nakashima I.,Tohoku University | Coutinho E.,University of Oxford | Woodhall M.,University of Oxford | And 17 more authors.
Neurology | Year: 2016

Objective: To investigate the association between neuromyelitis optica spectrum disorder (NMOSD) and pregnancy outcome. Methods: An international cohort of women with aquaporin-4 antibody-positive NMOSD and ≥1 pregnancy was studied retrospectively. Multivariate logistic regression was used to investigate whether pregnancy after NMOSD onset was associated with an increased risk of miscarriage (cohort of 40 women) or preeclampsia (cohort of 57 women). Results: Miscarriage rate was higher in pregnancies after NMOSD onset (42.9% [95% confidence interval 17.7%-71.1%] vs 7.04% [2.33%-15.7%]). Pregnancies conceived after, or up to 3 years before, NMOSD onset had an increased odds ratio of miscarriage (7.28 [1.03-51.6] and 11.6 [1.05-128], respectively), independent of maternal age or history of miscarriage. Pregnancies after, or up to 1 year before, NMOSD onset ending in miscarriage were associated with increased disease activity from 9 months before conception to the end of pregnancy, compared to viable pregnancies (mean annualized relapse rate 0.707 vs 0.100). The preeclampsia rate (11.5% [6.27%-18.9%]) was significantly higher than reported in population studies. The odds of preeclampsia were greater in women with multiple other autoimmune disorders or miscarriage in the most recent previous pregnancy, but NMOSD onset was not a risk factor. Conclusions: Pregnancy after NMOSD onset is an independent risk factor for miscarriage, and pregnancies conceived at times of high disease activity may be at increased risk of miscarriage. Women who develop NMOSD and have multiple other autoimmune disorders have greater odds of preeclampsia, independent of NMOSD onset timing. © 2015 American Academy of Neurology.

Costa B.M.,University of Minho | Caeiro C.,Hospital S. Joao | Guimaraes I.,University of Minho | Martinho O.,University of Minho | And 22 more authors.
Oncology Reports | Year: 2010

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. The identification of novel molecular prognostic markers of GBM has recently been an area of great interest in neuro-oncology. The methylation status of the MGMT gene promoter is currently a promising molecular prognostic marker, but some controversial data have precluded its clinical use. We analyzed MGMT methylation by methylation-specific PCR in 90 GBM patients from four Portuguese hospitals, uniformly treated with radiotherapy combined with concomitant and adjuvant temozolomide (Stupp protocol). The Kaplan-Meier method was used to construct survival curves, and the log-rank test and a Cox-regression model were used to analyze patient survival. The methylation status of MGMT was successfully determined in 89% (80/90) of the tumors. The frequency of tumoral MGMT promoter methylation was 47.5%. The median overall survivals (OSs) were 16 months (95% CI 12.2-19.8) and 13 months (95% CI 13.3-18.7) for patients whose tumors had a methylated or unmethylated MGMT, respectively. Univariate and multivariate analyses did not show any statistically significant association between MGMT methylation status and patient OS (P=0.583 by the log-rank test; P=0.617 by the Cox-regression test) or progression-free survival (P=0.775 by the log-rank test; P=0.691 by the Cox-regression test). None of the patient clinical features were significantly correlated with survival. This is the first study to report the frequency of MGMT methylation among Portuguese GBM patients. Our data did not show statistically significant associations between MGMT promoter methylation and the outcome of GBM patients treated with temozolomide. Additional robust prospective studies are warranted to clarify whether the MGMT status should be used in clinical decisions.

Miguelote R.F.,University of Minho | Miguelote R.F.,Centro Hospitalar Do Alto Ave | Vides B.,Hospital de Sao Marcos | Santos R.F.,Centro Hospitalar Do Alto Ave | And 3 more authors.
Prenatal Diagnosis | Year: 2011

Objectives: To determine the accuracy of measuring the corpus callosum (CC) length in reconstructed mid-sagittal views obtained by 3D multiplanar manipulations or volume contrast imaging in the C-plane (VCI-C) in comparison to measurements obtained by direct mid-sagittal view. Methods: Forty-six normal fetuses were examined by 2D and 3D ultrasound between 23 and 32 weeks of gestation. Direct mid-sagittal views were obtained by either the transabdominal or/and the transvaginal approach. 3D reconstructed mid-sagittal views were obtained by either 3D multiplanar manipulations or VCI-C. The CC length was measured in direct mid-sagittal views and in 3D reconstructed mid-sagittal views. Results: One hundred and thirty ultrasound examinations were performed. In 118 cases (91%) it was possible to obtain both a direct and a 3D reconstructed mid-sagittal view. Measurements of the CC length in direct mid-sagittal views correlated significantly with the measurements in reconstructed mid-sagittal views when the region underneath the comma-shaped echogenic structure was measured, but correlated poorly when this echogenic structure was included. Conclusions: Reconstructed mid-sagittal views obtained by 3D multiplanar manipulations or by VCI-C are valid approaches for measuring CC length. In these views the CC should be measured as the region underneath the comma-shaped echogenic structure. © 2011 John Wiley & Sons, Ltd.

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