Bloqueio Aurículo-Ventricular Completo Congénito. Caso Clínico e Revisão da Literatura

Introduction: Congenital complete atrioventricular block (AVB) without cardiac malformation is a rare and potentially fatal condition. In most cases it is associated with maternal systemic lupus erythematosus through transplacental passage of antibodies anti-SSA/Ro and/or anti-SSB/La. Antenatal fluorinated-steroids have been successful in reversing first and second degree congenital AVB but inconsistent in third degree block. Case Report:The authors report a case of fetal bradycardia diagnosed at 24 weeks of gestation. The fetal echocardiogram revealed a second/third degree AVB without structural heart disease. Maternal anti-SSA/Ro antibodies were detected. There was no blockage improvement with maternal oral fluorinated-steroids. An elective cesarean section was performed at term with the delivery of a healthy girl that required an epicardical pacemaker on the 8th day of life. Conclusion: In this case, treatment with maternal fluorinated corticosteroids was not effective in preventing progression of the heart block

Comparison of Three Classification Criteria Sets for Systemic Lupus Erythematosus: A Study Looking at Links to Outcome and Mortality

OBJECTIVE: To compare the ability of the American College of Rheumatology (ACR), Systemic Lupus International Collaborating Clinics (SLICC), and European League Against Rheumatism (EULAR)/ACR systemic lupus erythematosus (SLE) classification criteria sets to provide information regarding organ damage and mortality, over a 10‐year follow‐up period. METHODS: Using data from 100 patients, we completed each classification set at the time of diagnosis and recorded the SLICC/ACR Damage Index (SDI) score, renal damage, major cardiovascular events, and death, 10 years later. We reviewed the presence of other autoantibodies, linked to SLE but not included in the classification criteria sets, and assessed whether they impacted the predictive capacity of the classification sets. RESULTS: We found a statistically significant association between the EULAR/ACR set and renal damage and SDI score, the latter after adjustment for age and sex. In the patients negative for other autoantibodies, higher EULAR/ACR scores were associated with higher rates of organ damage. CONCLUSION: These data suggest that the EULAR/ACR set may offer useful prognostic information, because higher scores were associated with higher rates of organ damage. These findings were clearer in patients negative for nondiagnostic SLE autoantibodies, who may benefit more from the predictive capacity of the EULAR/ACR set

Completeness of Retention Data and Determinants of Attrition in Birth Cohorts of Very Preterm Infants: A Systematic Review

Background: Birth cohorts provided essential knowledge for clinical and public health decision-making. However, little is known about retention and determinants of attrition in these specific longitudinal studies, although characterizing predictors of attrition sets the path to mitigate its occurrence and to promote valid inferences. We systematically reviewed retention in follow-ups of birth cohorts of very preterm or very low birth weight infants and the determinants of attrition. PROSPERO registration number: CRD42017082672. Methods: Publications were identified through PubMed®, Scopus, Web of Science, and Cochrane Library databases from inception to December 2017. Studies were included when reporting at least one of the following: retention at follow-ups, reasons for attrition, or characteristics of non-participants. Quality assessment was conducted using the completeness of the report of participation features in the articles. Non-participant's characteristics were presented using descriptive statistics. Local polynomial regression was used to describe overall retention trends over years of follow-up. Results: We identified 57 eligible publications, reporting on 39 birth cohorts and describing 83 follow-up evaluations. The overall median retention was 87% (p25–p75:75.8–93.6), ranging from 14.6 to 100%. Overall, retention showed a downward trend with increasing child age. Completeness of retention report was considered “enough” in only 36.8% of publications. Considering the 33 (57.9%) publications providing information on participants and non-participants, and although no formal meta-analysis was performed, it was evident that participants lost to follow-up were more often male, had foreign-born, multiparous, and younger mothers, and with a lower socioeconomic status. Conclusion: This systematic review evidenced a lack of detailed data on retention, which may threaten the potential use of evidence derived from cohort studies of very preterm infants for clinical and public health purpose. It supports the requirement for a standardized presentation of retention features responding to current guidelines.This work was supported by RECAP-Preterm project that is funded by the European Union's Horizon 2020 research and innovation program under Grant Agreement No. 733280. This study was also funded by Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education), under the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04750/2020/PT); Ana Cristina Santos holds a FCT Investigator contract info:eu-repo/grantAgreement/FCT/Investigador FCT/IF/01060/2015/CP1319/CT0001/PT

Comparison of Cartesian and Non-Cartesian Real-Time MRI Sequences at 1.5T to Assess Velar Motion and Velopharyngeal Closure during Speech

This project is funded by CLEFT (CLEFT-2013-1) and an Institute of Physics and Engineering in Medicine (IPEM) Innovation and Research Award for computer equipment. MEM is partly (20%) funded by the National Institute for Health Research Cardiovascular Biomedical Research Unit at Barts. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript

Interaction of paraoxonase-192 polymorphism with low HDL-cholesterol in coronary artery disease risk.

A doença coronária (DC) é a principal causa de mortalidade nos países desenvolvidos. O aumento da peroxidação lipídica está associado com a progressão acelerada da arteriosclerose. A Paraoxonase (PON1) é uma enzima antioxidante, que protege contra a peroxidação lipídica e a DC. A actividade da PON1 está sob controlo genético e a sua base molecular consiste num polimorfismo do gene da PON1 que apresenta duas isoformas comuns: a forma nativa, Q (192 Gln) com elevada capacidade de protecção das LDL da peroxidação lipídica in vitro, e a isoforma mutada R (192 Arg) com baixa capacidade de protecção. Objectivo: O objectivo deste trabalho foi investigar a interacção entre o alelo R do gene da PON 1 e os níveis plasmáticos baixos de colesterol HDL, no risco do aparecimento da DC. Métodos: Participaram no estudo 818 indivíduos, 298 doentes coronários com idade média 55.0±10.3 anos, 78.9% do sexo masculino, e 520 controlos, com uma idade média de 53.3±11, 7 anos, 72, 5% do sexo masculino, tendo casos e controlos sido emparelhados por idade e sexo. Foi considerado um valor <de 40 mg/dl (0,90 mmol/L), nos homens e <de 50 mg/dl (1,11 mmol/L), nas mulheres como um nível baixo de Colesterol HDL. As comparações genotípicas, entre casos e controlos, foram efectuadas pelo teste do Chi-quadrado. A significância estatística foi aceite para valores de p <0,05. Para determinar o risco relativo de DC, em relação ao genótipo RR e aos níveis baixos de colesterol HDL, foi usada uma análise univariada e foram utilizadas as tabelas epidemiológicas 4x2 e medidas de sinergismo (modelo aditivo - SI e multiplicativo - SIM) para determinar a interacção entre o genótipo RR e os níveis baixos de colesterol HDL. Foi finalmente calculado o excesso de risco relativo (RERI) e proporção atribuída à interacção (AP). Resultados: A PON 1 192 RR está associada à DC [OR=1,61; p=0,043] para toda a população. A associação de níveis baixos de HDL com o genótipo 192 RR mostrou um aumento do risco de DC (OR=17,38; p <0,0001) comparada aos níveis normais de HDL associados ao mesmo genótipo (OR=1,39; p=0,348) e aos níveis baixos de HDL sem o genótipo RR (OR=7,79; p <0,0001). Índices de Sinergismo: SI= 2,3; SIM = 1.6; RERI=9,2; AP=0,53. Conclusão: Estes dados sugerem a existência de um efeito sinérgico entre o genótipo 192 RR da PON1 e os valores baixos de colesterol HDL, na emergência de DC, pois este genótipo aumentou o risco de DC, em especial, na população com níveis plasmáticos baixos de colesterol HDL. A proporção de DC que pode ser atribuída a esta interacção (AP) foi de 0,53 significando que 53% da DC que surgiu nestes indivíduos, foi explicada por esta interacção.INTRODUCTION: Coronary artery disease (CAD) is the main cause of mortality in developed countries. Increased lipid peroxidation is associated with accelerated progression of atherosclerosis. Paraoxonase (PON1) is an antioxidant enzyme bound to high-density lipoprotein (HDL), which protects against lipid peroxidation and coronary artery disease. PON1 activity is under genetic control and its molecular basis is a polymorphism in the PON1 gene that shows two common isoforms: the wild Q form (192 Gln) with high ability to protect LDL from lipid peroxidation in vitro, and the mutated R (Arg) form with lower ability. AIM: To explore the interaction of the R allele of the paraoxonase gene and low HDL-cholesterol concentrations in CAD risk. METHODS: The study population consisted of 818 individuals, 298 coronary patients, aged 55.0 +/- 10.3 years, 78.9% male, and 520 age and gender matched healthy controls, aged 53.3 +/- 11.7 years, 72.5% male. Low HDL-cholesterol was defined as < 0.90 mmol/l in men and < 1.11 mmol/l in women. Comparisons of genotypes between cases and controls were performed by a chi-square test. Statistical significance was accepted at p < 0.05. Odds ratios and 95% confidence intervals for the RR genotypes and HDL-deficient subjects were computed using univariate analysis (2 x 2 tables). To determine the interaction between the RR paraoxonase genotype and HDL-deficient subjects, we used 4 x 2 epidemiologic tables and synergy measures: the additive model (Rothman's synergy index, SI) and multiplicative model (Khoury's synergy index, SIM). The relative excess risk due to interaction (RERI) and the attributable proportion (AP) due to interaction (Rothman) were calculated. RESULTS: The PON1 RR192 polymorphism was associated with coronary heart disease (OR = 1.61; p = 0.043) in the whole population. HDL-deficient subjects with the RR192 genotype showed increased risk for CAD (OR = 17.38; p < 0.0001) compared to those with normal HDL and RR192 (OR = 1.39; p = 0.348) and HDL-deficient subjects not carrying the RR genotype (OR = 7.79; p < 0.0001). Synergy measures were SI = 2.3, SIM = 1.6; RERI = 9.2. CONCLUSION: These data suggest the existence of a synergistic effect of the PON1 RR192 genotype (with lower antioxidant ability) and HDL-deficient subjects in risk for development of CAD. The AP due to this interaction was 0.53, meaning that 53% of CAD was explained by this interaction.info:eu-repo/semantics/publishedVersio

Independent association of the variant rs1333049 at the 9p21 locus and coronary heart disease.

Introdução: Estudos recentes de associação genómica em larga escala (GWAS) identificaram vários polimorfismos de um único nucleótido (SNP), localizados no locus 9p21, associados com doença arterial coronária (DAC). De entre eles o SNP rs1333049 demonstrou uma associação consistente com a DAC tendo sido reproduzida, com sucesso, em várias populações. Objectivo: Investigar se a nova variante rs1333049, no cromossoma 9p21, é um factor de risco independente para DAC, na população Portuguesa. Material e métodos: Estudo caso-controlo, que incluiu 1406 indivíduos, 723 doentes coronários internados consecutivamente (idade média de 53,7±8,9 anos 79,9% do sexo masculino) e 683 controlos sem doença coronária (idade média de 53,3±10,5 anos, 73,9 % do sexo masculino) seleccionados para não serem significativamente diferentes quanto ao sexo e idade. Estudou-se o SNP rs1333049, em todos os indivíduos, com recurso à técnica convencionada de PCR combinada com a técnica TaqMan (Applied Biosystems). Determinou-se a distribuição alélica e genotípica (C/G), odds ratio e respectivo intervalo de confiança para risco de DAC. Foi construído um modelo de regressão logística forward wald ajustado para a idade, sexo, factores de risco convencionais, marcadores bioquímicos e genótipos em estudo, afim de avaliar quais as variáveis associadas de forma significativa e independente com DAC. Resultados: 60% dos doentes coronários e 53% dos controlos apresentaram o alelo C (OR=1,33; p=0,0002), 35,7% dos doentes e 29,3% dos controlos tinham o genótipo homozigoto CC (OR=1,34;p=0,010). O heterozigoto CG estava presente em 48,1% dos doentes e 47% nos controlos, não atingindo significância estatística, para risco vascular (OR=1,05;p=0,670). Após análise multivariada de regressão logística o genótipo CC do cromossoma 9p21 ficou na equação com um OR=1,7, p=0,018 e o genótipo heterozigoto CG com um OR=1,5, p=0,048. Conclusão: Com o presente trabalho replicou-se, numa população portuguesa, o risco coronário ligado à nova variante rs1333049 do cromossoma 9p21. A robustez deste genótipo, tanto em homo como em heterozigotia, tem sido consistente e relevante na estratificação de risco para a DAC, mesmo em contextos populacionais muito diversos. Nestas circunstâncias, a utilização do genótipo CC ou CG poderá vir a revelar-se útil para a previsão do risco de DAC na nossa população.INTRODUCTION: Recent genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). Among them, the SNP rs1333049 has demonstrated a consistent association with CAD, which has been successfully replicated in several populations. AIM: To investigate whether the SNP rs1333049 located on the 9p21 chromosome is an independent risk factor for CAD in a Portuguese population. METHODS: We performed a case-control study which included 1406 individuals, 723 consecutive coronary patients (mean age 53.71 +/- 8.9 years, 79.9% male and 683 controls without coronary disease (mean age 53.3 +/- 10.5 years, 73.9% male). Cases and controls were selected so as not to be significantly different in terms of gender and age. We studied the SNP rs1333049 at the 9p21 locus in all individuals, using standard PCR combined with the TaqMan technique (Applied Biosystems). The allelic and genotype distribution (C/G), odds ratios and corresponding confidence intervals for CAD risk were determined. A forward Wald logistic regression analysis model was constructed, adjusted for age, gender, conventional risk factors, biochemical markers and the genotypes under study, in order to determine which variables were linked significantly and independently with CAD. RESULTS: The C allele was found in 60% of the CAD patients and 53% of the controls, with OR = 1.33; p = 0.0002. The CC genotype appeared in 35.7% of CAD patients, with OR = 1.34, p = 0.010. The heterozygous CG genotype was present in 48.1% of the CAD patients and 47% of the controls, and did not present vascular risk (OR = 1.05, p = 0.670). After logistic regression analysis, the CC genotype remained in the equation with OR = 1.7; p = 0.018 and CG with OR = 1.5, p = 0.048. CONCLUSION: In the present study we replicated the coronary risk linked to the recently discovered variant rs1333049 on the 9p21 chromosome in a Portuguese population. Although the mechanism underlying the risk is still unknown, the robustness of this risk allele in risk stratification for CAD has been consistent, even in very different populations. The presence of the CC or CG genotype may thus prove to be useful for predicting the risk of developing CAD in the Portuguese population.info:eu-repo/semantics/publishedVersio

Follicular Fluid redox involvement for ovarian follicle growth

As the human ovarian follicle enlarges in the course of a regular cycle or following controlled ovarian stimulation, the changes in its structure reveal the oocyte environment composed of cumulus oophorus cells and the follicular fluid (FF).In contrast to the dynamic nature of cells, the fluid compartment appears as a reservoir rich in biomolecules. In some aspects, it is similar to the plasma, but it also exhibits differences that likely relate to its specific localization around the oocyte. The chemical composition indicates that the follicular fluid is able to detect and buffer excessive amounts of reactive oxygen species, employing a variety of antioxidants, some of them components of the intracellular milieu.An important part is played by albumin through specific cysteine residues. But the fluid contains other molecules whose cysteine residues may be involved in sensing and buffering the local oxidative conditions. How these molecules are recruited and regulated to intervene such process is unknown but it is a critical issue in reproduction.In fact, important proteins in the FF, that regulate follicle growth and oocyte quality, exhibit cysteine residues at specific points, whose untoward oxidation would result in functional loss. Therefore, preservation of controlled oxidative conditions in the FF is a requirement for the fine-tuned oocyte maturation process. In contrast, its disturbance enhances the susceptibility to the establishment of reproductive disorders that would require the intervention of reproductive medicine technology.info:eu-repo/semantics/publishedVersio

The Montreal Cognitive Assessment (MoCA) as a screening test for cognitive dysfunction in multiple sclerosis

This study investigates the utility of the Portuguese version of Montreal Cognitive Assessment (MoCA) as a screening-method for identifying cognitive dysfunction (CD) in multiple sclerosis (MS). The 118 participants with comprehensive neuropsychological assessment were divided into two subgroups: (I) MS group (n = 59) and (II) control group (n = 59). The MS patients were classified as cognitively intact (n = 26) or impaired (n = 33, 56%). The results indicated that the MoCA is a psychometrically valid instrument in assessment of MS patients. The Multiple Linear Regression analyses highlighted the significant influence of Modified Fatigue Impact Scale and Irregular Word Reading Test on MoCA performance. The MoCA total score showed a good discriminative capacity between cognitively impaired and cognitively intact subjects. In addition, there were significant differences in MoCA cognitive domain scores between groups. The MoCA total score cut-off point for identifying CD in MS patients was a score below 26 points (AUC = 0.837, CI = 0.736-0.937). A proposed EM-MoCA-Subscore for identifying the MS-related cognitive impairment (max. score = 19 points, cut-off <17 points, AUC = 0.871, CI = 0.784-0.958), can reduce administration time for cognitive screening in clinical settings. The MoCA is a useful and sensitive instrument to identify the MS-related cognitive impairment.info:eu-repo/semantics/publishedVersio

Gene-gene interaction affects coronary artery disease risk.

Introdução: Existem vários estudos que comparam doentes coronários e controlos, no sentido de determinar quais os polimorfismos que apresentam risco acrescido de doença das artérias coronárias (DC). Os seus resultados têm sido muitas vezes contraditórios, mas apresentam uma limitação suplementar: avaliam os polimorfismos um a um, quando na natureza os polimorfismos não existem isolados. Põe-se a questão se serão mais importantes associações de polimorfismos mutados no mesmo gene ou em genes diferentes. Objectivo: Com o presente trabalho pretendemos avaliar o risco da associação de polimorfismos em termos de aparecimento de DC no mesmo gene ou em genes diferentes. Metodologia: Estudámos em 298 doentes coronários e 298 controlos sãos o risco associado aos polimorfismos (genótipos considerados de risco), DD da Enzima de Converaão da Angiotensina (ECA) I/D; GG da ECA 8, MM do Angiotensinogénio (AGT) 174; TT do AGT 235; TT da Metiltetrahidrofolato Reductase (MTHFR) 677; AA da MTHFR 1298;RR da Paraoxonase1 (PON1) 192 e MM da PON1 55. Posteriormente avaliámos o risco ligado às associações no mesmo gene (DD da ECA + GG da ECA 8; MM do AGT174 + TT do AGT 235; TT da MTHFR 677 + AA da MTHFR 1298). Finalmente, nos polimorfismos que isoladamente apresentavam significância, avaliámos o risco das associações de polimorfismos a níveis funcionais diferentes (ECA + AGT; ECA + MTHFR; ECA + PON1. Finalmente através de um modelo de regressão logística fomos determinar quais as variáveis que se relacionavam de forma significativa e independente com a DC. Resultados: Os polimorfismos isolados como: ECA DD [P<0.0001], ECA 8 GG [P=0,023], e MTHFR 1298 AA [P=0,049]), apresentaram uma frequência mais elevada nos casos, associando-se de forma significativa ao grupo com DC. A associação de polimorfismos no mesmo gene não teve efeito sinergístico ou aditivo e não aumentou o risco de DC. A associação polimórfica em genes diferentes aumentou o risco de DC quando comparada com o risco do polimorfismo isolado. No caso da associação da ECA DD ou ECA 8 GG com a PON1 192 RR, o risco quadruplicou (OR passou de 1,8 para 4,2). Após regressão logística o hábito tabágico, a história familiar, o fibrinogénio, diabetes, a associação ECA DD ou ECA 8 GG com a MTHFR 1298 AA e a interacção ECA DD ou ECA 8 GG com a PON1 192 RR permaneceram na equação, mostrando ser factores de risco independente para DC. Conclusões: A associação de polimorfismos mutados no mesmo gene nunca aumentou o risco do polimorfismo isolado. A associação com interacção de polimorfismos mutados em genes diferentes, pertencentes a sistemas fisiopatológicos e enzimáticos diferentes, esteve sempre associada a maior risco do que cada polimorfismo por si. Este trabalho levanta, pela primeira vez, a possibilidade de tentativa de compreensão do risco genético coronário em conjunto e não de cada polimorfismo por si.INTRODUCTION: Various studies have compared coronary artery disease (CAD) patients with controls in order to determine which polymorphisms are associated with a higher risk of disease. The results have often been contradictory. Moreover, these studies evaluated polymorphisms in isolation and not in association, which is the way they occur in nature. OBJECTIVE: Our purpose was to evaluate the risk of CAD in patients with associated polymorphisms in the same gene or in differen genes. METHODS: We evaluated the risk associated with ACE DD, ACE 8 CC, ACT 174MM, AGT 235TT, MTHFR 677TT, MTHFR 1298AA, PON1 192RR and PON1 55MM in 298 CAD patients and 298 healthy individuals. We then evaluated the risk of associated polymorphisms in the same gene (ACE DD + ACE 8GG; AGT 174MM + AGT 235TT; MTHFR 677TT + MTHFR 1298AA). Finally, for the isolated polymorphisms which were significant, we evaluated the risk of polymorphism associations at different functional levels (ACE + AGT; ACE + MTHFR; ACE + PON1). Multiple logistic regression was used to identify independent risk factors for CAD. RESULTS: Isolated polymorphisms including ACE DD(p < 0.0001), ACE 8 gg (p=0.023), and MTHFR 1298AA (p = 0.049) presented with a significantly higher frequency in the CAD group. An association of polymorphisms in the same gene did not have an additive or synergistic effect, nor did it increase the risk of CAD. Polymorphic associations in different genes increased the risk of CAD, compared with the isolated polymorphisms. The association of ACE DD or ACE 8 GG with PON1 192RR increased the risk of CA fourfold (1.8 to 4.2). After logistic regression analysis, current smoking, family history, fibrinogen, diabetes, and the ACE DD or ACE 8 GG + MTHFR 1298AA and ACE DD or ACE 8 GG + PON1 192RR associations remained in the, model and proved to be independent predictors of CAD. CONCLUSIONS: The association of polymorphisms in the same gene did not increase the risk of the isolated polymorphism. The association of polymorphisms in genes belonging to different enzyme systems was always linked to increased risk compared to the isolated polymorphisms. This study may contribute to a better understanding of overall genetic risk for CAD rather than that associated with each polymorphism in isolation.info:eu-repo/semantics/publishedVersio

Bilateral versus ipsilesional cortico-subcortical activity patterns in stroke show hemispheric dependence

Background Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients, bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods We used an fMRI block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction ( n = 20, with balanced left/right lesion sites). Results Analysis of 10 right-hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left-hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right-hemispheric stroke. Left-hemispheric stroke was in general characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion The observed hemispheric-dependent activation/deactivation shifts are novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation.info:eu-repo/semantics/publishedVersio