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Gramene (http://www.gramene.org) is a knowledgebase for comparative functional analysis in major crops and model plant species. The current release, #54, includes over 1.7 million genes from 44 reference genomes, most of which were organized into 62,367 gene families through orthologous and paralogous gene classification, whole-genome alignments, and synteny. Additional gene annotations include ontology-based protein structure and function; genetic, epigenetic, and phenotypic diversity; and pathway associations. Gramene's Plant Reactome provides a knowledgebase of cellular-level plant pathway networks. Specifically, it uses curated rice reference pathways to derive pathway projections for an additional 66 species based on gene orthology, and facilitates display of gene expression, gene-gene interactions, and user-defined omics data in the context of these pathways. As a community portal, Gramene integrates best-of-class software and infrastructure components including the Ensembl genome browser, Reactome pathway browser, and Expression Atlas widgets, and undergoes periodic data and software upgrades. Via powerful, intuitive search interfaces, users can easily query across various portals and interactively analyze search results by clicking on diverse features such as genomic context, highly augmented gene trees, gene expression anatomograms, associated pathways, and external informatics resources. All data in Gramene are accessible through both visual and programmatic interfaces., (Published by Oxford University Press on behalf of Nucleic Acids Research 2017.)

Expression Atlas (http://www.ebi.ac.uk/gxa) is an added value database that provides information about gene and protein expression in different species and contexts, such as tissue, developmental stage, disease or cell type. The available public and controlled access data sets from different sources are curated and re-analysed using standardized, open source pipelines and made available for queries, download and visualization. As of August 2017, Expression Atlas holds data from 3,126 studies across 33 different species, including 731 from plants. Data from large-scale RNA sequencing studies including Blueprint, PCAWG, ENCODE, GTEx and HipSci can be visualized next to each other. In Expression Atlas, users can query genes or gene-sets of interest and explore their expression across or within species, tissues, developmental stages in a constitutive or differential context, representing the effects of diseases, conditions or experimental interventions. All processed data matrices are available for direct download in tab-delimited format or as R-data. In addition to the web interface, data sets can now be searched and downloaded through the Expression Atlas R package. Novel features and visualizations include the on-the-fly analysis of gene set overlaps and the option to view gene co-expression in experiments investigating constitutive gene expression across tissues or other conditions., (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the absence of transcriptional changes. By contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the three-dimensional organization of the genome results from the interplay of two independent mechanisms: cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; and cohesin-dependent formation of TADs, possibly by loop extrusion, which helps to guide distant enhancers to their target genes.

Introduction: Scientific medical publications are considered to be a source of unbiased and independent information. Authors are required to disclose relationships with the pharmaceutical industry for transparency purposes. The aim of this work was to assess conflict of interest disclosure in a Portuguese top-tier medical journal by comparing authors' self-reported conflicts of interest with payments listed in the official database of Portuguese Ministry of Health., Material and Methods: All articles published in the Portuguese Journal of Cardiology from December 2015 to May 2016 were reviewed. Articles based on clinical images, with authors affiliated to foreign institutions, editorials, letters to the editor, or submitted before January 1st 2015 were excluded. Authors were categorized on concordance between self-reported disclosures and payments listed in the database. Authors who authored multiple articles were counted as new authors, since each paper offered a new opportunity for financial disclosure., Results: Of the 155 authors surveyed, 82 (53%) were in perfect concordance with the sunshine database, while 73 authors (47%) had one or more undisclosed payments. Undisclosed payments totaled over € 210 000. Four (17%) articles mentioned a conflict of interest, 24 articles (96%) had at least one author with undisclosed payments., Discussion: None of the payments listed in the database was acknowledged in self-reported conflicts of interest. This might indicate that authors do not consider their financial relationships with the industry to be relevant., Conclusion: The lack of concordance between self-reported conflicts of interest and payments found in the database raises concerns about incomplete disclosure.

Gathering evidence supports the existence of a population of cells with stem-like characteristics, named cancer stem cells (CSC), which is involved not only in tumor recurrence but also in tumorigenicity, metastization and drug resistance. Several markers have been used to identify putative CSC sub-populations in different cancers. Notwithstanding, it has been acknowledged that breast CSC may originate from non-stem cancer cells (non-SCC), interconverting through an epithelial-to-mesenchymal transition-mediated process, and presenting several deregulated canonical and developmental signaling pathways. These support the heterogeneity that, directly or indirectly, influences fundamental biological features supporting breast tumor development. Accordingly, CSC have increasingly become highly relevant cellular targets. In this review, we will address the stemness concept in cancer, setting the perspective on CSC and their origin, by exploring their relation and regulation within the tumor microenvironment, in the context of emerging therapeutic targets. Within this framework, we will discuss nucleolin, a protein that has been associated with angiogenesis and, more recently, with the stemness phenotype, becoming a common denominator between CSC and non-SCC for multicellular targeting., (Copyright © 2017 Elsevier B.V. All rights reserved.)

4T1 metastatic breast cancer model have been widely used to study stage IV human breast cancer. However, the frequent inoculation of a large number of cells, gives rise to fast growing tumors, as well as to a surprisingly low metastatic take rate. The present work aimed at establishing the conditions enabling high metastatic take rate of the triple-negative murine 4T1 syngeneic breast cancer model. An 87% 4T1 tumor incidence was observed when as few as 500 cancer cells were implanted. 4T1 cancer cells colonized primarily the lungs with 100% efficiency, and distant lesions were also commonly identified in the mesentery and pancreas. The drastic reduction of the number of inoculated cells resulted in increased tumor doubling times and decreased specific growth rates, following a Gompertzian tumor expansion. The established conditions for the 4T1 mouse model were further validated in a therapeutic study with peguilated liposomal doxorubicin, in clinical used in the setting of metastatic breast cancer. Inoculated cell density was proven to be a key methodological aspect towards the reproducible development of macrometastases in the 4T1 mouse model and a more reliable pre-clinical assessment of antimetastatic therapies., Competing Interests: Author Vera Moura (VM) received funding from TREAT U, SA, a commercial company, in the form of salaries. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Breast cancer stem cells (CSC) are thought responsible for tumor growth and relapse, metastization and active evasion to standard chemotherapy. The recognition that CSC may originate from non-stem cancer cells (non-SCC) through plastic epithelial-to-mesenchymal transition turned these into relevant cell targets. Of crucial importance for successful therapeutic intervention is the identification of surface receptors overexpressed in both CSC and non-SCC. Cell surface nucleolin has been described as overexpressed in cancer cells as well as a tumor angiogenic marker. Herein we have addressed the questions on whether nucleolin was a common receptor among breast CSC and non-SCC and whether it could be exploited for targeting purposes. Liposomes functionalized with the nucleolin-binding F3 peptide, targeted simultaneously, nucleolin-overexpressing putative breast CSC and non-SCC, which was paralleled by OCT4 and NANOG mRNA levels in cells from triple negative breast cancer (TNBC) origin. In murine embryonic stem cells, both nucleolin mRNA levels and F3 peptide-targeted liposomes cellular association were dependent on the stemness status. An in vivo tumorigenic assay suggested that surface nucleolin overexpression per se, could be associated with the identification of highly tumorigenic TNBC cells. This proposed link between nucleolin expression and the stem-like phenotype in TNBC, enabled 100% cell death mediated by F3 peptide-targeted synergistic drug combination, suggesting the potential to abrogate the plasticity and adaptability associated with CSC and non-SCC. Ultimately, nucleolin-specific therapeutic tools capable of simultaneous debulk multiple cellular compartments of the tumor microenvironment may pave the way towards a specific treatment for TNBC patient care., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The authors report the case of a 52-year-old woman with depressive syndrome, treated with lamotrigine for about five months, who went to the emergency department for atypical precordial pain. The electrocardiogram (ECG) revealed a 2-mm downsloping ST-segment elevation and negative T waves in V1 and V2. Due to suspicion of ST-elevation acute coronary syndrome, cardiac catheterization was performed, which revealed normal coronary arteries. The initial ECG was suggestive of type 1 Brugada pattern, but subsequent serial ECGs were less typical. A flecainide test showed the same pattern. After discontinuation of lamotrigine reversal of the typical Brugada ECG pattern was observed. Although not currently contraindicated in Brugada syndrome, the antidepressant lamotrigine blocks sodium channels, which are usually inactivated in heart cell membranes in Brugada syndrome, and may be responsible for the expression of type 1 Brugada pattern., (Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Maximum-likelihood methods based on models of codon substitution have been widely used to infer positively selected amino acid sites that are responsible for adaptive changes. Nevertheless, in order to use such an approach, software applications are required to align protein and DNA sequences, infer a phylogenetic tree and run the maximum-likelihood models. Therefore, a significant effort is made in order to prepare input files for the different software applications and in the analysis of the output of every analysis. In this paper we present the ADOPS (Automatic Detection Of Positively Selected Sites) software. It was developed with the goal of providing an automatic and flexible tool for detecting positively selected sites given a set of unaligned nucleotide sequence data. An example of the usefulness of such a pipeline is given by showing, under different conditions, positively selected amino acid sites in a set of 54 Coffea putative S-RNase sequences. ADOPS software is freely available and can be downloaded from http://sing.ei.uvigo.es/ADOPS.

Breast screening is the regular examination of a woman's breasts to find breast cancer earlier. The sole exam approved for this purpose is mammography. Usually, findings are annotated through the Breast Imaging Reporting and Data System (BIRADS) created by the American College of Radiology. The BIRADS system determines a standard lexicon to be used by radiologists when studying each finding. Although the lexicon is standard, the annotation accuracy of the findings depends on the experience of the radiologist. Moreover, the accuracy of the classification of a mammography is also highly dependent on the expertise of the radiologist. A correct classification is paramount due to economical and humanitarian reasons. The main goal of this work is to produce machine learning models that predict the outcome of a mammography from a reduced set of annotated mammography findings. In the study we used a data set consisting of 348 consecutive breast masses that underwent image guided or surgical biopsy performed between October 2005 and December 2007 on 328 female subjects. The main conclusions are threefold: (1) automatic classification of a mammography, independent on information about mass density, can reach equal or better results than the classification performed by a physician; (2) mass density seems to be a good indicator of malignancy, as previous studies suggested; (3) a machine learning model can predict mass density with a quality as good as the specialist blind to biopsy, which is one of our main contributions. Our model can predict malignancy in the absence of the mass density attribute, since we can fill up this attribute using our mass density predictor.

It has been recognized that the development of new therapeutic drugs is a complex and expensive process. A large number of factors affect the activity in vivo of putative candidate molecules and the propensity for causing adverse and toxic effects is recognized as one of the major hurdles behind the current "target-rich, lead-poor" scenario. Structure-Activity Relationship (SAR) studies, using relational Machine Learning (ML) algorithms, have already been shown to be very useful in the complex process of rational drug design. Despite the ML successes, human expertise is still of the utmost importance in the drug development process. An iterative process and tight integration between the models developed by ML algorithms and the know-how of medicinal chemistry experts would be a very useful symbiotic approach. In this paper we describe a software tool that achieves that goal--iLogCHEM. The tool allows the use of Relational Learners in the task of identifying molecules or molecular fragments with potential to produce toxic effects, and thus help in stream-lining drug design in silico. It also allows the expert to guide the search for useful molecules without the need to know the details of the algorithms used. The models produced by the algorithms may be visualized using a graphical interface, that is of common use amongst researchers in structural biology and medicinal chemistry. The graphical interface enables the expert to provide feedback to the learning system. The developed tool has also facilities to handle the similarity bias typical of large chemical databases. For that purpose the user can filter out similar compounds when assembling a data set. Additionally, we propose ways of providing background knowledge for Relational Learners using the results of Graph Mining algorithms., (Copyright 2011 The Author(s). Published by Journal of Integrative Bioinformatics.)

Because of their sensitivity and high level of discrimination, short tandem repeat (STR) maker systems are currently the method of choice in routine forensic casework and data banking, usually in multiplexes up to 15-17 loci. Constraints related to sample amount and quality, frequently encountered in forensic casework, will not allow to change this picture in the near future, notwithstanding the technological developments. In this study, we present a free online calculator named PopAffiliator ( http://cracs.fc.up.pt/popaffiliator ) for individual population affiliation in the three main population groups, Eurasian, East Asian and sub-Saharan African, based on genotype profiles for the common set of STRs used in forensics. This calculator performs affiliation based on a model constructed using machine learning techniques. The model was constructed using a data set of approximately fifteen thousand individuals collected for this work. The accuracy of individual population affiliation is approximately 86%, showing that the common set of STRs routinely used in forensics provide a considerable amount of information for population assignment, in addition to being excellent for individual identification.

In gametophytic self-incompatibility systems, many specificities (different 'lock-and-key' combinations) are maintained by frequency-dependent selection for very long evolutionary times. In Solanaceae, trans-specific evolution (the observation that an allele from one species may be more closely related to an allele from another species than to others from the same species) has been taken as an argument for the very old age of specificities. In this work, by determining, for the first time, the age of extant Prunus species, we show that this reasoning cannot be applied to Prunoideae. Furthermore, since our sample size is large (all S-RNase encoding the female component and SFB encoding the male component GenBank sequences), we were able to estimate the age of the oldest Prunus specificities. By doing so, we show that the lower variability levels at the Prunus S-locus, in comparison with Solanaceae, is due to the younger age of Prunus alleles, and not to a difference in silent mutation rates. We show that the ancestor to extant Prunus species harboured at least 102 specificities, in contrast to the maximum of 33 observed in extant Prunus species. Since the number of specificities that can be maintained in a population depends on the effective population size, this observation suggests a bottleneck in Prunus evolutionary history. Loss of specificities may have occurred during this event. Using only information on amino acid sites that determine specificity differences, and a simulation approach, we show that a model that assumes closely related specificities are not preferentially lost during evolution, fails to predict the observed degree of specificity relatedness.

Introduction: Coronary artery disease (CAD) becomes an important cause of morbidity and mortality after the age of 45 years., Objective: To evaluate the epidemiology and clinical features of all patients under 45 years old admitted with myocardial infarction., Methods: We studied 595 patients admitted with myocardial infarction between January 2000 and December 2002. We analyzed risk factors for CAD, clinical profile, therapeutics and complications (arrhythmic, mechanical and ischemic). The patients were divided into two groups: A--under 45 years old and B-- aged 45 or over., Results: Group A--56 patients (9.4%); group B--539 patients (90.6 %). There was a higher prevalence of smoking in group A (57% vs. 23.6%; p < 0.01). Hypertension, diabetes and history of CAD were significantly more common in group B. There were no differences in hyperlipidemia (group A: 43% vs. group B: 43.5%). Fibrinolysis was performed in 28 patients (70%) from group A compared to 40 patients (45.9%; p < 0.01) from group B. Use of digitalis and inotropic agents was greater in group B. No differences were found in other pharmacological therapeutics. We found more complications in group B (24% vs. 11%)., Conclusions: There was a higher prevalence of smoking in patients under 45 years old and of hypertension, diabetes and CAD in patients aged over 45. The high rate of hyperlipidemia in both groups highlights the importance of primary prevention. Fibrinolysis was performed more frequently in younger patients. There were more complications in older patients.

Introduction: Stent implantation without predilation simplifies a large proportion of coronary intervention procedures, with a significant reduction in costs and procedure time., Objectives: To determine the variables associated with a higher probability of failure in direct stent implantation in daily practice in a wide range of clinical contexts and types of lesions., Population and Methods: Over a period of 28 months, direct implantation of 931 stents was attempted in our Center (811 patients, 83% male, mean age 62 +/- 12 years; 1.1 stent per patient). In 59 patients (7.3%), balloon predilation was necessary, and the factors associated with direct implant failure were determined., Results: The vessels treated were: anterior descending (373 lesions: 40.1%), right coronary artery (306 lesions: 32.9%, circumflex (210 lesions: 22.6%), saphenous vein (35 lesions: 3.8%), left main (5 lesions: 0.4%) and internal mammary artery (2 lesions: 0.2%). 54% of the lesions were of type B2/C (ACC/AHA classification). The characteristics significantly associated with, or with statistical tendency towards, a lower success rate in direct stent implantation were: Lesion in the circumflex (11% vs. 5.5%, p = 0.012); reference vessel diameter less than 3.0 mm (9.8% vs. 6.2%, p = 0.097); age over 65 years (8.5% vs. 4.5%, p = 0.017); left main disease, irrespective of the vessel treated (23.5%% vs. 6.5%, p = 0.023); B2/C lesion (7.8%, vs. 4.8%, p = 0.086); calcification (9.9% vs. 4.9%, p = 0.012); vessel angulation greater than 45 degrees (9.9% vs. 4.9%, p = 0.009); and Express stent implant (19.6% vs. 6.0%, p < 0.001). On multivariate analysis, independent predictors of failure in direct stent implantation were: left main lesion (RR 6.6; 95% CI 1.73-24.93; p = 0.013), presence of calcium (RR 1.9; 95% CI 1.02-3.37; p = 0.049), vessel curvature (RR 2.0; 95% CI 1.13-3.64; p = 0.018), reference vessel diameter less than 3 mm (RR 2.2; 95% CI 1.15-4.32; p = 0.023), lesion type B2/C (RR 1.9; 95% CI 1.0-3.52; p = 0.044) and Express stent (RR 2.7; 95% CI 1.07-6.79; p = 0.05)., Conclusion: In a large and heterogeneous series of patients, direct stenting was not possible in 7.3% of cases, which required balloon predilation. Certain clinical and angiographic features can predict when this is more like to occur.

Introduction: In patients (pts) with atrial fibrillation (AF) of more than 48 hours' duration, electrical cardioversion (ECV) should only be performed after 3 weeks of effective anticoagulation. Transesophageal echocardiography (TEE) allows earlier ECV; however, despite exclusion of thrombi in the atrium and left atrial appendage (LAA), cases of thromboembolism related to ECV have been documented in AF. To define a low-risk group for cardioversion without previous anticoagulation, pts were selected for immediate ECV if no thrombi or dynamic spontaneous echo contrast (auto-contrast) were found after TEE and if LAA velocity was more than 0.25 m/sec., Methods and Results: We performed TEE in 31 consecutive pts referred for ECV for AF of more than 48 hours' duration and without previous anticoagulation. After TEE the pts eligible for immediate ECV began anticoagulation with low molecular weight heparin (enoxaparin), subcutaneously in therapeutic doses, together with warfarin immediately before cardioversion. Enoxaparin was continued until an INR of over 2 was reached. Based on the TEE findings, the pts were divided in 2 groups: immediate ECV, group A, 20 pts with a mean age of 62 +/- 13 years, 6 female; and conventional therapy with warfarin before ECV, group B, 11 pts, mean age of 67 +/- 10 years (p < 0.05), 2 female. None of the pts in either group had mitral stenosis or previous episodes of thromboembolism. The mean transverse diameter of the left atrium in the 31 pts was 47 +/- 4.5 mm, without statistically significant differences between the 2 groups. Of the 11 pts in group B, 3 had a thrombus in the LAA, 6 dynamic spontaneous echo contrast and the remainder LAA velocities of less than 0.25 m/sec. ECV was achieved in all the pts, with no complications. Oral anticoagulation was maintained for at least a month. At one month, sinus rhythm was maintained in 75% of group A and 45% of group B (p < 0.01)., Conclusion: In pts with AF of more than 48 hours' duration and no previous history of thromboembolism, the use of our exclusion criteria during TEE enabled stratification of a low-risk population for immediate ECV, which was accomplished effectively and safely in 2/3 of the pts. This strategy is associated with early symptomatic improvement, and may contribute to maintenance of sinus rhythm after one month, which was significantly better than in the pts who had prolonged therapy with warfarin before ECV, despite the differences found in age and left ventricular function.

Introduction and Objective: Ventricular resynchronization therapy improves cardiac function in patients (pts) with dilated cardiomyopathy and intraventricular conduction disturbances. The effects of ventricular resynchronization on right ventricular function have been poorly studied. Tricuspid annular motion can be studied with tissue Doppler echocardiography, which enables quantitative assessment of right ventricular function. The aim of this study was to evaluate the effects of ventricular resynchronization on right ventricular function with pulsed tissue Doppler., Patients: We studied ten pts, eight male, mean age 65 +/- 10 years, with dilated cardiomyopathy, intraventricular conduction disturbances and heart failure, New York Heart Association functional class III or IV. Five pts had coronary artery disease and the others idiopathic dilated cardiomyopathy. All pts had an implanted cardioverter-defibrillator with ventricular resynchronization., Methods: Before and one month after device implantation right ventricular function was evaluated with pulsed wave tissue Doppler study of tricuspid annular motion. The maximum velocity of the S wave (MV-S), E wave (MV-E), and A wave (MV-A), E/A ratio, isovolumetric contraction time (IVCT) and ejection time (ET) were determined. Right ventricular size and left ventricular ejection fraction (EF) were measured. Functional class before and after implantation was assessed., Results: MV-S, MV-E and MV-A did not change significantly. The E/A ratio decreased significantly (p = 0.017). There were no differences in IVCT and ET, nor in right ventricular size before and after resynchronization. EF improved in all but one patient (p = 0.003). All pts had an improvement in functional class, except the one without increased EF., Conclusions: Ventricular resynchronization therapy does not appear to have a deleterious effect on right ventricular function in pts with dilated cardiomyopathy and intraventricular conduction disturbances. The main beneficial effect of this type of therapy appears to be improvement in left ventricular function.

Introduction and Objective: Ventricular resynchronization therapy optimizes cardiac function and induces reverse remodeling of the left ventricle (LV) in patients (pts) with dilated cardiomyopathy and intraventricular conduction disturbances. Improvement of LV mechanical synchrony seems to be the predominant mechanism. There is a growing interest in objective quantification of desynchronization. This study aims to evaluate the effect of ventricular resynchronization therapy on LV remodeling and on LV desynchronization, assessed by tissue Doppler echocardiography., Patients: We studied ten pts, eight male, mean age 65 +/- 10 years, with dilated cardiomyopathy, intraventricular conduction disturbances and heart failure, New York Heart Association functional class III or IV. Five pts had coronary artery disease and the others idiopathic dilated cardiomyopathy. All pts had an implanted cardioverter, defibrillator with cardiac resynchronization therapy. The LV pacing electrode was placed in the lateral or posterolateral vein., Methods: Before and one month after resynchronization therapy the following parameters were measured with conventional Doppler echocardiography: LV end-diastolic (LVd) and end-systolic (LVs) size, ejection fraction (EF) and mitral regurgitation (MR) area. For diastolic function the maximum velocity of the E wave (MV-E) and A wave (MV-A), E/A ratio, LV filling time (LV-FT) and isovolumetric relaxation time (IVRT) were meadured. Mitral longitudinal motion was studied with pulsed tissue Doppler. Maximum velocity of the systolic S wave (MV-S) and isovolumetric contraction time (IVCT) were measured in the tissue Doppler curve of the septum and lateral, inferior and anterior walls. To evaluate the degree of desynchronization the RV index was calculated for each patient, based on the difference between the maximum and minimum IVCT, normalized for the maximum IVCT., Results: There was a significant reduction in LVd and MR. EF increased significantly (p = 0.003). There were no differences in diastolic function parameters. MV-S did not increase significantly. IVCT increased significantly at the lateral wall (p = 0.037). The RV index demonstrated a significant reduction in ventricular desynchronization (p = 0.001)., Conclusions: Ventricular resynchronization therapy induces reverse remodeling and improves LV function in selected pts. Improvement of mechanical LV synchrony seems to be the predominant mechanism. Ventricular desynchronization can be measured by tissue Doppler echocardiography.

Introduction and Objective: In patients (pts) with dilated cardiomyopathy and intraventricular conduction disturbances, resynchronization therapy improves cardiac function and functional capacity. Determination of the optimal AV interval is essential to optimize the therapy results and various methods have been used in daily practice to obtain such an interval. The aim of this work is to assess optimal AV determined by impedance cardiography and compare it to the interval previously obtained by transmitral flow Doppler echocardiography., Patients: Seven pts were evaluated, five men, mean age of 61 +/- 10 years, with dilated cardiomyopathy, intra-ventricular conduction disturbances and heart failure, New York Heart Association functional class III or IV. Four pts had ischemic cardiomyopathy and three idiopathic. All pts had an implanted cardioverter-defibrillator with cardiac resynchronization., Methods: The optimal AV delay was estimated by transmitral flow pulsed Doppler using the method previously described by Ritter. Subsequently, cardiac output (CO) was determined by impedance cardiography. CO was estimated for different AV delays, beginning with 80 ms until occurrence of fusion QRS. The optimal AV delay was defined as the value corresponding to the highest measured CO. The ideal AV interval was compared between the two methods used., Results: The AV delay determined by echocardiography varied between 120 and 170 ms (134 +/- 17 ms). The optimum AV delay based on CO estimation varied between 110 and 190 ms (137 +/- 26 ms). There was a correlation between the delays determined by the two methods (r = 0.844; p = 0.017)., Conclusions: In pts undergoing ventricular resynchronization therapy, AV delay optimization based on CO determined by impedance cardiography is comparable to that measured by transmitral flow pulsed Doppler. However, impedance cardiography seems a more objective and simpler technique.

The authors present the case of a 25-year-old female patient, white, with mental retardation and proptosis, and a history of repeated cerebrovascular events. During investigation elevated levels of homocysteinemia and homocystinuria were demonstrated. The authors present a review of related literature.

Pulmonary valve stenosis and atrial septal defect are common forms of congenital heart disease; however, their association is relatively rare. When the two conditions are present simultaneously, significant left-to-right shunt is often prevented by the outflow obstruction, which protects the pulmonary bed until adulthood. This work describes a case of simultaneous percutaneous treatment of both congenital malformations. Although these procedures have been applied in isolation as methods of treatment, this case demonstrates the feasibility and effectiveness of a combined percutaneous treatment.

The authors present a case report of a patient with abdominal pain that began 6 months before hospital admission. Ambulatory abdominal echography and computed tomography (CT) revealed partial thrombosis of the inferior vena cava (IVC) with right atrial extension. During hospitalization, magnetic resonance imaging (MRI) revealed aspects suggesting a tumoral lesion of the right atrium, rather than a thrombus, with tumoral extension to the IVC. The echocardiogram showed images suggesting a right atrial tumor. Transesophageal echocardiography confirmed the diagnosis. During surgery, an IVC tumor was found invading the right atrium, which histopathology confirmed as a leiomyosarcoma. The authors present this case because this type of tumor is rare (21 cases worldwide at this anatomic site), it is difficult to diagnose, and its management has not been adequately described. The authors review the literature relevant to this case.