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We report a case of a 43-year-old man with situs inversus and dextrocardia who was admitted with syncope in the setting of complete atrioventricular block. The complex anatomy poses a considerable challenge to transvenous permanent pacemaker implantation. We employed a novel technique using vascular ultrasound and agitated saline solution to assist with lead positioning. This technique could be useful in pediatric populations or younger patients, in whom the use of ionizing radiation is an important issue., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Cardiovascular Echography.)

The European Bioinformatics Institute (EMBL-EBI) provides access to a wide range of core databases and analysis tools that are of key importance in bioinformatics. As well as providing web interfaces to these resources, web services are available using REST and SOAP protocols that enable programmatic access and allow their integration into other applications and analytical workflows and pipelines. This article describes the various options available to researchers and bioinformaticians who would like to use our resources via the web interface employing RESTful web service clients provided in Perl, Python, and Java, or would like to use Docker containers to integrate the resources into analysis pipelines and workflows. © 2019 by John Wiley & Sons, Inc., (© 2019 John Wiley & Sons, Inc.)

The InterPro database (http://www.ebi.ac.uk/interpro/) classifies protein sequences into families and predicts the presence of functionally important domains and sites. Here, we report recent developments with InterPro (version 70.0) and its associated software, including an 18% growth in the size of the database in terms on new InterPro entries, updates to content, the inclusion of an additional entry type, refined modelling of discontinuous domains, and the development of a new programmatic interface and website. These developments extend and enrich the information provided by InterPro, and provide greater flexibility in terms of data access. We also show that InterPro's sequence coverage has kept pace with the growth of UniProtKB, and discuss how our evaluation of residue coverage may help guide future curation activities.

Complexes of the type (R 2 Cyclam)ZrCl 2 (where R = CH 2 ═C(H)CH 2 (All), CH 2 ═C(Me)CH 2 ( Me All), and PhCH 2 (Bn)) react with suitable Grignard reagents to produce the corresponding alkyl derivatives (R 2 Cyclam)ZrR' 2 (R' = Me, CH 2 Ph). Thermally induced double metalation of the pending arms of the cyclam ligand led to the formation of complexes ((CH═C(H)CH 2 ) 2 Cyclam)Zr, 14, ((CH═C(Me)CH 2 ) 2 Cyclam)Zr, 15, or ((C 6 H 4 CH 2 ) 2 Cyclam)Zr, 16. These reactions proceed through C(sp 2 )-H bond activation and R'H elimination and convert the original dianionic tetracoordinated cyclam-based ligands in tetraanionic hexacoordinated ligands that establish two new Zr-C bonds. The cleavage of the Zr-C bonds may be readily achieved by treatment of the bis( ortho-metalated) species 16 with protic substrates ( tert-butanol, phenol, thiophenol, aniline, benzophenone hydrazone, pyrazole, and N, N'-diphenylhydrazine), to give rise to (Bn 2 Cyclam)ZrX 2 complexes (X = O t Bu, OPh, SPh, NHPh, NHNCPh 2 , C 3 H 3 N 2 , N, N'-PhNNPh). In catalytic conditions, complexes (All 2 Cyclam)Zr(NMe 2 ) 2 , 14, 15, or 16 convert 2,2-diphenyl-pent-4-enylamine to 2-methyl-4,4-diphenylpyrrolidine with 100% selectivity and conversion values varying between 61 and 88% in 4.5 h, at 115 °C. Complexes 14 and 15, which display metalated allyl and methallyl pending groups on the cyclam ring, are the most active species (1.7 < TOF < 2.0 h -1 ). The mechanism of this reaction was studied by density functional theory that revealed two competitive paths, one proceeding through an imido intermediate and another that occurs via an amido ligand. Both cases represent cooperative mechanisms with active participation of the cyclam, as proton exchange between the coordinated substrate and the ligand side arm with reversible C-H activation is a crucial feature of the mechanism.

The idea that noncrop habitat enhances pest control and represents a win-win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win-win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Mowat-Wilson syndrome (MWS) is characterized by severe intellectual disability, absent or impaired speech and microcephaly, with a gradual post-natal onset. The syndrome is often confused with other Angelman-like syndromes (ALS) during infancy, but in older children and adults, the characteristic facial gestalt of Mowat-Wilson syndrome allows it to be distinguished easily from ALS. We report two cases in which an exome-first approach of patients with MWS identified two novel deletions in the ZEB2 gene ranging from a 4 base deletion (case 1) to at least a 573 Kb deletion (case 2)., Competing Interests: The authors declare that they have no conflict of interest.

Software Containers are changing the way scientists and researchers develop, deploy and exchange scientific software. They allow labs of all sizes to easily install bioinformatics software, maintain multiple versions of the same software and combine tools into powerful analysis pipelines. However, containers and software packages should be produced under certain rules and standards in order to be reusable, compatible and easy to integrate into pipelines and analysis workflows. Here, we presented a set of recommendations developed by the BioContainers Community to produce standardized bioinformatics packages and containers. These recommendations provide practical guidelines to make bioinformatics software more discoverable, reusable and transparent.  They are aimed to guide developers, organisations, journals and funders to increase the quality and sustainability of research software., Competing Interests: No competing interests were disclosed.

Summary: JABAWS 2.2 is a computational framework that simplifies the deployment of web services for Bioinformatics. In addition to the five multiple sequence alignment (MSA) algorithms in JABAWS 1.0, JABAWS 2.2 includes three additional MSA programs (Clustal Omega, MSAprobs, GLprobs), four protein disorder prediction methods (DisEMBL, IUPred, Ronn, GlobPlot), 18 measures of protein conservation as implemented in AACon, and RNA secondary structure prediction by the RNAalifold program. JABAWS 2.2 can be deployed on a variety of in-house or hosted systems. JABAWS 2.2 web services may be accessed from the Jalview multiple sequence analysis workbench (Version 2.8 and later), as well as directly via the JABAWS command line interface (CLI) client. JABAWS 2.2 can be deployed on a local virtual server as a Virtual Appliance (VA) or simply as a Web Application Archive (WAR) for private use. Improvements in JABAWS 2.2 also include simplified installation and a range of utility tools for usage statistics collection, and web services querying and monitoring. The JABAWS CLI client has been updated to support all the new services and allow integration of JABAWS 2.2 services into conventional scripts. A public JABAWS 2 server has been in production since December 2011 and served over 800 000 analyses for users worldwide., Availability and Implementation: JABAWS 2.2 is made freely available under the Apache 2 license and can be obtained from: http://www.compbio.dundee.ac.uk/jabaws., Contact: g.j.barton@dundee.ac.uk.

Oenopia conglobata is one of the most common ladybird species in urban green areas of the Mediterranean region. We have obtained data about its prey acceptability and prey preferences. In a laboratory experiment, we investigated the acceptability of seven aphid and one psyllid species as prey for this coccinellid: the aphids Chaitophorus populeti, Aphis gossypii , Aphis craccivora Monelliopsis caryae , Eucallipterus tiliae , Aphis nerii (on white poplar, pomegranate, false acacia, black walnut, lime, and oleander, respectively), and the psyllid Acizzia jamatonica on Persian silk tree. These species are abundant in urban green areas in the Mediterranean region. In addition, we tested the acceptability of Rhopalosiphum padi on barley, an aphid species easily reared in the laboratory. We also tested preferences of the predator in cafeteria experiments with three aphid species and one aphid and the psyllid. Adults and larvae of the coccinellid accepted all of the preys offered, except A. nerii , with a clear preference for M. caryae . The predator also showed preference for M. caryae when it was offered in a cafeteria experiment with other aphid species or with the psyllid. The aphid R. padi obtained a good acceptability and could be used for rearing O. conglobata in the laboratory., Competing Interests: The authors declare no conflict of interest.

Introduction: Although uncommon, major vessel hemorrhage is the most feared complication of mediastinoscopy. Our goal was to determine the optimal management strategy and to develop a simple and accessible protocol for optimizing care in these situations., Methods: Data collection after reviewing the relevant literature. A literature review was conducted using the following databases: PubMed, Medline, Embase and ScienceDirect., Results: The protocol consists of three distinct parts - initial checklist, considerations in minor bleeding and performance in major bleeding. In this last section we propose an initial approach based mainly on fluid resuscitation and immediate surgical correction if the former has not been successful., Conclusion: Mediastinoscopy continues to be an important and effective diagnostic tool. However, it can cause important iatrogenic lesions which the anesthesiologist and surgical team must be prepared to diagnose early and treat properly.

Introduction: This study evaluated the effects of foot reflexotherapy on pain and postural balance in elderly individuals with low back pain., Design: Randomized, controlled pilot study. Participants ( n = 20) were randomly assigned to 2 groups: individuals submitted to conventional foot massage (control group) or foot reflexotherapy (RT, intervention group) for a period of 5 weeks. Questionnaires on pain and disability (visual analogue scale [VAS] and Roland-Morris Disability Questionnaire [RMDQ]), heart rate variability, and orthostatic balance and baropodometric analysis were assessed at two intervals: before and after intervention., Results: RT group showed statistically significant differences when compared to control group in the following parameters: decrease in VAS scores for pain throughout the study, decrease in parasympathetic activity, and improvement in RMDQ scores. The two groups did not statistically differ in either orthostatic balance or baropodometric analyses., Conclusion: This study demonstrated that foot reflexotherapy induced analgesia but did not affect postural balance in elderly individuals with low back pain.

Dendritic cells (DCs) play a pivotal role in the regulation of the immune response. DC development and activation is finely orchestrated through transcriptional programs. GATA1 transcription factor is required for murine DC development, and data suggest that it might be involved in the fine-tuning of the life span and function of activated DCs. We generated DC-specific Gata1 knockout mice (Gata1-KO DC ), which presented a 20% reduction of splenic DCs, partially explained by enhanced apoptosis. RNA sequencing analysis revealed a number of deregulated genes involved in cell survival, migration, and function. DC migration toward peripheral lymph nodes was impaired in Gata1-KO DC mice. Migration assays performed in vitro showed that this defect was selective for CCL21, but not CCL19. Interestingly, we show that Gata1-KO DC DCs have reduced polysialic acid levels on their surface, which is a known determinant for the proper migration of DCs toward CCL21., (Copyright © 2016 by The American Association of Immunologists, Inc.)

The Triatominae subfamily consists of 150 species in 18 genera, grouped into six tribes. In cytogenetics, triatomines are important biological models because they have holocentric chromosomes and nucleolar persistence in meiosis. The phenomenon of nucleolar persistence has been described for 23 species of triatomine in three genera: Triatoma, Rhodnius, and Panstrongylus. However, new species and genera should be analyzed to assess whether nucleolar persistence is a peculiarity of Triatominae. Thus, this study aimed to analyze nucleolar behavior during spermatogenesis of Meccus pallidipennis and M. longipennis, focusing on the nucleolar-persistence phenomenon. Through the analysis of spermatogenesis, more specifically of meiotic metaphase, we observed the phenomenon of nucleolar persistence in M. pallidipennis and M. longipennis, represented by remnants of nucleolar material in metaphase. Thus, although nucleologenesis of new species, and, especially, new genera, should be analyzed, this study confirms for the first time the phenomenon of nucleolar persistence in the genus Meccus. Therefore, we emphasize the importance of new studies in this area in order to assess whether this phenomenon is truly a synapomorphy of these hematophagous insects.

Ventricular oversensing in patients with defibrillators is an infrequent but deleterious condition. We report a patient with a cardiac resynchronization-defibrillation device that presented with hyperkalemia and syncope. Device interrogation revealed ventricular double-counting within the QRS of a slow ventricular tachycardia, resulting detection of the slow ventricular tachycardia in the ventricular fibrillation zone, and delivery of an effective therapy, below device programmed detection rate. This case of defibrillator inappropriate detection emphasizes the relevance of device electrogram interrogation in order to minimize inappropriate therapies.

Motivation: The 14-3-3 family of phosphoprotein-binding proteins regulates many cellular processes by docking onto pairs of phosphorylated Ser and Thr residues in a constellation of intracellular targets. Therefore, there is a pressing need to develop new prediction methods that use an updated set of 14-3-3-binding motifs for the identification of new 14-3-3 targets and to prioritize the downstream analysis of >2000 potential interactors identified in high-throughput experiments., Results: Here, a comprehensive set of 14-3-3-binding targets from the literature was used to develop 14-3-3-binding phosphosite predictors. Position-specific scoring matrix, support vector machines (SVM) and artificial neural network (ANN) classification methods were trained to discriminate experimentally determined 14-3-3-binding motifs from non-binding phosphopeptides. ANN, position-specific scoring matrix and SVM methods showed best performance for a motif window spanning from -6 to +4 around the binding phosphosite, achieving Matthews correlation coefficient of up to 0.60. Blind prediction showed that all three methods outperform two popular 14-3-3-binding site predictors, Scansite and ELM. The new methods were used for prediction of 14-3-3-binding phosphosites in the human proteome. Experimental analysis of high-scoring predictions in the FAM122A and FAM122B proteins confirms the predictions and suggests the new 14-3-3-predictors will be generally useful., Availability and Implementation: A standalone prediction web server is available at http://www.compbio.dundee.ac.uk/1433pred. Human candidate 14-3-3-binding phosphosites were integrated in ANIA: ANnotation and Integrated Analysis of the 14-3-3 interactome database., (© The Author 2015. Published by Oxford University Press.)

This work describes reactions of heteroallenes with diamido-diamine cyclam-based Zr(iv) complexes of the general formula (Bn2Cyclam)ZrX2 (X = O(t)Bu, , O(i)Pr, , SPh, , NH(t)Bu, ) as well as the di-orthometallated species ((C6H4CH2)2Cyclam)Zr, . The reactions of isocyanates or isothiocyanates with , or resulted in the formation of N-bonded ureate or thioureate cyclam complexes upon [2 + 2] cycloaddition of the Zr-Namido bonds of the cyclam to the heteroallene (). DFT calculations showed that κ(2)-N,N'-ureate bonding is favoured over κ(2)-N,O-ureates, which in turn may be formed in reactions with bulky isocyanates as 1-naphthyl isocyanate (NpN[double bond, length as m-dash]C[double bond, length as m-dash]O). The reactions of with N,N'-cyclohexylcarbodiimide (CyN[double bond, length as m-dash]C[double bond, length as m-dash]NCy) and carbon disulfide afforded guanidinate and dithiocarbamate fragments, respectively, appended to one of the nitrogen atoms of the cyclam ligand. These reactions represent a reliable method for the synthesis of asymmetrically N-functionalized cyclams giving rise to C1 symmetry Zr(iv) species by addition of one equivalent of heteroallenes. The reaction of (Bn2Cyclam)Zr(NH(t)Bu)2, , with one equivalent of mesityl isocyanate (MesN[double bond, length as m-dash]C[double bond, length as m-dash]O) also proceeds through insertion, involving one Zr-NH(t)Bu bond. However, it was observed that the reaction of (Bn2Cyclam)Zr(NH(t)Bu)2, , with MesN[double bond, length as m-dash]C[double bond, length as m-dash]O follows a different path if the reaction is carried out at 60 °C. In this case the reaction leads to [2 + 2] addition of the Zr-Ncyclam bond to the isocyanate, with a concomitant occurrence of orthometallation of the one benzyl pending group of the cyclam ring. The reaction of (t)BuN[double bond, length as m-dash]C[double bond, length as m-dash]O with the di-orthometallated complex ((C6H4CH2)2Cyclam)Zr, , also gave a κ(2)-N,N'-ureate fragment, by isocyanate addition to the macrocycle. DFT calculations on these systems were conducted in an attempt to rationalise the reactivity patterns observed.

Water immersion is widely used in physiotherapy and might relieve pain, probably by activating several distinct somatosensory modalities, including tactile, pressure, and thermal sensations. However, the endogenous mechanisms behind this effect remain poorly understood. This study examined whether warm water immersion therapy (WWIT) produces an antiallodynic effect in a model of localized inflammation and whether peripheral opioid, cannabinoid, and adenosine receptors are involved in this effect. Mice were injected with complete Freund's adjuvant (CFA; intraplantar; i.pl.). The withdrawal frequency to mechanical stimuli (von Frey test) was used to determine 1) the effect of WWIT against CFA-induced allodynia and 2) the effect of i.pl. preadministration of naloxone (a nonselective opioid receptor antagonist; 5 µg/paw), caffeine (a nonselective adenosine receptor antagonist; 150 nmol/paw), 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; a selective adenosine A1 receptor antagonist; 10 nmol/paw), and AM630 (a selective cannabinoid receptor type 2 antagonist; 4 µg/paw) on the antiallodynic effect of WWIT against CFA-induced allodynia. Moreover, the influence of WWIT on paw inflammatory edema was measured with a digital micrometer. WWIT produced a significant time-dependent reduction of paw inflammatory allodynia but did not influence paw edema induced by CFA. Naloxone, caffeine, DPCPX, and AM630 injected in the right, but not in the left, hind paw significantly reversed the antiallodynic effect of WWIT. This is the first study to demonstrate the involvement of peripheral receptors in the antiallodynic effect of WWIT in a murine model of persistent inflammatory pain., (© 2014 Wiley Periodicals, Inc.)

Based on a survey sent to Portuguese centers that perform diagnostic and interventional electrophysiology and/or implantable cardioverter-defibrillator (ICD) implantations, the authors analyze the number and type of procedures performed during 2012 and compare these data with previous years. In 2012, a total of 2561 diagnostic electrophysiologic studies were performed, which were followed by ablation in 2017 cases, representing a steady situation compared with the previous year. There was a 12% increase in the number of ablation procedures for atrial fibrillation, making it for the first time the most frequent indication for ablation, overtaking atrioventricular nodal reentrant tachycardia. The total number of first ICD implantations was 1048 (around 100 per million population), of which 375 were cardiac resynchronization devices (BiV ICDs). This represents a slight decrease (3.3%) in the total number of new implants, with an increase of 10% in the number of BiV ICDs compared to the previous year. However, there was a considerable increase in the number of ICD generator replacements, resulting in an overall increase of 3.5% in implantations performed in 2012. Some comments are made regarding developments in this activity and its current status, and on some factors that may influence the dynamics of this area of interventional cardiology., (Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

The dimeric 14-3-3 proteins dock onto pairs of phosphorylated Ser and Thr residues on hundreds of proteins, and thereby regulate many events in mammalian cells. To facilitate global analyses of these interactions, we developed a web resource named ANIA: ANnotation and Integrated Analysis of the 14-3-3 interactome, which integrates multiple data sets on 14-3-3-binding phosphoproteins. ANIA also pinpoints candidate 14-3-3-binding phosphosites using predictor algorithms, assisted by our recent discovery that the human 14-3-3-interactome is highly enriched in 2R-ohnologues. 2R-ohnologues are proteins in families of two to four, generated by two rounds of whole genome duplication at the origin of the vertebrate animals. ANIA identifies candidate 'lynchpins', which are 14-3-3-binding phosphosites that are conserved across members of a given 2R-ohnologue protein family. Other features of ANIA include a link to the catalogue of somatic mutations in cancer database to find cancer polymorphisms that map to 14-3-3-binding phosphosites, which would be expected to interfere with 14-3-3 interactions. We used ANIA to map known and candidate 14-3-3-binding enzymes within the 2R-ohnologue complement of the human kinome. Our projections indicate that 14-3-3s dock onto many more human kinases than has been realized. Guided by ANIA, PAK4, 6 and 7 (p21-activated kinases 4, 6 and 7) were experimentally validated as a 2R-ohnologue family of 14-3-3-binding phosphoproteins. PAK4 binding to 14-3-3 is stimulated by phorbol ester, and involves the 'lynchpin' site phosphoSer99 and a major contribution from Ser181. In contrast, PAK6 and PAK7 display strong phorbol ester-independent binding to 14-3-3, with Ser113 critical for the interaction with PAK6. These data point to differential 14-3-3 regulation of PAKs in control of cell morphology. Database URL: https://ania-1433.lifesci.dundee.ac.uk/prediction/webserver/index.py.

Objective: To elaborate figures that highlight the microscopic appearance of amastigote forms of the genus Leishmania and other structures subject to confusion during the routine of the direct examination of tegumentary leishmaniasis (TL)., Study Design: We reviewed imprint and scraping slides previously prepared from patients with a definite diagnosis. Smear examinations were performed with an immersion objective (×1,000) selecting structures of interest for photodocumentation and elaboration of the illustrations., Results: We elaborated two 13 × 17 cm figures containing photomicrographs of amastigote forms with typical and atypical morphology of Leishmania parasites and other microorganisms, mainly fungi in the yeast-like phase and bacteria which could be confused with amastigote forms during the direct examination., Conclusions: The production of material like we show here is important and should be encouraged because of the need for constant training of professionals working in the area of TL diagnosis., (© 2014 S. Karger AG, Basel.)

Asthma is an inflammatory disease of the airways associated with a T helper (Th)2 response. Such a response in the lungs requires complex interactions between innate cells and structural cells. Dendritic cells (DCs) are pivotal during sensitization to allergens but clearly require epithelium-derived signals to become activated. Epithelial cells also contribute to the activation and the survival of mast cells (MCs), basophils, and eosinophils and group 2 innate lymphoid cells (ILC2s). In turn, these innate cells can activate DCs to sustain Th2 immunity. Here, we review the role played by these different populations of immune cells in the pathogenesis of asthma and how they interact to orchestrate Th2 immunity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Radical reactions of titanium(III) [Ti((tBu2)O2NN')Cl(S)] (S = THF, 1; S = py, 2; (tBu2)O2NN' = Me2N(CH2)2N(CH2-2-O-3,5-(t)Bu2C6H2)2) are described. Reactions with neutral electron acceptors led to metal oxidation to Ti(IV), [Ti((tBu2)O2NN')Cl(TEMPO)] (4) being formed with the TEMPO radical and [Ti((tBu2)O2NN')Cl2] (9) with PhN═NPh. [Ti((tBu2)O2NN')Cl2] was also formed when [Ti((tBu2)O2NN')Cl(S)] was oxidized by [Cp2Fe][BPh4], but the [Cp2Fe][PF6] analogue yielded [Ti((tBu2)O2NN')ClF] (8). The reactions of [Ti((tBu2)O2NN')Cl(S)] with O2 gave [Ti((tBu2)O2NN')Cl]2(μ-O) (3). The DFT calculated Gibbs energy for the above reaction showed it to be exergonic (ΔG298 = -123.6 kcal·mol(-1)). [Ti((tBu2)O2NN')(CH2Ph)(S)] (S = THF, 5; py, 6) are not stable in solution for long periods and in diethyl ether gave 1:1 cocrystals of [Ti((tBu2)O2NN')(CH2Ph)2] (7) and [Ti((tBu2)O2NN')Cl]2(μ-O) (3), most probably resulting from a disproportionation process of titanium(III) followed by oxygen abstraction by the resulting Ti(II) species. The oxidation of [Ti((tBu2)O2NN')(κ(2)-{CH2-2-(NMe2)-C6H4})] (10), which is a Ti(III) benzyl stabilized by the intramolecular coordination of the NMe2 moiety, led to a complex mixture. Recrystallization of this mixture under air led to a 1:1 cocrystal of two coordination isomers of the titanium oxo dimer (3). In one of these isomers, one metal is pentacoordinate and the dimethylamine moiety of the diamine bis(phenolate) ligand is not bonded to the metal, displaying a coordination mode of the ligand never observed before. The other titanium center is distorted octahedral with two cis-phenolate moieties. In the second unit, the coordination of the two ancillary ligands to the titanium centers reveals mutually cis-phenolate groups in one-half of the molecule and trans-coordinated in the other titanium center, keeping a distorted octahedral environment around each titanium.

Dendritic cells (DCs) are crucial for mounting allergic airway inflammation, but it is unclear which subset of DCs performs this task. By using CD64 and MAR-1 staining, we reliably separated CD11b(+) monocyte-derived DCs (moDCs) from conventional DCs (cDCs) and studied antigen uptake, migration, and presentation assays of lung and lymph node (LN) DCs in response to inhaled house dust mite (HDM). Mainly CD11b(+) cDCs but not CD103(+) cDCs induced T helper 2 (Th2) cell immunity in HDM-specific T cells in vitro and asthma in vivo. Studies in Flt3l(-/-) mice, lacking all cDCs, revealed that moDCs were also sufficient to induce Th2 cell-mediated immunity but only when high-dose HDM was given. The main function of moDCs was the production of proinflammatory chemokines and allergen presentation in the lung during challenge. Thus, we have identified migratory CD11b(+) cDCs as the principal subset inducing Th2 cell-mediated immunity in the LN, whereas moDCs orchestrate allergic inflammation in the lung., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Based on a survey sent to Portuguese centers that perform diagnostic and interventional electrophysiology and/or implant cardioverter-defibrillators (ICDs), the authors analyze the number and type of procedures performed during 2010 and 2011 and compare these data with previous years. In 2011, a total of 2533 diagnostic electrophysiologic procedures were performed, which were followed by ablation in 2013 cases, a steady increase over previous years. The largest share of this increase compared to 2010 was in atrial fibrillation, which is now the second most frequent indication for ablation, after atrioventricular nodal reentrant tachycardia. The total number of ICDs implanted in 2011 was 1084, of which 339 were biventricular (BiV) cardiac resynchronization devices (BiV ICDs). This represents an increase in the total number relative to previous years, 2011 being the first year in which the rate of new ICD implantations in Portugal exceeded 100 per million population. However, compared to 2010, the number of BiV ICDs implanted decreased, despite the recent publication of updated European guidelines on device therapy in heart failure, which clarified and expanded the indications for implantation of these devices. Some comments are made on the current status of cardiac electrophysiology in Portugal and on factors that may influence its development in the coming years., (Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Introduction: Peripherally inserted central catheters, or PICC lines, are frequently used for central venous access because they reduce complications associated with large vein cannulation (CVC). Adequate position of the tip of the catheter is important to central venous pressure (CVP) measurement and drug administration. Inadequate positioning and procedural complications mandate radiologic confirmation. Divergent results have been published comparing techniques., Methodology: The authors analyzed the placement of 117 central venous lines and compared the position of the tip of the catheter by chest x-ray using SPSS&#95;20.0(®)., Results: Fifty-eight (49,6%) PICC inserted via right arm veins, 29(24.8%) PICC via left arm veins and 30(25.6%) internal jugular CVC were recorded. The tip was misplaced in 33(28.2%). Choice between PICC or CVC did not affect the position (p=0.22). Neither the vein [basilic, cephalic, median cubital or jugular] (p>0.4) nor the side [right or left arm] chosen compromised adequate positioning, although distal vein catheters are less likely be easily advanced. CVP measurements were accurate in >80% of the catheters and were no different in CVC or PICC (p>0.5). The catheter patency was a good indicator for adequate positioning., Conclusion: CVC or PICC are equally effective for central venous access and CVP measurements. No difference was found between left or right arm PICC. One third of the catheters had the tip misplaced, which reinforces the need for radiologic confirmation.

Objective: To describe how virtual patients are being used to simulate real-life clinical scenarios in undergraduate pharmacy education in Europe., Methods: One hundred ninety-four participants at the 2011 Congress of the European Pharmaceutical Students Association (EPSA) completed an exploratory cross-sectional survey instrument., Results: Of the 46 universities and 23 countries represented at the EPSA Congress, only 12 students from 6 universities in 6 different countries reported having experience with virtual patient technology. The students were satisfied with the virtual patient technology and considered it more useful as a teaching and learning tool than an assessment tool. Respondents who had not used virtual patient technology expressed support regarding its potential benefits in pharmacy education. French and Dutch students were significantly less interested in virtual patient technology than were their counterparts from other European countries., Conclusion: The limited use of virtual patients in pharmacy education in Europe suggests the need for initiatives to increase the use of virtual patient technology and the benefits of computer-assisted learning in pharmacy education.

Dendritic cells (DCs) regulate both immunity and tolerance. Here we have shown that the ubiquitin editing enzyme A20 (Tnfaip3) determines the activation threshold of DCs, via control of canonical NF-κB activation. Tnfaip3(fl/fl)Cd11c-cre(+) mice lacking A20 in DCs demonstrated spontaneous proliferation of conventional and double-negative T cells, their conversion to interferon-γ (IFN-γ)-producing effector cells, and expansion of plasma cells. They developed ds-DNA antibodies, nephritis, the antiphospholipid syndrome, and lymphosplenomegaly-features of systemic lupus erythematosus-and extramedullary hematopoiesis. A20-deficient DCs were resistant to apoptosis, caused by increased sensitivity to CD40L and RANKL prosurvival signals and upregulation of antiapoptotic proteins Bcl-2 and Bcl-x. They captured injected apoptotic cells more efficiently, resisted the inhibitory effects of apoptotic cells, and induced self-reactive effector lymphocytes. Because genetic polymorphisms in TNFAIP3 are associated with human autoimmune disorders, these findings identify A20-mediated control of DC activation as a crucial checkpoint in the development of systemic autoimmunity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Vanadium diaminebis(phenolate) complexes of the general formulas [LVCl(THF)] (L = Me(2)NCH(2)CH(R)N(CH(2)-2-O-3,5-C(6)H(2)(t)Bu(2))(2), where R = H, Me) and [LV(O)X] [X = Cl; R = H (2), Me (3), O(i)Pr (4), (mu-O)V(O)L (5)] are described. All compounds display octahedral geometry and trans-O(Ph) coordination. For compounds 2, 3, and 5, only one isomer, presenting the V=O ligand trans to the tripodal nitrogen, was formed, while for 4, two isomers were observed by NMR in solution. The UV-vis and circular dichroism spectra of 2 and 3 display very intense charge-transfer transition bands from the phenolate donors to the vanadium, which are in agreement with the (51)V low-field shifts observed. All vanadium(V) complexes were tested as thioanisole sulfoxidation catalysts, revealing very high selectivity when H(2)O(2) was used as the oxidant. However, no enantioselectivity was observed even when enantiopure 3 was used as the catalyst precursor. (1)H and (51)V NMR studies were conducted for the reactions of 2 with aqueous solutions of H(2)O(2) in methanol-d(4) and in acetonitrile-d(3); 2 reacts with the solvents, leading to [LV(O)OMe], by replacement of Cl by MeO in methanol, and to a new vanadium aminebis(phenolate) complex, where the dimethylamine fragment of the original ligand L was replaced by CH(3)CN. In either case, (51)V NMR spectra suggest the formation of peroxovanadium species upon the addition of a H(2)O(2) solution. The subsequent addition of thioanisole to the methanol-d(4) solution leads to regeneration of the original complex.

High mobility group box 1 (HMGB1) is a molecular alarm signal that triggers an immune response when released. It was assumed that the receptor for advanced glycation end-products (RAGE) would mediate the signal to the immune system. Recently pattern recognition receptors that are triggered by molecules of bacterial origin (the Toll-like receptor (TLR) family) were shown to also respond to HMGB1. Now two papers establish the TLR4-HMGB1 axis as proinflammatory, eventually leading to disparate conditions like seizures or skin cancer. These reports add a new twist to our understanding of the mode of action of the alarm signal HMGB1.

The aim of this prospective registry is to evaluate a new algorithm designed to reduce the percentage of unnecessary ventricular pacing (%VP) in patients implanted with a dual-chamber pacemaker, through a dedicated pacing mode (called AAISafeR2) operating in AAI mode with back-up ventricular pacing in DDD mode, and to describe the incidence and distribution of atrioventricular (AV) block in this population. Investigators were free to assign patients to AAISafeR2 mode or to standard DDD (if AAISafeR was contraindicated, mainly due to permanent high-degree AV block). Patients underwent routine follow-up visits at 3, 6, 12, 18 and 24 months after implantation. At each follow-up visit, data were retrieved from pacemaker memories and analyzed to extract %VP and incidence of AV block. Up to December 2006, 158 patients (94 men, mean age 69 +/- 14 years) from nine Portuguese centers had been consecutively included. We also determined the distribution of AV block (according to the criteria used by the pacemaker to classify AV block and switch to DDD mode). AAISafeR was shown to be effective in reducing unnecessary VP in our patient population. The analysis also reveals a high incidence of paroxysmal AV block, often unknown at the time of implantation. There were no complications associated with AAISafeR programming.

An implantable cardioverter defibrillator (ICD) is designed to sense life-threatening ventricular arrhythmias and terminate them, either by rapid pacing or by delivering an electrical shock. Nowadays it is a proven therapy for both primary and secondary prevention of sudden cardiac death. The typical configuration of an ICD consists of a right ventricular sensing/defibrillator lead with two coils (one distal, located in the right ventricle, and one proximal, located at the superior vena cava-right atrium junction) and an active can, the so-called "ventricular triad". Although effective in the vast majority of patients, it could be argued that this is not the most rational arrangement in electrical terms, since the main shock vector is anteriorly displaced in relation to the greater portion of the left ventricular mass. We describe a case of an ICD defibrillation failure that was solved by placing an additional defibrillator lead in a tributary of the coronary sinus.

Aim: Optimal lactate removal was reported to occur at work-rate between 30% and 70% VO2max. However, it has been recently recommended to quantify exercise intensity not in percentage of VO2max but in relation to validated metabolic reference points such as the individual anaerobic threshold (IAT) and the individual ventilatory threshold (IVT). The purpose of this study was to examine the effect on lactate removal of different recovery work-rates below the IAT defined calculating the difference (DT) between IAT and IVT, then choosing the IVT+50%DT, the IVT and the IVT-50%DT work-rates., Methods: Eight male triathletes (VO2max 69.7+/-4.7, VO2IAT 52.9+/-4, VO2IVT 41.1+/-4.7 mL x kg(-1) x min(-1)), after a 6-min treadmill run at 75% of difference between IAT and VO2max, performed in a random order the following 30-min recovery treatments: 1) run at IVT(plus;50%DT), 2) at IVT, 3) at IVT(-50%DT), 4) passive. Blood lactate was measured at 1, 3, 6, 9, 12, 15, 20, 25, 30 minutes of recovery., Results: All active recovery work-rates (from 50+/-5% to 67+/-4% VO2max) were within the range previously reported for optimal lactate removal, and significantly more efficient than passive recovery on lactate removal curve (% of accumulated lactate above rest value). However, significant differences (P<0.01) were found among active recovery intensities: the IVT(-50%DT) was the most efficient work-rate from the 9th minute to 30th minute., Conclusions: In triathletes, the IVT(-50%DT) was the optimal work-rate for lactate removal; moreover none of the studied active work-rate showed further lactate decrease after the 20th minute of recovery.

The aim of this study was to compare the lactate (La) removal during active recovery at three different work rates below the individual anaerobic threshold (IAT). Recently, it has been recommended that exercise intensity should be determined in relation to the IAT instead of the percentage of maximal oxygen uptake ( V(.)O(2max)), especially for training and research purposes. Therefore, we defined the recovery work rates by calculating 50% of the threshold difference (Delta T) between the IAT and the individual ventilatory threshold (IVT) work rates, then choosing the IVT(+50%DeltaT), the IVT and the IVT(-50%DeltaT). All these work rates fell within the range (30-70% V(.)O(2max)) previously reported for optimal La removal. After a 6-min treadmill run at 90% V(.)O(2max), soccer players [ n=12 male, age 22 (1) years] performed, in a random order, four 30-min recovery treatments: (1) run at IVT(+50%DeltaT), (2) at IVT, (3) at IVT(-50%DeltaT), (4) passive recovery. La was obtained at 1, 3, 6, 9, 12, 15, 20, 25 and 30 min of recovery. The La removal curve was significantly affected by treatments ( P<0.01) and recovery timing ( P<0.01), with a significant interaction between them ( P<0.01). Although they were more efficient than passive recovery, the studied work rates [between 39 (7) and 60 (4)% V(.)O(2max)) produced different lactate removal curves. IVT and IVT(-50%DeltaT) were significantly more efficient than IVT(+50%DeltaT), while no difference was found between IVT and IVT(-50%DeltaT) for any time point. In conclusion, both IVT(-50%DeltaT) and IVT were efficient individual work rates for La removal, and no further La decrease occurred after 20 min.

The problem of waiting lists has been widely debated in the Portuguese society. In this paper, the authors report the first results of a prioritization approach, started in March 2000. In this program cardiologists and general practitioners work in close proximity, coordinating efforts in order to improve the establishment of clinical priorities, and consequently optimize hospital referral. Working as cardiology consultants, the authors were able to reduce the number of first consultation requests by 77.9% (December 2002). For the first time it was possible to match the number of requests with the available consultation times, halting the growth of the waiting list.

Objectives: To evaluate the role of contrast Doppler echocardiography in the assessment of aortic stenosis severity, in comparison with the conventional method and using the catheterization study as the gold standard., Study Design: Prospective comparative study., Setting: Echocardiography Laboratory of Cardiology Department., Population: We included 36 consecutive patients, 20 male, aged 67 +/- 11 years, referred for catheterization study to evaluate aortic stenosis severity., Methods: All patients underwent conventional and contrast Doppler echocardiography and catheterization study. For contrast Doppler, we used Levovist (300 mg/ml infusion). We analyzed the following echocardiographic parameters: a) left ventricle dimensions, wall thickness and function; b) aortic valve morphology; c) post-stenotic aortic valve flow--peak velocity, velocity-time integral, peak gradient, mean gradient; d) left ventricle outflow tract flow--peak velocity, velocity-time integral; e) aortic valve functional area; f) acquisition time and Doppler signal intensity for post-stenotic aortic valve flow. Catheterization parameters analyzed: a) peak aortic valve gradient; b) mean aortic valve gradient., Results: Contrast Doppler yielded higher peak gradients than conventional Doppler (85.6 +/- 30.2 vs 72.6 +/- 26.1 mmHg, p < 0.001), as well as higher mean gradients (51.4 +/- 19.0 vs 44.2 +/- 15.9 mmHg, p < 0.001). Peak gradients obtained with contrast Doppler correlated with those obtained invasively (r = 0.88, p < 0.001), although the values were higher (85.6 +/- 30.2 vs 73.6 +/- 32.0 mmHg, p < 0.001). There was no difference between mean contrast Doppler gradients and mean catheterization gradients, which showed a high correlation (r = 0.89, p < 0.001). There was no difference between peak and mean gradients obtained by conventional Doppler and invasively, which yielded correlations of 0.73 and 0.75, respectively (p < 0.001). The sensitivity of contrast Doppler for detection of severe aortic stenosis was 100% for peak gradient and 84% for mean gradient, while for conventional Doppler it was 68% and 58%. The specificity of contrast Doppler was 65% for peak gradient and 88% for mean gradient, while for conventional Doppler it was, respectively, 58% and 88%. Acquisition time for aortic flow visualization was lower (p < 0.001) and flow intensity higher for contrast Doppler, in comparison with conventional Doppler., Conclusions: In this study, contrast Doppler yielded high correlations with invasive data and higher sensitivity and specificity for detection of severe aortic stenosis than conventional Doppler. It is a useful method for evaluation of aortic stenosis severity.

Objectives: To evaluate the association between patterns of pulmonary transvalvular and venous flows in patients with ischemic heart disease, assessed by Doppler echocardiography, and invasive measurements of left ventricular (LV) diastolic pressures., Population: Thirty-seven patients with clinical diagnosis or suspicion of coronary heart disease and referred for coronary angiography; all were in sinus rhythm, and had no known valvular heart or chronic pulmonary disease., Methods: The following were recorded during transthoracic Doppler echocardiography: acceleration time (AT) and total ejection time (ET) of right ventricular outflow; duration of the flow at atrial contraction (a duration) and duration of the "A" wave of mitral inflow (A duration). These data were correlated with the values of LV filling pressures previously obtained by cardiac catheterization., Results: We found a significant correlation of LV end-diastolic pressures with the difference a-A duration (r = 0.75; p < 0.001) and also with the ratio AT/ET (r = -0.73;.

Objective: To evaluate operated type A aortic dissection by Magnetic Resonance Imaging (MRI), in order to detect long-term complications and identify prognostic indexes of evolution., Design: Prospective study with a three-year period of follow-up. Prognosis evaluation., Settings: Outpatient Clinic at Hospital de Santa Maria and Magnetic Resonance Imaging Center at Hospital da Cruz Vermelha., Patients: A sample of 37 patients submitted to type A aortic dissection surgery, included sequentially, after exclusion of those with contraindication to MRI., Methods: Initial evaluation (clinical and MRI study) at 3 to 4 months and at 1, 2 and 3 years after surgery. The mean follow-up time was 39.3 +/- 2.9 months. We evaluated the following complications over the aorta (aortic graft and five segments of residual aorta) and the aortic valve: aneurysm, pseudoaneurysm, rupture, re-dissection, progressive aortic valve regurgitation, reoperation and death. The prognostic indexes analysed were: presence of residual flap; false lumen patency; presence of re-entry points; false lumen to aorta dimension ratio; initial aortic dimension; increase of aortic dimension., Results: All patients, with the exception of three that died, remained asymptomatic., Complications: Aneurysm was detected in 45.9% of patients, located in one or more segments; rupture occurred in three patients, preceded by aneurysm and pseudoaneurysm development; moderate or severe aortic regurgitation was detected in 47.8% of patients. Prognostic indexes: 1. Aneurysm development in each segment yeilded a significant association with: presence of residual flap in the same and other segments; higher initial dimension of the same and other segments, with the exception of the abdominal segment; higher increase in dimension of the same and other segments, with the exception of the abdominal segment; 2. Moderate or severe aortic regurgitation development showed a tendency to association with higher increase in dimension of proximal ascending aorta. 3. No association was found between aneurysm and aortic regurgitation development., Conclusions: Patients operated for type A aortic dissection had a high incidence of late complications which lead to reoperation and in some cases death. The presence of a residual flap, increased aortic dimensions and higher increase rate of aortic dimensions were associated with a complicated evolution. MRI was a very useful technique for long-term monitoring and to identify prognostic indexes of evolution.

Objective: To compare the epidemiological characteristics and immediate results of all first single lead VDD pacemaker (PM) implantations with those of an equal number of dual chamber DDD PM, implanted during a 5-year period in a tertiary-care hospital., Population and Methods: A total of 41 patients (pts) (25 males, mean age of 69.0 +/- 11.8 years) underwent a VDD PM implantation, from 30-11-92 to 15-9-97. This group was compared with an equal number of patients (28 males, mean age of 69.9 +/- 7.31 years) with a DDD PM implanted in the same period, selected by a criterion of immediate temporal proximity of procedure. For each patient we collected the clinical and electrocardiographic (ECG) indications for PM implantation, parameters of atrial (AS) and ventricular (VS) sensing and ventricular pacing (VP), X-ray exposure time (XRT) and complications., Results: In the VDD group, 46.3% of the patients had syncope, 51.2% had complete AV block on the ECG, and 14.6% were PM-dependent. Analyzed procedure-related parameters were as follows: P-wave amplitude: 2.1 +/- 0.6 V; AS threshold: 1.2 +/- 0.7 V; R-wave amplitude: 9.1 +/- 3.3 V; VS threshold: 7.0 +/- 2.0 V; VP thresholds: 0.68 +/- 0.24 mA, 0.43 +/- 0.12 V (for a spike duration of 0.5 ms); ventricular impedance: 644.9 +/- 132.0 ohm; XRT; 7' 43" +/- 8' 23". There were two minor complications, for an incidence of 4.9% (one local hematoma and a vagal reaction). In the DDD group the clinical and ECG characteristics were similar, but there was a 22.0% prevalence of sinus-node dysfunction, VS 0% in the VDD group). The P-wave amplitude and AS threshold were significantly (p < 0.005) better (2.8 +/- 0.9 V and 2.8 +/- 0.9 V respectively). The other parameters were similar to those of the VDD group., Conclusions: The immediate results of VDD PM implantation are good and comparable with those of DDD PM, although with worse acute AS parameters.

The genus Didelphis (Marsupialia, Didelphidae) has the unique capacity of supporting both multiplication cycles of Trypanosoma cruzi simultaneously; besides the intracellular forms, the epimastigotes can be found multiplying and differentiating abundantly in the lumen of the scent glands. The biological significance of the life cycle of T. cruzi within the scent glands of Didelphis marsupialis, as well as its contribution to the epidemiology of the disease, is presently unclear. In order to clarify the mechanisms involved in the colonization of this singular habitat by T. cruzi, as well as to understand its biological role, we have carried out a serological and parasitological follow-up of both natural and experimental infections of young and adult opossums. Although all natural infections were stable and long lasting, no infected scent glands were found, indicating that the stability of the systemic infections does not depend on the presence of flagellates in the scent gland. In 84% of the experimentally infected animals the colonization of the scent glands was preceded by a period of patent parasitemia. Parasitism of the scent glands was essentially permanent and bilateral, and its maintenance was independent of circulating parasites. Moreover, the course of the infection differed depending on the source (scent glands versus axenic culture-derived) of the metacyclic forms. Our results suggest that parasitism of the SG of D. marsupialis is most likely a secondary acquisition, a step toward independence from the insect vector, similarly to what is accepted for Trypanosoma equiperdum.

"Given the importance of information on the population age structure when planning short, medium and long-term needs within the different social strata, this paper is a proposal to deepen...the study of changes in the population pyramids.... Based on the most recent methodologies a study of age discontinuities is carried out and a method of follow-up by cohorts is suggested, taking the 15-19 and 20-24 age groups as an example. The purpose is to show that, as a...cohort ascends in the age pyramid, new and different necessities arise and also different responses are demanded on the part of the social system." Data are for Brazil as a whole and for the state of Sao Paulo. (SUMMARY IN ENG), (excerpt)

The high rate of natural Trypanosoma cruzi infection found in opossums does not always correlate with appreciable densities of local triatomid populations. One alternative method which might bypass the invertebrate vector is direct transmission from mother to offspring. This possibility was investigated in five T. cruzi infected females and their litters (24 young). The influence of maternal antibodies transferred via lactation, on the course of experimental infection, was also examined. Our results show that neonatal transmission is probably not responsible for the high rate of natural T. cruzi infection among opossums. In addition antibodies of maternal origin confer a partial protection to the young. This was demonstrated by the finding of a double prepatency period and 4, 5 fold lower levels of circulating parasites, in experimentally infected pouch young from infected as compared to control uninfected mothers. On the other hand, the duration of patent parasitemia was twice as long as that observed in the control group.

The aim of this preliminary study was to determine the relationship between exercise, magnesium (Mg) status, oxidative stress, and antioxidant defence systems. Some corresponding indices have been evaluated: plasma Mg, ascorbate, uric acid, adrenaline, creatine kinase (CK), thiobarbiturate reactive substances, adrenochrome; and in erythrocytes (RBC): reduced and oxidized glutathione (GSH and GSSG) and Mg. Venous blood samples were withdrawn before and 3 min after completion of a 40 min run. Only two significant changes were observed after effort: plasma Mg decreased (P < 0.009) and plasma adrenaline increased (P < 0.005). There was a non-significant tendency for indices of oxidative stress and antioxidant capacity to increase. The significant correlations between plasma Mg and CK (r = -0.88) and between RBC Mg and plasma ascorbate (r = -0.76) disappeared after the effort. Further research is necessary, with a larger number of subjects and variables, to obtain a better understanding of these interactions.