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BACKGROUND: It is estimated that atrial fibrillation (AF) affects approximately 1.5 million people in Brazil; however, epidemiological data are limited. We sought to evaluate the characteristics, treatment patterns, and clinical outcomes in patients with AF in Brazil by creating the first nationwide prospective registry. METHODS: RECALL was a multicenter, prospective registry that included and followed for 1 year 4,585 patients with AF at 89 sites across Brazil from April 2012 to August 2019. Patient characteristics, concomitant medication use, and clinical outcomes were analyzed using descriptive statistics and multivariable models. RESULTS: Of 4,585 patients enrolled, the median age was 70 (61, 78) years, 46% were women, and 53.8% had permanent AF. Only 4.4% of patients had a history of previous AF ablation and 25.2% had a previous cardioversion. The mean (SD) CHA2DS2-VASc score was 3.2 (1.6); median HAS-BLED score was 2 (2, 3). At baseline, 22% were not on anticoagulants. Of those taking anticoagulants, 62.6% were taking vitamin K antagonists and 37.4% were taking direct oral anticoagulants. The primary reasons for not using an oral anticoagulant were physician judgment (24.6%) and difficulty in controlling (14.7%) or performing (9.9%) INR. Mean (SD) TTR for the study period was 49.5% (27.5). During follow-up, the use of anticoagulants and INR in the therapeutic range increased to 87.1% and 59.1%, respectively. The rates/100 patient-years of death, hospitalization due to AF, AF ablation, cardioversion, stroke, systemic embolism, and major bleeding were 5.76 (5.12-6.47), 15.8 (14.6-17.0), 5.0 (4.4-5.7), 1.8 (1.4-2.2), 2.77 (2.32-3.32), 1.01 (0.75-1.36), and 2.21 (1.81-2.70). Older age, permanent AF, New York Heart Association class III/IV, chronic kidney disease, peripheral arterial disease, stroke, chronic obstructive pulmonary disease, and dementia were independently associated with increased mortality while the use of anticoagulant was associated with lower risk of death. CONCLUSIONS: RECALL represents the largest prospective registry of patients with AF in Latin America. Our findings highlight important gaps in treatment, which can inform clinical practice and guide future interventions to improve the care of these patients.
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Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Masculino , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Fibrilação Atrial/complicações , Brasil/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Anticoagulantes , Hemorragia/induzido quimicamente , Sistema de RegistrosRESUMO
The mRNA cap-binding protein, eIF4E, mediates the recognition of the mRNA 5' end and, as part of the heterotrimeric eIF4F complex, facilitates the recruitment of the ribosomal subunits to initiate eukaryotic translation. Various regulatory events involving eIF4E and a second eIF4F subunit, eIF4G, are required for proper control of translation initiation. In pathogenic trypanosomatids, six eIF4Es and five eIF4Gs have been described, several forming different eIF4F-like complexes with yet unresolved roles. EIF4E5 is one of the least known of the trypanosomatid eIF4Es and has not been characterized in Leishmania species. Here, we used immunoprecipitation assays, combined with mass-spectrometry, to identify major EIF4E5 interacting proteins in L. infantum. A constitutively expressed, HA-tagged, EIF4E5 co-precipitated mainly with EIF4G1 and binding partners previously described in Trypanosoma brucei, EIF4G1-IP, RBP43 and the 14-3-3 proteins. In contrast, no clear co-precipitation with EIF4G2, also previously reported, was observed. EIF4E5 also co-precipitated with protein kinases, possibly associated with cell-cycle regulation, selected RNA binding proteins and histones. Phosphorylated residues were identified and mapped to the Leishmania-specific C-terminal end. Mutagenesis of the tryptophan residue (W53) postulated to mediate interactions with protein partners or of a neighbouring tryptophan conserved in Leishmania (W45) did not substantially impair the identified interactions. Finally, the crystal structure of Leishmania EIF4E5 evidences remarkable differences in the eIF4G interfacing region, when compared with human eIF4E-1 and with its Trypanosoma orthologue. Mapping of its C-terminal end near the cap-binding site also imply relevant differences in cap-binding function and/or regulation.
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Fator de Iniciação 4E em Eucariotos/química , Fator de Iniciação 4E em Eucariotos/metabolismo , Leishmania/metabolismo , Mapas de Interação de Proteínas , Proteínas de Protozoários/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Cristalografia por Raios X , Fator de Iniciação 4E em Eucariotos/genética , Humanos , Leishmania/genética , Ligação Proteica , Conformação Proteica , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Homologia de SequênciaRESUMO
A 46-year-old man presented with left ventricle posteromedial papillary muscle ventricular tachycardia, presyncope, and a type-1 Brugada pattern on the post-electrical cardioversion electrocardiogram. There was a probability of a Brugada syndrome with the expression of its disease in the left ventricle; or a left monomorphic ventricular tachycardia as a part of Brugada phenocopy; or a Brugada syndrome with left monomorphic ventricular tachycardia as an epiphenomenon. Cardiac magnetic resonance, electrophysiological study, and ajmaline test were the key diagnostic tools employed.
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Síndrome de Brugada , Taquicardia Ventricular , Síndrome de Brugada/complicações , Síndrome de Brugada/diagnóstico , Eletrocardiografia , Ventrículos do Coração , Humanos , Masculino , Pessoa de Meia-Idade , Músculos Papilares , Taquicardia Ventricular/diagnósticoRESUMO
BioMAX is the first macromolecular crystallography beamline at the MAXâ IV Laboratory 3â GeV storage ring, which is the first operational multi-bend achromat storage ring. Due to the low-emittance storage ring, BioMAX has a parallel, high-intensity X-ray beam, even when focused down to 20â µm × 5â µm using the bendable focusing mirrors. The beam is tunable in the energy range 5-25â keV using the in-vacuum undulator and the horizontally deflecting double-crystal monochromator. BioMAX is equipped with an MD3 diffractometer, an ISARA high-capacity sample changer and an EIGER 16M hybrid pixel detector. Data collection at BioMAX is controlled using the newly developed MXCuBE3 graphical user interface, and sample tracking is handled by ISPyB. The computing infrastructure includes data storage and processing both at MAXâ IV and the Lund University supercomputing center LUNARC. With state-of-the-art instrumentation, a high degree of automation, a user-friendly control system interface and remote operation, BioMAX provides an excellent facility for most macromolecular crystallography experiments. Serial crystallography using either a high-viscosity extruder injector or the MD3 as a fixed-target scanner is already implemented. The serial crystallography activities at MAXâ IV Laboratory will be further developed at the microfocus beamline MicroMAX, when it comes into operation in 2022. MicroMAX will have a 1â µm × 1â µm beam focus and a flux up to 1015â photonsâ s-1 with main applications in serial crystallography, room-temperature structure determinations and time-resolved experiments.
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Endothelial dysfunction is associated with increased cardiovascular risk and death in heart transplant recipients (HTx). Although the measurement of peripheral endothelial function is considered a significant predictor of cardiovascular events in several populations, few studies have investigated this outcome after therapeutic strategies, including different exercise types, duration, and intensity. This systematic review and meta-analysis aimed to investigate the effects of continuous moderate exercise (CON) or high-intensity interval training (HIIT) to improve endothelial function (EF) in HTx. The search was conducted in Cochrane Central Registry of Controlled Trials (CENTRAL), MEDLINE (via PubMed), Web of Science and Scopus/Elsevier, CINAHL/Ebsco, Physiotherapy Evidence Database (PEDro), LILACS/BIREME, and SciELO databases. Quality of the evidence was assessed using the Grading of Recommendations Assessment Development and Evaluation (GRADE). The search strategy retrieved 5192 titles. A total of four articles met the inclusion criteria and were included for the qualitative analysis. Meta-analysis showed that exercises improved EF ([mean difference-MD] 3.48 95% CI - 0.29 to 7.25, p = 0.007) when compared with the control. However, there was a poor quality of evidence to demonstrate that CON or HIIT is better than usual care to improve EF. Exercise training provides benefits to patients, but the poor quality of evidence does not allow us to state that exercise is related to endothelial function improvement in HTx.
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Endotélio Vascular/fisiopatologia , Terapia por Exercício/métodos , Transplante de Coração , Complicações Pós-Operatórias/reabilitação , Transplantados , Vasodilatação , Tolerância ao Exercício/fisiologia , Humanos , Complicações Pós-Operatórias/fisiopatologia , Qualidade de VidaRESUMO
In higher eukaryotic cells, pertubations in ER environment, called ER stress, usually activate unfolded protein response (UPR) pathway in an attempt to re-stablish the ER homeostasis and prevent cell death. Because trypanosomatids appear to lack the classical UPR, it is not clear how these parasites respond to ER stress. Thus, the aim of this work was to evaluate the effects of ER stressors tunicamycin (TM) or dithiothreitol (DTT) on Trypanosoma cruzi. The TM treatment showed strong trypanostatic effect. At 2.5⯵g/mL of TM, the mRNA levels of both binding protein (BiP) and calreticulin (CRT) increased significantly, whereas the protein levels of BiP remained stable. TM treatment induced ultrastructural changes compatible with an autophagic process. The DTT treatment inhibited the cell growth, induced drastic morphological changes, mitochondrial membrane depolarization and increased ROS production. The expression of BiP apparently was not affected by DTT, whereas the mRNA levels of BiP and CRT were significantly reduced. Our results suggest that TM induces autophagy/ER-phagy without causing substantial injury to the parasite. Conversely, the DTT treatment seems to rupture the mitochondrion homeostasis leading to parasite death. The comprehension of the mechanisms behind the susceptibility of T. cruzi to ER stress open perspectives for the development of chemotherapeutic agents addressed to these pathways.
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Ditiotreitol/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Tunicamicina/farmacologia , Calreticulina/genética , Calreticulina/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Testes de Sensibilidade Parasitária , Trypanosoma cruzi/genética , Trypanosoma cruzi/crescimento & desenvolvimento , Trypanosoma cruzi/ultraestrutura , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Resposta a Proteínas não Dobradas/genéticaRESUMO
INTRODUCTION: Gly389Arg ß1 adrenergic receptor polymorphisms seem to exert an influence on the modulation of the adrenergic effect in several types of patients. This study aimed to determine the prevalence of Gly389Arg polymorphisms among patients with evidence of double nodal pathway and to correlate the electrophysiological properties with the different genotypes of the respective polymorphisms. METHODS: A cross-sectional, descriptive and analytical study was designed to assess 49 patients, with evidence of double nodal pathway, submitted to electrophysiological study. Genomic DNA was extracted from peripheral blood leukocytes and the genotypes of the Arg389Gly polymorphisms were identified in all individuals by PCR/RFLP (polymerase chain reaction/restriction fragment length polymorphism). RESULTS: The majority of patients were female and had supraventricular tachycardia (75.5%). The prevalence of Arg389Arg genotype was found in 32 patients (65.3%), Arg389Gly genotype in 16 patients (32.7%) and Gly389Gly genotype in 1 patient (2%). With respect to the induction of nodal reentrant tachycardia, it was possible to induce non-isoproterenol tachycardia in 32 patients (65.3%), of whom 24 had the Arg389Arg genotype and 8 the Arg389Gly and Gly389Gly genotype (p = 0.05). The resting heart rate of patients of the Arg389Arg genotype was 81 ± 18 bpm and the Arg389Gly and Gly389Gly genotype of 71 ± 9 bpm (p = 0.044). Body mass index (BMI) among patients with genotype Arg389Gly and Gly389Gly was 29.8 ± 7.1 and patients with the Arg389Arg genotype was 26.2 ± 4.6 (p = 0.034). CONCLUSION: The Arg389Arg genotype was more easily related to triggering arrhythmia, higher resting heart rate and lower BMI.
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Hepatitis E virus (HEV), an emerging virus associated with acute hepatic disease, leads to thousands of deaths worldwide. HEV has already been reported in Brazil; however, there is a lack of epidemiological and molecular information on the genetic variability, taxonomy, and evolution of HEV. It is thus unclear whether hepatitis E is a neglected disease in Brazil or it has low relevance for public health in this country. Here, for the first time, we report the presence of HEV in Northeast Brazil. A total of 119 swine faecal samples were screened for the presence of HEV RNA using real-time polymerase chain reaction (RT-PCR) and further confirmed by conventional RT-PCR; among these, two samples were identified as positive. Molecular evolution analyses based on capsid sequences revealed that the samples had close proximities to HEV sequences belonging to genotype 3 and were genetically related to subtype 3f isolated in humans. Parsimony ancestral states analysis indicated gene flow events from HEV cross-species infection, suggesting an important role of pig hosts in viral spillover. HEV's ability for zoonotic transmission by inter-species host switching as well as its possible adaptation to new animal species remain important issues for human health.
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Fezes/virologia , Vírus da Hepatite E/genética , Vírus da Hepatite E/isolamento & purificação , Zoonoses/virologia , Animais , Brasil , Capsídeo/virologia , Genótipo , Hepatite E/virologia , Humanos , Filogenia , RNA Viral , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Suínos , Doenças dos Suínos/transmissãoRESUMO
BACKGROUND: Emergency department (ED) visits due to atrial fibrillation and flutter (AFF) are common, and provide an opportunity to define stroke risk. The prognostic impact of AFF duration on return ED visits is unknown. We aimed to investigate both the prognostic impact of AFF classification on ED visits and the adherence to guideline recommendations on anticoagulation. METHODS: This single-center historic cohort of every patient treated for AFF in our ED during 2012. Follow-up data was obtained on May 2015 (median follow-up of 863â¯days). RESULTS: Among 1112 patients (495 Paroxysmal AF - parAF, 475 Persistent AF - persAF, and 142 flutter), those with parAF were less frequently under oral anticoagulation than persAF and flutter patients (15.8%, 39.4%, 40.1%, pâ¯<â¯0.01). Mean CHA2DS2-VASc scores of parAF were lower than persAF (2.2 vs. 3.12, pâ¯<â¯0.01), and did not differ from those with flutter. Return visits to the ED were highest among flutter patients and lowest among parAF (49.3% vs. 37.2%, pâ¯<â¯0.01). Heart failure, hypertension, female gender and atrial flutter were independent risk factors for repeated visits on multivariate regression. CONCLUSIONS: AFF duration provide prognostic information in the ED. ED return visits were common and particularly incident among flutter patients. Furthermore, stroke risk was high and anticoagulation rates were low across all groups. Patients with paroxysmal AF were less commonly anticoagulated even though their mean CHA2DS2-VASc scores were 2.2. These results reveal that guideline adherence is still lacking and should raise awareness to a stricter patient follow-up after ED visits.
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Fibrilação Atrial , Flutter Atrial , Acidente Vascular Cerebral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Flutter Atrial/tratamento farmacológico , Eletrocardiografia , Serviço Hospitalar de Emergência , Feminino , Humanos , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/prevenção & controleRESUMO
BACKGROUND: The potential for thromboembolism in atrial flutter (AFL) is different from atrial fibrillation. AFL cycle length (AFL-CL) may be related to reduced left atrial appendage (LAA) function. Very rapid AFL-CL can lead to mechanical and electrophysiological disorders that contribute to lower LAA emptying velocity (LAEV). The aim of this study is to relate atrial flutter cycle length with LAEV and its role in thrombogenesis. METHODS: Cross-sectional study of patients with atrial flutter AFL who underwent transoesophageal echocardiography (TEE) before catheter ablation or electric cardioversion. AFL-CL in milliseconds was measured with a 12-lead EKG or in intracardiac records. RESULTS: We included 123 patients. There was correlation between AFL-CL and LAEV (râ¯=â¯0.34; pâ¯=â¯0.003) in typical AFL. Cycle length, LA size and atypical flutter were predictors of low LAEV on multivariate analysis. An index multiplying atrial rate (bpm) during the arrhythmia versus left atrial size(mm) >11,728 was associated with spontaneous echogenic contrast and/or left atrial thrombus on TEE (C-statisticâ¯=â¯0.71; CI95%0.60-0.81). CONCLUSIONS: There was a significant relationship between the AFL-CL and LAEV. The LAEV was affected by the LA size, the type of atrial flutter and the AFL-CL. A new index, relating the atrial rate with the left atrial size, was able to identify a higher occurrence of spontaneous echogenic contrast and/or left atrial thrombus.
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Apêndice Atrial/fisiopatologia , Flutter Atrial/complicações , Flutter Atrial/fisiopatologia , Trombose Coronária/etiologia , Trombose Coronária/fisiopatologia , Idoso , Apêndice Atrial/diagnóstico por imagem , Flutter Atrial/diagnóstico por imagem , Trombose Coronária/diagnóstico por imagem , Estudos Transversais , Ecocardiografia Transesofagiana , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
This study was carried out in order to determine the effects of different combinations of on-farm fasting intervals (8, 12, 16, 20 h) and 1.5 h of transport plus lairage periods (1, 3, 6 h) at different seasons (summer/winter) on blood stress parameters (cortisol and lactate), stomach content and weight, skin lesion and meat quality in a total of 960 pigs from eight farms. Blood lactate levels were greater in the summer (P < 0.001) and stomach content was affected (P < 0.05) by season, on-farm fasting interval (P < 0.001), lairage time (P < 0.0001). Stomach content weight reduces as the total feed withdrawal time increases up to on-farm fasting of 17 and 1 h of lairage. Stomach content can be influenced by feed and water in different ways according to treatments. Only 8 h of on-farm fasting is not enough to empty stomachs from feed content. However, an on-farm fasting period of 16 h or longer can also increase the occurrence of more water in the stomachs. Carcass lesions caused by fighting were greater (P ≤ 0.005) in the winter, mainly after 3 and 6 h of lairage (P ≤ 0.005). Loin and ham pHu was lower (P ≤ 0.05) for pigs slaughtered after 6 h of lairage during the summer. The application of 12 h of on-farm fasting with 6 h of lairage seemed to be best combination to reduce stomach content weight (feed and water). In the winter, shorter lairage period can be used to reduce percentage of skin lesions and better pork quality traits in pigs.
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Jejum , Carne , Animais , Fazendas , Hidrocortisona , Estações do Ano , SuínosRESUMO
BACKGROUND: Catheter ablation provides curative treatment for tachyarrhythmias. Fluoroscopy, the method used for this, presents several risks. The electroanatomical mapping (MEA) presents a three-dimensional image without using X-rays, and may be adjunct to fluoroscopy. OBJECTIVES: We evaluated the possibility of performing catheter ablation with the exclusive use of electroanatomical mapping (MEA), dispensing with fluoroscopy. We compared the total time of procedure and success rates against the technique using fluoroscopy (RX) with emission of X-rays. METHODS: Randomized, unicentric, uni-blind study of patients referred for tachyarrhythmia ablation. RESULTS: Twelve patients were randomized to the XR group and 11 to the EAM group. The mean age was 48.5 (±12.6) vs 46.3 (±16.6) (Pâ¯=â¯ns). Success occurred in 11 patients (91.7%) in the RX group and 9 (81.8%) in the MEA group (Pâ¯=â¯0.46). The procedure time in minutes was higher in the MEA group than in the RX group (79-47-125min vs 49-30-100min; Pâ¯=â¯0.006). The mean fluoroscopy time was 11⯱â¯9â¯min versus zero (RX vs MEA: Pâ¯<â¯0.001). The mean radiofrequency applications were lower in the RX group against the MEA group (6⯱â¯3.5â¯×â¯13.2⯱â¯18.2 pâ¯<â¯0.019). There were no complications. CONCLUSION: MEA opened new therapeutic possibilities for patients with arrhythmias, reducing the risk of radiation. In this study, it was possible to demonstrate that it is feasible to perform ablation only with the use of MEA, with similar success with fluoroscopy, at the expense of a longer procedure time.
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INTRODUCTION: Common clinical teaching, for invasive electrophysiology, is that if the first year fellow cannulates the coronary sinus (CS) in his first attempt, the arrhythmia is more likely to be atrioventricular nodal reentry tachycardia (AVNRT). This general perception has not yet been clinically tested. We evaluated this theory in prospective patients undergoing an electrophysiological study (EPS) for paroxysmal supraventricular tachycardia (PSVT). METHODS: Cohort study. CS ease of cannulation (CSCS) was graded as: 1) 1st year fellow cannulates in first attempt; 2) 1st year fellow needs more than one attempt or maneuver to cannulate the CS; 3) staff physician cannulates in first attempt after the fellow was unsuccessful; 4) staff physician requires more than one maneuver to cannulate the CS; 5) staff physician judges that the cannulation process was extremely difficult. RESULTS: Of the 1361 patients undergoing EPS in our institution, 165 were selected. Age was 49⯱â¯15 years. AVNRT occurred in 77.6%, atrioventricular reentry tachycardia (AVRT) in 15.1% and atrial tachycardia (AT) in 7.3% of cases. The CSCSâ¯=â¯1 was more prevalent in AVNRT, 89% versus 68% AVRT and 58.3% of AT (Pâ¯=â¯0.0005). Patients with CSCSâ¯=â¯1 have a higher chance of the PSVT being AVNRT (odds ratio: 4.41; 95CI: 1.84-10.56; Pâ¯=â¯0.0009). CONCLUSION: The CSCS predicts the likelihood of the induced PSVT being AVNRT as compared to AVRT and AT. More studies are required to try to associate this finding to clinical patient characteristics to create a score for PSVT mechanism prediction.
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BACKGROUND: The Ceratocystis genus harbors a large number of phytopathogenic fungi that cause xylem parenchyma degradation and vascular destruction on a broad range of economically important plants. Ceratocystis cacaofunesta is a necrotrophic fungus responsible for lethal wilt disease in cacao. The aim of this work is to analyze the genome of C. cacaofunesta through a comparative approach with genomes of other Sordariomycetes in order to better understand the molecular basis of pathogenicity in the Ceratocystis genus. RESULTS: We present an analysis of the C. cacaofunesta genome focusing on secreted proteins that might constitute pathogenicity factors. Comparative genome analyses among five Ceratocystidaceae species and 23 other Sordariomycetes fungi showed a strong reduction in gene content of the Ceratocystis genus. However, some gene families displayed a remarkable expansion, in particular, the Phosphatidylinositol specific phospholipases-C (PI-PLC) family. Also, evolutionary rate calculations suggest that the evolution process of this family was guided by positive selection. Interestingly, among the 82 PI-PLCs genes identified in the C. cacaofunesta genome, 70 genes encoding extracellular PI-PLCs are grouped in eight small scaffolds surrounded by transposon fragments and scars that could be involved in the rapid evolution of the PI-PLC family. Experimental secretome using LC-MS/MS validated 24% (86 proteins) of the total predicted secretome (342 proteins), including four PI-PLCs and other important pathogenicity factors. CONCLUSION: Analysis of the Ceratocystis cacaofunesta genome provides evidence that PI-PLCs may play a role in pathogenicity. Subsequent functional studies will be aimed at evaluating this hypothesis. The observed genetic arsenals, together with the analysis of the PI-PLC family shown in this work, reveal significant differences in the Ceratocystis genome compared to the classical vascular fungi, Verticillium and Fusarium. Altogether, our analyses provide new insights into the evolution and the molecular basis of plant pathogenicity.
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Ascomicetos/genética , Cacau/microbiologia , Proteínas Fúngicas/genética , Regulação da Expressão Gênica de Plantas , Genoma Fúngico , Genômica/métodos , Fosfoinositídeo Fosfolipase C/genética , Ascomicetos/metabolismo , Evolução Molecular , Proteínas Fúngicas/metabolismo , Fosfatidilinositóis/química , Fosfatidilinositóis/metabolismo , Fosfoinositídeo Fosfolipase C/química , Fosfoinositídeo Fosfolipase C/metabolismo , Filogenia , Conformação ProteicaRESUMO
Industrial pipelines must be inspected to detect typical failures, such as obstructions and deformations, during their lifetime. In the petroleum industry, the most used non-destructive technique to inspect buried pipelines is pigging. This technique consists of launching a Pipeline Inspection Gauge (PIG) inside the pipeline, which is driven by the pressure differential produced by fluid flow. The purpose of this work is to study the application of artificial neural networks to calculate the PIG's velocity based on the pressure differential. We launch a prototype PIG inside a testing pipeline, where this PIG gathers velocity data from an odometer-based system, while a supervisory system gathers pressure data from the testing pipeline. Then we train a Multilayer Perceptron (MLP) and a Nonlinear Autoregressive Network with eXogenous Inputs (NARX) network with the gathered data to predict velocity. The results suggest it is possible to use a neural network to model the PIG's velocity from pressure differential measurements. Our method is a new approach to the typical speed measurements based only on odometer, since the odometer is prone to fail and present poor results under some circumstances. Moreover, it can be used to provide redundancy, improving reliability of data obtained during the test.
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Chagas disease, Sleeping Sickness, Nagana and Leishmaniasis are serious infections caused by protozoa of the order Kinetoplastidae. They were described over a century ago by seminal work of different physician-researchers and, despite the initial discoveries, few drugs have been made available for the treatment of these infections. The drugs available present serious efficacy and toxicity problems. Moreover, the emergence of resistant strains has rendered the development of novel chemotherapeutic strategies a priority. Auranofin is currently in use to treat rheumatoid arthritis in humans. Previous reports showed that this compound presents activity against Trypanosoma brucei and Leishmania cells. In Trypanosoma cruzi cells, auranofin resulted in a more potent compound than benznidazole in vitro when tested in different DTUs. In vivo experiments, although not decreasing T. cruzi parasitemia, decreases host mortality. Therefore, we propose auranofin as a potential alternative for a new chemotherapy in Chagas disease with the added advantage of already being approved for use in humans.
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Auranofina/farmacologia , Doença de Chagas/tratamento farmacológico , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Auranofina/uso terapêutico , Linhagem Celular , Doença de Chagas/parasitologia , Feminino , Fibroblastos/parasitologia , Humanos , Concentração Inibidora 50 , Dose Letal Mediana , Camundongos , Camundongos Endogâmicos BALB C , Nitroimidazóis/farmacologia , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Distribuição Aleatória , Organismos Livres de Patógenos Específicos , Tripanossomicidas/uso terapêuticoRESUMO
BACKGROUND: New evidence suggests that the CHA(2)DS(2)VASc (congestive heart failure, hypertension [HTN], age, diabetes, stroke, vascular disease, and female gender) score may be a reliable tool to predict the risk of thromboembolic events in patients without documented atrial fibrillation (AF). METHODS: We performed a prospective cohort study of outpatients without AF or flutter, who were not using oral anticoagulation. Clinical characteristics were assessed and patients were stratified according to the CHA(2)DS(2)VASc score. We evaluated the incidence of major adverse cardiac outcomes and its relation to the CHA(2)DS(2)VASc score during the follow-up. RESULTS: Four hundred sixty-eight patients without AF were enrolled with a mean follow-up of 12 ± 6 months. Age was 64.9 ± 11.3 years. The prevalence of HTN was 88.4%, diabetes 37.6%, heart failure 26.3%, and vascular disease 61.7%. Overall, CHA(2)DS(2)VASc score was 3.4 ± 1.4. There were 15 major adverse cardiac outcomes during 12.2 months of follow-up (overall incidence of 3.2 per 100 person-years). We found significant differences in relation to gender, age, previous stroke, and follow-up length in patients with and without adverse outcomes. The CHA(2)DS(2)VASc score was higher in those with adverse outcomes (4.2 ± 1.7 vs 3.4 ± 1.4; P = 0.035). Patients with a CHA(2)DS(2)VASc ≥6 had a relative risk for adverse outcomes of 4.2 (95% confidence interval: 1.27-13.90). CONCLUSIONS: In our population, CHA(2)DS(2)VASc score predicts major adverse cardiac outcomes, including stroke and death, in a cohort of patients without AF.
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Doenças Cardiovasculares/mortalidade , Complicações do Diabetes/mortalidade , Modelos de Riscos Proporcionais , Medição de Risco/métodos , Acidente Vascular Cerebral/mortalidade , Distribuição por Idade , Idoso , Assistência Ambulatorial , Fibrilação Atrial , Brasil/epidemiologia , Comorbidade , Morte Súbita Cardíaca , Feminino , Humanos , Incidência , Masculino , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição por Sexo , Taxa de SobrevidaRESUMO
Background: Fetal echocardiography can diagnose neonatal atrial flutter, which can cause heart failure in newborns. Little is known about catheter ablation in this population. Methods: Case report that aimed to review a successful ablation in a 20-day-old patient with refractory atrial flutter. Results: This is the first report of a successful neonatal atrial flutter ablation without any early recurrence after the procedure. Conclusions: Atrial flutter ablation performed on newborns is a reliable and long-lasting treatment option.
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Background: Programmed ventricular stimulation (PVS) during electrophysiological study (EPS), is a globally accepted tool for risk stratification of sudden cardiac death (SCD) in some specific clinical situations. The aim of this study was to evaluate the prognosis of ventricular arrhythmia induction in a cohort of patients with syncope of undetermined origin (SUO). Methods: This is a historical cohort study in a population of patients with SUO referred for EPS between the years 2008-2021. In this interval, 575 patients underwent the procedure. Results: Patients with induced ventricular arrhythmias had a higher occurrence of structural heart disease (36.7% vs. 76.5%), ischemic heart disease (28.2 vs. 57.1%), heart failure (15.5% vs. 34.4%), and lower left ventricular ejection fraction (59.16% vs. 47.51%), when compared to the outcome with a negative study. PVS triggered ventricular arrhythmias in 98 patients, 62 monomorphic and 36 polymorphic. During a median follow-up of 37.6 months, 100 deaths occurred. Only the induction of sustained ventricular arrhythmias showed a significant association with the primary outcome (all-cause mortality) with a p value <.001. After the performance of EPS, 142 patients underwent cardioverter-defibrillator (ICD) implantation. At study follow-up, 30 patients had therapies by the device. Only the induction of sustained monomorphic ventricular arrhythmia showed statistically significant association with appropriate therapies by the device (p = .012). Conclusion: In patients with SUO, the induction of sustained monomorphic ventricular arrhythmia after programmed ventricular pacing is related to a worse prognosis, with a higher incidence of mortality and appropriate therapies by the ICD.
RESUMO
Recognition of the mRNA 5' end is a critical step needed for translation initiation. This step is performed by the cap binding protein eIF4E, which joins the larger eIF4G subunit to form the eIF4F complex. Trypanosomatids have a minimum of five different eIF4F-like complexes formed through specific but not well-defined interactions between four different eIF4E and five eIF4G homologues. The EIF4E6/EIF4G5 complex has been linked with the stage-specific translation of mRNAs encoding the major Trypanosoma brucei virulence factors. Here, to better define the molecular basis for the TbEIF4E6/TbEIF4G5 interaction, we describe the identification of the peptide interacting with TbEIF4E6 in the region comprising residues 79-166 of TbEIF4G5. The TbEIF4E6-TbEIF4G5_79-116 complex reconstituted with recombinant proteins is highly stable even in the absence of cap-4. The crystal structure of the complex was subsequently solved, revealing extensive interacting surfaces. Comparative analyses highlight the conservation of the overall structural arrangement of different eIF4E/eIF4G complexes. However, highly different interacting surfaces are formed with distinct binding contacts occurring both in the canonical and noncanonical elements within eIF4G and the respective eIF4E counterpart. These specific pairs of complementary interacting surfaces are likely responsible for the selective association needed for the formation of distinct eIF4F complexes in trypanosomatids.