Time course and mechanisms of left ventricular systolic and diastolic dysfunction in monocrotaline-induced pulmonary hypertension

Although pulmonary hypertension (PH) selectively overloads the right ventricle (RV), neuroendocrine activation and intrinsic myocardial dysfunction have been described in the left ventricle (LV). In order to establish the timing of LV dysfunction development in PH and to clarify underlying molecular changes, Wistar rats were studied 4 and 6 weeks after subcutaneous injection of monocrotaline (MCT) 60 mg/kg (MCT-4, n = 11; MCT-6, n = 11) or vehicle (Ctrl-4, n = 11; Ctrl-6, n = 11). Acute single beat stepwise increases of systolic pressure were performed from baseline to isovolumetric (LVPiso). This hemodynamic stress was used to detect early changes in LV performance. Neurohumoral activation was evaluated by measuring angiotensin-converting enzyme (ACE) and endothelin-1 (ET-1) LV mRNA levels. Cardiomyocyte apoptosis was evaluated by TUNEL assay. Extracellular matrix composition was evaluated by tenascin-C mRNA levels and interstitial collagen content. Myosin heavy chain (MHC) composition of the LV was studied by protein quantification. MCT treatment increased RV pressures and RV/LV weight ratio, without changing LV end-diastolic pressures or dimensions. Baseline LV dysfunction were present only in MCT-6 rats. Afterload elevations prolonged tau and upward-shifted end-diastolic pressure dimension relations in MCT-4 and even more in MCT-6. MHC-isoform switch, ACE upregulation and cardiomyocyte apoptosis were present in both MCT groups. Rats with severe PH develop LV dysfunction associated with ET-1 and tenascin-C overexpression. Diastolic dysfunction, however, could be elicited at earlier stages in response to hemodynamic stress, when only LV molecular changes, such as MHC isoform switch, ACE upregulation, and myocardial apoptosis were present.Supported by Portuguese grants from FCT (POCI/SAU-FCF/60803/2004 and POCI/SAU-MMO/61547/2004) through Cardiovascular R&D Unit (FCT No. 51/94)

Characterization of the genetic diversity of Mycobacterium tuberculosis in São Paulo city, Brazil

<p>Abstract</p> <p>Background</p> <p>Tuberculosis is a major health problem in São Paulo, Brazil, which is the most populous and one of the most cosmopolitan cities in South America. To characterize the genetic diversity of <it>Mycobacterium tuberculosis </it>in the population of this city, the genotyping techniques of spoligotyping and MIRU were applied to 93 isolates collected in two consecutive years from 93 different tuberculosis patients residing in São Paulo city and attending the Clemente Ferreira Institute (the reference clinic for the treatment of tuberculosis).</p> <p>Findings</p> <p>Spoligotyping generated 53 different spoligotype patterns. Fifty-one isolates (54.8%) were grouped into 13 spoligotyping clusters. Seventy- two strains (77.4%) showed spoligotypes described in the international databases (SpolDB4, SITVIT), and 21 (22.6%) showed unidentified patterns. The most frequent spoligotype families were Latin American Mediterranean (LAM) (26 isolates), followed by the T family (24 isolates) and Haarlem (H) (11 isolates), which together accounted for 65.4% of all the isolates. These three families represent the major genotypes found in Africa, Central America, South America and Europe. Six Spoligo-International-types (designated SITs by the database) comprised 51.8% (37/72) of all the identified spoligotypes (SIT53, SIT50, SIT42, SIT60, SIT17 and SIT1). Other SITs found in this study indicated the great genetic diversity of <it>M. tuberculosis</it>, reflecting the remarkable ethnic diversity of São Paulo city inhabitants. The MIRU technique was more discriminatory and did not identify any genetic clusters with 100% similarity among the 93 isolates. The allelic analysis showed that MIRU loci 26, 40, 23 and 10 were the most discriminatory. When MIRU and spoligotyping techniques were combined, all isolates grouped in the 13 spoligotyping clusters were separated.</p> <p>Conclusions</p> <p>Our data indicated the genomic stability of over 50% of spoligotypes identified in São Paulo and the great genetic diversity of <it>M. tuberculosis </it>isolates in the remaining SITs, reflecting the large ethnic mix of the São Paulo city inhabitants. The results also indicated that in this city, <it>M. tuberculosis </it>isolates acquired drug resistance independently of genotype and that resistance was more dependent on the selective pressure of treatment failure and the environmental circumstances of patients.</p

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Construction and validation of indicators and respective definitions for the nursing outcome Swallowing Status

;;OBJETIVO:;; construir e validar por especialistas e clinicamente os indicadores para o resultado de enfermagem Estado da deglutição e suas definições conceituais e operacionais em pacientes após acidente vascular cerebral.;;;;MÉTODO:;; estudo metodológico, com análise de conceito e validações de conteúdo e clínica. Verificou-se o Índice de Validade de Conteúdo para as notas atribuídas por 11 especialistas aos indicadores revisados. Na validação clínica, examinaram-se 81 pacientes por duas duplas de enfermeiros, uma usando instrumento com as definições construídas e outra com instrumento sem definições. As avaliações foram comparadas pelo Coeficiente de Correlação Intraclasse, teste de Friedman e Diferença Mínima Significante.;;;;RESULTADOS:;; exceto o indicador Captura do alimento, todos apresentaram Índice de Validade de Conteúdo superior a 0,80. A dupla de enfermeiros com instrumento contendo as definições construídas apresentou Coeficiente de Correlação Intraclasse superior a 0,80 para todos os indicadores e pelo cálculo da Diferença Mínima Significante houve similaridade entre todas as avaliações. Na dupla que estava sem as definições elaboradas, o coeficiente foi baixo (ρ;;;;CONCLUSÃO:;; os dados evidenciaram aumento na uniformidade e acurácia entre as avaliações dos enfermeiros ao utilizar as definições conceituais e operacionais para os indicadores do resultado de enfermagem Estado da deglutição.;;;;OBJECTIVE:;; to develop indicators for the nursing outcome Swallowing Status and the respective conceptual and operational definitions validated by experts and in a clinical setting among patients after having experienced a stroke.;;;;METHOD:;; methodological study with concept analysis and content and clinical validations. The Content Validation Index was verified for the scores assigned by 11 experts to indicators. Two pairs of nurses assessed 81 patients during the clinical validation: one pair used an instrument with definitions and the other used an instrument without definitions. The resulting assessments were compared using Intraclass Correlation Coefficient, Friedman's test, and Minimal Important Difference calculation.;;;;RESULTS:;; All the indicators, with the exception of the indicator Ability to bring food to mouth, presented Content Validation Index above 0.80. The pair using the instrument with definitions presented an Intraclass Correlation Coefficient above 0.80 for all the indicators and similarity was found in all the assessments, according to the Minimal Important Difference calculation. The pair using the instrument without definitions presented a low coefficient (ρ;;OBJETIVO:;; construir y validar por especialistas y clínicamente los indicadores para el resultado de enfermería Estado de la deglución y sus definiciones conceptuales y operacionales en pacientes después de accidente vascular cerebral.;;;;MÉTODO:;; estudio metodológico, con análisis de concepto y validaciones de contenido y clínicas. Se verificó el Índice de Validez de Contenido para las notas atribuidas por 11 especialistas a los indicadores revisados. En la validación clínica, fueron examinados 81 pacientes por dos parejas de enfermeros, una usando instrumento con las definiciones construidas y la otra con instrumento sin definiciones. Las evaluaciones fueron comparadas por el Coeficiente de Correlación Intraclase, test de Friedman y Diferencia Mínima Significativa.;;;;RESULTADOS:;; exceptuando el indicador Captura del alimento, todos presentaron Índice de Validez de Contenido superior a 0,80. La pareja de enfermeros con instrumento conteniendo las definiciones construidas presentó Coeficiente de Correlación Intraclase superior a 0,80 para todos los indicadores y por el cálculo de la Diferencia Mínima Significativa hubo semejanza entre todas las evaluaciones. En la pareja que estaba sin las definiciones elaboradas, el coeficiente fue bajo (

Search for High-Mass Resonances Decaying to τν in pp Collisions at √s=13 TeV with the ATLAS Detector

A search for high-mass resonances decaying to τν using proton-proton collisions at √s=13 TeV produced by the Large Hadron Collider is presented. Only τ-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible τν production cross section. Heavy W′ bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2–3.8 TeV depending on the coupling in the nonuniversal G(221) model are excluded at the 95% credibility level

Measurement of differential cross sections and W + /W − cross-section ratios for W boson production in association with jets at √s =8 TeV with the ATLAS detector

This paper presents a measurement of the W boson production cross section and the W + /W − cross-section ratio, both in association with jets, in proton--proton collisions at s √ =8 TeV with the ATLAS experiment at the Large Hadron Collider. The measurement is performed in final states containing one electron and missing transverse momentum using data corresponding to an integrated luminosity of 20.2 fb −1 . Differential cross sections for events with one or two jets are presented for a range of observables, including jet transverse momenta and rapidities, the scalar sum of transverse momenta of the visible particles and the missing transverse momentum in the event, and the transverse momentum of the W boson. For a subset of the observables, the differential cross sections of positively and negatively charged W bosons are measured separately. In the cross-section ratio of W + /W − the dominant systematic uncertainties cancel out, improving the measurement precision by up to a factor of nine. The observables and ratios selected for this paper provide valuable input for the up quark, down quark, and gluon parton distribution functions of the proto