Mutual diffusivity in binary mixtures of n-heptane with n-hexane isomers

This paper presents a study of the influence of branching in the binary diffusion coefficients of n-heptane+n-hexane isomers, in the liquid state. The measurements have been made with the Taylor dispersion technique, at several compositions, at 283 and 298 K, for the X+n-heptane mixtures, where X=n-hexane, 3-methylpentane, 2, 3-dimethylbutane, and 2, 2-dimethylbutane. The results show a very interesting behavior of the composition dependence of the binary diffusion coefficients, presenting a maximum, for compositions about a molar fraction of n-heptane of 0.5, which increases with the increase in the degree of branching, suggesting the possibility of order~tisorder effects caused by stereochemically favored packing in the liquid phase and energetically favored segment interaction in the liquid mixtures. An attempt to apply the van der Waals model to these data could not predict the experimental binary diffusion coefficients of these systems within the experimental accuracy

Fibroblast growth factor receptor 1 signaling in adult cardiomyocytes increases contractility and results in a hypertrophic cardiomyopathy

Fibroblast growth factors (FGFs) and their receptors are highly conserved signaling molecules that have been implicated in postnatal cardiac remodeling. However, it is not known whether cardiomyocyte-expressed FGF receptors are necessary or sufficient for ventricular remodeling in the adult heart. To determine whether cardiomyocytes were competent to respond to an activated FGF receptor, and to determine if this signal would result in the development of hypertrophy, we engineered a doxycycline (DOX)-inducible, cardiomyocyte-specific, constitutively active FGF receptor mouse model (αMHC-rtTA, TRE-caFgfr1-myc). Echocardiographic and hemodynamic analysis indicated that acute expression of caFGFR1 rapidly and directly increased cardiac contractility, while chronic expression resulted in significant hypertrophy with preservation of systolic function. Subsequent histologic analysis showed increased cardiomyocyte cross-sectional area and regions of myocyte disarray and fibrosis, classic features of hypertrophic cardiomyopathy (HCM). Analysis of downstream pathways revealed a lack of clear activation of classical FGF-mediated signaling pathways, but did demonstrate a reduction in Serca2 expression and troponin I phosphorylation. Isolated ventricular myocytes showed enhanced contractility and reduced relaxation, an effect that was partially reversed by inhibition of actin-myosin interactions. We conclude that adult cardiomyocytes are competent to transduce FGF signaling and that FGF signaling is sufficient to promote increased cardiomyocyte contractility in vitro and in vivo through enhanced intrinsic actin-myosin interactions. Long-term, FGFR overexpression results in HCM with a dynamic outflow tract obstruction, and may serve as a unique model of HCM

Subacute and chronic hypersensitivity pneumonitis: Histopathological patterns and survival

Background: in hypersensitivity pneumonitis (HP), survival can be predicted on the basis of the severity of fibrosis in surgical lung biopsy, but few data are available on the influence of clinical, functional, tomographic and histologic findings on prognosis. Objectives: To describe the impact on survival. of clinical data, histological patterns, and HRCT findings in subacute/chronic HP.Methods: A retrospective analysis of 103 patients diagnosed with HP submitted to surgical lung biopsy. Chronic HP was characterized by HRCT findings indicative of fibrosis (n = 76).Results: the most relevant exposures were to molds and birds. Lung biopsies revealed typical HP with granulomas in 46 patients, bronchiolocentric interstitial pneumonia in 27, and nonspecific interstitial pneumonia (NSIP) in 16. By univariate analysis, several findings were predictors of mortality: older age, mate sex, velcro crackles, higher FEV(1)/FVC ratio, lower oxygen saturation during exercise, and absence of mosaic pattern/air trapping and presence of fibrosis on HRCT. By multivariate analysis, remained significant: age (p = 0.007), oxygen saturation during exercise (p = 0.003), and mosaic pattern/air trapping on HRCT (p = 0.004). Patients with NSIP had a greater survival than did those with typical histology and those with bronchiolocentric pneumonia (p = 0.033).Conclusions: A wide range of histological features are found in FIR Typical findings are seen in 45% of cases, Other common patterns are NSIP and centriacinar lesions. Survival is better in patients with NSIP and worse in those with older age, desaturation during exercise, and absence of mosaic pattern/air trapping on HRCT. (c) 2009 Etsevier Ltd. All rights reserved.Universidade Federal de São Paulo, Div Resp Dis, Dept Med, Escola Paulista Med, BR-04023062 São Paulo, BrazilHosp Servidor Publ Estadual, Div Resp Dis, Dept Med, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Div Resp Dis, Dept Med, Escola Paulista Med, BR-04023062 São Paulo, BrazilWeb of Scienc

Recurrent apparent life-threatening event as the first manifestation of congenital myasthenia

OBJECTIVE: To alert pediatricians about the importance of a careful investigation on recurrent apparent life-threatening events. Reports of the association of these events with congenital myasthenic syndromes were not found. CASE DESCRIPTION: A seven-month-old infant with recurrent apparent life-threatening events was admitted for investigation. During hospital stay, she presented cyanosis and respiratory failure, requiring mechanical ventilation for three days. After clinical improvement, hypotheses of gastroesophageal reflux and pulmonary aspiration were ruled out. The presence of eyelid ptosis, general hypotonia and weak crying led to the suspicion of congenital myasthenia, which was confirmed. Treatment with oral piridostigmine led to neurological and nutritional normalization, without any other apparent life-threatening event during the next three years. COMMENTS: The careful etiological investigation of apparent life-threatening events may lead to rare diagnosis that requires specific treatments, such as congenital myasthenia.OBJETIVO: Alertar os pediatras sobre a necessidade de investigar criteriosamente a etiologia de eventos com aparente risco de morte recorrente. Não foram encontrados relatos associando tais eventos à miastenia congênita. DESCRIÇÃO DO CASO: Lactente de sete meses apresentando história de eventos com aparente risco de morte recorrente foi internado para investigação. Durante a internação, apresentou cianose e dispneia progressiva, com necessidade de ventilação mecânica por três dias. Após a melhora clínica, e tendo sido descartadas as hipóteses de doença do refluxo gastroesofágico e aspiração pulmonar como desencadeantes, notou-se ptose palpebral bilateral, hipotonia apendicular e choro fraco, que conduziram à suspeita clínica de miastenia congênita. Após confirmação do diagnóstico, foi mantido tratamento ambulatorial com piridostigmina, com recuperação nutricional e neurológica, sem novos eventos com aparente risco de morte nos três anos seguintes. COMENTÁRIOS: A investigação minuciosa das causas de eventos com aparente risco de morte pode levar a diagnósticos menos frequentes que exigem tratamento específico, como a miastenia congênita.OBJETIVO: Alertar a los pediatras sobre la necesidad de investigar criteriosamente la etiología de eventos con aparente riesgo de muerte recurrente. No se encontraron relatos asociando tales eventos a la miastenia congénita. DESCRIPCIÓN DEL CASO: Lactante de siete meses presentando historia de eventos con aparente riesgo de muerte recurrente fue internado para investigación. Durante la internación, presentó cianosis y disnea progresiva, con necesidad de ventilación mecánica por tres días. Después de la mejora clínica, y habiendo sido rechazadas las hipótesis de enfermedad del reflujo gastroesofágico y aspiración pulmonar como desencadenantes, se notó ptosis palpebral bilateral, hipotonía apendicular y lloro débil, que condujeron a la sospecha clínica de miastenia congénita. Después de la confirmación del diagnóstico, se mantuvo el tratamiento ambulatorial con piridostigmina, con recuperación nutricional y neurológica, sin nuevos eventos con aparente riesgo de muerte en los tres años siguientes. COMENTARIOS: La investigación minuciosa de las causas de eventos con aparente riesgo de muerte puede llevar a diagnósticos menos frecuentes que exigen tratamiento específico, como la miastenia congénita.12112

Mitochondrial Redox Metabolism in Trypanosomatids Is Independent of Tryparedoxin Activity

Tryparedoxins (TXNs) are oxidoreductases unique to trypanosomatids (including Leishmania and Trypanosoma parasites) that transfer reducing equivalents from trypanothione, the major thiol in these organisms, to sulfur-dependent peroxidases and other dithiol proteins. The existence of a TXN within the mitochondrion of trypanosomatids, capable of driving crucial redox pathways, is considered a requisite for normal parasite metabolism. Here this concept is shown not to apply to Leishmania. First, removal of the Leishmania infantum mitochondrial TXN (LiTXN2) by gene-targeting, had no significant effect on parasite survival, even in the context of an animal infection. Second, evidence is presented that no other TXN is capable of replacing LiTXN2. In fact, although a candidate substitute for LiTXN2 (LiTXN3) was found in the genome of L. infantum, this was shown in biochemical assays to be poorly reduced by trypanothione and to be unable to reduce sulfur-containing peroxidases. Definitive conclusion that LiTXN3 cannot directly reduce proteins located within inner mitochondrial compartments was provided by analysis of its subcellular localization and membrane topology, which revealed that LiTXN3 is a tail-anchored (TA) mitochondrial outer membrane protein presenting, as characteristic of TA proteins, its N-terminal end (containing the redox-active domain) exposed to the cytosol. This manuscript further proposes the separation of trypanosomatid TXN sequences into two classes and this is supported by phylogenetic analysis: i) class I, encoding active TXNs, and ii) class II, coding for TA proteins unlikely to function as TXNs. Trypanosoma possess only two TXNs, one belonging to class I (which is cytosolic) and the other to class II. Thus, as demonstrated for Leishmania, the mitochondrial redox metabolism in Trypanosoma may also be independent of TXN activity. The major implication of these findings is that mitochondrial functions previously thought to depend on the provision of electrons by a TXN enzyme must proceed differently

Universal Genotyping in Tuberculosis Control Program, New York City, 2001–2003

Real-time universal genotyping decreased unnecessary treatment

Spirometric changes in obstructive disease: after all, how much is significant?

OBJECTIVE: To establish the upper limits for changes in FEV1, slow vital capacity (SVC), FVC, and inspiratory capacity (IC) after placebo administration in patients with airflow obstruction. METHODS: One hundred and two adults with airflow obstruction (FEV1 = 62 ± 19% of predicted) were included in the study. All of the participants performed SVC and FVC maneuvers before and after the administration of placebo spray. The changes in FEV1, SVC, FVC, and IC were expressed as absolute values, percentage of change from baseline values, and percentage of predicted values, 95% CIs and 95th percentiles being calculated. Factor analysis was performed in order to determine how those changes clustered. RESULTS: Considering the 95% CIs and 95th percentiles and after rounding the values, we found that the upper limits for a significant response were as follows: FEV1 = 0.20 L, FVC = 0.20 L, SVC = 0.25 L, and IC = 0.30 L (expressed as absolute values); FEV1 = 12%, FVC = 7%, SVC = 10%, and IC = 15% (expressed as percentage of change from baseline values); and FEV1 = 7%, FVC = 6%, SVC = 7%, and IC = 12% (expressed as percentage of predicted values). CONCLUSIONS: In patients with airflow obstruction, IC varies more widely than do FVC and SVC. For IC, values greater than 0.30 L and 15% of change from the baseline value can be considered significant. For FVC, values greater than 0.20 L and 7% of change from the baseline value are significant. Alternatively, changes exceeding 0.20 L and 7% of the predicted value can be considered significant for FEV1 and FVC. On factor analysis, spirometric parameters clustered into three dimensions, expressing changes in flows, volumes, and dynamic hyperinflation.OBJETIVO: Estabelecer os limites superiores para mudanças em VEF1, capacidade vital lenta (CVL), CVF e capacidade inspiratória (CI) após o uso de placebo em pacientes com obstrução ao fluxo aéreo. MÉTODOS: Cento e dois adultos com obstrução ao fluxo aéreo (VEF1 = 62 ± 19% do previsto) foram incluídos neste estudo. Todos os participantes realizaram manobras de CVL e CVF antes e depois do uso de spray de placebo. As mudanças em VEF1, CVL, CVF e CI foram expressas em valores absolutos, porcentagem de variação em relação aos valores basais e porcentagem dos valores previstos, e foram calculados os IC95% e os percentis 95. A análise fatorial foi realizada a fim de determinar como essas alterações se agrupavam. RESULTADOS: Considerando os IC95% e percentis 95 e após o arredondamento dos valores, obtivemos os seguintes limites superiores para resposta significante: VEF1 = 0,20 L, CVF = 0,20 L, CVL = 0,25 L e CI = 0,30 L (em valores absolutos); VEF1 = 12%, CVF = 7%, CVL = 10% e CI = 15% (em porcentagem de variação em relação aos valores basais) e VEF1 = 7%, CVF = 6%, CVL = 7% e CI = 12% (em porcentagem dos valores previstos). CONCLUSÕES: Em pacientes com obstrução ao fluxo aéreo, a CI apresenta maior variabilidade do que a CVF e a CVL. Para a CI, valores maiores que 0,30 L e 15% de variação em relação ao valor basal devem ser considerados significantes. Para CVF, valores maiores que 0,20L e 7% de variação em relação ao valor basal são significantes. Alternativamente, alterações de mais de 0,20 L e 7% do previsto no VEF1 e na CVF devem ser consideradas significantes. Na análise fatorial, os parâmetros espirométricos se agruparam em três dimensões, expressando mudanças no fluxo, volume e hiperinsuflação dinâmica.Universidade Federal do Rio Grande do NorteUniversidade Federal de São Paulo (UNIFESP)Hospital do Servidor Público Estadual de São PauloUNIFESPSciEL

Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis

While antibiotics are intended to specifically target bacteria, most are known to affect host cell physiology. In addition, some antibiotic classes are reported as immunosuppressive for reasons that remain unclear. Here, we show that Linezolid, a ribosomal-targeting antibiotic (RAbo), effectively blocked the course of a T cell mediated autoimmune disease. Linezolid and other RAbos were strong inhibitors of T helper-17 cell effector function in vitro, showing that this effect was independent of their antibiotic activity. Perturbing mitochondria! translation in differentiating T cells, either with RAbos or through the inhibition of mitochondria! elongation factor G1 (mEF-G1) progressively compromised the integrity of the electron transport chain. Ultimately, this led to deficient oxidative phosphorylation, diminishing nicotinamide adenine dinucleotide concentrations and impairing cytokine production in differentiating T cells. In accordance, mice lacking mEF-G1 in T cells were protected from experimental autoimmune encephalomyelitis, demonstrating that this pathway is crucial in maintaining T cell function and pathogenicity

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011