Investigação de variantes gênicas de canais iônicos em pacientes com síndrome do QT longo

FUNDAMENTO: A síndrome do QT longo (SQTL) é uma síndrome arrítmica herdada com aumento do intervalo QT e risco de morte súbita. Mutações nos genes KCNQ1, KCNH2 e SCN5A respondem por 90% dos casos com genótipo determinado, e a genotipagem é informativa para aconselhamento genético e melhor manejo da doença. OBJETIVO: Investigação molecular e análise computacional de variantes gênicas de KCNQ1, KCNH2 e SCN5A associadas à SQTL em famílias portadoras da doença. MÉTODOS: As regiões codificantes dos genes KCNQ1, KCNH2 e SCN5A de pacientes com SQTL e familiares foram sequenciadas e analisadas utilizando o software Geneious ProTM. RESULTADOS: Foram investigadas duas famílias com critérios clínicos para SQTL. A probanda da Família A apresentava QTC = 562 ms, Escore de Schwartz = 5,5. A genotipagem identificou a mutação G1714A no gene KCNH2. Foi observado QTC = 521 ± 42 ms nos familiares portadores da mutação contra QTC = 391 ± 21 ms de não portadores. A probanda da Família B apresentava QTc = 551 ms, Escore de Schwartz = 5. A genotipagem identificou a mutação G1600T, no mesmo gene. A análise dos familiares revelou QTC = 497 ± 42 ms nos portadores da mutação, contra QTC = 404 ± 29 ms nos não portadores. CONCLUSÃO: Foram encontradas duas variantes gênicas previamente associadas à SQTL em duas famílias com diagnóstico clínico de SQTL. Em todos os familiares portadores das mutações foi observado o prolongamento do intervalo QT. Foi desenvolvida uma estratégia para identificação de variantes dos genes KCNQ1, KCNH2 e SCN5A, possibilitando o treinamento de pessoal técnico para futura aplicação na rotina diagnóstica.

Impacto do uso de psicotrópicos na dispersão do intervalo QT em pacientes adultos

Fundamento: A dispersão do intervalo QT induzida por fármacos tem sido associada a arritmias ventriculares potencialmente fatais. Pouco se conhece sobre o uso de psicotrópicos, isolados ou em combinação com outros fármacos, na dispersão do QT. Objetivo: Avaliar o impacto do uso psicotrópicos na dispersão do intervalo QT em pacientes adultos. Métodos: Estudo de coorte observacional, envolvendo 161 pacientes hospitalizados em um departamento de emergência de hospital terciário, estratificados em usuários e não usuários de psicotrópicos. Dados demográficos, clínicos, laboratoriais e de fármacos em uso foram coletados à admissão, bem como o eletrocardiograma de 12 derivações, com a mensuração do intervalo e da dispersão do QT. Resultados: A dispersão do intervalo QT foi significativamente maior no grupo de usuário de psicotrópicos comparado ao grupo não usuário (69,25 ± 25,5 ms vs. 57,08 ± 23,4 ms; p = 0,002). O intervalo QT corrigido pela fórmula de Bazzett também se mostrou maior no grupo de usuário de psicotrópicos, com significância estatística (439,79 ± 31,14 ms vs. 427,71 ± 28,42 ms; p = 0,011). A análise por regressão linear mostrou associação positiva entre o número absoluto de psicotrópicos utilizados e a dispersão do intervalo QT, com r = 0,341 e p < 0,001. Conclusão: Na população amostral estudada, o uso de psicotrópicos se mostrou associado ao aumento da dispersão do intervalo QT, e esse incremento se acentuou em função do maior número de psicotrópicos utilizados.

Molecular phylogenies, chromosomes and dispersion in Brazilian akodontines (Rodentia, Sigmodontinae)

A new molecular phylogeny for akodontine rodents from Brazil was proposed. The phylogenetic tree was enriched with the area of occurrence and with information on the karyotype of the samples. Based on this enriched tree, and with a described methodology, hypotheses were proposed on the karyotype and area of occurrence of the ancestors of each Clade. Thus it was possible to discuss hypotheses on chromosome evolution of the group, and on dispersion events from the "area of original differentiation" of akodontines in the Andes. Chromosome evolution started with high diploid numbers (2n=52) and showed a tendency to reduction (until 2n=14 in more recent clades). Independent side-branches of the tree showed 2n reduction and in one case the 2n increased. At least four dispersion events from the Andes down to South-eastern Brazil were proposed. The results should suggest the direction of new studies on comparative karyology.

Trade disclosure and price dispersion

This paper determines the effects of post-trade opaqueness on market performance. We find that the degree of market transparency has important effects on market equilibria. In particular, we show that dealers operating in a transparent structure set regret-free prices at each period making zero expected profits in each of the two trading rounds, whereas in the opaque market dealers invest in acquiring information at the beginning of the trading day. Moreover, we obtain that if there is no trading activity in the first period, then market makers only change their quotes in the opaque market. Additionally, we show that trade disclosure increases the informational efficiency of transaction prices and reduces volatility. Finally, concerning welfare of market participants, we obtain ambiguous results. Keywords: Market microstructure, Post-trade transparency, Price experimentation, Price dispersion.

Epidemiologia de la leishmaniasis tegumentaria en merida, Venezuela. I. Diversidade y dispersion de especies flebotominas en tres pisos altitudinales y su possible rôle en la transmission de enfermedad

Como parte de un estudio epidemiológico sobre leishmaniasis en el Estado Mérida, Venezuela, se presenta la diversidad y dispersión de las especies flebotominas identificadas en 15 localidades ubicadas en 3 pisos altitudinales entre los 175 y los 1.960 m.s.n.m. De 7.126 espécimes capturados (5.132 hombres y 1.994 femenino) se registran 24 especies de Lutzomyia, reconociéndose 10 de las llmadas antropofílicas. Se detalla la distribución de las especies en cada piso altitudinal y en el domicilio humano, el peridomicilio y el ambiente silvestre. Se discute el posible papel que juegan las diferentes especies en la transmisión de la leishmaniasis tegumentaria en cada piso altitudinal en particular y en la región andino-venezolana, en general.

Evaluation of the reconstruction limits of a frequency-independent crosshole georadar waveform inversion scheme in the presence of dispersion

Waveform tomographic imaging of crosshole georadar data is a powerful method to investigate the shallow subsurface because of its ability to provide images of pertinent petrophysical parameters with extremely high spatial resolution. All current crosshole georadar waveform inversion strategies are based on the assumption of frequency-independent electromagnetic constitutive parameters. However, in reality, these parameters are known to be frequency-dependent and complex and thus recorded georadar data may show significant dispersive behavior. In this paper, we evaluate synthetically the reconstruction limits of a recently published crosshole georadar waveform inversion scheme in the presence of varying degrees of dielectric dispersion. Our results indicate that, when combined with a source wavelet estimation procedure that provides a means of partially accounting for the frequency-dependent effects through an "effective" wavelet, the inversion algorithm performs remarkably well in weakly to moderately dispersive environments and has the ability to provide adequate tomographic reconstructions.

Permeability estimates from poro-elastic dispersion analyses of sonic logs

Modern sonic logging tools designed for shallow environmental and engineering applications allow for P-wave phase velocity measurements over a wide frequency band. Methodological considerations indicate that, for saturated unconsolidated sediments in the silt to sand range and source frequencies ranging from approximately 1 to 30 kHz, the observable poro-elastic P-wave velocity dispersion is sufficiently pronounced to allow for reliable first-order estimations of the underlying permeability structure. These predictions have been tested on and verified for a surficial alluvial aquifer. Our results indicate that, even without any further calibration, the thus obtained permeability estimates as well as their variabilities within the pertinent lithological units are remarkably close to those expected based on the corresponding granulometric characteristics.

Information Dispersion and Equilibrium Multiplicity

This paper studies the implications of correlation of private signals about the liquidation value of a risky asset in a variation of a standard noisy rational expectations model in which traders receive endowment shocks which are private information and have a common component. We …nd that a necessary condition to generate multiple linear partially revealing rational expectations equilibria is the existence of several sources of information dispersion. In this context equilibrium multiplicity tends to occur when information is more dispersed. A necessary condition to have strategic complementarity in information acquisition is to have mul- tiple equilibria. When the equilibrium is unique there is strategic substi- tutability in information acquisition, corroborating the result obtained in Grossman and Stiglitz (1980). JEL Classi…cation: D82, D83, G14 Keywords: Multiplicity of equilibria, strategic complementarity, asym- metric information.

Prevalence and determinants of QT interval prolongation in medical inpatients.

BACKGROUND: QT interval prolongation carries an increased risk of torsade de pointes and death. AIM: We sought to determine the prevalence of QT prolongation in medical inpatients and to identify determinants of this condition. METHODS: We enrolled consecutive patients who were admitted to the internal medicine ward and who had an electrocardiogram performed within 24 h of admission. We collected information on baseline patient characteristics and the use of QT-prolonging drugs. Two blinded readers manually measured the QT intervals. QT intervals were corrected for heart rate using the traditional Bazett formula and the linear regression-based Framingham formula. We used logistic regression to identify patient characteristics and drugs that were independently associated with QTc prolongation. RESULTS: Of 537 inpatients, 22.3% had a prolonged QTc based on the Bazett formula. The adjusted odds for QTc prolongation based on the Bazett correction were significantly higher in patients who had liver disease (OR 2.9, 95% CI: 1.5-5.6), hypokalaemia (OR 3.3, 95% CI: 1.9-5.6) and who were taking ≥1 QT-prolonging drug at admission (OR 1.7, 95% CI: 1.1-2.6). Overall, 50.8% of patients with QTc prolongation received additional QT-prolonging drugs during hospitalisation. CONCLUSIONS: The prevalence of QTc prolongation was high among medical inpatients but depended on the method used to correct for heart rate. The use of QT-prolonging drugs, hypokalaemia and liver disease increased the risk of QTc prolongation. Many patients with QTc prolongation received additional QT-prolonging drugs during hospitalisation, further increasing the risk of torsade de pointes and death.

Simultaneous cell morphometry and refractive index measurement with dual-wavelength digital holographic microscopy and dye-enhanced dispersion of perfusion medium.

Digital holographic microscopy (DHM) allows optical-path-difference (OPD) measurements with nanometric accuracy. OPD induced by transparent cells depends on both the refractive index (RI) of cells and their morphology. This Letter presents a dual-wavelength DHM that allows us to separately measure both the RI and the cellular thickness by exploiting an enhanced dispersion of the perfusion medium achieved by the utilization of an extracellular dye. The two wavelengths are chosen in the vicinity of the absorption peak of the dye, where the absorption is accompanied by a significant variation of the RI as a function of the wavelength.