ABSTRACT
Glucosylceramidase beta 1 (GBA1) variants have attracted enormous attention as the most promising and important genetic candidates for precision medicine in Parkinson’s disease (PD). A substantial correlation between GBA1 genotypes and PD phenotypes could inform the prediction of disease progression and promote the development of a preventive intervention for individuals at a higher risk of a worse disease prognosis. Moreover, the GBA1-regulated pathway provides new perspectives on the pathogenesis of PD, such as dysregulated sphingolipid metabolism, impaired protein quality control, and disrupted endoplasmic reticulum-Golgi trafficking. These perspectives have led to the development of novel disease-modifying therapies for PD targeting the GBA1-regulated pathway by repositioning treatment strategies for Gaucher’s disease. This review summarizes the current hypotheses on a mechanistic link between GBA1 variants and PD and possible therapeutic options for modulating GBA1-regulated pathways in PD patients.
ABSTRACT
Because of the continued importance of correct condom-use in controlling the HIV epidemic and the limited availability of tools for assessing correct condom-use, methods for assessing condom-application skills, especially when direct observation is not feasible, are needed. Accordingly, in the context of a high-risk population (The Bahamas) for HIV, a 17-item scale—the Condom-use Skills Checklist (CUSC)—was developed for use among young adolescents and adults. The rationale and approach to developing the scale and some measures of internal consistency, construct validity, and criterion-related validity have been described. It is concluded that the scale offers a reasonable alternative to direct observation among older subjects and that further development may make it more useful among pre-adolescents.
ABSTRACT
A doença causada pelo virus da hepatite A (VHA) costuma ser considerada como benigna, afetando principalmente os pré-escolares. Contudo, nesta revisäo se discutem os vários grupos da populaçäo em geral, nos quais a infecçäo pelo VHA pode apresentar consequências mais graves. Em consequência da alteraçäo epidemiológica verificada na América Latina, um número cada vez maior de adolescentes e adultos jovens se mantêm suscetíveis à infecçäo pelo VHA. A infecçäo por esse vírus, neste grupo etário, irá representar grave impacto no futuro, ausência prolongada ao trabalho e/ou escola e custos maiores para os sistemas locais de saúde. Em estudos recentes na Argentina e Chile, o VHA foi, também, o agente etiológico mais prevalente nos casos de insuficiência hepática fulminante em pré-escolares. A hepatite A aguda em pacientes com doença hepática crônica subjacente, especialmente hepatite C crônica, tem sido associada à insuficiência hepática grave ou fulminante. A prevençäo da hepatite A através da vacinaçäo parece ser o meio mais potente de se conter o VHA. As vacinas inativadas contra a hepatite A comprovaram ser seguras, altamente imunogênicas e indutoras de proteçäo duradoura contra infecçöes pelo VHA
Subject(s)
Humans , Child, Preschool , Child , Adolescent , Adult , Viral Hepatitis Vaccines , Hepatovirus , Hepatitis A/complications , Hepatitis A/prevention & control , Hepatitis A/epidemiology , Disease Outbreaks/prevention & controlABSTRACT
The procoagulant activities of Russell's viper venom were assessed in an in vitro whole blood model. Sequential samplings showed that the generation of fibrinopeptide A (FPA), a marker of thrombin activity, and platelet factor 4 (PF4), a marker of platelet activity, exhibited bi-phasic kinetics with an initial slow phase followed by a rapid phase of secretion. In the presence of Russell's viper venom, the generation of both FPA and PF4 was accelerated with the bi-phasic kinetics of PF4 being maintained while that of FPA completely disappeared. Administration of either antivenom (1,600 ng) or 10 IU antithrombin III (AT-III) had no antagonistic effect against the venom but combination of both resulted in a significant prolongation of both FPA and PF4 release (p < 0.05). High dose AT-III (20 IU) resulted in normalization of both FPA and PF4 kinetics and serial levels of both parameters were lower than those treated with the combined regimen, although these were not statistically significant. Unlike the untreated venom activated whole blood, there was no clot formation following treatment with either the combined regimen or high dose AT-III. The results of this study suggested that the effect of Russell's viper venom on the clotting cascade is more potent and direct than that on platelet activity. There were complementary effects between antivenom and AT-III is controlling of both FPA and PF4 release induced by the venom. Furthermore, in this in vitro experiment, AT-III alone when administered in a sufficient dose, abolished the procoagulant effects of Russell's viper venom.