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Editorial for neurobiology of disease special issue on dystonia progress in the neurobiology of dystonia
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An evaluative model for lead distribution in roadside ecosystems
No full textIn roadside ecosystems lead concentrations in different environmental materials decrease with the distance from the road, following a typical pattern. A model that expresses this distribution pattern is proposed to evaluate lead contamination in these ecosystems. © 1987
[The treatment for Fabry disease: focus on agalsidase alpha and beta]
No full text: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from the deficiency of the hydrolytic enzyme α-galactosidase A (α-Gal A), with consequent accumulation of globotrioasoylceramide in cells and tissues of the body, resulting in a multi-system pathology. Classically affected hemizygous males may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), and cerebrovascular (transient ischemic attacks, strokes) signs of the disease, while heterozygous females have symptoms ranging from very mild to severe. End-stage renal disease and cardiovascular or cerebrovascular complications limit life-expectancy of untreated patients. Demonstration of α-Gal A deficiency is the definitive method for the diagnosis of hemizygous males, while it's often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping) of females is mandatory. The treatment options for FD are enzyme replacement therapy (ERT), and the oral pharmacological chaperone migalastat. Two different products, agalsidase alfa and agalsidase beta, have been commercially available in Europe for 20 years and they are both indicated for long-term ERT. In fact, clinical trials, observational studies and registry data have provided abundant evidence for the safety and efficacy of ERT in improving symptoms and disease progression. Agalsidase alpha and beta are two almost identical recombinant proteins although they are used clinically with a different dosage regimen. In this chapter we aim to clarify the differences between the two ERTs and how these can affect the pharmacokinetic/pharmacodynamic (PK/PD) characteristics and ultimately the risk/benefit profile. The chaperone migalastat, available in Europe since 2016, is the only oral treatment for FD, and acts stabilizing specific mutant forms of α-Gal, defined "amenable" to migalastat. A multitude of therapies are now under investigation in various phases of clinical trials. These include pegylated form of α-Gal (pegunigalsidase alpha), gene therapy (both in-vivo and ex-vivo methods), mRNA therapy (inducing production of α-Gal) and substrate reduction therapy (inhibitors of glucosylceramide synthase leading to reduction of Gb-3)
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Author response: Alterations of functional connectivity of the motor cortex in Fabry disease: An RS-fMRI study
No full textVariations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Homeostatic changes of the endocannabinoid system in Parkinson's disease
No full textEndocannabinoids (eCBs) are endogenous lipids that bind principally type-1 and type-2 cannabinoid (CB(1) and CB(2)) receptors. N-Arachidonoylethanolamine (AEA, anandamide) and 2-arachidonoylglycerol (2-AG) are the best characterized eCBs that are released from membrane phospholipid precursors through multiple biosynthetic pathways. Together with their receptors and metabolic enzymes, eCBs form the so-called "eCB system". The later has been involved in a wide variety of actions, including modulation of basal ganglia function. Consistently, both eCB levels and CB(1) receptor expression are high in several basal ganglia regions, and more specifically in the striatum and in its target projection areas. In these regions, the eCB system establishes a close functional interaction with dopaminergic neurotransmission, supporting a relevant role for eCBs in the control of voluntary movements. Accordingly, compelling experimental and clinical evidence suggests that a profound rearrangement of the eCB system in the basal ganglia follows dopamine depletion, as it occurs in Parkinson's disease (PD). In this article, we provide a brief survey of the evidence that the eCB system changes in both animal models of, and patients suffering from, PD. A striking convergence of findings is observed between both rodent and primate models and PD patients, indicating that the eCB system undergoes dynamic, adaptive changes, aimed at restoring an apparent homeostasis within the basal ganglia network
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