1,720,961 research outputs found
Cardiologist and Diabetologist crosstalk in the era of cardiovascular outcome trials of novel glucose-lowering drugs
No full textThe prevalence of type 2 diabetes continues to increase and cardiovascular (CV) diseases remain the leading cause of death in diabetic patients. Diabetologists and Cardiologists have to work together in order to provide the best management to these patients. After years of disappointing studies showing no reduction of CV events with strict glycaemic control, some of the novel glucose-lowering drugs (GLDs) seem to offer a new approach to tackle the problem, since the CV outcome trials (CVOTs-D) of liraglutide, semaglutide, empagliflozin and canagliflozin have demonstrated not only their CV safety but also their efficacy in the reduction of CV morbidity and mortality. Along with the initial enthusiasm, concerns have been raised about the economical sustainability of long-term therapies considering higher costs of new molecules relative to the traditional ones. As expenses in the medical field are on the rise, healthcare systems need to balance the positive impact of an intervention and its overall cost. This review is meant to offer the Cardiologists a different point of view on the positive influence of GLDs, in the light of the main trials in the CV fields they are familiar with. The purpose of this article is to critically review the magnitude of the CVOTs-D results by the analysis of their statistical determinants, to establish the extent of the GLDs positive impact on patients with both diabetes and CV disease. The analysis has been performed taking into account models and statistical determinants used in the main landmark cardiology trials. It is fundamental to translate the result of CVOTs-D in clinical practice: the interdisciplinary crosstalk between the Cardiologist and Diabetologist is of paramount importance in order to fully exploit the power of the new available pharmacological strategies. Keywords: Cardiovascular outcome trials, Glucose-lowering drugs, Type 2 diabetes, Crosstalk, Cardiovascular ris
Photoacoustic molecular imaging for in vivo liver iron quantitation
Full text linkA recent study showed that ferritin is a suitable endogenous contrast agent for photoacoustic molecular
imaging in cultured mammalian cells. We have therefore tested whether this imaging technique can be used
for in vivo quantification of iron in mouse livers. To verify this hypothesis, we used multispectral optoacoustic
tomography (MSOT) to image albino CD1 mice before and after experimental iron loading. Postmortem assays
showed that the iron treatment caused a 15-fold increase in liver iron and a 40-fold increase in liver ferritin levels,
while in vivo longitudinal analysis using MSOT revealed just a 1.6-fold increase in the ferritin/iron photoacoustic
signal in the same animals. We conclude that MSOT can monitor changes in ferritin/iron levels in vivo, but its
sensitivity is much lower than that of ex vivo iron assays
Hepcidin antagonists for potential treatments of disorders with hepcidin excess
No full textThe discovery of hepcidin clarified the basic mechanism of the control of systemic iron homeostasis. Hepcidin is mainly produced by the liver as a propeptide and processed by furin into the mature active peptide. Hepcidin binds ferroportin, the only cellular iron exporter, causing the internalization and degradation of both. Thus hepcidin blocks iron export from the key cells for dietary iron absorption (enterocytes), recycling of hemoglobin iron (the macrophages) and the release of storage iron from hepatocytes, resulting in the reduction of systemic iron availability. The BMP/HJV/SMAD pathway is the major regulator of hepcidin expression that responds to iron status. Also inflammation stimulates hepcidin via the IL6/STAT3 pathway with a support of an active BMP/HJV/SMAD pathway. In some pathological conditions hepcidin level is inadequately elevated and reduces iron availability in the body, resulting in anemia. These conditions occur in the genetic iron refractory iron deficiency anemia and the common anemia of chronic disease (ACD) or anemia of inflammation. Currently, there is no definite treatment for ACD. Erythropoiesis-stimulating agents and intravenous iron have been proposed in some cases but they are scarcely effective and may have adverse effects. Alternative approaches aimed to a pharmacological control of hepcidin expression have been attempted, targeting different regulatory steps. They include hepcidin sequestering agents (antibodies, anticalins, and aptamers), inhibitors of BMP/SMAD or of IL6/STAT3 pathway or of hepcidin transduction (siRNA/shRNA) or ferroportin stabilizers. In this review we summarized the biochemical interactions of the proteins involved in the BMP/HJV/SMAD pathway and its natural inhibitors, the murine and rat models with high hepcidin levels currently available and finally the progresses in the development of hepcidin antagonists, with particular attention to the role of heparins and heparin sulfate proteoglycans in hepcidin expression and modulation of the BMP6/SMAD pathway
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
Mitochondrial ferritin deficiency reduces male fertility in mice
Full text linkMitochondrial ferritin (FtMt) is a functional ferritin targeted to mitochondria that is highly expressed in the
testis. To investigate the role of FtMt in the testis we set up a series of controlled matings between FtMt gene-deletion mice
(FtMt/) with FtMtþ/þ mice. We found that the number of newborns per litter and the fertility rate were strongly reduced
for the FtMt/ males, but not for the females, indicating that FtMt has an important role for male fertility. The
morphology of the testis and of the spermatozoa of FtMt/ mice was normal and we did not detect alterations in sperm
parameters or in oxidative stress indices. In contrast, we observed that the cauda epididymides of FtMt/ mice were
significantly lighter and contained a lower number of spermatozoa compared with the controls. Also, the ATP content of
FtMt/ spermatozoa was found to be lower than that of FtMtþ/þ spermatozoa. These data show that FtMt contributes to
sperm epididymis maturation and to male fertility
Variations 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
Adult-Onset Alexander Disease: New Causal Sequence Variant in the GFAP Gene
No full textOBJECTIVES: Alexander disease (AD) is a rare disorder of the CNS. Diagnosis is based on clinical symptoms, typical MRI findings, and mutations in the glial fibrillary acid protein (GFAP) gene. In this case study, we describe a new mutation (p.L58P) in GFAP that caused a phenotype of adult-onset AD (AOAD). METHODS: In our outpatient clinic, a patient presented with cerebellar and bulbar symptoms after brain concussion. We used MRI and performed next-generation exome sequencing (NGS) to find mutations in GFAP to diagnose AD. The mutation was then transfected into HeLa cell lines to prove its pathogenicity. RESULTS: The brain MRI finding showed typical AD alterations. The NGS found a heterozygous variant of unknown significance in GFAP (c.173T>C; p.L58P). After transfecting HeLa cell lines with this mutation, we showed that GFAP-L58P formed pathogenic clusters of cytoplasmic aggregates. DISCUSSION: We have found a new mutation that causes AOAD. We recommend that AOAD is included in the diagnostic workup in adult patients with gait ataxia and cerebellar and bulbar symptoms in association with a traumatic head injury
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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