1,721,065 research outputs found

    Cardiovascular risk assessment and diagnostic work-up in rare diseases: focus on hyperaldosteronism and primary antibody deficiency

    Full text link
    Introduction: Unilateral form of primary aldosteronism (PA) is the main curable cause of endocrine hypertension cause of PA and it is in up to 66% of all cases investigated with adrenal vein sampling (AVS). Mutations in the KCNJ5 potassium channel involve up to 70% of unilateral PA. The in vitro evidences of macrolide antibiotics specifically inhibit the altered function of mutated KCNJ5 channels has opened new horizons for the diagnosis and treatment of unilateral PA with KCNJ5 mutations in that it can allow identification and target treatment of PA patients harbouring a mutated unilateral PA. Aim: To test the effect of roxithromycin on aldosterone secretion and blood pressure in vivo in patients without PA, and in those with PA subtyped by AVS and examined according to the presence or absence of KCNJ5 mutation. Methods: We enrolled consecutive hypertensive patients undergoing screening for secondary hypertension, from January 2018 to June 2022. Each patient received a single oral dose of roxithromycin and, after the diagnostic work-up, baseline values of plasma aldosterone concentration (PAC) and blood pressure were compared with post-roxithromycin values. Next- generation sequencing (NGS) was used to identify KCNJ5 mutated from wild-type forms of unilateral PA. Response to roxithromycin was compared between non-PA, non-unilateral PA and unilateral PA. In unilateral PA we focused on KCNJ5 mutated vs wild-type patients. Results: After roxithromycin administration, patients with unilateral PA carring KCNJ5 mutation showed a decrease in PAC (p=0.030) that did not occur in unilateral PA KCNJ5 wild-type. In these groups systolic blood pressure (SBP) and diastolic blood pressure (DBP) did not change in response to roxithromycin. However, in non-PA group a decrease in PAC was observed (p<0.001) with a decrease in plasma cortisol concentration (PCC) (p<0.001) and systolic (p<0.001) but not diastolic blood pressure. After adrenalectomy, roxithromycin did not induce any change in PAC in KCNJ5 mutated unilateral PA. Conclusion: Roxithromycin administration induces a decrease in aldosterone production in patients with KCNJ5 mutation but not in wild-type, confirming its ability in vivo to blunt aldosterone production by blocking the mutated Kir3.4 sodium channel without affecting wild-type forms. As the decrease in PAC in the same patients did not occur after adrenalectomy, the roxithromycin effect is unequivocally attributable to the KCNJ5 mutated unilateral PA.Introduction: Although the immune system is involved in vascular disorders, the actual role of B cells in atherosclerotic cardiovascular disease (ASCVD) remains unclear. Inflammatory conditions like Rheumatoid Arthritis and Systemic Lupus Erythematosus present an accelerated atherosclerotic process, that is somehow limited by appropriate treatment, including B cell depleting therapies. Common Variable Immunodeficiency (CVID) is a rare primary immunodeficiency of adulthood and represents a pathological condition suitable for studying the role of B cells in ASCVD. The cardiovascular risk profile of patients affected by this rare disease is unexplored and it is unclear whether CVID patients are protected towards atherogenesis. Aim: We investigated the prevalence of cardiovascular risk factors and the presence of subclinical ASCVD in CVID patients. Methods: We collected anamnestic clinical and biochemical data related to CVID and to ASCVD in a single center cohort of CVID patients, grouped according to clinical and immunological phenotype. At follow-up visit vascular structural and functional investigation was performed by SphygmoCor(R) XCEL instrument while droplet digital PCR analysis was used to assess gene expression. Results: 127 CVID patients were enrolled in the study. Patients with complicated phenotype presented significantly lower levels of cholesterol and blood glucose, despite a significantly higher use of corticosteroids (p=0.014) due to higher frequency of GLILD (p<0.001) and autoimmunity(p=0.007), particularly ITP (p<0.001). Patients with Chapel phenotype 2 and 3 presented the lowest cholesterol and HbA1c levels. No significant difference was found in terms of metabolic syndrome, hypertension, diabetes, anti-hypertensive, anti diabetic and lipid lowering ongoing treatment, as well as acute cardiovascular events between complicated and uncomplicated phenotype. Lower IgA, IgM IgG levels at diagnosis, SmB cells % as well as higher T-LGL % (CD3+CD8+CD57+) and monthly dosage of IgRT in the complicated group were the main between groups significantly different immunologic parameters. In vivo measurement by SphygmoCor(R) XCEL instrument in a subgroup of 55 patients showed significant difference pulse pressure and augmentation pressure, with a tendence towards higher arterial thickness in patients with only infections. In the same subgroup, B lymphocytes isolated from pheripheral blood of patients with complicated phenotype presented a borderline-significantly higher expression of LDL receptor gene at droplet digital PCR analysis (p=0.053). Conclusion: Our data suggest that clinical phenotypes of CVID may be associated with different cardiovascular risk profiles, possibly based on the different underlying immunological alterations. Preliminary data suggests that B cell defects in CVID patients might influence the development of cardiovascular disease leading to different cardiovascular risk profile. The role of IgRT also needs to be explored. Follow-up studies will unravel the significance of our subclinical findings in terms of development of overt disease, with possible implications in terms of new therapeutic strategies for ASCVD

    Weak social ties improve content delivery in behavior-aware opportunistic networks

    No full text
    In the era of pervasive mobile computing, human encounters can be leveraged to enable new forms of social interactions mediated by the personal devices of individuals. In this framework, emerging needs, such as content dissemination, social discovery and question and answering, advocate the raising of novel communication paradigms where the binding content-recipients is not provided by the sender (in the classical IP addressing style), but directly executed by specific recipients with interest in it. This paper proposes a novel communication protocol, named InterestCast, or ICast, solving the problem for a wide range of social scenarios and applying to an opportunistic network whose nodes are the personal devices of moving individuals, possibly interacting with fixed road-side devices. The protocol is able to chase users’ interests decoupling content tags from locations and social communities. In order to cross community boundaries and reach farthest destinations, ICast adopts mechanisms that properly extract weak ties, i.e. encounters between nodes that rarely interact, but that connect different communities. The main advantages the proposal achieves are: it ensures remarkable performance results; it is simple and feasible and it keeps computational and networking costs low; it can preserve users’ privacy

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Full text link
    The 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

    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

    Appropriate Similarity Measures for Author Cocitation Analysis

    Full text link
    We 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 link
    We 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

    Author Index

    No full text
    Nao informado

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

    No full text
    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
    corecore