1,721,376 research outputs found
Nuovi approcci molecolari nello studio della fisiopatologia del diabete gestazionale
Full text linkAbstract research study 1
Cross-talk between foetal membranes and visceral adipose tissue involves HMGB1-RAGE and VIP-VPAC2 pathways in human gestational diabetes mellitus
Introduction: Gestational diabetes mellitus (GDM) is defined as glucose intolerance that is first diagnosed during pregnancy. Foetal membranes (FMs) and maternal visceral adipose tissue (VAT) secrete various molecules that are relevant players in the pathogenesis of GDM.
Aim: This pilot study aimed to comparatively evaluate the expression of high mobility group box 1 protein (HMGB1) and its receptor for advanced glycation end products (RAGE), and vasoactive intestinal peptide (VIP) and its receptors (VPAC1, VPAC2) in FMs and VAT in GDM and in healthy pregnant women.
Patients and Methods: FMs, omental VAT explants, and serum samples were obtained from twelve patients with GDM and twelve pregnant women with normal glucose tolerance (NGT) at delivery. The expression of HMGB1, RAGE and VIP, VPAC1 and VPAC2 was detected by Western Blotting in explants; circulating levels and in vitro release of HMGB1 and VIP were measured by ELISA tests.
Results: HMGB1 tissue expression was higher in FMs obtained from GDM patients (p=0.02) than in FMs from NGT women. VPAC2 (p=0.03) and RAGE (p=0.03) tissue expressions were significantly increased in VAT from GDM patients compared to NGT. Only FMs of NGT released detectable levels of HMGB1, which was not observed in samples obtained from GDM. VAT of GDM released lower levels of VIP (p=0.05) than NGT samples.
Conclusions: This study suggests that a fine tuned regulation exists between FMs and VAT throughout pregnancy to maintain immune metabolic homeostasis. In GDM a balance between pro-inflammatory and anti-inflammatory mediators has been observed. Further studies are needed to establish their exact role on foetal and maternal outcomes in GDM.
Abstract research study 2
MicroRNA expression profile in circulating exosomes and plasma of patients with GDM and healthy pregnant women
Introduction: MicroRNAs are small non-coding RNAs, playing critical roles in modulating gene expression. The deregulation of microRNAs has been observed in GDM, highlighting their crucial involvement both in the pathogenic mechanisms of this condition and in the development of its complications. Circulating microRNAs can be packaged into exosomes, and exosome signalling has emerged as a novel mechanism of cell-to-cell communication. Through exosomes, microRNAs are delivered in distant target cells and are able to affect gene expression.
Aim: The aim of this study was to explore microRNA expression in circulating exosomes and in plasma obtained from patients with GDM and healthy control subjects in the third trimester of gestation, to potentially elucidate some relevant aspects of GDM pathophysiology and individuate novel potential candidate biomarkers for GDM.
Patients and Methods: A profiling cohort of plasma samples collected from GDM (n=3, age: 34.7 ± 4.9 years; BMI 27.0 ± 3.7 Kg/m2) and NGT women (n=3, age: 34.3 ± 3.1 years; BMI 26.4 ± 1.1 Kg/m2) was recruited. In addition, a profiling cohort of healthy non-pregnant age- and BMI-matched women (NP, n=5) was used as negative control. The microRNA patterns of expression in exosomes and plasma have been assessed with the innovative technology NanoString nCounter microRNA expression (NanoString Technologies inc., Seattle, WA, USA). Target gene identification and bioinformatics analysis of the differentially expressed microRNAs have been performed with Ingenuity Pathway Analysis (IPA, QIAGEN Redwood City, USA).
Results: A specific set of microRNAs resulted to be differentially expressed in exosomes and plasma from GDM patients compared to NGT. Specifically, five exosomal microRNAs were significantly upregulated, while 23 were downregulated in GDM compared to NGT. As for plasma, 4 microRNA were upregulated, while 9 were downregulated in GDM compared to NGT. In addition, two microRNAs, miR-196a-5p and miR-652, resulted to be significantly downregulated in GDM compared both to NGT and NP in exosomes and plasma, respectively, suggesting that their deregulation might hallmark GDM pregnancy. In bioinformatics analysis the major predicted target genes and biological processes of the deregulated microRNAs were associated with insulin resistance, abnormal glucose and lipid metabolism, consistently linked to GDM pathophysiology.
Conclusions: GDM might markedly alter microRNA profile in exosomes and plasma, conceivably mirroring the metabolic alterations described in GDM pregnancy. In light of this, exploring circulating microRNA expression might help unravel the molecular events leading to the metabolic alterations observed in GDM
Inhibition of BACE-1 by hydroxyethylsulfide, hydroxyethylamine and hydroxyethylurea isosteric replacements
No full textNew inhibitors of the beta-site amyloid precursor protein cleaving enzyme (BACE-1) are described. The hydroxyethyl transition state isostere of GT1017 has been replaced by the hydroxyethylamine (HEA), the hydroxyethylsulfide or the hydroxyethylurea groups. Biological evaluation has shown that the HEA analogue, obtained as epimeric mixture, inhibited BACE-1 with an IC50=0.12 mu M. Stereoselective synthesis showed surprisingly that the most active stereoisomer was the (R)-HEA transition state analogue with an IC50=0-014 mu M
Natural history, endocrine complications and testicular dysfunction in Klinefelter syndrome and high-grade sex chromosome aneuploidies
Full text linkDespite celebrating 80 years since the original description of the first case of Klinefelter syndrome in 1942, several aspects relating to the morbidity of KS and HGAs are still unclear and are object of active research. In Chapter 2 we sought to describe the natural history of KS, from infancy into adulthood. We employed a semi-longitudinal approach in a large cohort of KS patients, describing how testicular dysfunction is not hormonally-detected in KS before Tanner stages 3-4. Specifically: a) INHB levels are maintained in the normal (adult) range until stage 4, b) the INHB/FSH ratio sharply declines between stages 3 and 4, c) T and cfT levels are highest between Tanner stage 5 and transition age and d) the T/LH ratio declines during Tanner stage 4. We further demonstrated the capability of quantitaty testicular ultrasound in revealing damage evolution in KS, and specifically how: a) the bitesticular volume gradually increases during puberty until Tanner stage 4, with subsequent regression, b) parenchymal echotexture progressively worsen throughout puberty, transition age, into adulthood and c) how the presence of hypoechoic testicular lesions, microlithiasis and higher entropy are independent predictors of worse testicular endocrine function. From our results we speculate that this combined approach could be used in the future as a clinical tool to more accurately identify the onset of testicular dysfunction, possibly guiding the start of TRT or the timing of (m)TESE procedures. In Chapter 3 we addressed the complex phenotypic spectrum of HGAs by comparison to KS, with regards to endocrine, metabolic and cardiac features. Specifically we assessed the hypothesis of a genotype-phenotype relationship dependent on the number of supernumerary X chromosomes in determining certain phenotypic traits, by adjusting for the number of supernumerary Y chromosomes. Indeed, the results of our study show that the increase in supernumerary X chromosomes determines several significant trends towards a progressive reduction in height, a worsening of testicular volume and function, a reduced overall steroidogenic activity, impaired glucose and lipid homeostasis, as well as cardiac structure and function. As no guidelines are currently available for the management of these complex syndromes; we believe that a better understanding of their intrinsic characteristics can guide researchers towards recognizing HGAs as indipendent clinical entities, and medical practitioners towards earlier identification of complications, and thus allow for a more tailored management and appropriate treatment of the individual HGA patient. In Chapter 4 we approached thyroid alterations specific to KS, revealing a more more complex and broader nature than previously proposed, characterized by reduced thyroid hormone levels, inappropriately normal/low TSH levels, altered pituitary deiodination mediated by reduced T, increased thyroid autoimmunity, and structural parenchymal changes. These findings are particularly relevant also in light of the recent evidence suggesting a stronger association of free thyroid hormones (and especially fT4), as compared to TSH levels, to clinical outcomes (e.g., atrial fibrillation, features of metabolic syndrome, osteoporosis, dementia, etc.). In this respect, it is noteworthy that several complications of KS are also seen in hypothyroidism, including metabolic syndrome, increased cardiovascular risk, cognitive dysfunction, reduced bone mass, and sexual dysfunction, and could thus possibly contribute to our understanding of the missing link between genoype and phenotype in KS morbidity. Whether the alterations in the HPT axis of KS contribute to the poorer outcome of the syndrome, or whether hypogonadism is involved the pathogenesis of thyroid structural and functional impairment warrant further studies. In Chapter 5 we took on the study of testicular vascularisation and microvascular dynamics by means of contrast-enhanced ultrasound (CEUS). We could show the presence of slower testicular perfusion kinetics in subjects with KS than in age-matched controls, and, specifically, the wash-in time, mean transit time, time to peak, and washout time were all prolonged. Most strikingly, faster testicular blood flow was associated with higher circulating total T levels. We then applied principal component analysis (PCA) and multiple linear regression analyses which supported a role for reduced venous blood flow as an independent predictor of testicular T peripheral release, consistent with previous reaserch highlighting increased intratesticular T levels in KS subjects. In Chapter 6 we explored for the first time the bone-testicular axis in the context of male hypogonadism, specifically by exploiting a model of hypergonadotropic hypogonadism represented by KS. We did so by a retrospective longitudinal approach at a single academic referral centre for KS, and evaluated subjects taking into account pubertal stage, gonadal
status as well as TRT commencement. We could demonstrate the relationship between T and total osteocalcin (tOCN), and specifically the directionality of the association, which implicates OCN in regulating the HPG axis at a central (hypothalamic and/or pituitary) rather than peripheral (testicular) level, in the context of an LH-T feedback loop already stretched to its maximum capability.
To conclude, this thesis aimed to provide further insight in the natural history, endocrine complications and testicular dysfunction in KS and HGAs. Although progress has been made in the understanding of these complex syndromes, some issues that were described above remain unsolved and warrant further study. Furthermore, the effects of T were studied. Despite the great clinical efficacy of TRT on some clinical endpoints, many other endocrine, metabolic, bone and cardiovascular complications of the syndromes generally remain unchanged. Whether timely hormonal therapy with T (and levothyroxine) can ultimately ameliorate the clinical burden of these conditions remains to be investigated
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
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 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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
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