1,720,994 research outputs found
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
Immune and metabolic profile in acromegalic patients and the impact of the current medical treatment. Results from the PROMISE study
Full text linkIntroduction: Acromegaly is associated with several comorbidities, mainly cardiovascular, respiratory and metabolic diseases, with an increase in the last years of cancer as main cause of mortality. Conversely, little is known about the immune function in acromegaly, even if GH/IGF1 axis has long been supposed to play a role in immune modulation, mainly by affecting lymphocytes and monocytes. We aimed to evaluate the peripheral blood mononuclear cells (PBMCs) subpopulations in acromegalic patients (ACRO) in comparison with controls (CTRLs) and to investigate the impact of disease control and different medical treatments on PBMCs, metabolism and body composition.
Material and Methods: This is an observational, prospective, single site, pilot study (NCT05069324). Twenty-nine patients (16 M and 13 F, mean age 51.3 15.6 years) with an active disease and 25 sex and age-matched healthy volunteers entered the study according to inclusion criteria. Twenty-five acromegalic patients underwent neurosurgery, 15 were on SSA treatment, and 10 patients on PEG (monotherapy or combined with SSA). Six patients with uncontrolled disease (IGF1 1.2 x ULN) on SSA treatment changed therapy (add or switch to PEG) and were evaluated after 8 weeks from the treatment change together with another group of 8 patients with stable disease. Anthropometric, metabolic and hormonal parameters were recorded along with full quantification of PBMCs evaluated by flow cytometry. Data are expressed as means SD or median (IQR) and statistical analysis was performed with parametric and non-parametric tests, as appropriate.
Results: Immune cell profiling revealed in ACRO compared to CTRLs decreased monocytes with a higher proportion of non-classical and a lower proportion of intermediate subset. Moreover, ACRO had lower NK cells and CD16high NK with an increased proportion of the more naturally cytotoxic subset (CD56dim) and a decreased proportion of the NK cells more responsible of cytokine production (CD56bright), without changes in T and B-lymphocytes. In ACRO group no differences were found according to disease control and medical treatment. Conversely, in treated acromegalic patients body composition parameters were similar to CTRLs, with a higher fat mass, particularly localized at trunk, in PEG treated patients compared to SSA treatment. The introduction of PEG, in comparison with the stable treatment, improved after 8 weeks glycaemia and influenced the immune cells redistribution by increasing the proportion of non-classical monocytes and CD56bright NK cells, without body composition changes.
Discussion: To the best of our knowledge, this study demonstrated for the first time that acromegalic patients showed an immunological fingerprint, characterised by decreased monocytes and NK cells and by an imbalance of immune innate cells subset, supporting the role of GH/IGF1 axis in immune system modulation. These results could represent the background for further studies, particularly considering the relationship between immune function and cancer and the higher cancer risk reported in acromegaly. The treatment change (add or switch to PEG) may influence immune cells redistribution, without body composition effects, supporting a potential role of PEG in immune regulation. However, further studies are needed to confirm these data and to better clarify the underlying mechanisms and their potential clinical implications
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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