87,509 research outputs found
Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes: evidence to date
No full textFrancesca Cinti,* Simona Moffa,* Flavia Impronta,* Chiara MA Cefalo, Vinsin A Sun, Gian Pio Sorice, Teresa Mezza, Andrea Giaccari Center for Endocrine and Metabolic Diseases, Fondazione Policlinico Universitario A Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy *These authors contributed equally to this work Abstract: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the latest therapeutic strategy in the treatment of type 2 diabetes mellitus (T2DM). Using an insulin-independent mechanism (glycosuria), they reduce glucose toxicity and improve insulin sensitivity and β-cell function. The promising results obtained in clinical trials show that SGLT2 significantly improves glycemic control and provides greater cardiovascular protection, combined with a reduction in body weight and blood pressure (BP). This review focuses on ertugliflozin, a new, highly selective, and reversible SGLT2 inhibitor. Clinical trials published to date show that ertugliflozin, both as a monotherapy and as an add-on to oral antidiabetic agents, is safe and effective in reducing glycosylated hemoglobin (HbA1c), body weight, and BP in T2DM patients. Keywords: antidiabetic drugs, glycosylated hemoglobin, glycemic control, sodium-glucose cotransporter 2 inhibitors, precision medicine, type 1 diabetes mellitus, type 2 diabetes mellitus, weight reduction 
A proposal for a standard procedure for moderately accelerated electromigration tests on metal lines
No full textThis work is aimed at proposing a standard procedure for moderately accelerated Electromigration (EM) tests applied to interconnection lines of the present and the next future generation of integrated circuits. The procedure has been tested on one metal level test structures using an Al-alloy metallization scheme, but can be easily applied to other materials as well as to metal lines with vias. Di erent existing standards have been taken into consideration to define this proposal: ASTM F1260-89, JEDEC JESD33-A, JESSI AC41. In the PROPHECY project, the focus was on wafer level reliability evaluation with fast methods, but fast EM methods using extremely accelerated stress conditions usually induce side-e ects which can invalidate the results. As a consequence, this procedure suggests the use of moderately accelerated tests, together with a method for reducing the number of tests needed for a complete EM characterization. This procedure gives advice on the test structures to be used and on the preliminary steps to be performed before the EM tests. A measurement system, complying with the requirements of this procedure, is also brie ̄y described. The methods described in this document apply to both package- and wafer-level
measurements. In order to validate this procedure, EM tests have been performed on JESSI AC41 specimens
Are High Resolution Resistometric Methods Really Useful for the Early Detection of Electromigration Damage
No full textA proposal for a standard procedure for moderately accelerated electromigration tests on metal lines
No full textThis work is aimed at proposing a standard procedure for moderately accelerated Electromigration (EM) tests applied to interconnection lines of the present and the next future generation of integrated circuits. The procedure has been tested on one metal level test structures using an AI-alloy metallization scheme, but can be easily applied to other materials as well as to metal lines with vias. Different existing standards have been taken into consideration to define this proposal: ASTM F1260-89, JEDEC JESD33-A, JESSI AC41. In the PROPHECY project, the focus was on wafer level reliability evaluation with fast methods, but fast EM methods using extremely accelerated stress conditions usually induce side-effects which can invalidate the results. As a consequence, this procedure suggests the use of moderately accelerated tests, together with a method for reducing the number of tests needed for a complete EM characterization. This procedure gives advice on the test structures to be used and on the preliminary steps to be performed before the EM tests. A measurement system, complying with the requirements of this procedure, is also briefly described. The methods described in this document apply to both package- and wafer-level measurements. In order to validate this procedure, EM tests have been performed on JESSI AC41 specimens. (C) 1999 Elsevier Science Ltd. All rights reserved
Impronta genómica en la placenta y su relación con la preeclampsia
No full text[ES] Introducción: La impronta genómica es un proceso epigenético por el cual la expresión de un alelo varía en función del progenitor de que haya sido heredado. Se ha demostrado una alta expresión de genes improntados en la placenta y se cree que pueden estar implicados en la regulación de su desarrollo, además de en ciertas patologías como la preeclampsia. La preeclampsia es una enfermedad multisistémica que se caracteriza por la aparición de hipertensión y proteinuria inducida por el embarazo. Se asocia a una importante morbimortalidad tanto materna como fetal. Aunque en los últimos años se han producido avances en el campo de la fisiopatología y prevención, su etiología sigue siendo desconocida. Por todo ello resulta interesante estudiar el papel que podría tener la impronta genómica en la preeclampsia.
Material y Métodos: Se realizó una revisión sistemática de la literatura entre marzo de 2019 y marzo de 2020 en la base de datos Pubmed, seleccionándose un total de 49 artículos.
Resultados: Se han encontrado diferencias en la expresión de los genes improntados CDKN1C, DLX5, PEG10, PHLDA2, H19, MEST, DLK1 e IGF2 en placentas con preeclampsia respecto a placentas control. Además, se han descubierto más de 100 genes sujetos a impronta en la placenta, muchos de ellos relacionados con la regulación del desarrollo placentario y fetal. La pérdida de expresión o de impronta de ciertos genes improntados produce sobrecrecimiento o restricción del crecimiento fetal y/o placentario.
Discusión: Las patologías asociadas a alteraciones de la impronta genómica han servido para comprender la importancia de los genes improntados en el desarrollo de la placenta y sus patologías. Sin embargo, son pocos los estudios que han analizado de forma experimental la relación de la impronta genómica con la preeclampsia. No obstante, los artículos publicados hasta el momento dejan claro que se trata de un campo con mucho potencial de estudio. De cara a futuros estudios, resultaría indispensable solucionar las limitaciones descritas en esta revisión.
Conclusiones: Los estudios analizados sugieren que las alteraciones de la impronta genómica están relacionadas con la preeclampsia. Sin embargo, es necesario realizar más estudios y solucionar las limitaciones existentes hoy en día
Epicardial fat: the role of testosterone and lipid metabolism in a cohort of patients with Klinefelter syndrome
No full textContext: Klinefelter syndrome (KS), in which subjects have additional copies of X chromosomes, is the most common male sex chromosome abnormality, with a prevalence of 1 in 660 and an incidence of about 1 in 500–700 newborns. Its sign and symptoms include infertility, generally low testosterone levels, and an increased prevalence of obesity and metabolic syndrome. Epicardial fat thickness (EFT) reflects visceral adiposity rather than general obesity. Objective: The aim of this study was to analyze echocardiographic EFT in a cohort of patients with KS in comparison with non-obese and obese euploid controls, and to evaluate its correlation with biochemical parameters. Design, setting and participants: Two hundred and twenty-one KS patients referred to our Rare Endocrine Diseases clinic and 77 age-matched controls underwent Doppler echocardiography and a full investigation of anthropometric and body composition, Serum levels of total testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG), fasting plasma glucose, insulin, cholesterol and triglycerides were obtained. All participants underwent dual energy X-ray absorptiometry (DEXA) scan to assess truncal body fat (TrBF). Main outcome measure: EFT, body composition and metabolic parameters in KS patients and how they are affected by genotype. Results: EFT was greater in KS patients than in healthy non-obese (NOb) controls, but lower than in obese (OB) controls. When KS patients were divided into groups (hypogonadal; eugonadal; receiving testosterone replacement therapy [TRT]), EFT was greater in hypogonadal patients than in NOb controls and eugonadal patients, but showed no difference from the OB controls or TRT patients. Hypogonadal patients showed increased TrBF in comparison with NOb controls and eugonadal and TRT patients, and similar TrBF to OB controls. As expected, there was a strong correlation between BMI and EFT in both KS patients and controls (P < 0.0001). In contrast, there was a strong inverse correlation between testosterone and EFT in the control group, but not in KS patients. EFT was significantly correlated with TrBF in both populations (P < 0.0001). Multivariate analyses showed that the major determinants of both EFT and TrBF were BMI and the presence of KS itself. Testosterone and triglycerides were not included as variables in the models. Conclusion: EFT in hypogonadal KS subjects was similar to that of the obese eugonadal controls. Even though there was a direct correlation between BMI and EFT in both populations, the influence of TrBF on EFT was stronger. The presence of the supernumerary X chromosome appeared to be one of the strongest determinants of EFT and TrBF, independent of testosterone levels
Sotagliflozin, the first dual SGLT inhibitor. Current outlook and perspectives
No full textSotagliflozin is a dual sodium-glucose co-transporter-2 and 1 (SGLT2/1) inhibitor for the treatment of both type 1 (T1D) and type 2 diabetes (T2D). Sotagliflozin inhibits renal sodium-glucose co-transporter 2 (determining significant excretion of glucose in the urine, in the same way as other, already available SGLT-2 selective inhibitors) and intestinal SGLT-1, delaying glucose absorption and therefore reducing post prandial glucose. Well-designed clinical trials, have shown that sotagliflozin (as monotherapy or add-on therapy to other anti-hyperglycemic agents) improves glycated hemoglobin in adults with T2D, with beneficial effects on bodyweight and blood pressure. Similar results have been obtained in adults with T1D treated with either continuous subcutaneous insulin infusion or multiple daily insulin injections, even after insulin optimization. A still ongoing phase 3 study is currently evaluating the effect of sotagliflozin on cardiovascular outcomes (ClinicalTrials.gov NCT03315143). In this review we illustrate the advantages and disadvantages of dual SGLT 2/1 inhibition, in order to better characterize and investigate its mechanisms of action and potentialities
Variations on the Author
No full text“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
Impronta genómica en la placenta y su relación con la preeclampsia
No full text[ES] Introducción: La impronta genómica es un proceso epigenético por el cual la expresión de un alelo varía en función del progenitor de que haya sido heredado. Se ha demostrado una alta expresión de genes improntados en la placenta y se cree que pueden estar implicados en la regulación de su desarrollo, además de en ciertas patologías como la preeclampsia. La preeclampsia es una enfermedad multisistémica que se caracteriza por la aparición de hipertensión y proteinuria inducida por el embarazo. Se asocia a una importante morbimortalidad tanto materna como fetal. Aunque en los últimos años se han producido avances en el campo de la fisiopatología y prevención, su etiología sigue siendo desconocida. Por todo ello resulta interesante estudiar el papel que podría tener la impronta genómica en la preeclampsia.
Material y Métodos: Se realizó una revisión sistemática de la literatura entre marzo de 2019 y marzo de 2020 en la base de datos Pubmed, seleccionándose un total de 49 artículos.
Resultados: Se han encontrado diferencias en la expresión de los genes improntados CDKN1C, DLX5, PEG10, PHLDA2, H19, MEST, DLK1 e IGF2 en placentas con preeclampsia respecto a placentas control. Además, se han descubierto más de 100 genes sujetos a impronta en la placenta, muchos de ellos relacionados con la regulación del desarrollo placentario y fetal. La pérdida de expresión o de impronta de ciertos genes improntados produce sobrecrecimiento o restricción del crecimiento fetal y/o placentario.
Discusión: Las patologías asociadas a alteraciones de la impronta genómica han servido para comprender la importancia de los genes improntados en el desarrollo de la placenta y sus patologías. Sin embargo, son pocos los estudios que han analizado de forma experimental la relación de la impronta genómica con la preeclampsia. No obstante, los artículos publicados hasta el momento dejan claro que se trata de un campo con mucho potencial de estudio. De cara a futuros estudios, resultaría indispensable solucionar las limitaciones descritas en esta revisión.
Conclusiones: Los estudios analizados sugieren que las alteraciones de la impronta genómica están relacionadas con la preeclampsia. Sin embargo, es necesario realizar más estudios y solucionar las limitaciones existentes hoy en día
[Newspaper Clipping: Author Claims Evidence of Second JFK Assassin #1]
No full textNewspaper article titled "Author Claims Evidence of Second JFK Assassin." The article states that author Richard J. Whalen concluded "that there is circumstantial evidence to support the theory of a second assassin in the shooting of President John F. Kennedy.
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