Ductus venosus blood flow velocity characteristics of fetuses with single umbilical artery

Objectives: Sonographic Doppler evaluation of the fetal ductus venosus has been proved to be useful in the evaluation of fetal cardiac function. The aim of this study was to investigate the ductus venosus blood flow profile in fetuses with single umbilical artery and to correlate it with the umbilical cord morphology. Methods: Fetuses at > 20 weeks' gestation with single umbilical artery who were otherwise healthy were consecutively enrolled into the study. The sonographic examination included evaluation of the following Doppler parameters: umbilical artery resistance index, maximum blood flow velocity of the ductus venosus during ventricular systole (S-peak) and atrial contraction (A-wave), ductus venosus time-averaged maximum velocity (TAMXV), and pulsatility index for veins (PIV). The cross-sectional area of the umbilical cord and its vessels were measured in all cases. The Doppler and morphometric values obtained were plotted on reference ranges. Results: A total of 88 fetuses with single umbilical artery were scanned during the study period. Of these 52 met the inclusion criteria. The S-peak velocity, A-wave velocity, and TAMXV were below the 5th centile for gestational age in 57.7%, 59.6%, and 57.7% of cases, respectively. The PIV was within the normal range in 80.1% of cases. The umbilical vein cross-sectional area of fetuses with single umbilical artery was above the 95th centile for gestational age in 34.6% cases. Conclusions: The ductus venosus blood flow pattern is different in fetuses with single umbilical artery from that in those with a three-vessel cord. This difference may be caused in part by the particular morphology of umbilical cords with a single artery. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd

Brafv600e and Ctbn1 Mutational Study in Rathke's Cleft Cysts

Aim: Rathke's cleft cysts and craniopharyngiomas tipically involve sellar region and their histogenetic relationship is still matter of debate. Clinical and histopathologic differentiation of cystic lesions from the sellar region, that is, craniopharyngiomas (CPs) and Rathke cleft cysts (RCCs), is challenging and has great importance with respect to variable clinical manifestation and adapted surgical treatment strategies in both entities. The recent acquisition that adamantinomatous and papillary craniopharyngiomas bear distinct molecular alterations i.e., β-catenin (CTNNB1) and BRAFv600 mutations respectively, has suggest to screen for such alteration a series of Rathke cyst to seek a possible relation with one of the two craniopharyngioma type. Methods: Seven Rathke's cleft cysts were analyzed for BRAF and CTNNB1 mutational status by sequencing and immunohistochemistry. Radiological, clinical and histological features were performed. Results: None of the 7 Rathke's cleft cysts harbor BRAFV600E mutation. No CTNNB1 mutation was found. Radiological, clinical and histological re-evaluation of the cases confirmed the diagnosis of Rathke's cleft cysts. Conclusion: BRAFV600E and CTNNB1 mutations appeared, as most reliable factor for the differentiation between purely cystic CPs and RCCs, whereas tumor location, tumor size, and radiological parameter of the tumor were less consistent parameters. This study again confirms that craniopharyngiomas (CPs) and Rathke cleft cysts (RCCs), are associated with distinct pathogenic pathways

Dime como educas y te diré como es tu ambiente

La crisis ambiental es un problema de conocimiento, por ello involucra a la educación, siendo el desafío de ella el de pasar de una cultura economicista, que refuerza y que es reforzada por la globalización, a una cultura de pertenencia, de compromiso, de resistencia, de solidaridad. Debemos focalizar los esfuerzos por construir desde la complejidad ambiental una ciencia para la sustentabilidad que hunda sus raíces en la justicia ambiental y que destierre las ideas simplificadoras y reduccionistas de la sociedad y comience a fundar el nuevo paradigma basado en la interdisciplinaridad y la transdisciplinariedad. Este proyecto didáctico se elabora para aplicar en dos cursos "paralelos" de diferentes escuelas de la ciudad de Rafaela, provincia de Santa Fe. Se formarán equipos de trabajo que interactuarán en esta propuesta: docentes (biología, historia, derecho, lengua, geografía, economía), directivos y los alumnos, con las adaptaciones a sus problemáticas, su universo y territorialidad, implementando ILS-indicadores locales de sustentabilidad.Trabajos del área Ciencias NaturalesDepartamento de Ciencias Exactas y Naturale

Dual inhibition of CDK12 and CDK13 uncovers actionable vulnerabilities in patient-derived ovarian cancer organoids

Background: High grade serous ovarian cancer (HGSOC) is highly lethal, partly due to chemotherapy resistance and limited availability of targeted approaches. Cyclin dependent kinases 12 and 13 (CDK12/13) are promising therapeutic targets in human cancers, including HGSOC. Nevertheless, the effects of their inhibition in HGSOC and the potential synergy with other drugs are poorly known. Methods: We analyzed the effects of the CDK12/13 inhibitor THZ531 in HGSOC cells and patient-derived organoids (PDOs). RNA sequencing and quantitative PCR analyses were performed to identify the genome-wide effects of short-term CDK12/13 inhibition on the transcriptome of HGSOC cells. Viability assays with HGSOC cells and PDOs were performed to assess the efficacy of THZ531 as single agent or in combination with clinically relevant drugs. Results: The CDK12 and CDK13 genes are deregulated in HGSOC and their concomitant up-regulation with the oncogene MYC predicts poor prognosis. HGSOC cells and PDOs display high sensitivity to CDK12/13 inhibition, which synergizes with drugs in clinical use for HGSOC. Transcriptome analyses revealed cancer-relevant genes whose expression is repressed by dual CDK12/13 inhibition through impaired splicing. Combined treatment with THZ531 and inhibitors of pathways regulated by these cancer relevant genes (EGFR, RPTOR, ATRIP) exerted synergic effects on HGSOC PDO viability. Conclusions: CDK12 and CDK13 represent valuable therapeutic targets for HGSOC. We uncovered a wide spectrum of CDK12/13 targets as potential therapeutic vulnerabilities for HGSOC. Moreover, our study indicates that CDK12/13 inhibition enhances the efficacy of approved drugs that are already in use for HGSOC or other human cancers

Access to administrative documents and to public sector information in Italy

Law No. 241 of 1990 on administrative procedure (Italian APA) established general rules on the right of access to administrative documents for the first time in the Italian legal system, which partly reproduced rules defined in sectorial legislations. From such very restrictive regime of access to administrative documents\u2014lately accompanied by a rather demagogical obligation imposed on public administrations to disclose a set of information in the context of the so-called open data policies\u2014Italy has recently moved forth to public access to data and documents held by public administrations

Expression of hormone receptors in oropharyngeal squamous cell carcinoma

Hormone receptors play an important role in many types of cancers. Alongside factors associated with human papillomavirus (HPV) infection, hormonal receptors may impact the tumorigenesis of oropharyngeal cancer. This study consists of 199 consecutive oropharyngeal squamous cell carcinoma (OPSCC) patients diagnosed and treated with a curative intent. We examined androgen (AR), estrogen (ER; both alpha and beta), and progesterone receptor (PR) expressions using immunohistochemistry comparing tumor and patient characteristics. AR was expressed in 16%, PR in 27% and ER-beta in 63% of the tumors. HPV- and p16-positive tumors expressed more AR and less PR than their negative counterparts. High PR expression was associated with poor disease-specific and locoregional recurrence-free survival. AR, PR, and ER-beta are expressed in OPSCC, and AR and PR expressions are associated with HPV and p16 status. Furthermore, PR appears to have prognostic significance. This may allow us to investigate the role of anti-hormone receptors in the treatment of OPSCC.Peer reviewe