Embriogenesi e malformazioni dell’apparato urinario e genitale maschile

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miR-21-mediated regulation of 15-hydroxyprostaglandin dehydrogenase in colon cancer

This work is licensed under a Creative Commons Attribution 4.0 International License.Elevated prostaglandin E2 (PGE2) levels are observed in colorectal cancer (CRC) patients, and this increase is associated with poor prognosis. Increased synthesis of PGE2 in CRC has been shown to occur through COX-2-dependent mechanisms; however, loss of the PGE2-catabolizing enzyme, 15-hydroxyprostaglandin dehydrogenase (15-PGDH, HPGD), in colonic tumors contributes to increased prostaglandin levels and poor patient survival. While loss of 15-PGDH can occur through transcriptional mechanisms, we demonstrate that 15-PGDH can be additionally regulated by a miRNA-mediated mechanism. We show that 15-PGDH and miR-21 are inversely correlated in CRC patients, with increased miR-21 levels associating with low 15-PGDH expression. 15-PGDH can be directly regulated by miR-21 through distinct sites in its 3′ untranslated region (3′UTR), and miR-21 expression in CRC cells attenuates 15-PGDH and promotes increased PGE2 levels. Additionally, epithelial growth factor (EGF) signaling suppresses 15-PGDH expression while simultaneously enhancing miR-21 levels. miR-21 inhibition represses CRC cell proliferation, which is enhanced with EGF receptor (EGFR) inhibition. These findings present a novel regulatory mechanism of 15-PGDH by miR-21, and how dysregulated expression of miR-21 may contribute to loss of 15-PGDH expression and promote CRC progression via increased accumulation of PGE2.NIH R01 CA134609NIH R01 AR069044NIH/NCI Cancer Center Support Grant (P30 CA168524)New Jersey Commission on Cancer ResearchAmerican Heart Association (15GRNT23240019

Loop colostomies are safe in anorectal malformations

Aim of the study: Divided colostomy (DC) has been recommended in anorectal malformations (ARMs) with previously reported advantages of decreasing overflow into the distal limb and urinary tract infections (UTIs). Skin bridge loop colostomy (LC) is a technically easier alternative without an increase in these complications. We report our institutional experience of LC in ARM. Methods: Retrospective study (Institution-approved Clinical Audit) reviewing the clinical records of all patients with ARM undergoing stoma formation in a single UK tertiary pediatric surgical center (2000–2015). Data collected included type of ARM, associated anomalies, type and level of colostomy, time to stoma closure, complications and UTIs. Results: One hundred and eighty-two (95 female) patients underwent colostomy formation for ARM. The vast majority (171/ 94%) underwent LC; 9 (5%) had a divided colostomy (DC) and 2 (1%) had no available data. The spectrum of defects in girls included rectovestibular (62/65%), rectovaginal (4/4%) and cloaca (29/31%). In boys, 71 (82%) had a fistula to the urinary tract and 16 (18%) presented with a perineal fistula. Urological abnormalities coexisted in 87 (47.8%) patients. Thirty five (21%) patients developed UTIs. Among the 19 girls who developed UTI, 8 had rectovestibular fistula and 11 had cloaca. Of the 16 boys who developed UTI, 14 had a fistula to the urinary tract and 11 had an independent urological abnormality. The mean time from stoma formation to stoma closure was 10 (3–52) months. Complications were reported in 22 (12%) LCs. Fifteen patients (9%) developed a stoma prolapse following LC with 10 (6%) requiring surgical revision. Conclusions: This is the largest reported series of outcomes following LC for ARM. LC is easier to perform and to close, requiring minimal surgical access, with comparable complications and outcomes to those published for DC. Type of study: Retrospective comparative study. Level of evidence: III

Chemotherapy cardiotoxicity: cardioprotective drugs and early identification of cardiac dysfunction.

Background: Chemotherapy cardiotoxicity is an emerging problem and it is very important to prevent cardiac dysfunction caused by anticancer drugs. The aim of this study was to assess the alterations of the cardiac function induced by chemotherapy in a follow-up of 2 years and to evaluate the cardioprotective role of angiotensin-converting enzyme inhibitors (ACEIs) in the prevention of cardiac dysfunction. Methods: A prospective study was carried out using patients with breast cancer (85 women; median age 57W12years) and other inclusion and exclusion criteria. On the basis of treatment, patients were divided into six groups: fluorouracil-epirubicincyclophosphamide, FEC (group A); FEC and trastuzumab (B); trastuzumab (C); FEC and taxotere (D); FEC, paclitaxel and trastuzumab (E); and chemotherapy and cardioprotective drugs (F). Cardiological evaluation including electrocardiogram and conventional echocardiogram with tissue Doppler imaging (TDI) was carried out at T0 (before starting chemotherapy), T1 (after 6months from the start of chemotherapy) and T2 (2 years after the end of chemotherapy). Results: Significant changes in the TDI parameters of systolic and diastolic function were observed at T1 and T2 in all patients. A significant reduction of left ventricular ejection fraction (LVEF) was observed only at T2. In the patients treated with ACEI (F), these changes were less significant than in other groups and they do not have significant changes in the indices of diastolic function. Conclusion: TDI is more sensitive than conventional echocardiogram in the early diagnosis of cardiac dysfunction and ACEIs seem to have an important role in the prevention of cardiotoxicity

Role of interface region on the optoelectronic properties of silicon nanocrystals embedded in SiO2

Light emitting silicon nanocrystals embedded in SiO2 have been investigated by x-ray absorption measurements in total electron and photoluminescence yields, by energy filtered TEM analysis and by ab-initio total energy calculations. Both experimental and theoretical results show that the interface between the silicon nanocrystals and the surrounding SiO2 is not sharp: an intermediate region of amorphous nature and of variable composition links the crystalline Si with the amorphous stoichiometric SiO2. This region plays an active role in the light emission process

Atomic characterization of Si nanoclusters embedded in SiO2 by atom probe tomography

Silicon nanoclusters are of prime interest for new generation of optoelectronic and microelectronics components. Physical properties (light emission, carrier storage...) of systems using such nanoclusters are strongly dependent on nanostructural characteristics. These characteristics (size, composition, distribution, and interface nature) are until now obtained using conventional high-resolution analytic methods, such as high-resolution transmission electron microscopy, EFTEM, or EELS. In this article, a complementary technique, the atom probe tomography, was used for studying a multilayer (ML) system containing silicon clusters. Such a technique and its analysis give information on the structure at the atomic level and allow obtaining complementary information with respect to other techniques. A description of the different steps for such analysis: sample preparation, atom probe analysis, and data treatment are detailed. An atomic scale description of the Si nanoclusters/SiO2 ML will be fully described. This system is composed of 3.8-nm-thick SiO layers and 4-nm-thick SiO2 layers annealed 1 h at 900°C