I tumori nel primo anno di vita: aspetti generali e casi clinici osservati presso l’U.O. Oncoematologia pediatrica dell’Azienda Ospedaliero-Universitaria Pisana

I tumori nel primo anno di vita sono un evento molto raro, con incidenza pari a 230 nuovi casi/milione/anno. Le patologie più frequenti sono, in ordine decrescente, il neuroblastoma, le leucemie acute, i tumori cerebrali, più raramente si riscontrano tumori renali, retinoblastoma, epatoblastoma, sarcomi. Le sequele a lungo termine e la mortalità sono generalmente più importanti rispetto al resto della popolazione pediatrica, inoltre questa classe di pazienti richiede un’assistenza peculiare per le caratteristiche uniche di bambini così piccoli. Lo studio della casistica è di tipo retrospettivo e ha lo scopo di valutare la popolazione in esame osservata presso la nostra U.O. dal 2002 al novembre 2010; sono stati presi in esame tutti i pazienti con diagnosi effettuata nei primi 12 mesi di vita, valutandone il tipo di patologia oncologica, le modalità di esordio, il protocollo seguito per la terapia, e l’esito al momento dello studio. I risultati sono abbastanza in accordo con i dati presenti in letteratura; su 23 pazienti ci sono state 4 diagnosi di neuroblastoma, 6 di leucemia acuta, 5 tumori cerebrali, 3 tumori renali, 2 diagnosi di epatoblastoma, 1 di retinoblastoma, 1 di fibrosarcoma congenito, 1 di istiocitosi a cellule di Langherans; la mortalità è stata, allo stato attuale, di 4 pazienti deceduti su 23

Dynamic modeling of levitation of a superconducting bulk by coupled HH-magnetic field and Arbitrary Lagrangian-Eulerian formulations

Intrinsically stable magnetic levitation between superconductors and permanent magnets can be exploited in a variety of applications of great technical interest in the field of transportation (rail transportation), energy (flywheels) and industry. In this contribution, we present a new model for the calculation of levitation forces between superconducting bulks and permanent magnet, based on the $H$-formulation of Maxwell's equations coupled with an Arbitrary Lagrangian-Eulerian formulation. The model uses a moving mesh that adapts at each time step based on the time-change of the distance between a superconductor bulk and a permanent magnet. The model is validated against a fixed mesh model (recently in turn validated against experiments) that uses an analytical approach for calculating the magnetic field generated by the moving permanent magnet. Then, it is used to analyze the magnetic field dynamics both in field-cooled and zero-field-cooled conditions and successively used to test different configurations of permanent magnets and to compare them in terms of levitation forces. The easiness of implementation of this model and its flexibility in handling different geometries, material properties, and application scenarios make the model an attractive tool for the analysis and optimization of magnetic levitation-based applications

Metastases risk in thin cutaneous melanoma: Prognostic value of clinical-pathologic characteristics and mutation profile

Background: A high percentage of patients with thin melanoma (TM), defined as lesions with Breslow thickness ≤1 mm, presents excellent long-term survival, however, some patients develop metastases. Existing prognostic factors cannot reliably differentiate TM patients at risk for metastases. Objective: We aimed at characterizing the clinical-pathologic and mutation profile of metastatic and not-metastatic TM in order to distinguish lesions at risk of metastases. Methods: Clinical-pathologic characteristics were recorded for the TM cases analyzed. We used a Next Generation Sequencing (NGS) multi-gene panel to characterize TM for multiple somatic mutations. Results: A statistically significant association emerged between the presence of metastases and Breslow thickness ≥0.6 mm (p=0.003). None of TM with lymph-node involvement had Breslow thickness < 0.6 mm. Somatic mutations were identified in 19 of 21 TM analyzed (90.5%). No mutations were observed in two not-metastatic cases with the lowest Breslow thickness (≤0.4 mm), whereas mutations in more than one gene were detected in one metastatic case with the highest Breslow thickness (1.00 mm). Conclusion: Our study indicates Breslow thickness ≥0.6 mm as a valid prognostic factor to distinguish TM at risk for metastases

Studies of Complex Biological Systems with Applications to Molecular Medicine: The Need to Integrate Transcriptomic and Proteomic Approaches

Omics approaches to the study of complex biological systems with potential applications to molecular medicine are attracting great interest in clinical as well as in basic biological research. Genomics, transcriptomics and proteomics are characterized by the lack of an a priori definition of scope, and this gives sufficient leeway for investigators (a) to discern all at once a globally altered pattern of gene/protein expression and (b) to examine the complex interactions that regulate entire biological processes. Two popular platforms in “omics” are DNA microarrays, which measure messenger RNA transcript levels, and proteomic analyses, which identify and quantify proteins. Because of their intrinsic strengths and weaknesses, no single approach can fully unravel the complexities of fundamental biological events. However, an appropriate combination of different tools could lead to integrative analyses that would furnish new insights not accessible through one-dimensional datasets. In this review, we will outline some of the challenges associated with integrative analyses relating to the changes in metabolic pathways that occur in complex pathophysiological conditions (viz. ageing and altered thyroid state) in relevant metabolically active tissues. In addition, we discuss several new applications of proteomic analysis to the investigation of mitochondrial activity

Differential Effects of 3,5-Diiodo-L-Thyronine and 3,5,3'-Triiodo-L-Thyronine On Mitochondrial Respiratory Pathways in Liver from Hypothyroid Rats.

Both 3,5-diiodo-L-thyronine (3,5-T2) and 3,5,3'-triiodo-L-tyronine (T3) affect energy metabolism having mitochondria as a major target. However, the underlying mechanisms are poorly understood. Here, using a model of chemically induced hypothyroidism in male Wistar rats, we investigated the effect of administration of either 3,5-T2 or T3 on liver oxidative capacity through their influence on mitochondrial processes including: proton-leak across the mitochondrial inner membrane; complex I-, complex II- and glycerol-3-phosphate-linked respiratory pathways; respiratory complex abundance and activities as well as individual complex aggregation into supercomplexes. Background/Aims: Both 3,5-diiodo-L-thyronine (3,5-T2) and 3,5,3'-triiodo-L-tyronine (T3) affect energy metabolism having mitochondria as a major target. However, the underlying mechanisms are poorly understood. Here, using a model of chemically induced hypothyroidism in male Wistar rats, we investigated the effect of administration of either 3,5-T2 or T3 on liver oxidative capacity through their influence on mitochondrial processes including: proton-leak across the mitochondrial inner membrane; complex I-, complex II- and glycerol-3-phosphate-linked respiratory pathways; respiratory complex abundance and activities as well as individual complex aggregation into supercomplexes. Methods: Hypothyroidism was induced by propylthiouracil and iopanoic acid; 3,5-T2 and T3 were intraperitoneally administered at 25 and 15 μg/100 g BW for 1 week, respectively. Resulting alterations in mitochondrial function were studied by combining respirometry, Blue Native-PAGE followed by in-gel activity, and Western blot analyses. Results: Administration of 3,5-T2 and T3 to hypothyroid (hypo) rats enhanced mitochondrial respiration rate with only T3 effectively stimulating proton-leak (450% vs. Hypo). T3 significantly enhanced complex I (+145% vs. Hypo), complex II (+66% vs. Hypo), and glycerol-3 phosphate dehydrogenase (G3PDH)-linked oxygen consumptions (about 6- fold those obtained in Hypo), while 3,5-T2 administration selectively restored Euthyroid values of complex II- and increased G3PDH- linked respiratory pathways (+165% vs. Hypo). The mitochondrial abundance of all respiratory complexes and of G3PDH was increased by T3 administration whereas 3,5-T2 only increased complex V and G3PDH abundance. 3,5-T2 enhanced complex I and complex II in gel activities with less intensity than did T3, and T3 also enhanced the activity of all other respiratory complexes tested. In addition, only T3 enhanced individual respiratory component complex assembly into supercomplexes. Conclusions: The reported data highlight novel molecular mechanisms underlying the effect elicited by iodothyronine administration to hypothyroid rats on mitochondrial processes related to alteration in oxidative capacity in the liver. The differential effects elicited by the two iodothyronines indicate that 3,5-T2, by influencing the kinetic properties of specific mitochondrial respiratory pathways, would promote a rapid response of the organelle, while T3, by enhancing the abundance of respiratory chain component and favoring the organization of respiratory chain complex in supercomplexes, would induce a slower and prolonged response of the organelle

Eyelid skin metastasis as first sign of breast cancer recurrence.

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Subsidence due to peatland oxidation in the Venice Lagoon catchment

Abstract. The Venice Lagoon is characterized by a fast morphodynamics appreciable not only over the geological scale but also in historical and modern times. The lagoon environment proves very sensitive to even minor modifications of the natural and anthropogenic controlling factors. An important human endeavor accomplished in the past century is the reclamation of the southernmost lagoon area that has been turned into a fertile farmland. The reclaimed soil is reach in organic matter (peat) that may oxidize with release of carbon dioxide to the atmosphere. The continuous loss of carbon is causing a pronounced settlement of the farmland that lies below the present sea/lagoon level. This enhances the flood hazard and impacts noticeably on the maintenance and operational costs of the drainage system. Total peatland subsidence is estimated at 1.5 m over the last 70 years with a current rate of 1.5-2 cm/year. The geochemical reaction is primarily controlled by soil water content and temperature, and is much influenced by agricultural practices, crop rotation, and depth to the water table. A small (24 km2) controlled catchment located in the area has been instrumented for accurately monitoring the basic parameters and recording the ground motion. The in situ measurements have been integrated with the combined use of remote sensing data to help cast light on the process and identify the mitigation strategies.Published81-906A. Monitoraggio ambientale, sicurezza e territorioope