Fertility preservation in ovarian tumours

A considerable number of patients with a cancer diagnosis are of childbearing age and have not satisfied their desire for a family. Despite ovarian cancer (OC) usually occurring in older patients, 3%–14% are diagnosed at a fertile age with the overall 5-year survival rate being 91.2% in women ≤44 years of age when it is found at 1A–B stage. In this scenario, testing the safety and the efficacy of fertility sparing strategies in OC patients is very important overall in terms of quality of life. Unfortunately, the lack of randomised trials to validate conservative approaches does not guarantee the safety of fertility preservation strategies. However, evidence-based data from descriptive series suggest that in selected cases, the preservation of the uterus and at least one part of the ovary does not lead to a high risk of relapse. This conservative surgery helps to maintain organ function, giving patients of childbearing age the possibility to preserve their fertility. We hereby analysed the main evidence from the international literature on this topic in order to highlight the selected criteria for conservative management of OC patients, including healthy BRCA mutations carriers

Report on advances for pediatricians in 2018: allergy, cardiology, critical care, endocrinology, hereditary metabolic diseases, gastroenterology, infectious diseases, neonatology, nutrition, respiratory tract disorders and surgery.

This review reported notable advances in pediatrics that have been published in 2018. We have highlighted progresses in allergy, cardiology, critical care, endocrinology, hereditary metabolic diseases, gastroenterology, infectious diseases, neonatology, nutrition, respiratory tract disorders and surgery. Many studies have informed on epidemiologic observations. Promising outcomes in prevention, diagnosis and treatment have been reported. We think that advances realized in 2018 can now be utilized to ameliorate patient car

Characterisation of AMS H35 HV-CMOS monolithic active pixel sensor prototypes for HEP applications

Monolithic active pixel sensors produced in High Voltage CMOS (HV-CMOS) technology are being considered for High Energy Physics applications due to the ease of production and the reduced costs. Such technology is especially appealing when large areas to be covered and material budget are concerned. This is the case of the outermost pixel layers of the future ATLAS tracking detector for the HL-LHC. For experiments at hadron colliders, radiation hardness is a key requirement which is not fulfilled by standard CMOS sensor designs that collect charge by diffusion. This issue has been addressed by depleted active pixel sensors in which electronics are embedded into a large deep implantation ensuring uniform charge collection by drift. Very first small prototypes of hybrid depleted active pixel sensors have already shown a radiation hardness compatible with the ATLAS requirements. Nevertheless, to compete with the present hybrid solutions a further reduction in costs achievable by a fully monolithic design is desirable. The H35DEMO is a large electrode full reticle demonstrator chip produced in AMS 350 nm HV-CMOS technology by the collaboration of Karlsruher Institut f\"ur Technologie (KIT), Institut de F\'isica d'Altes Energies (IFAE), University of Liverpool and University of Geneva. It includes two large monolithic pixel matrices which can be operated standalone. One of these two matrices has been characterised at beam test before and after irradiation with protons and neutrons. Results demonstrated the feasibility of producing radiation hard large area fully monolithic pixel sensors in HV-CMOS technology. H35DEMO chips with a substrate resistivity of 200$\Omega$ cm irradiated with neutrons showed a radiation hardness up to a fluence of $10^{15}$n$_{eq}$cm$^{-2}$ with a hit efficiency of about 99% and a noise occupancy lower than $10^{-6}$ hits in a LHC bunch crossing of 25ns at 150V

Selected amino acid changes in HIV-1 subtype-C gp41 are associated with specific gp120(V3) signatures in the regulation of co-receptor usage

The majority of studies have characterized the tropism of HIV-1 subtype-B isolates, but little is known about the determinants of tropism in other subtypes. So, the goal of the present study was to genetically characterize the envelope of viral proteins in terms of co-receptor usage by analyzing 356 full-length env sequences derived from HIV-1 subtype-C infected individuals. The co-receptor usage of V3 sequences was inferred by using the Geno2Pheno and PSSM algorithms, and also analyzed to the "11/25 rule". All reported env sequences were also analyzed with regard to N-linked glycosylation sites, net charge and hydrophilicity, as well as the binomial correlation phi coefficient to assess covariation among gp120(V3) and gp41 signatures and the average linkage hierarchical agglomerative clustering were also performed. Among env sequences present in Los Alamos Database, 255 and 101 sequences predicted as CCR5 and CXCR4 were selected, respectively. The classical V3 signatures at positions 11 and 25, and other specific V3 and gp41 amino acid changes were found statistically associated with different co-receptor usage. Furthermore, several statistically significant associations between V3 and gp41 signatures were also observed. The dendrogram topology showed a cluster associated with CCR5-usage composed by five gp41 mutated positions, A22V, R133M, E136G, N140L, and N166Q that clustered with T2V(V3) and G24T(V3) (bootstrap=1). Conversely, a heterogeneous cluster with CXCR4-usage, involving S11GR(V3), 13-14insIG/LG(V3), P16RQ(V3), Q18KR(V3), F20ILV(V3), D25KRQ(V3), Q32KR(V3) along with A30T(gp41), S107N(gp41), D148E(gp41), A189S(gp41) was identified (bootstrap=0.86). Our results show that as observed for HIV-1 subtype-B, also in subtype-C specific and different gp41 and gp120V3 amino acid changes are associated individually or together with CXCR4 and/or CCR5 usage. These findings strengthen previous observations that determinants of tropism may also reside in the gp41 protein

Pathogenesis and molecular mechanisms of anderson–fabry disease and possible new molecular addressed therapeutic strategies

Anderson–Fabry disease (AFD) is a rare disease with an incidenceof approxi-mately 1:117,000 male births. Lysosomal accumulation of globotriaosylceramide (Gb3) is the element characterizing Fabry disease due to a hereditary deficiency α-galactosidase A (GLA) enzyme. The accumulation of Gb3 causes lysosomal dysfunction that compromises cell signaling pathways. Deposition of sphingolipids occurs in the autonomic nervous system, dorsal root ganglia, kidney epithelial cells, vascular system cells, and myocardial cells, resulting in organ failure. This manuscript will review the molecular pathogenetic pathways involved in Anderson–Fabry disease and in its organ damage. Some studies reported that inhibition of mitochondrial function and energy metabolism plays a signif-icant role in AFD cardiomyopathy and in kidney disease of AFD patients. Furthermore, mitochondrial dysfunction has been reported as linked to the dysregulation of the au-tophagy–lysosomal pathway which inhibits the mechanistic target of rapamycin kinase (mTOR) mediated control of mitochondrial metabolism in AFD cells. Cerebrovascular complications due to AFD are caused by cerebral micro vessel stenosis. These are caused by wall thickening resulting from the intramural accumulation of glycolipids, luminal oc-clusion or thrombosis. Other pathogenetic mechanisms involved in organ damage linked to Gb3 accumulation are endocytosis and lysosomal degradation of endothelial calcium-activated intermediate-conductance potassium ion channel 3.1 (KCa3.1) via a clathrin-de-pendent process. This process represents a crucial event in endothelial dysfunction. Several studies have identified the deacylated form of Gb3, globotriaosylsphingosine (Lyso-Gb3), as the main catabolite that increases in plasma and urine in patients with AFD. The mean concentrations of Gb3 in all organs and plasma of Galactosidase A knockout mice were significantly higher than those of wild-type mice. The distributions of Gb3 isoforms vary from organ to organ. Various Gb3 isoforms were observed mainly in the kidneys, and kidney-specific Gb3 isoforms were hydroxylated. Furthermore, the action of Gb3 on the KCa3.1 channel suggests a possible contribution of this interaction to the Fabry disease process, as this channel is expressed in various cells, including endothelial cells, fibro-blasts, smooth muscle cells in proliferation, microglia, and lymphocytes. These molecular pathways could be considered a potential therapeutic target to correct the enzyme in ad-dition to the traditional enzyme replacement therapies (ERT) or drug chaperone therapy

DEFORMAZIONI DEL SUOLO MEDIANTE ANALISI DEI DATI MAREOGRAFICI NELL’AREA VULCANICA NAPOLETANA NEL PERIODO 1999-2006

Osservatorio Vesuviano, department of Istituto Nazionale di Geofisica e Vulcanologia, is in charge of the surveillance monitoring of the Campanian volcanic areas, to promptly recognize any variation of the physical-chemical parameters helpful as precursors of eruption. The ground deformations in the Vesuvius and Phlegrean area are monitored by means of classical technique (like optical leveling and tiltmetry) and satellite technique (like global positioning system). Moreover, due to the vicinity of a coastline for both the volcanic system, the ground deformations are also monitored by the continuous recording of the sea level, using suitable tide gauge stations. Tide gauge data are also used to analyze the local characteristics of the sea wave even in presence of extreme phenomena. The Vesuvius Observatory tide gauge network, used in this paper, is operating since 1970 and reached, in the eighties, the consistency of 6 stations, Napoli, Nisida, Pozzuoli, Miseno,Castellamare di Stabia and Torre del Greco. Data since 1999 are retrieved and a database have been organized, corrected and validated up today, spanning over 8 years, using were necessary statistical gap filling technique. Data have been analyzed in the frequency domain and the local astronomical components have been defined by harmonic analysis, inferring amplitude and phase for the main diurnal and semi-diurnal components The obtained residual respect to the astronomical tide contains information about meteorological component, eustatic variation, ground deformation and noise. The residual sea level variation, for each site, can be represented by two terms: sea level background and local sea level variations due to noise, site effects and ground deformation. Removing, by deconvolution, the differential behavior of the sea-level respect to a reference station, provide an estimation of the ground level variation. This analysis shows no significant level variation at Vesuvius, while in the Campi Flegrei caldera, tide gauge data, put in evidence the presence of the so-called mini-uplift during last 7 years

CD40 ligand and MCP-1 as predictors of cardiovascular events in diabetic patients with stroke

Aim: Up-regulation of soluble CD40 ligand (sCD40L) and of monocyte chemoattractant protein-1 (MCP-1) has been found in diabetes and in patients with acute cerebral ischemia. We asked whether (i) the two molecules are similarly upregulated among non-lacunar and lacunar diabetic strokes and (ii) sCD40L and/or MCP-1 predict the risk of cardiovascular events in this setting.Methods: Ninety patients with type 2 diabetes mellitus presenting with an acute ischemic stroke (compared with 45 control subjects) were evaluated on admission and up to 36 months (median 24 months) after the event.Results: Diabetic patients with acute stroke had higher plasma CD40L and MCP-1 than controls (p<0.0001), with no significant differences among lacunar and non-lacunar strokes. On multiple regres-sion analysis, only higher sCD40L quartiles and older age were associated with higher MCP-1 quar-tiles. Forty-eight percent of patients experienced vascular events. Cox regression analysis showed that only the presence of higher sCD40L values independently predicted the recurrence of vascular events.Conclusion: Up-regulation of inflammatory molecules, such as CD40L and MCP-1, is involved in the advanced stage of atherosclerotic cerebro-vascular disease and is associated with increased risk of recurrence of cardiovascular events.AIM: Up-regulation of soluble CD40 ligand (sCD40L) and of monocyte chemoattractant protein-1 (MCP-1) has been found in diabetes and in patients with acute cerebral ischemia. We asked whether (i) the two molecules are similarly upregulated among non-lacunar and lacunar diabetic strokes and (ii) sCD40L and/or MCP-1 predict the risk of cardiovascular events in this setting. METHODS: Ninety patients with type 2 diabetes mellitus presenting with an acute ischemic stroke (compared with 45 control subjects) were evaluated on admission and up to 36 months (median 24 months) after the event. RESULTS: Diabetic patients with acute stroke had higher plasma CD40L and MCP-1 than controls (p<0.0001), with no significant differences among lacunar and non-lacunar strokes. On multiple regression analysis, only higher sCD40L quartiles and older age were associated with higher MCP-1 quartiles. Forty-eight percent of patients experienced vascular events. Cox regression analysis showed that only the presence of higher sCD40L values independently predicted the recurrence of vascular events. CONCLUSION: Up-regulation of inflammatory molecules, such as CD40L and MCP-1, is involved in the advanced stage of atherosclerotic cerebro-vascular disease and is associated with increased risk of recurrence of cardiovascular events

Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: A multicenter feasibility study

BEAM is a widely used conditioning regimen for relapsed/refractory lymphoma patients undergoing auto-SCT. We conducted a multicenter study with an alternative regimen (fotemustine plus etoposide, cytarabine and melphalan (FEAM)) in which BCNU was substituted by the chloroethylnitrosourea fotemustine (FTM). Eighty-four patients with relapsed/refractory Hodgkin's (n20) and non-Hodgkin's lymphoma (n64) were conditioned with a FEAM regimen (FTM 150 mg/m 2 on days -7, -6, etoposide 200 mg/m 2 and cytarabine 400 mg/m 2 on days -5, -4, -3, -2 and melphalan 140 mg/m 2 on day -1). Patients were evaluated for toxicity and engraftment parameters. Median times to neutrophil (500 × 10 9 /l) and plt (20 000 × 10 9 /l) engraftment were 11 and 13 days, respectively. Grade 3 mucositis occurred in 19 patients (23%), while G3 nausea/vomiting and G3 diarrhea were observed in 13 (15%) and 6 (7%) patients, respectively. No severe hepatic, renal or pulmonary toxicity was detected. Seven patients (7%) experienced G4 mucositis, while no other G4 toxicities or unexpected adverse events of any grade were recorded. Transplant-related mortality was 2.4%. We conclude that a FEAM regimen is feasible and safe. Although toxicity and engraftment times compared favorably with BEAM, longer follow-up is needed to evaluate fully its efficacy and long-term safety. © 2010 Macmillan Publishers Limited All rights reserved

Examining the nature of the ultraluminous X-ray source Holmberg II X-1

© 2024 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/We present a comprehensive spectral analysis of the ultraluminous X-ray source Holmberg II X-1 using broadband and high-resolution X-ray spectra taken with the XMM-Newton satellite over a period of 19 yr, taking advantage of data from a recent campaign. We tested several models for the broadband spectra, including a double thermal component provided a reasonable description for the continuum between 0.3 and 10 keV and enabled us to constrain the properties of the accretion disc. The luminosity–temperature trends of the inner and outer disc components broadly agree with the expectations for a thin disc, although the exact values of the slopes are slightly sensitive to the adopted model. However, all tested models show L − T trends that deviate from a power law above a bolometric luminosity of about 5 × 1039 erg s−1, particularly for the hot thermal component associated with the inner accretion flow. Assuming that such deviations are due to the accretion rate exceeding its Eddington limit or, most likely, the super-critical rate, a compact object with a mass of 16–36 M⊙ was inferred, specifically, a stellar-mass black hole. The time-averaged (2021) high-resolution spectra present narrow emission lines at 1 keV primarily from Ne IX-X and a very strong at 0.5 keV from N VII, which indicate Ne–N-rich gas with non-solar abundances. This favours a nitrogen-rich donor star, such as a blue or red supergiant, which has escaped from its native stellar cluster characterised by a low-metallicity environment.Peer reviewe