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

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

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

Performance of the diamond active target prototype for the PADME experiment at the DAΦ\PhiNE BTF

The PADME experiment at the DA$\Phi$NE Beam-Test Facility (BTF) is designed to search for the gauge boson of a new $\rm U(1)$ interaction in the process e$^+$e$^-\rightarrow\gamma$+$\rm A'$, using the intense positron beam hitting a light target. The $\rm A'$, usually referred as dark photon, is assumed to decay into invisible particles of a secluded sector and it can be observed by searching for an anomalous peak in the spectrum of the missing mass measured in events with a single photon in the final state. The measurement requires the determination of the 4-momentum of the recoil photon, performed by a homogeneous, highly segmented BGO crystals calorimeter. A significant improvement of the missing mass resolution is possible using an active target capable to determine the average position of the positron bunch with a resolution of less than 1 mm. This report presents the performance of a real size $\rm (2x2 cm^2)$ PADME active target made of a thin (50 $\mu$m) diamond sensor, with graphitic strips produced via laser irradiation on both sides. The measurements are based on data collected in a beam test at the BTF in November 2015.Comment: 7 pages, 10 figure

Second-line chemotherapy in advanced pancreatic cancer patients before nab-paclitaxel introduction. Retrospective study in Reggio Emilia Clinical Cancer Centre

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Cardiac remodeling according to the nocturnal fall of blood pressure in hypertensive subjects: The whole assessment of cardiac abnormalities in non-dipper subjects with arterial hypertension (wacanda) study

Objective: Several epidemiological studies suggest that the preservation of the physiological circadian rhythm of blood pressure or its disruption affects the extent of the organ damage developed by the patient. If we classify the circadian rhythm of blood pressure into four nocturnal profiles, significant differences emerge in terms of organ damage burden and prognosis: reverse dippers have the worst prognosis while dippers and mild dippers fall into an intermediate risk range. The risk profile of extreme dippers is still debated, and the available data are very conflicting and inconclusive. Starting from this gap of knowledge, we aimed to evaluate, retrospectively, in a cohort of hypertensive subjects, the degree of cardiac involvement in relation to the different nocturnal blood pressure profiles. Methods: We retrospectively evaluated 900 patients with essential hypertension, of whom 510 met our study criteria. We graded the 510 patients in relation to the percentage of reduction in mean systolic blood pressure (SBP) at night-time compared with day-time, considering this as a continuous variable, and then compared the extreme quintiles with each other and with the middle quintile (considered as reference). Results: Patients with less (or no) reduction in nocturnal SBP (reverse dipper) showed a higher level of organ damage and comorbidities. With regard to echocardiographic indexes, patients with maximum nocturnal pressure reduction (extreme dipper) showed a lower level of remodeling and/or impairment of E/e’ ratio, Right Atrium Area, Basal Right Ventricular Diameter, Inferior Vena Cava Average Diameter, and Tricuspidal Anular Plane Systolic Excursion compared also with hypertensive patients with a physiological nocturnal pressure reduction, even after correction for the main confounders. Conclusions: These data suggest that extreme dippers may constitute the subgroup of hypertensive patients with the lowest 24-h pressure load and, therefore, less cardiac remodeling

Anatomy of the AGN in NGC 5548: V. A clear view of the X-ray narrow emission lines

Context. Our consortium performed an extensive multi-wavelength campaign of the nearby Seyfert 1 galaxy NGC 5548 in 2013-14. The source appeared unusually heavily absorbed in the soft X-rays, and signatures of outflowing absorption were also present in the UV. He-like triplets of neon, oxygen and nitrogen, and radiative recombination continuum (RRC) features were found to dominate the soft X-ray spectrum due to the low continuum flux. Aims. Here we focus on characterising these narrow emission features using data obtained from the XMM-Newton RGS (770 ks stacked spectrum). Methods. We use SPEX for our initial analysis of these features. Self-consistent photoionisation models from Cloudy are then compared with the data to characterise the physical conditions of the emitting region. Results. Outflow velocity discrepancies within the O VII triplet lines can be explained if the X-ray narrow-line region (NLR) in NGC 5548 is absorbed by at least one of the six warm absorber components found by previous analyses. The RRCs allow us to directly calculate a temperature of the emitting gas of a few eV ($\sim10^{4}$ K), favouring photoionised conditions. We fit the data with a Cloudy model of log $\xi = 1.45 \pm 0.05$ erg cm s$^{-1}$, log $N_H = 22.9 \pm 0.4$ cm$^{-2}$ and log v$_{turb} = 2.25 \pm 0.5$ km s$^{-1}$ for the emitting gas; this is the first time the X-ray NLR gas in this source has been modelled so comprehensively. This allows us to estimate the distance from the central source to the illuminated face of the emitting clouds as $13.9 \pm 0.6$ pc, consistent with previous work.Comment: Accepted by A&A, 15 pages, 6 figure

TOWARDS BENZ[A]ANTHRACENE XENOME ELUCIDATION IN PLANTS AND GREEN MICROALGAE

In only 12,000 years the Homo sapiens sapiens has completely modified the face of the Earth. The human pressure on the atmosphere, water and soil has been accelerate from the industrial revolution from which chemicals and energy have been released in the environment. Therefore, chemical environmental pollution and world climate changes are two of the main concerns that modern human must deal. Among chemicals released in the ecosystem the polycyclic aromatic hydrocarbon (PAHs) have gathered significant environment concerns for their detrimental biological effects, toxicity, mutagenicity, and carcinogenicity. The distribution of PAHs in the three environment compartments is related to the number of fused benzene rings. Two or three benzene rings have been occurring in the atmosphere whereas 5 or more rings are largely bounds in the soil particles. Intermediate, 4-rings, such as benz(a)anthracene (B[a]A) are partitioned between air and soil. The molecular mechanism involved to degrade PAHs into less toxic compounds by bacteria and fungi in soil has been elucidated. On the other hands, the metabolism of PAHs in plant and microalgae remain unknown. Signalling, transport, biotransformation of PAHs to less toxic molecules and compartmentalization are the main steps involved for their detoxification in photosynthetic cell. The expression of genes involved in these xenobiotics detoxification steps constitutes the xenome. The final aim of this work is to determine the B[a]A xenome in plants of tomato and in microalgae. So far, we have assessed the ability of tomato plants to grow in vitro and take up the B[a]A. Tomato seedlings were transplanted to MS medium added with 50 and 100 μg g -1 B[a]A and cultivated for 30 days. The detection of B[a]A in shoots infer a translocation from roots to shoots. However, the content of the PAH in shoots was much lower than in the root apparatus indicating that B[a]A was translocated very little from roots to shoots. The identification of microalgae species B[a]A capable of growing in presence of has been performed on 14 different species belonging to the genera Chlorella, Scenedesmus, Chlamydomonas, Ankistrodesmus, Botriococcus and Selenastrum, with six different concentrations of B[a]A. Four microalgae species showed a growth inhibition percentage less than 50% in a medium containing 43.8 μM B[a]A. The capacity to degrade B[a]A and affect the photosynthetic pigment content has been evaluated in the identified microalgae grown for 21 days in the medium containing B[a]A. The four microalgae strains reached 90% B[a]A degradation. Then, in silico analysis was carried out on C. reinhardtii proteome to identify potential laccase involved in the degradation process. Finally, the response of intracellular and extracellular activity in the absence and presence of the B[a]A was analysed by ABTS and 2,6-DMP assays

Hydrogen sulfide-induced dual vascular effect involves arachidonic acid cascade in rat mesenteric arterial bed.

Hydrogen sulfide (H(2)S), a novel gaseous transmitter, is considered a physiological regulator of vascular homeostasis. Recent evidence suggests H(2)S as an endothelium-hyperpolarizing factor (EDHF) candidate. To address this issue, we evaluated the vascular effect of sodium hydrogen sulfide (NaHS), an H(2)S donor, on the rat mesenteric arterial bed. NaHS concentration-response curve was performed on preconstricted mesenteric arterial bed. To assess the contribution of EDHF, we performed a pharmacologic dissection using indomethacin, N(G)-nitro-L-arginine methyl ester (L-NAME), or apamin and charybdotoxin as cyclooxygenase, nitric-oxide synthase, and calcium-dependent potassium channel inhibitors, respectively. In another set of experiments, we used 4-(4-octadecylphenyl)-4-oxobutenoic acid, baicalein, or proadifen as phospholipase A(2) (PLA(2)), lipoxygenase, and cytochrome P450 inhibitors, respectively. Finally, an immunofluorescence study was performed to support the involvement of PLA(2) in mesenteric artery challenged by NaHS. NaHS promoted a dual vascular effect (i.e., vasoconstriction and vasodilation). L-NAME or baicalein administration affected neither NaHS-mediated vasodilation nor vasoconstriction, whereas apamin and charybdotoxin significantly inhibited NaHS-induced relaxation. Pretreatment with PLA(2) inhibitor abolished both the contracting and the relaxant effect, whereas P450 cytochrome blocker significantly reduced NaHS-mediated relaxation. The immunofluorescence study showed that NaHS caused a migration of cytosolic PLA(2) close to the nucleus, which implicates activation of this enzyme. Our data indicate that H(2)S could activate PLA(2), which in turn releases arachidonic acid leading, initially, to vasoconstriction followed by vasodilation mediated by cytochrome P450-derived metabolites. Because EDHF has been presumed to be a cytochrome P450 derivative of the arachidonic acid, our results suggest that H(2)S acts through EHDF release