1,072 research outputs found
Metformin and Everolimus: A Promising Combination for Neuroendocrine Tumors Treatment
Introduction: Treatment options for neuroendocrine tumors (NETs) are rarely curative, as NETs frequently show resistance to medical therapy. The use of everolimus, an mTOR inhibitor, is limited by the development of resistance, probably due to the activation of Akt signaling. In this context, the antidiabetic drug metformin is able to inhibit mTOR, providing a rationale for the use of metformin and everolimus in combination.
Methods: We investigated the effects of the metformin and everolimus combination on NET cell proliferation, apoptosis, colony formation, cell viability, NET spheroids growth and the involvement of the Akt and mTOR pathways, and also developed everolimus-resistant NET cells to further study this combination.
Results: Metformin and everolimus in combination are more effective than monotherapy in inhibiting pancreatic NET (PAN-NET) cell proliferation (-71% \ub1 13%, p < 0.0001 vs. basal), whereas no additive effects were observed on pulmonary neuroendocrine tumor (PNT) cell proliferation. The combinatorial treatment is more effective than monotherapy in inhibiting colony formation, cell viability, NET spheroids growth rate and mTOR phosphorylation in both NET cell lines. In a PAN-NET cell line, metformin did not affect Akt phosphorylation; conversely, it significantly decreased Akt phosphorylation in a PNT cell line. Using everolimus-resistant NET cells, we confirmed that metformin maintained its effects, acting by two different pathways: Akt-dependent or independent, depending on the cell type, with both leading to mTOR suppression.
Conclusions: Considering the promising effects of the everolimus and metformin combination in NET cells, our results provide a rationale for its use in NET patients
The Straw Tube Trackers of the PANDA Experiment
The PANDA experiment will be built at the FAIR facility at Darmstadt
(Germany) to perform accurate tests of the strong interaction through bar pp
and bar pA annihilation's studies. To track charged particles, two systems
consisting of a set of planar, closed-packed, self-supporting straw tube layers
are under construction. The PANDA straw tubes will have also unique
characteristics in term of material budget and performance. They consist of
very thin mylar-aluminized cathodes which are made self-supporting by means of
the operation gas-mixture over-pressure. This solution allows to reduce at
maximum the weight of the mechanical support frame and hence the detector
material budget. The PANDA straw tube central tracker will not only reconstruct
charged particle trajectories, but also will help in low momentum (< 1 GeV)
particle identification via dE/dx measurements. This is a quite new approach
that PANDA tracking group has first tested with detailed Monte Carlo
simulations, and then with experimental tests of detector prototypes. This
paper addresses the design issues of the PANDA straw tube trackers and the
performance obtained in prototype tests.Comment: 7 pages,16 figure
Brain iron accumulation in unexplained fetal and infant death victims with smoker mothers-The possible involvement of maternal methemoglobinemia
<p>Abstract</p> <p>Background</p> <p>Iron is involved in important vital functions as an essential component of the oxygen-transporting heme mechanism. In this study we aimed to evaluate whether oxidative metabolites from maternal cigarette smoke could affect iron homeostasis in the brain of victims of sudden unexplained fetal and infant death, maybe through the induction of maternal hemoglobin damage, such as in case of methemoglobinemia.</p> <p>Methods</p> <p>Histochemical investigations by Prussian blue reaction were made on brain nonheme ferric iron deposits, gaining detailed data on their localization in the brainstem and cerebellum of victims of sudden death and controls. The Gless and Marsland's modification of Bielschowsky's was used to identify neuronal cell bodies and neurofilaments.</p> <p>Results</p> <p>Our approach highlighted accumulations of blue granulations, indicative of iron positive reactions, in the brainstem and cerebellum of 33% of victims of sudden death and in none of the control group. The modified Bielschowsky's method confirmed that the cells with iron accumulations were neuronal cells.</p> <p>Conclusions</p> <p>We propose that the free iron deposition in the brain of sudden fetal and infant death victims could be a catabolic product of maternal methemoglobinemia, a biomarker of oxidative stress likely due to nicotine absorption.</p
A Cylindrical GEM Inner Tracker for the BESIII experiment at IHEP
The Beijing Electron Spectrometer III (BESIII) is a multipurpose detector
that collects data provided by the collision in the Beijing Electron Positron
Collider II (BEPCII), hosted at the Institute of High Energy Physics of
Beijing. Since the beginning of its operation, BESIII has collected the world
largest sample of J/{\psi} and {\psi}(2s). Due to the increase of the
luminosity up to its nominal value of 10^33 cm-2 s-1 and aging effect, the MDC
decreases its efficiency in the first layers up to 35% with respect to the
value in 2014. Since BESIII has to take data up to 2022 with the chance to
continue up to 2027, the Italian collaboration proposed to replace the inner
part of the MDC with three independent layers of Cylindrical triple-GEM (CGEM).
The CGEM-IT project will deploy several new features and innovation with
respect the other current GEM based detector: the {\mu}TPC and analog readout,
with time and charge measurements will allow to reach the 130 {\mu}m spatial
resolution in 1 T magnetic field requested by the BESIII collaboration. In this
proceeding, an update of the status of the project will be presented, with a
particular focus on the results with planar and cylindrical prototypes with
test beams data. These results are beyond the state of the art for GEM
technology in magnetic field
From intensive care to rehabilitation: survey on the satisfaction with care received during prolonged hospitalization for COVID-19 at a northern Italian university hospital
Objective: Investigating the experiences perceived by COVID-19 inpatients is a fundamental research area that is starting to be explored. For this reason, our objective was to provide the first Italian survey on COVID-19 inpatients' satisfaction, obtained through a self-completed questionnaire previously used in a reference study in a UK cohort of COVID-19 patients.
Subjects and methods: Hospitalized COVID-19 patients (>20 days) admitted to Ferrara University Hospital who underwent rehabilitation during their hospital stay were invited to complete an anonymous questionnaire. The survey's questions explored the patients' satisfaction with the health services received, and their completion took place approximately one year after hospitalization. Information on sex, number of wards, ICU stays, and hospital discharge dates was collected.
Results: Sixty-two completed questionnaires were analyzed. The average overall satisfaction score obtained from the answers indicated by the participants in the tenth question was 4.7 out of 5.0. Very positive responses were observed for information about discharge plans, privacy, management of pain, sleep quality, and feeling of safety. The possibility of being consulted about medications and side effects received a very low satisfaction score. Considering overall satisfaction, no significant differences were noted for sex or ICU stay. The obtained results were almost superimposable to those reported in the cohort of COVID-19 patients of the reference study.
Conclusions: This survey suggested that COVID-19 patients' healthcare satisfaction was high. Nevertheless, some areas must be improved, such as the communication and involvement of the patients in the decision-making of care and the discussion about medications or possible side effects
A straw tube detector for the PANDA experiment
The PANDA experiment will be built at the FAIR facility in Darmstadt (Germany) to perform accurate tests of the strong interaction through pp and pA annihilations. This paper will address the design issue of the Straw Tube Tracker
(STT), one of the two options proposed for the PANDA Central Tracker
Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets
This document is the Technical Design Report covering the two large
spectrometer magnets of the PANDA detector set-up. It shows the conceptual
design of the magnets and their anticipated performance. It precedes the tender
and procurement of the magnets and, hence, is subject to possible modifications
arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti
Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski,
Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy),
Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy
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