Prevention of Chemotherapy-Induced Anemia and Thrombocytopenia by Constant Administration of Stem Cell Factor

Purpose: Chemotherapy-induced apoptosis of immature hematopoietic cells is a major cause of anemia and thrombocytopenia in cancer patients. Although hematopoietic growth factors such as erythropoietin and colony-stimulating factors cannot prevent the occurrence of drug-induced myelosuppression, stem cell factor (SCF) has been previously shown to protect immature erythroid and megakaryocytic cells in vitro from drug-induced apoptosis. However, the effect of SCF in vivo as a single myeloprotective agent has never been elucidated. Experimental Design: The ability of SCF to prevent the occurrence of chemotherapy-induced anemia and thrombocytopenia was tested in a mouse model of cisplatin-induced myelosuppression. To highlight the importance of maintaining a continuous antiapoptotic signal in immature hematopoietic cells, we compared two treatment schedules: in the first schedule, SCF administration was interrupted during chemotherapy treatment and resumed thereafter, whereas in the second schedule, SCF was administered without interruption for 7 days, including the day of chemotherapy treatment. Results: The administration of SCF to cisplatin-treated mice could preserve bone marrow integrity, inhibit apoptosis of erythroid and megakaryocytic precursors, prevent chemotherapy-induced anemia, and rapidly restore normal platelet production. Treatment with SCF increased the frequency of Bcl-2/Bcl-XL\u2013 positive bone marrow erythroid cells and sustained Akt activation in megakaryocytes. Myeloprotection was observed only when SCF was administered concomitantly with cisplatin and kept constantly present during the days following chemotherapy treatment. Conclusions: SCF treatment can prevent the occurrence of chemotherapy-induced anemia and thrombocytopenia in mice, indicating a potential use of this cytokine in the supportive therapy of cancer patients

Metabolic enhancers supporting 1-carbon cycle affect sperm functionality: an in vitro comparative study

The sperm plasma membrane is a sensitive target to oxidative stress. The most representative reactive oxygen species (ROS) scavengers in the genital tract, hypotaurine and glutathione, require, for their synthesis, cysteine whose availability is associated with the 1-carbon cycle (1-CC). Human, bovine and ascidian spermatozoa were incubated with compounds supporting the 1-CC (Vitamin B6, Methylcobalamin, 5 Methyl Tetrahydrofolate, Zinc Bisglycinate and N-acetyl-cysteine) (TRT) and compared to the effects induced solely by N-acetyl-cysteine (NAC). In control groups (CNTRL), spermatozoa were incubated with medium alone. After 90 and 180 minutes of incubation, the mitochondrial membrane potential (ΔΨM) in TRT and NAC was significantly (P < 0.01) higher than in CNTRL. At H2DCFDA evaluation, ROS production differed between species whereas, at 2-OH Ethidium, it significantly decreased in bovine TRT group. Intracellular pH (pHi) did not significantly vary in relation to treatment. In ascidian spermatozoa, the NAC supplementation decreased external pH, which in turn brought to a pHi lowering. Buffering seawater with NaHCO3 reversed the beneficial effects of N-acetyl-cysteine supplementation. In conclusion, both fully supporting the 1-CC and treatment with N-acetyl-cysteine alone improved kinetics, ΔΨM and ROS production in mammalian sperm demonstrating for the first time the direct in vitro effects of these compounds on sperm functionality

The antidepressant fluoxetine acts on energy balance and leptin sensitivity via BDNF

Leptin and Brain Derived Neurotrophic Factor (BDNF) pathways are critical players in body weight homeostasis. Noninvasive treatments like environmental stimulation are able to increase response to leptin and induce BDNF expression in the brain. Emerging evidences point to the antidepressant selective serotonin reuptake inhibitor Fluoxetine (FLX) as a drug with effects similar to environmental stimulation. FLX is known to impact on body weight, with mechanisms yet to be elucidated. We herein asked whether FLX affects energy balance, the leptin system and BDNF function. Adult lean male mice chronically treated with FLX showed reduced weight gain, higher energy expenditure, increased sensitivity to acute leptin, increased hypothalamic BDNF expression, associated to changes in white adipose tissue expression typical of "brownization". In the Ntrk2tm1Ddg/J model, carrying a mutation in the BDNF receptor Tyrosine kinase B (TrkB), these effects are partially or totally reversed. Wild type obese mice treated with FLX showed reduced weight gain, increased energy output, and differently from untreated obese mice, a preserved acute response to leptin in terms of activation of the intracellular leptin transducer STAT3. In conclusion, FLX impacts on energy balance and induces leptin sensitivity and an intact TrkB function is required for these effects to take place

Displacement power spectrum measurement of a macroscopic optomechanical system at thermal equilibrium

The mirror relative motion of a suspended Fabry-Perot cavity is studied in the frequency range 3-10 Hz. The experimental measurements presented in this paper, have been performed at the Low Frequency Facility, a high finesse optical cavity 1 cm long suspended to a mechanical seismic isolation system identical to that one used in the VIRGO experiment. The measured relative displacement power spectrum is compatible with a system at thermal equilibrium within its environmental. In the frequency region above 3 Hz, where seismic noise contamination is negligible, the measurement distribution is stationary and Gaussian, as expected for a system at thermal equilibrium. Through a simple mechanical model it is shown that: applying the fluctuation dissipation theorem the measured power spectrum is reproduced below 90 Hz and noise induced by external sources are below the measurement.Comment: 11 pages, 9 figures, 2 tables, to be submitte

Inertial control of the mirror suspensions of the VIRGO interferometer for gravitational wave detection

In order to achieve full detection sensitivity at low frequencies, the mirrors of interferometric gravitational wave detectors must be isolated from seismic noise. The VIRGO vibration isolator, called 'superattenuator', is fully effective at frequencies above 4 Hz. Nevertheless, the residual motion of the mirror at the mechanical resonant frequencies of the system are too large for the interferometer locking system and must be damped. A multidimensional feedback system, using inertial sensors and digital processing, has been designed for this purpose. An experimental procedure for determining the feedback control of the system has been defined. In this paper a full description of the system is given and experimental results are presented.Comment: 17 pages, 11 figures, accepted for publication on Review of Scientific Instrument

An instrumented baffle for the Advanced Virgo Input Mode Cleaner End Mirror

A novel instrumented baffle surrounding the suspended end mirror in the input mode cleaner cavity of the Virgo interferometer was installed in spring 2021. Since then, the device has been regularly operated in the experiment and the obtained results indicate a good agreement with simulations of the stray light inside the optical cavity. The baffle will operate in the upcoming O4 observation run, serving as a demonstrator of the technology designed to instrument the baffles in front of the main mirrors in time for O5. In this paper we present a detailed description of the baffle design, including mechanics, front-end electronics, data acquisition, as well as optical and vacuum tests, calibration and installation procedures, and performance results.Comment: 12 pages, 21 figures, 3 tables, to be submitted to PR

Reconstruction of the gravitational wave signal h(t)h(t) during the Virgo science runs and independent validation with a photon calibrator

The Virgo detector is a kilometer-scale interferometer for gravitational wave detection located near Pisa (Italy). About 13 months of data were accumulated during four science runs (VSR1, VSR2, VSR3 and VSR4) between May 2007 and September 2011, with increasing sensitivity. In this paper, the method used to reconstruct, in the range 10 Hz-10 kHz, the gravitational wave strain time series $h(t)$ from the detector signals is described. The standard consistency checks of the reconstruction are discussed and used to estimate the systematic uncertainties of the $h(t)$ signal as a function of frequency. Finally, an independent setup, the photon calibrator, is described and used to validate the reconstructed $h(t)$ signal and the associated uncertainties. The uncertainties of the $h(t)$ time series are estimated to be 8% in amplitude. The uncertainty of the phase of $h(t)$ is 50 mrad at 10 Hz with a frequency dependence following a delay of 8 $\mu$s at high frequency. A bias lower than $4\,\mathrm{\mu s}$ and depending on the sky direction of the GW is also present.Comment: 35 pages, 16 figures. Accepted by CQ

Natural Course of COVID-19 and Independent Predictors of Mortality.

Background: During the SARS-CoV-2 pandemic, several biomarkers were shown to be helpful in determining the prognosis of COVID-19 patients. The aim of our study was to evaluate the prognostic value of N-terminal pro-Brain Natriuretic Peptide (NT-pro-BNP) in a cohort of patients with COVID-19. Methods: One-hundred and seven patients admitted to the Covid Hospital of Messina University between June 2022 and January 2023 were enrolled in our study. The demographic, clinical, biochemical, instrumental, and therapeutic parameters were recorded. The primary outcome was in-hospital mortality. A comparison between patients who recovered and were discharged and those who died during the hospitalization was performed. The independent parameters associated with in-hospital death were assessed by multivariable analysis and a stepwise regression logistic model. Results: A total of 27 events with an in-hospital mortality rate of 25.2% occurred during our study. Those who died during hospitalization were older, with lower GCS and PaO2/FiO2 ratio, elevated D-dimer values, INR, creatinine values and shorter PT (prothrombin time). They had an increased frequency of diagnosis of heart failure (p < 0.0001) and higher NT-pro-BNP values. A multivariate logistic regression analysis showed that higher NT-pro-BNP values and lower PT and PaO2/FiO2 at admission were independent predictors of mortality during hospitalization. Conclusions: This study shows that NT-pro-BNP levels, PT, and PaO2/FiO2 ratio are independently associated with in-hospital mortality in subjects with COVID-19 pneumonia. Further longitudinal studies are warranted to confirm the results of this study

Virgo calibration and reconstruction of the gravitational wave strain during VSR1

Virgo is a kilometer-length interferometer for gravitational waves detection located near Pisa. Its first science run, VSR1, occured from May to October 2007. The aims of the calibration are to measure the detector sensitivity and to reconstruct the time series of the gravitational wave strain h(t). The absolute length calibration is based on an original non-linear reconstruction of the differential arm length variations in free swinging Michelson configurations. It uses the laser wavelength as length standard. This method is used to calibrate the frequency dependent response of the Virgo mirror actuators and derive the detector in-loop response and sensitivity within ~5%. The principle of the strain reconstruction is highlighted and the h(t) systematic errors are estimated. A photon calibrator is used to check the sign of h(t). The reconstructed h(t) during VSR1 is valid from 10 Hz up to 10 kHz with systematic errors estimated to 6% in amplitude. The phase error is estimated to be 70 mrad below 1.9 kHz and 6 micro-seconds above.Comment: 8 pages, 8 figures, proceedings of Amaldi 8 conference, to be published in Journal of Physics Conference Series (JPCS). Second release: correct typo

Calibration and sensitivity of the Virgo detector during its second science run

The Virgo detector is a kilometer-length interferometer for gravitational wave detection located near Pisa (Italy). During its second science run (VSR2) in 2009, six months of data were accumulated with a sensitivity close to its design. In this paper, the methods used to determine the parameters for sensitivity estimation and gravitational wave reconstruction are described. The main quantities to be calibrated are the frequency response of the mirror actuation and the sensing of the output power. Focus is also put on their absolute timing. The monitoring of the calibration data as well as the parameter estimation with independent techniques are discussed to provide an estimation of the calibration uncertainties. Finally, the estimation of the Virgo sensitivity in the frequency-domain is described and typical sensitivities measured during VSR2 are shown.Comment: 30 pages, 23 figures, 1 table. Published in Classical and Quantum Gravity (CQG), Corrigendum include