Labelling and clinical performance of human leukocytes labelled with 99m Tc-HMPAO using leukokit® with gelofusine versus leukokit® with HES as sedimentation agent

The scintigraphy with radiolabelled autologous leukocytes (WBCs) is considered the gold-standard technique for imaging infections. Leukokit (R) is a commercially available, disposable, sterile kit for labelling WBCs ex vivo. In this kit, WBCs isolation from red blood cells (RBCs) was performed using poly(O-2-hydroxyethyl)starch (HES) as the RBCs sedimentation agent. Due to its poor availability, HES has been recently replaced by Gelofusine as the RBC sedimentation agent. The aim of this study was to compare the labelling efficiency and the diagnostic accuracy of WBCs labelled with Leukokit (R) with HES vs Leukokit (R) with Gelofusine. WBCs were isolated using HES or Gelofusine for 45minutes and then purified from platelets (PLTs) and labelled with 1.1 +/- 0.3 GBq of freshly prepared Tc-99m- HMPAO. The following parameters were evaluated: the number and type of recovered WBCs, RBCs contamination, PLTs contamination, vitality of neutrophils, and chemotactic properties of neutrophils. Clinical comparison was performed between 80 patients (33 males; age 67.5 +/- 14.2) injected with Tc-99m-HMPAO-WBCs, using HES as the sedimentation agent, and 92 patients (38 males; age 68.2 +/- 12.8) injected with Tc-99m-HMPAO-WBCs using Gelofusine as the sedimentation agent. Patients were affected by prosthetic joint infections, peripheral bone osteomyelitis, or vascular graft infection. We compared radiolabelling efficiency (LE), final recovery yield (RY), and diagnostic outcome based on microbiology or 2-year follow-up. Results showed that HES provides the lowest RBCs and PLTs contamination, but Gelofusine provides the highest WBC recovery. Both agents did not influence the chemotactic properties of WBCs, and no differences were found in terms of LE and RY. Sensitivity, specificity, and accuracy were also not significantly different for WBCs labelled with both agents (diagnostic accuracy 90.9%, CI = 74.9-96.1 vs 98.3%, CI = 90.8-100, for HES and Gelofusine, respectively). In conclusion, Gelofusine can be considered a suitable alternative of HES for WBCs separation and labelling

Stringent Constraint on Galactic Positron Production

The intense 0.511 MeV gamma-ray line emission from the Galactic Center observed by INTEGRAL requires a large annihilation rate of nonrelativistic positrons. If these positrons are injected at even mildly relativistic energies, higher-energy gamma rays will also be produced. We calculate the gamma-ray spectrum due to inflight annihilation and compare to the observed diffuse Galactic gamma-ray data. Even in a simplified but conservative treatment, we find that the positron injection energies must be $\lesssim 3$ MeV, which strongly constrains models for Galactic positron production.Comment: 4 pages, 2 figures; minor revisions, accepted for publication in PR

Gravitational waveforms from the evaporating ACO cosmic string loop

The linearly polarized gravitational waveforms from a certain type of rotating, evaporating cosmic string - the Allen-Casper-Ottewill loop - are constructed and plotted over the lifetime of the loop. The formulas for the waveforms are simple and exact, and describe waves which attenuate self-similarly, with the amplitude and period of the waves falling off linearly with time.Comment: 30 pages, 16 figure

Emergency contraception: unresolved clinical, ethical and legal quandaries still linger

Emergency contraception (EC) has been prescribed for decades, in order to lessen the risk of unplanned and unwanted pregnancy following unprotected intercourse, ordinary contraceptive failure, or rape. EC and the linked aspect of unintended pregnancy undoubtedly constitute highly relevant public health issues, in that they involve women's self-determination, reproductive freedom and family planning. Most European countries regulate EC access quite effectively, with solid information campaigns and supply mechanisms, based on various recommendations from international institutions herein examined. However, there is still disagreement on whether EC drugs should be available without a physician's prescription and on the reimbursement policies that should be implemented. In addition, the rights of health care professionals who object to EC on conscience grounds have been subject to considerable legal and ethical scrutiny, in light of their potential to damage patients who need EC drugs in a timely fashion. Ultimately, reproductive health, freedom and conscience-based refusal on the part of operators are elements that have proven extremely hard to reconcile; hence, it is essential to strike a reasonable balance for the sake of everyone's rights and well-being

MeV Right-handed Neutrinos and Dark Matter

We consider the possibility of having a MeV right-handed neutrino as a dark matter constituent. The initial reason for this study was the 511 keV spectral line observed by the satellite experiment INTEGRAL: could it be due to an interaction between dark matter and baryons? Independently of this, we find a number of constraints on the assumed right-handed interactions. They arise in particular from the measurements by solar neutrino experiments. We come to the conclusion that such particles interactions are possible, and could reproduce the peculiar angular distribution, but not the rate of the INTEGRAL signal. However, we stress that solar neutrino experiments are susceptible to provide further constraints in the future.Comment: 7 pages, figure 1 changed, added reference

Towards personalized medicine: Non-coding rnas and endometrial cancer

Endometrial cancer (EC) is the most frequent female cancer associated with excellent prognosis if diagnosed at an early stage. The risk factors on which clinical staging is based are constantly updated and genetic and epigenetic characteristics have recently been emerging as prognostic markers. The evidence shows that non-coding RNAs (ncRNAs) play a fundamental role in various biological processes associated with the pathogenesis of EC and many of them also have a prognosis prediction function, of remarkable importance in defining the therapeutic and surveillance path of EC patients. Personalized medicine focuses on the continuous updating of risk factors that are identifiable early during the EC staging to tailor treatments to patients. This review aims to show a summary of the current classification systems and to encourage the integration of various risk factors, introducing the prognostic role of non-coding RNAs, to avoid aggressive therapies where not necessary and to treat and strictly monitor subjects at greater risk of relapse

Non-coding RNAs as prognostic markers for endometrial cancer

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs

In vitro and in vivo evaluation of 99mTc-polymyxin B for specific targeting of gram-bacteria

Background: Infectious diseases are one of the main causes of morbidity and mortality worldwide. Nuclear molecular imaging would be of great help to non-invasively discriminate between septic and sterile inflammation through available radiopharmaceuticals, as none is currently available for clinical practice. Here, we describe the radiolabeling procedure and in vitro and in vivo studies of99mTc-polymyxin B sulfate (PMB) as a new single photon emission imaging agent for the characterization of infections due to Gram-negative bacteria. Results: Labeling efficiency was 97 ± 2% with an average molar activity of 29.5 ± 0.6 MBq/nmol. The product was highly stable in saline and serum up to 6 h. In vitro binding assay showed significant displaceable binding to Gram-negative bacteria but not to Gram-positive controls. In mice,99mTc-HYNIC-PMB was mainly taken up by liver and kidneys. Targeting studies confirmed the specificity of99mTc-HYNIC-PMB obtained in vitro, showing significantly higher T/B ratios for Gram-negative bacteria than Gram-positive controls. Conclusions: In vitro and in vivo results suggest that99mTc-HYNIC-PMB has a potential for in vivo identification of Gram-negative bacteria in patients with infections of unknown etiology. However, further investigations are needed to deeply understand the mechanism of action and behavior of99mTc-HYNIC-PMB in other animal models and in humans

Triple Experiment Spectrum of the Sunyaev-Zeldovich Effect in the Coma Cluster: H_0

The Sunyaev-Zeldovich (SZ) effect was previously measured in the Coma cluster by the Owens Valley Radio Observatory and Millimeter and IR Testa Grigia Observatory experiments and recently also with the Wilkinson Microwave Anisotropy Probe satellite. We assess the consistency of these results and their implications on the feasibility of high-frequency SZ work with ground-based telescopes. The unique data set from the combined measurements at six frequency bands is jointly analyzed, resulting in a best-fit value for the Thomson optical depth at the cluster center, tau_{0}=(5.35 \pm 0.67) 10^{-3}. The combined X-ray and SZ determined properties of the gas are used to determine the Hubble constant. For isothermal gas with a \beta density profile we derive H_0 = 84 \pm 26 km/(s\cdot Mpc); the (1\sigma) error includes only observational SZ and X-ray uncertainties.Comment: 11 pages, 1 figur

Proteomic Modulation in TGF-β-Treated Cholangiocytes Induced by Curcumin Nanoparticles

Curcumin is a natural polyphenol that exhibits a variety of beneficial effects on health, including anti-inflammatory, antioxidant, and hepato-protective properties. Due to its poor water solubility and membrane permeability, in the present study, we prepared and characterized a water-stable, freely dispersible nanoformulation of curcumin. Although the potential of curcumin nanoformulations in the hepatic field has been studied, there are no investigations on their effect in fibrotic pathological conditions involving cholangiocytes. Exploiting an in vitro model of transforming growth factor-  (TGF- )-stimulated cholangiocytes, we applied the Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS)-based quantitative proteomic approaches to study the proteome modulation induced by curcumin nanoformulation. Our results confirmed the well-documented anti-inflammatory properties of this nutraceutic, highlighting the induction of programmed cell death as a mechanism to counteract the cellular damages induced by TGF- . Moreover, curcumin nanoformulation positively influenced the expression of several proteins involved in TGF- -mediated fibrosis. Given the crucial importance of deregulated cholangiocyte functions during cholangiopathies, our results provide the basis for a better understanding of the mechanisms associated with this pathology and could represent a rationale for the development of more targeted therapies