Dissolution of Molybdenum in Hydrogen Peroxide: A Thermodynamic, Kinetic and Microscopic Study of a Green Process for 99mTc Production

99mTc-based radiopharmaceuticals are the most commonly used medical radioactive tracers in nuclear medicine for diagnostic imaging. Due to the expected global shortage of 99Mo, the parent radionuclide from which 99mTc is produced, new production methods should be developed. The SORGENTINA-RF (SRF) project aims at developing a prototypical medium-intensity D-T 14-MeV fusion neutron source specifically designed for production of medical radioisotopes with a focus on 99Mo. The scope of this work was to develop an efficient, cost-effective and green procedure for dissolution of solid molybdenum in hydrogen peroxide solutions compatible for 99mTc production via the SRF neutron source. The dissolution process was extensively studied for two different target geometries: pellets and powder. The first showed better characteristics and properties for the dissolution procedure, and up to 100 g of pellets were successfully dissolved in 250–280 min. The dissolution mechanism on the pellets was investigated by means of scanning electron microscopy and energy-dispersive X-ray spectroscopy. After the procedure, sodium molybdate crystals were characterized via X-ray diffraction, Raman and infrared spectroscopy and the high purity of the compound was established by means of inductively coupled plasma mass spectroscopy. The study confirmed the feasibility of the procedure for production of 99mTc in SRF as it is very cost-effective, with minimal consumption of peroxide and controlled low temperature

Manufacturing of PAV-ONE, a Permeator against Vacuum Mock-Up with Niobium Membrane

The Permeator Against Vacuum (PAV) is one of the proposed technologies for the Tritium Extraction System of the WCLL BB (Water-Cooled Lithium-Lead Breeding Blanket) of the EU DEMO reactor. In this paper, the manufacturing of the first PAV mock-up with a niobium membrane with a cylindrical configuration is presented. This work aimed to demonstrate the possibility of manufacturing a relevant-size PAV to be later tested in the TRIEX-II facility. The adopted prototypical solutions are described in detail, starting with the methodology developed to join the Nb tubes with a 10CrMo9-10 (A182 F22) plate. Dedicated manufacturing and welding procedures, based on vacuum brazing with a nickel-based brazing alloy, were developed to solve the problem. This new kind of brazing was first analyzed to check the morphology of the joint and then tested to check its capability to withstand the TRIEX-II operative conditions. In parallel, the compatibility with a lithium-lead environment was analyzed by exposing samples of niobium and 10CrMo9-10 (A335 P22) to a flow of the eutectic alloy at 500 °C up to 4000 h. Finally, the PAV mock-up was installed in the TRIEX-II facility

Preparation and Characterization of Isostructural Na2MoO4 and Na2WO4 and a Study of the Composition of Their Mixed System

Na2MoO4 and Na2WO4 are isostructural semiconductors, belonging to the spinel class. They have interesting properties and find applications in numerous sectors. These properties can be tuned by controlling the composition of their solid solutions. Here, different methods to obtain these compounds are presented, both wet and solid-state synthesis. The obtained results show a possible dependence of the material properties on the chosen synthesis method. The pure compounds and their mixtures were characterized by Raman spectroscopy, scanning electron microscopy, and X-ray diffraction

Neonatal Hypersusceptibility to Endotoxin Correlates with Increased Tumor Necrosis Factor Production in Mice

Septic shock is a major cause of mortality in neonates. The hypothesis was tested that neonatal, age is associated with altered sensitivity to shock-inducing bacterial products or proinflammatory, cytokines (or both). Mice of different ages were inoculated with various doses of lipopolysaccharide, (LPS), superantigenic staphylococcal enterotoxin B (SEB), or recombinant tumor necrosis factor-α, (rTNF-α), alone or in combination with the sensitizing agent D-galactosamine. Neonatal mice were, markedly more susceptible to LPS-induced lethality but more resistant to SEB than were adults (P, \u3c .05). Mice of different ages did not differ, however, in their sensitivity to lethal activities of rTNFα. Neonatal susceptibility to LPS and SEB correlated directly with plasma TNF-α but not IFN-γ, levels, which was confirmed by TNF-α and IFN-γ blockade experiments. These data document, marked age-related differences in the pathophysiology of septic shock and suggest that IFN-γ is, not an obligatory mediator of either LPS- or SEB-induced lethality in neonates

Molecular and computational diagnostic approach identifies FOXP3, ICOS, CD52 and CASP1 as the most informative biomarkers in acute graft versus host disease.

BACKGROUND: Acute graft-versus-host disease is a severe complication of allogeneic stem cell transplantation in which the functional immune cells of the donor recognize the recipient as foreign and mount an immunological attack. There is an urgent need for better diagnostic instruments for the assessment of acute graft-versus-host disease. In the present study, a novel bioinformatics framework was used to identify gene expression patterns associated with acute graft-versushost disease in patients undergoing allogeneic hematopoietic stem cell transplantation. DESIGN AND METHODS: Peripheral blood cells were collected prospectively from patients who did develop acute graftversus-host disease (YES) and from those who did not (NO). Gene expression profiling was performed using a panel of 47 candidate genes potentially involved in alloreactive responses. The entire population of YES/NO acute graft-versus-host disease patients formed the experimental validation set. Personalized modeling based on a gene selection technique was applied to identify the most significant mRNA transcripts, which were then used to profile individual data samples for training and testing the classification/prediction framework. RESULTS: A leave-one-out cross-validation procedure was performed to investigate the robustness of the classification framework producing the following results: 100% on the training dataset and 97% on the testing dataset. According to our integrated methodology, transcripts for FOXP3, ICOS, CD52 and CASP1, genes involved in immune alloreactive responses and participating in immune cell interactions, were identified as the most informative biomarkers in allogeneic stem cell transplant recipients experiencing acute graft-versus-host disease. CONCLUSIONS: This study demonstrates that the integrated methodology proposed is useful for the selection of valid gene targets for the diagnosis of acute graft-versus-host disease, producing satisfactory accuracy over independent clinical features of the allogeneic transplanted population

Translational Research on Azacitidine Post-Remission Therapy of Acute Myeloid Leukemia in Elderly Patients (QOL-ONE Trans-2)

The achievement of complete remission (CR) is crucial for acute myeloid leukemia (AML) patients undertaking curative therapy, but relapse often occurs within months, highlighting the need for strategies to prolong disease-free survival (DFS). Our phase III study compared the efficacy and safety of azacitidine (AZA) to best supportive care (BSC) in elderly AML patients who achieved CR following intensive induction and consolidation therapy. This ancillary study (QOL-ONE Trans-2) evaluated biological changes in bone marrow using Next-Generation Sequencing (NGS). We analyzed baseline, randomization, and 6-month post-remission samples from 24 patients (median age of 71 and 12 males). High-throughput NGS targeted 350 myeloid malignancy-related genes, considering variants with a variant allele frequency ≥ 4%. At diagnosis, all patients had 5 to 17 (median = 10) mutations, with DNMT3A (42%), NPM1 (33%), and TET2 (33%) being most frequent. FANCA mutations in four patients were linked to a higher relapse risk (HR = 4.96, p = 0.02) for DFS at both 2 and 5 years. Further HLA-specific NGS analyses are ongoing to confirm these results and their therapeutic implications

Translational Research on Azacitidine Post-Remission Therapy of Acute Myeloid Leukemia in Elderly Patients (QOL-ONE Trans-2)

The achievement of complete remission (CR) is crucial for acute myeloid leukemia (AML) patients undertaking curative therapy, but relapse often occurs within months, highlighting the need for strategies to prolong disease-free survival (DFS). Our phase III study compared the efficacy and safety of azacitidine (AZA) to best supportive care (BSC) in elderly AML patients who achieved CR following intensive induction and consolidation therapy. This ancillary study (QOL-ONE Trans-2) evaluated biological changes in bone marrow using Next-Generation Sequencing (NGS). We analyzed baseline, randomization, and 6-month post-remission samples from 24 patients (median age of 71 and 12 males). High-throughput NGS targeted 350 myeloid malignancy-related genes, considering variants with a variant allele frequency ≥ 4%. At diagnosis, all patients had 5 to 17 (median = 10) mutations, with DNMT3A (42%), NPM1 (33%), and TET2 (33%) being most frequent. FANCA mutations in four patients were linked to a higher relapse risk (HR = 4.96, p = 0.02) for DFS at both 2 and 5 years. Further HLA-specific NGS analyses are ongoing to confirm these results and their therapeutic implications