Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction

Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15\u201320 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801\u20133). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E \u3b3 \u2009\u2009>\u2009\u2009200\u2009keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7\u201319.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc

Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2H)-one as Novel Scaffold for FABP4 Inhibition

Fatty acid binding protein (FABP4) inhibitors are of synthetic and therapeutic interest and ongoing clinical studies indicate that they may be a promise for the treatment of cancer, as well as other diseases. As part of a broader research effort to develop more effective FABP4 inhibitors, we sought to identify new structures through a two-step computing assisted molecular design based on the established scaffold of a co-crystallized ligand. Novel and potent FABP4 inhibitors have been developed using this approach and herein we report the synthesis, biological evaluation and molecular docking of the 4-amino and 4-ureido pyridazinone-based series

Turbulent friction in flows over permeable walls

Peer reviewedPublisher PD

The SURF (Italian observational study for renal insufficiency evaluation in liver transplant recipients): A post-hoc between-sex analysis

Background: Female sex has been reported as an independent predictor of severe post-liver transplantation (LT) chronic kidney disease. We performed a by sex post-hoc analysis of the SURF study, that investigated the prevalence of renal impairment following LT, aimed at exploring possible differences between sexes in the prevalence and course of post-LT renal damage. Methods: All patients enrolled in the SURF study were considered evaluable for this sex-based analysis, whose primary objective was to evaluate by sex the proportion of patients with estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73m2 at inclusion and follow-up visit. Results: Seven hundred thirty-eight patients were included in our analysis, 76% males. The proportion of patients with eGFR < 60 mL/min/1.73 m2 was significantly higher in females at initial study visit (33.3 vs 22.8%; p = 0.005), but also before, at time of transplantation (22.9 vs 14.7%; p = 0.0159), as analyzed retrospectively. At follow-up, such proportion increased more in males than in females (33.9 vs 26.0%, p = 0.04). Mean eGFR values decreased over the study in both sexes, with no significant differences. Statistically significant M/F differences in patient distribution by O'Riordan eGFR levels were observed at time of transplant and study initial visit (p = 0.0005 and 0.0299 respectively), but not at follow-up. Conclusions: Though the limitation of being performed post-hoc, this analysis suggests potential sex differences in the prevalence of renal impairment before and after LT, encouraging further clinical research to explore such differences more in depth

Periostin Responds to Mechanical Stress and Tension by Activating the MTOR Signaling Pathway

Current knowledge about Periostin biology has expanded from its recognized functions in embryogenesis and bone metabolism to its roles in tissue repair and remodeling and its clinical implications in cancer. Emerging evidence suggests that Periostin plays a critical role in the mechanism of wound healing; however, the paracrine effect of Periostin in epithelial cell biology is still poorly understood. We found that epithelial cells are capable of producing endogenous Periostin that, unlike mesenchymal cell, cannot be secreted. Epithelial cells responded to Periostin paracrine stimuli by enhancing cellular migration and proliferation and by activating the mTOR signaling pathway. Interestingly, biomechanical stimulation of epithelial cells, which simulates tension forces that occur during initial steps of tissue healing, induced Periostin production and mTOR activation. The molecular association of Periostin and mTOR signaling was further dissected by administering rapamycin, a selective pharmacological inhibitor of mTOR, and by disruption of Raptor and Rictor scaffold proteins implicated in the regulation of mTORC1 and mTORC2 complex assembly. Both strategies resulted in ablation of Periostin-induced mitogenic and migratory activity. These results indicate that Periostin-induced epithelial migration and proliferation requires mTOR signaling. Collectively, our findings identify Periostin as a mechanical stress responsive molecule that is primarily secreted by fibroblasts during wound healing and expressed endogenously in epithelial cells resulting in the control of cellular physiology through a mechanism mediated by the mTOR signaling cascade.This work was funded by the National Institutes of Health (NIH/NCI) P50-CA97248 (University of Michigan Head and Neck SPORE)

Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action

In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-gamma+GM-CSF+IL-17+ subset. This was linked with changes in SC CD11b+CD45+TCR alpha beta- microglia/proinflammatory monocyte progeny, substantiated in a more prominent increase in the frequency of anti-inflammatory phygocyting CD163+ cells and the cells expressing high surface levels of immunoregulatory CD83 molecule (associated with apoptotic cells phagocytosis and implicated in downregulation of CD4+ T lymphocyte reactivation) among CD11b+CD45+TCR alpha beta- cells in male rat SC. These changes were associated with greater increase in the nuclear factor (erythroid-derived 2)-like 2 expression in male rats administered with DMF. In accordance with the previous findings, DMF diminished reactive nitrogen and oxygen species generation and consistently, SC level of advanced oxidation protein products, to the greater extent in male rats. Overall, our study indicates sex-specificity in the sensitivity of DMF cellular and molecular targets and encourages sex-based clinical research to define significance of sex for action of therapeutic agents moderating autoimmune neuroinflammation-/oxidative stress-related nervous tissue damage

Pneumococcal septic shock after neonatal respiratory syncytial virus bronchiolitis: A case report and literature review

Background: Bronchiolitis is a common cause of hospitalisation of infants less than a year old, with most infants recovering without complications. Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis. Antimicrobial stewardship programmes do not recommend antibiotics for viral infections in neonates unless documented evidence of secondary bacterial infection is present. Case report: We present the case of a 7-day-old infant admitted to hospital with chest retractions and fever. The baby was hospitalised, empirical antibiotic therapy was administered, and non-invasive ventilation was started. When the viral aetiology was identified and clinical conditions improved, antibiotics were discontinued. However, after 48 hours, the newborn’s condition worsened because of pneumococcal septic shock. Intravenous fluids, catecholamine support, and wide-spectrum antibiotics were administered. Non-invasive ventilation was re-started and continued until the full recovery. Conclusions: There is increasing evidence that RSV and S. pneumoniae co-infect and interact with each other, thus increasing respiratory diseases’ severity. We provide a brief overview of the main international guidelines for managing bronchiolitis. Guidelines suggest avoidance of antibiotics use when the diagnosis of viral bronchiolitis is confirmed. We discuss the uncertainties regarding antibiotic use, especially in younger infants, who are more exposed to risks of bacterial superinfection. (www.actabiomedica.it)

Turbulent boundary layers over permeable walls: scaling and near wall structure

This paper presents an experimental study devoted to investigating the effects of permeability on wall turbulence. Velocity measurements were performed by means of laser Doppler anemometry in open channel flows over walls characterized by a wide range of permeability. Previous studies proposed that the von Kármán coefficient associated with mean velocity profiles over permeable walls is significantly lower than the standard values reported for flows over smooth and rough walls. Furthermore, it was observed that turbulent flows over permeable walls do not fully respect the widely accepted paradigm of outer-layer similarity. Our data suggest that both anomalies can be explained as an effect of poor inner–outer scale separation if the depth of shear penetration within the permeable wall is considered as the representative length scale of the inner layer. We observed that with increasing permeability, the near-wall structure progressively evolves towards a more organized state until it reaches the condition of a perturbed mixing layer where the shear instability of the inflectional mean velocity profile dictates the scale of the dominant eddies. In our experiments such shear instability eddies were detected only over the wall with the highest permeability. In contrast attached eddies were present over all the other wall conditions. On the basis of these findings, we argue that the near-wall structure of turbulent flows over permeable walls is regulated by a competing mechanism between attached and shear instability eddies. We also argue that the ratio between the shear penetration depth and the boundary layer thickness quantifies the ratio between such eddy scales and, therefore, can be used as a diagnostic parameter to assess which eddy structure dominates the near-wall region for different wall permeability and flow condition

Deep water: Predicting water meter failures through a human-machine intelligence collaboration

Take an AI learning algorithm and a human trainer with an experience in machine intelligence. Take piles of data, in the form of labeled examples. If you think that the task of training a machine that makes accurate decisions is easy as pie, you could not be further from reality. That is what has been missing from this story: getting off on the right foot. For a good start, crucial is the value of data which come large in quantity but low in quality. Beyond how we design our AI, fundamental is making our data valid for learning. We report here our experience in the creation of highly accurate training examples, based on the idea of filtering out all the impurities from a dataset containing 15 million water readings, provided by an Italian water supply company. This was accomplished allowing a human-machine collaboration, down to the implementation of an AI model capable to predict water meter failure