Chemical and physical modifications of polyethylene containing nanostructures

The polyethylene is an interesting polymer with a good mechanical strength, ductility, biocompatibility and chemical inertia. It founds several applications in many fields, such as chemistry, engineering, bio-medicine and micro-electronics. The polyethylene chemical and physical properties can be modified embedding different nanostructures in its bulk. Carbon nanotubes, metallic oxides, coloured pigments and other species can be inserted at different concentrations in the polymer material during the preparation phase of thin films and sheets. Mechanical, optical, thermal and chemical properties can be modified significantly depending on the filler concentration. The absorption coefficient at different radiations can be controlled by the amount of doping structure. In the visible region, for example, the high transparency of pure polyethylene can be strongly reduced by low concentrations of carbon nanotubes. The colour, the mechanical resistance, the wet ability of the polyethylene and other parameters can be changed by the doping species in order to prepare special devices useful for many applications

Laser-generated nanoparticles to change physical properties of solids, liquids and gases

Synthesis of nanoparticles was possible employing a Nd: YAG pulsed laser at fundamental harmonic. The production of nanoparticles in water depends mainly on the laser parameters (pulse duration, energy, wavelength), the irradiation conditions (focal spot, repetition rate, irradiation time) and the medium where the ablation occurs (solid target, water, solution concentration). The nanoparticles can be introduced in solids, liquids or gases to change many physical characteristics. The optical properties of polymers and solutions, the wetting ability of liquids, the electron density of laser-generated plasma, represent some examples that can be controlled by the concentration of metallic nanoparticles (Au, Ag, Ti, Cu). Some bio-medical applications will be presented and discussed

Post-Marketing Surveillance of CAR-T-Cell Therapies: Analysis of the FDA Adverse Event Reporting System (FAERS) Database

Introduction As chimeric antigen receptor T-cell therapies are becoming increasingly available in the armamentarium of the hematologist, there is an emerging need to monitor post-marketing safety. Objective We aimed to better characterize their safety profile by focusing on cytokine release syndrome and identifying emerging signals. Methods We queried the US Food and Drug Administration Adverse Event Reporting System (October 2017-September 2020) to analyze suspected adverse drug reactions to tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). Disproportionality analyses (reporting odds ratio) were performed by comparing chimeric antigen receptor T-cell therapies with (a) all other drugs (reference group 1) and (b) other onco-hematological drugs with a similar indication, irrespective of age (reference group 2), or (c) restricted to adults (reference group 3). Notoriety was assessed through package inserts and risk management plans. Adverse drug reaction time to onset and cytokine release syndrome features were investigated. Results Overall, 3225 reports (1793 axi-cel; 1433 tisa-cel) were identified. The reported toxicities were mainly: cytokine release syndrome (52.2%), febrile disorders (27.7%), and neurotoxicity (27.2%). Cytokine release syndrome and neurotoxicity were often co-reported and 75% of the events occurred in the first 10 days. Disproportionalities confirmed known adverse drug reactions and showed unexpected associations: for example, axi-cel with cardiomyopathies (reporting odds ratio = 2.3; 95% confidence interval 1.2-4.4) and gastrointestinal perforations (2.9; 1.2-7.3), tisa-cel with hepatotoxicity (2.5; 1.1-5.7) and pupil disorders (15.3; 6-39.1). Conclusions Our study confirms the well-known adverse drug reactions and detects potentially emerging safety issues specific for each chimeric antigen receptor T-cell therapy, also providing insights into a stronger role for tisa-cel in inducing some immunodeficiency-related events (e.g., hypogammaglobulinemia, infections) and coagulopathies, and for axi-cel in neurotoxicity

Protons accelerated in the target normal sheath acceleration regime by a femtosecond laser

Advanced targets based on thin films of graphene oxide covered by metallic layers have been irradiated at high laser intensity (∼1019 W/cm2) with 40 fs laser pulses to investigate the forward ion acceleration in the target normal sheath acceleration regime. A time-of-flight technique was employed with silicon-carbide detectors and ion collectors as fast on-line plasma diagnostics. At the optimized conditions of the laser focus position with respect to the target surface was measured the maximum proton energy using Au metallic films. A maximum proton energy of 2.85 MeV was measured using the Au metallization of 200 nm. The presence of graphene oxide facilitates the electron crossing of the foil minimizing the electron scattering and increasing the electric field driving the ion acceleration. The effect of plasma electron density control using the graphene oxide is presented and discussed

Production and characterization of micro-size pores for ion track etching applications

For many years the applications of ion track etch materials have increased considerably, like charged particles detection, molecular identification with nanopores, ion track filters, magnetic studies with nanowires and so on. Over the materials generally used as track detector, the Poly-Allyl-Diglycol Carbonate (PADC), offers many advantages, like its nearly 100 % detection efficiency for charged particle, a high resistance to harsh environment, the lowest detection threshold, a high abrasion resistance and a low production costs. All of these properties have made it particularly attractive material, even if due to its brittleness, obtaining a thin film (less than 500 μm) is still a challenge. In this work, PADC foils have been exposed to a-particles emitted by a thin radioactive source of 241Am and to C ions from the Tandetron 4130 MC accelerator. The latent tracks generated in the polymer have been developed using a standard etching procedure in 6.25 NaOH solution. The dependence of the ion tracks' geometry on the ion beam energy and fluence has been evaluated combining the information obtained through a semiautomatic computer script that selects the etched ion tracks according to their diameter and mean grey value and nanometric resolution images by atomic force microscopy

Safety and tolerability of antipsychotic drugs in pediatric patients: data from a 1-year naturalistic study

Background: Antipsychotic drugs (APs) are increasingly used to treat a variety of psychiatric disorders in children and adolescents. However, their safety and tolerability profiles, when used in a developmental age context, show different characteristics from the ones observed in adult patients. Treatment with APs in pediatric patients is often long-term. However, the tolerability data regarding these patients mostly derive from short-term studies. Methods: Starting from April 2017, for a 1-year period, patients between 4 and 18 years of age followed by five units of developmental age neuropsychiatry, who initiated a treatment with at least an AP (ATC class N05A) were included into the study. Patient-related data have been collected at baseline and regularly thereafter, as allowed by the clinical routine. Changes to continuous variables over time have been analyzed using a linear mixed model in subsamples of our population treated with risperidone or aripiprazole. Results: During the observation period, 158 patients were initially enrolled, but only 116 completed 12 months of therapy with an AP. Risperidone was the most used AP (n = 52) followed by aripiprazole (n = 44) and olanzapine (n = 7). For both the aripiprazole and risperidone groups, the mean body mass index (BMI) (P < 0.001 for both groups) and heart rate (P = 0.026 for aripiprazole group and P < 0.001 for the risperidone one) values significantly increased over time. The mean prolactin concentration value significantly increased over time only in the risperidone group (P = 0.04). Eighty-six patients experienced at least one adverse drug reaction (ADR), accounting for a total of 238 specific reactions, with the most frequent being weight gain (n = 34), increased serum prolactin levels (n = 21), hyperphagia (n = 20), and hypercholesterolemia (n = 14). Among these, only 24 ADRs were classifiable as serious. Conclusions: The results of this study confirm that risperidone and aripiprazole are relatively well-tolerated therapeutic options for the treatment of a variety of psychiatric disorders in pediatric patients. However, in findings such as statistically significant increments of BMI and heart rate mean values, the variations over time in prolactin levels observed with risperidone and the differences between the two drugs remark the necessity of systematic monitoring

mev ion beams generated by intense pulsed laser monitored by silicon carbide detectors

The high energy ions produced with intense pulsed laser were analyzed with Silicon Carbide detectors. In order to realize high performances and radiation resistant detectors, high quality and thick epitaxial layer were grown on a substrate and a Schottky diodes were then realized. These detectors were employed to probe the plasma generated with a 300 ps laser at intensity of 1016 W/cm2 operating at Prague Asterix Laser System Laboratory. They show a fast response and a high sensitivity to high energy ions. Metallic and polymeric thin films were irradiated and the produced plasmas were monitored in forward and backward directions. The analysis of the time-of-flight spectra evidences the emission of protons and ions at different energies. The spectra were deconvolved with a shifted Maxwell Boltzmann distribution. In our experimental conditions we detected protons in the energy range 1.2 – 3.0 MeV and heavy ions between 1.0 MeV up to 40 MeV depending on the target and the laser energy. The results were compared with the ones obtained by Thompson Parabola Spectrometer

C/EBPβ-Thr217 Phosphorylation Signaling Contributes to the Development of Lung Injury and Fibrosis in Mice

mice are refractory to Bleomycin-induced lung fibrosis the molecular mechanisms remain unknown. Here we show that blocking the ribosomal S-6 kinase (RSK) phosphorylation of the CCAAT/Enhancer Binding Protein (C/EBP)-β on Thr217 (a RSK phosphoacceptor) with either a single point mutation (Ala217), dominant negative transgene or a blocking peptide containing the mutated phosphoacceptor ameliorates the progression of lung injury and fibrosis induced by Bleomycin in mice. mice with a cell permeant, C/EBPβ peptide that inhibits phosphorylation of C/EBPβ on Thr217 (40 µg instilled intracheally on day-2 and day-6 after the single Bleomycin dose) also blocked the progression of lung injury and fibrosis induced by Bleomycin. Phosphorylation of human C/EBPβ on Thr266 (human homologue phosphoacceptor) was induced in collagen-activated human lung fibroblasts in culture as well as in activated lung fibroblasts in situ in lungs of patients with severe lung fibrosis but not in control lungs, suggesting that this signaling pathway may be also relevant in human lung injury and fibrosis.These data suggest that the RSK-C/EBPβ phosphorylation pathway may contribute to the development of lung injury and fibrosis