Recent Applications of Melanin-like Nanoparticles as Antioxidant Agents

Nanosized antioxidants are highly advantageous in terms of versatility and pharmacokinetics, with respect to conventional molecular ones. Melanin-like materials, artificial species inspired by natural melanin, combine recognized antioxidant (AOX) activity with a unique versatility of preparation and modification. Due to this versatility and documented biocompatibility, artificial melanin has been incorporated into a variety of nanoparticles (NP) in order to give new platforms for nanomedicine with enhanced AOX activity. In this review article, we first discuss the chemical mechanisms behind the AOX activity of materials in the context of the inhibition of the radical chain reaction responsible for the peroxidation of biomolecules. We also focus briefly on the AOX properties of melanin-like NP, considering the effect of parameters such as size, preparation methods and surface functionalization on them. Then, we consider the most recent and relevant applications of AOX melanin-like NPs that are able to counteract ferroptosis and be involved in the treatment of important diseases that affect, e.g., the cardiovascular and nervous systems, as well as the kidneys, liver and articulations. A specific section will be dedicated to cancer treatment, since the role of melanin in this context is still very debated. Finally, we propose future strategies in AOX development for a better chemical understanding of melanin-like materials. In particular, the composition and structure of these materials are still debated, and they present a high level of variability. Thus, a better understanding of the mechanism behind the interaction of melanin-like nanostructures with different radicals and highly reactive species would be highly advantageous for the design of more effective and specific AOX nano-agents

Incidence and Outcome of Invasive Fungal Diseases after Allogeneic Stem Cell Transplantation: A Prospective Study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

AbstractEpidemiologic investigation of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be useful to identify subpopulations who might benefit from targeted treatment strategies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) prospectively registered data on 1858 consecutive patients undergoing allo-HSCT between 2008 and 2010. Logistic regression analysis was performed to identify risk factors for proven/probable IFD (PP-IFD) during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT and to evaluate the impact of PP-IFDs on 1-year overall survival. The cumulative incidence of PP-IFDs was 5.1% at 40 days, 6.7% at 100 days, and 8.8% at 12 months post-transplantation. Multivariate analysis identified the following variables as associated with PP-IFDs: transplant from an unrelated volunteer donor or cord blood, active acute leukemia at the time of transplantation, and an IFD before transplantation in the early phase; transplant from an unrelated volunteer donor or cord blood and grade II-IV acute graft-versus-host disease (GVHD) in the late phase; and grade II-IV acute GVHD and extensive chronic GVHD in the very late phase. The risk for PP-IFD was significantly higher when acute GVHD was followed by chronic GVHD and when acute GVHD occurred in patients undergoing transplantation with grafts from other than matched related donors. The presence of PP-IFD was an independent factor in long-term survival (hazard ratio, 2.90; 95% confidence interval, 2.32 to 3.62; P < .0001). Our findings indicate that tailored prevention strategies may be useful in subpopulations at differing levels of risk for PP-IFDs

Mid-IR cosmological spectrophotometric surveys from space: Measuring AGN and star formation at the cosmic noon with a SPICA-like mission

We use the SPace Infrared telescope for Cosmology and Astrophysics (SPICA) project as a template to demonstrate how deep spectrophotometric surveys covering large cosmological volumes over extended fields (1- 15 deg2) with a mid-IR imaging spectrometer (17- 36 um) in conjunction with deep 70 um photometry with a far-IR camera, at wavelengths which are not affected by dust extinction can answer the most crucial questions in current galaxy evolution studies. A SPICA-like mission will be able for the first time to provide an unobscured three-dimensional (3D, i.e. x, y, and redshift z) view of galaxy evolution back to an age of the universe of less than ~ 2 Gyrs, in the mid-IR rest frame. This survey strategy will produce a full census of the Star Formation Rate (SFR) in the universe, using polycyclic aromatic hydrocarbons (PAH) bands and fine-structure ionic lines, reaching the characteristic knee of the galaxy luminosity function, where the bulk of the population is distributed, at any redshift up to z ~ 3.5. Deep follow-up pointed spectroscopic observations with grating spectrometers onboard the satellite, across the full IR spectral range (17-210 um) would simultaneously measure Black Hole Accretion Rate (BHAR), from high-ionisation fine-structure lines, and SFR, from PAH and low- to mid-ionisation lines in thousands of galaxies from solar to low metallicities, down to the knee of their luminosity functions. The analysis of the resulting atlas of IR spectra will reveal the physical processes at play in evolving galaxies across cosmic time, especially its heavily dust-embedded phase during the activity peak at the cosmic noon (z~1-3), through IR emission lines and features that are insensitive to the dust obscuration

Evaluation of an automated method for arterial input function detection for first-pass myocardial perfusion cardiovascular magnetic resonance

ABSTRACT: Background: Quantitative assessment of myocardial blood flow (MBF) with first-pass perfusion cardiovascular magnetic resonance (CMR) requires a measurement of the arterial input function (AIF). This study presents an automated method to improve the objectivity and reduce processing time for measuring the AIF from first-pass perfusion CMR images. This automated method is used to compare the impact of different AIF measurements on MBF quantification.Methods: Gadolinium-enhanced perfusion CMR was performed on a 1.5 T scanner using a saturation recovery dual-sequence technique. Rest and stress perfusion series from 270 clinical studies were analyzed. Automated image processing steps included motion correction, intensity correction, detection of the left ventricle (LV), independent component analysis, and LV pixel thresholding to calculate the AIF signal. The results were compared with manual reference measurements using several quality metrics based on the contrast enhancement and timing characteristics of the AIF. The median and 95 % confidence interval (CI) of the median were reported. Finally, MBF was calculated and compared in a subset of 21 clinical studies using the automated and manual AIF measurements.Results: Two clinical studies were excluded from the comparison due to a congenital heart defect present in one and a contrast administration issue in the other. The proposed method successfully processed 99.63 % of the remaining image series. Manual and automatic AIF time-signal intensity curves were strongly correlated with median correlation coefficient of 0.999 (95 % CI [0.999, 0.999]). The automated method effectively selected bright LV pixels, excluded papillary muscles, and required less processing time than the manual approach. There was no significant difference in MBF estimates between manually and automatically measured AIFs (p = NS). However, different sizes of regions of interest selection in the LV cavity could change the AIF measurement and affect MBF calculation (p = NS to p = 0.03).Conclusion: The proposed automatic method produced AIFs similar to the reference manual method but required less processing time and was more objective. The automated algorithm may improve AIF measurement from the first-pass perfusion CMR images and make quantitative myocardial perfusion analysis more robust and readily available