Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach

Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.     

Analgesic,Anxiolytic and Anaesthetic Effects of Melatonin: New Potential Uses in Pediatrics

Exogenous melatonin is used in a number of situations, first and foremost in the treatment of sleep disorders and jet leg. However, the hypnotic, antinociceptive, and anticonvulsant properties of melatonin endow this neurohormone with the profile of a drug that modulates effects of anesthetic agents, supporting its potential use at different stages during anesthetic procedures, in both adults and children. In light of these properties, melatonin has been administered to children undergoing diagnostic procedures requiring sedation or general anesthesia, such as magnetic resonance imaging, auditory brainstem response tests and electroencephalogram. Controversial data support the use of melatonin as anxiolytic and antinociceptive agents in pediatric patients undergoing surgery. The aim of this review was to evaluate available evidence relating to efficacy and safety of melatonin as an analgesic and as a sedative agent in children. Melatonin and its analogs may have a role in antinociceptive therapies and as an alternative to midazolam in premedication of adults and children, although its effectiveness is still controversial and available data are clearly incomplete.     

3D‐Printing of High‐κ Thiol‐Ene Resins with Spiro‐Orthoesters as Anti‐Shrinkage Additive

Tri(ethylene glycol) divinyl ether and the spiro‐orthoester 2‐((allyloxy)methy)‐1,4,6‐trioxospiro[4.4]nonane can be formulated in different ratios and crosslinked by thiol‐ene reactions. The spiro‐orthoester is used as anti‐shrinkage additive, enabling shrinkage reduction of up to 39%. Addition of a radical photoinitiator for the thiol‐ene reaction and a cationic photoinitiator for the double ring‐opening of the spiro‐orthoester enables dual‐curing for application in 3D‐printing. The formulation free of the spiro‐orthoester shows gelation during the printing process and, correspondingly, low resolution. The formulations containing the spiro‐orthoester exhibit higher resolutions in the range of 50 µm. The resins containing mixtures of tri(ethylene glycol) divinyl ether and the spiro‐orthoester show permittivities as high as 10⁴. The dielectric loss factor of the resins is in the range of 0.5–7.6, and the conductivity in the range of 1.3?10^?11 to 2.0?10^?11 S cm^?1. These high‐κ materials can be 3D‐printed by digital light processing for the next generation of electronic materials.     

Glycidols Esters, 2-Chloropropane-1,3-Diols,and 3-Chloropropane-1,2-Diols Contents in Real Olive Oil Samples and their Relation with Diacylglycerols

A series of authentic virgin, refined, and mixtures of olive oils was analyzed for their content of 2-and 3-chloropropanediol (MCPD) esters expressed as 2−/3-MCPD, glycidol (and related glycidyl esters) (GE), and diglycerides (DAG). High concentrations of MCPD and GE were found, above all, in pomace oils, which come from the poorer starting raw materials, while virgin olive oils, as expected, do not contain any process contaminant. On the other hand, DAGs are present in all samples, demonstrating that their involvement in the formation of such contaminants only occurs when temperatures are higher than that used during the refining steps. The lack of correlation between the amounts of MCPD and GE can be ascribed to their completely different chemical stability as the epoxy ring of the GE opens easily, leading to both short-chain derivatives and/or MCPD itself. This finding can also explain the data about the absence of 2-MCPD in all the analyzed oil samples: other than the statistical probability and the steric effect of the SN2 formation mechanism, both in favor of the 3- derivative, we have also to consider the MCPD formation pathway involving glycidol that, under opportune conditions of refining, can increase the whole amount of 3-MCPD (under thermodynamic control, 3-MCPD is more stable).     

Hydrogen Production by the Thermophilic Bacterium Thermotoga neapolitana

As the only fuel that is not chemically bound to carbon, hydrogen has gained interest as an energy carrier to face the current environmental issues of greenhouse gas emissions and to substitute the depleting non-renewable reserves. In the last years, there has been a significant increase in the number of publications about the bacterium Thermotoga neapolitana that is responsible for production yields of H₂ that are among the highest achievements reported in the literature. Here we present an extensive overview of the most recent studies on this hyperthermophilic bacterium together with a critical discussion of the potential of fermentative production by this bacterium. The review article is organized into sections focused on biochemical, microbiological and technical issues, including the effect of substrate, reactor type, gas sparging, temperature, pH, hydraulic retention time and organic loading parameters on rate and yield of gas production.     

On the Linear Structure of Betting Criterion and the Checking of Coherence

We use imprecise probabilities, based on a concept of generalized coherence, for the management of uncertainty in artificial intelligence. With the aim of reducing the computational difficulties, in the checking of generalized coherence we propose a method which exploits, in the framework of the betting criterion, suitable subsets of the sets of values of the random gains. We give an algorithm in each step of which a linear system with a reduced number of unknowns can be used. Our method improves a procedure already existing in literature and could be integrated with recent approaches of other authors, who exploit suitable logical conditions with the aim of splitting the problem into subproblems. We remark that our approach could be also used in combination with efficient methods like column generation techniques. Finally, to illustrate our method, we give some examples.     

Relative quantification of <Emphasis Type="Italic">Vitis vinifera</Emphasis> L. varieties in musts by microsatellite DNA analysis

Varietal wines are defined as made primarily from a single variety of grape, which is identified on the label. However the inclusion of other varieties in their production is permitted under defined percentages. The fact that different grape varieties/varietal wines present far different economical values can attract fraudulent practices. Thus the development of methods, which allow the quantification of those varieties, is of crucial importance. The first approach to the method for the relative quantification of must containing two varieties based on microsatellite DNA analysis is presented. Quantification was achieved by densitometry measurements of the amplification products of the pooled varieties, obtained with loci VVMD6 and VVMD7, after their separation and staining on polyacrilamide gels. We have found that a good correlation between the proportion of each variety in must and the signal intensity of the alleles are dependent on the variety (varietal effect) and the microsatellite locus used. The relative quantification of musts can be accomplished by the presented method depending on the presence of overlapping alleles, and the composition of the varieties and their relative amounts.     

Diffusion bonding of SU 263

Using a specially constructed apparatus, diffusion bonding of SU 263 alloy was studied in the temperature range of 1123–1323 K and compressive stress of 90% of its yield strength at the corresponding temperatures to determine the relative importance of the process parameters, the mechanism(s) responsible for bonding and the joint characteristics. Bond quality was assessed by optical metallography and lap shear testing. The mechanism of bonding was evaluated by grain growth equation. The experimental results were compared with a model developed by Pilling [Pilling, J., 1988. The kinetics of isostatic diffusion bonding in superplastic materials. Mater. Sci. Eng. 100, 137–144] in which the void closure by creep flow and diffusion are considered. Quantified EPMA line scan analysis was carried out to confirm the bonding mechanism and to determine the composition at the interface.