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Immunotherapy delivered a new therapeutic option to oncologist: Ipilimumab (anti-CTLA-4), Nivolumab and Pembrolizumab (anti-PD1) and Atezolizumab (anti-PD-L1) increase overall survival and show a better safety profile compared to chemotherapy in patients with metastatic melanoma, lung, renal cancer among others. But all that glitters is not gold and there is an increasing number of reports of adverse effect while using Immune-checkpoint inhibitors. While chemotherapy could weaken the immune system, this novel immunotherapy could hiper-activate it, resulting in a unique and distinct spectrum of adverse events, called Immunes-related adverse events irAEs. irAEs ranging from mild to potentially lifethreatening events can involve many systems, and their management is radically different from that of cytotoxic drugs: immunosuppressive treatments, such as corticoids, infliximab or mycophenolate mofetil usually results in complete reversibility, but failing to do so can lead to severe toxicity or even death. Patient selection is an indirect way to reduce adverse events minimizing the number of subjects exposed to this drugs: unfortunately PDL-1, the actual predictive biomarker wouldn’t allow clinicians select or exclude patients for treatment with checkpoint inhibitors.

Most of the biological and application-oriented studies of synthetic melanins have so far been performed on commercial materials or on dopa melanins with low DHICA content, although it is well known that DHICA is a key constituent of human pigments. Recently, it has been reported that DHICA melanin exhibits potent hydroxyl radical-scavenging properties in the Fenton reaction, whereas DHI melanin does not (Jiang et al., Free Radic. Biol. Med. 2010, 48, 1144–1151). We show now that synthetic DHICA melanin is a highly efficient antioxidant compared to other synthetic eumelanins, proving to be a more efficient scavenger than DHI or dopa melanin in the 1,1-diphenyl- 2-picrylhydrazyl (DPPH), 2,2′-azinobis(3-ethylbenzothiazoline-6- sulfonic acid) (ABTS), and nitric oxide (NO) scavenging assays. Analysis of the optical, paramagnetic and morphological properties of DHICA melanin revealed features far different from those of DHI and dopa melanins. These can be accounted for by prevalent intermolecular interactions compensating for conformationally-hindered p-electron delocalization across the polymer backbone. Thus the somewhat counterintuitive conclusion is that the efficient antioxidant properties of DHICA melanin would be primarily determined by non-planar structures with monomer-like behavior and weak aggregating interactions. Formation of weak aggregates may account moreover for a greater accessibility of free radicals to DHICA compared to compact p- stacked DHI and dopa melanins. These results offer the first chemical explanation as to why Nature selected DHICA to confer (photo)protective properties to skin melanins, a fundamental conundrum of human pigmentation, and provide unprecedented insights to orient the design and to engineer eumelanins with superior antioxidant properties for diverse applications.

In the Mediterranean Sea, the biological invasion by the green algae Caulerpa racemosa var. cylindracea is maybe the most striking marine sea-bottom landscape change of the last decades. In this paper, we have synthesized the results of 5 years of studies about the C. cylindracea effects on fish of ecological and economic importance, such as the white sea bream Diplodus sargus. We found that a secondary metabolite of C. cylindracea has the potential to enter in trophic chains and accumulate in fish tissues. Ecotoxicological analyses made on tissues of the D. sargus specimens showed alterations of some of main antioxidant systems, such as catalase, glutathione peroxidases and total glutathione, and a significant induction of P450 biotransformation system. We found also that the C. cylindracea based-diet can alter muscle fatty acids composition in the white sea bream by reducing the percentage of polyunsaturated fatty acids (PUFA) of the n-3 and n-6 series, such as eicosapentaenoic (EPA, C20:5), docosahexaenoic (DHA, C22:6) and arachidonic acids (AA, C20:4). On the whole, this work sheds light on an unexplored and critical aspect of biological invasions with implication on the health of both humans and the environment.

A numerical methodology to simulate the high pressure spray evolution and the fuel-air mixing in Diesel engines is presented. Attention is focused on the employed atomization model, a modified version of the Huh and Gosman, on the definition of a turbulence length scale limiter and of an adaptive local mesh refinement technique to minimize the result grid dependency. All the discussed models were implemented into Lib-ICE, which is a set of libraries and solvers, specifically tailored for engine simulations, which runs under the open-source CFD technology OpenFOAM. To provide a comprehensive assessment of the proposed methodology, the validation procedure consisted into simulating, with a unique and coherent set-up of all models, two different set of experiments: a non-evaporating Diesel fuel spray in a constant-volume vessel with optical access and an evaporating non-reacting Diesel fuel spray in an optical engine. The first of these experiments were carried out by the authors by analyzing optical pictures of the jets taken at different instants by imaging technique. A Common-Rail based injection apparatus was used for injecting commercial Diesel fuel at pressures ranging from 50 to 123 MPa inside a constant volume vessel at engine-like density conditions and operating in single shot mode. Literature data were then used to validate the vapor fuel-air mixing at engine conditions.

CFD codes are now widely used to investigate the in-cylinder thermofluid-dynamic processes. Despite the availability of complex physical models, the results are strongly influenced by the mesh quality, which should be kept high for the whole simulation even in presence of extreme boundary deformations like valve penetration into the piston bowl or piston approaching the cylinder head at the top dead center. For this reason the whole simulation is generally covered by using a different number of meshes and each one of them is used for a certain crank angle interval. This provides good mesh quality and resolution when efficient algorithms for field mapping and grid point motion are available: interpolation-related errors should be avoided and the number of target meshes should be kept at minimum to reduce the user turnaround time required for mesh generation and motion. In this context, the authors have implemented in the OpenFOAM code moving mesh algorithms for internal combustion engine simulations. The grid points motion is described by a vertex-based unstructured mesh motion solver: the Laplace equation of motion is solved with variable diffusion on the mesh vertices, using a Finite Element method with polyhedral cell support. This guarantees that an initial valid mesh remains valid for arbitrary boundary motion. Different expressions for the motion diffusion can be used to improve the quality of the mesh during motion. A cell based, distance weighted interpolation technique is used to interpolate the geometric fields from the source to the target mesh. The proposed approach has been applied to simulate the in-cylinder flows in different engine geometries. Firstly a flat-head geometry with a centrally located valve was used to evaluate the efficiency of the field mapping and mesh motion algorithms. Then two real engine configurations were modeled: for both of them the simulation of the intake, compression and combustion phases was performed and a comparison with experimental data of in-cylinder pressure is provided.

The use of implantable medical devices has increased in “modern” medical and surgical practice, and the rate of their infections is variable, depending on the type of device and the population risk profile. The overall risk of device-related infection across the population is around 1%, but it might be significantly increased in specific populations as vulnerability to microbial pathogens increases in elderly, immuno-compromised, and hospitalized patients. Device-related infection results from the multifaceted interaction of bacterial, device, and host factor. Multiresistant nosocomial pathogens are the most common organisms colonizing the surface of devices, and a full understanding of how a biofilm formation is crucial to understand the pathogenesis of their infection and define the most suitable treatment. This chapter describes the most relevant implantable medical devices of interest to nuclear medicine and the corresponding diagnostic strategy for each of them with particular regard to the role of nuclear medicine procedure in the diagnostic algorithm.

Cardiovascular infections are associated with high morbidity and mortality. Early diagnosis is crucial for adequate patient’s management, as early treatment improves the prognosis. Cardiovascular infections are difficult to diagnose on the basis of a single symptom, sign, or diagnostic test. Rather, the diagnosis requires a multidisciplinary discussion in addition to the integration of clinical signs, microbiology data, and imaging data. The application of multimodality imaging, including molecular imaging techniques, has improved the sensitivity to detect infections involving heart valves and vessels and implanted cardiovascular devices, while also allowing for early detection of septic emboli and metastatic infections before these become clinically apparent. This chapter describes the main epidemiological, clinical, and diagnostic challenges in infective endocarditis and infections associated with cardiovascular implantable electronic devices, with particular regard to the role of WBC SPECT/CT and [18F]FDG PET/CT in each diagnostic algorithm. In addition, the needs of proper hybrid equipment, dedicated imaging acquisition protocols, specific expertise for imaging reading and imaging interpretations in this field are discussed, emphasizing the need of a specific reference framework within a cardiovascular multidisciplinary team approach.