Microemulsion Synthesis of Superparamagnetic Nanoparticles for Bioapplications

Superparamagnetic nanoparticles have seen increased potential in medical and environmental applications. Their preparation is traditionally made by the coprecipitation method, with limited control over the particle size distribution. Microemulsion methods could be advantageous due to the efficient control of the size, shape, and composition of the nanoparticles obtained. Water-in-oil (W/O) microemulsions consist of aqueous microdomains dispersed in a continuous oil phase, stabilized by surfactant molecules. These work as nanoreactors where the synthesis of the desired nanoparticles takes place through a co-precipitation chemical reaction. In this work, superparamagnetic magnetite nanoparticles with average diameters between 5.4 and 7.2 nm and large monodispersity have been synthesized through precipitation in a W/O microemulsion, with Cetyl Trimethyl Ammonium Bromide (CTAB) as a main surfactant, 1-butanol as a cosurfactant, and with 1-hexanol as the continuous oily phase. The optimization of the corresponding washing protocol has also been established since a strict control is required when using these materials for bioapplications. Their applicability in those has been proved by their encapsulation in liposomes, being tested as signal enhancers for lateral flow immunoassays by using the affinity neutravidin-biotin model system. Due to their magnetic behaviour, they were also tested for magnetic separation. These novel materials have been found to be useful for analytical applications requiring high sensitivity and the removal of interferences.     

The PI3Kδ Inhibitor Idelalisib Diminishes Platelet Function and Shows Antithrombotic Potential

Background: Clinical management of ischemic events and prevention of vascular disease is based on antiplatelet drugs. Given the relevance of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) as a candidate target in thrombosis, the main goal of the present study was to identify novel antiplatelet agents within the existing inhibitors blocking PI3K isoforms. Methods: We performed a biological evaluation of the pharmacological activity of PI3K inhibitors in platelets. The effect of the inhibitors was evaluated in intracellular calcium release and platelet functional assays, the latter including aggregation, adhesion, and viability assays. The in vivo drug antithrombotic potential was assessed in mice undergoing chemically induced arterial occlusion, and the associated hemorrhagic risk evaluated by measuring the tail bleeding time. Results: We show that PI3K Class IA inhibitors potently block calcium mobilization in human platelets. The PI3K p110δ inhibitor Idelalisib inhibits platelet aggregation mediated by ITAM receptors GPVI and CLEC-2, preferentially by the former. Moreover, Idelalisib also inhibits platelet adhesion and aggregation under shear and adhesion to collagen. Interestingly, an antithrombotic effect was observed in mice treated with Idelalisib, with mild bleeding effects at high doses of the drug. Conclusion: Idelalisib may have antiplatelet effects with minor bleeding effects, which provides a rationale to evaluate its antithrombotic efficacy in humans.     

PET and SPECT Imaging of the EGFR Family (RTK Class I) in Oncology

The human epidermal growth factor receptor family (EGFR-family, other designations: HER family, RTK Class I) is strongly linked to oncogenic transformation. Its members are frequently overexpressed in cancer and have become attractive targets for cancer therapy. To ensure effective patient care, potential responders to HER-targeted therapy need to be identified. Radionuclide molecular imaging can be a key asset for the detection of overexpression of EGFR-family members. It meets the need for repeatable whole-body assessment of the molecular disease profile, solving problems of heterogeneity and expression alterations over time. Tracer development is a multifactorial process. The optimal tracer design depends on the application and the particular challenges of the molecular target (target expression in tumors, endogenous expression in healthy tissue, accessibility). We have herein summarized the recent preclinical and clinical data on agents for Positron Emission Tomography (PET) and Single Photon Emission Tomography (SPECT) imaging of EGFR-family receptors in oncology. Antibody-based tracers are still extensively investigated. However, their dominance starts to be challenged by a number of tracers based on different classes of targeting proteins. Among these, engineered scaffold proteins (ESP) and single domain antibodies (sdAb) show highly encouraging results in clinical studies marking a noticeable trend towards the use of smaller sized agents for HER imaging.     

Infections and Immunotherapy in Lung Cancer: A Bad Relationship?

Infectious diseases represent a relevant issue in lung cancer patients. Bacterial and viral infections might influence the patients’ prognosis, both directly affecting the immune system and indirectly impairing the outcome of anticancer treatments, mainly immunotherapy. In this analysis, we aimed to review the current evidence in order to clarify the complex correlation between infections and lung cancer. In detail, we mainly explored the potential impact on immunotherapy outcome/safety of (1) bacterial infections, with a detailed focus on antibiotics; and (2) viral infections, discriminating among (a) human immune-deficiency virus (HIV), (b) hepatitis B/C virus (HBV-HCV), and (c) Sars-Cov-2. A series of studies suggested the prognostic impact of antibiotic therapy administration, timing, and exposure ratio in patients treated with immune checkpoint inhibitors, probably through an antibiotic-related microbiota dysbiosis. Although cancer patients with HIV, HBV, and HCV were usually excluded from clinical trials evaluating immunotherapy, some retrospective and prospective trials performed in these patient subgroups reported similar results compared to those described in not-infected patients, with a favorable safety profile. Moreover, patients with thoracic cancers are particularly at risk of COVID-19 severe outcomes and mortality. Few reports speculated about the prognostic implications of anticancer therapy, including immunotherapy, in lung cancer patients with concomitant Sars-Cov-2 infection, showing, to date, inconsistent results. The correlation between infectious diseases and immunotherapy remains to be further explored and clarified in the context of dedicated trials. In clinical practice, the accurate and prompt multidisciplinary management of lung cancer patients with infections should be encouraged in order to select the best treatment options for these patients, avoiding unexpected toxicities, while maintaining the anticancer effect.     

Kynurenine/Tryptophan Ratio as a Potential Blood-Based Biomarker in Non-Small Cell Lung Cancer

The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) degrade tryptophan (Trp) into kynurenine (Kyn) at the initial step of an enzymatic pathway affecting T cell proliferation. IDO1 is highly expressed in various cancer types and associated with poor prognosis. Nevertheless, the serum Kyn/Trp concentration ratio has been suggested as a marker of cancer-associated immune suppression. We measured Kyn and Trp in blood samples of a wide cohort of non-small-cell lung cancer (NSCLC) patients, before they underwent surgery, and analyzed possible correlations of the Kyn/Trp ratio with either IDO1 expression or clinical–pathological parameters. Low Kyn/Trp significantly correlated with low IDO1 expression and never-smoker patients; while high Kyn/Trp was significantly associated with older (≥68 years) patients, advanced tumor stage, and squamous cell carcinoma (Sqcc), rather than the adenocarcinoma (Adc) histotype. Moreover, high Kyn/Trp was associated, among the Adc group, with higher tumor stages (II and III), and, among the Sqcc group, with a high density of tumor-infiltrating lymphocytes. A trend correlating the high Kyn/Trp ratio with the probability of recurrences from NSCLC was also found. In conclusion, high serum Kyn/Trp ratio, associated with clinical and histopathological parameters, may serve as a serum biomarker to optimize risk stratification and therapy of NSCLC patients.     

Phasor‐FLIM analysis of Thioflavin T self‐quenching in Concanavalin amyloid fibrils

The formation of amyloid structures has traditionally been related to human neurodegenerative pathologies and, in recent years, the interest in these highly stable nanostructures was extended to biomaterial sciences. A common method to monitor amyloid growth is the analysis of Thioflavin T fluorescence. The use of this highly selective dye, diffused worldwide, allows mechanistic studies of supramolecular assemblies also giving back important insight on the structure of these aggregates. Here we present experimental evidence of self‐quenching effect of Thioflavin T in presence of amyloid fibrils. A significant reduction of fluorescence lifetime of this dye which is not related to the properties of analyzed amyloid structures is found. This result is achieved by coupling Fluorescence Lifetime Imaging Microscopy with phasor approach as suitable model‐free methods and constitute a serious warning that have to be taken in account if is dye is used for quantitative studies.     

Graphene and carbon nanotube structures supported on mesoporous xerogel carbon as catalysts for oxygen reduction reaction in proton-exchange-membrane fuel cells

Non-precious metal catalysts for the oxygen reduction reaction (ORR) in proton-exchange-membrane fuel cells (PEMFCs) were obtained by pyrolysis of iron citrate and polyacrylonitrile on mesoporous xerogel carbon support. Chemical-physical characterizations, electrochemical studies by the rotating disc electrode, and electrochemical tests in a PEMFC configuration demonstrated that the porosity of the pristine carbon promotes the formation of graphene and carbon nanotube structures featuring ORR catalytic activity.     

A framework for integrating multi-accuracy spatial data in geographical applications

In recent years the integration of spatial data coming from different sources has become a crucial issue for many geographical applications, especially in the process of building and maintaining a Spatial Data Infrastructure (SDI). In such context new methodologies are necessary in order to acquire and update spatial datasets by collecting new measurements from different sources. The traditional approach implemented in GIS systems for updating spatial data does not usually consider the accuracy of these data, but just replaces the old geometries with the new ones. The application of such approach in the case of an SDI, where continuous and incremental updates occur, will lead very soon to an inconsistent spatial dataset with respect to spatial relations and relative distances among objects. This paper addresses such problem and proposes a framework for representing multi-accuracy spatial databases, based on a statistical representation of the objects geometry, together with a method for the incremental and consistent update of the objects, that applies a customized version of the Kalman filter. Moreover, the framework considers also the spatial relations among objects, since they represent a particular kind of observation that could be derived from geometries or be observed independently in the real world. Spatial relations among objects need also to be compared in spatial data integration and we show that they are necessary in order to obtain a correct result in merging objects geometries.     

The policy of attraction. Comparing three cities on their policy toward international and nongovernmental organizations: The Hague,Geneva and Vienna

The Hague, Geneva and Vienna are three cities that historically grew into global centers, specialized in human rights, nonproliferation, security, and peace and justice-related topics. The aim of this paper is to compare the policy of these cities on international organizations (IOs) and international nongovernmental organizations (INGOs). These cities experience increased competition from other international cities hosting IOs and INGOs due to globalization. Therefore, the need exists to reformulate strategies in attracting and retaining IOs and INGOs. Through an intensive comparative method, this paper seeks to describe the parallels and differences between these three cities, concerning their strategies. Furthermore, it describes the current need to make use of well-coordinated lobbying strategies, policy networks and thematic policy coalitions in order to gain and retain IOs and INGOs in a successful way.     

A Comparative Life Cycle Assessment of Disposable and Reusable Packaging for the Distribution of Italian Fruit and Vegetables

Each year in Italy, millions of tons of fruits and vegetables are harvested, packed and transported to national and foreign retail outlets. Packaging is an essential component of this system, but what is its environmental impact? This study takes into consideration the delivery from the field to the retail outlet of 12 types of fruits and vegetables grown and harvested in Italy and sold in Italy and Europe. The study compares two different packaging and distribution systems: one‐way with corrugated boxes and reusable with plastic containers. A number of different scenarios were generated by combining the most diffused packaging sizes with the most important production and selling locations for each type of fruit and vegetable and by considering the specific route required to perform the transportation with each distribution system. The environmental impact of each system in each scenario has then been analysed using the life cycle assessment methodology. Two algorithms and a number of coefficients were derived to simplify data collection and impact analysis for all scenarios. This provides an easy tool to evaluate the potential environmental burden of the two alternative distribution systems in a specific scenario by taking into consideration only a few variables (such as size of packaging and transportation distance). These algorithms and coefficients are presented in the work, along with the process that led to their generation and with considerations about the main critical environmental aspects for both distribution systems. The work aims to suggest possible design solutions that can make each system more sustainable. Copyright © 2011 John Wiley & Sons, Ltd.