Solvation of cationic copper clusters in molecular hydrogen.

Multiply charged superfluid helium nanodroplets are utilized to facilitate the growth of cationic copper clusters (Cun+, where n = 1-8) that are subsequently solvated with up to 50 H2 molecules. Production of both pristine and protonated cationic Cu clusters are detected mass spectrometrically. A joint effort between experiment and theory allows us to understand the nature of the interactions determining the bonding between pristine and protonated Cu+ and Cu2+ cations and molecular hydrogen. The analysis reveals that in all investigated cationic clusters, the primary solvation shell predominantly exhibits a covalent bonding character, which gradually decreases in strength, while for the subsequent shells an exclusive non-covalent behaviour is found. Interestingly, the calculated evaporation energies associated with the first solvation shell markedly surpass thermal values, positioning them within the desirable range for hydrogen storage applications. This comprehensive study not only provides insights into the solvation of pristine and protonated cationic Cu clusters but also sheds light on their unique bonding properties.

Aggregation of coronene: the effect of carboxyl and amine functional groups.

The aggregation of coronene is relevant to understand the formation of carbon nanomaterials, including graphene quantum dots (GQDs) that show exceptional photophysical properties. This article evaluates the influence of carboxyl and amine substituting groups on the aggregation of coronene by performing a global optimization study based on a new potential energy surface. The structures of clusters with substituted coronene are similar to those formed by un-substituted monomers, that is, stacked (non-stacked) motifs are favoured for small-size (large-size) clusters. Nonetheless, the presence of carboxyl and amine groups leads to an increase of the number of local minima of comparable energy. The clusters with substituted monomers have also shown to enhance the attractive component interaction, which can be attributed to weak induction and charge transfer effects and to stronger electrostatic contributions. Moreover, the calculated height of magic-number structures of the clusters in this work is compatible with the morphology of the GQDs reported in the literature.

Impact of the SARS-CoV2 pandemic dissemination on the management of neuroendocrine neoplasia in Italy: a report from the Italian Association for Neuroendocrine Tumors (Itanet).

INTRODUCTION: The organization of the healthcare system has significantly changed after the recent COVID-19 outbreak, with a negative impact on the management of oncological patients. The present survey reports data collected by the Italian Association for Neuroendocrine Tumors on the management of patients with neuroendocrine neoplasia (NEN) during the pandemic dissemination. METHODS: A survey with 57 questions was sent to NEN-dedicated Italian centers regarding the management of patients in the period March 9, 2020, to May 9, 2020 RESULTS: The main modification in the centers' activity consisted of decreases in newly diagnosed NEN patients (- 76.8%), decreases in performed surgical procedures (- 58%), delays to starting peptide receptor radionuclide therapy (45.5%), postponed/canceled follow-up examinations (26%), and canceled multidisciplinary teams' activity (20.8%). A low proportion of centers (< 10%) reported having to withdraw systemic anti-tumor medical treatment due to concerns about the pandemic situation, whereas PRRT was withdrawn from no patients. CONCLUSION: Although the COVID-19 outbreak induced the centers to reduce some important activities in the management of NEN patients, the Italian network was able to provide continuity in care without withdrawing anti-tumor treatment for the majority of patients.

Aggregation enhancement of coronene molecules by seeding with alkali-metal ions.

Microsolvation constitutes the first step in the formation of cluster structures of molecules that surround a solute in the bulk and it allows for a deep insight into the relationship between the structure of the solvation shells and other physical properties. We propose semiempirical potential energy functions that are able to describe the interaction between K+ or Cs+ with coronene. Such functions were calibrated through the comparison with accurate estimations of the interaction between the cation and the planar hydrocarbon, obtained by means of ab initio electronic-structure calculations. By employing the potential energy functions and an evolutionary algorithm (EA), we have investigated the structure and energetics of the clusters resulting from the microsolvation of either K+ or Cs+ with coronene molecules. The reliability of the results for smaller clusters was checked by performing geometry re-optimization exploiting a suitable DFT level of theory. This has allowed for the characterization of the first solvation shells of planar molecules of coronene around an alkali-metal ion. It has also been found that the presence of metal ion impurities considerably enhances the formation of small coronene clusters leading to much stronger binding energies for heterogeneous with respect to homogeneous aggregates. These clusters could represent relevant species involved in the early stages of soot nucleation.

Transgenerational inheritance of chronic adolescent stress: Effects of stress response and the amygdala transcriptome.

Adolescent stress can impact health and well-being not only during adulthood of the exposed individual but even in future generations. To investigate the molecular mechanisms underlying these long-term effects, we exposed adolescent males to stress and measured anxiety behaviors and gene expression in the amygdala-a critical region in the control of emotional states-in their progeny for two generations, offspring and grandoffspring. Male C57BL/6 mice underwent chronic unpredictable stress (CUS) for 2 weeks during adolescence and were used to produce two generations of offspring. Male and female offspring and grandoffspring were tested in behavioral assays to measure affective behavior and stress reactivity. Remarkably, transgenerational inheritance of paternal stress exposure produced a protective phenotype in the male, but not the female lineage. RNA-seq analysis of the amygdala from male offspring and grandoffspring identified differentially expressed genes (DEGs) in mice derived from fathers exposed to CUS. The DEGSs clustered into numerous pathways, and the "notch signaling" pathway was the most significantly altered in male grandoffspring. Therefore, we show that paternal stress exposure impacts future generations which manifest in behavioral changes and molecular adaptations.

Transgenerational effects of maternal bisphenol: a exposure on offspring metabolic health.

Exposure to the endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with health abnormalities that persist in subsequent generations. However, transgenerational effects of BPA on metabolic health are not widely studied. In a maternal C57BL/6J mice (F0) exposure model using BPA doses that are relevant to human exposure levels (10 µg/kg/day, LowerB; 10 mg/kg/day, UpperB), we showed male- and dose-specific effects on pancreatic islets of the first (F1) and second generation (F2) offspring relative to controls (7% corn oil diet; control). In this study, we determined the transgenerational effects (F3) of BPA on metabolic health and pancreatic islets in our model. Adult F3 LowerB and UpperB male offspring had increased body weight relative to Controls, however glucose tolerance was similar in the three groups. F3 LowerB, but not UpperB, males had reduced ß-cell mass and smaller islets which was associated with increased glucose-stimulated insulin secretion. Similar to F1 and F2 BPA male offspring, staining for markers of T-cells and macrophages (CD3 and F4/80) was increased in pancreas of F3 LowerB and UpperB male offspring, which was associated with changes in cytokine levels. In contrast to F3 BPA males, LowerB and UpperB female offspring had comparable body weight, glucose tolerance and insulin secretion as Controls. Thus, maternal BPA exposure resulted in fewer metabolic defects in F3 than F1 and F2 offspring, and these were sex- and dose-specific.

A global optimization perspective on molecular clusters.

Although there is a long history behind the idea of chemical structure, this is a key concept that continues to challenge chemists. Chemical structure is fundamental to understanding most of the properties of matter and its knowledge for complex systems requires the use of state-of-the-art techniques, either experimental or theoretical. From the theoretical view point, one needs to establish the interaction potential among the atoms or molecules of the system, which contains all the information regarding the energy landscape, and employ optimization algorithms to discover the relevant stationary points. In particular, global optimization methods are of major importance to search for the low-energy structures of molecular aggregates. We review the application of global optimization techniques to several molecular clusters; some new results are also reported. Emphasis is given to evolutionary algorithms and their application in the study of the microsolvation of alkali-metal and Ca2+ ions with various types of solvents.This article is part of the themed issue 'Theoretical and computational studies of non-equilibrium and non-statistical dynamics in the gas phase, in the condensed phase and at interfaces'.

Enhanced Flexibility of the O2 + N2 Interaction and Its Effect on Collisional Vibrational Energy Exchange.

Prompted by a comparison of measured and computed rate coefficients of Vibration-to-Vibration and Vibration-to-Translation energy transfer in O2 + N2 non-reactive collisions, extended semiclassical calculations of the related cross sections were performed to rationalize the role played by attractive and repulsive components of the interaction on two different potential energy surfaces. By exploiting the distributed concurrent scheme of the Grid Empowered Molecular Simulator we extended the computational work to quasiclassical techniques, investigated in this way more in detail the underlying microscopic mechanisms, singled out the interaction components facilitating the energy transfer, improved the formulation of the potential, and performed additional calculations that confirmed the effectiveness of the improvement introduced.

Efficiency of Collisional O2 + N2 Vibrational Energy Exchange.

By following the scheme of the Grid Empowered Molecular Simulator (GEMS), a new O2 + N2 intermolecular potential, built on ab initio calculations and experimental (scattering and second virial coefficient) data, has been coupled with an appropriate intramolecular one. On the resulting potential energy surface detailed rate coefficients for collision induced vibrational energy exchanges have been computed using a semiclassical method. A cross comparison of the computed rate coefficients with the outcomes of previous semiclassical calculations and kinetic experiments has provided a foundation for characterizing the main features of the vibrational energy transfer processes of the title system as well as a critical reading of the trajectory outcomes and kinetic data. On the implemented procedures massive trajectory runs for the proper interval of initial conditions have singled out structures of the vibrational distributions useful to formulate scaling relationships for complex molecular simulations.

Low-energy structures of benzene clusters with a novel accurate potential surface.

The benzene-benzene (Bz-Bz) interaction is present in several chemical systems and it is known to be crucial in understanding the specificity of important biological phenomena. In this work, we propose a novel Bz-Bz analytical potential energy surface which is fine-tuned on accurate ab initio calculations in order to improve its reliability. Once the Bz-Bz interaction is modeled, an analytical function for the energy of the Bzn clusters may be obtained by summing up over all pair potentials. We apply an evolutionary algorithm (EA) to discover the lowest-energy structures of Bzn clusters (for n=2-25), and the results are compared with previous global optimization studies where different potential functions were employed. Besides the global minimum, the EA also gives the structures of other low-lying isomers ranked by the corresponding energy. Additional ab initio calculations are carried out for the low-lying isomers of Bz3 and Bz4 clusters, and the global minimum is confirmed as the most stable structure for both sizes. Finally, a detailed analysis of the low-energy isomers of the n = 13 and 19 magic-number clusters is performed. The two lowest-energy Bz13 isomers show S6 and C3 symmetry, respectively, which is compatible with the experimental results available in the literature. The Bz19 structures reported here are all non-symmetric, showing two central Bz molecules surrounded by 12 nearest-neighbor monomers in the case of the five lowest-energy structures.

Chemical Interactions and Spin Structure in (O2)4: Implications for the ε-O2 Phase.

The chemical interactions and spin structure of (O2)4 in its ground singlet state are analyzed by means of Quantum Chemical Topology descriptors. The energetic contributions of the Interacting Quantum Atoms approach are used to obtain information about the class of interactions displayed along the dissociation path of (O2)4. The exchange-correlation contribution to the binding energy is non-negligible for the O2-O2 interactions at intermolecular distances close to those found for the pressure induced ε phase of solid (O2) and this strengthening of the intermolecular bonding is built up from a simultaneous weakening of the intramolecular bond. This result is of interest in connection with the observed softening of the IR vibron frequency in the lower pressure range of the ε phase. The spin structure in the real space along the dissociation process is interpreted with the help of the so-called electron number distribution functions. At large distances, the four triplet O2 molecules are arranged in a way consistent with an antiferromagnetic structure, whereas at short distances, a significant spin redistribution is driven by the exchange process and it involves a propensity toward a null magnetic moment per molecule. Such probability behavior can be related with the magnetic evolution of solid oxygen across the δ → ε phase transition. Additional calculations of (O2)4 excited states support the conclusion that the relative stabilization and magnetic features of the ground singlet state are due to the onset of the new intermolecular bonds, and not to an exclusive modification of the electronic character within the O2 molecules.

Quantitative evaluation on [9°Y] DOTATOC PET and SPECT imaging by phantom acquisitions and clinical applications in locoregional and systemic treatments.

AIM: The aim of this paper was to compare [9°Y]-PET and SPECT imaging quantification for dosimetric applications in targeted radionuclide therapy. METHODS: Imaging studies were carried out by SPECT-CT and PET equipment performing phantom tests first. [9°Y]-SPECT and PET scans were compared in terms of sensitivity, minimum detectable activity concentration, recovery coefficients (RCs) and system spatial resolution (FWHM). Quantitative evaluations by PET and SPECT acquisitions were then assessed in patients who received therapeutic activity of [9°Y]-DOTATOC directly injected into the surgical cavity by locoregional route in glioma treatment and by systemic route in neuroendocrine tumour patients who underwent intravenous infusion. Finally 3D-dose distributions by SPECT and PET images were obtained. RESULTS: Sensitivity was proven to be about fivefold higher for SPECT than for PET. To obtain a good-quality PET imaging, the minimum detectable activity concentration was determined to be equal to 1 MBq/mL compared with 0.05 MBq/mL that was sufficient to assess adequate SPECT imaging. RCs were 100% for volume ≥ 25.5 mL for PET and ≥ 110 mL for SPECT. FWHM was 7 mm for PET and 19 mm for SPECT scans. With regard to locoregional therapy, excellent imaging was obtained with both PET and SPECT. On the contrary, systemic administration did not permit us to obtain suitable PET imaging. PET and SPECT images were affected by considerable noise, whose influence is much more important in the quantitative evaluation of dose volume histograms rather than in the visual interpretation of images. CONCLUSION: [9°Y]-activity quantification is feasible by SPECT and PET imaging. For clinical applications, SPECT-CT is the best technique for visualizing the radiopharmaceuticals following systemic infusion, while both SPECT and PET scans are effective in analyzing locoregional distribution. Nevertheless PET study demonstrates the best spatial definition.

Short-term changes in the optic nerve head and visual field after trabeculectomy.

UNLABELLED: AIMS OR PURPOSE: To evaluate short-term changes in optic nerve head topography and visual field induced by surgical reduction of intraocular pressure. METHODS: A prospective study was performed on 56 eyes of 56 patients with uncontrolled primary open-angle glaucoma despite maximum medical therapy, which underwent trabeculectomy. Optic nerve head evaluations by means of Heidelberg Retina Tomograph, and visual field tests were performed pre-operatively, and at 3 and 6 months after surgery. Differences in intraocular pressure, visual field indices, and Heidelberg Retina Tomograph parameters were evaluated with the t-test for paired data. A linear regression model was calculated to analyze the relationship between intraocular pressure reduction and visual field changes, and optic nerve head changes. RESULTS: Mean intraocular pressure decreased from 24.4 ± 5.0 mm Hg to 12.1 ± 3.1 mm Hg (month 3, P<0.001), and 10.6 ± 2.8 mm Hg (month 6, P<0.001) after trabeculectomy. Mean retinal nerve fiber layer thickness (baseline, 0.19 ± 0.034; month 3, 0.24 ± 0.039, P=0.05; month 6, 0.21 ± 0.037, P=0.05) showed a statistical significant change compared with baseline values. CONCLUSIONS: In this 6-months study, a significant increase in retinal nerve fiber layer thickness was detected after glaucoma filtration surgery.

"For export only" medicines come back to Europe: a RP-LC method for the screening of six glucocorticoids in illegal and counterfeit anti-inflammatory and lightening creams.

"For export only" anti-inflammatory and lightening creams are medicinal products sold in African countries for their skin whitening action. In the last years, Rapid Alerts from European Medicinal Regulatory Agencies evidenced the presence of a large number of illegal and counterfeit anti-inflammatory products advertised for their whitening action on black skin in the European market. These drugs, containing glucocorticoids, are illegally sold in Europe in unauthorized ethno-cosmetics-shops and mainly bought by immigrants. This paper reports a new RP-LC method for the rapid simultaneous screening of six different active ingredients in anti-inflammatory and whitening products (creams, ointment and suspension): betamethasone dipropionate, dexamethasone, fluocinonide, fluocinolone acetonide, clobetasol propionate, methyl-prednisolone acetate. The method was developed and validated in view of its possible application in quality control laboratories, mainly those appointed to the control of illegal/counterfeit medicinal products. The associated measurement uncertainty was calculated from validation data. The method was then applied to the analysis of whitening products obtained from the Italian illegal market.

Dosimetry for treatment with radiolabelled somatostatin analogues. A review.

Peptide Receptor Radionuclide Therapy (PRRT) has proven its efficacy in the treatment of neuroendocrine and other somatostatin receptor expressing tumours (SR-tumours). Several clinical trials have confirmed that adverse effects are represented by possible renal impairment, which is the major concern, and low but not absent hematological toxicity. High kidney irradiation is a constant, despite the sparing of dose obtained by renal protectors. Hematological toxicity, although low, needs to be monitored. The clinical and dosimetry results collected in more than a decade have recognized weak points to unravel, increased knowledge, offering new views. When planning therapy with radiopeptides, the large patients' variability as for biodistribution and tumour uptake must be taken into account in order to tailor the therapy, or at least to avoid foreseeable gross treatments. Reliable and personalized dosimetry is more and more requested. This paper reviews through the literature the methods to study the biokinetics, the dosimetry outcomes, some clue information and correlations obtained once applying the radiobiological models. Special focus is given on recent improvements and indications for critical organ protection that light up challenging perspectives for PRRT.

A bond-bond description of the intermolecular interaction energy: the case of the weakly bound acetylene-hydrogen complex.

A new semiempirical potential energy surface (PES) for the acetylene-hydrogen system has been derived by using the recently introduced bond-bond methodology. The proposed PES, expressed in an analytic form suitable for molecular dynamics simulations, involves a limited number of parameters, each one having a physical meaning and allowing the accurate description of the system also in the less stable configurations. The analysis of novel integral cross sections data, measured with nearly effusive molecular beams, combined with that of available pressure broadening coefficients of isotropic Raman lines at 143 K and IR lines at 173 and 295 K of C(2)H(2) in H(2), provides a test of the reliability of the proposed PES and suggests also some refinements. An extensive comparison with a recent ab initio potential is also exploited.

A bond-bond description of the intermolecular interaction energy: the case of weakly bound N(2)-H(2) and N(2)-N(2) complexes.

The atom-bond pairwise additive approach, recently introduced by us to describe the potential energy surface for atom-molecule cases, is extended here for the first time to molecule-molecule systems. The idea is to decompose the van der Waals interaction energy into bond-bond pair contributions. This must be considered an improvement with respect to the familiar atom-atom pairwise additive representation since, still using a simple formulation, it indirectly accounts for three body effects. Such an approach also allows to include, in a straightforward way, the effect of the bond length on the intermolecular interaction energy. Cases of study are the weakly bound complexes involving the H(2) and N(2) molecules, namely N(2)-H(2) and N(2)-N(2), here described as a single bond-bond pair. For both systems ab initio calculations and experimental molecular beam scattering data, as well as second virial coefficients, have been employed to test the accuracy of the chosen representation of the interaction and to improve the obtained potential energy surfaces. The results of this work are important also for the generalization to the cases involving molecular ions and polyatomic molecules.

An LC method for the simultaneous screening of some common counterfeit and sub-standard antibiotics Validation and uncertainty estimation.

Pharmaceutical counterfeiting is a worldwide public health problem, often under-recognised, especially in developing countries where the percentage of counterfeit and sub-standard medicines is dramatically high. Antibiotics, among the most widespread drugs, have been particularly targeted by counterfeiters. World Health Organization emphasizes the need for development and distribution of screening methods explicitly targeted to counterfeit drugs. In this paper is presented a single method for the simultaneous analysis of some of the most common and counterfeited essential antibiotics: ampicillin, amoxicillin+clavulanic acid, doxycycline, cloxacillin, chloramphenicol. A full validation was performed in terms of linearity, precision, robustness and trueness; an assessment of uncertainty was carried out exploiting these data. A wide linearity range was investigated considering the specific nature of counterfeit and sub-standard drugs, whose content in active substance may be rather far from the declared amount. A large span in robustness parameters was considered and a complete intermediate precision assessment was conducted, envisaging the possibility of transferring the method to quality control laboratories, hopefully in developing countries. Finally, the method was successfully applied to the analysis of antibiotics purchased on the informal market in Chad, among which counterfeit and sub-standard samples were detected.

Institutional guidelines and ongoing studies in management of liver tumours: the experience of the European Institute of Oncology.

BACKGROUND: An institutional task force on upper gastrointestinal tumours is active at the European Institute of Oncology (EIO). Members decided to collate the institutional guidelines on management of liver tumours (primary and metastatic) into a document. This article is aimed at presenting the current treatment guidelines as well as ongoing research protocols and trials in this field at the EIO. METHODS: A steering committee convened to assign tasks to individual members. Contributions from experts in each treatment area were collated in a single document, in order to produce a draft for subsequent review from the aforementioned committee. Six drafts have been discussed and the final version approved. RESULTS: Surgical, medical oncology, interventional radiology, nuclear medicine and radiation therapy approaches, their roles in management of liver tumours and ongoing research trials are presented and discussed in this article. CONCLUSIONS: At the EIO a multi-disciplinary integrated approach to liver tumours is standard and several ongoing research projects are currently active in this field.