Chronically Sun-damaged Melanomas Express Low Levels of Nuclear Glutathione-S-transferase-π: An Epidemiological and Clinicopathological Study in Italy

The detoxifying enzyme glutathione–s–transferase pi (GST–π) is present in keratinocytes and melanocytes and exerts a protective role against tumour progression. Melanomas close to melanocytic naevus remnants occur less frequently on sun-exposed areas, whereas solar dermal elastosis, hallmark of chronic sun-damage, characterise melanomas on sun-exposed skin. We evaluated the expression of GST-π in 113 melanomas associated to melanocytic naevus remnants or to solar dermal elastosis, classified according to clinical characteristics, history of sun exposure, histological subtypes and AJCC staging. Chronically sun-damaged melanomas, identified by moderate–severe solar dermal elastosis, showed a lower nuclear GST-π expression and a higher thickness than those related to melanocytic naevus remnants (p < 0.03). Multivariate logistic regression analysis demonstrated that male gender and chronic sun-exposure are independent risk factors significantly associated to melanomas localised on the trunk (OR = 3.36, 95% CI: 1.31–8.65; OR = 5.97, 95% CI: 1.71–20.87). If confirmed on a larger series, lower expression of nuclear GST-π in melanom

Toward a simulation approach for alkene ring-closing metathesis : scope and limitations of a model for RCM

A published model for revealing solvent effects on the ring-closing metathesis (RCM) reaction of di-Et diallylmalonate 7 has been evaluated over a wider range of conditions, to assess its suitability for new applications. Unfortunately, the model is too flexible and the published rate consts. do not agree with exptl. studies in the literature. However, by fixing the values of important rate consts. and restricting the concn. ranges studied, useful conclusions can be drawn about the relative rates of RCM of different substrates, precatalyst concn. can be simulated accurately and the effect of precatalyst loading can be anticipated. Progress has also been made toward applying the model to precatalyst evaluation, but further modifications to the model are necessary to achieve much broader aims

Charged particle decay of hot and rotating 88^{88}Mo nuclei in fusion-evaporation reactions

A study of fusion-evaporation and (partly) fusion-fission channels for the $^{88}$Mo compound nucleus, produced at different excitation energies in the reaction $^{48}$Ti + $^{40}$Ca at 300, 450 and 600 MeV beam energies, is presented. Fusion-evaporation and fusion-fission cross sections have been extracted and compared with the existing systematics. Experimental data concerning light charged particles have been compared with the prediction of the statistical model in its implementation in the Gemini++ code, well suited even for high spin systems, in order to tune the main model parameters in a mass region not abundantly covered by exclusive experimental data. Multiplicities for light charged particles emitted in fusion evaporation events are also presented. Some discrepancies with respect to the prediction of the statistical model have been found for forward emitted $\alpha$-particles; they may be due both to pre-equilibrium emission and to reaction channels (such as Deep Inelastic Collisions, QuasiFission/QuasiFusion) different from the compound nucleus formation.Comment: 14 pages, 14 figure

Theory of Light Hydrogenlike Atoms

The present status and recent developments in the theory of light hydrogenic atoms, electronic and muonic, are extensively reviewed. The discussion is based on the quantum field theoretical approach to loosely bound composite systems. The basics of the quantum field theoretical approach, which provide the framework needed for a systematic derivation of all higher order corrections to the energy levels, are briefly discussed. The main physical ideas behind the derivation of all binding, recoil, radiative, radiative-recoil, and nonelectromagnetic spin-dependent and spin-independent corrections to energy levels of hydrogenic atoms are discussed and, wherever possible, the fundamental elements of the derivations of these corrections are provided. The emphasis is on new theoretical results which were not available in earlier reviews. An up-to-date set of all theoretical contributions to the energy levels is contained in the paper. The status of modern theory is tested by comparing the theoretical results for the energy levels with the most precise experimental results for the Lamb shifts and gross structure intervals in hydrogen, deuterium, and helium ion $He^+$, and with the experimental data on the hyperfine splitting in muonium, hydrogen and deuterium.Comment: 230 pages, 106 figures, 24 tables. Discussion of muonic hydrogen is added, list of references expanded, some minor corrections and amendment

Complications and Mortality Rate of Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: Italian Peritoneal Surface Malignancies Oncoteam Results Analysis

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy may significantly improve survival for selected patients with peritoneal surface malignancies, but it has always been criticized due to the high incidence of postoperative morbidity and mortality. Methods: Data were collected from nine Italian centers with peritoneal surface malignancies expertise within a collaborative group of the Italian Society of Surgical Oncology. Complications and mortality rates were recorded, and multivariate Cox analysis was used to identify risk factors. Results: The study included 2576 patients. The procedure was mostly performed for ovarian (27.4%) and colon cancer (22.4%). The median peritoneal cancer index was 13. Overall postoperative morbidity and mortality rates were 34% and 1.6%. A total of 232 (9%) patients required surgical reoperation. Multivariate regression logistic analysis identified the type of perfusion (p ≤ 0.0001), body mass index (p ≤ 0.0001), number of resections (p ≤ 0.0001) and colorectal resections (p ≤ 0.0001) as the strongest predictors of complications, whereas the number of resections (p ≤ 0.0001) and age (p = 0.01) were the strongest predictors of mortality. Conclusions: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is a valuable option of treatment for selected patients with peritoneal carcinomatosis providing low postoperative morbidity and mortality rates, if performed in high-volume specialized centers

Modeling Parkinson’s disease neuropathology and symptoms by intranigral inoculation of preformed human α-synuclein oligomers

The accumulation of aggregated α-synuclein (αSyn) is a hallmark of Parkinson’s disease (PD). Current evidence indicates that small soluble αSyn oligomers (αSynOs) are the most toxic species among the forms of αSyn aggregates, and that size and topological structural properties are crucial factors for αSynOs-mediated toxicity, involving the interaction with either neurons or glial cells. We previously characterized a human αSynO (H-αSynO) with specific structural properties promoting toxicity against neuronal membranes. Here, we tested the neurotoxic potential of these H-αSynOs in vivo, in relation to the neuropathological and symptomatic features of PD. The H-αSynOs were unilaterally infused into the rat substantia nigra pars compacta (SNpc). Phosphorylated αSyn (p129-αSyn), reactive microglia, and cytokine levels were measured at progressive time points. Additionally, a phagocytosis assay in vitro was performed after microglia pre-exposure to αsynOs. Dopaminergic loss, motor, and cognitive performances were assessed. H-αSynOs triggered p129-αSyn deposition in SNpc neurons and microglia and spread to the striatum. Early and persistent neuroinflammatory responses were induced in the SNpc. In vitro, H-αSynOs inhibited the phagocytic function of microglia. H-αsynOs-infused rats displayed early mitochondrial loss and abnormalities in SNpc neurons, followed by a gradual nigrostriatal dopaminergic loss, associated with motor and cognitive impairment. The intracerebral inoculation of structurally characterized H-αSynOs provides a model of progressive PD neuropathology in rats, which will be helpful for testing neuroprotective therapies

Vitamin D responsive elements within the HLA-DRB1 promoter region in Sardinian multiple sclerosis associated alleles

Vitamin D response elements (VDREs) have been found in the promoter region of the MS-associated allele HLA-DRB1*15:01, suggesting that with low vitamin D availability VDREs are incapable of inducing *15:01 expression allowing in early life autoreactive T-cells to escape central thymic deletion. The Italian island of Sardinia exhibits a very high frequency of MS and high solar radiation exposure. We test the contribution of VDREs analysing the promoter region of the MS-associated DRB1 *04:05, *03:01, *13:01 and *15:01 and non-MS-associated *16:01, *01, *11, *07:01 alleles in a cohort of Sardinians (44 MS patients and 112 healthy subjects). Sequencing of the DRB1 promoter region revealed a homozygous canonical VDRE in all *15:01, *16:01, *11 and in 45/73 *03:01 and in heterozygous state in 28/73 *03:01 and all *01 alleles. A new mutated homozygous VDRE was found in all *13:03, *04:05 and *07:01 alleles. Functionality of mutated and canonical VDREs was assessed for its potential to modulate levels of DRB1 gene expression using an in vitro transactivation assay after stimulation with active vitamin D metabolite. Vitamin D failed to increase promoter activity of the *04:05 and *03:01 alleles carrying the new mutated VDRE, while the *16:01 and *03:01 alleles carrying the canonical VDRE sequence showed significantly increased transcriptional activity. The ability of VDR to bind the mutant VDRE in the DRB1 promoter was evaluated by EMSA. Efficient binding of VDR to the VDRE sequence found in the *16:01 and in the *15:01 allele reduced electrophoretic mobility when either an anti-VDR or an anti-RXR monoclonal antibody was added. Conversely, the Sardinian mutated VDRE sample showed very low affinity for the RXR/VDR heterodimer. These data seem to exclude a role of VDREs in the promoter region of the DRB1 gene in susceptibility to MS carried by DRB1* alleles in Sardinian patients