A systematic study of the valence electronic structure of cyclo(Gly-Phe), cyclo(Trp-Tyr) and cyclo(Trp-Trp) dipeptides in the gas phase.

The electronic energy levels of cyclo(glycine-phenylalanine), cyclo(tryptophan-tyrosine) and cyclo(tryptophan-tryptophan) dipeptides are investigated with a joint experimental and theoretical approach. Experimentally, valence photoelectron spectra in the gas phase are measured using VUV radiation. Theoretically, we first obtain low-energy conformers through an automated conformer-rotamer ensemble sampling scheme based on tight-binding simulations. Then, different first principles computational schemes are considered to simulate the spectra: Hartree-Fock (HF), density functional theory (DFT) within the B3LYP approximation, the quasi-particle GW correction, and the quantum-chemistry CCSD method. Theory allows assignment of the main features of the spectra. A discussion on the role of electronic correlation is provided, by comparing computationally cheaper DFT scheme (and GW) results with the accurate CCSD method.

Few-femtosecond electron transfer dynamics in photoionized donor-π-acceptor molecules.

The exposure of molecules to attosecond extreme-ultraviolet (XUV) pulses offers a unique opportunity to study the early stages of coupled electron-nuclear dynamics in which the role played by the different degrees of freedom is beyond standard chemical intuition. We investigate, both experimentally and theoretically, the first steps of charge-transfer processes initiated by prompt ionization in prototype donor-π-acceptor molecules, namely nitroanilines. Time-resolved measurement of this process is performed by combining attosecond XUV-pump/few-femtosecond infrared-probe spectroscopy with advanced many-body quantum chemistry calculations. We show that a concerted nuclear and electronic motion drives electron transfer from the donor group on a sub-10-fs timescale. This is followed by a sub-30-fs relaxation process due to the probing of the continuously spreading nuclear wave packet in the excited electronic states of the molecular cation. These findings shed light on the role played by electron-nuclear coupling in donor-π-acceptor systems in response to photoionization.

Insights into the Thermally Activated Cyclization Mechanism in a Linear Phenylalanine-Alanine Dipeptide.

Dipeptides, the prototype peptides, exist in both linear (l-) and cyclo (c-) structures. Since the first mass spectrometry experiments, it has been observed that some l-structures may turn into the cyclo ones, likely via a temperature-induced process. In this work, combining several different experimental techniques (mass spectrometry, infrared and Raman spectroscopy, and thermogravimetric analysis) with tight-binding and ab initio simulations, we provide evidence that, in the case of l-phenylalanyl-l-alanine, an irreversible cyclization mechanism, catalyzed by water and driven by temperature, occurs in the condensed phase. This process can be considered as a very efficient strategy to improve dipeptide stability by turning the comparatively fragile linear structure into the robust and more stable cyclic one. This mechanism may have played a role in prebiotic chemistry and can be further exploited in the preparation of nanomaterials and drugs.

"Smart Decomposition" of Cyclic Alanine-Alanine Dipeptide by VUV Radiation: A Seed for the Synthesis of Biologically Relevant Species.

A combined experimental and theoretical study shows how the interaction of VUV radiation with cyclo-(alanine-alanine), one of the 2,5-diketopiperazines (DKPs), produces reactive oxazolidinone intermediates. The theoretical simulations reveal that the interaction of these intermediates with other neutral and charged fragments, released in the molecular decomposition, leads either to the reconstruction of the cyclic dipeptide or to the formation of longer linear peptide chains. These results may explain how DKPs could have, on one hand, survived hostile chemical environments and, on the other, provided the seed for amino acid polymerization. Shedding light on the mechanisms of production of such prebiotic building blocks is of paramount importance to understanding the abiotic synthesis of relevant biologically active compounds.

Adjuvant treatment with concomitant radiotherapy and chemotherapy in high-risk endometrial cancer: a clinical experience.

OBJECTIVE: The concurrent use of radiotherapy (RT) and chemotherapy (CT) as adjuvant treatment after surgery in high-risk endometrial cancer has been generally considered cautiously. Recently some of us have reported preliminary data on the efficacy and tolerability of concomitant CT and RT. In this paper, we update our experience. METHODS: A total of 47 patients aged >18 years and <80 years with histological diagnosis of high-risk endometrial endometrioid carcinomas entered the study. Inclusion criteria were stages IC G3, IIB, IIIA (patients with positive washing without other unfavourable prognostic factors were omitted), IIIB and IIIC. The radiation plan consisted of a total dose of 50.4 Gy, given in five fractions per week (1.8 Gy: daily dose) for 6 weeks. Paclitaxel (P) at a dose of 60 mg/m(2) was infused intravenously in 250 mL of normal saline for 1 h once weekly during RT for 5 weeks. Three further cycles of Paclitaxel, at a dose of 80 mg/m(2), have been given weekly at the end of RT. RESULTS: There was no life-threatening toxicity. The overall 5-year relapse-free survival was 81.8% (95% CI, 65.2-90.9). The 5-year percent overall disease-specific survival was 88.4% (95% CI, 71.1-95.6). CONCLUSIONS: These results, based on a larger series, support our previous data: Paclitaxel plus RT may represent an effective and well-tolerated treatment in high-risk endometrial cancer patients.

Safer-by-design biocides made of tri-thiol bridged silver nanoparticle assemblies.

Silver nanoparticles (AgNPs) are efficient biocides increasingly used in consumer products and medical devices. Their activity is due to their capacity to release bioavailable Ag(i) ions making them long-lasting biocides but AgNPs themselves are usually easily released from the product. Besides, AgNPs are highly sensitive to various chemical environments that triggers their transformation, decreasing their activity. Altogether, widespread use of AgNPs leads to bacterial resistance and safety concerns for humans and the environment. There is thus a crucial need for improvement. Herein, a proof of concept for a novel biocide based on AgNP assemblies bridged together by a tri-thiol bioinspired ligand is presented. The final nanomaterial is stable and less sensitive to chemical environments with AgNPs completely covered by organic molecules tightly bound via their thiol functions. Therefore, these AgNP assemblies can be considered as safer-by-design and innovative biocides, since they deliver a sufficient amount of Ag(i) for biocidal activity with no release of AgNPs, which are insensitive to transformations in the nanomaterial.

Highly Hydrophilic Gold Nanoparticles as Carrier for Anticancer Copper(I) Complexes: Loading and Release Studies for Biomedical Applications.

Gold nanoparticles (AuNPs), which are strongly hydrophilic and dimensionally suitable for drug delivery, were used in loading and release studies of two different copper(I)-based antitumor complexes, namely [Cu(PTA)4]+ [BF4]- (A; PTA = 1, 3, 5-triaza-7-phosphadamantane) and [HB(pz)3Cu(PCN)] (B; HB(pz)3 = tris(pyrazolyl)borate, PCN = tris(cyanoethyl)phosphane). In the homoleptic, water-soluble compound A, the metal is tetrahedrally arranged in a cationic moiety. Compound B is instead a mixed-ligand (scorpionate/phosphane), neutral complex insoluble in water. In this work, the loading procedures and the loading efficiency of A and B complexes on the AuNPs were investigated, with the aim to improve their bioavailability and to obtain a controlled release. The non-covalent interactions of A and B with the AuNPs surface were studied by means of dynamic light scattering (DLS), UV-Vis, FT-IR and high-resolution x-ray photoelectron spectroscopy (HR-XPS) measurements. As a result, the AuNPs-A system proved to be more stable and efficient than the AuNPs-B system. In fact, for AuNPs-A the drug loading reached 90%, whereas for AuNPs-B it reached 65%. For AuNPs-A conjugated systems, a release study in water solution was performed over 4 days, showing a slow release up to 10%.

A secondary abdominal pregnancy with unusual placental implantation in the fallopian tube: a diagnostic challenge.

We reported a case of secondary abdominal pregnancy with placental implantation into the fallopian tube, diagnosed at 16 weeks, in a woman admitted to the emergency room complaining of syncopal attacks. The best approach would be termination of the pregnancy, taking into consideration the high risk to the mother and the low possibility of alive and healthy birth. We had to perform an urgent surgical intervention due to the fact that the patient was in a clinically unstable condition, which was related to hemoperitoneum. If placental implantation is on abdominal organs or vessel the best approach would be to ligate the cord and to leave placenta in situ. Taking into consideration the place of placental implant, the removal of the fallopian tube with the placenta was the safest approach in this case. The best and most acceptable form of treatment would be individualized in case of rare form of ectopic pregnancy.

Plasmonic Sensor Based on Interaction between Silver Nanoparticles and Ni2+ or Co2+ in Water.

Silver nanoparticles capped with 3-mercapto-1propanesulfonic acid sodium salt (AgNPs-3MPS), able to interact with Ni2+ or Co2+, have been prepared to detect these heavy metal ions in water. This system works as an optical sensor and it is based on the change of the intensity and shape of optical absorption peak due to the surface plasmon resonance (SPR) when the AgNPs-3MPS are in presence of metals ions in a water solution. We obtain a specific sensitivity to Ni2+ and Co2+ up to 500 ppb (part per billion). For a concentration of 1 ppm (part per million), the change in the optical absorption is strong enough to produce a colorimetric effect on the solution, easily visible with the naked eye. In addition to the UV-VIS characterizations, morphological and dimensional studies were carried out by transmission electron microscopy (TEM). Moreover, the systems were investigated by means of dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and high-resolution X-ray photoelectron spectroscopy (HR-XPS). On the basis of the results, the mechanism responsible for the AgNPs-3MPS interaction with Ni2+ and Co2+ (in the range of 0.5⁻2.0 ppm) looks like based on the coordination compounds formation.

Gold nanoparticles functionalized by rhodamine B isothiocyanate: A new tool to control plasmonic effects.

Gold nanoparticles with an average diameter of 10 nm, functionalized by the dye molecule rhodamine B isothiocyanate, have been synthesized. The resulting material has been extensively characterized both chemically, to investigate the bonding between the dye molecules and the nanoparticles, and physically, to understand the details of the aggregation induced by interaction between dye molecules on different nanoparticles. The plasmonic response of the system has been further characterized by measurement and theoretical simulation of the static UV-Vis extinction spectra of the aggregates produced following different synthesis procedures. The model parameters used in the simulation gave further useful information on the aggregation and its relationship to the plasmonic response. Finally, we investigated the time dependence of the plasmonic effects of the nanoparticles and fluorescence of the dye molecule using an ultrafast pump-probe optical method. By modulating the quantity of dye molecules on the surface of the nanoparticles it was possible to exert fine control over the plasmonic response of nanoparticles.

Nanocomposite Based on Functionalized Gold Nanoparticles and Sulfonated Poly(ether ether ketone) Membranes: Synthesis and Characterization.

Gold nanoparticles, capped by 3-mercapto propane sulfonate (Au-3MPS), were synthesized inside a swollen sulfonated poly(ether ether ketone) membrane (sPEEK). The formation of the Au-3MPS nanoparticles in the swollen sPEEK membrane was observed by spectroscopic and microscopic techniques. The nanocomposite containing the gold nanoparticles grown in the sPEEK membrane, showed the plasmon resonance λmax at about 520 nm, which remained stable over a testing period of three months. The size distribution of the nanoparticles was assessed, and the sPEEK membrane roughness, both before and after the synthesis of nanoparticles, was studied by AFM. The XPS measurements confirm Au-3MPS formation in the sPEEK membrane. Moreover, AFM experiments recorded in fluid allowed the production of images of the Au-3MPS@sPEEK composite in water at different pH levels, achieving a better understanding of the membrane behavior in a water environment; the dynamic hydration process of the Au-3MPS@sPEEK membrane was investigated. These preliminary results suggest that the newly developed nanocomposite membranes could be promising materials for fuel cell applications.

Selective uterine artery embolization: a new therapeutic approach in a patient with low-risk gestational trophoblastic disease.

We report a case of persistent gestational trophoblastic disease (GTD) in which a selective uterine artery embolization instead of invasive surgery achieved both the control of pelvic hemorrhage and of disease.

Salt-induced reentrant stability of polyion-decorated particles with tunable surface charge density.

The electrostatic complexation between DOTAP/DOPC unilamellar liposomes and an oppositely charged polyelectrolyte (NaPA) has been investigated in a wide range of the liposome surface charge density. We systematically characterized the reentrant condensation and the charge inversion of polyelectrolyte-decorated liposomes by means of dynamic light scattering and electrophoresis. We explored the stability of this model polyelectrolyte/colloid system at different values of the surface charge of the bare liposomes and by changing two independent control parameters of the suspensions: the polyelectrolyte/colloid charge ratio and the ionic strength of the aqueous suspending medium. The progressive addition of neutral DOPC lipid within the liposome membrane gave rise to an interesting phenomenon which has not been observed previously: the stability diagram of the suspensions showed a novel reentrance due to the crossing of the desorption threshold of the polyelectrolyte. Indeed, at fixed charge density of the bare DOTAP/DOPC liposomes and for a wide range of polyion concentrations, we showed that the simple electrolyte addition first (low salt regime) destabilizes the suspensions because of the enhanced screening of the residual repulsion between the complexes, and then (high salt regime) determines the onset of a new stable phase, originated by the absence of polyelectrolyte adsorption on the particle surfaces. We show that the observed phenomenology can be rationalized within the modified Velegol-Thwar model for heterogeneously charged particles and that the polyelectrolyte desorption fits well the predictions of the adsorption theory of Winkler and Cherstvy [1]. Our findings unambiguously support the picture of the reentrant condensation as driven by the correlated adsorption of the polyelectrolyte chains on the particle surface, providing interesting insights into possible mechanisms for tailoring complex colloids via salt-induced effects.

Synthesis and Structural Characterization of Silver Nanoparticles Stabilized with 3-Mercapto-1-Propansulfonate and 1-Thioglucose Mixed Thiols for Antibacterial Applications.

The synthesis, characterization and assessment of the antibacterial properties of hydrophilic silver nanoparticles (AgNPs) were investigated with the aim to probe their suitability for innovative applications in the field of nanobiotechnology. First, silver nanoparticles were synthetized and functionalized with two capping agents, namely 3-mercapto-1-propansulfonate (3MPS) and 1-ß-thio-d-glucose (TG). The investigation of the structural and electronic properties of the nano-systems was carried out by means of X-ray Photoelectron Spectroscopy (XPS) and X-ray Absorption Spectroscopy (XAS). XPS data provided information about the system stability and the interactions between the metallic surface and the organic ligands. In addition, XPS data allowed us to achieve a deep understanding of the influence of the thiols stoichiometric ratio on the electronic properties and stability of AgNPs. In order to shed light on the structural and electronic local properties at Ag atoms sites, XAS at Ag K-Edge was successfully applied; furthermore, the combination of Dynamic Light Scattering (DLS) and XAS results allowed determining AgNPs sizes, ranging between 3 and 13 nm. Finally, preliminary studies on the antibacterial properties of AgNPs showed promising results on four of six multidrug-resistant bacteria belonging to the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp.).

A rare melanoma feature with primary ovarian origin: a case report and the literature review

Primary ovarian melanoma arising on a mature ovarian cystic teratoma is extremely rare. As best of our knowledge, to date, 49 cases have been reported in literature. Few information was reported about best management and therapy. We present a case occurred in a 69-year-old woman, without symptoms, who come to our unit for stress incontinence. A pelvic mass was detected and, after imaging evaluation, surgery was performed. The diagnosis was ovarian melanoma arose on a mature teratoma. No other adjuvant treatment was proposed after surgery. She died 9 months after the first diagnosis. Primary ovarian melanoma is a definite entity associated with a variable natural history and poor prognosis. Differential diagnosis is a challenge for the pathologist, because it must be differentiated by metastatic melanoma. The corner stone treatment of this disease is surgery; however, chemotherapy, immunotherapy, and target therapy seem to have a role.

Estimate of the effects of ultraviolet radiation on the mortality of Artemia franciscana in naupliar and adult stages.

The impact of different doses of artificial ultraviolet (UV) radiation on the growth stages of a marine zooplankton was investigated using laboratory microcosms. Mortality percentages of naupliar and adult samples of Artemia franciscana were recorded in relation to different UV doses (single exposure: 75, 150, 300, 600, 1,200, 2,400, 3,900, 7,800 J m(-2)) at specific observation times after exposure (24, 48, 72, 96 and 120 h). The relationship between mortality percentage and UV dose showed significant differences in relation to the zooplankton growth stage. The elevated susceptibility of the naupliar samples to UV radiation is described through a mortality model based on a logistic equation. The data analysis shows that the slope of mortality versus dose remains the same for the two growth stages while the lethal dose in the naupliar stage was 3.3 smaller than that determined for the adult stage. The slope of the UV mortality rate versus post-incubation time was found to be significantly different (P<0.05) at low UV doses for the two life stages examined, i.e. naupliar and adult. The lower value of LD(50) in naupliar stages compared to that for adults confirms that in the early growth stage this marine zooplankton is more susceptible to UV radiation.

Risk factors for spontaneous preterm birth: a Northern Italian multicenter case-control study.

Preterm birth remains one of the most serious problems facing obstetricians. The aim of this study was to investigate the risk factors for spontaneous preterm birth in northern Italy. Nine different collaborating institutions participated in this multicenter case-control study. Cases were defined as women who were spontaneously delivered of a live singleton newborn between 20 and 37 weeks of gestation. One control was matched to each case by delivery date, maternal age and parity. Seven hundred and fifty-four cases and 754 controls were available for data analysis. Demographic and clinical characteristics were obtained using a standardized questionnaire. At the time of hospital admission, urine and cervico-vaginal samples were collected and tested for bacterial infections and bacterial vaginosis, respectively. Variables found to be statistically significant in the univariate analysis were entered in a multivariate model to examine their independent effects. In order of decreasing odds ratios (ORs), the factors that showed a significant association with preterm delivery were: previous preterm birth (OR 5.7, confidence interval (CI) 2.5-12.9); second-trimester miscarriages (OR 4.4, CI 1.3-15.3); genital bleeding before 24 weeks of gestation (OR 2.5, CI 1.6-3.8); bacterial vaginosis (OR 2.0, CI 1.3-3.1), and previous genital infections (OR 1.6, CI 1.1-2.5). This study confirms that infections play a role in the etiology of preterm birth and that reproductive history is still the most important factor in identifying women at increased risk.