Clinical characteristics of Polish patients with ANCA-associated vasculitides-retrospective analysis of POLVAS registry

Objective Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). Methods We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). Results Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3–12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06–9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05–6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3–25.5), skin involvement (OR = 4.4; 95% CI = 1.02– 19.6), and age > 65 (OR = 6.3; 95% CI = 1.18–33.7). Conclusions In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease

Photoelectron spectroscopic and density functional theoretical studies of the 2′-deoxycytidine homodimer radical anion Photoelectron spectroscopic and density functional theoretical studies of the 2 -deoxycytidine homodimer radical anion

The intact (parent) 2 -deoxycytidine homodimer anion, (dC) 2 •− , was generated in the gas phase (in vacuo) using an infrared desorption/photoemission source and its photoelectron spectrum was recorded using a pulsed, magnetic bottle photoelectron spectrometer. The photoelectron spectrum (PES) revealed a broad peak with the maximum at an electron binding energy between 1.6 and 1.9 eV and with a threshold at ∼1.2 eV. The relative energies and vertical detachment energies of possible anion radicals were calculated at the B3LYP/6-31++G * * level of theory. The most stable anion radicals are the complexes involving combinations of the sugar · · · base and base · · · base interactions. The calculated adiabatic electron affinities and vertical detachment energies of the most stable (dC) 2 •− anions agree with the experimental values. In contrast with previous experimentalcomputational studies on the anionic complexes involving nucleobases with various proton-donors, the electron-induced proton transferred structures of (dC) 2 •− are not responsible for the shape of PES. © 2013 AIP Publishing LLC. [http://d

Intermolecular proton transfer induced by excess electron attachment to adenine(formic acid) n (n = 2, 3) hydrogen-bonded complexes

Abstract The propensity of the neutral complexes between both adenine and 9-methyladenine (A/MA) with formic acid (FA) in 1:2 and 1:3 stoichiometries to bind an excess electron was studied using photoelectron spectroscopy and quantum chemistry computational methods. Although an isolated canonical adenine does not support bound valence anions, solvation by one formic acid molecule stabilizes the excess electron on adenine. The adiabatic electron affinities of the A/MA(FA) 2,3 complexes span a range of 0.8-1.23 eV indicating that the anions of 1:2 and 1:3 stoichiometries are substantially more stable than the anionic A-FA dimer (EA = 0.67 eV), which we studied previously and an attachment of electron triggers double-BFPT, confirmed at the MPW1K level of theory, in all the considered systems. Hence, the simultaneous involvement of several molecules capable of forming cyclic hydrogen bonds with adenine remarkably increases its ability to bind an excess electron. The calculated vertical detachment energies for the most stable anions correspond well with those obtained using photoelectron spectroscopy. The possible biological significance of our findings is briefly discussed

Excess Electron Attachment to the Nucleoside Pair 2′-Deoxyadenosine (dA)–2′-Deoxythymidine (dT)

The 2′-deoxyadenosine···2′-deoxythymidine (dAdT^•–) radical anion nucleoside pair has been investigated both experimentally and theoretically in the gas phase. The vertical detachment energy (VDE) and adiabatic electron affinity (AEA) were determined by anion photoelectron spectroscopy (PES). The measured photoelectron spectrum features a broad band having an onset at ∼1.1 eV and a maximum at the electron binding energy (EBE) ranging from 1.7 to 1.9 eV. Calculations performed at the M06-2X/6-31++G** level reveal that the observed PES signal is probably due to a dAdT^•– complex in which the thymine of the dT nucleoside forms hydrogen bonds that engage its O7 and O8 atoms as well as the 3′- and 5′-hydroxyl groups of 2′-deoxyadenosine (dA), while dT’s 3′-hydroxyl group interacts with the N1 of dA. In this heterodimer, the excess electron is entirely located on thymine. The biologically relevant Watson–Crick arrangement of the dAdT^•– dimer was found to be substantially less stable (by ∼19 kcal mol^–1 in Gibbs free energy scale) than the above-mentioned configuration; hence, it is not populated in the gas phase

Photoelectron Spectroscopy and Computational Modeling of Thymidine Homodimer Anions

The intact thymidine homodimer anion (dT₂^–) was generated in the gas phase using an infrared desorption/photoemission source and recorded by a pulsed photoelectron spectrometer. The photoelectron spectrum (PES) revealed a broad signal with the maximum at electron binding energy ∼2.0 eV and the threshold value at 1.1 eV. The relative energies and vertical detachment energies of the possible anion structures were calculated at the B3LYP/6-31++G­(d,p) level. Here we report that the most stable anion radical homodimer geometries observed in the PES are the anionic nucleoside coordinated by the O8 atom of thymine to the deoxyribose of the second neutral nucleoside. Unlike previous experimental–computational studies on anionic complexes involving nucleobases with proton donors, the electron-induced proton-transferred structures are not responsible for the shape of the PES of dT₂^–