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This article discusses the challenges of studying pulmonary hypertension (PH) in animal models, particularly in mice. PH is characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance, and understanding its pathophysiological mechanisms is difficult due to the diverse clinical conditions associated with the disease. The article highlights the use of combined stimuli to induce experimental PH, similar to the "two-hit" model in humans, where two insults are required to induce clinical disease. The authors attempted to develop a new model of severe and persistent PH in mice by combining surgical pneumonectomy with different stimuli, but the results were essentially negative. The study emphasizes the resilience of mice to PH stimuli compared to rats and humans, but also acknowledges the progress made in the field of PH research through murine studies. The authors suggest considering the addition of multiple concurrent stimuli in future studies to better mimic the complexity of human disease. The article concludes by commending the authors for publishing a well-performed negative result, which adds to the scientific literature and helps other researchers avoid unnecessary efforts in creating the same model. [Extracted from the article]

The purpose of this study is to identify the determinants of listed Brazilian banks' credit ratings during the period 2006-2015. We applied an ordered logistic model, using an unbalanced panel. Results show evidence that profitability, liquidity, asset adequacy and quality, and size variables significantly affect bank credit-rating levels. Findings also suggested that credit ratings trended down, which could be explained by the significant contraction of economic activity in Brazil during the period. [ABSTRACT FROM AUTHOR]

Predicting NMR properties is a valuable tool to assist the experimentalists in the characterization of molecular structure. For heavy metals, such as Pt-195, only a few computational protocols are available. In the present contribution, all-electron Gaussian basis sets, suitable to calculate the Pt-195 NMR chemical shift, are presented for Pt and all elements commonly found as Pt-ligands. The new basis sets identified as NMR-DKH were partially contracted as a triple-zeta doubly polarized scheme with all coefficients obtained from a Douglas-Kroll-Hess (DKH) second-order scalar relativistic calculation. The Pt-195 chemical shift was predicted through empirical models fitted to reproduce experimental data for a set of 183 Pt(II) complexes which NMR sign ranges from −1000 to −6000 ppm. Furthermore, the models were validated using a new set of 75 Pt(II) complexes, not included in the descriptive set. The models were constructed using non-relativistic Hamiltonian at density functional theory (DFT-PBEPBE) level with NMR-DKH basis set for all atoms. For the best model, the mean absolute deviation (MAD) and the mean relative deviation (MRD) were 150 ppm and 6%, respectively, for the validation set (75 Pt-complexes) and 168 ppm (MAD) and 5% (MRD) for all 258 Pt(II) complexes. These results were comparable with relativistic DFT calculation, 200 ppm (MAD) and 6% (MRD). © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Recent progress in the solution of three- and four-particle scattering equations including the Coulomb interaction is reviewed. The method of screening and renormalization in the framework of momentum-space integral equations is used and its reliability demonstrated. We also review results for observable's in three- and four-nucleon scattering as well as applications to nuclear reactions that display three-body degrees of freedom. [ABSTRACT FROM AUTHOR]

In this study, we have investigated 12 tautomers of the DNA base adenine at the BP86/TZ2P and BP86/QZ4P levels of density functional theory. The vertical and adiabatic ionization energies of all tautomers were determined as the difference in energy between the radical cation and the corresponding neutral system. Furthermore, an evaluation is made for the eigenvalue spectra calculated with the SAOP functional, which is shown to lead to substantial improvements for orbital energies compared to BP86. We have also explored the correlations between the Kohn−Sham orbitals of the different tautomers at the BP86/QZ4P and SAOP/QZ4P levels. Finally, we discuss implications of the existence of the tautomeric forms of adenine for the DNA replication. [ABSTRACT FROM AUTHOR]

Cyanide reacts with tetracyanomethane towards the tricyanomethyl anion via cyanophilic substitution; this is suggested by nitrogen isotope-labeling experiments and proven by density functional calculations at OLYP/TZ2P. [Copyright &y& Elsevier]

Acute high-altitude (HA) exposure can induce several pathologies. Dexamethasone (DEX) can be taken prophylactically to prevent HA disease, but the mechanism by which it acts in this setting is unclear. We studied the transcriptome of peripheral blood mononuclear cells (PBMCs) from 16 subjects at low altitude (LA, 225 m) and then 3 days after acute travel to HA (3500 m) during the India-Leh-Dexamethasone-Expedition-2020 (INDEX2020). Half of the participants received oral DEX prophylaxis 4 mg twice daily in an unblinded manner, starting 1 day prior to travel to HA, and 12 h prior to the first PBMC collection. PBMC transcriptome data were obtained from 16 subjects, half of whom received DEX. The principal component analysis demonstrated a clear separation of the groups by altitude and treatment. HA exposure resulted in a large number of gene expression changes, particularly in pathways of inflammation or the regulation of cell division, translation, or transcription. DEX prophylaxis resulted in changes in fewer genes, particularly in immune pathways. The gene sets modulated by HA and DEX were distinct. Deconvolution analysis to assess PBMC subpopulations suggested changes in B-cell, T-cell, dendritic cell, and myeloid cell numbers with HA and DEX exposures. Acute HA travel and DEX prophylaxis induce significant changes in the PBMC transcriptome. The observed benefit of DEX prophylaxis against HA disease may be mediated by suppression of inflammatory pathways and changing leukocyte population distributions. [ABSTRACT FROM AUTHOR]

Rifampicin is a semi-synthetic drug derived from rifamycin B, and currently integrates the fixed dose combination tablet formulations used in the treatment of tuberculosis. It is also used in the leprosy polychemotherapy and prophylaxis, which are diseases classified as neglected according to the World Health Organization. Rifampicin is a polymorphic drug and its desirable polymorphic form is labeled as II, being the main goal of this study the elucidation of its crystalline structure. Polymorph II is characterized by two molecules with different conformations in the asymmetric unit and the following lattice parameters: a = 14.0760 (10) Å, b = 17.5450 (10) Å, c = 17.5270 (10) Å, β = 92.15°. Differently to the previously reported structures, a charge transference from the hydroxyl group of the naphthoquinone of one conformer to the nitrogen of the piperazine group of the second conformer was observed. The relevance of the knowledge of this crystalline structure, which is the preferred polymorph for pharmaceutical formulations, was evidenced by analyzing raw materials with polymorphic mixtures. Thus, the results presented in this contribution close an old information gap allowing the complete solid-state characterization of rifampicin. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) can occur as a complication of schistosomiasis. In humans, schistosomiasis-PH persists despite antihelminthic therapy and parasite eradication. We hypothesized that persistent disease arises as a consequence of exposure repetition. Methods: Following intraperitoneal sensitization, mice were experimentally exposed to Schistosoma eggs by intravenous injection, either once or three times repeatedly. The phenotype was characterized by right heart catheterization and tissue analysis. Results: Following intraperitoneal sensitization, a single intravenous Schistosoma egg exposure resulted in a PH phenotype that peaked at 7-14 days, followed by spontaneous resolution. Three sequential exposures resulted in a persistent PH phenotype. Inflammatory cytokines were not significantly different between mice exposed to one or three egg doses, but there was an increase in perivascular fibrosis in those who received three egg doses. Significant perivascular fibrosis was also observed in autopsy specimens from patients who died of this condition. Conclusions: Repeatedly exposing mice to schistosomiasis causes a persistent PH phenotype, accompanied by perivascular fibrosis. Perivascular fibrosis may contribute to the persistent schistosomiasis-PH observed in humans with this disease. [ABSTRACT FROM AUTHOR]

The most polar bond in chemistry is that between a fluorine and an alkalimetal atom. Inspired by our recent finding that other polar bonds (C&bond;M and H&bond;M) have important covalent contributions (i.e., stabilization due to bond overlap), we herein address the question if covalency is also essential in the F&bond;M bond. Thus, we have theoretically studied the alkalimetal fluoride monomers, FM, and (distorted) cubic tetramers, (FM)4, with M = Li, Na, K, and Rb, using density functional theory at the BP86/TZ2P level. Our objective is to determine how the structure and thermochemistry (e.g., F&bond;M bond lengths and strengths, oligomerization energies, etc.) of alkalimetal fluorides depend on the metal atom, and to understand the emerging trends in terms of quantitative Kohn–Sham molecular orbital theory. The analyses confirm the extreme polarity of the F&bond;M bond (dipole moment, Voronoi deformation density and Hirshfeld atomic charges), and they reveal that bond overlap-derived stabilization (ca. -6, -6, and -2 kcal/mol) contributes only little to the bond strength (-136, -112, and -114 kcal/mol) and the trend therein along Li, Na, and K. According to this and other criteria, the F&bond;M bond is not only strongly polar, but also has a truly ionic bonding mechanism. Interestingly, the polarity is reduced on tetramerization. For the lithium and sodium fluoride tetramers, the F4 tetrahedron is larger than and surrounds the M4 cluster (i.e., F&bond;F ≫ M&bond;M). But in the potassium and rubidium fluoride tetramers, the F4 tetrahedron is smaller than and inside the M4 cluster (i.e., F&bond;F < M&bond;M). © 2006 Wiley Periodicals, Inc. J Comput Chem 28: 238–250, 2007 [ABSTRACT FROM AUTHOR]

We acquired H α spectroscopic observations from 2005 to 2019 showing Pleione has transitioned from a Be phase to a Be-shell phase during this period. Using the radiative transfer code hdust, we created a grid of ∼100,000 disk models for Pleione. We successfully reproduced the observed transition with a disk model that varies in inclination while maintaining an equatorial density of ρ 0 (r) = 3 Ă— 10 âˆ' 11 (r / R eq) âˆ' 2.7 g cm âˆ' 3 , and an H α -emitting region extending to 15 R eq. We use a precessing disk model to extrapolate the changing disk inclination over 120 yr and follow the variability in archival observations. The best-fit disk model precesses over a line-of-sight inclination between ∼25° and ∼144° with a precessional period of ∼80.5 yr. Our precessing models match some of the observed variability but fail to reproduce all of the historical data available. Therefore, we propose an ad hoc model based on our precessing disk model inspired by recent smoothed particle hydrodynamics simulations of similar systems, where the disk tears due to the tidal influence of a companion star. In this model, a single disk is slowly tilted to an angle of 30° from the stellar equator over 34 yr. Then, the disk is torn by the companion’s tidal torque, with the outer region separating from the innermost disk. The small inner disk returns to the stellar equator as mass injection remains constant. The outer disk precesses for ∼15 yr before gradually dissipating. The process repeats every 34 yr and reproduces all trends in Pleione’s variability. [ABSTRACT FROM AUTHOR]

Reports on the finding of research which observes selective oxidation of guanines in DNA. Effective energy of a positive charge at the middle guanine sequence; Experimental observation of the analysis; Distribution of excess charge on guanines in duplexes.

The evolution of fossoriality in Squamata often leads to a phenotypic syndrome involving snake-like body form, relatively low preferred temperature ( TP) and low critical maximum temperatures (CTmax). However, how traits interacted among them and with the environment during the evolution of such syndrome remains poorly understood., We studied this process in ten species of gymnophthalmid lizards from the Brazilian Caatinga representing one full transition from typical lacertoid species to fossorial snake-like (FSL) ones. We tested whether different morphotypes exhibited different burrowing performances in response to heat, and also different TP and CTmax. Then, we estimated how changes in burrowing performance would relate to thermoregulation costs in terms of the number of daily hours for which preferred temperatures are available and of risk of overheating., Fossorial snake-like species burrowed deeper, exhibited lower TP but kept very high CTmax, comparable to lacertoid species. A better burrowing performance and lower TP allowed increasing the daily amount of time during which TP was accessible within the soil of the study region. In addition, temperatures above CTmax of the studied species were present down to 5 cm deep, suggesting that just burrowing does not protect against exposure to extreme temperatures in species that are surface-active during the day (all lacertoids and some FSL). Nonetheless, FSL species active at cool hours of the day exhibited lower CTmax than diurnal and syntopic, lacertoid and FSL species., Based on our data and previous literature, we propose a sequential explanation for the acquisition of the fossorial syndrome in Squamata. [ABSTRACT FROM AUTHOR]

Mast cell tumors (MCTs) are common neoplasms in dogs, and treatments for these diseases include surgery, polychemotherapy and targeted therapy with tyrosine kinase inhibitors. This study aimed to evaluate the response and the adverse events of treatment with imatinib mesylate (IM) compared to conventional therapy using vinblastine and prednisolone (VP) in canine cutaneous MCTs. Twenty-four dogs were included in the study; 13 animals were treated with IM and 11 with VP. Tumor tissue samples were submitted for histological diagnosis, grading and KIT immunostaining. The response to treatment was assessed by tomographic measurements according to VCOG criteria. Adverse events were classified according to VCOG-CTCAE criteria. The IM and VP groups had dogs with similar breeds, gender, ages, MCT localization, WHO stages and lymph node metastasis profiles. Most MCTs were grade 2/low and had KIT- patterns 2 and 3. The objective response rate (ORR) was significantly higher (30.79%) in the IM group then in VP group (9.09%). Adverse events (AE) in IM group were all grade 1, significantly different from VP. In conclusion, IM presented better ORR and less severe adverse events when compared to VP, representing a suitable option for the treatment of low-grade canine MCTs. [ABSTRACT FROM AUTHOR]

Particulate systems composed of polyelectrolyte complexes (PEC) based on chitosan and poly(methacrylic acid) were obtained via template polymerization. The resultant particles were characterized as having regions with different charge densities:  chitosan predominating in the core and poly(methacrylic acid) at the surface, the particles being negatively charged, as a consequence. Albumin was adsorbed on these particles (after cross-linking with glutardialdehyde), and pH was controlled to obtain two conditions:  (i) adsorption of positively charged albumin and (ii) adsorption of albumin at its isoelectric point. Adsorption isotherms and -potential measurements showed that albumin adsorption was controlled by hydrogen bonding/van der Waals interactions and that brush-like structures may enhance the adsorption of albumin on these particles. It was also found that shearing can induce desorption of albumin from the PEC surface, depending on the continuous phase albumin concentration. [ABSTRACT FROM AUTHOR]

1. Metoprolol, indoramine, codeine, tamoxifen and prodipine, compounds which are clinically used, and MDMA (ecstasy) were fitted in a small molecule model for substrates of human cytochrome P4502D6. 2. For both the R - and S -enantiomer of metoprolol, the R - and S -enantiomer of MDMA, and for indoramine and codeine (all proven substrates of cytochrome P4502D6) an acceptable fit in the substrate model was obtained. 3. For tamoxifen, for which the involvement of cytochrome P4502D6 in the 4- hydroxylation is uncertain, no acceptable fit could be obtained in the substrate model. 4. For prodipine, a competitive inhibitor of P4502D6, for which the involvement of P4502D6 in the metabolism is uncertain, no acceptable fit in the substrate model could be obtained. 5. The substrate model was extended in a direction in which two large known substrates extend from the original substrate model. This extension did not change the flat hydrophobic region of the original substrate model. [ABSTRACT FROM AUTHOR]