Pretreatment resistin levels are associated with erosive disease in early rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs and infliximab.

OBJECTIVE: Resistin is an adipocytokine related to insulin resistance and inflammation. We investigated whether resistin is associated with disease activity and inflammation in disease-modifying anti-rheumatic drug (DMARD)-naïve rheumatoid arthritis (RA) patients, whether it has predictive value for radiological disease progression, and whether tumour necrosis factor-α (TNF-α) is involved in these effects. METHOD: Ninety-nine patients with early, DMARD-naïve RA participated in the NEO-RACo study. Patients were treated for the first 4 weeks with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone (FIN-RACo treatment). Thereafter, they were randomized to receive either infliximab or placebo added to the combination for 6 months. Patients were followed for 5 years. Disease activity was evaluated using the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate, radiographs were scored with the modified Sharp-van der Heijde method, and plasma resistin concentrations were measured by immunoassay. Human THP-1 macrophages were used in the in vitro studies. RESULTS: A high resistin level at baseline was associated with active inflammatory disease and predicted more rapid radiological progression during 5 year follow-up. Adding infliximab to the DMARD combination delayed radiological progression and overcame the poor predictive value of resistin. Resistin increased TNF-α production in human macrophages, indicating a possible connection between resistin and TNF-α. CONCLUSION: The results suggest that high resistin concentration may be a useful marker to distinguish patients with an increased risk of erosive disease in early active RA, and that adding TNF-α antagonist to the traditional DMARD combination may delay radiological progression of the disease in these patients. The study has been registered at https://www.clinicaltrials.gov(NCT00908089).

Aprotinin Impacts 8-Isoprostane after Coronary Artery Bypass Grafting.

BACKGROUND AND AIMS:: The lungs participate in the modulation of the circulating inflammatory factors induced by coronary artery bypass grafting. We investigated whether aprotinin-which has been suggested to interact with inflammation-influences lung passage of key inflammatory factors after coronary artery bypass grafting. MATERIAL AND METHODS:: A total of 40 patients undergoing coronary artery bypass grafting were randomized into four groups according to aprotinin dose: (1) high dose, (2) early low dose, (3) late low dose, and (4) without aprotinin. Pulmonary artery and radial artery blood samples were collected for the evaluation of calculated lung passage (pulmonary artery/radial artery) of the pro-inflammatory factors interleukin 6 and interleukin 8, 8-isoprostane, myeloperoxidase and the anti-inflammatory interleukin 10 immediately after induction of anesthesia (T1), 1 min after releasing aortic cross clamp (T2), 15 min after releasing aortic cross clamp (T3), 1 h after releasing aortic cross clamp (T4), and 20 h after releasing aortic cross clamp (T5). RESULTS:: Pulmonary artery/radial artery 8-isoprostane increased in patients with high aprotinin dose as compared with lower doses (1.1 range 0.97 vs 0.9 range 1.39, p = 0.001). The main effect comparing high aprotinin dose with lower doses was significant (F(1, 38) = 7.338, p = 0.01, partial eta squared = 0.16) further supporting difference in the effectiveness of high aprotinin dose for pulmonary artery/radial artery 8-isoprostane. CONCLUSION:: According to the pulmonary artery/radial artery equation, the impact of aprotinin on 8-isoprostane after coronary artery bypass grafting is dose dependent. Aprotinin may aid the lung passage of circulating factors toward a beneficial anti-inflammatory milieu.

Substitutional carbon doping of free-standing and Ru-supported BN sheets: a first-principles study.

The development of spatially homogeneous mixed structures with boron (B), nitrogen (N) and carbon (C) atoms arranged in a honeycomb lattice is highly desirable, as they open the possibility of creating stable two-dimensional materials with tunable band gaps. However, at least in the free-standing form, the mixed BCN system is energetically driven towards phase segregation to graphene and hexagonal BN. It is possible to overcome the segregation when BCN material is grown on a particular metal substrate, for example Ru(0 0 0 1), but the stabilization mechanism is still unknown. With the use of density-functional theory we study the energetics of BN/Ru slabs, with different types of configurations of C substitutional defects introduced to the h-BN overlayer. The results are compared to the energetics of free-standing BCN materials. We found that the substrate facilitates the C substitution process in the h-BN overlayer. Thus, more homogeneous BCN material can be grown, overcoming the segregation into graphene and h-BN. In addition, we investigate the electronic and transport gaps in free-standing BCN structures, and assess their mechanical properties and stability. The band gap in mixed BCN free-standing material depends on the concentration of the constituent elements and ranges from zero in pristine graphene to nearly 5 eV in free-standing h-BN. This makes BCN attractive for application in modern electronics.

The Impact of Lung Ventilation on Some Cytokines after Coronary Artery Bypass Grafting.

BACKGROUND AND AIMS: Cardiopulmonary bypass induces a systematic inflammatory response, which is partly understood by investigation of peripheral blood cytokine levels alone; the lungs may interfere with the net cytokine concentration. We investigated whether lung ventilation influences lung passage of some cytokines after coronary artery bypass grafting. MATERIAL AND METHODS: In total, 47 patients undergoing coronary artery bypass grafting were enrolled, and 37 were randomized according to the ventilation technique: (1) No-ventilation group, with intubation tube detached from the ventilator; (2) low tidal volume group, with continuous low tidal volume ventilation; and (3) continuous 10 cm H2O positive airway pressure. Ten selected patients undergoing surgery without cardiopulmonary bypass served as a referral group. Representative pulmonary and radial artery blood samples were collected for the evaluation of calculated lung passage (pulmonary/radial artery) of the pro-inflammatory cytokines (interleukin 6 and interleukin 8) and the anti-inflammatory interleukin 10 immediately after induction of anesthesia (T1), 1 h after restoring ventilation/return of flow in all grafts (T2), and 20 h after restoring ventilation/return of flow in all grafts (T3). RESULTS: Pulmonary/radial artery interleukin 6 and pulmonary/radial artery interleukin 8 ratios ( p = 0.001 and p = 0.05, respectively) decreased, while pulmonary/radial artery interleukin 10 ratio ( p = 0.001) increased in patients without cardiopulmonary bypass as compared with patients with cardiopulmonary bypass. CONCLUSIONS: The pulmonary/radial artery equation is an innovative means for the evaluation of cytokine lung passage after coronary artery bypass grafting. The mode of lung ventilation has no impact on some cytokines after coronary artery bypass grafting in patients treated with cardiopulmonary bypass.

Monosodium iodoacetate-induced inflammation and joint pain are reduced in TRPA1 deficient mice--potential role of TRPA1 in osteoarthritis.

OBJECTIVES: Intra-articularly injected monosodium iodoacetate (MIA) induces joint pathology mimicking osteoarthritis (OA) and it is a widely used experimental model of OA. MIA induces acute inflammation, cartilage degradation and joint pain. Transient Receptor Potential Ankyrin 1 (TRPA1) is an ion channel known to mediate nociception and neurogenic inflammation. Here, we tested the hypothesis that TRPA1 would be involved in the development of MIA-induced acute inflammation, cartilage changes and joint pain. METHODS: The effects of pharmacological blockade (by TCS 5861528) and genetic depletion of TRPA1 were studied in MIA-induced acute paw inflammation. Cartilage changes (histological scoring) and joint pain (weight-bearing test) in MIA-induced experimental OA were compared between wild type and TRPA1 deficient mice. The effects of MIA were also studied in primary human OA chondrocytes and in mouse cartilage. RESULTS: MIA evoked acute inflammation, degenerative cartilage changes and joint pain in wild type mice. Interestingly, these responses were attenuated in TRPA1 deficient animals. MIA-induced paw inflammation was associated with increased tissue levels of substance P; and the inflammatory edema was reduced by pretreatment with catalase, with the TRPA1 antagonist TCS 5861528 and with the neurokinin 1 receptor antagonist L703,606. In chondrocytes, MIA enhanced interleukin-1 induced cyclooxygenase-2 (COX-2) expression, an effect that was blunted by pharmacological inhibition and genetic depletion of TRPA1. CONCLUSIONS: TRPA1 was found to mediate acute inflammation and the development of degenerative cartilage changes and joint pain in MIA-induced experimental OA in the mouse. The results reveal TRPA1 as a potential mediator and drug target in OA.

Formation, migration, and clustering of point defects in CuInSe2 from first principles.

The electronic properties of high-efficiency CuInSe(2) (CIS)-based solar cells are affected by the microstructural features of the absorber layer, such as point defect types and their distribution. Recently, there has been controversy over whether some of the typical point defects in CIS--V(Cu), V(Se), In(Cu), Cu(In)--can form stable complexes in the material. In this work, we demonstrate that the presence of defect complexes during device operational time can be justified by taking into account the thermodynamic and kinetic driving forces acting behind defect microstructure formation. Our conclusions are backed up by thorough state-of-the-art calculations of defect interaction potentials as well as the activation barriers surrounding the complexes. Defect complexes such as In(Cu)-2V(Cu), In(Cu)-Cu(In), and V(Se)-V(Cu) are shown to be stable against thermal dissociation at device operating temperatures, but can anneal out within tens of minutes at temperatures higher than 150-200 °C (V(Cu)-related complexes) or 400 °C (antisite pair). Our results suggest that the presence of these complexes can be controlled via growth temperatures, which provides a mechanism for tuning the electronic activity of defects and the device altogether.

Distinct regulation of tonsillar immune response in virus infection.

BACKGROUND: The relationships between tonsillar immune responses, and viral infection and allergy are incompletely known. OBJECTIVE: To study intratonsillar/nasopharyngeal virus detections and in vivo expressions of T-cell- and innate immune response-specific cytokines, transcription factors, and type I/II/III interferons in human tonsils. METHODS: Palatine tonsil samples were obtained from 143 elective tonsillectomy patients. Adenovirus, bocavirus-1, coronavirus, enteroviruses, influenza virus, metapneumovirus, parainfluenza virus, rhinovirus, and respiratory syncytial virus were detected using PCR. The mRNA expression levels of IFN-α, IFN-ß, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-ß, FOXP3, GATA3, RORC2, and Tbet were directly analyzed by quantitative RT-PCR. RESULTS: Fifty percentage of subjects reported allergy, 59% had ≥1 nasopharyngeal viruses, and 24% had ≥1 intratonsillar viruses. Tonsillar virus detection showed a strong negative association with age; especially rhinovirus or parainfluenza virus detection showed positive association with IFN-γ and Tbet expressions. IL-37 expression was positively associated with atopic dermatitis, whereas IFN-α, IL-13, IL-28, and Tbet expressions were negatively associated with allergic diseases. Network analyses demonstrated strongly polarized clusters of immune regulatory (IL-10, IL-17, TGF-ß, FOXP3, GATA3, RORC2, Tbet) and antiviral (IFN-α, IFN-ß, IL-28, IL-29) genes. These two clusters became more distinctive in the presence of viral infection or allergy. A negative correlation between antiviral cytokines and IL-10, IL-17, IL-37, FOXP3, and RORC2 was observed only in the presence of viruses, and interestingly, IL-13 strongly correlated with antiviral cytokines. CONCLUSIONS: Tonsillar cytokine expression is closely related to existing viral infections, age, and allergic illnesses and shows distinct clusters between antiviral and immune regulatory genes.

First-principles study of layered antiferromagnetic CuCrX2 (X = S, Se and Te).

We present detailed electronic band-structure calculations for antiferromagnetic chromium compounds, CuCrX(2) (X = S, Se or Te), carried out using spin-polarized density functional theory within the generalized-gradient approximation (GGA). A narrow-band semiconductor-to-metal transition is observed upon replacement of S or Se by Te. The indirect bandgap is found at 0.58 eV and 0.157 eV for CuCrS(2) and CuCrSe(2), respectively. The results for our theoretical calculations are well in line with the electronic transport properties experimentally observed for CuCrS(2) and CuCrSe(2).

Are we van der Waals ready?

We apply a range of density-functional-theory-based methods capable of describing van der Waals interactions with weakly bonded layered solids in order to investigate their accuracy for extended systems. The methods under investigation are the local-density approximation, semi-empirical force fields, non-local van der Waals density functionals and the random-phase approximation. We investigate the equilibrium geometries, elastic constants and binding energies of a large and diverse set of compounds and arrive at conclusions about the reliability of the different methods. The study also points to some directions of further development for the non-local van der Waals density functionals.

d0 ferromagnetic interface between nonmagnetic perovskites.

We use computational and experimental methods to study d(0) ferromagnetism at a charge-imbalanced interface between two perovskites. In SrTiO(3)/KTaO(3) superlattice calculations, the charge imbalance introduces holes in the SrTiO(3) layer, inducing a d(0) ferromagnetic half-metallic 2D hole gas at the interface oxygen 2p orbitals. The charge imbalance overrides doping by vacancies at realistic concentrations. Varying the constituent materials shows ferromagnetism to be a general property of hole-type d(0) perovskite interfaces. Atomically sharp epitaxial d(0) SrTiO(3)/KTaO(3), SrTiO(3)/KNbO(3), and SrTiO(3)/NaNbO(3) interfaces are found to exhibit ferromagnetic hysteresis at room temperature. We suggest that the behavior is due to the high density of states and exchange coupling at the oxygen t(1g) band in comparison with the more studied d band t(2g) symmetry electron gas.

van der Waals bonding in layered compounds from advanced density-functional first-principles calculations.

Although the precise microscopic knowledge of van der Waals interactions is crucial for understanding bonding in weakly bonded layered compounds, very little quantitative information on the strength of interlayer interaction in these materials is available, either from experiments or simulations. Here, using many-body perturbation and advanced density-functional theory techniques, we calculate the interlayer binding and exfoliation energies for a large number of layered compounds and show that, independent of the electronic structure of the material, the energies for most systems are around 20 meV/Å2. This universality explains the successful exfoliation of a wide class of layered materials to produce two-dimensional systems, and furthers our understanding the properties of layered compounds in general.

Vacancies in CuInSe2: new insights from hybrid-functional calculations.

We calculate the energetics of vacancies in CuInSe(2) using a hybrid functional (HSE06, HSE standing for Heyd, Scuseria and Ernzerhof), which gives a better description of the band gap compared to (semi)local exchange-correlation functionals. We show that, contrary to present beliefs, copper and indium vacancies induce no defect levels within the band gap and therefore cannot account for any experimentally observed levels. The selenium vacancy is responsible for only one level, namely, a deep acceptor level ε(0/2-). We find strong preference for V(Cu) and V(Se) over V(In) under practically all chemical conditions.

Resistin is linked to inflammation, and leptin to metabolic syndrome, in women with inflammatory arthritis.

OBJECTIVE: To investigate how inflammation and metabolic syndrome (MetS) are associated with adipokine levels in patients with inflammatory arthritis. METHODS: Fifty-four female patients with arthritis were enrolled in the study. Twenty (37%) of these patients had MetS, which was diagnosed according to the definition of the International Diabetes Federation (IDF). Interleukin (IL)-6 and four adipokines (resistin, leptin, adiponectin, and adipsin) were determined by immunoassay. Healthy women with body mass index (BMI) between 22 and 25 kg/m(2) served as controls. RESULTS: The patients with arthritis had higher levels of resistin than the healthy controls. This difference was clear in patients without MetS (17.4 in patients vs. 10.8 ng/mL in controls, p < 0.001), and even higher resistin levels were found in the patients with MetS (20.7 ng/mL; p < 0.001 vs. healthy controls; and p = 0.095 vs. patients without MetS). In the patients with arthritis and MetS, resistin correlated positively with IL-6 (Pearson's r = 0.5, p = 0.03). Leptin levels were increased in arthritis patients with MetS as compared to healthy controls, but not in patients without MetS. The statistically significant difference between patients with MetS and controls remained when leptin was adjusted with BMI. Accordingly, adiponectin levels were lower in patients with MetS than in healthy controls (p < 0.05). Leptin, adiponectin, and adipsin did not correlate with the inflammatory cytokine IL-6 or with C-reactive protein (CRP). CONCLUSIONS: The results show that high resistin levels are associated with arthritis independently of MetS, whereas leptin is increased only in arthritis patients with MetS.

Effect of gating and pressure on the electronic transport properties of crossed nanotube junctions: formation of a Schottky barrier.

The electronic transport properties of crossed carbon nanotube junctions are investigated using ab initio methods. The optimal atomic structures and the intertube distances of the junctions are obtained using van der Waals corrected density functional theory. The effect of gating on the intertube conductance of the junctions is explored, showing the charge accumulation to the nanotube contact and the charge depletion region at the metal-semiconductor Schottky contact. Finally, it is shown how the conductance of the junctions under the gate voltage is affected by pressure applied to the nanotube film.

Evidence for strain-induced ferroelectric order in epitaxial thin-film KTaO3.

In perovskite-structure epitaxial films, it has been theoretically predicted that the polarization and the coherence of polar order can increase with increasing crystallographic strain. Experimental evidence of strain-induced long-range ferroelectric order has not been obtained thus far, posing the fundamental question of whether or not strain can induce the long-range polar order. Here we demonstrate the existence of strain-induced ferroelectric order in quantum paraelectric KTaO3 by combining experimental investigations of epitaxial KTaO3 films and density-functional-theory calculations. The long-range ferroelectric order does exist under a large enough epitaxial strain. We suggest that a region of short-range polar order might appear between paraelectric and ferroelectric states in the strain-temperature phase diagrams.

Postconditioning and remote postconditioning of ischemic rat cardiac grafts.

BACKGROUND: Global warm ischemia of transplanted cardiac grafts is associated with apoptosis and subsequent tissue necrosis. It is suggested that postconditioning (PostC) may ameliorate the early outcome of cardiac grafts after ischemia-reperfusion. We investigated whether PostC and remote postconditioning (RPostC) have a histopathologic impact after transplantation of warm ischemic rat cardiac grafts. MATERIALS AND METHODS: Thirteen rats were randomized to undergo either PostC or RPostC after heterotopic transplantation of ischemic cardiac grafts. Six rats without intervention besides transplantation served as controls (control). The recipient rats were sacrificed 24 h after transplantation to evaluate histopathology and apoptotic index. RESULTS: No significant differences were observed between the study groups in terms of graft heat shock protein 70 and oxygen radical absorbing capacity, an indicator of antioxidant capacity. While apoptosis and PCARB, a marker of protein oxidation and oxidative stress, decreased after RPostC (p < 0.05), contraction band necrosis was less prominent in both PostC and RPostC. CONCLUSION: Both PostC and RPostC have a histopathologic impact after 24 h of reperfusion of warm ischemic rat cardiac grafts.

Elevated cerebrospinal fluid adiponectin and adipsin levels in patients with multiple sclerosis: a Finnish co-twin study.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the levels of three adipocytokines: leptin, adiponectin and adipsin, in serum and cerebrospinal fluid (CSF) of twins discordant for multiple sclerosis (MS). Adipose tissue is an important component connecting immune system and several tissues and organs including CNS. Fat cells produce adipocytokines, which seem to have a role in various autoimmune disorders including MS. METHODS: Plasma samples were collected from twelve twins and CSF samples from four twins discordant for MS. The concentrations of interleukine (IL)-6, adiponectin, adipsin and leptin in plasma and CSF samples were determined by enzyme immuno assay. RESULTS: A significant difference was seen in the adipocytokine levels in CSF samples. Twins with MS had higher concentrations of adiponectin (P = 0.039) and adipsin (P = 0.039), than their asymptomatic co-twins. CONCLUSION: As adiponectin and adipsin levels in CSF did not correlate with their levels in plasma, it seems that there could be a secondary intrathecal synthesis of these adipocytokines in MS.

Bronchial nitric oxide is related to symptom relief during fluticasone treatment in COPD.

High levels of exhaled nitric oxide (NO) predict favourable response to inhaled corticosteroids in asthma, but the ability of exhaled NO or inflammatory markers in exhaled breath condensate (EBC) to predict steroid responsiveness in chronic obstructive pulmonary disease (COPD) is not known. We measured alveolar and bronchial NO output, levels of leukotriene B(4) (LTB(4)), cysteinyl leukotrienes (cysLTs) and 8-isoprostane in EBC, spirometry, body plethysmography and symptoms in 40 subjects with COPD before and after 4 weeks of treatment with inhaled fluticasone (500 microg b.i.d.). Five subjects (12.5%) with COPD had significant improvement in lung function during fluticasone treatment, whereas 20 subjects (50%) had significant decrease in symptoms. High baseline bronchial NO flux was associated with higher increase in forced expiratory volume in 1 s to forced vital capacity ratio (r = 0.334, p = 0.038) and more symptom relief (r = -0.317, p = 0.049) during the treatment. Baseline EBC levels of LTB(4), cysLTs or 8-isoprostane were not related to response to fluticasone treatment. Inhaled fluticasone decreased bronchial NO flux but not alveolar NO concentration or markers in EBC. High levels of bronchial NO flux are related to symptom relief and improvement of airway obstruction during treatment with inhaled fluticasone in COPD. Markers of inflammation or oxidative stress in EBC are not related to steroid responsiveness in COPD.

Electronic structure calculations with GPAW: a real-space implementation of the projector augmented-wave method.

Electronic structure calculations have become an indispensable tool in many areas of materials science and quantum chemistry. Even though the Kohn-Sham formulation of the density-functional theory (DFT) simplifies the many-body problem significantly, one is still confronted with several numerical challenges. In this article we present the projector augmented-wave (PAW) method as implemented in the GPAW program package (https://wiki.fysik.dtu.dk/gpaw) using a uniform real-space grid representation of the electronic wavefunctions. Compared to more traditional plane wave or localized basis set approaches, real-space grids offer several advantages, most notably good computational scalability and systematic convergence properties. However, as a unique feature GPAW also facilitates a localized atomic-orbital basis set in addition to the grid. The efficient atomic basis set is complementary to the more accurate grid, and the possibility to seamlessly switch between the two representations provides great flexibility. While DFT allows one to study ground state properties, time-dependent density-functional theory (TDDFT) provides access to the excited states. We have implemented the two common formulations of TDDFT, namely the linear-response and the time propagation schemes. Electron transport calculations under finite-bias conditions can be performed with GPAW using non-equilibrium Green functions and the localized basis set. In addition to the basic features of the real-space PAW method, we also describe the implementation of selected exchange-correlation functionals, parallelization schemes, ΔSCF-method, x-ray absorption spectra, and maximally localized Wannier orbitals.

Multiscale study of hydrogen diffusion and clustering on carbon nanotube.

In this paper we report the results of a multiscale study of hydrogen clusterization at the surface of (10,0) carbon nanotube. For this purpose, a systematic study of the binding energies and migration barriers of hydrogen adatom and various close adatom pairs of has been undertaken using density-functional theory approach. The interaction between hydrogen atoms on the surface of nanotube is shown to be long ranged and anisotropic. On applying the obtained potential energy surfaces for lattice kinetic Monte Carlo simulations of chemisorbed hydrogen annealihg, a noticeable influence of the annealing conditions on cluster sizes, shapes and relative populations has bean revealed, which opens a possibility for the control of hydrogen clusterization kinetics. The effect on carbon nanotube electronic structure from hydrogen dimers and trimers most frequently met in lattice kinetic Monte Carlo simulations is discussed.