Quantitative sensory testing in painful hand osteoarthritis demonstrates features of peripheral sensitisation.

Hand osteoarthritis (HOA) is a prevalent condition for which treatments are based on analgesia and physical therapies. Our primary objective was to evaluate pain perception in participants with HOA by assessing the characteristics of nodal involvement, pain threshold in each hand joint, and radiological severity. We hypothesised that inflammation in hand osteoarthritis joints enhances sensitivity and firing of peripheral nociceptors, thereby causing chronic pain. Participants with proximal and distal interphalangeal (PIP and DIP) joint HOA and non-OA controls were recruited. Clinical parameters of joint involvement were measured including clinical nodes, VAS (visual analogue score) for pain (0-100 mm scale), HAQ (health assessment questionnaire), and Kellgren-Lawrence scores for radiological severity and pain threshold measurement were performed. The mean VAS in HOA participants was 59.3 mm ± 8.19 compared with 4.0 mm ± 1.89 in the control group (P < 0.0001). Quantitative sensory testing (QST) demonstrated lower pain thresholds in DIP/PIP joints and other subgroups in the OA group including the thumb, metacarpophalangeal (MCPs), joints, and wrists (P < 0.008) but not in controls (P = 0.348). Our data demonstrate that HOA subjects are sensitised to pain due to increased firing of peripheral nociceptors. Future work to evaluate mechanisms of peripheral sensitisation warrants further investigation

Tenascin-C fragments are endogenous inducers of cartilage matrix degradation

Cartilage destruction is a hallmark of osteoarthritis (OA) and is characterized by increased protease activity resulting in the degradation of critical extracellular matrix (ECM) proteins essential for maintaining cartilage integrity. Tenascin-C (TN-C) is an ECM glycoprotein, and its expression is upregulated in OA cartilage. We aimed to investigate the presence of TN-C fragments in arthritic cartilage and establish whether they promote cartilage degradation. Expression of TN-C and its fragments was evaluated in cartilage from subjects undergoing joint replacement surgery for OA and RA compared with normal subjects by western blotting. The localization of TN-C in arthritic cartilage was also established by immunohistochemistry. Recombinant TN-C fragments were then tested to evaluate which regions of TN-C are responsible for cartilage-degrading activity in an ex vivo cartilage explant assay measuring glycosaminoglycan (GAG) release, aggrecanase and matrix metalloproteinase (MMP) activity. We found that specific TN-C fragments are highly upregulated in arthritic cartilage. Recombinant TN-C fragments containing the same regions as those identified from OA cartilage mediate cartilage degradation by the induction of aggrecanase activity. TN-C fragments mapping to the EGF-L and FN type III domains 3-8 of TN-C had the highest levels of aggrecan-degrading ability that was not observed either with full-length TN-C or with other domains of TN-C. TN-C fragments represent a novel mechanism for cartilage degradation in arthritis and may present new therapeutic targets for the inhibition of cartilage degradation

Many competing ceria (110) oxygen vacancy structures: from small to large supercells

We present periodic “DFT+U” studies of single oxygen vacancies on the CeO2(110) surface using a number of different supercells, finding a range of different local minimum structures for the vacancy and its two accompanying Ce(III) ions. We find three different geometrical structures in combination with a variety of different Ce(III) localization patterns, several of which have not been studied before. The desired trapping of electrons was achieved in a two-stage optimization procedure. We find that the surface oxygen nearest to the vacancy either moves within the plane towards the vacancy, or rises out of the surface into either a symmetric or an unsymmetric bridge structure. Results are shown in seven slab geometry supercells, p(2 × 1), p(2 × 2), p(2 × 3), p(3 × 2), p(2 × 4), p(4 × 2), and p(3 × 3), and indicate that the choice of supercell can affect the results qualitatively and quantitatively. An unsymmetric bridge structure with one nearest and one next-nearest neighbour Ce(III) ion (a combination of localizations not previously found) is the ground state in all (but one) of the supercells studied here, and the relative stability of other structures depends strongly on supercell size. Within any one supercell the formation energies of the different vacancy structures differ by up to 0.5 eV, but the same structure can vary by up to ∼1 eV between supercells. Furthermore, finite size scaling suggests that the remaining errors (compared to still larger supercells) can also be ∼1 eV for some vacancy structures

Description of polarons in ceria using Density Functional Theory

The performance of various density functional theory (DFT) functionals in reproducing the localization of Ce4f electrons to form polarons in cerium dioxide (ceria) is studied. It is found that LDA+U with U=6eV provides the best description, followed by GGA+U with U=5 eV. Hybrids perform worse, with PBE0 better than HSE06 and HSE03. It is also demonstrated that the improvement in the description of the polarons obtained from LDA+U and GGA+U is due primarily to the effect the U has on the filled Ce4f states, but the improvement obtained using the hybrids is primarily due to their effect on the empty states. This difference can be expected to strongly impact some detailed predictions for the properties of ceria obtained using the two classes of functional

B3LYP calculations of cerium oxides RID C-3994-2009

In this paper we evaluate the performance of density functional theory with the B3LYP functional for calculations on ceria (CeO2) and cerium sesquioxide (Ce2O3). We demonstrate that B3LYP is able to describe CeO2 and Ce2O3 reasonably well. When compared to other functionals, B3LYP performs slightly better than the hybrid functional PBE0 for the electronic properties but slightly worse for the structural properties, although neither performs as well as LDA+U(U=6 eV) or PBE+U(U=5 eV).We also make an extensive comparison of atomic basis sets suitable for periodic calculations of these cerium oxides. Here we conclude that there is currently only one type of cerium basis set available in the literature that is able to give a reasonable description of the electronic structure of both CeO2 and Ce2O3. These basis sets are based on a 28 electron effective core potential (ECP) and 30 electrons are attributed to the valence space of cerium. Basis sets based on 46 electron ECPs fail for these materials

Hydrodynamic modelling of the microbial water quality in a drinking water source as input for risk reduction management

To mitigate the faecal contamination of drinking water sources and, consequently, to prevent waterborne disease outbreaks, an estimation of the contribution from different sources to the total faecal contamination at the raw water intake of a drinking water treatment plant is needed. The aim of this article was to estimate how much different sources contributed to the faecal contamination at the water intake in a drinking water source, Lake Rådasjön in Sweden. For this purpose, the fate and transport of faecal indicator Escherichia coli within Lake Rådasjön were simulated by a three-dimensional hydrodynamic model. The calibrated hydrodynamic model described the measured data on vertical temperature distribution in the lake well (the Pearson correlation coefficient was 0.99). The data on the E. coli load from the identified contamination sources were gathered and the fate and transport of E. coli released from these sources within the lake were simulated using the developed hydrodynamic model, taking the decay of the E. coli into account. The obtained modelling results were compared to the observed E. coli concentrations at the water intake. The results illustrated that the sources that contributed the most to the faecal contamination at the water intake in Lake Rådasjön were the discharges from the on-site sewers and the main inflow to the lake – the river Mölndalsån. Based on the modelling results recommendations for water producers were formulated. The study demonstrated that this modelling approach is a useful tool for estimating the contribution from different sources to the faecal contamination at the water intake of a drinking water treatment plant and provided decision-support information for the reduction of risks posed to the drinking water source

Development and Validation of a ReaxFF Reactive Force Field for Cu Cation/Water Interactions and Copper Metal/Metal Oxide/Metal Hydroxide Condensed Phases

To enable large-scale reactive dynamic simulations of copper oxide/water and copper ion/water interactions we have extended the ReaxFF reactive force field framework to Cu/O/H interactions. To this end, we employed a multistage force field development strategy, where the initial training set (containing metal/metal oxide/metal hydroxide condensed phase data and [Cu(H_2O)_n]^(2+) cluster structures and energies) is augmented by single-point quantum mechanices (QM) energies from [Cu(H_2O)_n]^(2+) clusters abstracted from a ReaxFF molecular dynamics simulation. This provides a convenient strategy to both enrich the training set and to validate the final force field. To further validate the force field description we performed molecular dynamics simulations on Cu^(2+)/water systems. We found good agreement between our results and earlier experimental and QM-based molecular dynamics work for the average Cu/water coordination, Jahn−Teller distortion, and inversion in [Cu(H_2O)_6]^(2+) clusters and first- and second-shell O−Cu−O angular distributions, indicating that this force field gives a satisfactory description of the Cu-cation/water interactions. We believe that this force field provides a computationally convenient method for studying the solution and surface chemistry of metal cations and metal oxides and, as such, has applications for studying protein/metal cation complexes, pH-dependent crystal growth/dissolution, and surface catalysis

Electromagnetic finite-size effects to the hadronic vacuum polarization

In order to reduce the current hadronic uncertainties in the theory prediction for the anomalous magnetic moment of the muon, lattice calculations need to reach sub-percent accuracy on the hadronic-vacuum-polarization contribution. This requires the inclusion of $\mathcal{O}(\alpha)$ electromagnetic corrections. The inclusion of electromagnetic interactions in lattice simulations is known to generate potentially large finite-size effects suppressed only by powers of the inverse spatial extent. In this paper we derive an analytic expression for the $\mathrm{QED}_{\mathrm{L}}$ finite-volume corrections to the two-pion contribution to the hadronic vacuum polarization at next-to-leading order in the electromagnetic coupling in scalar QED. The leading term is found to be of order $1/L^{3}$ where $L$ is the spatial extent. A $1/L^{2}$ term is absent since the current is neutral and a photon far away thus sees no charge and we show that this result is universal. Our analytical results agree with results from the numerical evaluation of loop integrals as well as simulations of lattice scalar $U(1)$ gauge theory with stochastically generated photon fields. In the latter case the agreement is up to exponentially suppressed finite-volume effects. For completeness we also calculate the hadronic vacuum polarization in infinite volume using a basis of 2-loop master integrals.Comment: 42 pages, 11 figure