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

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

The SITS-UTMOST: a registry-based prospective study in Europe investigating the impact of regulatory approval of intravenous Actilyse in the extended time window (3–4.5 h) in acute ischaemic stroke

Introduction: The SITS-UTMOST (Safe Implementation of Thrombolysis in Upper Time window Monitoring Study) was a registry-based prospective study of intravenous alteplase used in the extended time window (3–4.5 h) in acute ischaemic stroke to evaluate the impact of the approval of the extended time window on routine clinical practice. Patients and methods: Inclusion of at least 1000 patients treated within 3–4.5 h according to the licensed criteria and actively registered in the SITS-International Stroke Thrombolysis Registry was planned. Prospective data collection started 2 May 2012 and ended 2 November 2014. A historical cohort was identified for 2 years preceding May 2012. Clinical management and outcome were contrasted between patients treated within 3 h versus 3–4.5 h in the prospective cohort and between historical and prospective cohorts for the 3 h time window. Outcomes were functional independency (modified Rankin scale, mRS) 0–2, favourable outcome (mRS 0–1), and death at 3 months and symptomatic intracerebral haemorrhage (SICH) per SITS. Results: 4157 patients from 81 centres in 12 EU countries were entered prospectively (N ¼ 1118 in the 3–4.5 h, N ¼ 3039 in the 0–3 h time window) and 3454 retrospective patients in the 0–3 h time window who met the marketing approval conditions. In the prospective cohort, median arrival to treatment time was longer in the 3–4.5 h than 3 h window (79 vs. 55 min). Within the 3 h time window, treatment delays were shorter for prospective than historical patients (55 vs. 63). There was no significant difference between the 3–4.5 h versus 3 h prospective cohort with regard to percentage of reported SICH (1.6 vs. 1.7), death (11.6 vs. 11.1), functional independency (66 vs. 65) at 3 months or favourable outcome (51 vs. 50). Discussion: Main weakness is the observational design of the study. Conclusion: This study neither identified negative impact on treatment delay, nor on outcome, following extension of the approved time window to 4.5 h for use of alteplase in stroke

Charge transfer and adhesion in Rh/MgO(001)

Ab initio density functional calculations are reported for Rh adlayers on MgO(001) at coverages of 1, 1/2 and 1/8 monolayers. It is shown that charge is transferred from oxide surface to the Rh adatoms. The transfer ranges from 0.06 e to 0.27 e, depending upon adsorption site and coverage. In comparison, transfers of 0.08 e from adatom to surface and 0.32 e surface to adatom are found for monolayer coverages of Mg and O, respectively. With the Rh adatoms, significant charge polarization of both Rh and the surface are also seen, but it is never-the-less found that the adhesion energy is linearly related to the charge transfer, with the most stable adsorption site at any particular coverage being the one at which the charge transfer is a maximum

Comment on "First-principles study of the influence of (110)-oriented strain on the ferroelectric properties of rutile TiO2"

In a recent article, Gr\"{u}nebohm et al. [Phys. Rev. B 84 132105 (2011), arXiv:1106.2820] report that they fail to reproduce the A2u ferroelectric instability of TiO2 in the rutile structure calculated with density functional theory within the PBE-GGA approximation by Montanari et al. [Chem. Phys. Lett 364, 528 (2002)]. We demonstrate that this disagreement arises from an erroneous treatment of Ti 3s and 3p semi-core electrons as core in their calculations. Fortuitously the effect of the frozen semi-core pseudopotential cancels the phonon instability of the PBE exchange-correlation, and the combination yields phonon frequencies similar to the LDA harmonic values. Gr\"{u}nebohm et al. also attempted and failed to reproduce the soft acoustic phonon mode instability under (110) strain reported by Mitev et al. [Phys. Rev. B 81 134303 (2010)]. For this mode the combination of PBE-GGA and frozen semi-core yields a small imaginary frequency of 9.8i. The failure of Gr\"{u}nebohm et al. to find this mode probably arose from numerical limitations of the geometry optimization approach in the presence of a shallow double well potential; the optimization method is not suitable for locating such instabilities.Comment: 5 page

Interacting supernovae and supernova impostors. SN 2007sv: the major eruption of a massive star in UGC 5979

We report the results of the photometric and spectroscopic monitoring campaign of the transient SN 2007sv. The observables are similar to those of type IIn supernovae, a well-known class of objects whose ejecta interact with pre-existing circum-stellar material. The spectra show a blue continuum at early phases and prominent Balmer lines in emission, however, the absolute magnitude at the discovery of SN 2007sv (M_R = - 14.25 +/- 0.38) indicate it to be most likely a supernova impostor. This classification is also supported by the lack of evidence in the spectra of very high velocity material as expected in supernova ejecta. In addition we find no unequivocal evidence of broad lines of alpha - and/or Fe-peak elements. The comparison with the absolute light curves of other interacting objects (including type IIn supernovae) highlights the overall similarity with the prototypical impostor SN 1997bs. This supports our claim that SN 2007sv was not a genuine supernova, and was instead a supernova impostor, most likely similar to the major eruption of a luminous blue variable.Comment: Accepted for publication in MNRAS. 15 pages, 11 figures, 5 table

Design of a secondary combustion chamber for a 350 kW wood-chips Gred furnace.

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Identifying and assessing benefit–risk in primary care—a family physician’s perspective

For the family physician, NSAIDs, both traditional and cyclo-oxgenase-2 inhibitors, are a valuable contribution to managing arthritis and other rheumatological conditions in primary care. Yet, many of the patients seen by the family doctor have complex comorbidities and polypharmacy issues. This review looks at the main considerations for primary-care physicians while choosing an anti-inflammatory treatment for a hypothetical patient case study. In addition to looking at the evidence for gastrointestinal and cardiovascular risk, the concomitant use of aspirin with an NSAID is also examined. New evidence for interaction between selective serotonin re-uptake inhibitors is reviewed and the interaction between angiotensin-converting enzyme inhibitors and NSAIDs is considered. Making careful judgements based on individual needs, medical history and comorbidities is recommended based on the evidence reviewed