Human articular chondrocytes express ChemR23 and chemerin; ChemR23 promotes inflammatory signalling upon binding the ligand chemerin21-157

Chemerin is a chemotactic peptide which directs leukocytes expressing the chemokine-like receptor ChemR23 towards sites of inflammation. ChemR23 is a G protein-coupled receptor which binds several different ligands, and it is also expressed by other cell types such as adipocytes. In addition to chemotaxis, recent reports suggest that ChemR23 is capable of mediating either inflammatory or anti-inflammatory effects, depending on the type of ligand it binds. In the present study, we aimed to clarify whether human chondrocytes express ChemR23 and chemerin, and whether chemerin/ChemR23 signalling could affect secretion of inflammatory mediators. Tissue sections were taken from human knee joints and labelled with antibodies towards chemerin and ChemR23. Chondrocytes from cartilage tissue were isolated, cultured and assessed for chemerin and ChemR23 expression by PCR and immunolabelling. Receptor activation and intracellular signalling were studied by assessment of phosphorylated mitogen activated protein kinases (MAPKs) and phosphorylated Akt after stimulating cells with recombinant chemerin21-157. Biological effects of chemerin21-157 were investigated by measuring secretion of pro-inflammatory cytokines and metalloproteases in cell supernatants. Both serially cultured human articular chondrocytes and resident cells in native cartilage expressed chemerin and ChemR23. Stimulating cells with chemerin21-157 resulted in phosphorylation of p44/p42 MAPKs (ERK 1/2) and Akt (Ser 473). Also, significantly enhanced levels of the pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and the matrix metalloproteases MMP-1, MMP-2, MMP-3, MMP-8 and MMP-13 were detected. These results demonstrate that human chondrocytes express both the receptor ChemR23 and the ligand chemerin. Chemerin21-157 stimulation engaged signal-transduction pathways that further promoted inflammatory signalling in chondrocytes, as judged by an enhanced secretion of cytokines and metalloproteases. Taken together, the previously reported chemotaxis and the present findings suggest that the receptor and its ligand may play pivotal roles in joint inflammation

Serum osteoprotegerin levels are related to height loss: The Tromsø Study

Severe loss of body height is often a consequence of osteoporotic vertebral fractures. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL) are cytokines essential for the regulation of bone resorption. The aim of this study was to assess the relationship between the OPG/RANKL system and height loss. A total of 4,435 inhabitants from the municipality of Tromsø, Norway (2,169 men and 2,266 women) were followed for 6 years. Baseline measurements included height, weight, bone mineral density, OPG, RANKL, serum parathyroid hormone and information about lifestyle, prevalent diseases and use of medication. Height was measured again at follow-up, and the loss of height was categorized into 4 groups: ≤1, 1.1–2, 2.1–3, >3 cm. We found increasing height loss with increasing baseline OPG levels in both men and women (P trend = 0.02 and 0.001, respectively), after adjustments for age and other confounders. However, when the women were stratified according to menopausal status and use of hormone replacement therapy (HRT), a significant relationship was present only among postmenopausal women not using HRT (P trend = 0.02). No relations between OPG and height loss were found in post-menopausal HRT-users and premenopausal women (P trend ≥0.39). We conclude that height loss is positively associated with OPG in men and in postmenopausal women not using HRT. No relationship was found between RANKL and height loss

Nonlinear dynamics of semiconductor lasers with active optical feedback

An in-depth theoretical as well as experimental analysis of the nonlinear dynamics in semiconductor lasers with active optical feedback is presented. Use of a monolithically integrated multi-section device of sub-mm total length provides access to the short-cavity regime. By introducing an amplifier section as novel feature, phase and strength of the feedback can be separately tuned. In this way, the number of modes involved in the laser action can be adjusted. We predict and observe specific dynamical scenarios. Bifurcations mediate various transitions in the device output, from single-mode steady-state to self-pulsation and between different kinds of self-pulsations, reaching eventually chaotic behavior in the multi-mode limit

High-frequency pulsations in DFB-lasers with amplified feedback

We describe the basic ideas behind the concept of DFB-lasers with short optical feedback for the generation of high-frequency self-pulsations (SPs) and show the theoretical background describing realized devices. It is predicted by theory that the SP frequency increases with increasing feedback strength. To provide evidence for this we propose a novel device design which employs an amplifier section in the integrated feedback cavity of a DFB-laser. We present results from numerical simulations and experiments. It has been shown experimentally that a continuous tuning of the SP frequency from 12 to 45GHz can be adjusted via the control of the feedback strength. The numerical simulations which are in good accordance with experimental investigations give an explanation for a self stabilizing effect of the SPs due to the additional carrier dynamic in the integrated feedback cavity

Serum osteoprotegerin and renal function in the general population: The Tromsø Study

The following article: Vik, A., Brodin, E.E., Mathiesen, E.B., Brox, J., Jørgensen, L., Njølstad, I., ... Hansen, J.-B. (2017). Serum osteoprotegerin and renal function in the general population: The Tromsø Study. Clinical Kidney Journal, 10(1), 38-44. https://doi.org/10.1093/ckj/sfw095, has been accepted for publication in Clinical Kidney Journal Published by Oxford University Press. Source at https://doi.org/10.1093/ckj/sfw095. Published manuscript version, licensed CC BY-NC-ND 4.0.Background: Serum osteoprotegerin (OPG) is elevated in patients with chronic kidney disease (CKD) and increases with decreasing renal function. However, there are limited data regarding the association between OPG and renal function in the general population. The aim of the present study was to explore the relation between serum OPG and renal function in subjects recruited from the general population. Methods: We conducted a cross-sectional study with 6689 participants recruited from the general population in Tromsø, Norway. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equations. OPG was modelled both as a continuous and categorical variable. General linear models and linear regression with adjustment for possible confounders were used to study the association between OPG and eGFR. Analyses were stratified by the median age, as serum OPG and age displayed a significant interaction on eGFR. Results: In participants ≤62.2 years with normal renal function (eGFR ≥90 mL/min/1.73 m2) eGFR increased by 0.35 mL/min/1.73 m2 (95% CI 0.13–0.56) per 1 standard deviation (SD) increase in serum OPG after multiple adjustment. In participants older than the median age with impaired renal function (eGFR 2), eGFR decreased by 1.54 (95% CI −2.06 to −1.01) per 1 SD increase in serum OPG. Conclusions: OPG was associated with an increased eGFR in younger subjects with normal renal function and with a decreased eGFR in older subjects with reduced renal function. Our findings imply that the association between OPG and eGFR varies with age and renal function

Amoxicillin did not Reduce Modic Change Oedema in Patients with Chronic Low Back pain - subgroup Analyses of a Randomised Trial (the AIM study)

Study Design. Exploratory subgroup analyses of a randomised trial [Antibiotics in Modic changes (AIM) study]. Objective. The aim was to assess the effect of amoxicillin versus placebo in reducing Modic change (MC) edema in patients with chronic low back pain. Summary of Background Data. The AIM study showed a small, clinically insignificant effect of amoxicillin on pain-related disability in patients with chronic low back pain and MC type 1 (edema type) on magnetic resonance imaging (MRI). Materials and Methods. A total of 180 patients were randomised to receive 100 days of amoxicillin or placebo. MC edema was assessed on MRI at baseline and one-year follow-up. Per-protocol analyses were conducted in subgroups with MC edema on short tau inversion recovery (STIR) or T1/T2-weighted MRI at baseline. MC edema reductions (yes/no) in STIR and T1/T2 series were analyzed separately. The effect of amoxicillin in reducing MC edema was analyzed using logistic regression adjusted for prior disk surgery. To assess the effect of amoxicillin versus placebo within the group with the most abundant MC edema on STIR at baseline (“STIR3” group), we added age, STIR3 (yes/no), and STIR3×treatment group (interaction term) as independent variables and compared the marginal means (probabilities of edema reduction). Results. Compared to placebo, amoxicillin did not reduce MC edema on STIR (volume/intensity) in the total sample with edema on STIR at baseline (odds ratio 1.0, 95% CI: 0.5, 2.0; n=141) or within the STIR3 group (probability of edema reduction 0.69, 95% CI: 0.47, 0.92 with amoxicillin and 0.61, 95% CI: 0.43, 0.80 with placebo; n=41). Compared with placebo, amoxicillin did not reduce MC edema in T1/T2 series (volume of the type 1 part of MCs) (odds ratio: 1.0, 95% CI: 0.5, 2.3, n=104). Edema declined in >50% of patients in both treatment groups. Conclusions. From baseline to one-year follow-up, amoxicillin did not reduce MC edema compared with placebo.publishedVersio

Amoxicillin did not Reduce Modic Change Oedema in Patients with Chronic Low Back pain - subgroup Analyses of a Randomised Trial (the AIM study)

Study Design. Exploratory subgroup analyses of a randomised trial (Antibiotics In Modic changes (AIM) study). Objective. To assess the effect of amoxicillin versus placebo in reducing Modic change (MC) oedema in patients with chronic low back pain (LBP). Summary of Background Data. The AIM study showed a small, clinically insignificant effect of amoxicillin on pain-related disability in patients with chronic LBP and MC type 1 (oedema type) on magnetic resonance imaging (MRI). Methods. A total of 180 patients were randomised to receive 100 days of amoxicillin or placebo. MC oedema was assessed on MRI at baseline and one-year follow-up. Per-protocol analyses were conducted in subgroups with MC oedema on short tau inversion recovery (STIR) or T1/T2-weighted MRI at baseline. MC oedema reductions (yes/no) in STIR and T1/T2-series were analysed separately. The effect of amoxicillin in reducing MC oedema was analysed using logistic regression adjusted for prior disc surgery. To assess the effect of amoxicillin versus placebo within the group with the most abundant MC oedema on STIR at baseline (‘STIR3’ group), we added age, STIR3 (yes/no), and STIR3×treatment group (interaction term) as independent variables and compared the marginal means (probabilities of oedema reduction). Results. Compared to placebo, amoxicillin did not reduce MC oedema on STIR (volume/intensity) in the total sample with oedema on STIR at baseline (odds ratio 1.0, 95% confidence interval (95%CI) [0.5, 2.0]; n=141) or within the STIR3 group (probability of oedema reduction 0.69, 95%CI [0.47, 0.92] with amoxicillin and 0.61, 95%CI [0.43, 0.80] with placebo; n=41). Compared with placebo, amoxicillin did not reduce MC oedema in T1/T2-series (volume of the type 1 part of MCs) (odds ratio 1.0, 95%CI [0.5, 2.3], n=104). Oedema declined in >50% of patients in both treatment groups. Conclusions. From baseline to one-year follow-up, amoxicillin did not reduce MC oedema compared with placebo. Level of Evidence. Level 2

A competitive strategy for atrial and aortic tract segmentation based on deformable models

Multiple strategies have previously been described for atrial region (i.e. atrial bodies and aortic tract) segmentation. Although these techniques have proven their accuracy, inadequate results in the mid atrial walls are common, restricting their application for specific cardiac interventions. In this work, we introduce a novel competitive strategy to perform atrial region segmentation with correct delineation of the thin mid walls, and integrated it into the B-spline Explicit Active Surfaces framework. A double stage segmentation process is used, which starts with a fast contour growing followed by a refinement stage with local descriptors. Independent functions are used to define each region, being afterward combined to compete for the optimal boundary. The competition locally constrains the surface evolution, prevents overlaps and allows refinement to the walls. Three different scenarios were used to demonstrate the advantages of the proposed approach, through the evaluation of its segmentation accuracy, and its performance for heterogeneous mid walls. Both computed tomography and magnetic resonance imaging datasets were used, presenting results similar to the state-of-the-art methods for both atria and aorta. The competitive strategy showed its superior performance with statistically significant differences against the traditional free-evolution approach in cases with bad image quality or missed atrial/aortic walls. Moreover, only the competitive approach was able to accurately segment the atrial/aortic wall. Overall, the proposed strategy showed to be suitable for atrial region segmentation with a correct segmentation of the mid thin walls, demonstrating its added value with respect to the traditional techniques.The authors acknowledge Fundacao para a Ciencia e a Tecnologia (FCT), in Portugal, and the European Social Found, European Union, for funding support through the "Programa Operacional Capital Humano" (POCH) in the scope of the PhD grants SFRH/BD/95438/2013 (P. Morais) and SFRH/BD/93443/2013 (S. Queiros).Authors gratefully acknowledge the funding of projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000022, co-financed by "Programa Operacional Regional do Norte" (NORTE2020), through "Fundo Europeu de Desenvolvimento Regional" (FEDER).info:eu-repo/semantics/publishedVersio