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68 result(s) for "Christensen, Tove"
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Biomarkers of Inflammation and Axonal Degeneration/Damage in Patients with Newly Diagnosed Multiple Sclerosis: Contributions of the Soluble CD163 CSF/Serum Ratio to a Biomarker Panel
Expression of soluble CD163 (sCD163), a macrophage/microglia biomarker, is increased in inflammatory conditions, and sCD163 levels in the cerebrospinal fluid (CSF) have recently been shown to be elevated in patients with multiple sclerosis (MS): the sCD163 CSF/serum ratio was elevated in patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and clinically isolated syndrome (CIS) compared with symptomatic controls. To investigate the contributions of the sCD163 CSF/serum ratio to a biomarker panel focusing on inflammation and axonal degeneration in newly diagnosed MS; thus optimising a diagnostic biomarker panel for MS. After a full MS diagnostic work-up, including collection of paired samples of CSF and serum, 125 patients were included in this study. Patients were divided into groups based on their diagnosis, and patients with normal clinical and paraclinical findings were defined as symptomatic controls. Serum and CSF levels, ratios, and indices of sCD163, CXCL13, osteopontin, neopterin, and CSF levels of neurofilament light polypeptide were determined by enzyme-linked immunosorbent assays (ELISAs). For sCD163 the results constitute a post-hoc analysis of already published data. All tested biomarkers, notably the sCD163 ratio, the CXCL13 ratio, the NEO ratio, the CSF level of NfL, the IgG index, and the serum level of OPN, were significantly correlated to RRMS, PPMS, and/or CIS. The individual biomarkers in single tests had a lower performance than the IgG index, however, their combined receiver operating characteristic (ROC) curve demonstrated excellent diagnostic discriminatory power. The biomarker panel showed distinct profiles for each patient group and could be a valuable tool for clinical differentiation of MS subgroups. The combined ROC analysis showed that sCD163 contributes positively as a diagnostic marker to a panel of established MS biomarkers. Patients with PPMS were demonstrated to have significantly elevated levels of both inflammatory and degenerative markers.
Citrullination of Histone H3 Interferes with HP1-Mediated Transcriptional Repression
Multiple Sclerosis (MS) is an autoimmune disease associated with abnormal expression of a subset of cytokines, resulting in inappropriate T-lymphocyte activation and uncontrolled immune response. A key issue in the field is the need to understand why these cytokines are transcriptionally activated in the patients. Here, we have examined several transcription units subject to pathological reactivation in MS, including the TNFα and IL8 cytokine genes and also several Human Endogenous RetroViruses (HERVs). We find that both the immune genes and the HERVs require the heterochromatin protein HP1α for their transcriptional repression. We further show that the Peptidylarginine Deiminase 4 (PADI4), an enzyme with a suspected role in MS, weakens the binding of HP1α to tri-methylated histone H3 lysine 9 by citrullinating histone H3 arginine 8. The resulting de-repression of both cytokines and HERVs can be reversed with the PADI-inhibitor Cl-amidine. Finally, we show that in peripheral blood mononuclear cells (PBMCs) from MS patients, the promoters of TNFα, and several HERVs share a deficit in HP1α recruitment and an augmented accumulation of histone H3 with a double citrulline 8 tri-methyl lysine 9 modifications. Thus, our study provides compelling evidence that HP1α and PADI4 are regulators of both immune genes and HERVs, and that multiple events of transcriptional reactivation in MS patients can be explained by the deficiency of a single mechanism of gene silencing.
Soluble CD163 as a Marker of Macrophage Activity in Newly Diagnosed Patients with Multiple Sclerosis
Soluble CD163 (sCD163) is a macrophage specific protein known to be up-regulated in serum from patients with multiple sclerosis (MS). To investigate sCD163 in serum and CSF (cerebrospinal fluid) from patients undergoing MS diagnostic work-up and analyse its potential as a diagnostic biomarker. After a full MS diagnostic work-up, including collection of paired samples of CSF and serum, 183 patients were evaluated for inclusion in this study. Patients were divided into groups based on their diagnosis. Patients with normal clinical and paraclinical findings were grouped as symptomatic controls. Serum and CSF levels of sCD163 were determined by enzyme-linked immunosorbent assay (ELISA). sCD163 could be measured in all serum and CSF samples. A high sCD163 CSF/serum ratio in relation to molecular weight was found, strongly indicating local production in the CNS. Median levels of sCD163 were significantly decreased in serum and significantly elevated in CSF in patients with relapsing-remitting, and primary-progressive MS. There were, however, some overlaps of the measures between groups. In a receiver operating characteristic (ROC) analysis sCD163 CSF/serum ratio had an area under the curve of 0.72. The sCD163 CSF/serum ratio was significantly increased in patients with MS and may reflect macrophage activation in MS lesions. These results suggest that primary progressive MS also is driven by inflammation in which the innate immune system plays a pivotal role.
Benchmarking Farm Animal Welfare—A Novel Tool for Cross-Country Comparison Applied to Pig Production and Pork Consumption
A pluralist approach to farm animal welfare, combining animal welfare legislation with market-driven initiatives, has developed in many countries. To enable cross-country comparisons of pig welfare, a number of welfare dimensions, covering the features typically modified in legislative and market-driven welfare initiatives aimed at pig production, were defined. Five academic welfare experts valued the different welfare states within each dimension on a 0–10 scale, then assessed the relative contribution of each dimension to overall welfare on a 1–5 scale. By combining these values and weights with an inventory of pig welfare initiatives in five countries, the additional welfare generated by each initiative was calculated. Together with information on the national coverage of each initiative, the Benchmark value for each country’s production and consumption of pork could be calculated on a scale from 0 to 100. Two (Sweden and the UK) had a much higher Benchmark value than the rest. However, there was a drop in the Benchmark for consumption in Sweden and the UK (indicating imports from countries with lower-Benchmark values for production). Even though the experts differed in the values and weights ascribed to different initiatives, they were largely in agreement in their ranking of the countries.
Moral Convictions and Meat Consumption—A Comparative Study of the Animal Ethics Orientations of Consumers of Pork in Denmark, Germany, and Sweden
Background: The relationship between animal ethics orientations and consumer demand for meat with high standards of animal welfare, and the way this relationship plays out in different countries, is not well understood. Using pork as a case study, this comparative study aims to identify the animal ethics orientations that drive purchases of welfare meat in Denmark, Germany, and Sweden. Methods: Cross-sectional questionnaire data from representative samples of approximately 1600 consumers in each country were collected. A segmentation of pork consumers (using latent profile analysis) was carried out. Results: In all three countries, two subgroups were concerned about farm animal welfare: the first subgroup was driven by animal rights values; the second subgroup by animal protection values, where the main principle was that “it is all right to use animals as long as they are treated well”. Other consumer groups are less concerned about farm animal welfare and display little or no preference for welfare pork. Conclusions: In all three countries, dual demand for welfare pork exists. The findings of this study can be used, among others, to understand the marketability of enhanced welfare animal products and the potential for market-driven animal welfare improvements.
Pig Farmers' Perceptions of Economic Incentives to Control Salmonella Prevalence at Herd Level
This paper investigates how perceived costs and benefits of Salmonella control among Danish pig farmers affect the farmers' choice of action toward reducing the prevalence of Salmonella in their herds. Based on data from an online questionnaire involving 163 Danish pig farmers, we find a considerable uncertainty among pig farmers about the perceived effects of the Salmonella reducing actions. The results indicate large variations in the perceived costs of implementing different types of Salmonella reducing actions (management-, hygiene- and feed-related). For some cases, farmers associate net benefits and positive productivity effects with implementation of the actions while studies by the industry indicate net costs to the farmers. Differences among farmers support the idea of an outcome-based Salmonella penalty scheme but the large uncertainties about costs and effects of actions toward Salmonella control might hamper the effectiveness of such a penalty scheme as a regulatory instrument to affect farmer behavior.
B cells and monocytes from patients with active multiple sclerosis exhibit increased surface expression of both HERV-H Env and HERV-W Env, accompanied by increased seroreactivity
Background The etiology of the neurogenerative disease multiple sclerosis (MS) is unknown. The leading hypotheses suggest that MS is the result of exposure of genetically susceptible individuals to certain environmental factor(s). Herpesviruses and human endogenous retroviruses (HERVs) represent potentially important factors in MS development. Herpesviruses can activate HERVs, and HERVs are activated in MS patients. Results Using flow cytometry, we have analyzed HERV-H Env and HERV-W Env epitope expression on the surface of PBMCs from MS patients with active and stable disease, and from control individuals. We have also analyzed serum antibody levels to the expressed HERV-H and HERV-W Env epitopes. We found a significantly higher expression of HERV-H and HERV-W Env epitopes on B cells and monocytes from patients with active MS compared with patients with stable MS or control individuals. Furthermore, patients with active disease had relatively higher numbers of B cells in the PBMC population, and higher antibody reactivities towards HERV-H Env and HERV-W Env epitopes. The higher antibody reactivities in sera from patients with active MS correlate with the higher levels of HERV-H Env and HERV-W Env expression on B cells and monocytes. We did not find such correlations for stable MS patients or for controls. Conclusion These findings indicate that both HERV-H Env and HERV-W Env are expressed in higher quantities on the surface of B cells and monocytes in patients with active MS, and that the expression of these proteins may be associated with exacerbation of the disease.
HERVs in Neuropathogenesis
In humans, exogenous retroviruses are known to cause immunodeficiency and neurological disease. While endogenous retroviruses are firmly established pathogens in other species, the human endogenous retroviruses (HERVs) may well be considered as emerging pathogens. HERVs also exhibit complex interactions with exogenous retroviruses and herpesviruses. Two neurological disorders in particular are associated with HERVs: multiple sclerosis (MS) and schizophrenia. HERV-H/F and HERV-W are specifically activated both in the circulation and the central nervous system (CNS) in a majority of MS patients, and particularly, the envelopes ( env transcription and Env proteins) appear strongly associated with disease activity. Interferon beta (IFN-β) therapy is well-established for MS. IFN-β is also known to have anti-retroviral activities toward exogenous retroviruses (HIV and HTLV-I). New reports show that IFN-β also mediate down-regulation of HERV-H/F and HERV-W in MS patients. HERV-W and HERV-K transcription ( gag and pol ) appears, to some extent, to be up-regulated in the circulation and the CNS of patients with schizophrenia. The expression of anti-HERV-W Gag reactive epitopes is reported to be down-regulated in the brain but up-regulated in the blood from schizophrenia patients. The pathogenic potential of HERVs certainly merits further studies.
The Prospect of Market-Driven Improvements in Animal Welfare: Lessons from the Case of Grass Milk in Denmark
Citizens in many European countries urge that the welfare of farm animals should be improved. Policy-makers propose that this could, at least to some extent, be achieved through increased consumption of animal products produced under labeling schemes guaranteeing higher standards of animal welfare. Yet considerable uncertainties exist about the ability of the market to promote animal welfare. So far the consumption of most welfare-friendly products has been limited, and the impact of driving and limiting factors is poorly understood. Reviewing market studies, we identify the factors that have shaped the relatively successful market for grass milk in Denmark. We conclude that the positive drivers such as an appealing animal welfare attribute and animal welfare being bundled with other qualities are essentially the same as those operating in connection with less successful animal welfare-friendly products. It is therefore to be expected that other animal welfare-friendly food products marketed via “natural behaviors” in the farm animals will catch the interest of consumers. However, grass milk consumption has been supported by proper labeling, ready availability and low price premiums as well as multifaceted public support. This suggests that successful cases require the joint presence of a number of positive drivers as well as low consumption barriers.
Three perspectives on motivation and multicriteria assessment of organic food systems
Organic food systems are based on a complex of value criteria that often are not explicitly considered when agents think, communicate, and make decisions concerning organic food. Multicriteria assessment (MCA) refers to a group of tools that help the user to tackle such highly complex issues. The question is how an MCA tool should be designed to facilitate reflections, communication, and decision making in relation to organic food systems. A key issue is motivation. There are several divergent theories of motivation, and the question cannot be adequately answered by using any single theory. We discuss an economic, a psychosocial, and a relational perspective on motivation and MCA. Using the example of a consumer assessing and choosing products in the supermarket, the economic conception of motivation offers a focus on decision-making processes. The psychosocial approach to motivation draws attention to the influence of cognitive structures and experience-based emotional drivers. Finally, the relational approach stresses that motivation is situated in the relations between agents. We discuss how the three perspectives converge and diverge regarding the purpose of using an MCA tool, the scope of the MCA, the strategic focus, and challenges and potentials associated with an MCA tool. Through this multiple-perspective approach, the general idea of MCA is expanded and elaborated to refine the design of an MCA tool for organic food systems.