Background and objectives
Commercial blood bags are predominantly made of polyvinyl chloride (PVC) plasticized with di(2‐ethylhexyl) phthalate (DEHP). DEHP is favourable for storage of red blood ...cells (RBC). Historically, removal of DEHP from blood bags has been linked to unacceptable haemolysis levels. Oncoming regulatory restrictions for DEHP due to toxicity concerns increase the urgency to replace DEHP without compromising RBC quality. Di(2‐ethylhexyl) terephthalate (DEHT) is one suggested substitute. The aim of this study was to compare PVC‐DEHT to PVC‐DEHP blood bags using additive solutions saline–adenine–glucose–mannitol (SAGM) and phosphate–adenine–glucose–guanosine–saline–mannitol (PAGGSM), to determine whether DEHT can maintain acceptable component quality.
Materials and methods
RBC concentrates (N = 64), platelet concentrates (N = 16) and fresh frozen plasma (N = 32) were produced from whole blood collected into either DEHT or DEHP plasticized systems. Using a pool‐and‐split study design, pairs of identical RBC content were created within each plasticizer arm and assigned either SAGM or PAGGSM. Storage effects were assessed weekly for 49 days (RBC), 7 days (platelets) and before/after freezing (plasma).
Results
Though haemolysis was slightly higher in DEHT, all study arms remained below half of the European limit 0·8%. K+ was lower in DEHT than in DEHP independent of additive solution. The metabolic parameters were not influenced by choice of plasticizer. Platelet activation/metabolism and plasma content were similarly preserved.
Conclusion
Our study demonstrates that the plasticizer DEHT provides adequate blood component quality. We propose DEHT as a strong future candidate for replacement of DEHP in blood bags.
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.
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.
Endogenous retroviruses are pathogenic – in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic ...cause‐effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV‐H/F and HERV‐W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV‐associated dementia (HAD), indications are accumulating for involvement of the HERV‐K family, and also HERV‐H/F and/or HERV‐W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non‐pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV‐directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential.
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.
Two kinds of initiatives exist to ensure welfare in broiler production: welfare legislation, where all broiler production in a country or region must comply with legally defined welfare standards; ...and market driven initiatives, where part of the production must meet specific welfare standards and is sold with a particular label, typically at a price premium, or as part of minimum welfare standards defined by a retailer, a fast-food chain or the like. While the effects of national legislation may be undermined by price competition from lower welfare imported products, the effects of market driven initiatives may be limited by lack of willingness from consumers to pay the extra cost. To investigate how this works out in practice, we compared broiler welfare requirements in 5 European countries, Denmark, Germany, United Kingdom, the Netherlands, and Sweden, in 2018, by means of the Benchmark method. A number of welfare dimensions, covering the input features typically modified in broiler welfare initiatives, were defined. A total of 27 academic welfare experts (response rate 75%) valued the different levels within each dimension on a 0 to 10 scale, and then weighted the relative contribution of each dimension to overall welfare on a 1 to 5 scale. By combining these values and weights with an inventory of existing welfare initiatives, the additional welfare generated by each initiative was calculated. Together with information on national coverage of each initiative, the Benchmark score for each country's production and consumption of chicken meat was calculated. Sweden achieved a much higher Benchmark for national production due to higher legal standards than any of the four other countries. The Netherlands, on the other hand, achieved a Benchmark for national consumption of chicken at the same level as that found in Sweden, because market driven initiatives complemented more welfare-limited Dutch legislation. So, despite some uncertainties in the Benchmark method, it appears that market driven initiatives can have a strong impact on improving broiler welfare, building on those standards achieved by animal welfare legislation.
AbstractBackgroundLivestock-acquired methicillin-resistant Staphylococcus aureus (LA-MRSA) is a concern in healthcare and a political priority in some countries. ObjectiveThis study investigates the ...net societal costs of 2 alternative strategies for controlling LA-MRSA in Denmark: (1) eradicating LA-MRSA in all pig housing units, and (2) containing LA-MRSA within the units. MethodsBenefits and costs are considered for affected economic sectors: healthcare, pig production, pig-related industries, and public administration. ResultsThe cost to society of eradication is estimated at €2.3 to €2.5 billion (present value). Containment will cost €55 to €93 million. For both strategies, the main cost lies in primary pig production—for containment this is mainly due to establishing and operating anterooms and shower rooms, and for eradication it is due to production losses, loss of genetic resources, and costs of cleaning and disinfection. ConclusionCompared with these costs, health economic benefits are moderate for both strategies. Containment is superior to eradication when measured by a benefit-cost ratio.
•CSA addresses productivity, GHG emission and climate change resilience but needs contextualization with existing farming systems and policy targets.•Alongside the three basic CSA outcomes, CSA ...farming practices and technologies were assessed for biodiversity, water and energy efficiency and animal welfare improvement.•Agroecological farming practices, particularly those incorporating legume cropping contribute to the majority of contextualized CSA outcome.•SFTs positively contribute to the achievement of contextualized CSA outcomes in the majority of CSA categories.•Legume-based feed additives and pasture grazing could support livestock climate-smart agricultural outcomes achievement.
The aim of this review was to provide an overview of existing farming practices and technologies in Europe by assessing their contribution to climate-smart agricultural (CSA) outcomes. Following the PRISMA protocol, 110 final selected studies were scrutinized. Altogether 74 different practices and technologies were identified. Using an inductive approach, the identified practices and technologies were categorized, and their potential contribution towards contextualized CSA outcomes—productivity, resilience, GHG mitigation, biodiversity improvement, animal welfare support, water and energy use efficiency—was assessed. Among CSA farming practices, this review highlighted legume-based cover crops, crop rotation, intercropping, and crop diversification as having promising potential to achieve CSA outcomes. Among CSA technologies, precision fertilization, crop protection, and irrigation showed promising potential. Moreover, pasture grazing, legume-based feed additives, improved forage production and holistic husbandry management with precision technologies were identified as promising contributors to CSA outcomes. The review emphasizes that the utilization of smart farming technologies and practices in crop and livestock production systems could positively contribute to achieving one or more outcomes. Overall, the GHG mitigation and farm productivity improvement outcomes were relatively well covered in the reviewed literature. Improvements in biodiversity, water and energy use efficiency, and animal welfare outcomes are not well demonstrated within the identified studies.
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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.
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