Airway eosinophils accumulate in the mediastinal lymph nodes but lack antigen-presenting potential for naive T cells

Asthma is characterized by infiltration of the airway wall with eosinophils. Although eosinophils are considered to be effector cells, recent studies have reported their ability to activate primed Th2 cells. In this study, we investigated whether eosinophils are capable of presenting Ag to unprimed T cells in draining lymph nodes (DLN) of the lung and compared this capacity with professional dendritic cells (DC). During development of eosinophilic airway inflammation in OVA-sensitized and challenged mice, CCR3(+) eosinophils accumulated in the DLN. To study their function, eosinophils were isolated from the bronchoalveolar lavage fluid of mice by sorting on CCR3(+)B220(-)CD3(-)CD11c(dim) low autofluorescent cells, avoiding contamination with other APCs, and were intratracheally injected into mice that previously received CFSE-labeled OVA TCR-transgenic T cells. Eosinophils did not induce divisions of T cells in the DLN, whereas DC induced on average 3.7 divisions in 45.7% of T cells. To circumvent the need for Ag processing or migration in vivo, eosinophils were pulsed with OVA peptide and were still not able to induce T cell priming in vitro, whereas DC induced vigorous proliferation. This lack of Ag-presenting ability was explained by the very weak expression of MHC class II on fresh eosinophils, despite expression of the costimulatory molecules CD80 and ICAM-1. This investigation does not support any role for airway eosinophils as APCs to naive T cells, despite their migration to the DLN at times of allergen exposure. DC are clearly superior in activating T cells in the DLN of the lung

Lipopolysaccharide-induced suppression of airway Th2 responses does not require IL-12 production by dendritic cells

The prevalence of atopic asthma, a Th2-dependent disease, is reaching epidemic proportions partly due to improved hygiene in industrialized countries. There is an inverse correlation between the level of environmental endotoxin exposure and the prevalence of atopic sensitization. As dendritic cells (DC) have been implicated in causing sensitization to inhaled Ag, we studied the effect of endotoxin on Th2 development induced by bone marrow DC in vitro and by intratracheal injection in vivo, with particular emphasis on the role played by the polarizing cytokine IL-12. Bone marrow-derived DC stimulated with Escherichia coli O26:B6 LPS produced IL-12p70 for a limited period of time, after which production became refractory to further stimulation with CD40 ligand, a phenomenon previously called "exhaustion." The level of IL-12 production of DC did not correlate with Th1 development, as exhausted OVA-pulsed DC were still capable of shifting the cytokine pattern of responding OVA-specific Th cells toward Th1 in vitro and in vivo. When mice were first immunized by intratracheal injection of OVA-DC and subsequently challenged with OVA aerosol, prior in vitro stimulation of DC with LPS reduced the development of airway eosinophilia and Th2 cytokine production. Most surprisingly, the capacity of LPS to reduce Th2-dependent eosinophilic airway inflammation was IL-12-independent altogether, as IL-12p40 knockout DC had a similar reduced capacity to prime for Th2 responses. These results suggest that LPS reduces sensitization to inhaled Ag by reducing DC-driven Th2 development, but that IL-12 is not necessary for this effect

Sustainability of Global Golden Inland Waterways

Sustainable inland waterways should meet the needs of navigation without compromising the health of riverine ecosystems. Here we propose a hierarchical model to describe sustainable development of the Golden Inland Waterways (GIWs) which are characterized by great bearing capacity and transport need. Based on datasets from 66 large rivers (basin area > 100,000 km2) worldwide, we identify 34 GIWs, mostly distributed in Asia, Europe, North America, and South America, typically following a three-stage development path from the initial, through to the developing and on to the developed stage. For most GIWs, the exploitation ratio, defined as the ratio of actual to idealized bearing capacity, should be less than 80% due to ecological considerations. Combined with the indices of regional development, GIWs exploitation, and riverine ecosystem, we reveal the global diversity and evolution of GIWs' sustainability from 2015 to 2050, which highlights the importance of river-specific strategies for waterway exploitation worldwide

Dutch and American waterway development: identification and classification of tools for value creation

Waterways can serve society in a variety of ways. However, authorities responsible for maintenance and development of waterways often have a sectoral focus. They strive for cost efficient solutions within their restricted scope; broader development of socio-economic value receives little attention. This can be seen in e.g. the Netherlands and the USA. Both countries have strong national authorities responsible for the navigation function of waterways. The societal call for broader optimization is recognized, but a systemized response to this call is lacking. Nevertheless both authorities make attempts towards increasing the socio-economic value of their capital waterway projects by deploying tools for broader optimization. Six recent cases, in which such attempts were made, are studied with the aim of identifying and classifying the tools deployed. Identification and classification is needed to evaluate where gaps and opportunities lie for more systemized responses. From these cases a total of 15 tools are identified which stimulated broad optimization. These tools are classified by identifying the transaction characteristics associated with these tools. These characteristics can relate to cost, benefits or value capturing and can be of informative, coordinative or legislative nature. The results show overlaps and voids in the domains these tools address. For practitioners the results can be helpful to navigate through the planning and implementation phase of waterway projects. More broadly the study shows that in the waterway sector, a sector in need for adaptation and renewal, the application of a variety of mixes of governance is an emerging issue

The leukoaraiosis is more prevalent in the large artery atherosclerosis stroke subtype among Korean patients with ischemic stroke

<p>Abstract</p> <p>Background</p> <p>Several studies have suggested that the specific stroke subtype may influence the presence of leukoaraiosis in patients with ischemic stroke. We investigated the association between stroke subtype and leukoaraiosis in Korean patients with ischemic stroke by MRI.</p> <p>Methods</p> <p>There were 594 patients included in this study that were classified as large artery disease, lacune and cardioembolic stroke. For large-artery disease, the analysis focused on the intracranial or extracranial location of the stenosis, and the multiplicity of the stenotic lesions. Leukoaraiosis grading was performed according to the Atherosclerosis Risk in Communities Study.</p> <p>Results</p> <p>There was a significant association between leukoaraiosis and the stroke subtypes; the large-artery-disease group had a higher prevalence of leukoaraiosis than did the other groups (55.4% in the large-artery-disease group, 30.3% in the lacunar group and 14.3% in the cardioembolic group, P = 0.016 by chi-square test). On the multivariate linear regression analysis, age, the presence of hypertension, previous stroke and stroke subtype were independently associated with the presence of leukoaraiosis. In the sub analysis of the large-artery-disease group, the leukoaraiosis had a tendency to be more prevalent in the mixed and intracranial stenosis group than did the extracranial stenosis group (45.5% in the mixed group, 40.3% in the intracranial group and 26.9% in the extracranial group, P = 0.08 by chi-square test).</p> <p>Conclusion</p> <p>The association of leukoaraiosis with large-artery disease in this study might be due to the relatively high prevalence of intracranial occlusive lesions in Korean stroke patients compared to other ethnic groups.</p

Size of third and fourth ventricle in obstructive and communicating acute hydrocephalus after aneurysmal subarachnoid hemorrhage

In patients with acute hydrocephalus after aneurysmal subarachnoid haemorrhage (SAH), lumbar drainage is possible if the obstruction is in the subarachnoid space (communicating hydrocephalus). In case of intraventricular obstruction (obstructive hydrocephalus), ventricular drainage is the only option. A small fourth ventricle is often considered a sign of obstructive hydrocephalus. We investigated whether the absolute or relative size of the fourth ventricle can indeed distinguish between these two types of hydrocephalus. On CT-scans of 76 consecutive patients with acute headache but normal CT and CSF, we measured the cross-sectional surface of the third and fourth ventricle to obtain normal planimetric values. Subsequently we performed the same measurements on 117 consecutive SAH patients with acute hydrocephalus. These patients were divided according to the distribution of blood on CT-scan into three groups: mainly intraventricular blood (n = 15), mainly subarachnoid blood (n = 54) and both intraventricular and subarachnoid blood (n = 48). The size of the fourth ventricle exceeded the upper limit of normal in 2 of the 6 (33%) patients with intraventricular blood but without haematocephalus, and in 15 of the 54 (28%) patients with mainly subarachnoid blood. The mean ratio between the third and fourth ventricle was 1.45 (SD 0.66) in patients with intraventricular blood and 1.42 (SD 0.91) in those with mainly subarachnoid blood. Neither fourth ventricular size nor the ratio between the third and fourth ventricles discriminates between the two groups. A small fourth ventricle does not necessarily accompany obstructive hydrocephalus and is therefore not a contraindication for lumbar drainage

Secondary infarction in single or in multiple vascular territories: two different entities following subarachnoid hemorrhage?

The pathogenesis of secondary infarctions (SI) after aneurysmal subarachnoid hemorrhage (SAH) is poorly understood. To assess whether SI in single (SSI) or multiple (MSI) vascular territories represent different disease entities, we compared clinical profiles of patients with these patterns of SI. CT/MRI-examinations of 448 patients were reviewed for new infarctions within 28 days after SAH, and categorized into SSI or MSI. Only patients with adequate follow-up imaging excluding any new infarctions were included for analysis (269 patients). Procedure-related infarctions were excluded. Odds ratios (ORs) with corresponding 95% confidence intervals (CI) were calculated for patients with SSI or MSI versus patients without SI to analyze differences in demographic characteristics, vascular risk factors, disease-related characteristics and treatment modalities. Thirty-six patients had SSI, 53 MSI and 180 no SI. ORs in MSI-patients were >1.5 times higher compared with ORs in SSI-patients for multiple vascular risk factors [MSI:5.4 (2.3–13) versus SSI:1.2 (0.5–2.8)], poor clinical condition on admission [MSI:4.6 (2.4–8.9) versus SSI:2.4 (1.1–5.2)], initial loss of consciousness [MSI:2.6 (1.3–5.3) versus SSI:1.1 (0.5–2.3)] and large amounts of intraventricular blood [MSI:2.9 (1.4–5.8) versus SSI:1.5 (0.7–3.2)]. In multivariate analysis ORs remained higher in MSI for presence of multiple vascular risk factors [MSI:1.9 (1.2–2.9) versus SSI:1.1 (0.8–1.7)] and initial loss of consciousness [MSI:3.0 (1.0–8.9) versus SSI:1.6 (0.6–4.0)]. Our findings suggest that SSI and MSI after SAH are not distinct disease entities. MSI was related to the same characteristics as SSI but to a larger extent, specifically to the presence of multiple vascular risk factors, initial loss of consciousness, larger amounts of intraventricular blood, and poor clinical status on admission

Do we need to rethink our waterways? Values of ageing waterways in current and future society

In the past canals were developed, and some rivers were heavily altered, driven by the need for good transportation infrastructure. Major investments were made in navigation locks, weirs and artificial embankments, and many of these assets are now reaching the end of their technical lifetime. Since then the concept of integrated water resource management (IWRM) emerged as a concept to manage and develop water-bodies in general. Two pressing problems arise from these developments: (1) major reinvestment is needed in order to maintain the transportation function of these waterways, and (2), it is not clear how the implementation of the concept of IWRM can be brought into harmony with such reinvestment. This paper aims to illustrate the problems in capital-intensive parts of waterway systems, and argues for exploring value-driven solutions that rely on the inclusion of multiple values, thus solving both funding problems and stakeholder conflicts. The focus on value in cooperative strategies is key to defining viable implementation strategies for waterway projects

Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis

In sarcoidosis, the proinflammatory cytokines interferon gamma, tumour necrosis factor and interleukin-6 are released by monocyte-derived macrophages and lymphocytes in the lungs and other affected tissues. Regulatory receptors expressed on monocytes and macrophages act to suppress cytokine production, and reduced expression of regulatory receptors may thus promote tissue inflammation. The aim of this study was to characterise the role of regulatory receptors on blood monocytes in patients with sarcoidosis. Cytokine release in response to stimulation of whole blood was measured in healthy controls and Caucasian non-smoking patients with sarcoidosis who were not taking disease modifying therapy. Expression of the regulatory molecules IL-10R, SIRP-α/β, CD47, CD200R, and CD200L was measured by flow cytometry, and functional activity was assessed using blocking antibodies. Stimulated whole blood and monocytes from patients with sarcoidosis produced more TNF and IL-6 compared with healthy controls. 52.9% of sarcoidosis patients had monocytes characterised by low expression of CD200R, compared with 11.7% of controls (p < 0.0001). Patients with low monocyte CD200R expression produced higher levels of proinflammatory cytokines. In functional studies, blocking the CD200 axis increased production of TNF and IL-6. Reduced expression of CD200R on monocytes may be a mechanism contributing to monocyte and macrophage hyper-activation in sarcoidosis