KCa 3.1-a microglial target ready for drug repurposing?

Over the past decade, glial cells have attracted attention for harboring unexploited targets for drug discovery. Several glial targets have attracted de novo drug discovery programs, as highlighted in this GLIA Special Issue. Drug repurposing, which has the objective of utilizing existing drugs as well as abandoned, failed, or not yet pursued clinical development candidates for new indications, might provide a faster opportunity to bring drugs for glial targets to patients with unmet needs. Here, we review the potential of the intermediate-conductance calcium-activated potassium channels KCa 3.1 as the target for such a repurposing effort. We discuss the data on KCa 3.1 expression on microglia in vitro and in vivo and review the relevant literature on the two KCa 3.1 inhibitors TRAM-34 and Senicapoc. Finally, we provide an outlook of what it might take to harness the potential of KCa 3.1 as a bona fide microglial drug target. GLIA 2016;64:1733-1741

The assessment of efforts to return to work in the European Union

Background: Assessment of efforts to promote return-to-work (RTW) includes all efforts (vocational and non-vocational) designed to improve the work ability of the sick-listed employee and increase the chance to return to work. Aim of the study was to investigate whether in 13 European countries these RTW efforts are assessed and to compare the procedures by means of six criteria. METHODS: Data were gathered in the taxonomy project of the European Union of Medicine in Assurance and Social Security and by means of an additional questionnaire. RESULTS: In seven countries RTW efforts are subject of the assessment in relation to the application for disability benefits. Description of RTW efforts is a prerequisite in five countries. Guidelines on the assessment of RTW efforts are only available in the Netherlands and no countries report the use of the ICF model. Based on the results of the additional questionnaire, the assessor is a social scientist or a physician. The information used to assess RTW efforts differs, from a report on the RTW process to medical information. A negative outcome of the assessment leads to delay of the application for disability benefits or to application for rehabilitation subsidy. Conclusion: RTW efforts are assessed in half of the participating European countries. When compared, the characteristics of the assessment of RTW efforts in the participating European countries show both similarities and differences. This study may facilitate the gathering and exchange of knowledge and experience between countries on the assessment of RTW efforts

UOLO - automatic object detection and segmentation in biomedical images

We propose UOLO, a novel framework for the simultaneous detection and segmentation of structures of interest in medical images. UOLO consists of an object segmentation module which intermediate abstract representations are processed and used as input for object detection. The resulting system is optimized simultaneously for detecting a class of objects and segmenting an optionally different class of structures. UOLO is trained on a set of bounding boxes enclosing the objects to detect, as well as pixel-wise segmentation information, when available. A new loss function is devised, taking into account whether a reference segmentation is accessible for each training image, in order to suitably backpropagate the error. We validate UOLO on the task of simultaneous optic disc (OD) detection, fovea detection, and OD segmentation from retinal images, achieving state-of-the-art performance on public datasets.Comment: Publised on DLMIA 2018. Licensed under the Creative Commons CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0

Integrated systems research for sustainable smallholder agriculture in the Central Mekong: Achievements and challenges of implementing integrated systems research

Internal Revie

Neutralizing Antibody-Resistant Hepatitis C Virus Cell-to-Cell Transmission

Hepatitis C virus (HCV) can initiate infection by cell-free particle and cell-cell contact-dependent transmission. In this study we use a novel infectious coculture system to examine these alternative modes of infection. Cell-to-cell transmission is relatively resistant to anti-HCV glycoprotein monoclonal anti- bodies and polyclonal immunoglobulin isolated from infected individuals, providing an effective strategy for escaping host humoral immune responses. Chimeric viruses expressing the structural proteins rep- resenting the seven major HCV genotypes demonstrate neutralizing antibody-resistant cell-to-cell trans- mission. HCV entry is a multistep process involving numerous receptors. In this study we demonstrate that, in contrast to earlier reports, CD81 and the tight-junction components claudin-1 and occludin are all essential for both cell-free and cell-to-cell viral transmission. However, scavenger receptor BI (SR-BI) has a more prominent role in cell-to-cell transmission of the virus, with SR-BI-specific antibodies and small-molecule inhibitors showing preferential inhibition of this infection route. These observations highlight the importance of targeting host cell receptors, in particular SR-BI, to control viral infection and spread in the liver

Indigenous markets for dairy products in Africa: trade-offs between food safety and economics

In the absence of information on which to base policies in emerging dairy markets in developing countries, public officials have tended to rely on models for dairy product marketing and health assurance derived from industrialised countries where large-scale production systems, cold-chain pathways and milk pasteurization and packaging are key features. These models have invariably failed in many African market situations where small-scale dairy systems without cold-chain market pathways currently dominate and will continue to do so in the foreseeable future. The main reason is simple: many resource-poor consumers simply refuse to pay the extra costs that pasteurized, packaged milk incurs, and prefer to buy raw milk and boil it themselves. But the role of traditional preferences should not be discounted: in Kenya, high-income consumers express the same preference for raw milk as do those with lower income, and often end up buying more of it. As a result, informal or raw milk and traditional product markets generally dominate in developing countries, comprising over 90% of the market in Tanzania and Uganda, for example, and some 83% of the market of the world’s largest milk producer, India. In Kenya, the informal market has some 85% market share. The issue, of course, is public health concerns linked to raw milk. Current dairy market policies throughout the developing world have largely been adopted from the West, and reflect international standards of food safety, etc. However, as the percentages above show, they are being systematically ignored, and as a result, most consumers buy milk and dairy products that are completely outside any regulatory environment. It is possible that to better address the public health issues, policies may need to take a more pro-active approach to informal milk trading, and which better address the realities of consumer willingness to pay for higher standards. The policy question which needs to be answered is thus: is it preferable to maintain strict milk standards which result in higher costs and thereby free most marketed milk into informal channels, or is the public better off by standards that are relaxed but capture more of the informal market? If standards were relaxed to allow raw milk marketing, yet maintain some regulations regarding handling and if some incentives were given to milk traders to comply (e.g., training and certification), then a much larger proportion of the milk market may fall under regulatory control, improving the average standards of milk in the market. An important step to addressing this issue is to collect quantitative and qualitative information about milk-borne health risks under different production and marketing situations. This paper describes specific dairy marketing studies in Kenya, Ghana and Tanzania aimed at assessing public health risks from informally marketed milk and examines the economic trade-offs that policy makers should consider. Preliminary results from Kenya are presented and recommendations on cost-effective and practical interventions to improve milk safety made