The safety and effectiveness of chenodeoxycholic acid treatment in patients withcerebrotendinous xanthomatosis:two retrospective cohort studies.

Objective: To evaluate the safety and effectiveness of chenodeoxycholic acid (CDCA) treatment in patients with cerebrotendinous xanthomatosis (CTX). Methods: Two retrospective cohort studies were conducted in CTX patients who underwent CDCA treatment: one in the Netherlands (NL; CDCA-STUK-15-001) and one in Italy (IT; CDCA-STRCH-CR-14-001). Eligible patients were aged 2–75 years, had been diagnosed with CTX, and were treated with CDCA orally for ≥1 year. The impact of CDCA treatment on biochemical markers (including serum cholestanol levels) and disease signs and symptoms were assessed, in addition to the safety and tolerability of CDCA treatment. Results: A total of 35 patients were screened in the NL study and were diagnosed with CTX at 25.6 (± 13.7 SD) years on average. These patients were treated with CDCA and followed up for a median of 9.00 (range: 0.4–26.3) years. In addition, 28 patients were enrolled in the IT study and were diagnosed at 35.0 (± 11.4 SD) years on average (median duration of CDCA treatment: 5.75 [range: 0.0–25.0] years). Signs and symptoms of disease resolved, improved, or remained stable in many patients, with concomitant improvements in biochemical marker levels (serum cholestanol, p < 0.001; 7α-hydroxy-4-cholesten-3-one, p < 0.001 [IT study]). Conclusions: The outcomes of these retrospective cohort studies indicate that CDCA is effective in the long-term treatment of CTX, with an acceptable safety profile. © 2019, The Author(s)

Lactobacillli expressing llama VHH fragments neutralise Lactococcus phages

<p>Abstract</p> <p>Background</p> <p>Bacteriophages infecting lactic acid bacteria (LAB) are widely acknowledged as the main cause of milk fermentation failures. In this study, we describe the surface-expression as well as the secretion of two functional llama heavy-chain antibody fragments, one binding to the major capsid protein (MCP) and the other to the receptor-binding proteins (RBP) of the lactococcal bacteriophage p2, by lactobacilli in order to neutralise lactococcal phages.</p> <p>Results</p> <p>The antibody fragment VHH5 that is directed against the RBP, was fused to a c-<it>myc </it>tag and expressed in a secreted form by a <it>Lactobacillus </it>strain. The fragment VHH2 that is binding to the MCP, was fused to an E-tag and anchored on the surface of the lactobacilli. Surface expression of VHH2 was confirmed by flow cytometry using an anti-E-tag antibody. Efficient binding of both the VHH2 and the secreted VHH5 fragment to the phage antigens was shown in ELISA. Scanning electron microscopy showed that lactobacilli expressing VHH2 anchored at their surface were able to bind lactococcal phages. A neutralisation assay also confirmed that the secreted VHH5 and the anchored VHH2 fragments prevented the adsorption of lactococcal phages to their host cells.</p> <p>Conclusion</p> <p>Lactobacilli were able to express functional VHH fragments in both a secreted and a cell surface form and reduced phage infection of lactococcal cells. Lactobacilli expressing llama heavy-chain antibody fragments represent a novel way to limit phage infection.</p

"Driven to distraction?" Children's experiences of car travel

This is an Author's Accepted Manuscript of an article published in volume, 4, issue 1, pages 59-76 in Mobilities 2009. Copyright @ 2009 Taylor & Francis, available online at: http://www.tandfonline.com/doi/abs/10.1080/17450100802657962.Cars have become increasingly significant features in the lives of many children and adults in the UK and elsewhere. Whilst there is a growing body of research considering how adults experience automobility, that is the increasingly central role of cars within societies, there has been little equivalent research exploring children's perspectives. Drawing upon a variety of methods including personal diaries, photographs, in‐depth interviews and surveys amongst schools within Buckinghamshire and North London, the paper contributes to filling this gap in existing research through exploring how cars are not only journey spaces for children, but are also sites for play, relaxation, homework, companionship, technology and the consumption of commodities. Using a Foucauldian analysis of power, insights into wider familial processes relating to mobility are provided by exploring how cars are sites of conflicting power relations between parents and children. The paper also explores how children's everyday experiences of cars were framed by wider sets of power relations, including car corporations which design and manufacture these spaces, and the role of capital which commodifies everyday activities in cars. In doing so, the paper challenges existing research on automobility for only focusing upon adults' experiences of cars and begins to theorise a more inclusive account of automobility which incorporates children and young people

AThEME: Advancing the European Multilingual Experience

AThEME is a collaborative research project studying multilingualism in Europe. This 5-year research project was set up with funding from the European Commission, and it runs from March 2014 until March 2019. The main objectives of the project are: (1) to investigate cognitive, linguistic and sociological issues in multilingual Europe, (2) to assess existing public policies and practices within the areas of education and health as well as their impact on multilingualism and (3) to contribute to evidence-based policy making. AThEME uses a range of research methodology and aims to raise awareness of multilingualism among policy makers, health professionals, academics and educators.Theoretical and Experimental Linguistic

神戸大学大学教育推進機構開設記念公開シンポジウム:学生の力を活かす教育システムをめざして

textabstractWe present a two-week old girl who was diagnosed with cerebrotendinous xanthomatosis (CTX), an inborn error of bile acid synthesis, after a diagnostic workup for convulsions which were shown to be caused by a parechovirus encephalitis. The diagnosis of CTX was confirmed with CYP27A1 mutation analysis. She was started on chenodeoxycholic acid (CDCA) supplementation, which inhibits cholestanol production through a feedback mechanism, at the advised dosage of 15 mg/kg/day. Within 6 weeks, she developed jaundice with hepatomegaly. CDCA supplementation was stopped after which liver size and function rapidly normalised. CDCA supplementation was then restarted and maintained at 5 mg/kg/day. Cholestanol, liver enzymes and total bilirubin were frequently monitored in the patient, who is now 2.8 years of age, and have remained within normal range. Her psychomotor development has been normal. Conclusion: adequate metabolic control was achieved in an infant with CTX with CDCA supplementation at a dosage of 5 mg/kg/day and was well tolerated. CDCA supplementation at 15 mg/kg/day seems hepatotoxic in infants and should not be used. This is relevant in view of the possible inclusion of CTX in newborn screening programs in the near future.What is Known:• Cerebrotendinous xanthomatosis (CTX), an inborn error of bile acid synthesis, is a progressive neurological disorder.• Symptoms of CTX can be halted, and likely prevented, with chenodeoxycholic acid (CDCA) supplementation, making CTX a good candidate for newborn screening.What is New:• CDCA supplementation at the advised dosage of 15 mg/kg/day in children seems hepatoxic in infants with CTX.• Adequate metabolic control in an infant with CTX was achieved with CDCA supplementation at 5 mg/kg/day and well tolerated