Insights into olfactory ensheathing cell development from a laser-microdissection and transcriptome-profiling approach.

Olfactory ensheathing cells (OECs) are neural crest-derived glia that ensheath bundles of olfactory axons from their peripheral origins in the olfactory epithelium to their central targets in the olfactory bulb. We took an unbiased laser microdissection and differential RNA-seq approach, validated by in situ hybridization, to identify candidate molecular mechanisms underlying mouse OEC development and differences with the neural crest-derived Schwann cells developing on other peripheral nerves. We identified 25 novel markers for developing OECs in the olfactory mucosa and/or the olfactory nerve layer surrounding the olfactory bulb, of which 15 were OEC-specific (that is, not expressed by Schwann cells). One pan-OEC-specific gene, Ptprz1, encodes a receptor-like tyrosine phosphatase that blocks oligodendrocyte differentiation. Mutant analysis suggests Ptprz1 may also act as a brake on OEC differentiation, and that its loss disrupts olfactory axon targeting. Overall, our results provide new insights into OEC development and the diversification of neural crest-derived glia.Cambridge Commonwealth Trust Cambridge Philosophical Societ

Postgraduate education for Chinese medicine practitioners: a Hong Kong perspective

<b>Background</b> Despite Hong Kong government's official commitment to the development of traditional Chinese medicine (TCM) over the last ten years, there appears to have been limited progress in public sector initiated career development and postgraduate training (PGT) for public university trained TCM practitioners. Instead, the private TCM sector is expected to play a major role in nurturing the next generation of TCM practitioners. In the present study we evaluated TCM graduates' perspectives on their career prospects and their views regarding PGT.<p></p> <b>Method</b> Three focus group discussions with 19 local TCM graduates who had worked full time in a clinical setting for fewer than 5 years. <p></p> <b>Results</b> Graduates were generally uncertain about how to develop their career pathways in Hong Kong with few postgraduate development opportunities; because of this some were planning to leave the profession altogether. Despite their expressed needs, they were dissatisfied with the current quality of local PGT and suggested various ways for improvement including supervised practice-based learning, competency-based training, and accreditation of training with trainee involvement in design and evaluation. In addition they identified educational needs beyond TCM, in particular a better understanding of western medicine and team working so that primary care provision might be more integrated in the future. <p></p> <b>Conclusion</b> TCM graduates in Hong Kong feel let down by the lack of public PGT opportunities which is hindering career development. To develop a new generation of TCM practitioners with the capacity to provide quality and comprehensive care, a stronger role for the government, including sufficient public funding, in promoting TCM graduates' careers and training development is suggested. Recent British and Australian experiences in prevocational western medicine training reform may serve as a source of references when relevant program for TCM graduates is planned in the futur

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Aspects of the life history of skates from southeastern Australia

The age and growth, reproduction and diet of several skate species in south-east Australia were studied. From studying these life history characteristics it was determined that skates have a relatively low productivity and may therefore be at risk of local extinction if increasingly exploited without appropriate management

Assessment and Treatment of Hepatitis C Virus Infection Among People Who Inject Drugs in the Opioid Substitution Setting: ETHOS Study

Vertical rainfall profile retrieval based on reflectivity data collected by spaceborne rain radars can be improved through the techniques that exploit an estimation of the sea surface Normalised Radar Cross Section (NRCS) as an additional information. However, errors that can currently be made in predicting the sea surface NRCS may significantly affect their performance. Therefore, in this paper we first address the problem to evaluate the NCRS of the sea surface perturbed by rain, when observed at nadir. For this purpose, the dominant effect of ring waves generated by rainfall is considered. The joint effect of wind is also considered. The proposed model is based on the Full Wave Model (FWM) theory. Some comparisons are made with an alternative, less flexible model based on the Integral Equation Model (IEM) theory, and partial comparisons are also made with experimental data, which authorize to consider the proposed model well grounded and exploitable for application. then, we show that the model can be usefully exploited to improve rainfall rate vertical profile retrieval over the sea surface, inthe case of nadir looking, single frequency radars

The effect of social functioning and living arrangement on treatment intent, specialist assessment and treatment uptake for hepatitis C virus infection among people who inject drugs: the ETHOS study

Background: The objective was to assess social functioning and its association with treatment intent, specialist assessment and treatment uptake for hepatitis C virus (HCV) infection among people with a history of injecting drug use. Methods: ETHOS is a prospective observational cohort evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from nine community health centres and opioid substitution treatment clinics (NSW, Australia). Social functioning was assessed using a short form of the Opioid Treatment Index social functioning scale. Those classified in the highest quartile (score >6) were considered having lower social functioning. Analyses were performed using logistic regression. Results: Among 415 participants (mean age 41 years, 71% male), 24% were considered having lower social functioning, 70% had early HCV treatment intent (intention to be treated in the next 12 months), 53% were assessed by a specialist and 27% initiated treatment. Lower social functioning was independently associated with unemployment, unstable housing, recent injecting drug use and moderate to extremely severe symptoms of depression, anxiety and stress. Lower social functioning was independently associated with reduced early HCV treatment intent (aOR 0.51, 95% CI 0.30-0.84) and lower specialist assessment (aOR 0.48, 95% CI 0.29-0.79), but not HCV treatment uptake (aOR 0.76, 95% CI 0.40-1.43). Living with someone was independently associated with HCV treatment uptake (with someone and children: aOR 2.28, 95% CI 1.01-5.14; with someone and no children: aOR 2.36, 95% CI 1.30-4.31), but not early HCV treatment intent or specialist assessment. Conclusions: This study highlights the need for the development and implementation of strategies targeting people who inject drugs with lower social functioning to enhance HCV treatment intent and specialist assessment. Further, strategies to enhance social support may play a role in increasing HCV treatment uptake.This work was supported by the National Health and Medical Research Council (NHMRC, 568985) and New South Wales Health. The Centre for Social Research in Health is supported by a grant from the Australian Government Department of Health and Ageing. This publication was funded by the Australian Government Department of Health and Ageing. GD and PH are supported through NHMRC Practitioner Fellowships. JG is supported through a NHMRC Career Development Fellowship