Objective biomarkers for clinical relapse in multiple sclerosis: a metabolomics approach.

Accurate determination of relapses in multiple sclerosis is important for diagnosis, classification of clinical course and therapeutic decision making. The identification of biofluid markers for multiple sclerosis relapses would add to our current diagnostic armamentarium and increase our understanding of the biology underlying the clinical expression of inflammation in multiple sclerosis. However, there is presently no biofluid marker capable of objectively determining multiple sclerosis relapses although some, in particular neurofilament-light chain, have shown promise. In this study, we sought to determine if metabolic perturbations are present during multiple sclerosis relapses, and, if so, identify candidate metabolite biomarkers and evaluate their discriminatory abilities at both group and individual levels, in comparison with neurofilament-light chain. High-resolution global and targeted 1H nuclear magnetic resonance metabolomics as well as neurofilament-light chain measurements were performed on the serum in four groups of relapsing-remitting multiple sclerosis patients, stratified by time since relapse onset: (i) in relapse (R); (ii) last relapse (LR) ≥ 1 month (M) to < 6 M ago; (iii) LR ≥ 6 M to < 24 M ago; and (iv) LR ≥ 24 M ago. Two hundred and one relapsing-remitting multiple sclerosis patients were recruited: R (n = 38), LR 1-6 M (n = 28), LR 6-24 M (n = 34), LR ≥ 24 M (n = 101). Using supervised multivariate analysis, we found that the global metabolomics profile of R patients was significantly perturbed compared to LR ≥ 24 M patients. Identified discriminatory metabolites were then quantified using targeted metabolomics. Lysine and asparagine (higher in R), as well as, isoleucine and leucine (lower in R), were shortlisted as potential metabolite biomarkers. ANOVA of these metabolites revealed significant differences across the four patient groups, with a clear trend with time since relapse onset. Multivariable receiver operating characteristics analysis of these four metabolites in discriminating R versus LR ≥ 24 M showed an area under the curve of 0.758, while the area under the curve for serum neurofilament-light chain was 0.575. Within individual patients with paired relapse-remission samples, all four metabolites were significantly different in relapse versus remission, with the direction of change consistent with that observed at group level, while neurofilament-light chain was not discriminatory. The perturbations in the identified metabolites point towards energy deficiency and immune activation in multiple sclerosis relapses, and the measurement of these metabolites, either singly or in combination, are useful as biomarkers to differentiate relapse from remission at both group and individual levels.

A blood-based metabolomics test to distinguish relapsing-remitting and secondary progressive multiple sclerosis: addressing practical considerations for clinical application.

The transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS) represents a huge clinical challenge. We previously demonstrated that serum metabolomics could distinguish RRMS from SPMS with high diagnostic accuracy. As differing sample-handling protocols can affect the blood metabolite profile, it is vital to understand which factors may influence the accuracy of this metabolomics-based test in a clinical setting. Herein, we aim to further validate the high accuracy of this metabolomics test and to determine if this is maintained in a 'real-life' clinical environment. Blood from 31 RRMS and 28 SPMS patients was subjected to different sample-handling protocols representing variations encountered in clinics. The effect of freeze-thaw cycles (0 or 1) and time to erythrocyte removal (30, 120, or 240 min) on the accuracy of the test was investigated. For test development, samples from the optimised protocol (30 min standing time, 0 freeze-thaw) were used, resulting in high diagnostic accuracy (mean ± SD, 91.0 ± 3.0%). This test remained able to discriminate RRMS and SPMS samples that had experienced additional freeze-thaw, and increased standing times of 120 and 240 min with accuracies ranging from 85.5 to 88.0%, because the top discriminatory metabolite biomarkers from the optimised protocol remained discriminatory between RRMS and SPMS despite these sample-handling variations. In conclusion, while strict sample-handling is essential for the development of metabolomics-based blood tests, the results confirmed that the RRMS vs. SPMS test is resistant to sample-handling variations and can distinguish these two MS stages in the clinics.

Duck liver-associated outbreak of Campylobacteriosis among humans, United Kingdom, 2011.

Campylobacter- spp.-related gastroenteritis in diners at a catering college restaurant was associated with consumption of duck liver pâté. Population genetic analysis indicated that isolates from duck samples were typical of isolates from farmed poultry. Campylobacter spp. contamination of duck liver may present a hazard similar to the increasingly recognized contamination of chicken liver.

Extensively drug-resistant tuberculosis case in the Thames Valley, UK and public health interventions.

This study describes the first case of extensively drug-resistant tuberculosis (XDR-TB) in the Thames Valley and South East Region and discuss the public health implications, highlighting the need to integrate current epidemiological knowledge with clinical expertise in order to diagnose drug-resistant tuberculosis (TB) early. The management of the XDR-TB patients is challenging with few treatment options, expensive therapy, side effects of drugs and a longer course of the treatment.

An outbreak of norovirus infection linked to oyster consumption at a UK restaurant, February 2010.

BACKGROUND: We present the investigation of an outbreak of gastroenteritis at a UK restaurant incorporating both epidemiological and microbiological analysis. METHODS: Structured postal questionnaires were sent to 30 diners who ate at the restaurant during the outbreak period (5-7 February 2010). Stool specimens collected from staff and diners were submitted for bacterial culture and norovirus testing, and 15 Pacific oysters (Crassostrea gigas) from the batch served during the outbreak period were tested for norovirus. RESULTS: A strong association was observed between illness and oyster consumption (odds ratio undefined, confidence interval: 11.7 to infinity, P = 0.00001). Multiple different sequences of norovirus RNA were present in both stool and oyster specimens, typical of a shellfish origin. Several contemporaneous norovirus outbreaks throughout the UK were linked to oysters, particularly, though not exclusively, those sourced from Carlingford Lough in Ireland (as in this study), which were subsequently withdrawn from distribution. CONCLUSION: Despite the risk to human health, there is significant uncertainty surrounding the quantitative correlation between oyster norovirus levels and consumer illness. Continued research should help further our understanding of this crucial correlation and identify ways in which viral depuration of oysters can be enhanced.

[Social reproduction of families with children under the age of 7]. / Reprodución social de familias de niños menores de 7 años.

Through a casual-stratified-proportional sample, this study characterized the social reproduction profiles of 80 families with children under age 7 living within the area of assistance of the University of São Paulo's Hospital Universitário. The profiles were constructed using a theoretical-methodological-operational basis that predefined 3 homogeneous social groups. Of the total sample, 36.1 percent of the families showed the most precarious ways of reproduction in both production and consumption; 48.2 percent seemed to struggle for integration in social life; and 15.7 percent fulfilled the qualifications for their adequate integration in social production, seemed to be protected from irregular work, showing a differentiated pattem of consumption and of collective representation and betterpossibilities to use the geo-social space. The results demonstrated that the methodology employed is adequate for the characterization of the social reproduction profiles, highlighting the fact that the social groups that comprise a society have different working and living conditions, and that each of them is exposed to specific patterns of strength and proneness to diseases.

Reprodución social de familias de niños menores de 7 años / Social reproduction of families with children under the age of 7

Por medio de muestreo casual-estratificado- proporcional, en este estudio se caracterizaron las formas de reproducción social de 80 familias con niños menores de 7 años, residentes en el área de influencia del HU-USP. Los perfiles de reproducción social fueron construidos utilizándose una base teórico-metodológica- operacional que pre definió tres grupos sociales homogéneos. De la muestra total, 36,1% fueron más excluidas, tanto en el momento de la producción como en el de consumo, 48,2% parecían luchar por la integración en la vida social y 15,7% presentaron inserción apropiada en la producción, mostrándose protegidas de la precariedad del trabajo, con un patrón diferenciado de consumo y de representación colectiva y con mayor posibilidad de uso del espacio geo-social. Los resultados demostraron que la metodología utilizada es adecuada para caracterizar los perfiles de reproducción social, evidenciando que los grupos sociales que componen una misma sociedad presentaron condiciones de trabajo y de vida distintas y que cada grupo social está expuesto a determinados patrones de fortalecimiento y de desgaste.