High resolution, on-line identification of strains from the Mycobacterium tuberculosis complex based on tandem repeat typing

BACKGROUND: Currently available reference methods for the molecular epidemiology of the Mycobacterium tuberculosis complex either lack sensitivity or are still too tedious and slow for routine application. Recently, tandem repeat typing has emerged as a potential alternative. This report contributes to the development of tandem repeat typing for M. tuberculosis by summarising the existing data, developing additional markers, and setting up a freely accessible, fast, and easy to use, internet-based service for strain identification. RESULTS: A collection of 21 VNTRs incorporating 13 previously described loci and 8 newly evaluated markers was used to genotype 90 strains from the M. tuberculosis complex (M. tuberculosis (64 strains), M. bovis (9 strains including 4 BCG representatives), M. africanum (17 strains)). Eighty-four different genotypes are defined. Clustering analysis shows that the M. africanum strains fall into three main groups, one of which is closer to the M. tuberculosis strains, and an other one is closer to the M. bovis strains. The resulting data has been made freely accessible over the internet to allow direct strain identification queries. CONCLUSIONS: Tandem-repeat typing is a PCR-based assay which may prove to be a powerful complement to the existing epidemiological tools for the M. tuberculosis complex. The number of markers to type depends on the identification precision which is required, so that identification can be achieved quickly at low cost in terms of consumables, technical expertise and equipment

The dynamics of causes and conditions: the rareness of diseases in French and Portuguese patients' organizations' engagement in research

http://www.csi.mines-paristech.fr/Items/WorkingPapers/Download/DLWP.php?wp=WP_CSI_026.pdfHighlights the emergence of a "hybrid collective model" of collaboration between patients and experts through a systematic study in the field of rare diseases in France and Portugal, with attention to the reflexive work carried out by patients' organizations on the notion of rareness

Changes in leisure-time physical activity and sedentary behaviour at retirement: a prospective study in middle-aged French subjects

<p>Abstract</p> <p>Background</p> <p>Longitudinal studies on physical activity patterns around retirement age are scarce and provide divergent findings. Little is known about changes in sedentary behaviour in this context. Our aim was to investigate relationships between retirement and 3-year changes in leisure-time physical activity (LTPA) patterns and sedentary behaviour in middle-aged French adults.</p> <p>Methods</p> <p>Past-year LTPA and sedentary behaviour (watching television) were assessed in 1998 and 2001 using the Modifiable Activity Questionnaire on participants in the SU.VI.MAX (Supplementation with Antioxidants and Minerals) study. A total of 698 men and 691 women aged 45-64 were included in this analysis. Comparisons were made between subjects who had retired between 1998 and 2001 and those who continued to work, using the Chi-square test, Student t-test, Wilcoxon rank test or covariance analysis where appropriate.</p> <p>Results</p> <p>20.1% of men and 15.6% of women retired during follow-up. The baseline LTPA level was similar between subjects who retired during follow-up and those who continued to work. Mean LTPA increased by about 2 h/week in men and women who had retired, whereas no change was observed in employed persons. The positive change in LTPA following retirement was mainly related to an increase in activities of moderate intensity, such as walking. Retirement did not modify the ranking of the most frequently performed LTPAs, but the number of participants and the duration increased through retirement. In men, the increase in time spent watching TV was more than twice as high in retirees as in workers (+40.5 vs. +15.0 min/day, P < 0.0001). The same tendency was observed among women, but was borderline non-significant (+33.5 vs. +19.9 min/day, P = 0.05). In women, retirees who increased their walking duration by 2 h/week or more also decreased time spent watching TV by 11.5 min/day.</p> <p>Conclusions</p> <p>Retirement was associated with both an increase in LTPAs and in time spent watching TV, suggesting that retirement is an important period not only for promoting physical activity, but also for limiting sedentary behaviour.</p

Острый рабдомиолиз

Rhabdomyolysis results from the rapid breakdown of skeletal muscle fibers, which leads to leakage of potentially toxic cellular contents into the systemic circulation. Acquired causes by direct injury to the sarcolemma are the most frequent. The inherited causes are: metabolic with failure of energy production, including mitochondrial fatty acid ß-oxidation defects, LPIN1 mutations, inborn errors of glycogenolysis and glycolysis, more rarely mitochondrial respiratory chain deficiency, purine defects and peroxysomalα-Methylacyl-CoA-racemase defect (AMACR); dystrophinopathies and myopathies; calcic causes with RYR1 mutations; inflammatory with myositis. Irrespective of the cause of rhabdomyolysis, the pathophysiologic events follow a common pathway, the ATP depletion leading to an increased intracellular calcium concentration and necrosis. Most episodes of rhabdomyolysis are triggered by an environmental stress, mostly fever. This condition is associated with two events, elevated temperature and high circulating levels of pro-inflammatory mediators such as cytokines and chemokines. We describe here an example of rhabdomyolysis related to high temperature, aldolase deficiency, in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses. We show that the underlying mechanism involves an exacerbation of aldolase A deficiency at high temperatures that affected myoblasts but not erythrocytes. Thermolability was enhanced in patient myoblasts compared to control. The aldolase A deficiency was rescued by arginine supplementation in vitro. Lipid droplets accumulated in patient myoblasts relative to control and this was increased by cytokines. Lipotoxicity may participate to myolysis. Our results expand the clinical spectrum of aldolase A deficiency to isolated temperature-dependent rhabdomyolysis, and suggest that thermolability may be tissue specific. We also propose a treatment for this severe disease. Some other diseases involved in rhabdomyolysis may implicate pro-inflammatory cytokines and may be proinflammatory diseases.Острый рабдомиолиз – драматичное внезапное разрушение мышечных волокон скелетных мышц. К генетическим этиологическим факторам относят: метаболические расстройства, сопровождаемые дефицитом окисления жирных кислот, дефицитом липина-1, аномалии гликогенолиза и гликолиза, реже – дефицит митохондриальной дыхательной цепи, дефицит пурина и пероксизмальный дефицит α-метил-ацил-КоА-рацемазы (α-methyl-acyl-CoA-acemase, AMACR); структурные патологии в рамках дистрофинопатий и миопатий; аномалии кальциевого обмена с мутациями в гене RYR1; воспалительные реакции, ассоциированные с миозитом. Независимо от причины, дефицит аденозинтрифосфата в миоците приводит к повышению содержания внутриклеточного кальция и некрозу мышечных волокон. Провоцирующим фактором рабдомиолиза могут быть экзогенные факторы, среди которых травматизация мышц является самой частой причиной рабдомиолиза метаболического генеза. В случае лихорадки следует учитывать 2 фактора: повышение температуры тела и существование провоспалительных цитокинов. В статье описан случай рабдомиолиза у 3 детей от близкородственного брака, спровоцированный гипертермией и вызванный дефицитом альдолазы А, не сопровождаемой гемолитической анемией. В рассматриваемом случае миоглобинурия была всегда вызвана фебрильной температурой. В свою очередь, фермент альдолаза-А обладает тканеспецифичной термолабильностью: при тестируемых температурах он обнаружен в миобластах, но не в эритроцитах, что объясняет специфическую симптоматику у описываемых пациентов. Существуют предположения, что в клеточной липотоксичности участвуют так называемые жировые капли. В ходе исследований in vitro дефицит альдолазы А был возмещен добавлением аргинина. Другие типы рабдомиолиза метаболического генеза, вероятно, являются провоспалительными заболеваниями.перевод: Мария Олеговна Ковальчу

Post Genome-Wide Association Studies of Novel Genes Associated with Type 2 Diabetes Show Gene-Gene Interaction and High Predictive Value

Recently, several Genome Wide Association (GWA) studies in populations of European descent have identified and validated novel single nucleotide polymorphisms (SNPs), highly associated with type 2 diabetes (T2D). Our aims were to validate these markers in other European and non-European populations, then to assess their combined effect in a large French study comparing T2D and normal glucose tolerant (NGT) individuals. rs7903146 SNP, were combined (8.68-fold for the 14% of French individuals carrying 18 to 30 risk alleles with an allelic OR of 1.24). With an area under the ROC curve of 0.86, only 15 novel loci were necessary to discriminate French individuals susceptible to develop T2D. strongly associate with T2D in French individuals, and mostly in populations of Central European descent but not in Moroccan subjects. Genes expressed in the pancreas interact together and their combined effect dramatically increases the risk for T2D, opening avenues for the development of genetic prediction tests

Bone Marrow Transplant

Mucopolysaccharidosis type I-H (MPS I-H) is a rare lysosomal storage disorder caused by α-L-Iduronidase deficiency. Early haematopoietic stem cell transplantation (HSCT) is the sole available therapeutic option to preserve neurocognitive functions. We report long-term follow-up (median 9 years, interquartile range 8-16.5) for 51 MPS I-H patients who underwent HSCT between 1986 and 2018 in France. 4 patients died from complications of HSCT and one from disease progression. Complete chimerism and normal α-L-Iduronidase activity were obtained in 84% and 71% of patients respectively. No difference of outcomes was observed between bone marrow and cord blood stem cell sources. All patients acquired independent walking and 91% and 78% acquired intelligible language or reading and writing. Intelligence Quotient evaluation (n = 23) showed that 69% had IQ ≥ 70 at last follow-up. 58% of patients had normal or remedial schooling and 62% of the 13 adults had good socio-professional insertion. Skeletal dysplasia as well as vision and hearing impairments progressed despite HSCT, with significant disability. These results provide a long-term assessment of HSCT efficacy in MPS I-H and could be useful in the evaluation of novel promising treatments such as gene therapy

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries

De Revault d’Allonnes à une théorie du schème aujourd’hui.

International audienceLe concept de schème, introduit par Kant et considérablement développé par Revault d'Allonnes, a connu une grande fortune. Mais il a fait aussi l'objet d'interprétations très différentes et de malentendus. Ce qui manque le plus chez Revault d'Allonnes, en dépit de la richesse de sa contribution, ce sont les idées d'activité et de développement. C'est aussi de ces deux points de vue que le présent article considère les contributions de Janet, de Bartlett, et de Piaget. Dans la seconde partie de l'article est présenté l'état actuel d'une théorie qui propose une définition et une analyse relativement rigoureuses du concept de schème. Plusieurs sens du concept de représentation sont également analysés, tous utiles bien que différents : flux de la conscience, ensemble de concepts, systèmes de signifiants/signifiés, ensemble de schèmes. Trois homomorphismes distincts sont identifiés : entre réel et invariants opératoires, entre invariants et signifiés de la langue, entre signifiés et signifiants

De Revault d’Allonnes à une théorie du schème aujourd’hui.

International audienceLe concept de schème, introduit par Kant et considérablement développé par Revault d'Allonnes, a connu une grande fortune. Mais il a fait aussi l'objet d'interprétations très différentes et de malentendus. Ce qui manque le plus chez Revault d'Allonnes, en dépit de la richesse de sa contribution, ce sont les idées d'activité et de développement. C'est aussi de ces deux points de vue que le présent article considère les contributions de Janet, de Bartlett, et de Piaget. Dans la seconde partie de l'article est présenté l'état actuel d'une théorie qui propose une définition et une analyse relativement rigoureuses du concept de schème. Plusieurs sens du concept de représentation sont également analysés, tous utiles bien que différents : flux de la conscience, ensemble de concepts, systèmes de signifiants/signifiés, ensemble de schèmes. Trois homomorphismes distincts sont identifiés : entre réel et invariants opératoires, entre invariants et signifiés de la langue, entre signifiés et signifiants