Contribution of muscle MRI for diagnosis of myopathy.

Inherited myopathies are a group of disease, which, although distinct from a genetic and prognostic point of view, can lead to non-specific clinical pictures due to phenotypic overlap. Acquired immuno-mediated myopathies may also pose the problem of clinically accurate etiological orientation. The assessment of fatty infiltration and pathological increase in water volume of the muscle contingent on whole-body muscle MRI is becoming increasingly important in aiding the initial diagnosis of inherited and acquired myopathies. MRI helps orientating the clinical diagnostic hypotheses thanks to the patterns of muscle involved (more or less specific according to the entities), which led to the development of decision-making algorithms proposed in the literature. The aim of this article is to specify the proper MRI protocol for the evaluation of myopathies and the basis of the interpretation and to provide a summary of the most frequently inherited and acquired myopathies described in the literature.

Spatio-temporal patterns of foot-and-mouth disease transmission in cattle between 2007 and 2015 and quantitative assessment of the economic impact of the disease in Niger.

Foot-and-mouth disease (FMD) is endemic in Niger, with outbreaks occurring every year. Recently, there was an increasing interest from veterinary authorities to implement preventive and control measures against FMD. However, for an efficient control, improving the current knowledge on the disease dynamics and factors related to FMD occurrence is a prerequisite. The objective of this study was therefore to obtain insights into the incidence and the spatio-temporal patterns of transmission of FMD outbreaks in Niger based on the retrospective analysis of 9-year outbreak data. A regression tree analysis model was used to identify statistically significant predictors associated with FMD incidence, including the period (year and month), the location (region), the animal-contact density and the animal-contact frequency. This study provided also a first report on economic losses associated with FMD. From 2007 to 2015, 791 clinical FMD outbreaks were reported from the eight regions of Niger, with the number of outbreaks per region ranging from 5 to 309. The statistical analysis revealed that three regions (Dosso, Tillabery and Zinder), the months (September, corresponding to the end of rainy season, to December and January, i.e., during the dry and cold season), the years (2007 and 2015) and the density of contact were the main predictors of FMD occurrence. The quantitative assessment of the economic impacts showed that the average total cost of FMD at outbreak level was 499 euros, while the average price for FMD vaccination of one outbreak was estimated to be more than 314 euros. Despite some limitations of the clinical data used, this study will guide further research into the epidemiology of FMD in Niger and will promote a better understanding of the disease as well as an efficient control and prevention of FMD.

Biosecurity practices in Belgian cattle farming: Level of implementation, constraints and weaknesses.

Over the last few years, a shift from curative towards preventive medicine occurred in the livestock sector. This led to an increased importance of biosecurity to better control infectious diseases by preventing their introduction and/or reducing their spread. Farmers are the main responsible actors of biosecurity measures (BSM). Existing studies report a low implementation level of BSM by the cattle farmers. Barriers such as cost, usefulness, importance, workload and lack of knowledge were investigated but the decision-making process of farmers related to a given BSM is not yet clarified. The objectives of this study were to (i) assess the level of implementation of BSM in cattle farms, (ii) assess the correlation between the importance that farmers give to a BSM and its effective implementation and (iii) identify the main reasons of non-implementation. A randomized survey was implemented in Belgium from December 2016 up to April 2017 with face-to-face interviews conducted in 100 Belgian farms. A descriptive analysis of data was performed using Microsoft Excel® and Stata14® . Chi-square and Spearman's rank correlation tests, respectively, allowed comparing implementation levels in dairy herds vs. beef herds and investigating the correlation between the importance that farmers give to a BSM and its implementation level. Biosecurity measures were poorly implemented to prevent disease introduction through direct contact and almost not to avoid indirect transmission. Some measures showed a significant difference in terms of implementation level between beef and dairy herds. A positive correlation was highlighted between the importance that farmers give to a BSM and its actual effective implementation. Perceived lack of efficiency, feasibility and usefulness are the reasons most often mentioned for non-implementation. Other factors potentially influencing the decision-making process should be further investigated and clarified. Evidence-based studies would be useful to convince the farmers of the need of implementing BSM.

Rural veterinarian's perception and practices in terms of biosecurity across three European countries.

The implementation of biosecurity measures in the animal health and production context is quite broad and aims at limiting the risk of introduction and spread of diseases. Veterinarians play a major role in biosecurity as key informants on the subject for cattle holders, key players in terms of disease prevention/control and eradication programs, as well as key risk factor in terms of disease dissemination. Many biosecurity studies have highlighted professional visitors such as veterinary practitioners as representing a high-risk factor in terms of disease introduction in animal facilities but, to date, very few studies have focused on the implementation level of biosecurity measures by veterinarians. An online survey was implemented in three European countries (Belgium, France and Spain) to assess the behaviour of rural veterinarians towards biosecurity, as well as their implementation level of the biosecurity measures. A descriptive analysis of data and a scoring system were applied to assess the implementation level of measures. The influence of different factors on the implementation level of biosecurity measures was investigated through a negative binomial regression model. The study identified different strengths, weaknesses, possible constraints and solutions in terms of veterinary perspectives. Veterinarians are considered as key informants by the farmers and could therefore play a more active role in terms of guidance and improvement of biosecurity at farm level. Based on the survey outcomes, two factors seemed to influence significantly the implementation level of measures: the country where he/she practices and the veterinarian's perception level of biosecurity. The biosecurity stages with the lowest application level, therefore representing the biggest threats, were bio-exclusion (increasing the risk of disease introduction) and biocontainment (increasing the risk of inter-herd transmission).

MeQA: a pipeline for MeDIP-seq data quality assessment and analysis.

MOTIVATION: We present a pipeline for the pre-processing, quality assessment, read distribution and methylation estimation for methylated DNA immunoprecipitation (MeDIP)-sequence datasets. This is the first MeDIP-seq-specific analytic pipeline that starts at the output of the sequencers. This pipeline will reduce the data analysis load on staff and allows the easy and straightforward analysis of sequencing data for DNA methylation. The pipeline integrates customized scripting and several existing tools, which can deal with both paired and single end data. AVAILABILITY: The package and extensive documentation, and comparison to public data is available at http://life.tongji.edu.cn/meqa/.

The pro-longevity gene FoxO3 is a direct target of the p53 tumor suppressor.

FoxO transcription factors have a conserved role in longevity, and act as tissue-specific tumor suppressors in mammals. Several nodes of interaction have been identified between FoxO transcription factors and p53, a major tumor suppressor in humans and mice. However, the extent and importance of the functional interaction between FoxO and p53 have not been fully explored. Here, we show that p53 regulates the expression of FoxO3, one of the four mammalian FoxO genes, in response to DNA damaging agents in both mouse embryonic fibroblasts and thymocytes. We find that p53 transactivates FoxO3 in cells by binding to a site in the second intron of the FoxO3 gene, a genomic region recently found to be associated with extreme longevity in humans. While FoxO3 is not necessary for p53-dependent cell cycle arrest, FoxO3 appears to modulate p53-dependent apoptosis. We also find that FoxO3 loss does not interact with p53 loss for tumor development in vivo, although the tumor spectrum of p53-deficient mice appears to be affected by FoxO3 loss. Our findings indicate that FoxO3 is a p53 target gene, and suggest that FoxO3 and p53 are part of a regulatory transcriptional network that may have an important role during aging and cancer.

Satellite cell dysfunction contributes to the progressive muscle atrophy in myotonic dystrophy type 1.

AIMS: Myotonic dystrophy type 1 (DM1), one of the most common forms of inherited neuromuscular disorders in the adult, is characterized by progressive muscle weakness and wasting leading to distal muscle atrophy whereas proximal muscles of the same patients are spared during the early phase of the disease. In this report, the role of satellite cell dysfunction in the progressive muscular atrophy has been investigated. METHODS: Biopsies were obtained from distal and proximal muscles of the same DM1 patients. Histological and immunohistological analyses were carried out and the past regenerative history of the muscle was evaluated. Satellite cell number was quantified in vivo and proliferative capacity was determined in vitro. RESULTS: The size of the CTG expansion was positively correlated with the severity of the symptoms and the degree of muscle histopathology. Marked atrophy associated with typical DM1 features was observed in distal muscles of severely affected patients whereas proximal muscles were relatively spared. The number of satellite cells was significantly increased (twofold) in the distal muscles whereas very little regeneration was observed as confirmed by telomere analyses and developmental MyHC staining (0.3-3%). The satellite cells isolated from the DM1 distal muscles had a reduced proliferative capacity (36%) and stopped growing prematurely with telomeres longer than control cells (8.4 vs. 7.1 kb), indicating that the behaviour of these precursor cells was modified. CONCLUSIONS: Our results indicate that alterations in the basic functions of the satellite cells progressively impair the muscle mass maintenance and/or regeneration resulting in gradual muscular atrophy.

The mitotic clock in skeletal muscle regeneration, disease and cell mediated gene therapy.

The regenerative capacity of skeletal muscle will depend on the number of available satellite cells and their proliferative capacity. We have measured both parameters in ageing, and have shown that although the proliferative capacity of satellite cells is decreasing during muscle growth, it then stabilizes in the adult, whereas the number of satellite cells decreases during ageing. We have also developed a model to evaluate the regenerative capacity of human satellite cells by implantation into regenerating muscles of immunodeficient mice. Using telomere measurements, we have shown that the proliferative capacity of satellite cells is dramatically decreased in muscle dystrophies, thus hampering the possibilities of autologous cell therapy. Immortalization by telomerase was unsuccessful, and we currently investigate the factors involved in cell cycle exits in human myoblasts. We have also observed that insulin-like growth factor-1 (IGF-1), a factor known to provoke hypertrophy, does not increase the proliferative potential of satellite cells, which suggests that hypertrophy is provoked by increasing the number of satellite cells engaged in differentiation, thus possibly decreasing the compartment of reserve cells. We conclude that autologous cell therapy can be applied to specific targets when there is a source of satellite cells which is not yet exhausted. This is the case of Oculo-Pharyngeal Muscular Dystrophy (OPMD), a late onset muscular dystrophy, and we participate to a clinical trial using autologous satellite cells isolated from muscles spared by the disease.

Satellite cells and training in the elderly.

In the present review, we describe the effects of ageing on human muscle fibres, underlining that each human muscle is unique, meaning that the phenotype becomes specifically changed upon ageing in different muscles, and that the satellite cells are key cells in the regeneration and growth of muscle fibres. Satellite cells are closely associated with muscle fibres, located outside the muscle fibre sarcolemma but beneath the basement lamina. They are quiescent cells, which become activated by stimulation, like muscle fibre injury or increased muscle tension, start replicating and are responsible for the repair of injured muscle fibres and the growth of muscle fibres. The degree of replication is governed by the telomeric clock, which is affected upon excessive bouts of degeneration and regeneration as in muscular dystrophies. The telomeric clock, as in dystrophies, does not seem to be a limiting factor in ageing of human muscle. The number of satellite cells, although reduced in number in aged human muscles, has enough number of cell divisions left to ensure repair throughout the human life span. We propose that an active life, with sufficient general muscular activity, should be recommended to reduce the impairment of skeletal muscle function upon ageing.

Skeletal muscle regeneration and the mitotic clock.

Regeneration of muscle fibers following damage requires activation of quiescent satellite cells, their proliferation and finally their differentiation and fusion into multinucleated myotubes, which after maturation will replace the damaged fiber. The regenerative potential of human skeletal muscle will be determined, at least partly, by the proliferative capacity of the satellite cells. In this study, we have measured the proliferative life span of human satellite cells until they reach senescence. These analyses were performed on cell populations isolated from old and young donors as well as from one child suffering from Duchenne muscular dystrophy, where extensive regeneration had occurred. In order to see if there are any age-related changes in the myogenic program we have also compared the program of myogenic differentiation expressed by satellite cells from these subjects at different stages of their proliferative lifespan.

Regenerative capacity of human satellite cells: the mitotic clock in cell transplantation.

In this communication, we will review the problems caused by cell-mediated gene therapy, taking skeletal muscle as a physiological model. In particular we have utilised vectors transferring telomerase under the control of retroviral promoters into human satellite cells. The set of results presented here has several implications regarding gene therapy trials. Nevertheless, more experiments will be required to fully validate this cellular model and to use telomerase to safely extend the lifespan of putative gene therapy vectors.

[The uretheral syndrome in men or prostatodynia]. / Syndrome uréthral de l'homme ou prostatodynie.

Based on the results of the clinical and urodynamic investigation of 15 patients, presenting with functional genitourinary symptoms, the authors report the efficacy of treatment with alpha-blockers. They stress the importance of the clinical history and of static sphincterometry in this type of patient.

[Bladder sphincter disorders in multiple sclerosis: symptomatology and evolution. 100 cases]. / Les troubles vésico-sphinctériens dans la sclérose en plaques: sémiologie et évolution. A propos de cent cas.

The semiology and evolution of vesicosphincteral disorders have been studied in a series of 100 cases of multiple sclerosis. All the patients underwent a complete checkup and were followed over a period of 6 years. Mictional problems appear within the first five years in 60 p. cent of cases. When they occur later on, they tend to follow the evolution of the disease on their own. There exist regular correlations between the gravity of the motor and sphincteral handicap, and between the size of the postmictional residue (over 20 p. cent of the miction), the time elapsing since the onset of the mictional disorders, and the appearance of uronephrological complications.