Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional Observational Study.

BACKGROUND: Myotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity, challenging both medical management and clinical trials. The CTG expansion size is the main factor determining the age of onset although no factor can finely predict phenotype and prognosis. Differences between males and females have not been specifically reported. Our aim is to study gender impact on DM1 phenotype and severity. METHODS: We first performed cross-sectional analysis of main multiorgan clinical parameters in 1409 adult DM1 patients (>18 y) from the DM-Scope nationwide registry and observed different patterns in males and females. Then, we assessed gender impact on social and economic domains using the AFM-Téléthon DM1 survey (n = 970), and morbidity and mortality using the French National Health Service Database (n = 3301). RESULTS: Men more frequently had (1) severe muscular disability with marked myotonia, muscle weakness, cardiac, and respiratory involvement; (2) developmental abnormalities with facial dysmorphism and cognitive impairment inferred from low educational levels and work in specialized environments; and (3) lonely life. Alternatively, women more frequently had cataracts, dysphagia, digestive tract dysfunction, incontinence, thyroid disorder and obesity. Most differences were out of proportion to those observed in the general population. Compared to women, males were more affected in their social and economic life. In addition, they were more frequently hospitalized for cardiac problems, and had a higher mortality rate. CONCLUSION: Gender is a previously unrecognized factor influencing DM1 clinical profile and severity of the disease, with worse socio-economic consequences of the disease and higher morbidity and mortality in males. Gender should be considered in the design of both stratified medical management and clinical trials.

European and international standardisation progress in the field of engineered nanoparticles.

CEN-STAR supports researchers to be experts in standardization committees in new challenging issues: Standardization needs to reach consensus from new knowledge. In Europe, pre-normative and co-normative research can be supported financially by the FP7 for research. The area of nanoscience and nanotechnology is developing new standards in Europe within the CEN/TC 352, at the international level at the ISO/TC 229. Particular works are about measurement methods and tests for toxicity at the nanoscale. Some activities are done within the Organisation for Economic Cooperation and Development (OECD) and in some other parts of the world, such as the Asian Nano-Forum and the National Institute of Standards and Technology (NIST) in the United States. Main items for standardization include: definition terminology; metrology instrumentation, reference methods, and materials; measurement methods for applications (physical, chemical, material, electronics); and measurement methods for interface in health, environment, and safety. For toxicity at the nanoscale, particular issues have to be resolved, such as: reproducibility of experiments; reference protocols and use of quality management standards for research (ISO 9001); and intercomparability of results following "round robin" tests. The little information about standardization in nanotechnology in Europe includes the Code of Conduct for Responsible Nanosciences and Nanotechnologies Research and the European Commission mandate to CEN/TC 352, as well as the European Union (EU) projects NanoStrand, NanoInteract, NanoImpactNet, and others.