No abstract

We report the first case of a human neuromuscular transmission dysfunction due to mutations in the gene encoding the muscle-specific receptor tyrosine kinase (MuSK). Gene analysis identified two heteroallelic mutations, a frameshift mutation (c.220insC) and a missense mutation (V790M). The muscle biopsy showed dramatic pre- and postsynaptic structural abnormalities of the neuromuscular junction and severe decrease in acetylcholine receptor (AChR) epsilon-subunit and MuSK expression. In vitro and in vivo expression experiments were performed using mutant MuSK reproducing the human mutations. The frameshift mutation led to the absence of MuSK expression. The missense mutation did not affect MuSK catalytic kinase activity but diminished expression and stability of MuSK leading to decreased agrin-dependent AChR aggregation, a critical step in the formation of the neuromuscular junction. In electroporated mouse muscle, overexpression of the missense mutation induced, within a week, a phenotype similar to the patient muscle biopsy: a severe decrease in synaptic AChR and an aberrant axonal outgrowth. These results strongly suggest that the missense mutation, in the presence of a null mutation on the other allele, is responsible for the dramatic synaptic changes observed in the patient.

No abstract

No abstract

Summary The link between sleepiness and the risk of motor vehicle accidents is well known, but little is understood regarding the risk of home, work and car accidents of subjects with insomnia. An international cross‐sectional survey was conducted across 10 countries in a population of subjects with sleep disturbances. Primary care physicians administered a questionnaire that included assessment of sociodemographic characteristics, sleep disturbance and accidents (motor vehicle, work and home) related to sleep problems to each subject. Insomnia was defined using the International Classification of Sleep Disorders (ICSD‐10) criteria. A total of 5293 subjects were included in the study, of whom 20.9% reported having had at least one home accident within the past 12 months, 10.1% at least one work accident, 9% reported having fallen asleep while driving at least once and 4.1% reported having had at least one car accident related to their sleepiness. All types of accident were reported more commonly by subjects living in urban compared to other residential areas. Car accidents were reported more commonly by employed subjects, whereas home injuries were reported more frequently by the unemployed. Car accidents were reported more frequently by males than by females, whereas home accidents were reported more commonly by females. Patients with insomnia have high rates of home accidents, car accidents and work accidents related to sleep disturbances independently of any adverse effects of hypnotic treatments. Reduced total sleep time may be one factor explaining the high risk of accidents in individuals who complain of insomnia.

No abstract

Our data provide further epidemiologic evidence that with no specific selection in primary care medicine, usual short-sleep duration increases the risk of hypertension prevalence in adults over 40 years.

Objectives: This study examines the effects of sleep restricted to four hours for three consecutive nights on blood parameters, known to be associated with cardiovascular risk, in young healthy men. Material and methods: Eight young healthy men (age 24.5 ± 3.3 years) were studied in the sleep restricted group. Nine young healthy men (age 24 ± 2 years) were included in the control group and spent the days and nights in the sleep lab, while sleeping eight hours/night. One baseline night was followed by three nights of sleep restriction to four hours and by one recovery night of eight hours. Blood samplings were performed after the baseline night and after the third night of sleep restriction or without restriction for the control group. Results: A signifi cant increase in white blood cells (WBC) (5.79 ± 1.05 vs. 6.89 ± 1.31 10 3 cell/μl, p = 0.03), and neutrophils (3.17 ± 0.69 vs 4.24 ± 0.97 10 3 cell/μl, p = 0.01) was observed after the third night of sleep restriction. Other blood parameters were not affected. No signifi cant variation was observed in the control group. Conclusion: Sleep restriction affected WBC count, mainly neutrophils, considered as risk factor for cardiovascular disease. Stress induced by the short term sleep restriction could be involved in this observation.