Magnetic Resonance Imaging (MRI) of skeletal muscles in astronauts after 9 days of space flight

Skylab data indicated that prolonged exposure of human subjects to microgravity environment causes significant muscle atrophy accompanied by reduced muscle strength and fatigue resistance. The objective of this study was to determine decrements in muscle size, if any, in the soleus and gastrocnemius muscles of male and female astronauts after 9 days of space flight. Methods: Eight astronauts, one female and seven male, between the ages of 31 and 59 years 59-84 kg in body weight were examined by MRI 2-3 times preflight within 16 days before launch, and 2 days, (n=6) and seven days (n=3) after landing. The right leg muscles (gastroc-soleus) were imaged with a lower extremity coil in magnets operating at 1.0 or 1.5 Tsela. The imaging protocol consisted of spin echo with a Tr of 0.70 - 1.5 sec. Thirty to forty 3-5 mm thick slices were acquired in 256 x 128 or 256 x 256 matrices. Acquisition time lasted 20-40 minutes. Multiple slices were measured by computerized planimetry. Results: Compared to the preflight, the cross-sectoral areas (CSA) of the soleus, gastrocnemius, and the leg, at 2 days after landing were reduced (at least p less than 0.05) 8.9 percent, 13.2 percent, and 9.5 percent respectively. The soleus and the leg of three astronauts evaluated at 7 days postflight did not show full recovery compared to the preflight values. Conclusions: It is concluded that l9-days of space flight may cause significant decreases in CSA of the leg muscles. The factors responsible for this loss need further determination

Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype\u2013phenotype study in neurofibromatosis type 1

We report 281 individuals carrying a pathogenic recurrent NF1 missense variant at p.Met1149, p.Arg1276, or p.Lys1423, representing three nontruncating NF1 hotspots in the University of Alabama at Birmingham (UAB) cohort, together identified in 1.8% of unrelated NF1 individuals. About 25% (95% confidence interval: 20.5-31.2%) of individuals heterozygous for a pathogenic NF1 p.Met1149, p.Arg1276, or p.Lys1423 missense variant had a Noonan-like phenotype, which is significantly more compared with the "classic" NF1-affected cohorts (all p\u2009<\u2009.0001). Furthermore, p.Arg1276 and p.Lys1423 pathogenic missense variants were associated with a high prevalence of cardiovascular abnormalities, including pulmonic stenosis (all p\u2009<\u2009.0001), while p.Arg1276 variants had a high prevalence of symptomatic spinal neurofibromas (p\u2009<\u2009.0001) compared with "classic" NF1-affected cohorts. However, p.Met1149-positive individuals had a mild phenotype, characterized mainly by pigmentary manifestations without externally visible plexiform neurofibromas, symptomatic spinal neurofibromas or symptomatic optic pathway gliomas. As up to 0.4% of unrelated individuals in the UAB cohort carries a p.Met1149 missense variant, this finding will contribute to more accurate stratification of a significant number of NF1 individuals. Although clinically relevant genotype-phenotype correlations are rare in NF1, each affecting only a small percentage of individuals, together they impact counseling and management of a significant number of the NF1 population