Objective Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials (myotonia), producing muscle stiffness. In patients, muscle stiffness lessens with exercise, a change known as the warm-up phenomenon. Our goal was to identify the mechanism underlying warm up and to use this information to guide development of novel therapy. Methods To determine the mechanism underlying warm-up, we used a recently discovered drug to eliminate muscle contraction, thus allowing prolonged intracellular recording from individual muscle fibers during induction of warm-up in a mouse model of myotonia congenita. Results Changes in action potentials suggested slow inactivation of sodium channels as an important contributor to warm-up. These data suggested enhancing slow inactivation of sodium channels might offer effective therapy for myotonia. Lacosamide and ranolazine enhance slow inactivation of sodium channels and are FDA-approved for other uses in patients. We compared the efficacy of both drugs to mexiletine, a sodium channel blocker currently used to treat myotonia. In vitro studies suggested both lacosamide and ranolazine were superior to mexiletine. However, in vivo studies in a mouse model of myotonia congenita suggested side effects could limit the efficacy of lacosamide. Ranolazine produced fewer side effects and was as effective as mexiletine at a dose that produced none of mexiletine’s hypoexcitability side effects. Interpretation We conclude ranolazine has excellent therapeutic potential for treatment of patients with myotonia congenita.

OBJECTIVE-Determine normal T 1 and extracellular volume (ECV) of the pancreas in subjects with no pancreas disease and correlate with age and gender SUBJECTS AND METHODS-We imaged 120 healthy subjects (age range: 20-78 years) who are on annual screening with MRI/MRCP for the possibility of pancreatic cancer. Subjects had a predisposition to develop pancreatic cancer, but no history of pancreas disease or acute symptoms. Equal number (n=60) of subjects were scanned on either 1.5 T or 3 T scanner using dual flip angle spoiled gradient echo technique incorporating fat suppression and correction for B 1 field inhomogeneity. Optimization of imaging parameters were performed using a T 1 phantom. ECV was calculated using pre-and post-contrast T 1 of the pancreas and plasma. Regression analysis and Mann-Whitney tests were used for statistical analysis.

Background: Children and adolescents with neurodevelopmental disabilities may be less well integrated into their community than their peers. Online groups can be particularly accessible for individuals with neurodevelopmental disabilities, as individuals may be able to connect with a larger network than they would in their local community. This systematic review aimed at estimating the effectiveness of online peer mentorship programmes on children and adolescent's participation in life situations.Methods: A systematic review was conducted to search Medline, PsycINFO, Embase, CINAHL, and Education Research Complete (ERIC) electronic databases. Thematic analysis was done for studies that used qualitative methodology.Results: Eleven articles were included, and they examined the influences of five different structured online peer mentorship intervention programmes and six different online support groups. The disabilities included cerebral palsy (n = 3), autism spectrum disorder (n = 3), spina bifida (n = 2), attention deficit hyperactivity disorder (n = 2), and other neurodevelopmental disorders. The mentors included in the studies were caregivers of children with disabilities, youth and adults with disabilities, and a virtual peer actor. The mentees included in the studies were youth with disabilities (age 10-19 years) and their families. Intervention characteristics varied across the studies but consistently showed a unique potential to facilitate social networking and support. Intervention programmes with specific content and structure showed better participation outcomes than unstructured interventions. Presence of a moderator and participant characteristics (age and sociocultural background) was suggested to influence the outcomes of interventions.Conclusions: Online peer mentorship programmes appear to have positive influence on social engagement and participation in life situation for children and adolescents with disabilities. This paper discusses several areas that should be considered in future research studies to improve potential effectiveness and use of study designs that help to establish not only if interventions work but also for whom they work best and why.

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