Annals of the New York Academy of Sciences
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Benign paroxysmal positional vertigo (BPPV) presentations are unique opportunities to simultaneously improve the effectiveness and efficiency of care. The test and treatment for BPPV--the Dix-Hallpike test (DHT) and the canalith repositioning maneuver (CRM), respectively--are supported by two evidence-based guidelines (American Academy of Otolaryngology--Head and Neck Surgery and American Academy of Neurology). ⋯ Despite this large effect size, less than 10% of affected patients receive the treatment, which shows that the management of BPPV in routine care is suboptimal. Future research is necessary to disseminate and implement the DHT and the CRM into routine practice.
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Ann. N. Y. Acad. Sci. · Apr 2015
Splicing regulation in spinal muscular atrophy by an RNA structure formed by long-distance interactions.
Humans carry two copies of the survival motor neuron gene: SMN1 and SMN2. Loss of SMN1 coupled with skipping of SMN2 exon 7 causes spinal muscular atrophy (SMA), a leading genetic disease associated with infant mortality. Our discovery of intronic splicing silencer N1 (ISS-N1) is a promising target, currently in a phase III clinical trial, for an antisense oligonucleotide-mediated splicing correction in SMA. ⋯ Located in the middle of intron 7, the 3' strand of ISTL1 falls within an inhibitory region that we term ISS-N2. We demonstrate that an antisense oligonucleotide-mediated sequestration of ISS-N2 fully corrects SMN2 exon 7 splicing and restores high levels of SMN in SMA patient cells. These results underscore the therapeutic potential of the regulatory information present in a secondary and high-order RNA structure of a human intron.