Search results for "Cribratge"
showing 2 items of 2 documents
Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes
2018
Modification of SMN2 exon 7 (E7) splicing is a validated therapeutic strategy against spinal muscular atrophy (SMA). However, a target-based approach to identify small-molecule E7 splicing modifiers has not been attempted, which could reveal novel therapies with improved mechanistic insight. Here, we chose as a target the stem-loop RNA structure TSL2, which overlaps with the 5′ splicing site of E7. A small-molecule TSL2-binding compound, homocarbonyltopsentin (PK4C9), was identified that increases E7 splicing to therapeutic levels and rescues downstream molecular alterations in SMA cells. High-resolution NMR combined with molecular modelling revealed that PK4C9 binds to pentaloop conformati…
Multidimensional instruments with an integral approach to identify frailty in community-dwelling people: protocol for a systematic psychometric review
2019
IntroductionAn increasing number of investigations highlight the complex nature of frailty; therefore, the use of multidimensional assessment instruments could be useful in clinical decision-making. Frail people are found mainly in the community setting which is why this is the ideal environment for early screening and intervention. For this purpose, it is necessary to have valid, time-effective and easy-to-use frailty assessment instruments. The aim of this review is to critically appraise, compare and summarise the quality of the measurement properties of all multidimensional instruments with an integral approach to identify frailty in community-dwelling people.Methods and analysisMedline…