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"Skipping"
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The kids' guide to jumping rope
Readers learn about the sport of jumping rope, including how-to inf info on jumps and tricks.
Book
Development of DG9 peptide-conjugated single- and multi-exon skipping therapies for the treatment of Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is primarily caused by out-of-frame deletions in the dystrophin gene. Exon skipping using phosphorodiamidate morpholino oligomers (PMOs) converts out-of-frame to in-frame mutations, producing partially functional dystrophin. Four single-exon skipping PMOs are approved for DMD but treat only 8 to 14% of patients each, and some exhibit poor efficacy. Alternatively, exons 45 to 55 skipping could treat 40 to 47% of all patients and is associated with improved clinical outcomes. Here, we report the development of peptide-conjugated PMOs for exons 45 to 55 skipping. Experiments with immortalized patient myotubes revealed that exons 45 to 55 could be skipped by targeting as few as five exons. We also found that conjugating DG9, a cell-penetrating peptide, to PMOs improved single-exon 51 skipping, dystrophin restoration, and muscle function in hDMDdel52;mdx mice. Local administration of a minimized exons 45 to 55–skipping DG9-PMO mixture restored dystrophin production. This study provides proof of concept toward the development of a more economical and effective exons 45 to 55–skipping DMD therapy.
Journal Article
A skipping day
\"Jake and his friends Izzy and Cubby outsmart Captain Hook in this story based on the hit Disney Junior preschool series Jake and the Never Land Pirates.
Book
Eteplirsen in the treatment of Duchenne muscular dystrophy
Duchenne muscular dystrophy is a fatal neuromuscular disorder affecting around one in 3,500-5,000 male births that is characterized by progressive muscular deterioration. It is inherited in an X-linked recessive fashion and is caused by loss-of-function mutations in the
gene coding for dystrophin, a cytoskeletal protein that stabilizes the plasma membrane of muscle fibers. In September 2016, the US Food and Drug Administration granted accelerated approval for eteplirsen (or Exondys 51), a drug that acts to promote dystrophin production by restoring the translational reading frame of
through specific skipping of exon 51 in defective gene variants. Eteplirsen is applicable for approximately 14% of patients with
mutations. This article extensively reviews and discusses the available information on eteplirsen to date, focusing on pharmacological, efficacy, safety, and tolerability data from preclinical and clinical trials. Issues faced by eteplirsen, particularly those relating to its efficacy, will be identified. Finally, the place of eteplirsen and exon skipping as a general therapeutic strategy in Duchenne muscular dystrophy treatment will be discussed.
Journal Article
101 best jump rope workouts
\"A jump rope is the most effective fitness equipment you can own. It is versatile, portable, and efficient. Buddy Lee, recognized internationally as the world's expert at jump rope fitness, provides 100 challenging, dynamic and varied workouts in this unique collection. Simple and effective, these jump rope workouts can be done anywhere and anytime. Whether looking for a fun way to increase your fitness results or overcome a fitness plateau and reach new heights, The Jump Rope Workout Handbook shows you how. The Jump Rope Workout Handbook compiles a collection of more than 100 jump rope workouts optimized for effective weight loss, increased cardiovascular health, and improved athletic ability.\"--Provided by publisher.
Book
Associations of Skipping Breakfast, Lunch, and Dinner with Weight Gain and Overweight/Obesity in University Students: A Retrospective Cohort Study
Although multiple studies have identified skipping breakfast as a risk factor for weight gain, there is limited evidence on the clinical impact of skipping lunch and dinner on weight gain. This retrospective cohort study including 17,573 male and 8860 female university students at a national university in Japan, assessed the association of the frequency of breakfast, lunch, and dinner with the incidence of weight gain (≥10%) and overweight/obesity (body mass index ≥ 25 kg/m2), using annual participant health checkup data. Within the observation period of 3.0 ± 0.9 years, the incidence of ≥10% weight gain was observed in 1896 (10.8%) men and 1518 (17.1%) women, respectively. Skipping dinner was identified as a significant predictor of weight gain in multivariable-adjusted Poisson regression models for both men and women (skipping ≥ occasionally vs. eating every day, adjusted incidence rate ratios, 1.42 (95% confidence interval: 1.02–1.98) and 1.67 (1.33–2.09) in male and female students, respectively), whereas skipping breakfast and lunch were not. Similarly, skipping dinner, not breakfast or lunch, was associated with overweight/obesity (1.74 (1.07–2.84) and 1.68 (1.02–2.78) in men and women, respectively). In conclusion, skipping dinner predicted the incidence of weight gain and overweight/obesity in university students.
Journal Article
Multiple Exon Skipping in the Duchenne Muscular Dystrophy Hot Spots: Prospects and Challenges
Duchenne muscular dystrophy (DMD), a fatal X-linked recessive disorder, is caused mostly by frame-disrupting, out-of-frame deletions in the dystrophin (DMD) gene. Antisense oligonucleotide-mediated exon skipping is a promising therapy for DMD. Exon skipping aims to convert out-of-frame mRNA to in-frame mRNA and induce the production of internally-deleted dystrophin as seen in the less severe Becker muscular dystrophy. Currently, multiple exon skipping has gained special interest as a new therapeutic modality for this approach. Previous retrospective database studies represented a potential therapeutic application of multiple exon skipping. Since then, public DMD databases have become more useful with an increase in patient registration and advances in molecular diagnosis. Here, we provide an update on DMD genotype-phenotype associations using a global DMD database and further provide the rationale for multiple exon skipping development, particularly for exons 45–55 skipping and an emerging therapeutic concept, exons 3–9 skipping. Importantly, this review highlights the potential of multiple exon skipping for enabling the production of functionally-corrected dystrophin and for treating symptomatic patients not only with out-of-frame deletions but also those with in-frame deletions. We will also discuss prospects and challenges in multiple exon skipping therapy, referring to recent progress in antisense chemistry and design, as well as disease models.
Journal Article