Digital therapeutics are a new class of interventions that are software driven and are intended to treat various conditions. We developed and evaluated a dichoptic digital therapeutic for amblyopia, ...a neurodevelopmental disorder for which current treatments may be limited by poor adherence and residual vision deficits.
Randomized controlled trial.
One hundred five children 4 to 7 years of age with amblyopia were enrolled at 21 academic and community sites in the United States. Participants were randomized 1:1 to the treatment or comparison group, stratified by site.
We conducted a phase 3 randomized controlled trial to evaluate the safety and efficacy of a dichoptic digital therapeutic for amblyopia. Participants in the treatment group used the therapeutic at home for 1 hour per day, 6 days per week and wore glasses full-time. Participants in the comparison group continued wearing glasses full-time alone.
The primary efficacy outcome was change in amblyopic eye visual acuity (VA) from baseline at 12 weeks, and VA was measured by masked examiners. Safety was evaluated using the frequency and severity of study-related adverse events. Primary analyses were conducted using the intention-to-treat population.
Between January 16, 2019, and January 15, 2020, 105 participants were enrolled; 51 were randomized to the treatment group and 54 were randomized to the comparison group. At 12 weeks, amblyopic eye VA improved by 1.8 lines (95% confidence interval CI, 1.4–2.3 lines; n = 45) in the treatment group and by 0.8 lines (95% CI, 0.4–1.3 lines; n = 45) in the comparison group. At the planned interim analysis (adjusted α = 0.0193), the difference between groups was significant (1.0 lines; P = 0.0011; 96.14% CI, 0.33–1.63 lines) and the study was stopped early for success, according to the protocol. No serious adverse events were reported.
Our findings support the value of the therapeutic in clinical practice as an effective treatment. Future studies should evaluate the therapeutic compared with other methods and in additional patient populations.
The HMG-box proteins, one of the three classes of high mobility group (HMG) chromosomal proteins
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The recent revisions of the nomenclature for the HMG proteins are detailed on p.152 of this issue ...of
TiBS. The three families are now termed HMG-B, HMG-A and HMG-N.
, bend DNA and bind preferentially to distorted DNA structures. The proteins appear to act primarily as architectural facilitators in the assembly of nucleoprotein complexes; for example, in effecting recombination and in the initiation of transcription. HMG-box proteins might be targeted to particular DNA sites in chromatin by either protein–protein interactions or recognition of specific DNA structures.
The high‐mobility‐group B (HMGB) chromosomal proteins are characterized by the HMG box, a DNA‐binding domain that both introduces a tight bend into DNA and binds preferentially to a variety of ...distorted DNA structures. The HMGB proteins seem to act primarily as architectural facilitators in the manipulation of nucleoprotein complexes; for example, in the assembly of complexes involved in recombination and transcription. Recent genetic and biochemical evidence suggests that these proteins can facilitate nucleosome remodelling. One mechanism by which HMGB proteins could prime the nucleosome for migration is to loosen the wrapped DNA and so enhance accessibility to chromatin‐remodelling complexes and possibly also to transcription factors. By constraining a tight loop of untwisted DNA at the edge of a nucleosome, an HMGB protein could induce movements in the contacts between certain core histones that would result in an overall change in nucleosome structure.
The structural basis of DNA flexibility Travers, A. A.
Philosophical transactions of the Royal Society of London. Series A: Mathematical, physical, and engineering sciences,
07/2004, Letnik:
362, Številka:
1820
Journal Article
Recenzirano
Although the average physico-chemical properties of a long DNA molecule may approximate to those of a thin isotropic homogeneous rod, DNA behaves more locally as an anisotropic heterogeneous rod. ...This bending anisotropy is sequence dependent and to a first approximation reflects both the geometry and stability of individual base steps. The biological manipulation and packaging of the molecule often depend crucially on local variations in both bending and torsional flexibility. However, whereas the probability of DNA untwisting can be strongly correlated with a high bending flexibility, DNA bending, especially when the molecule is tightly wrapped on a protein surface, may be energetically favoured by a less flexible sequence whose preferred configuration conforms more closely to that of the complementary protein surface. In the latter situation the lower bending flexibility may be more than compensated for on binding by a reduced required deformation energy relative to a fully isotropic DNA molecule.
Athlete health and wellbeing requires a holistic, multidimensional approach to understanding, supporting, and treating individual athletes. Building more supportive, inclusive, and equitable ...environments for the health and wellbeing of women and gender expansive people further requires gender-responsive approaches that promote broader cultural change. Feminist sport and exercise medicine practitioners, sports scientists, and social science researchers are increasingly coming together in their efforts to do this work. However, working across disciplines inevitably includes an array of ontological, epistemological, and political challenges. In this paper, we offer a curated 'dialogue' with a group of feminist scholars engaged in research and practice across disciplines, bringing them together to discuss some of the most pressing gendered issues in sport today (i.e., ACL injury, concussion, menstruation in sport, mental health, gender categories). In so doing, we amplify the voices of those working (empirically and clinically) at the disciplinary intersections of gender, sport and health, and learn about some of the current and future possibilities for transdisciplinary innovations and strategies for building (responsiveness to) cultural change.
The systematics of the poriferan Order Haplosclerida (Class Demospongiae) has been under scrutiny for a number of years without resolution. Molecular data suggests that the order needs revision at ...all taxonomic levels. Here, we provide a comprehensive view of the phylogenetic relationships of the marine Haplosclerida using many species from across the order, and three gene regions. Gene trees generated using 28S rRNA, nad1 and cox1 gene data, under maximum likelihood and Bayesian approaches, are highly congruent and suggest the presence of four clades. Clade A is comprised primarily of species of Haliclona and Callyspongia, and clade B is comprised of H. simulans and H. vansoesti (Family Chalinidae), Amphimedon queenslandica (Family Niphatidae) and Tabulocalyx (Family Phloeodictyidae), Clade C is comprised primarily of members of the Families Petrosiidae and Niphatidae, while Clade D is comprised of Aka species. The polyphletic nature of the suborders, families and genera described in other studies is also found here.
A major question in chromatin biology is to what extent the sequence of DNA directly determines the genetic and chromatin organization of a eukaryotic genome? We consider two aspects to this ...question: the DNA sequence-specified positioning of nucleosomes and the determination of NDRs (nucleosome-depleted regions) or barriers. We argue that, in budding yeast, while DNA sequence-specified nucleosome positioning may contribute to positions flanking the regions lacking nucleosomes, DNA thermodynamic stability is a major component determinant of the genetic organization of this organism.
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