Feasibility of monitoring compliance with intermittent occlusion therapy glasses for amblyopia treatment

Background Liquid crystal glasses use an intermittent occlusion technique and may improve compliance compared to adhesive patches. Previous studies support the effectiveness of intermittent occlusion therapy (IO therapy) glasses for amblyopia treatment. However, objective compliance for these glasses has not been measured. The purpose of this study was to investigate the feasibility of using a microsensor to monitor objective compliance with IO therapy glasses. Methods Children 3 to ≤8 years of age with unilateral amblyopia were enrolled. All subjects had optimal refractive correction (if needed) for at least 5 weeks without improvement. Subjects were prescribed IO therapy glasses, set at 30-second opaque/transparent intervals (ie, occluded 50% of wear time). Wear time was prescribed according to amblyopia severity. For each patient, objective compliance with the IO therapy glasses was monitored by means of a microsensor. Results A total of 13 subjects returned with microsensor data. Compliance varied among and within individuals. General compliance averaged 51.6% (range, 10%-97%). Mean daily compliance decreased slightly over time. On average, patients’ visual acuity improved 0.14 ± 0.15 logMAR (range, −0.1 to 0.5 logMAR). No parents reported that their child had social concerns related to the attached microsensor. Conclusions Objective compliance with IO therapy glasses can be monitored by a simple microsensor reliably. In our study cohort, objective compliance with IO therapy glasses varied among individuals, but on average it declined slightly over time

Intense versus standard regimens of intermittent occlusion therapy for unilateral moderate amblyopia in children: study protocol for a randomized controlled trial

Background: We reported that in our previous study that wearing intermittent occlusion therapy glasses (IO-therapy) for 4 hours (h) was non-inferior to patching for 2 h in 3 to 8-year-old children with amblyopia. We hypothesize that an intense regimen of 12-h IO-therapy per day for 4 weeks could be as effective as the standard regimen of 4-h IO-therapy per day for 12 weeks in treating moderate amblyopia in 3 to 8-year-old children. Methods/design: A total of 56 children between 3 and 8 years of age with amblyopia in association with anisometropia and/or strabismus will be enrolled. All participants will be prescribed IO-therapy glasses (Amblyz™), set at 30-s opaque/transparent intervals (i.e., occluded 50% of wear time). They will be randomized to receive the standard regimen for 12 weeks or the intense regimen for 4 weeks. Adherence to using the IO-therapy glasses will be objectively monitored in each participant by means of a microsensor dose monitor. The primary study objective is to compare the effectiveness of an intense regimen to a standard regimen of IO-therapy in 3 to 8-year-old children with moderate amblyopia. The secondary study objectives are to determine whether adherence differs between an intense regimen and a standard regimen of IO-therapy, and to determine the dose-response relationship of IO-therapy. Discussion: In addition to testing the effectiveness, this study will test for the first time the association between treatment adherence and the visual outcome of IO-therapy, which will enhance our understanding of the dose-response relationship of IO-therapy. If an intense regimen is shown to be effective, it would alter amblyopia treatment strategies and improve visual outcomes. Trial registration: ClinicalTrials.gov: NCT02767856. Registered on 10 May 2016

SCARB2/LIMP-2 Regulates IFN Production of Plasmacytoid Dendritic Cells by Mediating Endosomal Translocation of TLR9 and Nuclear Translocation of IRF7

Scavenger receptor class B, member 2 (SCARB2) is essential for endosome biogenesis and reorganization and serves as a receptor for both β-glucocerebrosidase and enterovirus 71. However, little is known about its function in innate immune cells. In this study, we show that, among human peripheral blood cells, SCARB2 is most highly expressed in plasmacytoid dendritic cells (pDCs), and its expression is further upregulated by CpG oligodeoxynucleotide stimulation. Knockdown of SCARB2 in pDC cell line GEN2.2 dramatically reduces CpG-induced type I IFN production. Detailed studies reveal that SCARB2 localizes in late endosome/lysosome of pDCs, and knockdown of SCARB2 does not affect CpG oligodeoxynucleotide uptake but results in the retention of TLR9 in the endoplasmic reticulum and an impaired nuclear translocation of IFN regulatory factor 7. The IFN-I production by TLR7 ligand stimulation is also impaired by SCARB2 knockdown. However, SCARB2 is not essential for influenza virus or HSV-induced IFN-I production. These findings suggest that SCARB2 regulates TLR9-dependent IFN-I production of pDCs by mediating endosomal translocation of TLR9 and nuclear translocation of IFN regulatory factor 7

Porous hierarchical TiO2/MoS2/RGO nanoflowers as anode material for sodium ion batteries with high capacity and stability

To enhance the reversible capacity and cycle stability of MoS2 as anode materials for sodium ion batteries (SIBs), we constructed a hybrid architecture composed of MoS2 and TiO2 nanosheets, linking with reduced graphene oxide (RGO) to another TiO2/MoS2 to form a nanoflower structure. Owing to layered RGO coupled with TiO2/MoS2 hybrid, such a composite offered interconnected conductive channels to short shuttle path of Na+ ions and favorable transport kinetics under charge/discharge cycling. Moreover, this unique structure showed a porous and hierarchical architecture, which not only buffered volume changes but also provided more electrochemical active sites during insertion/deintercalation processes of Na ions. Outstanding electrochemical performances were identified by the component matching effect among TiO2, MoS2 and RGO with a three-dimensional (3D) interconnected network, exhibiting a good reversible capacity of 616 mA h g-1 after 100 cycles at 0.1 A g-1, an excellent rate capability of 250 mA h g-1 even at 5A g-1 and a long cycling stability of 460 mA h g-1 with a capacity fluctuation of 0.03% per cycle within 350 cycles at 1 A g-1

Activation Mode Effects on the Shear Bond Strength of Dual-cured Resin Cements

Objectives: This study evaluated the immediate (10-minute) and delayed (24-hour) bond strength of dual-cured resin cements that are light-activated either immediately or delayed (after five minutes) or chemically-activated only. Materials and Methods: Three dual-cured resin cements were evaluated: RelyX ARC, Panavia F and Enforce. Cylinders of resin cement were built up over resin composite blocks following the manufacturers’ instructions for each luting agent. The cements were mixed, inserted into the molds and light-activated either immediately or after five minutes (delayed light activation). When no light activation was performed, the materials were protected from light exposure until testing. Half of the samples were tested at 10 minutes; the remaining samples were stored at 100% relative humidity for 4 hours when they were then test ed (n=10). Data were submitted to three-way ANOVA and post-hoc Tukey’s tests (α=0.05). The failure mode was evaluated under SEM. Results: RelyX ARC presented the highest values of shear bond strength, followed by Enforce. Panavia F showed the lowest values. Both immediate and delayed light activation caused the cements to present the highest means of shear bond strength. There was an improvement in bond strength after 24 hours of storage. Conclusions: RelyX ARC produced the highest bond strength, which was improved by light activation and storage for 24 hours

Satellite testing of a gravitationally induced quantum decoherence model

Quantum mechanics and the general theory of relativity are two pillars of modern physics. However, a coherent unified framework of the two theories still remains an open problem. Attempts to quantize general relativity have led to many rival models of quantum gravity, which, however, generally lack experimental foundations. We report a quantum optical experimental test of event formalism of quantum fields, a theory which attempts to present a coherent description of quantum fields in exotic spacetimes containing closed timelike curves and ordinary spacetime. We experimentally test a prediction of the theory with the quantum satellite Micius that a pair of time-energy entangled particles probabilistically decorrelate passing through different regions of the gravitational potential of Earth. Our measurement results are consistent with the standard quantum theory and hence do not support the prediction of event formalism

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD