Time outdoors positively associates with academic performance: a school-based study with objective monitoring of outdoor time.

BACKGROUND: To explore the relationship between outdoor time and academic performance among school-aged children. METHODS: This study was designed as a cross-sectional study. Data were derived from a school-based prospective children myopia intervention study (STORM). Outdoor time was recorded by self-developed algorithm-validated wristwatches in real-time and calculated as the cumulative average of 10 months. The academic performance was recorded and provided by the participating schools and further standardized. Other information was collected using an online standardized questionnaire. Mixed-effects model and B-Spline method were used to investigate the association between time spent on different types of daily activity, including outdoor activity and academic performance. RESULTS: A total of 3291 children with mean age 9.25 years were included in the final analysis. Overall, outdoor time was associated with academic performance in a non-linear manner; specifically, not exceeding 2.3 h per day, outdoor time was positively associated with academic performance; exceeding 2.3 h per day, this association became non-significant. Likewise, daily sleep duration and out-of-school learning time were associated with academic performance in a non-linear manner, resulting in turning points of 11.3 and 1.4 h per day, respectively. Separate analysis showed that outdoor time and sleep duration but not out-of-school learning time were positively associated with academic performance in Chinese, mathematics and English. CONCLUSION: Outdoor time, sleep duration and out-of-school learning time were associated with academic performance in a non-linear manner. Promotion of outdoor time may not negatively impact on academic performance. TRIAL REGISTRATION: Our study was registered in ClinicalTrials.gov (Identifier: NCT02980445).

Time Outdoors in Reducing Myopia: A School-Based Cluster Randomized Trial with Objective Monitoring of Outdoor Time and Light Intensity.

PURPOSE: To evaluate the efficacy of time outdoors per school day over 2 years on myopia onset and shift. DESIGN: A prospective, cluster-randomized, examiner-masked, 3-arm trial. PARTICIPANTS: A total of 6295 students aged 6 to 9 years from 24 primary schools in Shanghai, China, stratified and randomized by school in a 1:1:1 ratio to control (n = 2037), test I (n = 2329), or test II (n = 1929) group. METHODS: An additional 40 or 80 minutes of outdoor time was allocated to each school day for test I and II groups. Children in the control group continued their habitual outdoor time. Objective monitoring of outdoor and indoor time and light intensity each day was measured with a wrist-worn wearable during the second-year follow-up. MAIN OUTCOME MEASURES: The 2-year cumulative incidence of myopia (defined as cycloplegic spherical equivalent [SE] of ≤-0.5 diopters [D] in the right eye) among the students without myopia at baseline and changes in SE and axial length (AL) after 2 years. RESULTS: The unadjusted 2-year cumulative incidence of myopia was 24.9%, 20.6%, and 23.8% for control, test I, and II groups, respectively. The adjusted incidence decreased by 16% (incidence risk ratio [IRR], 0.84; 95% confidence interval [CI], 0.72-0.99; P = 0.035) in test I and 11% (IRR = 0.89; 95% CI, 0.79-0.99; P = 0.041) in test II when compared with the control group. The test groups showed less myopic shift and axial elongation compared with the control group (test I: -0.84 D and 0.55 mm, test II: -0.91 D and 0.57 mm, control: -1.04 D and 0.65 mm). There was no significant difference in the adjusted incidence of myopia and myopic shift between the 2 test groups. The test groups had similar outdoor time and light intensity (test I: 127 ± 30 minutes/day and 3557 ± 970 lux/minute; test II: 127 ± 26 minutes/day and 3662 ± 803 lux/minute) but significantly more outdoor time and higher light intensity compared with the control group (106 ± 27 minutes/day and 2984 ± 806 lux/minute). Daily outdoor time of 120 to 150 minutes at 5000 lux/minutes or cumulative outdoor light intensity of 600 000 to 750 000 lux significantly reduced the IRR by 15%～ 24%. CONCLUSIONS: Increasing outdoor time reduced the risk of myopia onset and myopic shifts, especially in nonmyopic children. The protective effect of outdoor time was related to the duration of exposure and light intensity. The dose-response effect between test I and test II was not observed probably because of insufficient outdoor time achieved in the test groups, which suggests that proper monitoring on the compliance on outdoor intervention is critical if one wants to see the protective effect.

Prevalence of myopia and high myopia, and the association with education: Shanghai Child and Adolescent Large-scale Eye Study (SCALE): a cross-sectional study.

OBJECTIVES: To report on: (a) overall myopia and high myopia prevalence, and (b) the impact of education on the spherical equivalent refractive error in children across Shanghai. DESIGN: Cross-sectional study. SETTING: Across all 17 districts of Shanghai. PARTICIPANTS: 910 245 children aged 4-14 years from a school-based survey conducted between 2012 and 2013. MAIN OUTCOME MEASURES: Data of children with non-cycloplegic autorefraction, visual acuity assessment and questionnaire were analysed (67%, n=6 06 476). Prevalence of myopia (≤-1.0 D) and high myopia (≤-5.0 D) was determined. We used a regression discontinuity design to determine the impact of school entry cut-off date (1 September) by comparing refractive errors at each age, for children born pre-September to post-1 September, and performed a multivariate analysis to explore risk factors associated with myopia. Data analysis was performed in 2017-2018. RESULTS: Prevalence rates of myopia and high myopia were 32.9% (95% CI: 32.8% to 33.1%) and 4.2% (95% CI: 4.1% to 4.2%), respectively. From 6 years of age onwards, children born pre-September were more myopic compared with those born post-1 September (ahead in school by 1 year, discontinuity at 6 years: -0.19 D (95% CI: -0.09 to -0.30 D); 14 years: -0.67 D (95% CI: -0.21 to -1.14 D)). CONCLUSIONS: Our findings suggest that myopia is associated with education, that is primarily focused on near-based activities. Efforts to reduce the burden should be directed to public awareness, reform of education and health systems.

Zygotic Nuclear F-Actin Safeguards Embryonic Development.

After fertilization, sperm and oocyte nuclei are rapidly remodeled to form swollen pronuclei (PN) in mammalian zygotes, and the proper formation and function of PN are key to producing totipotent zygotes. However, how mature PN are formed has been unclear. We find that filamentous actin (F-actin) assembles in the PN of mouse zygotes and is required for fully functional PN. The perturbation of nuclear actin dynamics in zygotes results in the misregulation of genes related to genome integrity and abnormal development of mouse embryos. We show that nuclear F-actin ensures DNA damage repair, thus preventing the activation of a zygotic checkpoint. Furthermore, optogenetic control of cofilin nuclear localization reveals the dynamically regulated F-actin nucleoskeleton in zygotes, and its timely disassembly is needed for developmental progression. Nuclear F-actin is a hallmark of totipotent zygotic PN, and the temporal regulation of its polymerized state is necessary for normal embryonic development.

Discrimination of indoor versus outdoor environmental state with machine learning algorithms in myopia observational studies.

BACKGROUND: Wearable smart watches provide large amount of real-time data on the environmental state of the users and are useful to determine risk factors for onset and progression of myopia. We aim to evaluate the efficacy of machine learning algorithm in differentiating indoor and outdoor locations as collected by use of smart watches. METHODS: Real time data on luminance, ultraviolet light levels and number of steps obtained with smart watches from dataset A: 12 adults from 8 scenes and manually recorded true locations. 70% of data was considered training set and support vector machine (SVM) algorithm generated using the variables to create a classification system. Data collected manually by the adults was the reference. The algorithm was used for predicting the location of the remaining 30% of dataset A. Accuracy was defined as the number of correct predictions divided by all. Similarly, data was corrected from dataset B: 172 children from 3 schools and 12 supervisors recorded true locations. Data collected by the supervisors was the reference. SVM model trained from dataset A was used to predict the location of dataset B for validation. Finally, we predicted the location of dataset B using the SVM model self-trained from dataset B. We repeated these three predictions with traditional univariate threshold segmentation method. RESULTS: In both datasets, SVM outperformed the univariate threshold segmentation method. In dataset A, the accuracy and AUC of SVM were 99.55% and 0.99 as compared to 95.11% and 0.95 with the univariate threshold segmentation (p < 0.01). In validation, the accuracy and AUC of SVM were 82.67% and 0.90 compared to 80.88% and 0.85 with the univariate threshold segmentation method (p < 0.01). In dataset B, the accuracy and AUC of SVM and AUC were 92.43% and 0.96 compared to 80.88% and 0.85 with the univariate threshold segmentation (p < 0.01). CONCLUSIONS: Machine learning algorithm allows for discrimination of outdoor versus indoor environments with high accuracy and provides an opportunity to study and determine the role of environmental risk factors in onset and progression of myopia. The accuracy of machine learning algorithm could be improved if the model is trained with the dataset itself.

Myopia control with novel central and peripheral plus contact lenses and extended depth of focus contact lenses: 2 year results from a randomised clinical trial.

PURPOSE: We aimed to determine myopia control efficacy with novel contact lenses (CL) that (1) reduced both central and peripheral defocus, and (2) provided extended depth of focus with better global retinal image quality for points on, and anterior to, the retina and degraded for points posterior to the retina. METHODS: Children (n = 508, 8-13 years) with cycloplegic spherical equivalent (SE) -0.75 to -3.50D were enrolled in a prospective, double blind trial and randomised to one of five groups: (1) single vision, silicone hydrogel (SH) CL; (2) two groups wearing SH CL that imposed myopic defocus across peripheral and central retina (test CL I and II; +1.00D centrally and +2.50 and +1.50 for CL I and II at 3 mm semi-chord respectively); and (3) two groups wearing extended depth of focus (EDOF) hydrogel CL incorporating higher order aberrations to modulate retinal image quality (test CL III and IV; extended depth of focus of up to +1.75D and +2.50D respectively). Cycloplegic autorefraction and axial length (AL) measurements were conducted at six monthly intervals. Compliance to lens wear was assessed with a diary and collected at each visit. Additionally, subjective responses to various aspects of lens wear were assessed. The trial commenced in February 2014 and was terminated in January 2017 due to site closure. Myopia progression over time between groups was compared using linear mixed models and where needed post hoc analysis with Bonferroni corrections conducted. RESULTS: Myopia progressed with control CL -1.12 ± 0.51D/0.58 ± 0.27 mm for SE/AL at 24 months. In comparison, all test CL had reduced progression with SE/AL ranging from -0.78D to -0.87D/0.41-0.46 mm at 24 months (AL: p < 0.05 for all test CL; SE p < 0.05 for test CL III and IV) and represented a reduction in axial length elongation of about 22% to 32% and reduction in spherical equivalent of 24% to 32%. With test CL, a greater slowing ranging from 26% to 43% was observed in compliant wearers (≥6 days per week; Control CL: -0.64D/0.30 mm and -1.14D/0.58 mm vs test CL: -0.42D to -0.47D/0.12-0.18 mm and -0.70 to -0.81D/0.19-0.25 mm at 12 and 24 months respectively). CONCLUSIONS: Contact lenses that either imposed myopic defocus at the retina or modulated retinal image quality resulted in a slower progression of myopia with greater efficacy seen in compliant wearers. Importantly, there was no difference in the myopia control provided by either of these strategies.

Shanghai Time Outside to Reduce Myopia trial: design and baseline data.

IMPORTANCE: Myopia is a major public health concern worldwide, while outdoor time is indicated to be protective against the onset of myopia. BACKGROUND: To describe the methodology and baseline data of the Shanghai Time Outside to Reduce Myopia (STORM) trial. DESIGN: A 2-year, school-based, prospective, cluster randomized trial. PARTICIPANTS: Children from grade I and II classes of 24 schools from eight districts in Shanghai, China, were randomized to either a control group, a test group I (40-min outdoor time/day) or test group II (80-min outdoor time/day). METHODS: At baseline and annual intervals, cycloplegic autorefraction and axial length measurement will be performed. Time outdoors and light exposure will be monitored via parent/carer questionnaires and a wearable device. MAIN OUTCOME MEASURES: Spherical equivalent, prevalence of myopia and time outdoors in each group. RESULTS: A total of 6295 eligible children (age 7.2 ± 0.7 y [6-9 y]) were randomized to control (n = 2037), test group I (n = 2329) and test group II (n = 1929). At baseline, spherical equivalent was +0.98 ± 1.02D, +1.02 ± 1.02D and +1.00 ± 0.99D (P = 0.708), myopia prevalence was 8.9, 7.7 and 7.8% (P = 0.270) and time outdoors was 58.5 ± 35.8, 59.8 ± 34.7 and 58.5 ± 35.3 min/d (P = 0.886) for control, test groups I and II, respectively. CONCLUSIONS AND RELEVANCE: Myopia prevalence was high at nearly 8 to 9% in school children aged 7 years in Shanghai, China. The current trial will help evaluate if increased time outdoors has a role to play in reducing the incidence of myopia and/or slow the progression of myopia.

The Relationship between Progression in Axial Length/Corneal Radius of Curvature Ratio and Spherical Equivalent Refractive Error in Myopia.

SIGNIFICANCE: This study demonstrates that mean axial length/corneal radius of curvature ratio (AL/CR) can be used to detect low and high myopia but cannot clinically monitor myopia progression because the relationship between AL/CR and progression in myopia is different between low and high myopia. PURPOSE: The purpose of this study was to investigate the relationship of AL/CR with magnitude and progression of myopia. METHODS: Retrospective analysis was conducted comparing the right eyes of those with high myopia (n = 308; age, 7 to 16 years; myopia sphere, -6.00 diopters or worse) with those with low myopia (n = 732; age, 7 to 16 years; myopia sphere, between -0.50 and -3.50 diopters; cylinder, ≤1.00 diopters). Baseline axial length, corneal radii of curvature, and cycloplegic objective refraction were analyzed. Myopia progression in the low-myopia group at 6- and 12-month follow-up was measured, and the differences in slopes of AL/CR were compared for slow (<0.75 diopters) and fast progressing (≥0.75 diopters). RESULTS: Mean AL/CR values were significantly different (P < .001) between high myopia (3.46 ± 0.10) and low myopia (3.16 ± 0.07). In high and low myopia, slopes of axial length versus corneal curvature radius were not significantly different (P > .05), and slopes of AL/CR versus spherical equivalent were significantly different after adjusting for spherical equivalent and age (P < .05). Slopes of AL/CR progression and spherical equivalent progression were significantly different in low myopia between fast and slow progressing (P < .001), but the relationship between progression in AL/CR and progression in spherical equivalent was not strong. CONCLUSIONS: The AL/CR can be used to classify different grades of myopia, but it is not useful in determining the magnitude of myopia or monitoring progression because AL/CR is not linearly related to spherical equivalent and because progression in AL/CR is not strongly related to spherical equivalent progression.

Reduced vision in highly myopic eyes without ocular pathology: the ZOC-BHVI high myopia study.

BACKGROUND: The aim was to investigate the relationship of the magnitude of myopia with visual acuity in highly myopic eyes without ocular pathology. METHODS: Twelve hundred and ninety-two highly myopic eyes (up to -6.00 DS both eyes, no astigmatic cut-off) with no ocular pathology from the ZOC-BHVI high myopia study in China, had cycloplegic refraction, followed by subjective refraction and visual acuities and axial length measurement. Two logistic regression models were undertaken to test the association of age, gender, refractive error, axial length and parental myopia with reduced vision. RESULTS: Mean group age was 19.0 ± 8.6 years; subjective spherical equivalent refractive error was -9.03 ± 2.73 D; objective spherical equivalent refractive error was -8.90 ± 2.60 D and axial length was 27.0 ± 1.3 mm. Using visual acuity, 82.4 per cent had normal vision, 16.0 per cent had mildly reduced vision, 1.2 per cent had moderately reduced vision, 0.3 per cent had severely reduced vision and no subjects were blind. The percentage with reduced vision increased with spherical equivalent to 74.5 per cent from -15.00 to -39.99 D, axial length to 67.7 per cent of eyes from 30.01 to 32.00 mm and age to 22.9 per cent of those 41 years and over. Spherical equivalent and axial length were significantly associated with reduced vision (p < 0.0001). Age and parental myopia were not significantly associated with reduced vision. Gender was significant for one model (p = 0.04). CONCLUSION: Mildly reduced vision is common in high myopia without ocular pathology and is strongly correlated with greater magnitudes of refractive error and axial length. Better understanding is required to minimise reduced vision in high myopes.

Determination of scutellarin in breviscapine preparations using quantitative proton nuclear magnetic resonance spectroscopy.

The objective of the present study was to develop the selection criteria of proton signals for the determination of scutellarin using quantitative nuclear magnetic resonance (qNMR), which is the main bioactive compound in breviscapine preparations for the treatment of cerebrovascular disease. The methyl singlet signal of 3-(trimethylsilyl)propionic-2,2,3,3-d4 acid sodium salt was selected as the internal standard for quantification. The molar concentration of scutellarin was determined by employing different proton signals. To obtain optimum proton signals for the quantification, different combinations of proton signals were investigated according to two selection criteria: the recovery rate of qNMR method and quantitative results compared with those obtained with ultra-performance liquid chromatography. As a result, the chemical shift of H-2' and H-6' at δ 7.88 was demonstrated as the most suitable signal with excellent linearity range, precision, and recovery for determining scutellarin in breviscapine preparations from different manufacturers, batch numbers, and dosage forms. Hierarchical cluster analysis was employed to evaluate the determination results. The results demonstrated that the selection criteria of proton signals established in this work were reliable for the qNMR study of scutellarin in breviscapine preparations.

PACSIN 2 represses cellular migration through direct association with cyclin D1 but not its alternate splice form cyclin D1b.

Cyclin D1 overexpression is a common feature of many human malignancies. Genomic deletion analysis has demonstrated a key role for cyclin D1 in cellular proliferation, angiogenesis, and cellular migration. To investigate the mechanisms contributing to cyclin D1 functions, we purified cyclin D1a-associated complexes by affinity chromatography and identified the PACSIN 2 (protein kinase C and casein kinase substrate in neurons 2) protein by mass spectrometry. The PACSIN 2, but not the related PACSIN 1 and 3, directly bound wild-type cyclin D1 (cyclin D1a) at the carboxyl terminus, and failed to bind cyclin D1b, the alternative splicing variant of cyclin D1. PACSIN 2 knockdown induced cellular migration and reduced cell spreading in LNCaP cells expressing cyclin D1a. In cyclin D1(-/-) mouse embryonic fibroblasts (MEFs), cyclin D1a, but not cyclin D1b, reduced the cell spreading to a polarized morphology. siPACSIN 2 had no effect on cellular migration of cyclin D1(-/-) MEFs. Cyclin D1a restored the migratory ability of cyclin D1(-/-) MEFs, which was further enhanced by knocking down PACSIN 2 with siRNA. The cyclin D1-associated protein, PACSIN 2, regulates cell spreading and migration, which are dependent on cyclin D1 expression.