Unexpectedly high prevalence of asthenopia in Australian school children identified by the CISS survey tool

Background: To date there have been few systematic attempts to establish the general prevalence of asthenopia in unselected populations of school-aged children. Thus, the aim of this study was to determine whether the incorporation of Borsting et al’s 2003 Revised Convergence-Insufficiency Symptom Survey (CISS) into a general school vision screening could aid in the identification of children with visual discomfort and indicate the need for further investigation. Methods: Vision screening of an unselected middle school population investigated and analysed the incidence of self-reported nearwork-related visual discomfort via the CISS along with distance and near visual acuities plus non-cycloplegic autorefraction using a Shin-Nippon NVision-K 5001. Results: Of the 384 unselected students approached in Grades 6–9, 353 participated (92.2%, mean 13.2 ± 1.4 years). The mean CISS score for the population without amblyopia and/or strabismus (96.0% of all students) was 16.8 ± 0.6, i.e., 45% of students in this cohort had CISS scores greater than one standard deviation above the mean found by Borsting et al. in 2003 during their validation study of the CISS on 9 to 18 year old children without binocular anomalies. Regression analyses indicated significantly higher (p < 0.001) mean CISS scores for the 3.2% who were hyperopes ≥ + 2.00D by non-cycloplegic autorefraction (27.7 ± 14.7) and for those who were amblyopic (24.3 ± 6.6) or strabismic (34.0 ± 9.8). The mean CISS score of 31.6 ± 9.0 for non-amblyopic/strabismic students having near vision poorer than 0.1 LogMAR was significantly higher (p < 0.001) than for those with good acuity. Conclusion: The most important finding of this study was the high incidence of asthenopia in an unselected population and that refractive status per se was not a major contributor to CISS scores. The results highlight the usefulness of the CISS questionnaire for assessment of visual discomfort in school vision screenings and the need for future exploration of near binocular vision status as a potential driver of asthenopia in school students, especially given current trends for frequent daily use of computers and handheld devices and necessarily prolonged accommodative-convergence effort at near, both at school and at home

Potassium Channel and NKCC Cotransporter Involvement in Ocular Refractive Control Mechanisms

Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/−10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5mM Ba2+ and 10−5 M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba2+ but significant change only for negative lens defocus with bumetanide ; ; ; ; ; ). Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba2+ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a possible common mechanism. The selective inhibition of refractive compensation to negative lens in chick by loop diuretics such as bumetanide suggests that these drugs may be effective in the therapeutic management of human myopia

Longitudinal stroke recovery associated with dysregulation of complement system - A proteomics pathway analysis

Currently the longitudinal proteomic profile of post-ischemic stroke recovery is relativelyunknown with few well-accepted biomarkers or understanding of the biological systemsthat underpin recovery. We aimed to characterize plasma derived biological pathwaysassociated with recovery during the first year post event using a discovery proteomicsworkflow coupled with a topological pathway systems biology approach. Blood samples(n = 180, ethylenediaminetetraacetic acid plasma) were collected from a subgroup of60 first episode stroke survivors from the Australian START study at 3 timepoints: 3–7days (T1), 3-months (T2) and 12-months (T3) post-stroke. Samples were analyzed byliquid chromatography mass spectrometry using label-free quantification (data availableat ProteomeXchange with identifier PXD015006). Differential expression analysis revealedthat 29 proteins between T1 and T2, and 33 proteins between T1 and T3 weresignificantly different, with 18 proteins commonly differentially expressed across thetwo time periods. Pathway analysis was conducted using Gene Graph EnrichmentAnalysis on both the Kyoto Encyclopedia of Genes and Genomes and Reactomedatabases. Pathway analysis revealed that the significantly differentiated proteinsbetween T1 and T2 were consistently found to belong to the complement pathway.Further correlational analyses utilized to examine the changes in regulatory effects ofproteins over time identified significant inhibitory regulation of clusterin on complementcomponent 9. Longitudinal post-stroke blood proteomics profiles suggest that thealternative pathway of complement activation remains in a state of higher activation from3-7 days to 3 months post-stroke, while simultaneously being regulated by clusterin andvitronectin. These findings also suggest that post-stroke induced sterile inflammation andimmunosuppression could inhibit recovery within the 3-month window post-stroke

Identification and Replication of Three Novel Myopia Common Susceptibility Gene Loci on Chromosome 3q26 using Linkage and Linkage Disequilibrium Mapping

Refractive error is a highly heritable quantitative trait responsible for considerable morbidity. Following an initial genome-wide linkage study using microsatellite markers, we confirmed evidence for linkage to chromosome 3q26 and then conducted fine-scale association mapping using high-resolution linkage disequilibrium unit (LDU) maps. We used a preliminary discovery marker set across the 30-Mb region with an average SNP density of 1 SNP/15 kb (Map 1). Map 1 was divided into 51 LDU windows and additional SNPs were genotyped for six regions (Map 2) that showed preliminary evidence of multi-marker association using composite likelihood. A total of 575 cases and controls selected from the tails of the trait distribution were genotyped for the discovery sample. Malecot model estimates indicate three loci with putative common functional variants centred on MFN1 (180,566 kb; 95% confidence interval 180,505–180, 655 kb), approximately 156 kb upstream from alternate-splicing SOX2OT (182,595 kb; 95% CI 182,533–182,688 kb) and PSARL (184,386 kb; 95% CI 184,356–184,411 kb), with the loci showing modest to strong evidence of association for the Map 2 discovery samples (p<10−7, p<10−10, and p = 0.01, respectively). Using an unselected independent sample of 1,430 individuals, results replicated for the MFN1 (p = 0.006), SOX2OT (p = 0.0002), and PSARL (p = 0.0005) gene regions. MFN1 and PSARL both interact with OPA1 to regulate mitochondrial fusion and the inhibition of mitochondrial-led apoptosis, respectively. That two mitochondrial regulatory processes in the retina are implicated in the aetiology of myopia is surprising and is likely to provide novel insight into the molecular genetic basis of common myopia

Temporal whole field sawtooth flicker without a spatial component elicits a myopic shift following optical defocus irrespective of waveform direction in chicks.

Purpose: Myopia (short-sightedness) is the commonest visual disorder and greatest risk factor for sight threatening secondary pathologies. Myopia and hyperopia can be induced in animal models by rearing with optical lens defocus of opposite sign. The degree of refractive compensation to lens-induced defocus in chicks has been shown to be modified by directionally drifting sawtooth spatio-temporal luminance diamond plaids, with Fast-ON sawtooth spatio-temporal luminance profiles inhibiting the myopic shift in response to negative lenses, and Fast-OFF profiles inhibiting the hyperopic shift in response to positive lenses. What is unknown is whether similar sign-of-defocus dependent results produced by spatio-temporal modulation of sawtooth patterns could be achieved by rearing chicks under whole field low temporal frequency sawtooth luminance profiles at 1 or 4 Hz without a spatial component, or whether such stimuli would indiscriminately elicit a myopic shift such as that previously shown with symmetrical (or near-symmetrical) low frequency flicker across a range of species. Methods: Hatchling chicks (n = 166) were reared from days five to nine under one of three defocus conditions (No Lens, +10D lens, or -10D lens) and five light conditions (No Flicker, 1 Hz Fast-ON/Slow-OFF sawtooth flicker, 4 Hz Fast-ON/Slow-OFF sawtooth flicker, 1 Hz Fast-OFF/Slow-ON sawtooth flicker, or 4Hz Fast-OFF/Slow-ON sawtooth flicker). The sawtooth flicker was produced by light emitting diodes (white LEDs, 1.2 -183 Lux), and had no measurable dark phase. Biometrics (refraction and ocular axial dimensions) were measured on day nine. Results: Both 1 Hz and 4 Hz Fast-ON and Fast-OFF sawtooth flicker induced an increase in vitreous chamber depth that was greater in the presence of negative compared to positive lens defocus. Both sawtooth profiles at both temporal frequencies inhibited the hyperopic shift in response to +10D lenses, whilst full myopic compensation (or over-compensation) in response to -10D lenses was observed. Conclusions: Whole field low temporal frequency Fast-ON and Fast-OFF sawtooth flicker induces a generalized myopic shift, similar to that previously shown for symmetrical sine-wave and square-wave flicker. Our findings highlight that temporal modulation of retinal ON/OFF pathways per se (without a spatial component) is insufficient to produce strong sign-of-defocus dependent effect

Young children : YC ; the journal of the National Association for the Education of Young Children

The goal of this study was to investigate the effect of optical defocus and spatial contrast on refractive development and, in particular,on anterior chamber growth. Ninety chicks were raised from day 4-10 post-hatching wearing monocular lenses (+/-10 Dor 0 D), in an environment with either high, low or no spatial contrast patterns: 30%, 6% or 0% contrast, respectively. At day 10, the chicks' refractive state and ocular components were assessed using retinoscopy and A-scan ultrasonography. Ocular defocus resulted in sign-dependent significant differences in refractive error, axial length and vitreous chamber depth. Lens wear also led to significant spatial contrast dependent changes in anterior chamber depth. Varying ambient spatial contrast in the chick's environment did not inhibit emmetropization processes; however, anterior chamber growth was particularly susceptible to changes in spatial contrast

Effects of optical defocus and spatial contrast on anterior chamber depth in chicks.

The goal of this study was to investigate the effect of optical defocus and spatial contrast on refractive development and, in particular,on anterior chamber growth. Ninety chicks were raised from day 4-10 post-hatching wearing monocular lenses (+/-10 Dor 0 D), in an environment with either high, low or no spatial contrast patterns: 30%, 6% or 0% contrast, respectively. At day 10, the chicks' refractive state and ocular components were assessed using retinoscopy and A-scan ultrasonography. Ocular defocus resulted in sign-dependent significant differences in refractive error, axial length and vitreous chamber depth. Lens wear also led to significant spatial contrast dependent changes in anterior chamber depth. Varying ambient spatial contrast in the chick's environment did not inhibit emmetropization processes; however, anterior chamber growth was particularly susceptible to changes in spatial contrast

The application of quantitative analysis-parameters to detect and quantify the lung emphysema with HR-CT data

Das Ziel der vorliegenden HR-CT Untersuchung war die Detektion und Quantifizierung des Lungenemphysems mithilfe der computerbasierten Analyseparameter Emphysemindex, fraktale Dimension, Lungenvolumen und Lungendichte. In diese Studie gingen die HR-CT-Daten von 51 COPD Patienten und 23 gesunden Probanden ein. Mit Hilfe einer semiautomatischen Software wurden die HR-CT Bildserien segmentiert und analysiert. Für die fraktalen Dimensionen wurden anhand verschiedener Schwellenwerte fünf Analysebereiche festgelegt und mit der Masse-Radius Methode berechnet. Der Grenzwert für den Emphysemindex wurde bei -950 HE festgelegt. Die Ergebnisse zeigen hoch signifikante Korrelationen zwischen den einzelnen Parametern, insbesondere wenn die Gruppe der COPD Patienten separat betrachtet wird. Für die fraktale Dimension erreicht der Schwellenwertbereich von Th [-1000, -900] HE die höchsten Korrelationen. Darüber hinaus können signifikante Unterschiede zwischen den COPD Patienten und den gesunden Probanden für den Emphysemindex, das Lungenvolumen und die Lungendichte gefunden werden. Für das Anfangsstadium der COPD GOLD I resultierten keine signifikanten Ergebnisse. Die Berechnungen für die fraktale Dimension ergaben durchweg keine signifikanten Ergebnisse. Eine differenzierte Betrachtung zeigte, dass der Emphysemindex einen großen Überschneidungsbereich zwischen beiden Gruppen aufweist. Gesunde Probanden und COPD Patienten verfügen über einen Empyhsemindex von bis zu 12,3 %; dieser Bereich scheint somit noch physiologisch zu sein. In einer neuen Gruppeneinteilung wurde der Emphysemindex von 12,3 % als Grenzwert verwendet und anschließend erneut auf Unterschiede hinsichtlich der fraktalen Dimension untersucht. Es resultieren hoch signifikante Ergebnisse. Die Analyseparamter Emphysemindex, Lungenvolumen und -dichte sind geeignet um zwischen COPD Patienten und gesunden Probanden zu differenzieren. Schwierigkeiten bestehen in der reliablen Detektion milder Emphysem- Erscheinungsformen. Die neue Gruppeneinteilung führte auch bei der fraktalen Dimension zu signifikanten Ergebnissen, sodass auch dieser Parameter das Lun- genemphysem erfolgreich zu quantifizieren scheint.The purpose of this HR-CT study was the detection and quantification of pulmonary emphysema with computer-based parameters such as emphysema index, fractal dimension, lung volume and lung density. In this restrospective study, the HR-CT images of 51 COPD Patients and 23 healthy subjects were segmented and analyzed by a semi-automatically operating software. For the fractal dimensions five areas of analysis where defined based on different thresholds. They were calculated with the mass-radius-method. A cut-off threshold of -950 Hounsfield Units was used for the emphysema index. The results show highly significant correlations between the different parameters, especially when COPD patients were considered separately. For the fractal dimen- sion the highest correlation was achieved with a threshold of [-1000, -900] HU. In addition, significant differences were found between COPD patients and healthy subjects regarding emphysema index, lung volume and lung density. No significant results were found for the initial stage of COPD GOLD I. The calculation of the fractal dimension showed no significant results. A detailed analysis displayed a big overlap for the emphysema index between both groups. The emphysema index of the healthy subjects and COPD patients ranged up to 12,3 %;; thus this range can be considered physiological. Within a new group classification the emphysema index of 12,3 % was used as threshold and subsequently analyzed on differences in the fractal dimension. The results were of great significant. The parameters emphysema index, lung volume, and lung density are appropriate to distinguish between COPD patients and healthy subjects. Difficulties occur in the reliable detection of mild emphysema manifestations. The new group classification also led to significant results in the fractal dimension. On this account it seems to be a successful parameter to quantify pulmonary emphysema

Anxiety as a Common Biomarker for School Children With Additional Health and Developmental Needs Irrespective of Diagnosis.

Currently very little evidence is available regarding the biological characteristics and common comorbid behaviors that are associated with children characterized by learning difficulties who require additional support at school. These children are usually referred to as having Additional Health and Developmental Needs by the Australian Government and the associated public education system more broadly though the problems may arise from academic, social and/or emotional stressors and may or may not include children with clinically diagnosed Neurodevelopmental Disorders. Thus, the aim of this study was to investigate the relationship between anxiety levels (Spence Children's Anxiety Scale- Parent Report), autism traits (Autism Spectrum Quotient - Child Version) and sleep quality (Sleep Disturbance Scale for Children) in children with Additional Health and Developmental Needs without an intellectual disability, but with either a diagnosis of Autism Spectrum Disorder (ASD) (N = 25), Speech and Language Impairment (N = 37) or Other Diagnosis (N = 22). Our results demonstrated that these children with Additional Health and Developmental Needs showed atypically high levels of anxiety and impaired sleep quality, with the ASD group reporting more impairments associated with comorbid anxiety and sleep quality than either of the other clinically diagnosed groups. In fact, greater anxiety level was associated with a greater number of autism traits and poorer sleep quality regardless of diagnostic group suggesting that anxiety is a common experience for children with Additional Health and Developmental Needs. It is suggested that assessment of anxiety, sleep behaviors and autism traits may be useful markers for early identification of children within this population, thus providing scope for early and targeted intervention