Digital device viewing behaviour in children.

INTRODUCTION: Habitual viewing behaviour is widely believed to be an important contributing factor to the onset and progression of myopia and may be task dependent. The purpose of this study was to quantify the habitual viewing distance of children performing five different tasks on a smartphone digital device. METHODS: The real-time viewing distance in 38 children with their habitual correction was measured using software (MyopiaApp) on a handheld (Google Pixel 3) device. Five tasks were performed in a randomised sequence: playing a game, watching video in a light (680 lux) and dark (5.5 lux) environment and reading small (8 pt) and large (16 pt) text. ANCOVA statistical analysis was used to evaluate the effect of task, group (myope vs. non-myope) and arm length on the median relative viewing distance. RESULTS: Arm length was not correlated with viewing distance in any of the tasks, and there was no significant difference in viewing distance between any of the tasks. Specifically, a two-way mixed ANCOVA indicated that task, refractive group (myopic vs. non-myopic), age and arm length, as well as all two-way interactions were not significantly associated with viewing distance. Overall, 60% of the total variance in viewing distance was accounted for by individual differences. CONCLUSIONS: The average handheld viewing distance was similar across a variety of everyday tasks in a representative sample of myopic and emmetropic children. Neither arm length, age nor refractive group were associated with viewing distance in any of the tasks. Importantly, myopic children of a given size did not hold the smartphone digital device at a different distance for any task than their equally sized non-myopic peers. However, both groups exhibited high inter-individual variability in mean viewing distance, indicating some subjects performed all tasks at further distances while other subjects used at nearer distances.

The association between participant-reported ratings of comfort, dryness and vision quality in soft contact lens wearers.

INTRODUCTION: Previous literature has indicated an association between participant-reported perceptions (e.g., ratings) of comfort, dryness and vision quality during soft contact lens wear. However, these reports do not account for participant- and lens-specific factors which may impact the interpretation of these results. The purpose of this project was to quantify the association between these participant-reported ratings while accounting for both participant- and lens-specific factors. METHODS: Participant-reported ratings (scale 0-100) of comfort, dryness and quality of vision for 675 soft contact lens wearers (1207 eyes) were aggregated across 31 studies completed at Indiana University. Linear mixed-effects regression modelling was performed on each outcome rating individually. Covariate-adjusted models incorporated both participant- (e.g., age, sex) and lens-related (e.g., lens material, edge and optics) factors. The models were statistically adjusted for the duration of lens wear in hours and cumulative days of exposure. RESULTS: Consistent with estimates from covariate-adjusted regression models, pairwise Spearman correlations [95% CI] between dryness and comfort (rs = 0.71, [0.69, 0.74]), vision quality and comfort (rs = 0.53, [0.49, 0.57]) and vision quality and dryness (rs = 0.49, [0.42, 0.54]) were all positive and had p < 0.001. Average participant-reported ratings of comfort, dryness and vision quality decreased by (bs [95% CI]) = -0.81 [-1.15, -0.46] -0.34 [-0.67, 0.0005] and -0.90 [-1.19, -0.60] rating units, respectively, for each hour of lens wear. CONCLUSIONS: Significant positive associations were found between participant-reported measures of comfort, dryness and vision quality during soft contact lens wear. The associations between these ratings and the participant- and lens-related factors that drive them should be considered by clinicians and manufacturers when fitting and designing soft contact lenses.

On-eye centration of soft contact lenses.

PURPOSE: To evaluate the relative positions of modern soft contact lenses (SCLs) relative to the limbus/cornea and the pupil. METHODS: Sixty images of the anterior eyes of 101 subjects were acquired over 10 s while participants fixated the centre of the camera lens located 33 cm in front of the eye in a well-lit (300 lux) clinic. Custom validated image analysis software was used to locate the boundaries of the contact lenses, pupils and corneas (limbus). Horizontal and vertical relative positions of the contact lens, pupil and limbus were calculated from the fitted boundaries. RESULTS: The mean (standard deviation) pupil and corneal diameters for all subjects were 3.84 mm, (0.83) and 11.97 mm (0.48), respectively. The mean [95% confidence interval] pupil centre was located 0.28 mm [0.26, 0.30] nasally and 0.07 mm [0.05, 0.10] superiorly to the corneal centre. Consistent with clinical observations, the contact lenses centred accurately relative to the corneal centre both nasally 0.04 mm [0.01, 0.07] and inferiorly -0.01 mm [-0.06, 0.03]. However, regardless of the eye, the contact lens was significantly (p < 0.001) decentred relative to the pupil centre both temporally -0.23 mm [-0.26, -0.20] and inferiorly -0.08 mm [-0.12, -0.04]. Decentration magnitudes were significantly correlated between the right and left eyes. CONCLUSIONS: Spherical SCLs centred well on the cornea but temporally and inferiorly from the primary line of sight (pupil centre), due to the differences in the location of the pupil and corneal centres. Contrary to some previous reports, there was no evidence that lens optics or material affected lens centration significantly.

Inserting "OFF-to-ON" BODIPY Tags into Cytokines: A Fluorogenic Interleukin IL-33 for Real-Time Imaging of Immune Cells.

The essential functions that cytokine/immune cell interactions play in tissue homeostasis and during disease have prompted the molecular design of targeted fluorophores to monitor their activity in real time. Whereas activatable probes for imaging immune-related enzymes are common, many immunological functions are mediated by binding events between cytokines and their cognate receptors that are hard to monitor by live-cell imaging. A prime example is interleukin-33 (IL-33), a key cytokine in innate and adaptive immunity, whose interaction with the ST2 cell-surface receptor results in downstream signaling and activation of NF-κB and AP-1 pathways. In the present work, we have designed a chemical platform to site-specifically introduce OFF-to-ON BODIPY fluorophores into full cytokine proteins and generate the first nativelike fluorescent analogues of IL-33. Among different incorporation strategies, chemical aminoacylation followed by bioorthogonal derivatization led to the best labeling results. Importantly, the BODIPY-labeled IL-33 derivatives-unlike IL-33-GFP constructs-exhibited ST2-specific binding and downstream bioactivity profiles comparable to those of the wild-type interleukin. Real-time fluorescence microscopy assays under no wash conditions confirmed the internalization of IL-33 through ST2 receptors and its intracellular trafficking through the endosomal pathway. We envision that the modularity and versatility of our BODIPY labeling platform will facilitate the synthesis of minimally tagged fluorogenic cytokines as the next generation of imaging reagents for real-time visualization of signaling events in live immune cells.

Suppression of airway allergic eosinophilia by Hp-TGM, a helminth mimic of TGF-ß.

Type 2-high asthma is a chronic inflammatory disease of the airways which is increasingly prevalent in countries where helminth parasite infections are rare, and characterized by T helper 2 (Th2)-dependent accumulation of eosinophils in the lungs. Regulatory cytokines such as TGF-ß can restrain inflammatory reactions, dampen allergic Th2 responses, and control eosinophil activation. The murine helminth parasite Heligmosomoides polygyrus releases a TGF-ß mimic (Hp-TGM) that replicates the biological and functional properties of TGF-ß despite bearing no structural similarity to the mammalian protein. Here, we investigated if Hp-TGM could alleviate allergic airway inflammation in mice exposed to Alternaria alternata allergen, house dust mite (HDM) extract or alum-adjuvanted ovalbumin protein (OVA). Intranasal administration of Hp-TGM during Alternaria exposure sharply reduced airway and lung tissue eosinophilia along with bronchoalveolar lavage fluid IL-5 and lung IL-33 cytokine levels at 24 h. The protective effect of Hp-TGM on airway eosinophilia was also obtained in the longer T-cell mediated models of HDM or OVA sensitisation with significant inhibition of eotaxin-1, IL-4 and IL-13 responses depending on the model and time-point. Hp-TGM was also protective when administered parenterally either when given at the time of allergic sensitisation or during airway allergen challenge. This project has taken the first steps in identifying the role of Hp-TGM in allergic asthma and highlighted its ability to control lung inflammation and allergic pathology. Future research will investigate the mode of action of Hp-TGM against airway allergic eosinophilia, and further explore its potential to be developed as a biotherapeutic in allergic asthma.

A Truncated Form of HpARI Stabilizes IL-33, Amplifying Responses to the Cytokine.

The murine intestinal nematode Heligmosomoides polygyrus releases the H. polygyrus Alarmin Release Inhibitor (HpARI) - a protein which binds to IL-33 and to DNA, effectively tethering the cytokine in the nucleus of necrotic cells. Previous work showed that a non-natural truncation consisting of the first 2 domains of HpARI (HpARI_CCP1/2) retains binding to both DNA and IL-33, and inhibited IL-33 release in vivo. Here, we show that the affinity of HpARI_CCP1/2 for IL-33 is significantly lower than that of the full-length protein, and that HpARI_CCP1/2 lacks the ability to prevent interaction of IL-33 with its receptor. When HpARI_CCP1/2 was applied in vivo it potently amplified IL-33-dependent immune responses to Alternaria alternata allergen, Nippostrongylus brasiliensis infection and recombinant IL-33 injection, in direct contrast to the IL-33-suppressive effects of full-length HpARI. Mechanistically, we found that HpARI_CCP1/2 is able to bind to and stabilize IL-33, preventing its degradation and maintaining the cytokine in its active form. This study highlights the importance of IL-33 inactivation, the potential for IL-33 stabilization in vivo, and describes a new tool for IL-33 research.

Using hyperpolarised NMR and DFT to rationalise the unexpected hydrogenation of quinazoline to 3,4-dihydroquinazoline.

PHIP and SABRE hyperpolarized NMR methods are used to follow the unexpected metal-catalysed hydrogenation of quinazoline (Qu) to 3,4-dihydroquinazoline as the sole product. A solution of [IrCl(IMes)(COD)] in dichloromethane reacts with H2 and Qu to form [IrCl(H)2(IMes)(Qu)2] (2). The addition of methanol then results in its conversion to [Ir(H)2(IMes)(Qu)3]Cl (3) which catalyses the hydrogenation reaction. Density functional theory calculations are used to rationalise a proposed outer sphere mechanism in which (3) converts to [IrCl(H)2(H2)(IMes)(Qu)2]Cl (4) and neutral [Ir(H)3(IMes)(Qu)2] (6), both of which are involved in the formation of 3,4-dihydroquinazoline via the stepwise transfer of H+ and H-, with H2 identified as the reductant. Successive ligand exchange in 3 results in the production of thermodynamically stable [Ir(H)2(IMes)(3,4-dihydroquinazoline)3]Cl (5).

A reactive nitrone-based organogel that self-assembles from its constituents in chloroform.

The reversible reaction of an aldehyde with a hydroxylamine affords a nitrone which is capable of forming a stiff gel with chloroform at concentrations as low as 0.20 wt% (6 mM). The gelator forms dynamically from its constituents and the gel assembly can be degraded in a controlled manner through a recognition-mediated reaction that targets the nitrone component of the gel network.