Carlsenleth1660

Purpose The purpose of this study was to investigate the association between the choriocapillaris microcirculation and the visual function and cone photoreceptor structure in patients with diabetes. Methods Thirteen control subjects and 26 patients with type 2 diabetes were recruited. The patients with diabetes were divided into three groups based on the grade of diabetic retinopathy (DR). The retinal sensitivity (RS) was evaluated using microperimetry. Cone photoreceptor mosaics were imaged using an adaptive optics retinal camera, and the cone heterogeneity packing index (HPi) was calculated. Optical coherence tomography angiography (OCTA) images of the choriocapillaris were obtained using spectral-domain OCTA, and the area of flow deficit (FD) was evaluated. All parameters were evaluated in the foveal and parafoveal areas. Results The study included four patients with diabetes without retinopathy, 12 patients with nonproliferative diabetic retinopathy (NPDR), and 10 patients with proliferative diabetic retinopathy (PDR). The foveal and parafoveal FDs were correlated significantly (fovea, r = -0.58; P = 0.046 and r = -0.82; P = 0.003; parafovea, r = -0.59; P = 0.044 and r = -0.72; and P = 0.019, respectively) with the RS in patients with NPDR and PDR, but not in control and no diabetic retinopathy (NDR) groups. There were no differences in the foveal HPi among the groups. Conclusions Impaired choriocapillaris microcirculation is associated with impaired visual function but not cone photoreceptor integrity in eyes with DR.Purpose Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling is involved in regulating tumor angiogenesis and metastasis; however, the exact mechanism of action in retinal neovascularization (RNV) remains unclear. The purpose of this study was to determine the role and underlying mechanism of NF-κB in regulating RNV in retinal neovascularization mice. Methods Expression levels of NF-κB signaling were detected by immunofluorescence staining and western blotting in retinas of oxygen-induced retinopathy (OIR) mice. OIR mice were treated with either pyrrolidinedithiocarbamate (PDTC), a NF-κB signaling inhibitor, or PBS, and retinal flat-mounts were performed to quantify the area of RNV and the recruitment of retinal macrophages by immunofluorescence staining. Macrophage polarization detected by flow cytometric analysis and the expression of macrophage polarization-associated genes were evaluated by immunofluorescence staining, quantitative RT-PCR, and western blotting. Results Expression levels of phosphorylated IκBα (p-IκBα) and p-p65 increased in OIR mice. Inhibiting NF-κB signaling activation by PDTC significantly reduced RNV. After treatment with PDTC, a reduction in the quantity of macrophages was observed M1 polarized macrophages decreased, and M2 polarized macrophages increased; the expression of M1 macrophage-associated cytokines decreased and M2 macrophage-associated cytokines increased in the retinas of OIR mice. Conclusions Blocking activation of NF-κB signaling reduces RNV by promoting polarization of M1 macrophages to M2 macrophages in OIR mice.Purpose Acute anterior uveitis (AAU) is a common intraocular inflammatory disease. AAU occurs in 30% to 50% of patients with ankylosing spondylitis (AS), and both conditions are strongly associated with human leukocyte antigen (HLA)-B27, implying a shared etiology. find more This study aims to apply genomewide association study (GWAS) to characterize the genetic associations of AAU and their relationship to the genetics of AS. Methods We undertook the GWAS analyses in 2752 patients with AS with AAU (cases) and 3836 patients with AS without AAU (controls). There were 7,436,415 single-nucleotide polymorphisms (SNPs) available after SNP microarray genotyping, imputation, and quality-control filtering. Results We identified one locus associated with AAU at genomewide significance rs9378248 (P = 2.69 × 10-8, odds ratio [OR] = 0.78), lying close to HLA-B. Suggestive association was observed at 11 additional loci, including previously reported AS loci ERAP1 (rs27529, P = 2.19 × 10-7, OR = 1.22) and NOS2 (rs2274894, P = 8.22 × 10-7, OR = 0.83). Multiple novel suggestive associations were also identified, including MERTK (rs10171979, P = 2.56 × 10-6, OR = 1.20), KIFAP3 (rs508063, P = 5.64 × 10-7, OR = 1.20), CLCN7 (rs67412457, P = 1.33 × 10-6, OR = 1.25), ACAA2 (rs9947182, P = 9.70 × 10-7, OR = 1.37), and 5 intergenic loci. The SNP-based heritability is approximately 0.5 for AS alone, and is much higher (approximately 0.7) for AS with AAU. Consistent with the high heritability, a genomewide polygenic risk score shows strong power in identifying individuals at high risk of either AS with AAU or AS alone. Conclusions We report here the first GWAS for AAU and identify new susceptibility loci. Our findings confirm the strong overlap in etiopathogenesis of AAU with AS, and also provide new insights into the genetic basis of AAU.Purpose To investigate the initial events in the development of the human cornea, focusing on cell migration, and extracellular matrix synthesis and organization. To determine whether elastic fibers are present in the extracellular matrix during early human corneal development. Methods Human corneas were collected from week 7 to week 17 of development. An elastic fiber-enhancing stain, tannic acid-uranyl acetate, was applied to all tissue. Three-dimensional serial block-face scanning electron microscopy combined with conventional transmission electron microscopy was used to analyze the corneal stroma. Results An acellular collagenous primary stroma with an orthogonal arrangement of fibrils was identified in the central cornea from week 7 of corneal development. At week 7.5, mesenchymal cells migrated toward the central cornea and associated with the acellular collagenous matrix. Novel cell extensions from the endothelium were identified. Elastic fibers were found concentrated in the posterior peripheral corneal stroma from week 12 of corneal development. Conclusions This study provides novel evidence of an acellular primary stroma in the early development of the embryonic human cornea. Cell extensions exist as part of a communication system and are hypothesized to assist in the migration of the mesenchymal cells and the development of the mature cornea. Elastic fibers identified in early corneal development may play an important role in establishing corneal shape.Importance Recent European guidance supports a diminished role for exercise electrocardiography (ECG) in the assessment of suspected stable angina. Objective To evaluate the utility of exercise ECG in contemporary practice and assess the value of combined functional and anatomical testing. Design, setting, and participants This is a post hoc analysis of the Scottish Computed Tomography of the Heart (SCOT-HEART) open-label randomized clinical trial, conducted in 12 cardiology chest pain clinics across Scotland for patients with suspected angina secondary to coronary heart disease. Between November 18, 2010, and September 24, 2014, 4146 patients aged 18 to 75 years with stable angina underwent clinical evaluation and 1417 of 1651 (86%) underwent exercise ECG prior to randomization. Statistical analysis was conducted from October 10 to November 5, 2019. Interventions Patients were randomized in a 11 ratio to receive standard care plus coronary computed tomography (CT) angiography or to receive standard care alonsease death or nonfatal myocardial infarction (hazard ratio, 10.63; 95% CI, 2.32-48.70; P = .002). The greatest numerical difference in outcome with CT angiography compared with exercise ECG alone was observed for those with inconclusive results of exercise ECG (6 of 283 [2%] vs 18 of 283 [6%]), although this was not statistically significant (log-rank P = .05). Conclusions and relevance This study suggests that abnormal results of exercise ECG are associated with coronary revascularization and the future risk of adverse coronary events. However, coronary CT angiography more accurately detects coronary artery disease and is more strongly associated with future risk compared with exercise ECG. Trial registration ClinicalTrials.gov Identifier NCT01149590.Object shape is an important cue to material identity and for the estimation of material properties. Shape features can affect material perception at different levels at a microscale (surface roughness), mesoscale (textures and local object shape), or megascale (global object shape) level. Examples for local shape features include ripples in drapery, clots in viscous liquids, or spiraling creases in twisted objects. Here, we set out to test the role of such shape features on judgments of material properties softness and weight. For this, we created a large number of novel stimuli with varying surface shape features. We show that those features have distinct effects on softness and weight ratings depending on their type, as well as amplitude and frequency, for example, increasing numbers and pointedness of spikes makes objects appear harder and heavier. By also asking participants to name familiar objects, materials, and transformations they associate with our stimuli, we can show that softness and weight judgments do not merely follow from semantic associations between particular stimuli and real-world object shapes. Rather, softness and weight are estimated from surface shape, presumably based on learned heuristics about the relationship between a particular expression of surface features and material properties. In line with this, we show that correlations between perceived softness or weight and surface curvature vary depending on the type of surface feature. We conclude that local shape features have to be considered when testing the effects of shape on the perception of material properties such as softness and weight.Visual crowding-the deleterious influence of nearby objects on object recognition-is considered to be a major bottleneck for object recognition in cluttered environments. Although crowding has been studied for decades with static and artificial stimuli, it is still unclear how crowding operates when viewing natural dynamic scenes in real-life situations. For example, driving is a frequent and potentially fatal real-life situation where crowding may play a critical role. In order to investigate the role of crowding in this kind of situation, we presented observers with naturalistic driving videos and recorded their eye movements while they performed a simulated driving task. We found that the saccade localization on pedestrians was impacted by visual clutter, in a manner consistent with the diagnostic criteria of crowding (Bouma's rule of thumb, flanker similarity tuning, and the radial-tangential anisotropy). In order to further confirm that altered saccadic localization is a behavioral consequence of crowding, we also showed that crowding occurs in the recognition of cluttered pedestrians in a more conventional crowding paradigm. We asked participants to discriminate the gender of pedestrians in static video frames and found that the altered saccadic localization correlated with the degree of crowding of the saccade targets. Taken together, our results provide strong evidence that crowding impacts both recognition and goal-directed actions in natural driving situations.