Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye: A Computer Simulation Study

Choroidal neovascularization (CNV) of the macular area of the retina is the major cause of severe vision loss in adults. In CNV, after choriocapillaries initially penetrate Bruch's membrane (BrM), invading vessels may regress or expand (CNV initiation). Next, during Early and Late CNV, the expanding vasculature usually spreads in one of three distinct patterns: in a layer between BrM and the retinal pigment epithelium (sub-RPE or Type 1 CNV), in a layer between the RPE and the photoreceptors (sub-retinal or Type 2 CNV) or in both loci simultaneously (combined pattern or Type 3 CNV). While most studies hypothesize that CNV primarily results from growth-factor effects or holes in BrM, our three-dimensional simulations of multi-cell model of the normal and pathological maculae recapitulate the three growth patterns, under the hypothesis that CNV results from combinations of impairment of: 1) RPE-RPE epithelial junctional adhesion, 2) Adhesion of the RPE basement membrane complex to BrM (RPE-BrM adhesion), and 3) Adhesion of the RPE to the photoreceptor outer segments (RPE-POS adhesion). Our key findings are that when an endothelial tip cell penetrates BrM: 1) RPE with normal epithelial junctions, basal attachment to BrM and apical attachment to POS resists CNV. 2) Small holes in BrM do not, by themselves, initiate CNV. 3) RPE with normal epithelial junctions and normal apical RPE-POS adhesion, but weak adhesion to BrM (e.g. due to lipid accumulation in BrM) results in Early sub-RPE CNV. 4) Normal adhesion of RBaM to BrM, but reduced apical RPE-POS or epithelial RPE-RPE adhesion (e.g. due to inflammation) results in Early sub-retinal CNV. 5) Simultaneous reduction in RPE-RPE epithelial binding and RPE-BrM adhesion results in either sub-RPE or sub-retinal CNV which often progresses to combined pattern CNV. These findings suggest that defects in adhesion dominate CNV initiation and progression

The Patient Needs in Asthma Treatment (NEAT) questionnaire:Further evidence on its psychometric properties

Background: Building on previous psychometric work, we sought to assess the Patient Needs in Asthma Treatment (NEAT) questionnaire's validity, responsiveness to change, and the minimal important change (MIC) over a 3-year period (Study 1) and its reliability and the smallest detectable change (SDC) in a test-retest study (Study 2) among patients self-reporting physician-diagnosed asthma. Methods: In Study 1, a total of 207 patients completed a survey which included the NEAT, the Asthma Control Test (ACT), the Asthma Quality of Life QuestionnaireSydney (AQLQ-S), and a question on treatment satisfaction in 2014 and 2017. In Study 2, a total of 78 patients completed NEAT twice on average four weeks apart in 2018. Results: Concurrent validity: In linear regressions, unmet patient needs were crosssectionally associated with poorer asthma control (beta =-0.21; P = 0.01), asthma-related quality of life (QoL) (beta = 0.31; P < 0.01), and treatment satisfaction (beta =-0.59; P < 0.01). Predictive Validity: Higher unmet needs at baseline predicted worse treatment satisfaction at follow-up (beta =-0.28; P < 0.01), but neither asthma control nor asthma-related QoL. Responsiveness to change was demonstrated by linear regressions of changes in the total NEAT score and changes in AQLQ-S (beta = 0.21; P < 0.01) and treatment satisfaction (beta =-0.36; P < 0.01). MIC: Patients whose NEAT score increased between baseline and follow-up by the identified MIC (0.301) reported lower treatment satisfaction at follow-up (beta = -0.17; P = 0.01). Test-retest reliability was demonstrated by correlations between NEAT baseline and follow-up scores (eg, intra-class correlation coefficients for total score = 0.78). The SDC (0.384) was slightly larger than MIC. Conclusion: NEAT is a promising tool for assessing asthma treatment needs

Synovial Joints: from Development to Homeostasis

Synovial joint morphogenesis occurs through the condensation of mesenchymal cells into a non-cartilaginous region known as interzone, and the specification of progenitor cells that commit to the articular fate. Although several signaling molecules are expressed by the interzone, the mechanism is poorly understood. For treatments of cartilage injuries, it is critical to discover the presence of joint progenitor cells in adult tissues and their expression gene pattern. Potential stem cells niches have been found in different joint regions, such as the surface zone of articular cartilage, synovium and groove of Ranvier. Inherited joint malformation as well as joint degenerating conditions are often associated with other skeletal defects, and may be seen as the failure of morphogenic factors to establish the correct microenvironment in cartilage and bone. Therefore, exploring how joints form can help us understand how cartilage and bone are damaged and to develop drugs to reactivate this developing mechanism