Interactions between stem cells and their microenvironment are critical for regulation and maintenance of stem cell function. To elucidate the molecular interactions within the human limbal epithelial stem/progenitor cell (LEPC) niche, which is essential for maintaining corneal transparency and vision, we performed a comprehensive expression analysis of cell adhesion molecules (CAMs) using custom-made quantitative real-time polymerase chain reaction (qRT-PCR) arrays and laser capture-microdissected LEPC clusters, comprising LEPCs, melanocytes, mesenchymal cells, and transmigrating immune cells. We show that LEPCs are anchored to their supporting basement membrane by the laminin receptors a3b1 and a6b4 integrin and the dystroglycan complex, while intercellular contacts between LEPCs and melanocytes are mediated by N-, P-, and E-cadherin together with L1-CAM, a member of the immunoglobulin superfamily (Ig)CAMs. In addition to the LEPC-associated heparan sulfate proteoglycans syndecan-2, glypican-3, and glypican-4, the IgCAM members ICAM-1 and VCAM-1 were found to be variably expressed on LEPCs and associated niche cells and to be dynamically regulated in response to chemokines such as interferon-c to enhance interactions with immune cells. Moreover, junctional adhesion molecule JAM-C accumulating in the subepithelial limbal matrix, appeared to be involved in recruitment of immune cells, while mesenchymal stromal cells appeared to use the nephronectin receptor integrin a8 for approaching the limbal basement membrane. In summary, we identified a novel combination of cell surface receptors that may regulate both stable and dynamic cell-matrix and cell-cell interactions within the limbal niche. The findings provide a solid foundation for further functional studies and for advancement of our current therapeutic strategies for ocular surface reconstruction. STEM CELLS 2016;34:203-219 SIGNIFICANCE STATEMENTThe study provides novel data on the molecular composition of the human limbal stem cell niche by identification of a combination of cell surface receptors that regulate both stable and dynamic cell-matrix and cell-cell interactions within the limbal niche. Most of the molecules identified, i.e. dystroglycan-1, integrin a8, nephronectin, syndecan-2, glypicans-3 and -4, L1-CAM, and JAM-C, have not been described before in the context of the limbal niche. In addition, the ICAM-1/ VCAM-1-mediated interaction of limbal epithelial progenitor cells with immune cells, which could be regulated by chemokines such as interferon-c, provides a novel view of the dynamic nature of the limbal niche. Moreover, we demonstrated the usability of surface molecules such as L1-CAM for isolation and enrichment of limbal progenitor and niche cells.Although being still on a rather descriptive level, the findings provide insights into molecular mechanisms of progenitor cell-niche anchorage mediated by integrins, cadherins, and dystrophin-associated proteins, and into dynamic physical interactions with immune cells mediated by immunoglob...

BackgroundIn recent years, education and training in global health has been the subject of recurring debate in many countries. However, in Germany, there has been no analysis of the educational needs or demands of medical students, or the educational deficits or potential benefits involved in global health education. Our purpose is to analyse international health elective patterns of medical students enrolled at German universities and assess whether or how they prepare for their electives abroad. We examine the exposure of medical students enrolled at German universities to training courses in tropical medicine or global health and assess students' perceived needs and demands for education in global health.MethodsCross-sectional study among medical students in Germany including all 36 medical schools during the second half of the year 2007. All registered medical students were eligible to participate in the study. Recruitment occurred via electronic mailing-lists of students' unions. We developed a web-based, semi-structured questionnaire to capture students' international mobility patterns, preparation before electives, destination countries, exposure to and demand for global health learning opportunities.Results1126 online-replies were received and analysed from all registered medical students in Germany (N = 78.067). 33.0% of all respondents (370/1126) declared at least one international health elective and of these, 36.0% (133/370) completed their electives in developing countries. 36.0% (131/363) did not prepare specifically at all, 59.0% (214/363) prepared either by self-study or declared a participation in specific preparation programmes. 87.8% of 5th and 6th year students had never participated in a global health course and 72.6% (209/288) had not completed a course in tropical medicine. 94.0% (861/916) endorsed the idea of introducing global health into medical education.ConclusionStudents in our sample are highly mobile during their studies. International health electives are common, also in developing countries. Formal preparation beyond self-study is virtually non-existent amongst our sample and the participation rate in courses of tropical medicine or global health is appallingly low. We have identified unmet perceived needs and the demand for more learning opportunities in global health in our sample, urging for reforms to adjust curricula to a globalising world.

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Purpose: Meibomian gland disease is generally accepted as the leading cause for evaporative dry eye disease (DED). In a previous study, perfluorohexyloctane, a semifluorinated alkane, has been demonstrated to significantly increase tear film breakup time and to reduce corneal fluorescein staining in patients with evaporative DED, thereby vastly reducing dry eye-related symptoms. This study was set up to evaluate perfluorohexyloctane in a larger population of patients with Meibomian gland dysfunction.Methods: Seventy-two patients with Meibomian gland disease and associated dry eye received 1 drop of perfluorohexyloctane 4 times daily during an observational, prospective, multicenter, 6–8-week study. Clinical assessment included best-corrected visual acuity, intraocular pressure, Schirmer test I, tear film breakup time, anterior and posterior blepharitis assessment, number of expressible Meibomian glands, meibum quality and quantity, ocular surface fluorescein staining, lid margin and symptom assessment, and Ocular Surface Disease Index (OSDI©).Results: From the 72 patients recruited, 61 completed the trial per protocol. Nine patients did not apply the medication as recommended and 2 patients were lost to follow-up. Tear film breakup time, corneal and conjunctival fluorescein staining, number of expressible Meibomian glands, and severity of anterior and posterior blepharitis significantly improved after 6–8 weeks of perfluorohexyloctane application. In addition, symptoms improved as demonstrated by a significant decrease of OSDI-values from 37 (±13) to 26 (±16).Conclusions: In concordance with previous findings, 6–8 weeks of topical application of perfluorohexyloctane significantly improves clinical signs of Meibomian gland disease and associated mild to moderate DED.

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Background: X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by pathogenic variants of the gene EDA disrupting the prenatal development of ectodermal derivatives. Cardinal symptoms are hypotrichosis, lack of teeth, and hypo-or anhidrosis, but the disease may also evoke other clinical problems. This study aimed at investigating the clinical course of XLHED in early childhood as the basis for an evaluation of the efficacy of potential treatments. Methods: 25 children (19 boys and 6 girls between 11 and 35 months of age) with genetically confirmed XLHED were enrolled in a long-term natural history study. Clinical data were collected both retrospectively using parent questionnaires and medical records (pregnancy, birth, infancy) and prospectively until the age of 60 months. General development, dentition, sweating ability, ocular, respiratory, and skin involvement were assessed by standardized clinical examination and yearly quantitative surveys. Results: All male subjects suffered from persistent anhidrosis and heat intolerance, although a few sweat ducts were detected in some patients. Sweating ability of girls with XLHED ranged from strongly reduced to almost normal. In the male subjects, 1-12 deciduous teeth erupted and 0-8 tooth germs of the permanent dentition became detectable. Tooth numbers were higher but variable in the female group. Most affected boys had no more than three if any Meibomian glands per eyelid, most girls had fewer than 10. Many male subjects developed additional, sometimes severe health issues, such as obstructive airway conditions, chronic eczema, or dry eye disease. Adverse events included various XLHED-related infections, unexplained fever, allergic reactions, and retardation of psychomotor development. Conclusions: This first comprehensive study of the course of XLHED confirmed the early involvement of multiple organs, pointing to the need of early therapeutic intervention.

BackgroundIn Germany, educational deficits or potential benefits involved in global health education have not been analysed till now.ObjectiveWe assess the importance medical students place on learning about social determinants of health (SDH) and assess their knowledge of global health topics in relation to (i) mobility patterns, their education in (ii) tropical medicine or (iii) global health.MethodsCross-sectional study among medical students from all 36 medical schools in Germany using a web-based, semi-structured questionnaire. Participants were recruited via mailing-lists of students' unions, all medical students registered in 2007 were eligible to participate in the study. We captured international mobility patterns, exposure to global health learning opportunities and attitudes to learning about SDH. Both an objective and subjective knowledge assessment were performed.Results1126 online-replies were received and analysed. International health electives in developing countries correlated significantly with a higher importance placed on all provided SDH (p ≤ 0.006). Participation in tropical medicine (p < 0.03) and global health courses (p < 0.02) were significantly associated with a higher rating of 'culture, language and religion' and the 'economic system'. Global health trainings correlated with significantly higher ratings of the 'educational system' (p = 0.007) and the 'health system structure' (p = 0.007), while the item 'politics' was marginally significant (p = 0.053).In the knowledge assessment students achieved an average score of 3.6 (SD 1.5; Mdn 4.0), 75% achieved a score of 4.0 or less (Q25 = 3.0; Q75 = 4.0) from a maximum achievable score of 8.0. A better performance was associated with international health electives (p = 0.032), participation in tropical medicine (p = 0.038) and global health (p = 0.258) courses.ConclusionThe importance medical students in our sample placed on learning about SDH strongly interacts with students' mobility, and participation in tropical medicine and global health courses. The knowledge assessment revealed deficits and outlined needs to further analyse education gaps in global health. Developing concerted educational interventions aimed at fostering students' engagement with SDH could make full use of synergy effects inherent in student mobility, tropical medicine and global health education.

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