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Modelo animal; Medicina regenerativa; Retina ; Model animal; Medicina regenerativa; Retina ; Animal model; Regenerative medicine; Retina ; Background: The aim of this study was to test the feasibility and safety of subretinal transplantation of human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) cells into the healthy margins and within areas of degenerative retina in a swine model of geographic atrophy (GA). Methods: Well-delimited selective outer retinal damage was induced by subretinal injection of NaIO3 into one eye in minipigs (n = 10). Thirty days later, a suspension of hiPSC-derived RPE cells expressing green fluorescent protein was injected into the subretinal space, into the healthy margins, and within areas of degenerative retina. In vivo follow-up was performed by multimodal imaging. Post-mortem retinas were analyzed by immunohistochemistry and histology. Results: In vitro differentiated hiPSC-RPE cells showed a typical epithelial morphology, expressed RPE-related genes, and had phagocytic ability. Engrafted hiPSC-RPE cells were detected in 60% of the eyes, forming mature epithelium in healthy retina extending towards the border of the atrophy. Histological analysis revealed RPE interaction with host photoreceptors in the healthy retina. Engrafted cells in the atrophic zone were found in a patchy distribution but failed to form an epithelial-like layer. Conclusions: These results might support the use of hiPSC-RPE cells to treat atrophic GA by providing a housekeeping function to aid the overwhelmed remnant RPE, which might improve its survival and therefore slow down the progression of GA. ; This work was supported by Spanish Ministry of Science and Innovation (MICINN, RTI2018-095377-B-100), Instituto de Salud Carlos III ISCIII/FEDER (PRB2 PT13/0001/0041; TerCel RD16/0011/0024 and Oftared-RETICS RD16/0008), ERA-NET EuroNanoMed III/ISCIII (AC19/00080), the Catalan Government, AGAUR (2017-SGR-899), CERCA Programme/Generalitat de Catalunya, and by Fundació Carmen i Mª José Godó (Fundació CMJ Godó 2017).

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download ; Lipids are implicated in the pathogenesis of age-related macular degeneration (AMD). The relationship between systemic lipids and AMD has not been well characterized. The objective was to investigate the relationship between serum lipids and AMD in older adults using a lipidomic approach. In a case-control study, 240 adults, aged ≥66 years, a third each having geographic atrophy, neovascular AMD, or no signs of AMD, were selected from a population-based sample of participants in the Age Gene/Environment Susceptibility-Reykjavik Study. The exposure was serum lipids and risk factors for AMD. The outcome was late AMD, assessed through fundus images taken through dilated pupils using a 45-degree digital camera and grading for neovascular AMD and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Of 177 serum lipid species measured, there were no significant differences in serum lipids between controls and those with geographic atrophy or neovascular AMD, respectively. Adults with neovascular AMD had higher total serum lysophosphatidylcholine (LPC) (P = 0.004) and serum LPC 18:0 (P = 0.0002) compared to those with geographic atrophy. Late AMD was not characterized by alterations in systemic lipids compared with normal controls. These findings suggest that there may be differences in the LPC pathway between adults with neovascular AMD and geographic atrophy. ; National Institutes of Health National Institute on Aging National Eye Institute Iceland Heart Association Icelandic Parliament University of Iceland Research Fund

Publisher's version (útgefin grein) ; Background: Lipids are implicated in the pathogenesis of age-related macular degeneration (AMD). The relationship between systemic lipids and AMD has not been well characterized. The objective was to investigate the relationship between serum lipids and AMD in older adults using a lipidomic approach. Methods: In a case-control study, 240 adults, aged ≥66 years, a third each having geographic atrophy, neovascular AMD, or no signs of AMD, were selected from a population-based sample of participants in the Age Gene/Environment Susceptibility-Reykjavik Study. The exposure was serum lipids and risk factors for AMD. The outcome was late AMD, assessed through fundus images taken through dilated pupils using a 45-degree digital camera and grading for neovascular AMD and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Results: Of 177 serum lipid species measured, there were no significant differences in serum lipids between controls and those with geographic atrophy or neovascular AMD, respectively. Adults with neovascular AMD had higher total serum lysophosphatidylcholine (LPC) (P = 0.004) and serum LPC 18:0 (P = 0.0002) compared to those with geographic atrophy. Conclusion: Late AMD was not characterized by alterations in systemic lipids compared with normal controls. These findings suggest that there may be differences in the LPC pathway between adults with neovascular AMD and geographic atrophy. ; This work was supported by National Institutes of Health grants R01 AG027012 and R01 EY017362, the Intramural Research Programs of the National Institute on Aging and the National Eye Institute (ZIAEY00401 and National Institutes of Health contract numbers N01-AG-1-2100 and HHSN271201200022C), the Iceland Heart Association, the Icelandic Parliament, and the University of Iceland Research Fund. The National Eye Institute was involved in the design and conduct of the study in regard to collection of fundus photographs. The funders had no role in data collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. ; Peer Reviewed

Foveal-sparing scotomas are common in advanced dry macular degeneration (geographic atrophy). Foveal preservation may be present for a number of years. Despite good visual acuity, these patients have reduced reading rates. Magnification may not be effective if the text becomes too large to "fit" within the central spared area.

Circumstances in the MENA region invite us to redirect our attention to geographic areas that emerged as primary sites of power-contest. This paper looks into emerging trends in the unraveling of bounded sovereign territoriality in borderlands by examining the contest over military, economic, and socio-political spaces in the wake of the devolution of the monopoly of violence and the rise of a multitude of new and old actors to local prominence. Since 2011, borderlands in the MENA region transformed into considerable sites of contested power by a plethora of actors. The paper points out emergent patterns of deterritorialization and reterritorialization of power in its various forms and manifestations in borderlands. The dynamics of 'place and performance' in the borderlands of Syria and Iraq showcase the variety of ways borders were instrumentalized under circumstances of state atrophy and their destructive tendencies for borderlands.

Objective To test the hypothesis that age-related macular degeneration (AMD) and retinal microvascular signs are differentially associated with lobar and deep cerebral microbleeds (CMBs). Methods CMBs in lobar regions indicate cerebral amyloid angiopathy (CAA). β-Amyloid deposits are implicated in both CAA and AMD. Deep CMBs are associated with hypertension, a major risk factor for retinal microvascular damage. This population-based cohort study included 2,502 participants in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study who undertook binocular digital retinal photographs at baseline (2002–2006) to assess retinal microvascular signs and AMD and brain MRI scan at both baseline and follow-up (2007–2011) to assess CMBs. We assessed retinal microvascular lesion burden by counting the 3 retinal microvascular signs (focal arteriolar narrowing, arteriovenous nicking, and retinopathy) concurrently present in the participant. We used multiple logistic models to examine the association of baseline retinal pathology to incident CMBs detected at follow-up. Results During an average 5.2 years of follow-up, 461 people (18.3%) developed new CMBs, including 293 in exclusively lobar regions and 168 in deep regions. Pure geographic atrophy was significantly associated with strictly lobar CMBs (multivariable-adjusted odds ratio 2.59, 95% confidence interval [CI] 1.01–6.65) but not with deep CMBs. Concurrently having ≥2 retinal microvascular signs was associated with a 3-fold (95% CI 1.73–5.20) increased likelihood for deep CMBs but not exclusively lobar CMBs. Conclusions Retinal microvascular signs and pure geographic atrophy may be associated with deep and exclusively lobar CMBs, respectively, in older people. These results have implications for further research to define the role of small vessel disease in cognitive impairment. ; The AGES-Reykjavik Study was funded by the NIH (contract N01-AG-12100); the Intramural Research Program of the National Institute on Aging and the National Eye Institute (ZIAEY000401), NIH; and the Icelandic Heart Association and the Icelandic Parliament. None of the funding organizations or sponsors were involved in study design; in the collection, analysis, or interpretation of data; in writing of the report; or in the decision to submit the manuscript for publication. ; Peer Reviewed

Age-related macular degeneration (AMD) is one of the commonest causes of sight loss in the elderly population and to date there is no intervention that slows or prevents early AMD disease progressing to blinding neovascularization or geographic atrophy. AMD is a complex disease and factors proposed to contribute to the development and progression of disease include aging, genetics, epigenetics, oxidative stress, pro-inflammatory state, and life-style factors such as smoking, alcohol, and high fat diet. Here, we generate a knowledge repository of pathways and protein-protein interaction (PPI) networks likely to be implicated in AMD pathogenesis, such as complement activation, lipid trafficking and metabolism, vitamin A cycle, oxidative stress, proteostasis, bioenergetics, autophagy/mitophagy, extracellular matrix (ECM) turnover, and choroidal vascular dropout. Two disctinct clusters ermerged from the networks for parainflamation and ECM homeostasis, which may represent two different disease modules underlying AMD pathology. Our analyses also suggest that the disease manifests primarily in RPE/choroid and less in neural retina. The use of standardized syntax when generating maps of these biological processes (SBGN standard) and networks (PSI standard) enables visualization of complex information in graphical programs such as CellDesigner and Cytoscape and enhances reusability and extension of data. The ability to focus onto subnetworks, multiple visualizations and simulation options will enable the AMD research community to computationally model subnetworks or to test experimentally new hypotheses arising from connectivities in the AMD pathway map. ; This work has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 634479 (EYE-RISK—to P.J.L., L.S., and C.K.). This work was supported by the Spanish Ministry of Economy and Competitiveness, Plan Nacional BIO2012-39754 and the European Fund for Regional Development (to L.S.). L.S. acknowledges the support ...

AbstractThere are not many studies on subnational electoral bodies in Latin America, especially with a comparative approach. This article describes these bodies based on their main traits and presents the first hypotheses to explain their development or atrophy. It posits that the nations' geographic extension and the complexity of the different levels of government—federalism or significant levels of mid‐level autonomy—are associated with a greater degree of institutionalization, autonomy, and strength at the subnational electoral level, such that a smaller nation, or the absence of a mid‐level government, limits consolidation. The article uses a comparative approach.

Natural resources such as land, air, and water lay a critical foundation for the sustainable development of an urban community. The Pearl River Delta (PRD) is one of the most developed and rapidly developing regions in China, with abundant natural resources in water, intertidal zones, aquatic products, and a significant coastal estuary habitat. The PRD also covers two Special Administrative Regions (Hong Kong and Macao) and two Special Economic Zones (Shenzhen and Zhuhai), critically positioning it domestically and abroad. However, the increasing development of the economy has put pressure on the security of its water resources. These resources have sharply deteriorated in the PRD as the result of a mass and unordered overuse of water and soil resources and the lack of coordinated efforts among different functional departments. Various problems related to the water environment (such as flooding, rapid development of the deposition, water pollution, saltwater intrusion, and waterway atrophy) have directly threatened the social stability, sustainable development of the economy, and the supply of water in the region. To date, the population affected by a shortage of high-quality water has reached 16 million due to pollution of the water supply source in Guangdong province. At this time, the water pollution in the PRD has resulted in ever-increasing economic and environmental losses. Pollution coverage includes Hong Kong, Macao, and Guangdong and, because governmental functions and scientific technologies among these regions differ, there is little in the way of efficient, cooperative efforts to fully make use of their individual advantages to protect the water environment in the PRD. Moreover, the diversity and complexity of the problems even interfere with the abilities of functional departments within one region (e.g., flood prevention, pollution abatement, and channel maintenance) to make decisions and formulate protection policies using advanced spatial technologies such as remote sensing (RS) and geographic information systems (GIS). Consequently, the water environment in the PRD lacks unified and synergistic operations, and water resource protection is restricted to satisfying the demands of economic development and the requirements of sustainable development. To date, it is clear that cooperation amongst Guangdong, Hong Kong, and Macao should be strengthened. More research is also essential, specifically regarding the reduction of gross pollution emissions by 8 to 10 percent. In addition, the water environmental protection of the PRD has engaged with the Integrative Planning of the Environmental Protection in the PRD (2009-2020). This emphasizes strengthening the regional collaborative linkages, constructing an integrative platform of environmental monitoring, and realizing the shared and collaborative management of environmental information among different departments. With this in mind, the study on constructing a unified and synergistic system for water environment analysis in the PRD area are proposed as interdisciplinary and comprehensive research using multiple methods and fields. Based on the analysis of the fusion techniques of multisource, multi-date, and isomerous images, a database for integrating remote sensing monitoring data of water quality and quantity, actual measurement data, and relevant basic geographical data (watercourse data, section data, and a Digital Elevation Model) will be developed. Combining the research on general analytical methods and models, the capsulation mechanism of analytical methods and models will be designed. Lastly, using GIS integration techniques, an integrative monitoring demonstrative platform of water quality and quantity will be developed to assist collaborative research and decision making among the functional departments of the three regions. The goal is to promote the sustainable use of the water resources in the PRD, to achieve sustainable economic development and to increase the informatization of the PRD region. The construction of the system consists of four parts.

Natural resources such as land, air, and water lay a critical foundation for the sustainable development of an urban community. The Pearl River Delta (PRD) is one of the most developed and rapidly developing regions in China, with abundant natural resources in water, intertidal zones, aquatic products, and a significant coastal estuary habitat. The PRD also covers two Special Administrative Regions (Hong Kong and Macao) and two Special Economic Zones (Shenzhen and Zhuhai), critically positioning it domestically and abroad. However, the increasing development of the economy has put pressure on the security of its water resources. These resources have sharply deteriorated in the PRD as the result of a mass and unordered overuse of water and soil resources and the lack of coordinated efforts among different functional departments. Various problems related to the water environment (such as flooding, rapid development of the deposition, water pollution, saltwater intrusion, and waterway atrophy) have directly threatened the social stability, sustainable development of the economy, and the supply of water in the region. To date, the population affected by a shortage of high-quality water has reached 16 million due to pollution of the water supply source in Guangdong province. At this time, the water pollution in the PRD has resulted in ever-increasing economic and environmental losses. Pollution coverage includes Hong Kong, Macao, and Guangdong and, because governmental functions and scientific technologies among these regions differ, there is little in the way of efficient, cooperative efforts to fully make use of their individual advantages to protect the water environment in the PRD. Moreover, the diversity and complexity of the problems even interfere with the abilities of functional departments within one region (e.g., flood prevention, pollution abatement, and channel maintenance) to make decisions and formulate protection policies using advanced spatial technologies such as remote sensing (RS) and geographic information systems (GIS). Consequently, the water environment in the PRD lacks unified and synergistic operations, and water resource protection is restricted to satisfying the demands of economic development and the requirements of sustainable development. To date, it is clear that cooperation amongst Guangdong, Hong Kong, and Macao should be strengthened. More research is also essential, specifically regarding the reduction of gross pollution emissions by 8 to 10 percent. In addition, the water environmental protection of the PRD has engaged with the Integrative Planning of the Environmental Protection in the PRD (2009-2020). This emphasizes strengthening the regional collaborative linkages, constructing an integrative platform of environmental monitoring, and realizing the shared and collaborative management of environmental information among different departments. With this in mind, the study on constructing a unified and synergistic system for water environment analysis in the PRD area are proposed as interdisciplinary and comprehensive research using multiple methods and fields. Based on the analysis of the fusion techniques of multisource, multi-date, and isomerous images, a database for integrating remote sensing monitoring data of water quality and quantity, actual measurement data, and relevant basic geographical data (watercourse data, section data, and a Digital Elevation Model) will be developed. Combining the research on general analytical methods and models, the capsulation mechanism of analytical methods and models will be designed. Lastly, using GIS integration techniques, an integrative monitoring demonstrative platform of water quality and quantity will be developed to assist collaborative research and decision making among the functional departments of the three regions. The goal is to promote the sustainable use of the water resources in the PRD, to achieve sustainable economic development and to increase the informatization of the PRD region. The construction of the system consists of four parts.

Natural resources such as land, air, and water lay a critical foundation for the sustainable development of an urban community. The Pearl River Delta (PRD) is one of the most developed and rapidly developing regions in China, with abundant natural resources in water, intertidal zones, aquatic products, and a significant coastal estuary habitat. The PRD also covers two Special Administrative Regions (Hong Kong and Macao) and two Special Economic Zones (Shenzhen and Zhuhai), critically positioning it domestically and abroad. However, the increasing development of the economy has put pressure on the security of its water resources. These resources have sharply deteriorated in the PRD as the result of a mass and unordered overuse of water and soil resources and the lack of coordinated efforts among different functional departments. Various problems related to the water environment (such as flooding, rapid development of the deposition, water pollution, saltwater intrusion, and waterway atrophy) have directly threatened the social stability, sustainable development of the economy, and the supply of water in the region. To date, the population affected by a shortage of high-quality water has reached 16 million due to pollution of the water supply source in Guangdong province. At this time, the water pollution in the PRD has resulted in ever-increasing economic and environmental losses. Pollution coverage includes Hong Kong, Macao, and Guangdong and, because governmental functions and scientific technologies among these regions differ, there is little in the way of efficient, cooperative efforts to fully make use of their individual advantages to protect the water environment in the PRD. Moreover, the diversity and complexity of the problems even interfere with the abilities of functional departments within one region (e.g., flood prevention, pollution abatement, and channel maintenance) to make decisions and formulate protection policies using advanced spatial technologies such as remote sensing (RS) and geographic information systems (GIS). Consequently, the water environment in the PRD lacks unified and synergistic operations, and water resource protection is restricted to satisfying the demands of economic development and the requirements of sustainable development. To date, it is clear that cooperation amongst Guangdong, Hong Kong, and Macao should be strengthened. More research is also essential, specifically regarding the reduction of gross pollution emissions by 8 to 10 percent. In addition, the water environmental protection of the PRD has engaged with the Integrative Planning of the Environmental Protection in the PRD (2009-2020). This emphasizes strengthening the regional collaborative linkages, constructing an integrative platform of environmental monitoring, and realizing the shared and collaborative management of environmental information among different departments. With this in mind, the study on constructing a unified and synergistic system for water environment analysis in the PRD area are proposed as interdisciplinary and comprehensive research using multiple methods and fields. Based on the analysis of the fusion techniques of multisource, multi-date, and isomerous images, a database for integrating remote sensing monitoring data of water quality and quantity, actual measurement data, and relevant basic geographical data (watercourse data, section data, and a Digital Elevation Model) will be developed. Combining the research on general analytical methods and models, the capsulation mechanism of analytical methods and models will be designed. Lastly, using GIS integration techniques, an integrative monitoring demonstrative platform of water quality and quantity will be developed to assist collaborative research and decision making among the functional departments of the three regions. The goal is to promote the sustainable use of the water resources in the PRD, to achieve sustainable economic development and to increase the informatization of the PRD region. The construction of the system consists of four parts.