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BACKGROUND:Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. METHODS:Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55) or with bovine myelin basic protein (MBP), in TCR2D2 mice immunized with MOG35-55, and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP139-151). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. RESULTS:Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG35-55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2 months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG35-55-immunized TCR2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. CONCLUSIONS:Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG35-55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE.

Confocal scanning laser ophthalmoscopy (cSLO) is a non-invasive technique for real-time imaging of the retina. We developed a step-by-step protocol for the semi-automatic evaluation of myeloid cells in cSLO images from CX3CR1GFP mice, expressing green fluorescent protein (GFP) under control of the endogenous CX3C chemokine receptor 1 locus. We identified cSLO parameters allowing us to distinguish animals with experimental autoimmune encephalomyelitis (EAE) from sham-treated/naïve animals. Especially cell count (CC) and the total microglial area (SuA) turned out to be reliable parameters. Comparing the cSLO results with clinical parameters, we found significant correlations between the clinical EAE score and the SuA and of the inner retinal layer thickness, measured by optical coherence tomography, with the CC as well as the SuA. As a final step, we performed immunohistochemistry to confirm that the GFP-expressing cells visualized by the cSLO are Iba1 positive and validated the step-by-step protocol against manual counting. We present a semi-automatic step-by-step protocol with a balance between fast data evaluation and adequate accuracy, which is optimized by the option to manually adapt the contrast threshold. This protocol may be useful for numerous research questions on the role of microglial polarization in models of inflammatory and degenerating CNS diseases involving the retina. [ABSTRACT FROM AUTHOR]

Sumoylation is a multi-step protein modification reaction in which SUMO (small ubiquitin-like modifier) proteins are covalently attached to lysine residues of substrate proteins. Here, we compare the sequences and structures of modifiers and enzymes involved in sumoylation with those of the related ubiquitination and neddylation cascades. By using available structural data on modifier/enzyme/substrate interactions, we discuss and model sumoylation complexes that include SUMO-1 and the E1 and E2 enzymes Aos1-uba2 and ubc9, or SUMO-1 and E2 together with the E3 ligase RanBP2 and its substrate RanGAP1. Their comparison provides insight into the protein interactions underlying sumoylation, and suggests how SUMO proteins may be translocated between enzymes during the various steps of the protein modification reaction. [ABSTRACT FROM AUTHOR]

Background: Climate change because of anthropogenic greenhouse gas emissions increasingly triggers extreme weather events. Of all the continents, Europe is warming the fastest. Heat and drought, forest fires and floods will worsen in Europe even in optimistic global warming scenarios, affecting living conditions across the continent. Extreme weather events threaten energy and food security, ecosystems, infrastructure, water resources, financial stability, and people's healthcare. Many of these risks have already reached critical levels and could take on catastrophic proportions without immediate, decisive action., Objectives: This paper outlines current challenges for medical practices and clinics in the context of climate change and provides examples and guidance for strengthening crisis resilience., Materials and Methods: Selective literature review on the different requirements for crisis resilience in practices and clinics was performed., Results: Medical practices and clinics achieve crisis resilience by high degrees of adaptability and flexibility. They prepare for climate change-related challenges and are, therefore, able to protect themselves and maintain their function in the healthcare system. Recent weather events in Germany revealed insufficient resilience among the healthcare sector; hence, improvements are necessary., Conclusions: Changing environmental conditions urgently require the healthcare sector to adapt and effectively strengthen crisis resilience in order to ensure that critical infrastructure remains functional and the population has access to healthcare., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Ongoing high consumption of resources results in exceeding the planetary boundaries. Modern healthcare systems contribute to this problem. To address this issue, this article provides an overview of various aspects of sustainable actions in medical offices and clinics that can also be applied to dermatology. Specific fields of action include energy consumption, structural measures, traffic and mobility, organization including digitalization as well as personnel and evaluation. Moreover, we discuss specific topics such as hygiene and cleansing, dermatosurgery and prescription practices. External treatments and cosmetics are discussed separately as dermatological peculiarities. Finally, we provide information on established initiatives for more sustainable health care in Germany. We aim to encourage critical reappraisal of currently established practices and to stimulate the implementation of sustainable measures., (© 2023 Deutsche Dermatologische Gesellschaft (DDG).)

Background: Climate change as a consequence of anthropogenic greenhouse gas emissions (CO 2 e) favors weather extremes. This challenges the healthcare system to cope with negative consequences and to remain functional at the same time. Despite rising costs and shortage of staff, sick people in an aging society must be increasingly cared for in a resource-efficient and climate-neutral manner without compromising the quality of care., Aim: This article summarizes current challenges for practices and outpatient clinics due to climate change and societal transformation. In addition, steps to implement transformative interventions are discussed., Materials and Methods: Selective literature review in PubMed database was conducted on the impact of climate change on the healthcare system, crisis resilience, climate management, overprescription, and co-benefits., Results: Crisis-resilient practices are attuned to challenges resulting from climate change. Communicating co-benefits in the physician-patient conversation can accelerate the transformation to a sustainable society., Conclusion: Rapidly changing environmental conditions require adaptation on the part of the healthcare system. Education and prevention are key to meet this challenge. Transformation to sustainable practices is an ongoing process and it represents a holistic concept that encompasses social, environmental, and economic aspects, which are interdependent and cannot be considered separately., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Confocal scanning laser ophthalmoscopy (cSLO) is a non-invasive technique for real-time imaging of the retina. We developed a step-by-step protocol for the semi-automatic evaluation of myeloid cells in cSLO images from CX3CR1 GFP mice, expressing green fluorescent protein (GFP) under control of the endogenous CX3C chemokine receptor 1 locus. We identified cSLO parameters allowing us to distinguish animals with experimental autoimmune encephalomyelitis (EAE) from sham-treated/naïve animals. Especially cell count (CC) and the total microglial area (SuA) turned out to be reliable parameters. Comparing the cSLO results with clinical parameters, we found significant correlations between the clinical EAE score and the SuA and of the inner retinal layer thickness, measured by optical coherence tomography, with the CC as well as the SuA. As a final step, we performed immunohistochemistry to confirm that the GFP-expressing cells visualized by the cSLO are Iba1 positive and validated the step-by-step protocol against manual counting. We present a semi-automatic step-by-step protocol with a balance between fast data evaluation and adequate accuracy, which is optimized by the option to manually adapt the contrast threshold. This protocol may be useful for numerous research questions on the role of microglial polarization in models of inflammatory and degenerating CNS diseases involving the retina., Competing Interests: The following financial disclosures are unrelated to the work: H-PH has received fees for serving on steering and data monitoring committees from Bayer Healthcare, Biogen, Celgene BMS, CSL Behring, GeNeuro, MedImmune, Merck, Novartis, Octapharma, Roche, Sanofi Genzyme, TG Therapeutic sand Viela Bio; fees for serving on advisory boards from Biogen, Sanofi Genzyme, Merck, Novartis, Octapharma, and Roche; and lecture fees from Biogen, Celgene BMS, Merck, Novartis, Roche, Sanofi Genzyme. SM received honoraria for lecturing and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS, and Teva. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Else Kröner Fresenius Foundation, German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, German Foundation Neurology, and by Almirall, Amicus Therapeutics Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, Merck Serono, Novartis, ONO Pharma, Roche, and Teva. MD received speaker honoraria from Merck. PA received compensation for serving on Scientific Advisory Boards for Ipsen, Novartis, Biogen; he received speaker honoraria and travel support from Novartis, Teva, Biogen, Merz Pharmaceuticals, Ipsen, Allergan, Bayer Healthcare, Esai, UCB and Glaxo Smith Kline; he received research support from Novartis, Biogen, Teva, Merz Pharmaceuticals, Ipsen, and Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Frenger, Hecker, Sindi, Issberner, Hartung, Meuth, Dietrich and Albrecht.)