| 1. |
- Dispenzieri, Angela, et al.
(författare)
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Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS) : 14-year update
- 2022
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Ingår i: Orphanet Journal of Rare Diseases. - : BioMed Central (BMC). - 1750-1172. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs.Methods: Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021).Results: This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation.Conclusions: This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease.ClinicalTrials.gov Identifier: NCT00628745.
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| 2. |
- Ekoff, Maria, et al.
(författare)
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The BH3-only protein Puma plays an essential role in cytokine deprivation-induced apoptosis of mast cells
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 110:9, s. 3209-3217
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Tidskriftsartikel (refereegranskat)abstract
- Mast cells play critical roles in the regulation of inflammation. One characteristic feature of mast cells is their relatively long lifespan in vivo. Members of the Bcl-2 protein family are regulators of cell survival and apoptosis, where the BH3-only proteins are critical proapoptotic proteins. In this study we investigated the role of the BH3-only proteins Noxa, Bad, Bim, Bmf, Bid, and Puma in apoptosis of mucosal-like mast cells (MLMCs) and connective tissue-like mast cells (CTLMCs). We demonstrate that Puma is critical for the induction of mast-cell death following cytokine deprivation and treatment with the DNA-damaging agent etoposide in MLMCs and CTLMCs. Using p53-/- mast cells, we found that cytokine deprivation-induced apoptosis, in contrast to that elicited by etoposide, is p53-independent. Interestingly, mast cells deficient in FOXO3a, previously proposed as a transcription factor for Puma induction in response to growth factor deprivation, were markedly resistant to cytokine withdrawal compared with wildtype cells. Moreover, overexpression of phosphorylation-deficient, constitutively active FOXO3a caused an up-regulation of Puma. In conclusion, our data demonstrate a pivotal role for Puma in the regulation of cytokine deprivation-induced mast-cell apoptosis and suggest a plausible role for Puma in the regulation of mast cell numbers in vivo. © 2007 by The American Society of Hematology.
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| 3. |
- Acciari, V. A., et al.
(författare)
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Radio Imaging of the Very-High-Energy gamma-Ray Emission Region in the Central Engine of a Radio Galaxy
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5939, s. 444-448
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Tidskriftsartikel (refereegranskat)abstract
- The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.
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| 4. |
- de Goër de Herve, Mathilde
(författare)
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Disaster Risk Management for Sustainable Development : The Role of Justice and Temporality
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis investigates how disaster risk management can contribute to sustainable development through the consideration of justice and temporality. Sustainable development is the normative evolvement of society towards more wellbeing. Disaster risk management, defined as all the proactive and reactive strategies that are implemented to deal with disasters and disaster risks, can impact sustainable development in several ways. Notably, disasters are intrinsically unfair while sustainable development requires just processes, which makes justice considerations essential for disaster risk management to contribute to sustainable development. To address the many dimensions of sustainable development, justice considerations must encompass social, ecological, spatial, and temporal justice. After developing a conceptual framework addressing those issues, this thesis focuses on temporal justice because it is identified as a gap in flood risk management research and practice. This thesis is a compilation of four papers. The first one reviews scientific literature about flood risk management to understand why and how justice is considered in this field. The second paper develops the risk justice framework and uses it to analyze international guidelines for disaster risk management. The third one investigates time horizons included in disaster risk management evaluation and the determinants that explain if they are expanded or narrowed. The fourth paper is a case study of the temporal strategies implemented at two governance levels to strengthen disaster resilience following the 2021 flood events in the Vesdre river basin (Wallonia, Belgium). This thesis also discusses the role of evaluation and integrated management to improve policy-making in disaster risk management.
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| 5. |
- Edwards, Marten O. M., et al.
(författare)
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Increased photoelectron transmission in High-pressure photoelectron spectrometers using "swift acceleration"
- 2015
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 785, s. 191-196
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Tidskriftsartikel (refereegranskat)abstract
- A new operation mode of a HPXPS (high-pressure X-ray photoelectron spectroscopy) analyzer is evaluated on a HPXPS system fitted with an Al K alpha X-ray source. A variety of metal foil samples (gold, silver and copper) were measured in different sample gas environments (N-2 and H2O), and a front aperture diameter of 0.8 mm. The new design concept is based upon "swiftly" accelerating the photoelectrons to kinetic energies of several keV after they pass the analyzer front aperture. Compared to the standard mode, in which the front section between the two first apertures is field-free, this gives a wider angular collection and a lower tendency for electron losses in collisions with gas molecules within the analyzer. With the swift-acceleration mode we attain, depending on the experimental conditions, up to about 3 times higher peak intensities in vacuum and about 10 to 20 times higher peak intensities in the 6-9 mbar regime, depending on kinetic energy. These experimental findings agree well with simulated transmission functions for the analyzer. The new mode of operation enables faster data acquisition than the standard mode of operation, particularly valuable in a home laboratory environment. Further demonstrations of performance are highlighted by measurements of the valence band structure in dye sensitized solar cell photoelectrodes under a 2 mbar H2O atmosphere, a molecularly modified surface of interest in photoelectrochemical devices.
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| 6. |
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| 7. |
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| 8. |
- Hågvar, Sigmund, et al.
(författare)
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Ecosystem birth near melting glaciers : A review on the pioneer role of ground-dwelling arthropods
- 2020
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Ingår i: Insects. - : MDPI AG. - 2075-4450. ; 11:9, s. 1-35
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Forskningsöversikt (refereegranskat)abstract
- As glaciers retreat, their forelands represent “natural laboratories” for the study of primary succession. This review describes how certain arthropods conquer pristine ground and develop food webs before the establishment of vascular plants. Based on soil samples, pitfall traps, fallout and sticky traps, gut content studies, and some unpublished data, we compare early arthropod succession on glacial forelands of northern Europe (Iceland, Norway including Svalbard, and Sweden) and of the Alps (Austria, Italy). While macroarthropod predators like ground beetles (Coleoptera: Carabidae), harvestmen (Arachnida: Opiliones), and spiders (Arachnida: Araneae) have usually been considered as pioneers, assumed to feed on airborne prey, this review explains a different pattern. Here, we highlight that springtails (Collembola), probably feeding on biofilm made up of algae or cyanobacteria, are super-pioneers, even at high altitudes and under arctic conditions. We also point out that macroarthropod predators can use locally available prey, such as springtails or non-biting midges (Diptera: Chironomidae). Pioneer arthropod communities vary under different biogeographical and climatic conditions. Two pioneer food webs, from northern Europe and the Alps, respectively, differed in structure and function. However, certain genera and orders were common to both. Generalists and specialists live together in a pioneer community. Cold-adapted specialists are threatened by glacier melting.
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| 9. |
- Kaufmann, Odd Tore, et al.
(författare)
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Teachers’ Error-handling Practices Within and Across Lesson Phases in the Mathematics Classroom
- 2022
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Ingår i: International Journal of Science and Mathematics Education. - : Springer. - 1571-0068 .- 1573-1774.
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Tidskriftsartikel (refereegranskat)abstract
- Multiple studies have been conducted regarding teachers’ error-handling practices, and how errors can be treated as opportunities for learning, albeit in the context of whole-class discussions. The aim of the present research is to continue to investigate teachers’ error-handling practices as they occur in different phases of maths lessons: introduction of the task, when students are working alone, and when students are working in pairs and finally, as part of the whole-class discussion. The study included 51 lessons from twelve teachers. A cross-case analysis was made across the individual teacher cases to look for similarities and differences between different teachers’ error-handling practices across the lesson phases in order to create teaching profiles with similar handling of student errors across the lesson phases. Five error-handling teaching profiles were identified; correcting errors throughout all phases, correcting errors during students’ work while few errors are brought up in whole class, correcting errors during students’ work while using a variety of practices in whole class, ignoring errors while using some of them in whole class, and discussing and explaining errors.
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| 10. |
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| 11. |
- Oji, Satoru, et al.
(författare)
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Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord
- 2016
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 11:3, s. e0151244-
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Tidskriftsartikel (refereegranskat)abstract
- Neuromyelitis optica (NMO) is an acute inflammatory disease of the central nervous system (CNS) which predominantly affects spinal cord and optic nerves. Most patients harbor pathogenic autoantibodies, the so-called NMO-IgGs, which are directed against the water channel aquaporin 4 (AQP4) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do not profit from such treatments. How is I-IFN involved in NMO pathogenesis? To address this question, we made gene expression profiles of spinal cords from Lewis rat models of experimental neuromyelitis optica (ENMO) and experimental autoimmune encephalomyelitis (EAE). We found an upregulation of I-IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen-specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation of pathogenic T and B cells in the lymph nodes. We observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I-IFN.
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| 12. |
- Raška, Pavel, et al.
(författare)
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Identifying barriers for nature-based solutions in flood risk management : An interdisciplinary overview using expert community approach
- 2022
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Ingår i: Journal of Environmental Management. - : Elsevier BV. - 0301-4797 .- 1095-8630. ; 310
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Tidskriftsartikel (refereegranskat)abstract
- The major event that hit Europe in summer 2021 reminds society that floods are recurrent and among the costliest and deadliest natural hazards. The long-term flood risk management (FRM) efforts preferring sole technical measures to prevent and mitigate floods have shown to be not sufficiently effective and sensitive to the environment. Nature-Based Solutions (NBS) mark a recent paradigm shift of FRM towards solutions that use nature-derived features, processes and management options to improve water retention and mitigate floods. Yet, the empirical evidence on the effects of NBS across various settings remains fragmented and their implementation faces a series of institutional barriers. In this paper, we adopt a community expert perspective drawing upon LAND4FLOOD Natural flood retention on private land network (https://www.land4flood.eu) in order to identify a set of barriers and their cascading and compound interactions relevant to individual NBS. The experts identified a comprehensive set of 17 barriers affecting the implementation of 12 groups of NBS in both urban and rural settings in five European regional environmental domains (i.e., Boreal, Atlantic, Continental, Alpine-Carpathian, and Mediterranean). Based on the results, we define avenues for further research, connecting hydrology and soil science, on the one hand, and land use planning, social geography and economics, on the other. Our suggestions ultimately call for a transdisciplinary turn in the research of NBS in FRM.
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| 13. |
- Scheeren, Thomas W. L., et al.
(författare)
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Current use of inotropes in circulatory shock
- 2021
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Ingår i: Annals of Intensive Care. - : Springer. - 2110-5820. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTreatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock.MethodsFrom November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions.ResultsA total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81–90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement).ConclusionInotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.
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| 14. |
- Sønderby, Ida E., et al.
(författare)
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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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| 15. |
- Udechukwu, Obiora, et al.
(författare)
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Notes From the Field: Tradition
- 2013
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Ingår i: The Art Bulletin. - : Informa UK Limited. - 0004-3079 .- 1559-6478. ; 95:4, s. 526-527
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 16. |
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| 17. |
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| 18. |
- Walton, Esther, et al.
(författare)
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Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa : A Coordinated Analysis by the ENIGMA Eating Disorders Working Group
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 92:9, s. 730-738
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and de-pendencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data.METHODS: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251).RESULTS: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of un-dernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients.CONCLUSIONS: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.
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| 19. |
- Zeka, Bleranda, et al.
(författare)
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Aquaporin 4-specific T cells and NMO-IgG cause primary retinal damage in experimental NMO/SD.
- 2016
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Ingår i: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Neuromyelitis optica/spectrum disorder (NMO/SD) is a severe, inflammatory disease of the central nervous system (CNS). In the majority of patients, it is associated with the presence of pathogenic serum autoantibodies (the so-called NMO-IgGs) directed against the water channel aquaporin 4 (AQP4), and with the formation of large, astrocyte-destructive lesions in spinal cord and optic nerves. A large number of recent studies using optical coherence tomography (OCT) demonstrated that damage to optic nerves in NMO/SD is also associated with retinal injury, as evidenced by retinal nerve fiber layer (RNFL) thinning and microcystic inner nuclear layer abnormalities. These studies concluded that retinal injury in NMO/SD patients results from secondary neurodegeneration triggered by optic neuritis.However, the eye also contains cells expressing AQP4, i.e., Müller cells and astrocytes in the retina, epithelial cells of the ciliary body, and epithelial cells of the iris, which raised the question whether the eye can also be a primary target in NMO/SD. Here, we addressed this point in experimental NMO/SD (ENMO) induced in Lewis rat by transfer of AQP4268-285-specific T cells and NMO-IgG.We show that these animals show retinitis and subsequent dysfunction/damage of retinal axons and neurons, and that this pathology occurs independently of the action of NMO-IgG. We further show that in the retinae of ENMO animals Müller cell side branches lose AQP4 reactivity, while retinal astrocytes and Müller cell processes in the RNFL/ganglionic cell layers are spared. These changes only occur in the presence of both AQP4268-285-specific T cells and NMO-IgG.Cumulatively, our data show that damage to retinal cells can be a primary event in NMO/SD.
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