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- Agholme, Lotta
(författare)
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The involvement of degradation pathways and neuron-to-neuron transmission in Alzheimer’s disease
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although the vast majority of Alzheimer’s disease (AD) cases are of the sporadic type, mutations causing the familial form have been the focus of AD research for decades. The disease is pathologically characterised by β-amyloid (Aβ) and tau protein aggregates in neuritic plaques and neurofibrillary tangles. Furthermore, it is known that AD pathology spreads throughout the brain, most often along the same anatomical pattern. However, so far no cause for the sporadic form of the disease has been found. Accumulation of protein aggregates as well as decreased activity of the protein degradation systems, lysosomes and proteasomes, is found in diseased brains. This indicates that defective degradation contributes to sporadic AD.The aim of this thesis was to develop an improved neuronal model, and study the effects of decreased proteasome function on tau phosphorylation and axonal transport. In addition, the effects on Aβ accumulation and generation upon proteasome inhibition were investigated. Finally, the possibility that intracellularly accumulated Aβ oligomers could be transferred from one neuron to another was tested.Differentiation of human SH-SY5Y neuroblastoma cells in an extracellular matrix gel, using a set of neurotrophic factors, resulted in cells with neuronal phenotype, expressing neuron specific markers and all six adult isoforms of tau. Within this neuronal model, we found that reduced proteasome activity inhibited neuritic transport, and caused tau phosphorylation in a c-Jun and ERK 1/2 dependent manner. Using proteasome inhibition in APP overexpressing cells, we found an autophagy dependent intralysosomal Aβ accumulation, together with elevation of intra- and extracellular concentrations of Aβ. Autophagy inhibition protected the cells from the toxicity induced by decreased proteasome activity. Finally, we could, as the first group, show that Aβ can be directly transferred from one neuron to another through connected neurites. Furthermore, accumulation of Aβ in the endo-lysosomal compartment of receiving cells caused toxicity and neurodegeneration.We believe that cells not able to degrade accumulated Aβ, due to increased generation or reduced degradative capacity, instead tries to clear its content through transfer to connected neurons. If not properly degraded in the receiving cell, this can accelerate AD pathology and cause neuritic and neuronal degeneration spreading throughout the brain. Increasing the activity of the degradative systems, or inhibiting transmission of Aβ between neurons could therefore be novel treatments for AD.
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| 2. |
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| 3. |
- Bilén, Anna-Karin, et al.
(författare)
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Miljökvalitetsmålen 2016 : Årlig uppföljning av miljökvalitetsmålen
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I Blekinge bedöms inte något miljökvalitetsmål vara möjligt att nå till år 2020. För att kunna lämna över ett hållbart samhälle till nästa generation krävs förebyggande arbete, ef?????????????????r. Ambitionerna måste öka och miljöfrågorna prioriteras högre på den politiska agendan.De mål som rör biologisk mångfald och bevarande av kulturmiljö följer enneutral eller negativ trend. I odlingslandskapet leder färre lantbrukare ochbrist på betesdjur till igenväxning av hagmarker. Livsmiljöer försvinner och????????????????????????????????????????,främst möte insekter.För att god ekologisk status ska uppnås i vattendragen behövs ny vattenlagstiftning och mer resurser för tillsyn. I Blekinges kustvatten är övergödning ett stort miljöproblem och det krävs kraftfulla åtgärder för att minska näringsläckaget. Arbetet med vattenförsörjningsplaner behöver fortsätta för att trygga framtida dricksvattenförsörjning. De senaste årens fynd av PFAS i dricksvatten visar på vikten av att skydda vattentäkter, genomföra riskbedömningar och undersöka förekomst av föroreningar.Obalans mellan den tätbefolkade kusten och den glesbyggda landsbygden är en utmaning i länet. Byggandet vid kusten ställer krav på en hänsynsfull bebyggelseutveckling som tydligt beaktar miljökvalitetsmålen.Internationella överenskommelser om kemikalier och minskade utsläpp till luft och vatten är nödvändigt för att uppnå uppsatta mål. Dessutom behövs en omställning till ett samhälle som baseras på förnybar energi. För att skapa en hållbar framtid måste vi förändra vår livsstil och vår attityd till konsumtion. Lokala och regionala åtgärder såsom arbete för en giftfri förskola och minskade utsläpp av mikroplaster är steg i rätt riktning.Minskad biologisk mångfald påverkar tillsammans med klimatförändringar, övergödning och miljögifter många av de ekosystemtjänster som vi är beroende av för mänsklig välfärd och en hållbar samhällsutveckling. Det pågår insatser som förbättrar tillståndet i miljön, men det går för långsamt. Det krävs mer resurser och modiga politiska beslut för att möjliggöra en hållbar framtid, den framtid som vi är skyldiga våra barn!
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| 5. |
- Marcusson, Agneta, et al.
(författare)
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Alterations in occlusion and maxillary dental arch dimensions in adults with treated unilateral complete cleft lip and palate
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this stndy was to evaluate the occlusion and maxillary dental arch dimensions in adults with repaired complete unilateral cleft lip and palate (UCLP) and to investigate the patterns of change in early adulthood. Study models from 39 subjects (25 men, 14 women) (mean age 24.7 years, range 20.2-29.3) with the diagnosis complete UCLP taken at a follow-up examination were analysed and compared with the study models taken at baseline examination (mean age 19.1 years, range 16.0-20.6). Lip closure was made according to the Millard technique and palatal closure according to the Wardill-Kilner technique. All subjects had received orthodontic treatment with fixed appliances. The subjects were divided into three groups according to the type of retention in the upper jaw: no retention (n = 15), retention with bonded twisted retainer (n = 13), onlay or fixed bridge (n = 11).Occlusion was evaluated according to a scoring system (Huddart and Bodenham, 1972). The maxillary dental arch dimensions were measured with a video imaging system. In the total sample there was a significant deterioration in the total occlusal score during the follow-up period. The impairment was larger on the cleft side than on the non-cleft side. There were no significant differences in the frontal scores. A comparison of the transversal and sagittal maxillary arch dimensions revealed significant differences in all measurements during the follow-up interval. The reduction was largest for the maxillary second premolar width, followed by the first molar width. The oveijet differed significantly between the registrations. The occlusal score and the maxillary arch dimensions were reduced in all of the three subgroups, but there were no differences between the groups. No gender differences were found.
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| 7. |
- Marcusson, Agneta, 1956-, et al.
(författare)
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Changes in occlusion and maxillary dental arch dimensions in adults with treated unilateral complete cleft lip and palate : A follow-up study
- 2004
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Ingår i: European Journal of Orthodontics. - : Oxford University Press (OUP). - 0141-5387 .- 1460-2210. ; 26:4, s. 385-390
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the occlusion and maxillary dental arch dimensions in adults with repaired complete unilateral cleft lip and palate (UCLP) and to investigate the patterns of change in early adulthood. Study models from 39 patients (25 men, 14 women, mean age 24.7 years, range 20.2-29.3 years) with a diagnosis of complete UCLP taken at a follow-up examination were analysed and compared with the study models taken at baseline examination (mean age 19.1 years, range 16.0-20.6 years). Lip closure was carried out according to the Millard technique and palatal closure according to the Wardill-Kilner technique. All patients had received orthodontic treatment with fixed appliances. The patients were divided into three groups according to the type of retention in the upper arch: no retention (n = 15), retention with a bonded twisted retainer (n = 13), an onlay or fixed bridge (n = 11). Occlusion was evaluated according to a scoring system. The maxillary dental arch dimensions were measured with a video imaging system. There was a significant deterioration in the total occlusal score during the follow-up period and this was larger on the cleft than on the non-cleft side. There were no significant differences in the anterior scores. A comparison of the transversal and sagittal maxillary arch dimensions revealed significant differences in all measurements during the follow-up interval. The reduction was largest for the maxillary second premolar width, followed by the first molar width. The overjet differed significantly between the registrations. The occlusal score and the maxillary arch dimensions were reduced in all of the three subgroups, but there were no differences between the groups.
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| 8. |
- Marcusson, Agneta, et al.
(författare)
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Facial appearance in adults who had cleft lip and palate treated in childhood
- 2002
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 0284-4311 .- 1651-2073. ; 36:1, s. 16-23
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Tidskriftsartikel (refereegranskat)abstract
- Sixty-eight adults (44 men and 24 women) with treated total cleft lip and palate were compared with a group of 66 adults (49 men and 17 women) without clefts, matched by sex and age. The outcome measures included a self-report questionnaire about body image, quality of life in general, health-related quality of life, somatisation, and depression. The group with clefts were also asked if they had further need of treatment. They reported significantly more dissatisfaction with their facial appearance (nose, lips, mouth, profile, and overall facial appearance) than the group without clefts. Satisfaction with facial appearance was significantly correlated with a better quality of life in both groups, and significantly correlated with a better health-related quality of life and a lower grade of somatisation in the group with clefts. Dissatisfaction with facial appearance was the most significant predictor of depression in both groups. A panel of four professionals from a cleft lip and palate treatment team judged the outcome of treatment in 64 of the subjects on colour slides. The professionals and the subjects with clefts were generally not very satisfied with the results of the surgical outcome. Thirty of the subjects with clefts (47%) wished to have more operations. The professional group recommended further operations in 38 of the cases (59%), in particular, rhinoplasties. We conclude that the subjects with treated clefts were not satisfied with their facial appearance, although they seem to be psychosocially well-adjusted to their disability.
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| 9. |
- Marcusson, Agneta, 1956-, et al.
(författare)
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Quality of life in adults with repaired complete cleft lip and palate
- 2001
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Ingår i: The Cleft Palate-Craniofacial Journal. - 1055-6656 .- 1545-1569. ; 38:4, s. 379-385
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study evaluated the quality of life in adult Swedish subjects with repaired complete cleft lip and palate (CLP).Design/Patients: Sixty-eight adults with repaired CLP were compared with a group of 66 adults without cleft matched by gender and age.Outcome Measures: The outcome measures included a self-report questionnaire concerning quality of life in general, well-being, and health-related quality of life.Results: The CLP group rated their quality of life significantly lower than did the control group in the areas of life meaning (p < .05), family life (p < .0001), and private economy (p < .01). There were no significant differences between the groups concerning well-being. In the CLP group, the health-related quality of life was significantly lower concerning global life (p < .0001), disturbance to life (p < .01), well-being (p < .0001), social contacts (p < .0001), and family life (p < .05) but significantly higher concerning ability to make the most of leisure time (p < .001) and to be active (p < .001).Conclusions: The CLP group perceived a marked impact of the handicap on their lives concerning global aspects, well-being, and social life. More practical and tangible aspects of their daily living, however, were not affected, and only some minor aspects of their quality of life in general were poor in comparison with the control group, which indicates a fairly good life adjustment in spite of the handicap.
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| 10. |
- Marcusson, Agneta, 1956-, et al.
(författare)
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Reliability of a multidimensional questionnaire for adults with treated complete cleft lip and palate
- 2001
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 0284-4311 .- 1651-2073. ; 35:3, s. 271-278
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the reliability of a multidimensional questionnaire for Swedish adults with treated complete unilateral or bilateral cleft lip and palate (CLP). The questionnaire was designed to be used in the evaluation of adults with treated CLP after treatment. Before any conclusions were drawn from the results of the study we assessed the test-retest reliability of the questionnaire. The questionnaire included 168 questions and assessed the following domains: aesthetics, functions associated with CLP, satisfaction with treatment and perceived need for treatment, quality of life, depression and non-specific physical symptoms, body image, and jaw function. The subjects answered the questionnaire twice at a 2-3-week interval. Sixty-one adults (38 men, 23 women) mean age 24 years (range 20-29) participated in the study. The response rate for the questionnaire was acceptable at 75%. The test-retest reliability varied among the different domains. The reliability of questions regarding aesthetics, functions associated with CLP, and treatment satisfaction was good to excellent (intraclass correlation coefficient (ICC) = 0.51 to 0.89). Good to excellent (ICC = 0.61 to 1.0) reliability was also found for the quality of life in various life domains and the wellbeing scales. The reliability of the body image scale was moderate (kappa = 0.43-0.60) for most items and lower than that of other scales used in this study. The reliability of the mean depression symptom score (ICC = 0.93) and the mean non-specific physical symptoms score (ICC = 0.85) were excellent. The reliability of the mandibular function impairment was good (ICC = 0.67). The conclusion of the study is that an overall reliability was good for the multidimensional questionnaire.
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