| 1. |
- Ludvigsson, Johnny, et al.
(författare)
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GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus
- 2012
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 366:5, s. 433-442
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes.METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels.RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences.CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period.
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| 2. |
- Andersson, Lennart, et al.
(författare)
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Cancerframkallande ämnen i tätortsluft Lindesberg 2010/2011
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Inom Naturvårdsverkets programområdeHälsorelaterad miljöövervakning(HÄMI), delprogramLuftförorening – exponeringsstudier ingår personburenmätning av vissa cancerframkallande och luftvägsirriterande ämnen i tätortsluft.De övriga orter som ingår i projektet är Göteborg, Umeå, Stockholm och Malmö.Lindesberg får här representera enmindre inlands kommun.Mätningarna genomförs för att försöka skatta allmänbefolkningens exponering förhälsoskadliga ämnen och samtliga orter har nu genomfört två mätomgångar frånstarten år 2000. De ämnen som ska mätas är bensen, butadien, formaldehyd,kvävedioxid, pratiklar PM 2,5 och benso(a)pyren.Lindesberg genomför inga egna mätningar av bakgrundshalter och vi har därföräven vid denna mätomgång valt ut samma två platser som vid föregående mätning.Räddningstjänstens tak (Kristinavägen) som representerar en trafikerad centralgata och Bergslagens Miljö- och Byggförvaltning (Kungsgatan). De uppmättalufthalterna är på samma låga nivåer som vid mätningen år 2005.Bakgrundhalterna i Lindesberg är i jämförelse med övriga orter lägre, vilket kännstroligt då det rör sig om en mindre tätort.För de personburna mätningarna är nivåerna lika med eller i vissa fall något högrejämfört med de övriga orterna. Det uppmättes några höga bensen- ochbutadienhalter med det beror på en yrkesmässig exponering.
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| 3. |
- Arvidsson Segerkvist, Katarina, et al.
(författare)
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A systematic mapping of current literature on sustainability at farm-level in beef and lamb meat production
- 2021
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Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Beef and lamb meat production is associated with important cultural, economic and environmental impacts in most countries worldwide. However, it is also related with sustainability challenges. To enable cattle and sheep farming to develop in line with sustainability, existing knowledge need to be implemented and identified knowledge gaps filled. The purpose of this article was to systematically map the scientific literature on environmental, economic and social sustainability at farm-level beef and lamb meat production to identify knowledge gaps and to point to important future actions and areas of research. Papers published January 2000–August 2020 with a geographical origin in Europe, Northern America, and Australia-New Zealand were included. The systematic literature search resulted in a total of 1355 hits; however, after removing papers which were considered out of the scope of the study, and duplicate papers, only 22 and 11 papers related to beef and sheep farming, respectively were retained for further analysis. Of these, only 11 in total included all three sustainability dimensions. Several papers only mentioned one or two of the sustainability dimensions or put them in relation to that/those main dimension covered, thus limiting the extent to which possible synergies or tradeoffs between different sustainability aspects actually can be studied. This indicates a need for a more comprehensive approach when studying farm-level sustainability. Future research would benefit from a more holistic approach and include all dimensions of sustainability within the same study. Further, focus should also be on how to measure and assess sustainability aspects in a standardized way. © 2021 by the authors.
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| 4. |
- Arvidsson Segerkvist, Katarina, et al.
(författare)
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Research on Environmental, Economic, and Social Sustainability in Dairy Farming: A Systematic Mapping of Current Literature
- 2020
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Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 12
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Forskningsöversikt (refereegranskat)abstract
- Dairy cows are able to convert fibrous materials, such as grass, roughage, and by-products from the food industry, into milk and meat, which justifies their role in food production. However, modern dairy farming is associated with major sustainability challenges, including greenhouse gas emissions. In order to develop sustainable future production, it is important to implement existing knowledge and fill knowledge gaps. The aim of this study was to systematically map the scientific literature on environmental, economic, and social sustainability at farm level in dairy farming. Literature published between January 2000 and March 2020 and with the geographical focus on Europe, North America, and Australia-New Zealand was included. In total, the literature search resulted in 169 hits, but after removing duplicates and papers outside the study scope only 35 papers remained. Of these, only 11 dealt with the three dimensions of sustainability, and several of these only mentioned one or two of the dimensions or set them in relation to that/those actually studied. Overall, the selected literature did not clearly explain how aspects of sustainability are interlinked, so possible negative or positive interactions between different aspects of sustainability dimensions remain unidentified.
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| 5. |
- Björck, Lennart, et al.
(författare)
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Tveksam vinst med ekolantbruk
- 2009
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Ingår i: Svenska dagbladet. - 1101-2412. ; -
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 6. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 7. |
- Borgegard, Tomas, et al.
(författare)
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Alzheimers Disease: Presenilin 2-Sparing gamma-Secretase Inhibition Is a Tolerable A beta Peptide-Lowering Strategy
- 2012
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17297-17305
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Tidskriftsartikel (refereegranskat)abstract
- gamma-Secretase inhibition represents a major therapeutic strategy for lowering amyloid beta (A beta) peptide production in Alzheimers disease (AD). Progress toward clinical use of gamma-secretase inhibitors has, however, been hampered due to mechanism-based adverse events, primarily related to impairment of Notch signaling. The gamma-secretase inhibitor MRK-560 represents an exception as it is largely tolerable in vivo despite displaying only a small selectivity between A beta production and Notch signaling in vitro. In exploring the molecular basis for the observed tolerability, we show that MRK-560 displays a strong preference for the presenilin 1(PS1) over PS2 subclass of gamma-secretases and is tolerable in wild-type mice but causes dose-dependent Notch-related side effect in PS2-deficient mice at drug exposure levels resulting in a substantial decrease in brain A beta levels. This demonstrates that PS2 plays an important role in mediating essential Notch signaling in several peripheral organs during pharmacological inhibition of PS1 and provide preclinical in vivo proof of concept for PS2-sparing inhibition as a novel, tolerable and efficacious gamma-secretase targeting strategy for AD.
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| 8. |
- Borgegård, Tomas, et al.
(författare)
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Alzheimer's Disease : Presenilin 2-Sparing γ-Secretase Inhibition Is a Tolerable Aβ Peptide-Lowering Strategy
- 2012
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17297-17305
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Tidskriftsartikel (refereegranskat)abstract
- γ-Secretase inhibition represents a major therapeutic strategy for lowering amyloid β (Aβ) peptide production in Alzheimer's disease (AD). Progress toward clinical use of γ-secretase inhibitors has, however, been hampered due to mechanism-based adverse events, primarily related to impairment of Notch signaling. The γ-secretase inhibitor MRK-560 represents an exception as it is largely tolerable in vivo despite displaying only a small selectivity between Aβ production and Notch signaling in vitro. In exploring the molecular basis for the observed tolerability, we show that MRK-560 displays a strong preference for the presenilin 1 (PS1) over PS2 subclass of γ-secretases and is tolerable in wild-type mice but causes dose-dependent Notch-related side effect in PS2-deficient mice at drug exposure levels resulting in a substantial decrease in brain Aβ levels. This demonstrates that PS2 plays an important role in mediating essential Notch signaling in several peripheral organs during pharmacological inhibition of PS1 and provide preclinical in vivo proof of concept for PS2-sparing inhibition as a novel, tolerable and efficacious γ-secretase targeting strategy for AD.
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| 9. |
- Bybrant, M. C., et al.
(författare)
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Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes
- 2021
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 22:3, s. 417-424
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were >= 10 times the upper limit of normal (10x ULN) predicted CD in T1D. Methods Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005-2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhuber classification. Results All of the 60 children with anti-tTG >= 10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. Conclusions As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method.
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| 10. |
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