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Sökning: WFRF:(Nilsson Amanda)

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1.
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2.
  • Palmer, Nicholette D, et al. (författare)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
  • Tidskriftsartikel (refereegranskat)abstract
    • African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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3.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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4.
  • Fromell, Karin, et al. (författare)
  • Assessment of the Role of C3(H2O) in the Alternative Pathway
  • 2020
  • Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study we investigate the hydrolysis of C3 to C3(H2O) and its ability to initiate activation via the alternative pathway (AP) of the complement system. The internal thioester bond within C3 is hydrolyzed by water in plasma because of its inherent lability. This results in the formation of non-proteolytically activated C3(H2O) which is believed have C3b-like properties and be able to form an active initial fluid phase C3 convertase together with Factor B (FB). The generation of C3(H2O) occurs at a low but constant rate in blood, but the formation can be greatly accelerated by the interaction with various surfaces or nucleophilic and chaotropic agents. In order to more specifically elucidate the relevance of the C3(H2O) for AP activation, formation was induced in solution by repeated freeze/thawing, methylamine or KCSN treatment and named C3(x) where the x can be any of the reactive nucleophilic or chaotropic agents. Isolation and characterization of C3(x) showed that it exists in several forms with varying attributes, where some have more C3b-like properties and can be cleaved by Factor I in the presence of Factor H. However, in common for all these variants is that they are less active partners in initial formation of the AP convertase compared with the corresponding activity of C3b. These observations support the idea that formation of C3(x) in the fluid phase is not a strong initiator of the AP. It is rather likely that the AP mainly acts as an amplification mechanism of complement activation that is triggered by deposition of target-bound C3b molecules generated by other means.
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5.
  • Hellström, Amanda, et al. (författare)
  • Leg ulcers in older people : a national study addressing variation in diagnosis, pain and sleep disturbance
  • 2016
  • Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Leg ulcers commonly emerge as a symptom of other comorbidities, often in older people. As a consequence of the ulcer, pain and sleep disturbances might occur. Due to the complex illness, the responsibility of treatment is unclear between health caregivers. The interaction between ulcer type, sleep and pain has not previously been investigated. This study aimed to explore pain in older men and women (65 years and older) with different diagnoses of leg ulcers and to investigate the associations of sleep disturbances and pain in people with leg ulcer diagnosis. Methods: The study used a cross-sectional design and data from the Swedish Registry of Ulcer Treatment, collected between May 2009 and December 2013. One thousand and eight hundred and twenty four people were included, and 62.9 % were women. The mean age was 83.4 years (SD 8.8). For the analyses, the chi-square test, Mann-Whitney U-test, t-test, one-way ANOVA and logistic regression was performed. Pain was measured by the Numeric Rating Scale (NRS), and sleep disturbances was assessed dichotomously. Results: We found the prevalence of pain intensity >= 5 on the NRS to be 34.8 % in those reporting pain. Additionally, the pain intensity was associated with the number of ulcers (p = 0.003). Sleep disturbances were associated with pain (p < 0.001) and were found in 34.8 % of the total sample. Although more women than men reported pain and scored higher on the NRS, no significant gender difference in sleep disturbances was found (p = 0.606). The mean NRS scores did not differ significantly between the ulcer types; however, arterial and venousarterial ulcers increased the risk of sleep disturbances, as did higher pain scores. Conclusions: The majority of the participants were of advanced age (>80 years) and frequently suffered from pain and sleep disturbances. Further research is needed regarding pain, sleep and wound healing in the oldest old with leg ulcers. Ulcer pain sometimes appears to receive less attention in ulcer management, as do sleep disturbances, implying that individual needs might not be satisfactorily met. National guidelines in managing leg ulcers, which also consider consequences such as sleep disturbances, pain and discomfort, are needed.
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6.
  • Nilsson Ekdahl, Kristina, et al. (författare)
  • Is generation of C-3(H2O) necessary for activation of the alternative pathway in real life?
  • 2019
  • Ingår i: Molecular Immunology. - : Elsevier. - 0161-5890 .- 1872-9142. ; 114, s. 353-361
  • Tidskriftsartikel (refereegranskat)abstract
    • In the alternative pathway (AP) an amplification loop is formed, which is strictly controlled by various fluid-phase and cell-bound regulators resulting in a state of homeostasis. Generation of the "C3b-like" C3(H2O) has been described as essential for AP activation, since it conveniently explains how the initial fluid-phase AP convertase of the amplification loop is generated. Also, the AP has a status of being an unspecific pathway despite thorough regulation at different surfaces. During complement attack in pathological conditions and inflammation, large amounts of C3b are formed by the classical/lectin pathway (CP/LP) convertases. After the discovery of LP's recognition molecules and its tight interaction with the AP, it is increasingly likely that the AP acts in vivo mainly as a powerful amplification mechanism of complement activation that is triggered by previously generated C3b molecules initiated by the binding of specific recognition molecules. Also in many pathological conditions caused by a dysregulated AP amplification loop such as paroxysmal nocturnal hemoglobulinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), C3b is available due to minute LP and CP activation and/or generated by non-complement proteases. Therefore, C3(H2O) generation in vivo may be less important for AP activation during specific attack or dysregulated homeostasis, but may be an important ligand for C3 receptors in cell-cell interactions and a source of C3 for the intracellular complement reservoir.
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7.
  • Strom, Asa C., et al. (författare)
  • B regulatory cells are increased in hypercholesterolaemic mice and protect from lesion development via IL-10
  • 2015
  • Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 114:4, s. 835-847
  • Tidskriftsartikel (refereegranskat)abstract
    • Whilst innate B1-B cells are atheroprotective, adaptive B2-B cells are considered pro-atherogenic. Different subsets of B regulatory cells (B-reg) have been described. In experimental arthritis and lupus-like disease, B-reg are contained within the CD21(hi)CD23(hi)CD24(hi) B cell pool The existence and role of B-reg in vascular disease is not known. We sought to investigate the existence, identity and location of B-reg in vascular disease. The representation of B2-B cell subsets in the spleens and lymph nodes (LNs) of Apolipoprotein E-/- (ApoE(-/-)) mice compared to controls was characterised by flow cytometry. Additionally, we utilised a model of neointima formation based on the placement of a perivascular collar around the carotid artery in ApoE(-/-) mice to ascertain whether B cells and B cell subsets confer protection against lesion development. Adoptive transfer of B cells was performed from wild type or genetically modified mice. We showed that CD21(hi)CD23(hi)CD24(hi) B cells are unexpectedly increased in the draining LNs of ApoE(-/-) mice. Adoptive transfer of LN-derived B2-B cells or purified CD21(hi)CD23(hi)CD24(hi) B cells to syngeneic mice reduced lesion size and inflammation without changing serum cholesterol levels. Follicular B2-B cells did not confer protection. IL-10 blockade or transfer of IL10-deficient B cells prevented LN-derived B cell-mediated protection. This is the first identification of a specific LN-derived B2-B-reg subset that confers IL-10 mediated protection from neointima formation. This may open the way for immune modulatory approaches in cardiovascular disease.
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8.
  • Voight, Benjamin F., et al. (författare)
  • Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:7, s. 579-589
  • Tidskriftsartikel (refereegranskat)abstract
    • By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
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9.
  • Adanez-Rubio, Inaki, et al. (författare)
  • Cu-Mn oxygen carrier with improved mechanical resistance: Analyzing performance under CLC and CLOU environments
  • 2021
  • Ingår i: Fuel Processing Technology. - : Elsevier BV. - 0378-3820. ; 217
  • Tidskriftsartikel (refereegranskat)abstract
    • Chemical Looping Combustion process allows combustion of gaseous, liquid or solid fuels with CO capture. The oxygen necessary for combustion can be supplied using lattice oxygen (CLC) or oxygen uncoupling (CLOU) mechanisms. The present work studies the effects of kaolin addition on Cu–Mn oxygen carrier behavior for CLC and CLOU processes. Cu–Mn oxygen carrier was prepared by granulation with a composition: 27.2 wt% CuO, 52.8 wt% Mn O and 20 wt% kaolin. Oxygen release rates and fluidization behavior were analyzed by TGA and batch fluidized bed reactor. The oxygen carrier was studied for CH and synthetic biogas combustion in a 500 W CLC continuous unit for 50 h of combustion at temperatures up to 930 °C. No agglomeration problems were observed. Results found during biogas combustion were similar to methane combustion. The addition of 20 wt% kaolin changed the mixed oxide chemical composition generating Cu Mn O and improved significantly the oxygen carrier mechanical resistance, increasing the extrapolated lifetime to 19,000 h, 3.6 times over the value found for any Cu based oxygen carrier in CLC. However, the oxygen carrier reactivity had an important decrease with respect to a similar oxygen carrier without kaolin addition, whose fraction in oxygen carrier must be optimized. 2 3 4 4 th 1.2 1.8 4
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10.
  • Adelsjö, Igor, et al. (författare)
  • Communication about medication management during patient–physician consultations in primary care : a participant observation study
  • 2022
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To explore communication about medication management during annual consultations in primary care. Design: passive participant observations of primary care consultations.Setting Two primary care centres in southern Sweden.Participants Consultations between 18 patients (over the age of 60 years) with chronic diseases and 10 general practitioners (GPs) were observed, audio-recorded, transcribed and analysed using content analysis.Results Four categories emerged: communication barriers, striving for a shared understanding of medication management, evaluation of the current medication treatment and the plan ahead and behavioural changes in relation to medication management. Misunderstandings in communication, failure to report changes in the medication treatment and use of generic substitutes complicated mutual understanding and agreement on continued treatment. The need for behavioural changes to reduce the need for medication treatment was recognised but should be explored further.Conclusion Several pitfalls, including miscommunication and inaccurate medication lists, for safe medication management were identified. The purpose of annual consultations should be clarified, individual treatment plans could be used more actively during primary care consultations and efforts are needed to improve verbal communication and information continuity.No data are available.
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