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Sökning: WFRF:(Moberg Helena)

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  • Bunne, Joakim, et al. (författare)
  • Increase in allergic sensitization in schoolchildren : two cohorts compared 10 years apart
  • 2017
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 2213-2198 .- 2213-2201. ; 5:2, s. 457-463
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Time trends of incidence of allergic sensitization are unknown and recent trends of prevalence and risk factors are lacking.OBJECTIVE: To estimate the incidence, prevalence, remission, risk factors, and time trends for allergic sensitization among schoolchildren followed from age 7 to 8 years to age 11 to 12 years.METHODS: In 2006, all children in grades 1 and 2 aged 7 to 8 years in 2 municipalities in northern Sweden were invited to a questionnaire survey and to skin prick testing to 10 common airborne allergens. The cohort was reexamined in 2010, with additional blood sampling for specific IgE. Participation rates were 90% (n = 1700) at age 7 to 8 years and 85% (n = 1657) at age 11 to 12 years. The results were compared with a cohort examined by identical methods 10 years earlier.RESULTS: The prevalence of positive skin prick test result to any allergen increased from 30% at age 7 to 8 years to 41% at age 11 to 12 years (P < .001). The cumulative 4-year incidence was 18%, while remission was low. Sensitization to pollen and furred animals was most common. A family history of allergy was significantly associated with incident sensitization, whereas the presence of furred animals at home was negatively associated. The prevalence at age 7 to 8 years and at age 11 to 12 years and the 4-year incidence were all significantly higher compared with the cohort examined 10 years earlier.CONCLUSIONS: The prevalence of allergic sensitization increased by age as a consequence of a high incidence and a low remission. The trends of increasing incidence and prevalence among schoolchildren imply future increases in the prevalence of allergic diseases.
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3.
  • FitzGerald, Edward A., et al. (författare)
  • Multiplexed experimental strategies for fragment library screening using SPR biosensors
  • 2020
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Surface plasmon resonance biosensor technology (SPR) is ideally suited for fragment-based lead discovery. However, generally suitable experimental procedures or detailed protocols are lacking, especially for structurally or physico-chemically challenging targets or when tool compounds are lacking. Success depends on accounting for the features of both the target and the chemical library, purposely designing screening experiments for identification and validation of hits with desired specificity and mode-of-action, and availability of orthogonal methods capable of confirming fragment hits. By adopting a multiplexed strategy, the range of targets and libraries amenable to an SPR biosensor-based approach for identifying hits is considerably expanded. We here illustrate innovative strategies using five challenging targets and variants thereof. Two libraries of 90 and 1056 fragments were screened using two different flow-based SPR biosensor systems, allowing different experimental approaches. Practical considerations and procedures accounting for the characteristics of the proteins and libraries, and that increase robustness, sensitivity, throughput and versatility are highlighted.Competing Interest StatementAnna Moberg, Maria T. Lindgren and Claes Holmgren work for Cytiva, which produce Biacore systems.
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  • FitzGerald, Edward, et al. (författare)
  • Multiplexed experimental strategies for fragment library screening against challenging drug targets using SPR biosensors
  • 2024
  • Ingår i: SLAS Discovery. - : Elsevier. - 2472-5560 .- 2472-5552. ; :1, s. 40-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Surface plasmon resonance (SPR) biosensor methods are ideally suited for fragment-based lead discovery.  However, generally applicable experimental procedures and detailed protocols are lacking, especially for structurally or physico-chemically challenging targets or when tool compounds are not available. Success depends on accounting for the features of both the target and the chemical library, purposely designing screening experiments for identification and validation of hits with desired specificity and mode-of-action, and availability of orthogonal methods capable of confirming fragment hits. The range of targets and libraries amenable to an SPR biosensor-based approach for identifying hits is considerably expanded by adopting multiplexed strategies, using multiple complementary surfaces or experimental conditions. Here we illustrate principles and multiplexed approaches for using flow-based SPR biosensor systems for screening fragment libraries of different sizes (90 and 1056 compounds) against a selection of challenging targets. It shows strategies for the identification of fragments interacting with 1) large and structurally dynamic targets, represented by acetyl choline binding protein (AChBP), a Cys-loop receptor ligand gated ion channel homologue, 2) targets in multi protein complexes, represented by lysine demethylase 1 and a corepressor (LSD1/CoREST), 3) structurally variable or unstable targets, represented by farnesyl pyrophosphate synthase (FPPS), 4) targets containing intrinsically disordered regions, represented by protein tyrosine phosphatase 1B  (PTP1B), and 5) aggregation-prone proteins, represented by an engineered form of human tau  (tau K18M). Practical considerations and procedures accounting for the characteristics of the proteins and libraries, and that increase robustness, sensitivity, throughput and versatility are highlighted. The study shows that the challenges for addressing these types of targets is not identification of potentially useful fragments per se, but establishing methods for their validation and evolution into leads.
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6.
  • Horwath, Oscar, 1991-, et al. (författare)
  • Variablity in vastus lateralis fiber type distribution, fiber size and myonuclear content along and between the legs.
  • 2021
  • Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 131:1, s. 158-173
  • Tidskriftsartikel (refereegranskat)abstract
    • Human skeletal muscle characteristics such as fiber type composition, fiber size and myonuclear content are widely studied in clinical and sports related contexts. Being aware of the methodological and biological variability of the characteristics is a critical aspect in study design and outcome interpretation, but comprehensive data on the variability of morphological features in human skeletal muscle is currently limited. Accordingly, in the present study, m. vastus lateralis biopsies (10 per subject) from young and healthy individuals, collected in a systematic manner, were analyzed for various characteristics using immunohistochemistry (n=7) and SDS-PAGE (n=25). None of the analyzed parameters; fiber type % (FT%), type I and II CSA (fCSA), percentage fiber type area (fCSA%), myosin heavy chain composition (MyHC%), type IIX content, myonuclear content or myonuclear domain varied in a systematic manner longitudinally along the muscle or between the two legs. The average within subject coefficient of variation for FT%, fCSA, fCSA%, and MyHC% ranged between 13-18%, but was only 5% for fiber specific myonuclear content, which reduced the variability for myonuclear domain size to 11-12%. Pure type IIX fibers and type IIX MyHC were randomly distributed and present in <24% of the analyzed samples, with the average content being 0.1 and 1.1%, respectively. In conclusion, leg or longitudinal orientation does not seem to be an important aspect to consider when investigating human vastus lateralis characteristics. However, single muscle biopsies should preferably not be used when studying fiber type and fiber size related aspects given the notable sample to sample variability.
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  • Johansson, Helena, et al. (författare)
  • Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation
  • 2005
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:6, s. 1755-62
  • Tidskriftsartikel (refereegranskat)abstract
    • There are strong indications that only a small fraction of grafts successfully engraft in clinical islet transplantation. One explanation may be the instant blood-mediated inflammatory reaction (IBMIR) elicited by tissue factor, which is produced by the endocrine cells. In the present study, we show that islets intended for islet transplantation produce tissue factor in both the transmembrane and the alternatively spliced form and that the membrane-bound form is released as microparticles often associated with both insulin and glucagon granules. A low-molecular mass factor VIIa (FVIIa) inhibitor that indirectly blocks both forms of tissue factor was shown in vitro to be a promising drug to eliminate the IBMIR. Thrombin-antithrombin complex (TAT) and FVIIa-antithrombin complex (FVIIa-AT) were measured in nine patients who together received 20 infusions of isolated human islets. Both the TAT and FVIIa-AT complexes increased rapidly within 15-60 min after infusion. When the initial TAT and FVIIa-AT levels were plotted against the increase in C-peptide concentration after 7 days, patients with an initially strong IBMIR showed no significant increase in insulin synthesis after 7 days. In conclusion, tissue factor present in both the islets and the culture medium and elicits IBMIR, which affects the function of the transplanted islets.
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  • Moberg, Marianna, et al. (författare)
  • “Sometimes It Felt Great, and Sometimes It Just Went Pear-Shaped”: Experiences and Perceptions of School Nurses’ Motivational Interviewing Competence : A Convergent Mixed-Methods Study
  • 2022
  • Ingår i: Clinics and Practice. - : MDPI AG. - 2039-7275 .- 2039-7283. ; 12:3, s. 333-349
  • Tidskriftsartikel (refereegranskat)abstract
    • In this convergent mixed-methods study, the aim was to explore how objective and subjective quality ratings of school nurses’ motivational interviewing (MI) correlate whilst also considering the perceptions of delivering and participating in the same MI sessions. Quantitative and qualitative data were derived from seven intervention schools participating in the Healthy School Start Plus parenting support intervention. School nurses were trained in MI and conducted an MI session with parents of 6–7-year-old children to discuss children’s physical health and development. Quantitative data comprised objective ratings of school nurses’ MI competence using the Motivational Interviewing Treatment Integrity 4.2 [MITI-4] protocol, as well as parents’ and school nurses’ subjective ratings of the MI sessions. Qualitative data comprised semi-structured interviews with parents and school nurses about their perceptions of the MI sessions. First, quantitative data were analysed using Spearman’s rank correlation, and qualitative data were analysed using content analysis. Next, quantitative and qualitative findings were merged. Our findings suggest that school nurses’ MI performances were rated and perceived as valuable and family-centred by both school nurses and parents who had left the meeting feeling motivated and empowered to promote their children’s healthy behaviours. Nonetheless, school nurses were critical to their own MI technical performance, and they found that reflections were easier to deliver and to self-rate. Overall, MITI ratings were the lowest and parents’ ratings were the highest. Future studies should focus on relating clients’ subjective ratings of MI with clients’ behavioural outcomes.
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