| 1. |
- Bäcklund, Johan, et al.
(författare)
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Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis.
- 2002
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Ingår i: European Journal of Immunology. - 1521-4141. ; 32:12, s. 3776-3784
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Tidskriftsartikel (refereegranskat)abstract
- Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA). The common denominator of murine CIA and human RA is the presentation of an immunodominant CII-derived glycosylated peptide on murine Aq and human DR4 molecules, respectively. To investigate the importance of T cell recognition of glycosylated CII in CIA development after immunization with heterologous CII, we treated neonatal mice with different heterologous CII-peptides (non-modified, hydroxylated and galactosylated). Treatment with the galactosylated peptide (galactoseat position 264) was superior in protecting mice from CIA. Protection was accompanied by a reduced antibody response to CII and by an impaired T cell response to the glycopeptide. To investigate the importance of glycopeptide recognition in an autologous CIA model, we treated MMC-transgenic mice, which express the heterologous CII epitope with a glutamic acid in position 266 in cartilage, with CII-peptides. Again, a strong vaccination potential of the glycopeptide was seen. Hence CII-glycopeptides may be the optimal choice of vaccination target in RA, since humans share the same epitope as the MMC mouse
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| 2. |
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| 3. |
- Aragam, KG, et al.
(författare)
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Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:12, s. 1803-1815
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR–Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.
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| 4. |
- Aragam, KG, et al.
(författare)
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Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:12, s. 1803-1815
-
Tidskriftsartikel (refereegranskat)abstract
- The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR–Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.
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| 5. |
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Arkitekturteorier
- 1999
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Berin, Emilia, et al.
(författare)
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Effects of resistance training on quality of life in postmenopausal women with vasomotor symptoms
- 2022
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Ingår i: Climacteric. - : Taylor & Francis Ltd. - 1369-7137 .- 1473-0804. ; 25:3, s. 264-270
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Tidskriftsartikel (refereegranskat)abstract
- Objective Most women experience vasomotor symptoms (VMS) around menopause that may affect quality of life negatively. Effective pharmacological treatment exists but is not recommended for all women, and there is a demand for alternatives to reduce symptoms and improve quality of life. The objective of this study was to investigate the effect of a resistance training intervention on health-related quality of life (HRQoL) in postmenopausal women with VMS. Methods This open randomized controlled trial included 65 postmenopausal women >45 years old with daily VMS. The participants were randomized to 15 weeks of resistance training three times per week or an untreated control group. The Womens Health Questionnaire (WHQ) and Short Form Health Survey (SF-36) were used to assess HRQoL at baseline and after 15 weeks. Results The resistance training group improved compared to the control group in the WHQ domains of VMS (p = 0.002), sleep problems (p = 0.003) and menstrual symptoms (p = 0.01) from baseline to post intervention. No significant between-group differences were found in SF-36 summary scores, or in any of the domains. Conclusion In postmenopausal women with moderate to severe VMS, resistance training three times per week for 15 weeks improved menopause-specific HRQoL.
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| 7. |
- Berin, Emilia, et al.
(författare)
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Postmenopausal womens experiences of a resistance training intervention against vasomotor symptoms : a qualitative study
- 2022
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Ingår i: BMC Women's Health. - : BMC. - 1472-6874. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Resistance training may be an effective intervention to improve menopausal symptoms and increase womens quality of life. However, most postmenopausal women do not perform regular resistance training. The purpose of this study was to explore postmenopausal womens experiences of participation in a resistance-training intervention to find barriers and motivators for the training. Methods: Fifteen postmenopausal women with low physical activity, who participated in a randomized controlled trial evaluating the effect of a resistance-training program on vasomotor symptoms and health-related outcomes, were consecutively recruited to this qualitative study. After completion of the 15-week resistance-training program, they took part in individual semi-structured interviews, followed by a telephone interview 1 year later. All interviews were transcribed verbatim and thematic analysis was used to analyse the data. Results: The analysis generated three themes that were involved at different time points. These were: "Trigger-Hopes of symptom relief", "An evolving motivation as a driving force for change" and "Finding new triggers". Accountability, and continuous professional and emotional support, were factors that fueled the womens motivation to perform regular resistance training during the study. Resistance training improved general well-being and most women experienced improvement in vasomotor symptoms. The womens motivation changed from being driven by a wish to improve bothersome symptoms, into a wish to achieve feelings of well-being and enjoyment. The change was seen regardless of effects of the intervention on vasomotor symptoms. Conclusion: This first qualitative evaluation of physical exercise as an intervention to treat vasomotor symptoms in postmenopausal women, found that the symptoms acted as a motivational trigger to initiate resistance training in low-active women. The motivation to exercise changed during the intervention from a wish to ameliorate symptoms into something the women did for enjoyment and well-being in general. This change in motivating factors may have contributed to a behavior change since all participants had increased their physical activity after 1 year regardless of effects on VMS.
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| 8. |
- Berin, Emilia, 1992-
(författare)
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Resistance Training and Physical Activity in Postmenopausal Women : Effects on Vasomotor Symptoms, Quality of Life and Microcirculation
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Menopause is a physiological event, but is associated with bothersome symptoms as well as physical changes that affect women’s health. About 75 % of women experience vasomotor symptoms (hot flushes and night sweats) related to menopause that often reduce quality of life. The vasomotor symptoms may be attributed to dysfunctional temperature regulation centrally in the hypothalamus and peripherally in the skin’s circulation. The most effective treatment for vasomotor symptoms is menopausal hormone therapy, but not all women are able to, or want to, use it. In addition to the impact on quality of life, studies have associated vasomotor symptoms and menopause with macrovascular endothelial dysfunction. Previous studies on the association of these factors with the skin’s microcirculatory function are small and few. Observational studies have associated physical activity and exercise with less vasomotor symptoms, but the evidence from intervention trials is of low quality and the results are ambiguous. Physical activity has established general health effects, and could potentially decrease vasomotor symptoms by effects on endogenous opioids centrally, and by more efficient thermoregulation peripherally. The aim of this thesis was to investigate the effect of resistance training on vasomotor symptoms and health-related quality of life in postmenopausal women, and to explore the women’s experiences of the training to find barriers and facilitators. We also aimed to investigate whether the skin’s microcirculatory function differed between women regarding menopausal status, vasomotor symptoms, menopausal hormone therapy, and physical activity. Material and methods The first study was an open randomized controlled trial including 65 postmenopausal women with moderate to severe vasomotor symptoms and low physical activity levels. We randomized the women to 15 weeks of resistance training (intervention) or unchanged physical activity (control). The participants registered vasomotor symptoms daily in a diary, and answered health-related quality of life questionnaires at baseline and at 15 weeks. The first 15 women to finish the intervention were recruited to a qualitative study. The women’s experiences of the resistance training intervention were explored in individual interviews after the intervention period, and all were followed-up with telephone interviews after one year. The third study was cross-sectional, including 1148 women from Linköping, 50-64 years old, who participated in the Swedish CArdioPulmonary bioImage Study (SCAPIS). These women answered a questionnaire about menopausal status, vasomotor symptoms and menopausal hormone therapy use, and wore accelerometers for seven days to assess physical activity. The skin’s microcirculation was assessed at rest and during post-occlusive reactive hyperemia. Results Moderate to severe vasomotor symptoms per 24 hours decreased significantly more in the group of women randomized to resistance training compared with the control group (mean difference -2.7, 95% CI -4.2 to -1.3). The resistance training group improved in domains of menopause-specific health-related quality of life compared with the control group but there was little impact on generic health-related quality of life. In the qualitative study we found that the vasomotor symptoms acted as a “trigger” for the women to become motivated to exercise. Their motivation then evolved from being driven by hopes of symptom relief into being driven by a wish for general well-being, which was still a driving force after one year. Microvascular function did not differ between postmenopausal and premenopausal women, or between women with or without vasomotor symptoms or menopausal hormone therapy. Women with higher levels of objectively measured and self-reported physical activity had a better reactivity of the skin’s microcirculation. The differences remained significant after adjusting for BMI, smoking, hypertension, diabetes, and education. Conclusions Resistance training could be effective for decreasing vasomotor symptoms and improving some aspects of health-related quality of life in motivated postmenopausal women. The vasomotor symptoms themselves spurred motivation to exercise, indicating they present an opportunity to increase physical activity. When a woman seeks medical advice for vasomotor symptoms, this could be a chance for health care professionals to help her initiate or increase exercise. Women who performed more physical activity and exercise had better skin microvascular function, but no association with VMS was found. Future studies are needed to investigate what type and dose of exercise is the most effective to reduce vasomotor symptoms and whether there is a way to predict for whom exercise will or will not be an effective intervention.
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| 9. |
- Berin, Emilia, et al.
(författare)
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Resistance training for hot flushes in postmenopausal women: A randomised controlled trial
- 2019
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Ingår i: Maturitas. - : ELSEVIER IRELAND LTD. - 0378-5122 .- 1873-4111. ; 126, s. 55-60
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the effect of 15 weeks of resistance training on the frequency of moderate to severe hot flushes in postmenopausal women. Study design: Postmenopausal women with at least 4 moderate or severe hot flushes or night sweats per day day were randomized to a 15-week resistance training intervention or unchanged physical activity. Participants did not exercise regularly at baseline and had not used any therapy for hot flushes two months prior to study entry. The resistance training was performed three times per week and the program contained 8 exercises performed with 8-12 repetitions in 2 sets. Loads were set individually from eight-repetition maximum-strength tests and increased progressively. Main outcome measures: The primary outcome was change in mean moderate or severe hot flushes per day from baseline to week 15, assessed with symptom diaries. Secondary outcomes included change in hot flush score and time spent on physical activity. Results: Between November 19, 2013, and October 26, 2016, 65 women were enrolled; 58 completed the trial and were included in the analyses. The mean age was 55 and the mean number of moderate or severe hot flushes per day at baseline was 7.1; there were no baseline differences between groups. The frequency of hot flushes decreased more in the intervention group than in the control group (mean difference -2.7, 95% CI -4.2 to -1.3). The mean percentage change was -43.6% (-56.0 to -31.3) in the intervention group and -2.0% (16.4-12.4) in the control group. Conclusion: A 15-week resistance-training program decreased the frequency of moderate and severe hot flushes among postmenopausal women and could be an effective and safe treatment option to alleviate vasomotor symptoms.
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| 10. |
- Fernell, Elisabeth, 1948, et al.
(författare)
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Developmental profiles in preschool children with autism spectrum disorders referred for intervention.
- 2010
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Ingår i: Research in Developmental Disabilities. - : Elsevier BV. - 0891-4222 .- 1873-3379. ; 31:3, s. 790-799
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to characterize the panorama of developmental disorders in 208 preschool children with a clinical diagnosis of autism spectrum disorder (ASD), referred to a specialized centre, the Autism Centre for Young Children (ACYC), for intervention. At the centre, a research team examined all children according to structured protocols and interviews. All available test data from their assessments prior to referral were scrutinized. The boy:girl ratio was 5.5:1. In 22% of the total group a period of regression, including speech and language, had occurred. Epilepsy had been diagnosed in 6% of the children. In 38% of the children there was a definite or highly suspected learning disability/mental retardation according to cognitive test results. About the same proportion had a developmental delay that at the time of assessment could not be definitely classified and in 23% there were clear indications of a normal intellectual function. About 40% of the group exhibited hyperactivity. Differences in expressive vocabulary and adaptive functioning were strongly related to cognitive level. About 20% of the group had AD as the dominating developmental disorder, i.e., they represented a clinical picture of "classic" autism. The majority in this group also had learning disability. Another 20%, had ASD combined with a normal intellectual level, some of these conformed to the clinical picture of Asperger syndrome. In a relatively large group (more than half) learning disability or a general developmental delay was as evident as the ASD. In a smaller group (8%) ASD criteria were questionably met. In this group attention deficits in connection with speech and language problems were prominent. The highly individual developmental profiles seen in children with ASDs have to be taken into account when planning intervention and follow-up. The children's medical characteristics also vary considerably and will be detailed in a further report.
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| 11. |
- Fernell, Elisabeth, 1948, et al.
(författare)
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Early intervention in 208 Swedish preschoolers with autism spectrum disorder. A prospective naturalistic study.
- 2011
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Ingår i: Research in Developmental Disabilities. - : Elsevier BV. - 1873-3379 .- 0891-4222. ; 32:6, s. 2092-2101
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Tidskriftsartikel (refereegranskat)abstract
- Early intervention has been reported to improve outcome in children with autism spectrum disorders (ASDs). Several studies in the field have been randomized controlled trials (RCTs). The aim of this study was to assess ASD outcome in a large naturalistic study. Two hundred and eight children, aged 20-54 months, with a clinical diagnosis of ASD were given intervention and monitored prospectively in a naturalistic fashion over a period of 2 years. The toddlers were considered representative of all but the most severely multiple disabled preschool children with ASD in Stockholm county. They fell into three cognitive subgroups: one with learning disability, one with developmental delay, and one with normal intellectual functioning. Data on intervention type and intensity were gathered prospectively in a systematic fashion. Intervention was classified into intensive applied behaviour analysis (ABA) and non-intensive, targeted interventions, also based on ABA principles. Children were comprehensively assessed by a research team before the onset of intervention, and then, again, 2 years later. Change in Vineland adaptive behaviour scales composite scores from intake (T1) to leaving the study (T2) was set as the primary outcome variable. The research team remained blind to the type and intensity of interventions provided. One hundred and ninety-eight (95%) of the original samples stayed in the study throughout the whole 2-year period and 192 children had a complete Vineland composite score results both at T1 and T2. Vineland composite scores increased over the 2-year period. This increase was accounted for by the subgroup with normal cognitive functioning. There was no significant difference between the intensive and non-intensive groups. Individual variation was considerable, but no child in the study was "problem-free" at follow-up. Our data do not support that children with ASD generally benefit more from the most intensive ABA intervention programs than from less intensive interventions or targeted interventions based on ABA.
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| 12. |
- Gusarova, Viktoria, et al.
(författare)
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Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10-10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.
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| 13. |
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| 14. |
- Henning Loeb, Ingrid, 1962, et al.
(författare)
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Language and content learning in vocational subjects in Swedish upper secondary education
- 2016
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Ingår i: NORDYRK, konferens, Roskilde 8-10 juni 2016.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Vocational education (VET) is often regarded as a suitable ‘practical’ alternative for students who do not meet the eligibility requirements for higher education preparatory programs or for newly arrived young immigrants, a group of students which are increasing in upper secondary VET. However, the role of language in learning and the interrelationship between content and language has been pointed out by many (Fang & Schleppegrell 2008; Cummins 2003; Gibbons 2006). Also, the OECD and the Swedish National Board of Education advocates language and content learning through systematic support in all school subjects (OECD 2006; Skolverket 2012). Yet, there is no research on language and content learning in upper secondary VET. This paper draws on findings in a current pilot project of field studies in different VET programmes in four schools in western Sweden. Different techniques for field work (Czarniawska 2007) have been used, including audio recordings of VET teachers’ instructions and their dialogues with students. The researchers come from the educational sciences and humanities. Practice theories in education (Kemmis & Smith 2008) and systemic functional linguistics (Rothery 1996) are used for analysis. The paper will present some findings of critical aspects and examples that enable language and content learning.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Holm, Lotta, et al.
(författare)
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Quantitative Structure-Activity Relationship of Peptides Binding to the Class II Major Histocompatibility Complex Molecule A(q) Associated with Autoimmune Arthritis.
- 2007
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 1520-4804 .- 0022-2623. ; 50:9, s. 2049-2059
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Tidskriftsartikel (refereegranskat)abstract
- Presentation of (glyco)peptides by the class II major histocompatibility complex molecule Aq to T cells plays a central role in collagen-induced arthritis, an animal model for the autoimmune disease rheumatoid arthritis. A peptide library was designed using statistical molecular design in amino acid space in which five positions in the minimal mouse collagen type II binding epitope CII260-267 were varied. A substantially reduced peptide library of 24 peptides with diverse and representative molecular characteristics was selected, synthesized, and evaluated for the binding strength to Aq. A multivariate QSAR model was established by correlating calculated descriptors, compressed to its principle properties, with the binding data using partial least-square regression. The model was successfully validated by an external test set. Interpretation of the model provided a molecular property binding motif for peptides interacting with Aq. The information may be useful in future research directed toward new treatments of rheumatoid arthritis.
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| 19. |
- Holm, Lotta, et al.
(författare)
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Side-chain and backbone amide bond requirements for glycopeptide stimulation of T-cells obtained in a mouse model for rheumatoid arthritis
- 2006
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Ingår i: Bioorganic & Medicinal Chemistry. - Oxford : Elsevier BV. - 0968-0896 .- 1464-3391. ; 14:17, s. 5921-5932
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Tidskriftsartikel (refereegranskat)abstract
- Collagen induced arthritis (CIA) is the most studied animal model for rheumatoid arthritis and is associated with the MHC class II molecule A(q). T-cell recognition of a peptide from type II collagen, C11256-270, bound to A(q) is a requirement for development of CIA. Lysine 264 is the major T-cell recognition site of C11256-270 and CIA is in particular associated with recognition of lysine 264 after posttranslational hydroxylation and subsequent attachment of a beta-D-galactopyranosyl moiety. In this paper we have studied the structural requirements of collagenous glycopeptides required for T-cell stimulation, as an extension of earlier studies of the recognition of the galactose moiety. Synthesis and evaluation of alanine substituted glycopeptides revealed that there are T-cells that only recognise the galactosylated hydroxylysine 264, and no other amino acid side chains in the peptide. Other T-cells also require glutamic acid 266 as a T-cell contact point. Introduction of a methylene ether isostere instead of the amide bond between residues 260 and 261 allowed weaker recognition by some, but not all, of the T-cells. Altogether, these results allowed us to propose a model for glycopeptide recognition by the T-cells, where recognition from one or the other side of the galactose moiety could explain the different binding patterns of the T-cells. (c) 2006 Elsevier Ltd. All rights reserved.
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| 20. |
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| 21. |
- Holm, Lotta, 1973-
(författare)
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The MHC-glycopeptide-T cell interaction in collagen induced arthritis : a study using glycopeptides, isosteres and statistical molecular design in a mouse model for rheumatoid arthritis
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1% of the population in the western world. It is characterised by a tissue specific attack of cartilage in peripheral joints. Collagen induced arthritis (CIA) is one of the most commonly used animal models for (RA), with similar symptoms and histopathology. CIA is induced by immunisation of mice with type II collagen (CII), and the immunodominant part was previously found to be located between residues 256-270. This thesis describes the interaction between the MHC molecule, glycopeptide antigens from CII and the T cells that is essential in development of CIA. The glycopeptide properties for binding to the mouse MHC molecule Aq have been studied, as well as interaction points in the glycopeptide that are critical for stimulation of a T-cell response. The thesis is based on five studies. In the first paper the minimal glycopeptide core, that is required for binding to the Aq molecule while still giving a full T cell response was determined. The second paper studied the roles of amino acid side-chains and a backbone amide bond as T-cell contact points. In the third paper the hydrogen bond donor-acceptor characteristics of the 4-OH galactose hydroxyl group of the glycopeptide was studied in detail. In the fourth paper we established a structure activity relationship (QSAR model) for (glyco)peptide binding to the Aq molecule. Finally, the stereochemical requirements for glycopeptide binding to the Aq molecule and for T-cell recognition was studied in the fifth paper. The study was performed using collagen glycopeptide analogues, which were synthesised on solid phase. Amide bond and hydroxyl group isosteres were introduced for study of hydrogen bond donor-acceptor characteristics. Statistical methods were used to design a representative peptide test set and in establishing a QSAR model. The results give a deeper understanding of the interactions involved in the ternary MHC-glycopeptide-T cell complex. This information contributes to research directed towards finding new treatments for RA.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Kleberg, Agneta, et al.
(författare)
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Lower stress responses after newborn individualized developmental care and assessment program care during eye screening examinations for retinopathy of prematurity : A randomized study
- 2008
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 121:5, s. E1267-E1278
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE. Screening examination for retinopathy of prematurity is distressing and painful. The aim of the present study was to investigate whether a Newborn Individualized Developmental Care and Assessment Program intervention during a retinopathy of prematurity examination results in less adverse behavioral, pain, and stress responses as compared with standard care. METHODS. The first 2 eye examinations in 36 preterm infants were evaluated. The infants were randomly assigned at the first eye examination to receive either Newborn Individualized Developmental Care and Assessment Program care or standard care. At the second examination, crossover of subject assignment was performed. The assessments included behavioral responses, recordings of heart rate, respiration, and oxygenation, pain scores (premature infant pain profile), and salivary cortisol at defined time points up to 4 hours after the eye examination. The nursing support given during the eye examinations (intervention score) were scored using predefined criteria. RESULTS. Altogether, 68 examinations were evaluated. Newborn Individualized Developmental Care and Assessment Program care was associated with better behavioral scores during the examination but there was no difference in heart rate, respiratory rate, oxygenation, or premature infant pain profile score between the 2 care strategies before or after the eye examination. Salivary cortisol increased from baseline to 30 minutes after the eye examination independent of care strategy and decreased significantly between 30 and 60 minutes when infants were subjected to Newborn Individualized Developmental Care and Assessment Program care but not after standard care. During the study period the intervention score for standard care increased and approached the score for Newborn Individualized Developmental Care and Assessment Program care at the later eye examinations. CONCLUSION. A Newborn Individualized Developmental Care and Assessment Program-based intervention during eye examination does not decrease pain responses but results in faster recovery, as measured by lower salivary cortisol 60 minutes after the examination. The differences were seen despite the influence from the Newborn Individualized Developmental Care and Assessment Program intervention on the standard care treatment that occurred during the study period.
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| 27. |
- Klintwall, Lars, et al.
(författare)
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Sensory abnormalities in autism. A brief report.
- 2011
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Ingår i: Research in Developmental Disabilities. - : Elsevier BV. - 0891-4222 .- 1873-3379. ; 32:2, s. 795-800
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Tidskriftsartikel (refereegranskat)abstract
- Sensory abnormalities were assessed in a population-based group of 208 20-54-month-old children, diagnosed with autism spectrum disorder (ASD) and referred to a specialized habilitation centre for early intervention. The children were subgrouped based upon degree of autistic symptoms and cognitive level by a research team at the centre. Parents were interviewed systematically about any abnormal sensory reactions in the child. In the whole group, pain and hearing were the most commonly affected modalities. Children in the most typical autism subgroup (nuclear autism with no learning disability) had the highest number of affected modalities. The children who were classified in an "autistic features" subgroup had the lowest number of affected modalities. There were no group differences in number of affected sensory modalities between groups of different cognitive levels or level of expressive speech. The findings provide support for the notion that sensory abnormality is very common in young children with autism. This symptom has been proposed for inclusion among the diagnostic criteria for ASD in the upcoming DSM-V.
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| 28. |
- Lindh Åstrand, Lotta, et al.
(författare)
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Use of hormone therapy (HT) among Swedish women with contraindications - A pharmacoepidemiological cohort study
- 2019
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Ingår i: Maturitas. - : ELSEVIER IRELAND LTD. - 0378-5122 .- 1873-4111. ; 123, s. 55-60
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess how women in Sweden with breast cancer (BC), endometrial cancer (EC), and/or pulmonary embolism (PE) were dispensed menopausal hormone therapy (HT). Study design: A retrospective study of Swedish women aged 40 years or more on 31 December 2005 (n = 2,863,643), followed through to December 2011. The study analysed three mandatory national healthcare registries: the Swedish Prescribed Drug Register, the National Inpatient Register and the Cancer Register. New users were defined as having a first dispensation after at least a 9-month break, and thus were possible to identify from April 2006. New users with at least one of the diagnoses BC, EC or PE before the first dispensation were classified as having a relative or absolute contraindication for HT. Main outcome measures: The relative risks of having HT dispensed after being diagnosed with BC, EC and/or PE. Results: In total, 171,714 women had at least one of the diagnoses BC, EC or PE. The relative risk of having hormone therapy dispensed (current and new users) after being diagnosed with any of the diagnoses was significantly lower (PE, IRR 0.11, 95% CI 0.10-0.12;/ BC, IRR 0.12, 95% CI 0.11-0.13; EC, IRR 0.43, CI 0.40-0.46) than for women without these diagnoses. Conclusions: One in about 250 women started treatment with HT after being diagnosed with BC, PE or EC. Swedish prescribers seem to be well aware of the recommendations for HT use in women with contraindications. A few women, however, are prescribed HT despite having BC, EC or PE, possibly after careful evaluation of the risks and benefits and giving informed consent. Women with a history of PE were prescribed transdermal HT to a larger extent than women in general, in line with results from observational studies.
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| 29. |
- Liu, Haoyu, et al.
(författare)
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Growth Performance, digestibility and Gut Development of Broiler Chickens on Diets with Inclusion of Chicory (Cichorium intybus L.)
- 2011
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Ingår i: Poultry Science. - : Elsevier BV. - 0032-5791 .- 1525-3171. ; 90, s. 815-823
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Tidskriftsartikel (refereegranskat)abstract
- A total of 256 broiler chickens (1 d old) were used in a 32-d growth trial to study the effects of chicory (Cichorium intybus L.) forage and root inclusion on growth performance, digestibility, and gut development. The chicory forage originated from 2 harvests (June and September) and was included at 60 and 120 g/kg. The chicory root was included alone at 60 g/kg or together with chicory forage, from both harvests, in equal amounts (60 g/kg). The cereal-based control diet and 7 experimental diets were fed to each of 4 pens of chickens (8 chickens/pen). A higher BW gain and lower feed conversion ratio were found at 13 d of age in chickens fed the 60 g/kg chicory forage diet (P <= 0.05), whereas performance did not differ between the control and 60 g/kg chicory root diets. In contrast, a lower performance and digestibility of DM, organic matter, and ANTE as well as a thinner cecal mucosa layer were found for the 120 g/kg chicory forage diet (P <= 0.05). No diet effects on organ parameters or on pH of cecum digesta were detected. The soluble nonstarch polysaccharides fractions of chicory forage did not have any major negative effects on performance and gut development, and chicory forage from the September harvest was seen to have a higher nutritional value than that from the June harvest. Thus, results from the current study suggest that chicory forage is a potentially useful fiber-rich feed ingredient with high palatability for broiler chickens.
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| 30. |
- Lumbers, R. T., et al.
(författare)
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The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
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Tidskriftsartikel (refereegranskat)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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| 31. |
- Nygren, David, et al.
(författare)
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Proteomic characterization of plasma in Lemierre's syndrome
- 2024
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 124:05, s. 432-440
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Tidskriftsartikel (refereegranskat)abstract
- Background The underlying mechanisms of thrombosis in Lemierre's syndrome and other septic thrombophlebitis are incompletely understood. Therefore, in this case-control study we aimed to generate hypotheses on its pathogenesis by studying the plasma proteome in patients with these conditions. Methods All patients with Lemierre's syndrome in the Skåne Region, Sweden were enrolled prospectively during 2017-2021 as cases. Age-matched patients with other severe infections were enrolled as controls. Patient plasma samples were analyzed using label-free data-independent acquisition liquid chromatography tandem mass spectrometry. Differentially expressed proteins in Lemierre's syndrome vs. other severe infections were highlighted. Functions of differentially expressed proteins were defined based on a literature search focused on previous associations with thrombosis. Results Eight patients with Lemierre's syndrome and 15 with other severe infections were compared. Here, 20/449 identified proteins were differentially expressed between the groups. Of these, 14/20 had functions previously associated with thrombosis. 12/14 had a suggested prothrombotic effect in Lemierre's syndrome, whereas 2/14 had a suggested antithrombotic effect. Conclusion Proteins involved in several thrombogenic pathways were differentially expressed in Lemierre's syndrome compared to other severe infections. Among identified proteins, several were associated with endothelial damage, platelet activation and degranulation and warrant further targeted studies.
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| 32. |
- Shah, S, et al.
(författare)
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Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
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| 33. |
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| 34. |
- Strömsten, Lotta MJ, 1979-, et al.
(författare)
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Assessment of self-conscious emotions : a Swedish psychometric and structure evaluation of the test of self-conscious affect (TOSCA)
- 2009
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 50:1, s. 71-77
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Tidskriftsartikel (refereegranskat)abstract
- The Test of Self-Conscious Affect (TOSCA) is a well-established scenario-based questionnaire assessing self-conscious emotions, such as shame and guilt, which have been shown to be differentially associated with a variety of functional, motivational, behavioral and health outcomes. The aim of this study was to evaluate the psychometric properties and internal structure of a Swedish version of TOSCA in a sample of 361 healthy adults. The psychometric properties and internal consistency of the Swedish version were at level with the original US TOSCA version for shame, guilt and detachment. The internal structure of the Swedish version was acceptable for shame, guilt and detachment but contained shortcomings in assessment of externalization.
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| 35. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 36. |
- Ward, Liam, 1989-, et al.
(författare)
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Does resistance training have an effect on levels of ferritin and atherogenic lipids in postmenopausal women? - A pilot trial
- 2020
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to determine if 15 weeks of resistance training (RT) can alter the levels of blood lipids, body iron status, and oxidative stress in postmenopausal women with vasomotor symptoms. Postmenopausal women enrolled in a randomised controlled trial were allocated to either a sedentary control group (n=29) or a RT group (n=26). Blood samples were taken at week-0 and week-15 for all participants. Blood lipids and iron status were measured via routine clinical analyses. Immunoassays were used to measure oxidative stress markers. The RT group, with good compliance, was associated with significant reductions in ferritin, total cholesterol, low-density lipoprotein, and non-high-density lipoprotein cholesterol. Moreover, ferritin was positively correlated with atherogenic lipids while negatively correlated with high-density lipoprotein in RT women. This occurred without alterations in serum iron, transferrin, transferrin-saturation, C-reactive protein and oxidative stress markers. No differences were found in control women. This study suggests that RT in postmenopausal women both reduces levels of ferritin and counteracts atherogenic lipid profiles independent of an apparent oxidative mechanism. RT may be a beneficial intervention in postmenopausal women via an interaction between ferritin and lipids; however, further investigation in a larger cohort is essential.
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| 37. |
- Ward, Liam, et al.
(författare)
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Resistance training decreases plasma levels of adipokines in postmenopausal women
- 2020
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Ingår i: Scientific Reports. - : NATURE RESEARCH. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Physical inactivity and the onset of menopause increase the risk of cardiovascular disease amongst postmenopausal women. We aim to investigate the effect of resistance training (RT) on plasma levels of selected cytokines, adipokines, myokines, and sex hormones in postmenopausal women with vasomotor symptoms. This was a sub-study of a randomised controlled trial investigating the effects of RT on vasomotor symptoms in postmenopausal women. Women were randomised to join a 15-week RT program (n=26) or remain sedentary as control (n=29). Venous blood samples were taken at week-0 and week-15 for all participants. Enzyme-linked immunosorbent assays and multiple bead assays were used to measure cytokines, adipokines, myokines, and sex hormones in plasma. Plasma measurements of 16 of 33 analytes were within detectable limits. After adjusting for good compliance in the RT group (58% of RT participants), after 15 weeks, significantly lower plasma levels of adiponectin (p<0.001), lipocalin-2 (p<0.01) and resistin (p=0.04) were found. Comparing control and RT women, using change-over-time values, significant increases in median testosterone and sex hormone binding globulin levels were seen in RT women. RT intervention lowers the levels of adipokines, particularly adiponectin, in postmenopausal women with vasomotor symptoms. These results were secondary outcomes of a clinical trial, and further investigations in a larger cohort are essential with the additional control of diet control and body composition analyses. Nevertheless, our study shows RT may be a beneficial intervention in reducing inflammation amongst postmenopausal women.
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| 38. |
- West, Janne, et al.
(författare)
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Body Composition Analysis Combined with Individual Muscle Measurements using Dixon-MRI
- 2017
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Konferensbidrag (refereegranskat)abstract
- Body composition analysis is increasingly important for diagnosis and follow-up in many patient groups and medical conditions. The combined fat and muscle quantification on global and regional level is not commonly reported. In this study a Dixon-MRI based acquisition and body composition analysis was extended to quantify individual muscles. Test-retest reliability was established in a clinically relevant group of 36 postmenopausal women. This method enables advanced phenotyping combined with measurements of specific muscles to target clinical questions.
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| 39. |
- West, Janne, 1982-, et al.
(författare)
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Precision of MRI-based body composition measurements of postmenopausal women
- 2018
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Ingår i: PLOS ONE. - San Francisco, United States : Public Library of Science. - 1932-6203. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To determine precision of magnetic resonance imaging (MRI) based fat and muscle quantification in a group of postmenopausal women. Furthermore, to extend the method to individual muscles relevant to upper-body exercise. Materials and methods This was a sub-study to a randomized control trial investigating effects of resistance training to decrease hot flushes in postmenopausal women. Thirty-six women were included, mean age 56 +/- 6 years. Each subject was scanned twice with a 3.0T MR-scanner using a whole-body Dixon protocol. Water and fat images were calculated using a 6-peak lipid model including R2*-correction. Body composition analyses were performed to measure visceral and subcutaneous fat volumes, lean volumes and muscle fat infiltration (MFI) of the muscle groups thigh muscles, lower leg muscles, and abdominal muscles, as well as the three individual muscles pectoralis, latissimus, and rhomboideus. Analysis was performed using a multi-atlas, calibrated water-fat separated quantification method. Liver-fat was measured as average proton density fat-fraction (PDFF) of three regions-of-interest. Precision was determined with Bland-Altman analysis, repeatability, and coefficient of variation. Results All of the 36 included women were successfully scanned and analysed. The coefficient of variation was 1.1% to 1.5% for abdominal fat compartments (visceral and subcutaneous), 0.8% to 1.9% for volumes of muscle groups (thigh, lower leg, and abdomen), and 2.3% to 7.0% for individual muscle volumes (pectoralis, latissimus, and rhomboideus). Limits of agreement for MFI was within +/- 2.06% for muscle groups and within +/- 5.13% for individual muscles. The limits of agreement for liver PDFF was within +/- 1.9%. Conclusion Whole-body Dixon MRI could characterize a range of different fat and muscle compartments with high precision, including individual muscles, in the study-group of postmenopausal women. The inclusion of individual muscles, calculated from the same scan, enables analysis for specific intervention programs and studies.
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