| 1. |
- Brynhildsen, Jan, 1962-, et al.
(author)
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Oral contraceptive use among female elite athletes and age-matched controls and its relation to low back pain
- 1997
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In: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 76:9, s. 873-878
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Journal article (peer-reviewed)abstract
- Background: Exogenous and endogenous female sex steroids may influence the risk of low back pain. The fact that back pain is a very common symptom during pregnancy supports this theory. Back pain is also more common among female than male athletes. Oral contraceptives have been suggested to increase the risk of low back pain.Objective: To evaluate whether the prevalence of low back pain is higher among oral contraceptive users than non-users and if it differs between women taking part in different sports.Methods: A questionnaire was sent to female elite athletes in volleyball (n=205), basketball (n=150), and soccer (n=361) as well as to age-matched controls (n=113). The questionnaire comprised questions about age, constitution, occupation, parity and use of contraceptive method as well as previous and current back pain and possible consequences of the back problems.Results: The response rate was 85%. Between 42% and 52% of the women in the different groups used oral contraceptives. The groups were similar in most background variables, except that the volleyball and basketball players were taller. The prevalence of current low back pain was between 21% and 34% in the different athlete groups with an average of 30%, whereas only 18% of the controls suffered from low back pain (p<0.01). The prevalence of low back pain within each group, athletes as well as controls, was similar in women who used, and did not use oral contraceptives.Conclusions: This study does not support the theory that low back pain is affected by the use of oral contraceptives. Instead, constitutional factors and mechanical stress during intense physical activity is probably more important.
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| 2. |
- Kalushkova, Antonia, et al.
(author)
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One Omics Approach Does Not Rule Them All : The Metabolome and the Epigenome Join Forces in Haematological Malignancies
- 2021
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In: EPIGENOMES. - : MDPI. - 2075-4655. ; 5:4
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Journal article (peer-reviewed)abstract
- Aberrant DNA methylation, dysregulation of chromatin-modifying enzymes, and microRNAs (miRNAs) play a crucial role in haematological malignancies. These epimutations, with an impact on chromatin accessibility and transcriptional output, are often associated with genomic instability and the emergence of drug resistance, disease progression, and poor survival. In order to exert their functions, epigenetic enzymes utilize cellular metabolites as co-factors and are highly dependent on their availability. By affecting the expression of metabolic enzymes, epigenetic modifiers may aid the generation of metabolite signatures that could be utilized as targets and biomarkers in cancer. This interdependency remains often neglected and poorly represented in studies, despite well-established methods to study the cellular metabolome. This review critically summarizes the current knowledge in the field to provide an integral picture of the interplay between epigenomic alterations and the cellular metabolome in haematological malignancies. Our recent findings defining a distinct metabolic signature upon response to enhancer of zeste homolog 2 (EZH2) inhibition in multiple myeloma (MM) highlight how a shift of preferred metabolic pathways may potentiate novel treatments. The suggested link between the epigenome and the metabolome in haematopoietic tumours holds promise for the use of metabolic signatures as possible biomarkers of response to treatment.
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| 3. |
- Kirvalidze, Mariam, et al.
(author)
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Effectiveness of integrated person-centered interventions for older people's care : Review of Swedish experiences and experts' perspective
- 2024
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In: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796.
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Journal article (peer-reviewed)abstract
- Older adults have multiple medical and social care needs, requiring a shift toward an integrated person-centered model of care. Our objective was to describe and summarize Swedish experiences of integrated person-centered care by reviewing studies published between 2000 and 2023, and to identify the main challenges and scientific gaps through expert discussions. Seventy-three publications were identified by searching MEDLINE and contacting experts. Interventions were categorized using two World Health Organization frameworks: (1) Integrated Care for Older People (ICOPE), and (2) Integrated People-Centered Health Services (IPCHS). The included 73 publications were derived from 31 unique and heterogeneous interventions pertaining mainly to the micro- and meso-levels. Among publications measuring mortality, 15% were effective. Subjective health outcomes showed improvement in 24% of publications, morbidity outcomes in 42%, disability outcomes in 48%, and service utilization outcomes in 58%. Workshop discussions in Stockholm (Sweden), March 2023, were recorded, transcribed, and summarized. Experts emphasized: (1) lack of rigorous evaluation methods, (2) need for participatory designs, (3) scarcity of macro-level interventions, and (4) importance of transitioning from person- to people-centered integrated care. These challenges could explain the unexpected weak beneficial effects of the interventions on health outcomes, whereas service utilization outcomes were more positively impacted. Finally, we derived a list of recommendations, including the need to engage care organizations in interventions from their inception and to leverage researchers' scientific expertise. Although this review provides a comprehensive snapshot of interventions in the context of Sweden, the findings offer transferable perspectives on the real-world challenges encountered in this field. image
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| 4. |
- Nilsson, Helena Jernmark, et al.
(author)
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The transcriptional coregulator NAB2 is a target gene for the Wilms' tumor gene 1 protein (WT1) in leukemic cells
- 2017
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:50, s. 87136-87150
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Journal article (peer-reviewed)abstract
- The Wilms' tumor gene 1 (WT1) is recurrently mutated in acute myeloid leukemia. Mutations and high expression of WT1 associate with a poor prognosis. In mice, WT1 cooperates with the RUNX1/RUNX1T1 (AML1/ETO) fusion gene in the induction of acute leukemia, further emphasizing a role for WT1 in leukemia development. Molecular mechanisms for WT1 are, however, incompletely understood. Here, we identify the transcriptional coregulator NAB2 as a target gene of WT1. Analysis of gene expression profiles of leukemic samples revealed a positive correlation between the expression of WT1 and NAB2, as well as a non-zero partial correlation. Overexpression of WT1 in hematopoietic cells resulted in increased NAB2 levels, while suppression of WT1 decreased NAB2 expression. WT1 bound and transactivated the proximal NAB2 promoter, as shown by ChIP and reporter experiments, respectively. ChIP experiments also revealed that WT1 can recruit NAB2 to the IRF8 promoter, thus modulating the transcriptional activity of WT1, as shown by reporter experiments. Our results implicate NAB2 as a previously unreported target gene of WT1 and that NAB2 acts as a transcriptional cofactor of WT1.
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| 5. |
- Strömberg, Thomas, et al.
(author)
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IGF-1 receptor tyrosine kinase inhibition by the cyclolignan PPP induces G2/M-phase accumulation and apoptosis in multiple myeloma cells.
- 2006
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 107:2, s. 669-78
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Journal article (peer-reviewed)abstract
- Emerging evidence suggests the insulin-like growth factor-1 receptor (IGF-1R) to be an important mediator of tumor-cell survival and resistance to cytotoxic therapy in multiple myeloma (MM). Recently, members of the cyclolignan family have been shown to selectively inhibit the receptor tyrosine kinase (RTK) activity of the IGF-1R beta-chain. The effects of the cyclolignan picropodophyllin (PPP) were studied in vitro using a panel of 13 MM cell lines and freshly purified tumor cells from 10 patients with MM. PPP clearly inhibited growth in all MM cell lines and primary MM samples cultured in the presence or absence of bone marrow stromal cells. PPP induced a profound accumulation of cells in the G(2)/M-phase and an increased apoptosis. Importantly, IGF-1, IGF-2, insulin, or IL-6 did not reduce the inhibitory effects of PPP. As demonstrated by in vitro kinase assays, PPP down-regulated the IGF-1 RTK activity without inhibiting the insulin RTK activity. This conferred decreased phosphorylation of Erk1/2 and reduced cyclin dependent kinase (CDK1) activity. In addition, the expression of mcl-1 and survivin was reduced. Taken together, we suggest that interfering with the IGF-1 RTK by using the cyclolignan PPP offers a novel and selective therapeutic strategy for MM.
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| 6. |
- Thajudeen, Shamnath
(author)
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A product platform approach to support the design phase of industrialised house building : A framework conceptualisation when using mixed production strategies
- 2023
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Doctoral thesis (other academic/artistic)abstract
- The ability to offer unique solutions that meet customer demands has been considered a competitive advantage in the industrialised house building (IHB) industry. However, IHB companies are struggling due to varying customer needs and the simultaneous need to fulfil legal regulations, market demands, and production constraints. This has forced companies to develop unique solutions for every housing project to satisfy individual requirements, which automatically drives them to follow an engineer-to-order (ETO)-based strategy. The high involvement of customers in the design process results in the need for considerable engineering activities to validate and adjust to the customer demands, thereby providing individualised solutions. Moreover, designers adopt different production strategies based on the degree of pre-engineering. Product platform approaches have been acknowledged as one of the prominent means to improve both internal and external efficiencies. However, the use of traditional platform-based strategies does not suffice for the design of ETO-based components in an IHB system. A systematic approach is required to align the product platform and different production strategies so that customer requirements can be easily managed. Thus, this research aims to outline the means to support the design phase of IHB by applying a product platform approach when using a mixed production strategy.A Swedish multi-storey house building company that uses a glulam-based post and beam building system was used as the main case in this research. Empirical data were collected mainly from interviews, observations, workshops, and document analysis. This research proposes a framework for the systematic development and use of the product platform by following an inductive approach. Further, a parametric design platform method is proposed to achieve a platform-based development for ETO-based components by identifying, formalising, and reusing the design assets. The findings reveal how the transition of production strategies can be managed with supporting tools and methods. Moreover, this thesis emphasizes the importance of adopting the design for manufacturing and assembly (DfMA) in IHB. In addition, the research contributes to the existing knowledge on product platforms in IHB by providing the context of mixed production strategies and best practices to improve the IHB design process.
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| 7. |
- Theorell, Tores, et al.
(author)
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The use of saliva steroids (cortisol and DHEA-s) as biomarkers of changing stress levels in people with dementia and their caregivers : A pilot study.
- 2021
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In: Science Progress. - : SAGE Publications. - 0036-8504 .- 2047-7163. ; 104:2
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Journal article (peer-reviewed)abstract
- The rationale was to explore the efficacy/sensitivity of using morning and evening cortisol levels as biomarkers for stress reduction in persons with dementia (PWDs) and their family caregivers (FCGs) participating in a music intervention program. Thirty-two PWD and their FGC were recruited to an 8-week, home-based music intervention program. Daily home-based collection of saliva samples took place at bedtime and upon awakening. Cortisol was analyzed in the morning and evening saliva samples and DHEA-s in the morning samples. Trends over 40 workdays (15-40 observations per subject) were assessed using linear regression analysis. Twenty-three PWD (72% of invited, 16 men and 7 women, age 69-93) and 24 caregivers (75%, 8 men and 16 women, age 37-90) completed the intervention for at least 6 weeks and were included in the analysis. One-fourth of the PWD and FCG had decreasing evening cortisol, accompanied by decreasing morning cortisol levels. In one-fourth of the participants the ratio between cortisol and DHEA-S in the morning samples was improved, indicating improved balance between energy mobilization and regeneration. Several participants showed no significant endocrine change. There was a statistically significant (two-sided test) correlation within the PWD-caregiver dyads in evening cortisol trend and a statistically significant decrease (two-sided test) in the morning-evening cortisol slope for the FCG group. Reduction in stress, as measured by evening cortisol, was observed in a substantial number of the participants. Recording endocrine stress is helpful for the unbiased assessment of the intervention.
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| 8. |
- Ullmark, Tove, et al.
(author)
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Distinct global binding patterns of the Wilms' tumor gene 1 (WT1) -KTS and +KTS isoforms in leukemic cells
- 2017
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 102:2, s. 336-345
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Journal article (peer-reviewed)abstract
- The zinc finger transcription factor Wilms' tumor gene 1 (WT1) acts as an oncogene in acute myeloid leukemia. A naturally occurring alternative splice event between zinc fingers three and four, removing or retaining three amino acids (+/-KTS), is believed to change the DNA binding affinity of WT1, although there are conflicting data regarding the binding affinity and motifs of the different isoforms. Increased expression of WT1 -KTS at the expense of WT1 +KTS isoform associates with poor prognosis in acute myeloid leukemia. We determined the genome-wide binding pattern of WT1 -KTS and WT1 +KTS in leukemic K562 cells by chromatin immunoprecipitation and deep sequencing (ChIP-seq). Motif discovery revealed distinct binding motifs for the isoforms, some of which have been previously reported as WT1 binding sites. We discovered that the WT1 -KTS isoform predominantly binds close to transcription start sites and to enhancers, in a similar fashion to other transcription factors, whereas WT1 +KTS binding is rather enriched within gene bodies. We observed a significant overlap between WT1 -KTS and WT1 +KTS target genes, despite the binding sites being distinct. Motif discovery revealed distinct binding motifs for the isoforms, some of which have been previously reported as WT1 binding sites. Additional analyses showed that both WT1 -KTS and WT1 +KTS target genes are more likely to be transcribed than non-targets, and are involved in cell proliferation, cell death, and development. Our study provides evidence that WT1 -KTS and WT1 +KTS share target genes yet still bind distinct locations, indicating isoform-specific regulation in transcription of genes related to cell proliferation and differentiation, consistent with involvement of WT1 in acute myeloid leukemia.
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