| 31. |
- Karlsson, Ida K., et al.
(författare)
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Replicating associations between DNA methylation and body mass index in a longitudinal sample of older twins
- 2020
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Ingår i: International Journal of Obesity. - : Springer Nature. - 0307-0565 .- 1476-5497. ; 44:6, s. 1397-1405
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Tidskriftsartikel (refereegranskat)abstract
- Background:There is an important interplay between epigenetic factors and body weight, and previous work has identified ten sites where DNA methylation is robustly associated with body mass index (BMI) cross-sectionally. However, interpretation of the associations is complicated by the substantial changes in BMI often occurring in late-life, and the fact that methylation is often driven by genetic variation. This study therefore investigated the longitudinal association between these ten sites and BMI from midlife to late-life, and whether associations persist after controlling for genetic factors.Methods:We used data from 535 individuals (mean age 68) in the Swedish Adoption/Twin Study of Aging (SATSA) with longitudinal measures of both DNA methylation from blood samples and BMI, spanning up to 20 years. Methylation levels were measured with the Infinium Human Methylation 450K or Infinium MethylationEpic array, with seven of the ten sites passing quality control. Latent growth curve models were applied to investigate longitudinal associations between methylation and BMI, and between–within models to study associations within twin pairs, thus adjusting for genetic factors.Results:Baseline DNA methylation levels at five of the seven sites were associated with BMI level at age 65 (cg00574958 [CPT1A]; cg11024682 [SREBF1]), and/or change (cg06192883 [MYO5C]; cg06946797 [RMI2]; cg08857797 [VPS25]). For four of the five sites, the associations remained comparable within twin pairs. However, the effects of cg06192883 were substantially attenuated within pairs. No change in DNA methylation was detected for any of the seven evaluated sites.Conclusion:Five of the seven sites investigated were associated with late-life level and/or change in BMI. The effects for four of the sites remained similar when examined within twin pairs, indicating that the associations are mainly environmentally driven. However, the substantial attenuation in the association between cg06192883 and late-life BMI within pairs points to the importance of genetic factors in this association.
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| 32. |
- Kee, Nigel, et al.
(författare)
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Single-Cell Analysis Reveals a Close Relationship between Differentiating Dopamine and Subthalamic Nucleus Neuronal Lineages
- 2017
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Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909 .- 1875-9777. ; 20:1, s. 29-40
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Tidskriftsartikel (refereegranskat)abstract
- Stem cell engineering and grafting of mesencephalic dopamine (mesDA) neurons is a promising strategy for brain repair in Parkinson's disease (PD). Refinement of differentiation protocols to optimize this approach will require deeper understanding of mesDA neuron development. Here, we studied this process using transcriptome-wide single-cell RNA sequencing of mouse neural progenitors expressing the mesDA neuron determinant Lmx1a. This approach resolved the differentiation of mesDA and neighboring neuronal lineages and revealed a remarkably close relationship between developing mesDA and subthalamic nucleus (STN) neurons, while also highlighting a distinct transcription factor set that can distinguish between them. While previous hESC mesDA differentiation protocols have relied on markers that are shared between the two lineages, we found that application of these highlighted markers can help to refine current stem cell engineering protocols, increasing the proportion of appropriately patterned mesDA progenitors. Our results, therefore, have important implications for cell replacement therapy in PD.
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| 33. |
- Kjellsson, Sara, 1975-
(författare)
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Sick of Work? : Questions of Class, Gender and Self-Rated Health
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis examines two aspects of social inequalities in health with three empirical studies that are based on the Swedish Level of Living survey (LNU): The relationship between accumulated occupational class positions during adulthood and health and the class-specific nature of gender differences in health. Previous research continuously finds that there are health differences by class and gender, but less is known about the extent to which accumulated class experiences in adulthood are related to health or how gender differences vary by class. The overall conclusion in this thesis is that occupational class experiences matters for health, both as historical and current experiences. Furthermore, the results highlight the importance of taking class into consideration when examining health differences between men and women, as the mechanisms that underlie the gender gaps in health are not necessarily the same for all classes. The studies can be outlined as:Study I: Class differences in working conditions is a mechanism that underlies class inequalities in health. The working class is generally more exposed to adverse working environments than non-manual employees, and when the wear and tear of these conditions accumulate over time, the length of this exposure may contribute to class inequalities in health. Thereby, accumulated time in the working class is studied as a partial explanation for class differences in health. The results suggest that the duration of time in the working class is related to a higher probability of less than good self-rated general health (SRH), given current class position. This association was also found among individuals who were no longer in working class positions and thus show that duration of experience matters, both as current and past experience.Study II: The study addresses the research gap of class-specificity in gender health inequality and seeks to further disentangle class and gender by studying gender gaps separately by class. The results show that there are class-specific gender gaps for both SRH and musculoskeletal pain, while the gender gap in psychiatric distress appears to be more general across class. Working conditions do not explain the between-class differences in gender gaps but contribute to specific gender differences in health within classes.Study III: The labour market has changed over time and has “upgraded” the class structure while at the same time the share of women in paid employment has increased. Therefore, female health may be increasingly influenced by occupational factors, such as working conditions. This study explores the class-specific nature of gender differences and investigates musculoskeletal pain and working conditions among employed men and women within classes during a time-period that spanned more than 30 years. There were class-specific gender gaps in health throughout the period. The gender gap has increased more, and is wider, among non-manual employees compared to the working classes. This development could not be explained by changes in working conditions.
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| 34. |
- Linderholm, Klas R, et al.
(författare)
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Increased Levels of Kynurenine and Kynurenic Acid in the CSF of Patients With Schizophrenia
- 2012
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Ingår i: Schizophrenia Bulletin. - : Oxford University Press. - 0586-7614 .- 1745-1701. ; 38:3, s. 426-432
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Tidskriftsartikel (refereegranskat)abstract
- Background: The kynurenic acid (KYNA) hypothesis for schizophrenia is partly based on studies showing increased brain levels of KYNA in patients. KYNA is an endogenous metabolite of tryptophan (TRP) produced in astrocytes and antagonizes N-methyl-D-aspartate and alpha7* nicotinic receptors. Methods: The formation of KYNA is determined by the availability of substrate, and hence, we analyzed KYNA and its precursors, kynurenine (KYN) and TRP, in the cerebrospinal fluid (CSF) of patients with schizophrenia. CSF from male patients with schizophrenia on olanzapine treatment (n = 16) was compared with healthy male volunteers (n = 29). Results: KYN and KYNA concentrations were higher in patients with schizophrenia (60.7 +/- 4.37nM and 2.03 +/- 0.23nM, respectively) compared with healthy volunteers (28.6 +/- 1.44nM and 1.36 +/- 0.08nM, respectively), whereas TRP did not differ between the groups. In all subjects, KYN positively correlated to KYNA. Conclusion: Our results demonstrate increased levels of CSF KYN and KYNA in patients with schizophrenia and further support the hypothesis that KYNA is involved in the pathophysiology of schizophrenia.
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| 35. |
- Melander, Sara, et al.
(författare)
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Critical incidents and post-traumatic stress symptoms among experienced registered nurses during the COVID-19 pandemic : a cross-sectional study
- 2024
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Ingår i: International Journal of Nursing Studies Advances. - : Elsevier. - 2666-142X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Registered nurses working on the frontline during the COVID-19 pandemic encountered significant challenges, including exposure to critical incidents. Critical incidents refer to sudden unexpected clinical events that surpass an individual's ability to cope, leading to considerable psychological distress, which could potentially result in the development of post-traumatic stress disorder symptoms. Research has shown a high prevalence of post-traumatic stress disorder symptoms among healthcare workers, particularly those in close contact with COVID-19 patients.Objective: To assess the levels of post-traumatic stress symptoms among registered nurses in relation to exposure to working conditions during the COVID-19 pandemic, such as how much their work was affected by the pandemic, re-deployment, working hours hindering sufficient recovery between shifts and critical incidents.Design: Cross sectional study.Setting(s): The registered nurses working in multiple health care services covering all 21 geographic regions in Sweden.Participants: A total of 1,923 registered nurses, who are part of a Swedish national cohort and have been followed since their nursing education, were invited to participate in a survey in late September 2021 (15 to 19 years post graduation).Methods: The data were analyzed using descriptive statistics, unpaired t-tests, and one-way analysis of variance. Cohen's d was employed to quantify differences in mean levels between subgroups.Results: The response rate were 56.5 %. Over 50 % of experienced registered nurses reported significant disruptions to their work environments. In total, 85 % of registered nurses were exposed to at least one critical incident in their work during the pandemic, with 60 % facing organisational changes and nearly 50 % experiencing emotionally distressing situations. The exposure to work situations involving critical incidents consistently demonstrated strong associations with higher levels of post-traumatic stress disorder symptoms compared to those not exposed, with effect sizes ranging from moderate to high.Conclusions: This study underscores the profound impact that working conditions, such as redeployment and exposure to critical incidents, have on the mental health of registered nurses. We offer valuable insights into registered nurses’ pandemic-related challenges, highlighting the need for support and interventions to prevent and manage critical incidents, ultimately promoting their well-being. We also highlight the significance of thorough workforce readiness planning for future pandemics and other challenging health care scenarios, such as staff shortage.
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Odlén, Karin, et al.
(författare)
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Odontoblast-like MDPC-23 cells produce pro-inflammatory IL-6 in response to lipoteichoic acid and express the antimicrobial peptide CRAMP.
- 2020
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Ingår i: Acta Odontologica Scandinavica. - : Taylor & Francis. - 0001-6357 .- 1502-3850. ; 78:3, s. 210-216
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Tidskriftsartikel (refereegranskat)abstract
- Odontoblasts are thought to be involved in innate immunity but their precise role in this process is not fully understood. Here, we assess effects of lipopolysaccharide (LPS) and lipoteichoic acid (LTA), produced by Gram-negative and Gram-positive bacteria, respectively, on matrix metalloproteinase-8 (MMP-8), interleukin-6 (IL-6) and cathelin-related antimicrobial peptide (CRAMP) expression in odontoblast-like MDPC-23 cells. Gene activity and protein production was determined by quantitative real-time RT-PCR and ELISA, respectively. Cellular expression of CRAMP was determined by immunocytochemistry. Stimulation with LTA (5 and 25 µg/ml) but not LPS (1 and 5 µg/ml) for 24 h enhanced IL-6 mRNA expression. The LTA-induced up-regulation of IL-6 mRNA levels was associated with increased IL-6 protein levels. Stimulation with either LPS or LTA for 24 h lacked effect on both MMP-8 transcript and protein expression. Immunocytochemistry disclosed that MDPC-23 cells expressed immunoreactivity for CRAMP. MDPC-23 cells showed mRNA expression for CRAMP, but stimulation with either LPS or LTA did not modulate CRAMP transcript expression. We show that MDPC-23 cells possess immune-like cell properties such as LTA-induced IL-6 production and expression of the antimicrobial peptide CRAMP, suggesting that odontoblasts may modulate innate immunity via these mechanisms.
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| 40. |
- Oström, Maria, et al.
(författare)
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Retinoic acid promotes the generation of pancreatic endocrine progenitor cells and their further differentiation into beta-cells
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:7, s. e2841-
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Tidskriftsartikel (refereegranskat)abstract
- The identification of secreted factors that can selectively stimulate the generation of insulin producing beta-cells from stem and/or progenitor cells represent a significant step in the development of stem cell-based beta-cell replacement therapy. By elucidating the molecular mechanisms that regulate the generation of beta-cells during normal pancreatic development such putative factors may be identified. In the mouse, beta-cells increase markedly in numbers from embryonic day (e) 14.5 and onwards, but the extra-cellular signal(s) that promotes the selective generation of beta-cells at these stages remains to be identified. Here we show that the retinoic acid (RA) synthesizing enzyme Raldh1 is expressed in developing mouse and human pancreas at stages when beta-cells are generated. We also provide evidence that RA induces the generation of Ngn3(+) endocrine progenitor cells and stimulates their further differentiation into beta-cells by activating a program of cell differentiation that recapitulates the normal temporal program of beta-cell differentiation.
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