| 11. |
- Gong, Tong, et al.
(author)
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Understanding the relationship between asthma and autism spectrum disorder : a population-based family and twin study
- 2022
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In: Psychological Medicine. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0033-2917. ; 53:7, s. 3096-3104
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Journal article (peer-reviewed)abstract
- Background: There is some evidence that autism spectrum disorder (ASD) frequently co-occurs with immune-mediated conditions including asthma. We aimed to explore the familial co-aggregation of ASD and asthma using different genetically informed designs. Methods: We first examined familial co-aggregation of asthma and ASD in individuals born in Sweden from 1992 to 2007 (n = 1 569 944), including their full- and half-siblings (n = 1 704 388 and 356 544 pairs) and full cousins (n = 3 921 890 pairs), identified using Swedish register data. We then applied quantitative genetic modeling to siblings (n = 620 994 pairs) and twins who participated in the Child and Adolescent Twin Study in Sweden (n = 15 963 pairs) to estimate the contribution of genetic and environmental factors to the co-aggregation. Finally, we estimated genetic correlations between traits using linkage disequilibrium score regression (LDSC). Results: We observed a within-individual association [adjusted odds ratio (OR) 1.33, 95% confidence interval (CI) 1.28-1.37] and familial co-aggregation between asthma and ASD, and the magnitude of the associations decreased as the degree of relatedness decreased (full-siblings: OR 1.44, 95% CI 1.38-1.50, maternal half-siblings: OR 1.28, 95% CI 1.18-1.39, paternal half-siblings: OR 1.05, 95% CI 0.96-1.15, full cousins: OR 1.06, 95% CI 1.03-1.09), suggesting shared familial liability. Quantitative genetic models estimated statistically significant genetic correlations between ASD traits and asthma. Using the LDSC approach, we did not find statistically significant genetic correlations between asthma and ASD (coefficients between -0.09 and 0.12). Conclusions: Using different genetically informed designs, we found some evidence of familial co-aggregation between asthma and ASD, suggesting the weak association between these disorders was influenced by shared genetics.
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| 12. |
- Hammarström, Mattias, et al.
(author)
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Side effects of low-dose tamoxifen : results from a six-armed randomised controlled trial in healthy women
- 2023
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In: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 129:1, s. 61-71
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Journal article (peer-reviewed)abstract
- Background: Adherence to adjuvant tamoxifen therapy is suboptimal, and acceptance of tamoxifen for primary prevention is poor. Published results indicate effect of low-dose tamoxifen therapy. Using questionnaire data from a randomised controlled trial, we describe side effects of standard and low-dose tamoxifen in healthy women. Methods: In the KARISMA trial, 1440 healthy women were randomised to 6 months of daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. Participants completed a 48-item, five-graded Likert score symptom questionnaire at baseline and follow-up. Linear regression models were used to identify significant changes in severity levels across doses and by menopausal status. Results: Out of 48 predefined symptoms, five were associated with tamoxifen exposure (hot flashes, night sweats, cold sweats, vaginal discharge and muscle cramps). When comparing these side effects in premenopausal women randomised to low doses (2.5, 5 mg) versus high doses (10, 20 mg), the mean change was 34% lower in the low-dose group. No dose-dependent difference was seen in postmenopausal women. Conclusions: Symptoms related to tamoxifen therapy are influenced by menopausal status. Low-dose tamoxifen, in contrast to high-dose, was associated with less pronounced side effects, a finding restricted to premenopausal women. Our findings give new insights which may influence future dosing strategies of tamoxifen in both the adjuvant and preventive settings. Trial registration: ClinicalTrials.gov ID: NCT03346200.
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| 13. |
- Hedman, Anna M., et al.
(author)
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Longitudinal plasma inflammatory proteome profiling during pregnancy in the Born into Life study
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- The maternal immune system is going through considerable changes during pregnancy. However, little is known about the determinants of the inflammatory proteome and its relation to pregnancy stages. Our aim was to investigate the plasma inflammatory proteome before, during and after pregnancy. In addition we wanted to test whether maternal and child outcomes were associated with the proteome. A cohort of 94 healthy women, enrolled in a longitudinal study with assessments at up to five time points around pregnancy, ninety-two inflammatory proteins were analysed in plasma with a multiplex Proximity Extension Assay. First, principal components analysis were applied and thereafter regression modelling while correcting for multiple testing. We found profound shifts in the overall inflammatory proteome associated with pregnancy stage after multiple testing (p<.001). Moreover, maternal body mass index (BMI) was associated with inflammatory proteome primarily driven by VEGFA, CCL3 and CSF-1 (p<.05). The levels of most inflammatory proteins changed substantially during pregnancy and some of these were related to biological processes such as regulation of immune response. Maternal BMI was significantly associated with higher levels of three inflammation proteins calling for more research in the interplay between pregnancy, inflammation and BMI.
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| 14. |
- Iresjö, Britt-Marie, 1963, et al.
(author)
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Acute appendicitis: A block-randomized study on active observation with or without antibiotic treatment.
- 2024
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In: Surgery. - 0039-6060. ; 175:4, s. 929-935
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Journal article (peer-reviewed)abstract
- Antibiotic treatment of unselected patients with acute appendicitis is safe and effective. However, it is unknown to what extent early provision of antibiotic treatment may represent overtreatment due to spontaneous healing of appendix inflammation. The aim of the present study was to evaluate the role of antibiotic treatment versus active in-hospital observation on spontaneous regression of acute appendicitis.Patients who sought acute medical care at Sahlgrenska University Hospital were block-randomized according to age (18-60 years) and systemic inflammation (C-reactive protein <60 mg/L, white blood cell <13,000/μL), in combination with clinical and abdominal characteristics of acute appendicitis. Study patients received antibiotic treatment and active observation, while control patients were allocated to classic active "wait and see observation" for either disease regression or the need for surgical exploration. According to our standard surgical care, certified surgeons in charge decided whether and when appendectomy was necessary. In total, 1,019 patients were screened for eligibility; 203 patients met inclusion criteria, 126 were accepted to participate, 29 declined, and 48 were missed for inclusion.The antibiotic group (n= 69) and the control group (n= 57) were comparable at inclusion. Appendectomy at first hospital stay was 28% and 53% for study and control patients (χ2, P < .004). Life table analysis indicated a time-dependent difference in the need for appendectomy during follow-up (P < .03). Antibiotics prevented surgical exploration and appendectomy by 72% to 50% compared to 47% to 37% in the control group across the time course follow-ups between 5 and 1,200 days.Early antibiotic treatment is superior to traditional "wait and see observation" to avoid surgical exploration and appendectomy.
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| 15. |
- Iresjö, Britt-Marie, 1963, et al.
(author)
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Preoperative supportive nutrition at major cancer surgery in weight-losing patients. Effects on muscle transcriptome (abstract 5-03). : Abstract 5-03, sid 2422
- 2023
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In: Journal of Cachexia, Sarcopenia and Muscle. - 2190-5991 .- 2190-6009.
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Conference paper (other academic/artistic)abstract
- Preoperative supportive nutrition at major cancer surgery in weight-losing patients: effects on muscle transcriptome Britt-Marie Iresjö and Ulrika Smedh and Cecilia Engström and Jan Persson and Christian Mårtensson and Kent Lundholm Department of Surgery, University of Gothenburg and Sahlgrenska University Hospital, Göteborg, Sweden Introduction: Recommendations of strict pre-operative fasting have later on become replaced by provision of carbohydrate rich nutrition drinks prior to surgery. Carbohydrate (cho) drinks are shown to reduce postoperative insulin resistance and thus assumed to improve post-surgical muscle protein metabolism with expectations to reduce morbidity and complication rate, though meta-analyses indicate few clinical benefits. However, such studies investigating skeletal muscle metabolism are lacking. Therefore, our study evaluates skeletal muscle transcriptome alterations with relevance to carbohydrate and protein metabolism, by two different nutrition interventions. Method: Patients scheduled for major upper gastrointestinal cancer surgery were asked to participate. Mean weight loss in the patient group was 7%. Provision of either oral carbohydrate -rich nutrition drinks (804 kcal cho/96 kcal protein) or provision of peripheral total parenteral nutrition (TPN) (400 kcal cho/180 kcal protein/350 kcal fat) were administered in a 12-h over-night period prior to surgery. The control group received infusion of clear fluids only. Arterial blood samples and abdominal muscle biopsies were collected at operation start (n = 38). Blood amino acids were quantified by LC–MS/MS and muscle mRNA transcripts were analysed with Agilent SurePrint G3 Human GE v3 8x60K Microarrays. Data evaluation was done in Genespring software v.14.9.1. Results: Statistical analyses indicated ~1200 transcripts as altered among groups (Anova, P < 0.05). Post-Hoc analyses indicated ~500 transcripts as altered by each nutrition protocol with most alterations specific to each treatment. The results indicate that both carbohydrate rich nutrition drinks and total parenteral nutrition influenced muscle glucose metabolism, while transcript alterations related to protein translation were induced by parenteral nutrition only. Conclusions: Carbohydrate rich drinks were not sufficient to sustainably support muscle metabolism and should not be recommended in combination with major cancer surgery.
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| 16. |
- Jägerskog, Ann-Sofie, 1977-
(author)
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Making Possible by Making Visible : Learning through Visual Representations in Social Science
- 2020
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Doctoral thesis (other academic/artistic)abstract
- This thesis focuses upon the relationship between teaching and learning of dynamic phenomena and processes in social science and the use of visual representations in social science teaching. Teaching in social science uses many visual representations, such as models, flowcharts and diagrams, in order to help students to grasp phenomena, structures and processes in society. However, it is a challenge to use a visual simplification of a complex reality without reducing its complexity, and we often do not know what understanding is facilitated or even hindered through the use of different visual representations. We thus need to identify the relationship between how the content is visually illustrated and composed (compositional structure) and how students understand the content visualised. We also need to improve our understanding of the relationship between visual representations used in teaching and the teaching-learning practices established in the classroom. This thesis aims to contribute to these areas, with a focus on visual representations of pricing in economics, as an example of a complex and dynamic process in social science.Paper I uses phenomenography and variation theory to investigate students’ conceptions of causal relationships in pricing. Causality was identified as a central dimension of variation in understanding pricing. Different conceptions of causality in pricing were identified in upper secondary students’ written answers and critical aspects of causal relationships in pricing were identified. Paper II compares the outcome of using two different visual representations of pricing. This paper draws attention to the ways in which these representations helped students to discern the critical aspects identified in Paper I. A causal loop diagram was considerably more effective than supply/demand graphs in helping students to discern the critical aspects of causal relationships in pricing. A conclusion drawn is that the compositional structure of a visual representation used in teaching plays a vital role for how students understood the content visualised and which aspects of the phenomenon are more easily discerned, and which are not. Paper III uses a practice theory perspective to deepen the understanding of the results from Paper II. Results from Paper III suggest that the causal loop diagram, to a greater extent than the graph, contributed to the establishing of an epistemic practice, a practice where knowledge was developed and transformed. This was for instance seen in the causal loop diagram affording discussions concerning the causal relationships and encouraging further questions and reflections. A conclusion drawn is that a visual representation as an action-mediating tool plays a central role in forming the teaching-learning practices established in the classroom.The results from the three papers are also discussed in relation to two challenges: (i) how simplified visualisations of complex processes and structures may facilitate students developing a qualified understanding of such processes and structures and (ii) how disciplinary developed visual representations, when used in social science teaching, may be used with a different goal than when used in the discipline, where they were developed. The contributions of this thesis are both empirical, theoretical and practical and several practical implications for teaching and learning in social science were identified.
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| 17. |
- Khan, Maria, et al.
(author)
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Reduced tumor growth in EP2 knockout mice is related to signaling pathways favoring an increase local anti-tumor immunity in the tumor stroma
- 2022
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In: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 47:6
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Journal article (peer-reviewed)abstract
- Inflammatory signaling through prostaglandin E2 receptor subtype 2 (EP2) is associated with malignant tumor growth in both experimental models and cancer patients. Thus, the absence of EP2 receptors in host tissues appears to reduce tumor growth and systemic inflammation by inducing major alterations in gene expression levels across tumor tissue compartments. However, it is not yet well‑established how signaling pathways in tumor tissue relate to simultaneous signaling alterations in the surrounding tumor‑stroma, at conditions of reduced disease progression due to decreased host inflammation. In the present study, wild‑type tumor cells, producing high levels of prostaglandin E2 (MCG 101 cells, EP2+/+), were inoculated into EP2 knockout (EP2‑/‑) and EP2 wild‑type (EP2+/+) mice. Solid tumors were dissected into tumor‑ and tumor‑stroma tissue compartments for RNA expression microarray screening, followed by metabolic pathway analyses. Immunohistochemistry was used to confirm adequate dissections of tissue compartments, and to assess cell proliferation (Ki‑67), prostaglandin enzymes (cyclooxygenase 2) and immunity biomarkers (CD4 and CD8) at the protein level. Microarray analyses revealed statistically significant alterations in gene expression in the tumor‑stroma compartment, while significantly less pathway alterations occurred in the tumor tissue compartment. The host knockout of EP2 receptors led to a significant downregulation of cell cycle regulatory factors in the tumor‑stroma compartment, while interferon γ‑related pathways, chemokine signaling pathways and anti‑tumor chemokines [chemokine (C‑X‑C motif) ligand 9 and 10] were upregulated in the tumor compartment. Thus, such gene alterations were likely related to reduced tumor growth in EP2‑deficient hosts. On the whole, pathway analyses of both tumor‑ and tumor‑stroma compartments suggested that absence of host EP2 receptor signaling reduces ‘remodeling’ of tumor microenvironments and increase local immunity, probably by decreased productions of stimulating growth factors, perhaps similar to well‑recognized physiological observations in wound healing.
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| 18. |
- Liu, Bojing, et al.
(author)
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β2-adrenoreceptor agonists, montelukast, and Parkinson's disease risk
- 2023
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In: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 93:5, s. 1023-1028
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Journal article (peer-reviewed)abstract
- Objective: This study was undertaken to examine the association between montelukast use, beta 2-adrenoreceptor (beta 2AR) agonist use, and later Parkinson disease (PD).Methods: We ascertained use of beta 2AR agonists (430,885 individuals) and montelukast (23,315 individuals) from July 1, 2005 to June 30, 2007, and followed 5,186,886 PD-free individuals from July 1, 2007 to December 31, 2013 for incident PD diagnosis. We estimated hazard ratios and 95% confidence intervals using Cox regressions.Results: We observed 16,383 PD cases during on average 6.1 years of follow-up. Overall, use of beta 2AR agonists and montelukast were not related to PD incidence. A 38% lower PD incidence was noted among high-dose montelukast users when restricted to PD registered as the primary diagnosis.Interpretation: Overall, our data do not support inverse associations between beta 2AR agonists, montelukast, and PD. The prospect of lower PD incidence with high-dose montelukast exposure warrants further investigation, especially with adjustment for high-quality data on smoking. ANN NEUROL 2023
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| 19. |
- Lofthouse, Rachel, et al.
(author)
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Pre-service Teachers' conceptions of their own learning : does context make a difference?
- 2021
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In: Research Papers in Education. - : Informa UK Limited. - 0267-1522 .- 1470-1146. ; 36:6, s. 682-703
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Journal article (peer-reviewed)abstract
- We present an analysis of pre-service teachers' (PSTs) conceptions of their own learning, focusing on relationships between where PSTs learn and conceptions of their own learning. Our data come from in-depth interviews carried out over a six-month period with PSTs on different routes into teaching. We identify four components of learning to teach: beliefs about knowledge for teaching and the focus, timing and self-determination of reflection. We found weak relationships between PSTs' conceptions and their route into teaching (led by a school or university) and stronger relationships between conceptions of their own learning and their experience of mentoring in school.
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| 20. |
- Lundholm, Cecilia, et al.
(author)
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Asthma and subsequent school performance at age 15-16 years : A Swedish population-based sibling control study
- 2020
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Asthma may negatively affect children's school performance, such as grades and exam results. Results from previous studies have shown varying results and may have suffered from confounding and other biases. We used a Swedish population-based cohort of 570,595 children with data on asthma (including severity and control) in Grades 7-8 and 9, school performance from Grade 9 (grade point sum, non-eligibility for upper secondary school and national test results) and measured confounders from national registers. We used sibling comparisons to account for unmeasured familial factors. Children with asthma and severe asthma performed slightly better in school than children without asthma when adjusting for measured confounders, but the associations were attenuated in sibling comparisons. In contrast, children with uncontrolled asthma performed slightly worse (e.g. Grade 9: βadj = -9.9; 95% CI -12.8 to -7.0; Cohen's d = 0.16). This association remained for uncontrolled asthma in Grade 9 in sibling comparisons (Grade 9: β = -7.7 points; 95% CI -12.6 to -2.6; Cohen's d = 0.12), but not for Grades 7-8. The attenuation of estimates when controlling for familial factors using sibling comparisons suggests that the differences were due to familial factors, rather than being causal. The remaining associations in sibling comparisons between uncontrolled asthma in Grade 9 and school performance are consistent with a causal association.
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