| 1. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 2. |
- Fan, Y., et al.
(författare)
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The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice
- 2023
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Ingår i: Nature Microbiology. - : Nature Publishing Group. - 2058-5276. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral-bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our 'omics' and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis. Faecal metagenomics and serum metabolomics reveal compositional and functional alterations in the gut microbiota of women with anorexia nervosa, and faecal transplants could transfer an anorexia-associated phenotype to germ-free mice.
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| 3. |
- Brial, François, et al.
(författare)
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Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health
- 2021
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:11, s. 2105-2114
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Gut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health.DESIGN: In 271 middle-aged non-diabetic Danish individuals, who were stratified on habitual dietary intake, we applied 1H-nuclear magnetic resonance (NMR) spectroscopy of urine samples and shotgun-sequencing-based metagenomics of the gut microbiome to explore links between the urine level of hippurate, measures of the gut microbiome, dietary fat and markers of metabolic health. In mechanistic experiments with chronic subcutaneous infusion of hippurate to high-fat-diet-fed obese mice, we tested for causality between hippurate and metabolic phenotypes.RESULTS: In the human study, we showed that urine hippurate positively associates with microbial gene richness and functional modules for microbial benzoate biosynthetic pathways, one of which is less prevalent in the Bacteroides 2 enterotype compared with Ruminococcaceae or Prevotella enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate concentration, independently of gene richness, accounts for links with metabolic health. In the high-fat-fed mice experiments, we demonstrate causality through chronic infusion of hippurate (20 nmol/day) resulting in improved glucose tolerance and enhanced insulin secretion.CONCLUSION: Our human and experimental studies show that a high urine hippurate concentration is a general marker of metabolic health, and in the context of obesity induced by high-fat diets, hippurate contributes to metabolic improvements, highlighting its potential as a mediator of metabolic health.
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| 4. |
- Darvish, Bijan, 1969-, et al.
(författare)
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Management of accidental dural puncture and post-dural puncture headache after labour : a Nordic survey
- 2011
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Ingår i: Acta Anaesthesiologica Scandinavica. - : The Acta Anaesthesiologica Scandinavica Foundation. - 0001-5172 .- 1399-6576. ; 55:1, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- Background: A major risk with epidural analgesia is accidental dural puncture (ADP), which may result in post-dural puncture headache (PDPH). This survey was conducted to explore the incidence of ADP, the policy for management of PDPH and the educational practices in epidural analgesia during labour in the Nordic countries.Methods: A postal questionnaire was sent to the anaesthesiologist responsible for Obstetric anaesthesia service in all maternity units (n=153) with questions relating to the year 2008.Results: The overall response rate was 93%. About 32% (22-47%) of parturients received epidural analgesia for labour. There were databases for registering obstetric epidural complications in 13% of Danish, 24% of Norwegian and Swedish, 43% of Finnish and 100% of hospitals in Iceland. The estimated incidence of ADP was 1% (n approximate to 900). Epidural blood patch (EBP) was performed in 86% (n approximate to 780) of the parturients. The most common time interval from diagnosis to performing EBP was 24-48 h. The success rate for EBP was > 75% in 67% (62-79%) of hospitals. The use of diagnostic CT/MRI before the first or the second EBP was exceptional. No major complication was reported. Teaching of epidurals was commonest (86%) in the non-obstetric population and 53% hospitals desired a formal training programme in obstetric analgesia.Conclusion: We found the incidence of ADP to be approximately 1%. EBP was the commonest method used for its management, and the success rate was high in most hospitals. Formal training in epidural analgesia was absent in most countries and trainees first performed it in the non-obstetric population.
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| 5. |
- Hamre, Charlotta, et al.
(författare)
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Balance and Gait After First Minor Ischemic Stroke in People 70 Years of Age or Younger : A Prospective Observational Cohort Study
- 2020
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Ingår i: Physical Therapy. - : American Physical Therapy Association. - 0031-9023 .- 1538-6724. ; 100:5, s. 798-806
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Two-thirds of patients with stroke experience only mild impairments in the acute phase, and the proportion of patients < 70 years is increasing. Knowledge about balance and gait and predictive factors are scarce for this group.OBJECTIVE: The objective of this study was to explore balance and gait in the acute phase and after 3 and 12 months in patients ≤70 years with minor ischemic stroke (National Institute of Health Stroke Scale (NIHSS) score ≤3). This study also explored factors predicting impaired balance after 12 months.DESIGN: This study was designed as an explorative longitudinal cohort study.METHODS: Patients were recruited consecutively from two stroke units. Balance and gait were assessed with the Mini-BESTest, Timed Up and Go (TUG), and preferred gait speed. Predictors for impaired balance were explored using logistic regression.RESULTS: This study included 101 patients. Mean (SD) age was 55.5 (11.4) years, 20% were female and mean (SD) NIHSS score was 0.6 (0.9) points. The Mini-BESTest, gait speed, and TUG improved significantly from the acute phase to 3 months, gait speed also improved from 3 to 12 months. At 12 months, 26% had balance impairments and 33% walked slower than 1.0 m/s. Poor balance in the acute phase (odds ratio =0.92, 95% CI = 0.85 - 0.95) was the only predictor of balance impairments (Mini-BESTest score ≤ 22) at 12 months post-stroke.LIMITATIONS: Limitations include lack of information about pre-stroke balance and gait impairment, and post-stroke exercise. Few women limits the generalizability.CONCLUSIONS: This study observed improvements in both balance and gait during the follow-up, still about one third had balance or gait impairments at 12 months post-stroke. Balance in the acute phase predicted impaired balance at 12 months.
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| 6. |
- Jendle, Johan, 1963-, et al.
(författare)
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Improved treatment satisfaction in patients with type 2 diabetes treated with once-weekly semaglutide in the SUSTAIN trials
- 2019
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Ingår i: Diabetes, obesity and metabolism. - : John Wiley & Sons. - 1462-8902 .- 1463-1326. ; 21:10, s. 2315-2326
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate treatment satisfaction with semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, versus placebo/active comparators in theSUSTAIN clinical trial programme.METHODS: In SUSTAIN 2-5 and 7, the Diabetes Treatment Satisfaction Questionnaire was used to evaluate patient-perceived treatment satisfaction, hyperglycaemia and hypoglycaemia. Post hoc subgroup analyses were conducted to explore the effects of gastrointestinal adverse events (GI AEs), weight loss (>= 5%) or achieving glycaemic (HbA1c < 7%) targets on treatment satisfaction.RESULTS: Overall treatment satisfaction increased from baseline to end of treatment with all treatments across trials. Improvements were significantly greater with semaglutide versus comparators/placebo in SUSTAIN 2-5 (all P < 0.05), and generally greater in patients who achieved versus did not achieve weight loss and glycaemic targets, often with greater improvements with semaglutide 1.0 mg versus comparator/placebo in both weight loss groups. In SUSTAIN 7, improvements in overall treatment satisfaction were generally similar between semaglutide and dulaglutide, irrespective of weight loss or glycaemic control. In SUSTAIN 7, changes in overall treatment satisfaction score were generally lower in patients with versus without GI AEs at week 16 (except dulaglutide 0.75 mg), but similar by week 40. Perceived hyperglycaemia was significantly reduced from baseline to end of treatment with semaglutide versus all comparators/placebo (all P < 0.05). No differences between treatments were observed for perceived hypoglycaemia.CONCLUSIONS: Semaglutide was associated with significantly greater (SUSTAIN 2-5) or similar (SUSTAIN 7) improvements in overall treatment satisfaction versus comparators/placebo. Improvements in overall treatment satisfaction were generally greater in patients achieving versus not achieving treatment targets. Clinicaltrials.gov: NCT01930188 (SUSTAIN 2), NCT01885208 (SUSTAIN 3), NCT02128932 (SUSTAIN 4), NCT02305381 (SUSTAIN 5) and NCT02648204 (SUSTAIN 7). EudraCT: 2012-004827-19 (SUSTAIN 2), 2012-004826-92 (SUSTAIN 3), 2013-004392-12 (SUSTAIN 4), 2013-004502-26 (SUSTAIN 5) and 2014-005375-91 (SUSTAIN 7).
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| 7. |
- Kaas, A., et al.
(författare)
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Association between age, IL-10, IFN gamma, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes
- 2012
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Ingår i: Diabetic Medicine. - : Wiley-Blackwell. - 0742-3071 .- 1464-5491. ; 29:6, s. 734-741
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The relation of disease progression and age, serum interleukin 10 (IL-10) and interferon gamma (IFNγ) and their genetic correlates were studied in paediatric patients with newly diagnosed Type 1 diabetes.METHODS: Two hundred and twenty-seven patients from the Hvidoere Study Group were classified in four different progression groups as assessed by change in stimulated C-peptide from 1 to 6 months. CA repeat variants of the IL-10 and IFNγ gene were genotyped and serum levels of IL-10 and IFNγ were measured at 1, 6 and 12 months.RESULTS: IL-10 decreased (P < 0.001) by 7.7% (1 month), 10.4% (6 months) and 8.6% (12 months) per year increase in age of child, while a twofold higher C-peptide concentration at 1 month (p = 0.06), 6 months (P = 0.0003) and 12 months (P = 0.02) was associated with 9.7%, 18.6% and 9.7% lower IL-10 levels, independent of each other. IL-10 concentrations did not associate with the disease progression groups. By contrast, IFNγ concentrations differed between the four progression groups at 6 and 12 months (P = 0.02 and P = 0.01, respectively); patients with rapid progressing disease had the highest levels at both time points. Distribution of IL-10 and IFNγ genotypes was equal among patients from the progression groups.CONCLUSION: IL-10 serum levels associate inversely with age and C-peptide. As age and C-peptide also associate, a triangular association is proposed. Genetic influence on IL-10 production seems to be masked by distinct disease mechanisms. Increased serum IFNγ concentrations associate with rapid disease progression. Functional genetic variants do not associate with a single progression pattern group, implying that disease processes override genetically predisposed cytokine production.
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| 8. |
- Mackey, A. L., et al.
(författare)
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Enhanced satellite cell proliferation with resistance training in elderly men and women
- 2007
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 17:1, s. 34-42
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In addition to the well-documented loss of muscle mass and strength associated with aging, there is evidence for the attenuating effects of aging on the number of satellite cells in human skeletal muscle. The aim of this study was to investigate the response of satellite cells in elderly men and women to 12 weeks of resistance training. Biopsies were collected from the m. vastus lateralis of 13 healthy elderly men and 16 healthy elderly women (mean age 76+/-SD 3 years) before and after the training period. Satellite cells were visualized by immunohistochemical staining of muscle cross-sections with a monoclonal antibody against neural cell adhesion molecule (NCAM) and counterstaining with Mayer's hematoxylin. Compared with the pre-training values, there was a significant increase (P<0.05) in the number of NCAM-positively stained cells per fiber post-training in males (from 0.11+/-0.03 to 0.15+/-0.06; mean+/-SD) and females (from 0.11+/-0.04 to 0.13+/-0.05). These results suggest that 12 weeks of resistance training is effective in enhancing the satellite cell pool in skeletal muscle in the elderly.
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| 9. |
- Sataøen, Hogne L., 1979-, et al.
(författare)
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Municipal risk communication challenges in the Nordic context : Organizing risk ownership
- 2024
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Ingår i: Risk, Hazards & Crisis in Public Policy. - : Policy Studies Organization. - 1944-4079 .- 1944-4079.
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Tidskriftsartikel (refereegranskat)abstract
- At a time when disasters, pandemics, pollution, and other crises gain prominence, local governments bear a crucial responsibility for effective risk communication. Yet, there remains a gap in our understanding of how municipalities approach risk communication before a crisis occurs. This qualitative study, involving seven focus groups and 29 semistructured interviews across two Nordic countries, raises questions about ownership of municipal risk communication: What challenges do municipalities face in managing ownership in risk communication? How does the organization of communication influence municipal risk communication? The results underscore three key considerations: First, there is a critical need for municipalities to engage in definitional clarification of risk and crisis communication. Establishing a shared understanding is paramount for effective communication strategies. Second, reframing uncertainty in municipal risk communication ownership as an opportunity is suggested. Embracing the inherent uncertainties and dependencies can offer a valuable perspective. Lastly, recognizing the underappreciation of risk communication emphasizes the imperative for municipal decision makers to address resource allocation issues. This involves ensuring that communication professionals have the confidence and resources needed, vis-à-vis other functions involved in risk management.
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| 10. |
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