| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- Hagberg, Guri, et al.
(författare)
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No evidence for amyloid pathology as a key mediator of neurodegeneration post-stroke : a seven-year follow-up study
- 2020
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Ingår i: BMC Neurology. - : BioMed Central. - 1471-2377. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cognitive impairment (CI) with mixed vascular and neurodegenerative pathologies after stroke is common. The role of amyloid pathology in post-stroke CI is unclear. We hypothesize that amyloid deposition, measured with Flutemetamol (F-18-Flut) positron emission tomography (PET), is common in seven-year stroke survivors diagnosed with CI and, further, that quantitatively assessed F-18-Flut-PET uptake after 7 years correlates with amyloid-beta peptide (A beta(42)) levels in cerebrospinal fluid (CSF) at 1 year, and with measures of neurodegeneration and cognition at 7 years post-stroke.Methods: 208 patients with first-ever stroke or transient Ischemic Attack (TIA) without pre-existing CI were included during 2007 and 2008. At one- and seven-years post-stroke, cognitive status was assessed, and categorized into dementia, mild cognitive impairment or normal. Etiologic sub-classification was based on magnetic resonance imaging (MRI) findings, CSF biomarkers and clinical cognitive profile. At 7 years, patients were offered F-18-Flut-PET, and amyloid-positivity was assessed visually and semi-quantitatively. The associations between F-18-Flut-PET standardized uptake value ratios (SUVr) and measures of neurodegeneration (medial temporal lobe atrophy (MTLA), global cortical atrophy (GCA)) and cognition (Mini-Mental State Exam (MMSE), Trail-making test A (TMT-A)) and CSF A beta(42) levels were assessed using linear regression.Results: In total, 111 patients completed 7-year follow-up, and 26 patients agreed to PET imaging, of whom 13 had CSF biomarkers from 1 year. Thirteen out of 26 patients were diagnosed with CI 7 years post-stroke, but only one had visually assessed amyloid positivity. CSF A beta(42) levels at 1 year, MTA grade, GCA scale, MMSE score or TMT-A at 7 years did not correlate with F-18-Flut-PET SUVr in this cohort.Conclusions: Amyloid binding was not common in 7-year stroke survivors diagnosed with CI. Quantitatively assessed, cortical amyloid deposition did not correlate with other measures related to neurodegeneration or cognition. Therefore, amyloid pathology may not be a key mediator of neurodegeneration 7 years post-stroke.Trial registration: Clinicaltrials.gov(NCT00506818). July 23, 2007. Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007.
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| 5. |
- Kaas, Anne, et al.
(författare)
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Proinsulin, GLP-1, and glucagon are associated with partial remission in children and adolescents with newly diagnosed type 1 diabetes
- 2012
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Ingår i: Pediatric Diabetes. - : Wiley-Blackwell. - 1399-543X .- 1399-5448. ; 13:1, s. 51-58
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Proinsulin is a marker of beta-cell distress and dysfunction in type 2 diabetes and transplanted islets. Proinsulin levels are elevated in patients newly diagnosed with type 1 diabetes. Our aim was to assess the relationship between proinsulin, insulin dose-adjusted haemoglobin A1c (IDAA1C), glucagon-like peptide-1 (GLP-1), glucagon, and remission status the first year after diagnosis of type 1 diabetes.Methods: Juvenile patients (n = 275) were followed 1, 6, and 12 months after diagnosis. At each visit, partial remission was defined as IDAA1C = 9%. The patients had a liquid meal test at the 1-, 6-, and 12-month visits, which included measurement of C-peptide, proinsulin, GLP-1, glucagon, and insulin antibodies (IA).Results: Patients in remission at 6 and 12 months had significantly higher levels of proinsulin compared to non-remitting patients (p < 0.0001, p = 0.0002). An inverse association between proinsulin and IDAA1C was found at 1 and 6 months (p = 0.0008, p = 0.0022). Proinsulin was positively associated with C-peptide (p < 0.0001) and IA (p = 0.0024, p = 0.0068, p < 0.0001) at 1, 6, and 12 months. Glucagon (p < 0.0001 and p < 0.02) as well as GLP-1 (p = 0.0001 and p = 0.002) were significantly lower in remitters than in non-remitters at 6 and 12 months. Proinsulin associated positively with GLP-1 at 1 month (p = 0.004) and negatively at 6 (p = 0.002) and 12 months (p = 0.0002).Conclusions: In type 1 diabetes, patients in partial remission have higher levels of proinsulin together with lower levels of GLP-1 and glucagon compared to patients not in remission. In new onset type 1 diabetes proinsulin level may be a sign of better residual beta-cell function.
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| 6. |
- Rendtorff, Nanna D., et al.
(författare)
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Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment
- 2011
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Ingår i: American Journal of Medical Genetics. Part A. - : Wiley-Blackwell. - 1552-4825 .- 1552-4833. ; 155A:6, s. 1298-1313
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Tidskriftsartikel (refereegranskat)abstract
- Optic atrophy (OA) and sensorineural hearing loss (SNHL) are key abnormalities in several syndromes, including the recessively inherited Wolfram syndrome, caused by mutations in WFS1. In contrast, the association of autosomal dominant OA and SNHL without other phenotypic abnormalities is rare, and almost exclusively attributed to mutations in the Optic Atrophy-1 gene (OPA1), most commonly the p.R445H mutation. We present eight probands and their families from the US, Sweden, and UK with OA and SNHL, whom we analyzed for mutations in OPA1 and WFS1. Among these families, we found three heterozygous missense mutations in WFS1 segregating with OA and SNHL: p.A684V (six families), and two novel mutations, p.G780S and p.D797Y, all involving evolutionarily conserved amino acids and absent from 298 control chromosomes. Importantly, none of these families harbored the OPA1 p.R445H mutation. No mitochondrial DNA deletions were detected in muscle from one p.A684V patient analyzed. Finally, wolframin p.A684V mutant ectopically expressed in HEK cells showed reduced protein levels compared to wild-type wolframin, strongly indicating that the mutation is disease-causing. Our data support OA and SNHL as a phenotype caused by dominant mutations in WFS1 in these additional eight families. Importantly, our data provide the first evidence that a single, recurrent mutation in WFS1, p.A684V, may be a common cause of ADOA and SNHL, similar to the role played by the p.R445H mutation in OPA1. Our findings suggest that patients who are heterozygous for WFS1 missense mutations should be carefully clinically examined for OA and other manifestations of Wolfram syndrome.
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| 7. |
- 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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| 8. |
- Hansen, Kim, et al.
(författare)
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Updated framework on quality and safety in emergency medicine
- 2020
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Ingår i: Emergency Medicine Journal. - : BMJ Publishing Group Ltd. - 1472-0205 .- 1472-0213. ; 37:7, s. 437-442
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Quality and safety of emergency care is critical. Patients rely on emergency medicine (EM) for accessible, timely and high-quality care in addition to providing a 'safety-net' function. Demand is increasing, creating resource challenges in all settings. Where EM is well established, this is recognised through the implementation of quality standards and staff training for patient safety. In settings where EM is developing, immense system and patient pressures exist, thereby necessitating the availability of tiered standards appropriate to the local context.METHODS: The original quality framework arose from expert consensus at the International Federation of Emergency Medicine (IFEM) Symposium for Quality and Safety in Emergency Care (UK, 2011). The IFEM Quality and Safety Special Interest Group members have subsequently refined it to achieve a consensus in 2018.RESULTS: Patients should expect EDs to provide effective acute care. To do this, trained emergency personnel should make patient-centred, timely and expert decisions to provide care, supported by systems, processes, diagnostics, appropriate equipment and facilities. Enablers to high-quality care include appropriate staff, access to care (including financial), coordinated emergency care through the whole patient journey and monitoring of outcomes. Crowding directly impacts on patient quality of care, morbidity and mortality. Quality indicators should be pragmatic, measurable and prioritised as components of an improvement strategy which should be developed, tailored and implemented in each setting.CONCLUSION: EDs globally have a remit to deliver the best care possible. IFEM has defined and updated an international consensus framework for quality and safety.
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| 9. |
- 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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| 10. |
- Mortensen, Henrik B., et al.
(författare)
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New definition for the partial remission period in children and adolescents with type 1 diabetes
- 2009
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 32:8, s. 1384-1390
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To find a simple definition of partial remission in type 1 diabetes that reflects both residual beta-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS A total of 275 patients aged <16 years were followed from onset of type 1 diabetes. After 1, 6, and 12 months, stimulated C-peptide during a challenge was used as a measure of residual beta-cell function. RESULTS By multiple regression analysis, a negative association between stimulated C-peptide and A1C (regression coefficient -0.21, P < 0.001) and insulin dose (-0.94, P < 0.001) was shown. These results suggested the definition of an insulin dose-adjusted A1C (IDAA1C) as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)]. A calculated IDAA1C < or =9 corresponding to a predicted stimulated C-peptide >300 pmol/l was used to define partial remission. The IDAA1C < or =9 had a significantly higher agreement (P < 0.001) with residual beta-cell function than use of a definition of A1C < or =7.5%. Between 6 and 12 months after diagnosis, for IDAA1C < or =9 only 1 patient entered partial remission and 61 patients ended partial remission, for A1C < or =7.5% 15 patients entered partial remission and 53 ended, for a definition of insulin dose < or =0.5 units . kg(-1) . 24 h(-1) 5 patients entered partial remission and 66 ended, and for stimulated C-peptide (>300 pmol/l) 9 patients entered partial remission and 49 ended. IDAA1C at 6 months has good predictive power for stimulated C-peptide concentrations after both 6 and 12 months. CONCLUSIONS A new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual beta-cell function and has better stability compared with the conventional definitions.
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