| 1. |
- Hansen, Lea B.S., et al.
(author)
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A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- © 2018, The Author(s). Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.
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| 2. |
- Hollestelle, Antoinette, et al.
(author)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Journal article (peer-reviewed)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 3. |
- Munch Roager, Henrik, et al.
(author)
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Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: A randomised cross-over trial
- 2019
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In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:1, s. 83-93
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Journal article (peer-reviewed)abstract
- Objective T o investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of =6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. Results 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. Conclusion C ompared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic lowgrade inflammation.
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| 4. |
- Pedersen, Helle Krogh, et al.
(author)
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Human gut microbes impact host serum metabolome and insulin sensitivity
- 2016
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 535:7612, s. 376-381
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Journal article (peer-reviewed)abstract
- Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
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| 5. |
- Rostgaard, Nina, et al.
(author)
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TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3)
- 2017
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 59, s. 1-221
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Journal article (peer-reviewed)abstract
- Single-nucleotide polymorphisms in the TMEM106B gene have been identified as a risk factor in frontotemporal dementia (FTD). The major allele of SNP rs3173615 is a risk factor in sporadic FTD, whereas the minor allele seems protective in GRN- and C9orf72-mediated FTD. The role of apolipoprotein E (ApoE) in FTD is uncertain, though an established risk factor in Alzheimer's disease. In a unique Danish family, inherited FTD is caused by a mutation in the CHMP2B gene located on chromosome 3 (FTD-3). In this family, both risk factors TMEM106B and ApoE were analyzed and correlated to age at onset (AAO) and progression in terms of age at institutionalization (AAI) and age at death (AAD). Although TMEM106B and CHMP2B share cellular function in that both localize to endolysosomes, TMEM106B genotypes appeared to have no influence on the clinical disease course. ApoE ε4 was found to be a protective factor with later AAO and AAI, whereas ε2 seemed to aggravate the disease with earlier AAO and AAD. These results indicate ApoE ε2 as a risk factor in FTD-3 and suggest a protective role of ε4.
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| 6. |
- Sievers, Susanne, et al.
(author)
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The multicopy sRNA LhrC controls expression of the oligopeptide-binding protein OppA in Listeria monocytogenes
- 2015
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In: RNA Biology. - [Sievers, Susanne; Lund, Anja; Menendez-Gil, Pilar; Nielsen, Aaraby; Storm Mollerup, Maria; Lambert Nielsen, Stine; Buch Larsson, Pernille; Borch-Jensen, Jonas; Kallipolitis, Birgitte Haahr] Univ Southern Denmark, Dept Biochem & Mol Biol, Odense, Denmark. [Sievers, Susanne] Ernst Moritz Arndt Univ Greifswald, Inst Microbiol, Greifswald, Germany. [Johansson, Joergen] Umea Univ, Dept Mol Biol, Umea, Sweden. : Informa UK Limited. - 1547-6286 .- 1555-8584. ; 12:9, s. 985-997
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Journal article (peer-reviewed)abstract
- Listeria monocytogenes is the causative agent of the foodborne disease listeriosis. During infection, L. monocytogenes produces an array of non-coding RNAs, including the multicopy sRNA LhrC. These five, nearly identical sRNAs are highly induced in response to cell envelope stress and target the virulence adhesin lapB at the post-transcriptional level. Here, we demonstrate that LhrC controls expression of additional genes encoding cell envelope-associated proteins with virulence function. Using transcriptomics and proteomics, we identified a set of genes affected by LhrC in response to cell envelope stress. Three targets were significantly down-regulated by LhrC at both the RNA and protein level: lmo2349, tcsA and oppA. All three genes encode membrane-associated proteins: A putative substrate binding protein of an amino acid ABC transporter (Lmo2349); the CD4+ T cell-stimulating antigen TcsA, and the oligopeptide binding protein OppA, of which the latter 2 are required for full virulence of L. monocytogenes. For OppA, we show that LhrC acts by direct base paring to the ribosome binding site of the oppA mRNA, leading to an impediment of its translation and a decreased mRNA level. The sRNA-mRNA interaction depends on 2 of 3 CU-rich regions in LhrC allowing binding of 2 oppA mRNAs to a single LhrC molecule. Finally, we found that LhrC contributes to infection in macrophage-like cells. These findings demonstrate a central role for LhrC in controlling the level of OppA and other virulence-associated cell envelope proteins in response to cell envelope stress.
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| 7. |
- Andersson, Jenny, et al.
(author)
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Decision‐Making in Seeking Emergency Care for Stroke Symptoms
- 2022
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In: Stroke: Vascular and Interventional Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 2694-5746. ; 2:6
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Journal article (peer-reviewed)abstract
- BackgroundPrevious studies have shown that rapid treatment for stroke, especially ischemic stroke, reduces mortality and disability. The focus has mainly been on reducing time from arrival at hospital to start of treatment. However, the main reason for delay is often time from symptom onset to arrival at hospital. This study therefore aimed to explore decision‐making processes after the onset of stroke symptoms in patients experiencing a first‐time stroke.MethodsWe included 36 patients aged 18 and older, all of whom were hospitalized with a first‐time stroke between October 2018 and April 2020. All patients were interviewed once within 4 weeks of symptom onset and before hospital discharge. Eligible patients were identified retrospectively through a targeted review of medical records. The data were collected and analyzed according to the grounded theory methodology.ResultsIn total, 43 potential patients were identified and asked to participate. Overall, 36 patients were included in the study: 17 women (median age 77.0 years, interquartile range 17.5) and 19 men (median age 65.7 years, interquartile range 17.2). All interviewees felt fear, and this affected their decision to seek emergency care. The decision‐making processes were described by the core category of “Acting on fear.” The reason for feeling frightened determined the actions taken. The reasons were sorted into 3 main categories: (1) “seeking care”–recognized stroke symptoms and acted immediately; (2) “pending and reluctance”–suspected stroke but awaited to seek care; and (3) “seeking an explanation”–confused by symptoms.ConclusionWe found that decision‐making when experiencing stroke symptoms was complex. All patients felt fear, which determined their actions. Some patients knew about stroke symptoms and acted immediately. Others suspected stroke but still chose to wait, whereas others were confused and tried to find answers. These results could contribute to form future awareness campaigns.
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| 8. |
- Andersson, Jenny, et al.
(author)
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Patient´s description of onset stroke symptoms : Oral Presentations. ESOC 2023 Abstract Book
- 2023
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In: European Stroke Journal. - : Sage Publications. - 2396-9873 .- 2396-9881. ; 8:2, s. 427-427
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Journal article (peer-reviewed)abstract
- Background and aims: Stroke symptoms vary and could be hard to recognize. In addition, stroke severity has decreased according to the National Institutes of Health Stroke Scale (NISSH), with less pronounced symptoms expression. Knowledge on the patient’s description of stroke symptoms is therefore needed. The aim was to describe patient’s symptoms at stroke onset.Methods: A qualitative content analysis was used. Data were collected through individual interviews with 27 patients (16 men and 11 women, median age 70.4 years). All patients were hospitalized with a first-time stroke. The interviews were conducted within 4 weeks of symptoms onset and before hospital discharge.Results: All patients had symptoms that affected their daily life. Some patients described having multiple symptoms at the same time, others had symptoms that began insidiously and worsened over time. Symptoms such as overwhelming fatigue or nausea were described as Premonition of becoming ill, feeling unwell or that something was wrong. Motoric bodily changes were multifaceted as slurred speech or dizziness, balance difficulties and losing control of the body or motor dysfunction. But also, that the surroundings were distorted, and solid objects moved around. Symptoms of Dazed and affected senses included confusion and visual impairment or headache.Conclusions: Stroke is a complex disease with several different symptoms’ expressions and could be difficult to recognize, especially when symptoms are less typical or perceived as not serious. Increased awareness of stroke symptoms among caregivers and among members of the community is important and needed.
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| 9. |
- Andersson, Jenny, et al.
(author)
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Symptoms at stroke onset as described by patients: a qualitative study
- 2024
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In: BMC Neurology. - : Springer Nature. - 1471-2377. ; 24:1
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Journal article (peer-reviewed)abstract
- Background: Stroke is a common and severe disease that requires prompt care. Symptom expressions as one-sidedweakness and speech difficulties are common and included in public stroke campaigns. For some patients stroke canpresent with subtle and less common symptoms, difficult to interpret. The symptom severity assessed by the NationalInstitutes of Health Stroke Scale has decreased, and symptoms at onset may have changed. Therefore, we aimed toinvestigate how patients describe their symptoms at the onset of a first-time stroke.Methods:The study used a qualitative descriptive design and conventional content analysis. Data were collectedthrough recorded interviews with 27 patients aged 18 years and older hospitalised with a first-time stroke betweenOctober 2018 and April 2020. Data were analysed on a manifest level.Results: Symptoms at stroke onset were presented in two themes: Altered Reality and Discomfort and Changed BodyFunctions and described in five categories. Various types of symptoms were found. All symptoms were perceivedas sudden, persistent, and never experienced before and this appear as a “red thread” in the result. Regardless ofsymptom expressions, no specific symptom was described as more severe than another.Conclusions: Stroke symptoms were described with a variety of expressions. Many described complex symptomsnot typical of stroke, which can make it difficult to recognise the symptoms as a stroke and delay medical care. Publicstroke campaigns should emphasize the importance of seeking medical care at the slightest suspicion of stroke andcould be designed to help achieve this.
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| 10. |
- Baranowska, Julia, et al.
(author)
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Associations between medical therapy after surgical aortic valve replacement for aortic stenosis and long-term mortality: a report from the SWEDEHEART registry.
- 2022
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In: European heart journal. Cardiovascular pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 8:8, s. 837-846
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Journal article (peer-reviewed)abstract
- The association between use of statins, renin-angiotensin system (RAS) inhibitors and/or β-blockers and long-term mortality in patients with aortic stenosis who underwent surgical aortic valve replacement (SAVR) is unknown.All patients with aortic stenosis who underwent isolated first time SAVR in Sweden from 2006 to 2017 and survived six months after discharge were included. Individual patient data from four mandatory nationwide registries were merged. Cox proportional hazards models, with time-updated data on medication status and adjusted for age, sex, comorbidities, type of prosthesis, and year of surgery, were used to investigate associations between dispensed statins, RAS inhibitors, and β-blockers, and all-cause mortality. In total, 9553 patients were included, and median follow-up time was 4.9 years (range 0-11); 1738 patients (18.2%) died during follow-up. Statins were dispensed to 49.1% and 49.0% of the patients within six months of discharge from hospital and after ten years, respectively. Corresponding figures were 51.4% and 53.9% for RAS inhibitors, and 79.3% and 60.7% for β-blockers. Ongoing treatment was associated with lower mortality risk for statins [adjusted hazard ratio (aHR) 0.67 (95% confidence interval 0.60-0.74), p<0.001] and RAS inhibitors [aHR 0.84 (0.76-0.93), p<0.001] but not for β-blockers [aHR 1.17 (1.05-1.30), p=0.004]. The associations were robust in subgroups based on age, sex, and comorbidities (p for interactions>0.05).The results of this large population-based real-world study support the use of statins and RAS inhibitors for patients who underwent SAVR due to aortic stenosis.
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