| 1. |
- Forslund, Sofia K., et al.
(författare)
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Combinatorial, additive and dose-dependent drug–microbiome associations
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
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Tidskriftsartikel (refereegranskat)abstract
- During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
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| 2. |
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| 3. |
- Hasbak, Philip, et al.
(författare)
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The vasorelaxant effect of adrenomedullin, proadrenomedullin N-terminal 20 peptide and amylin in human skin
- 2006
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843. ; 99:2, s. 162-167
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Tidskriftsartikel (refereegranskat)abstract
- In this study we aimed to assess in vivo, the vasodilator effects of adrenomedullin, proadrenomedullin N-terminal 20 peptide (PAMP) and amylin in human skin vasculature and compare the responses to the effects mediated by the endogenenous neuropeptides calcitonin gene-related peptide (CGRP) and substance P and to examine the mRNA expression of calcitonin receptor-like receptor (CL-R) and receptor-activity modifying proteins, RAMP1, RAMP 2 and RAMP3 in human subcutaneous arteries. Changes in skin blood flow of the forearm were measured using a Laser Doppler Imager after intradermal injection of the peptides. The mRNA expression was assessed by real-time reverse transcriptase polymerase chain reaction (real-time PCR). CGRP, adrenomedullin and amylin induced concentration-dependent, long-lasting increases in skin blood flow. The response to PAMP was shorter in duration appearing similar to the transient response induced by substance P. PAMP (10(-6)-10(-5)M) caused distinct itch sensation and local erythema. This effect could be abolished when combining the histamine H-1-receptor antagonist mepyramin and PAMP. Real-time PCR data showed a higher level of mRNA for RAMP2 than CL-R, RAMP1 and RAMP3 in the tissue. Though the PCR data demonstrated the presence of mRNA for both CGRP1 and adrenomedullin receptors the rank order of potency (CGRP > adrenomedullin > amylin) for the blood flow increase indicated vasodilatation for these peptides was induced by activation of CGRP1 receptors. Intradermal injection of CGRP, adrenomedullin and amylin induces long lasting dilatation of human skin vasculature by activation of CGRP1 receptors. PAMP induces transient vasodilatation. PAMP but not CGRP, adrenomedullin and amylin causes itch sensation and local erythema. The transient effect on vasodilatation as response to PAMP is discussed.
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| 4. |
- Holst, Karen
(författare)
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Capturing the breath of the heart by magnetic resonance imaging : five-dimensional cardio-respiratory resolved cine imaging during free breathing
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiac imaging with cardiovascular magnetic resonance has the advantage of enabling dynamic visualizations, several quantifiable measures, and good soft-tissue contrast. However, a major drawback is the need for breath holding during many acquisitions to limit motion artifacts. Breath holding is often insufficient for artifact reduction and, furthermore, limits the image acquisition to only one respiratory phase. The aim of this work, therefore, was to develop a free breathing cardiovascular magnetic resonance imaging method for three-dimensional whole-heart cine imaging to measure the left ventricular (LV) volume in all combinations of cardiac and respiratory phases. Three-dimensional free-running acquisition was implemented as a double golden-angle radial trajectory. Respiratory self-gating signals were extracted from the center of k-space and used in combination with the measured electrocardiogram to bin data into combinations of cardiac and respiratory phase. Image volumes covering the whole heart were reconstructed and the LV endocardial border was manually segmented. In the first of four studies (Study I), the proposed technique was validated for LV volumes in end diastole (EDV) and systole in end expiration against gold standard two-dimensional breath held cine imaging in healthy volunteers. No difference was found between the two methods with regard to LV volumes and in test-retest variability of the volume measurements. Study II focused on the respiratory cycle where the same free breathing acquisition was used for measuring the respiratory-induced variation in LVEDV and the acquisition time was reduced from 40 minutes to 4.5 minutes by implementing parallel image reconstruction. The maximum respiratory variation in LVEDV was found to be 5-6% for healthy volunteers. An extension to the double golden-angle acquisition was implemented in Study III to reduce eddy current-induced artifacts, which improved image quality. A projection-based respiratory self-gating strategy was added to the improved trajectory in Study IV and used to measure respiratory variation in LVEDV in consecutive patients referred for cardiac evaluation with cardiovascular magnetic resonance imaging. In patients, the k-space based self-gating failed to measure the respiratory variation in LVEDV, whereas with the projection based self-gating yielded an 8% respiratory variation in LVEDV. In conclusion, this work presents a novel method for measuring the LVEDV resolved in a two-dimensional cardio-respiratory phase map and provides three-dimensional isotropicresolution image volumes enabling multiple view angles of the heart in one acquisition.
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| 5. |
- Holst, Karen, et al.
(författare)
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Projection-based respiratory-resolved left ventricular volume measurements in patients using free-breathing double golden-angle 3D radial acquisition.
- 2019
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Ingår i: Magma. - : Springer Science and Business Media LLC. - 1352-8661. ; 32:3, s. 331-341
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Tidskriftsartikel (refereegranskat)abstract
- To refine a new technique to measure respiratory-resolved left ventricular end-diastolic volume (LVEDV) in mid-inspiration and mid-expiration using a respiratory self-gating technique and demonstrate clinical feasibility in patients.Ten consecutive patients were imaged at 1.5T during 10min of free breathing using a 3D golden-angle radial trajectory. Two respiratory self-gating signals were extracted and compared: from the k-space center of all acquired spokes, and from a superior-inferior projection spoke repeated every 64ms. Data were binned into end-diastole and two respiratory phases of 15% respiratory cycle duration in mid-inspiration and mid-expiration. LVED volume and septal-lateral diameter were measured from manual segmentation of the endocardial border.Respiratory-induced variation in LVED size expressed as mid-inspiration relative to mid-expiration was, for volume, 1±8% with k-space-based self-gating and 8±2% with projection-based self-gating (P=0.04), and for septal-lateral diameter, 2±2% with k-space-based self-gating and 10±1% with projection-based self-gating (P=0.002).Measuring respiratory variation in LVED size was possible in clinical patients with projection-based respiratory self-gating, and the measured respiratory variation was consistent with previous studies on healthy volunteers. Projection-based self-gating detected a higher variation in LVED volume and diameter during respiration, compared to k-space-based self-gating.
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| 6. |
- Ikram, M. Arfan, et al.
(författare)
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Common variants at 6q22 and 17q21 are associated with intracranial volume
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 539-544
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Tidskriftsartikel (refereegranskat)abstract
- During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
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| 7. |
- Molinaro, Antonio, et al.
(författare)
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Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
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| 8. |
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| 9. |
- Skovgaard-Petersen, Karen, et al.
(författare)
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Fra støv til guld : Brugsbøger og skillingstryk fra Det Kongelige Bibliotek
- 2006
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Katalogbog udgivet i forbindelse med den første udstilling i Det Kongelige Biblioteks nye udstillingssal, Montanasalen. Emnet for udstillingen er ældre tiders danske brugsbøger, skillingstryk, romaner m.m. Udstillingen tager udgangspunkt i et citat af en engelsk biblioteksmand: ’The dust of one age is the gold of another, som ofte anvendes, når talen falder på bevaring af kulturarven verden over. Citatet udtrykker, at det, der i samtiden kan forekomme værdiløst og ligegyldigt – f.eks. en reklamebrochure – kan få stor betydning som kulturhistorisk kilde for senere generationer.Katalogbogen, der bærer samme navn som udstillingen, indeholder, foruden en indledning til emnet om ”De oversete bøger” af Karen Skovgaard-Petersen, 4 artikler som forholder sig til nogle af udstillingens emner: - Charlotte Appel: Når det almindelige bliver sjældent – om abc’en og andre skolebøger - Henrik Horstbøll: Kunsten at dø – ars moriendi - Jens Henrik Koudal: Musikere, amatører og en ny type dansksprogede lærebøger - Michael Harbsmeier: Et grønlandsk spejl. Katalogbogen kan læses uafhængigt af udstillingen og kan således ses som et supplement til et besøg i den nye sal. Katalogbogen har dansk/engelsk paralleltekst.
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| 10. |
- Taal, H. Rob, et al.
(författare)
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Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
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