| 1. |
- Andrikopoulos, Petros, et al.
(författare)
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Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
- 2023
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
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| 2. |
- 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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| 3. |
- Frykholm, Peter, 1961-, et al.
(författare)
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Pre-operative fasting in children : A guideline from the European Society of Anaesthesiology and Intensive Care
- 2022
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Ingår i: European Journal of Anaesthesiology. - : European Society of Anaesthesiology and Intensive Care. - 0265-0215 .- 1365-2346. ; 39:1, s. 4-25
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Tidskriftsartikel (refereegranskat)abstract
- Current paediatric anaesthetic fasting guidelines have recommended conservative fasting regimes for many years and have not altered much in the last decades. Recent publications have employed more liberal fasting regimes with no evidence of increased aspiration or regurgitation rates. In this first solely paediatric European Society of Anaesthesiology and Intensive Care (ESAIC) pre-operative fasting guideline, we aim to present aggregated and evidence-based summary recommendations to assist clinicians, healthcare providers, patients and parents.We identified six main topics for the literature search: studies comparing liberal with conservative regimens; impact of food composition; impact of comorbidity; the use of gastric ultrasound as a clinical tool; validation of gastric ultrasound for gastric content and gastric emptying studies; and early postoperative feeding. The literature search was performed by a professional librarian in collaboration with the ESAIC task force.Recommendations for reducing clear fluid fasting to 1 h, reducing breast milk fasting to 3 h, and allowing early postoperative feeding were the main results, with GRADE 1C or 1B evidence. The available evidence suggests that gastric ultrasound may be useful for clinical decision-making, and that allowing a ‘light breakfast’ may be well tolerated if the intake is well controlled. More research is needed in these areas as well as evaluation of how specific patient or treatment-related factors influence gastric emptying.
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| 4. |
- Goebel, Andreas, et al.
(författare)
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Passive transfer of fibromyalgia symptoms from patients to mice
- 2021
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Ingår i: Journal of Clinical Investigation. - : American Society For Clinical Investigation. - 0021-9738 .- 1558-8238. ; 131:13
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Tidskriftsartikel (refereegranskat)abstract
- Fibromyalgia syndrome (FMS) is characterized by widespread pain and tenderness, and patients typically experience fatigue and emotional distress. The etiology and pathophysiology of fibromyalgia are not fully explained and there are no effective drug treatments. Here we show that IgG from FMS patients produced sensory hypersensitivity by sensitizing nociceptive neurons. Mice treated with IgG from FMS patients displayed increased sensitivity to noxious mechanical and cold stimulation, and nociceptive fibers in skin-nerve preparations from mice treated with FMS IgG displayed an increased responsiveness to cold and mechanical stimulation. These mice also displayed reduced locomotor activity, reduced paw grip strength, and a loss of intraepidermal innervation. In contrast, transfer of IgG-depleted serum from FMS patients or IgG from healthy control subjects had no effect. Patient IgG did not activate naive sensory neurons directly. IgG from FMS patients labeled satellite glial cells and neurons in vivo and in vitro, as well as myelinated fiber tracts and a small number of macrophages and endothelial cells in mouse dorsal root ganglia (DRG), but no cells in the spinal cord. Furthermore, FMS IgG bound to human DRG. Our results demonstrate that IgG from FMS patients produces painful sensory hypersensitivities by sensitizing peripheral nociceptive afferents and suggest that therapies reducing patient IgG titers may be effective for fibromyalgia.
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| 5. |
- Haghighi, Mona, et al.
(författare)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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| 6. |
- Hedenborg, Susanna, 1964-, et al.
(författare)
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Hästsportens miljöarbete : Viljan finns – men också stora utmaningar
- 2023
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Ingår i: Idrottsforum.org/Nordic sport science forum. - : Malmö universitet. - 1652-7224. ; :231024
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med den här artikeln är att kartlägga och analysera hur personer inom hästsporten i Sverige och Norge definierar hästsportens miljöutmaningar, samt att, enligt COM-B-modellen, identifiera förmågor, möjligheter och motivation för att utveckla en mer miljömässigt hållbar hästsektor. Undersökningen är baserad på en enkät som besvarats av 697 personer. Sammanfattningsvis kan vi konstatera att hästsektorn utvecklat ett starkare miljöengagemang än man hade för 15 år sedan (jämf Svala 2008). Samtidigt upplever många att de saknar möjlighet att påverka. En analys av svaren med hjälp av COM-B-modellen (jämf Mitchie et al, 2011; Mitchie et al., 2014) visar att förmåga (Capability) till förändring och kunskap finns (även om det finns personer som önskar mer kunskap). Men om vi studerar komponenten möjlighet (Opportunity), ser det ut att finnas högre hinder för förändring. Fysiska möjligheter såsom plats, resurser och tid framstår som svåra att påverka för den enskilda aktören. Även ekonomiska faktorer pekas ut som hinder för förändring. Möjligheterna handlar även om kulturella normer. Här kan finnas en lösning. Stall och stallbacken utmärker sig inte som en nedskräpad plats om man exempelvis jämför med städer eller vägrenar, men nedskräpning skulle kunna innebära ett slags allmän oordning. I stallet förväntas alla hålla ordning på sina saker och på gemensamma utrymmen. Även om den här ordningssamheten inte i första hand berör det vi i vanliga fall menar med ekologiska utmaningar kanske den kan vara något att bygga på när det gäller miljöarbetet.
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| 7. |
- Hedenborg, Susanna, et al.
(författare)
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Pro-Environmental Transformation of the Equine Sector—Facilitators and Challenges
- 2024
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Ingår i: Animals. - : MDPI. - 2076-2615. ; 14:6
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Tidskriftsartikel (refereegranskat)abstract
- To improve horse welfare and ensure a sustainable equestrian future, we need to understand human behavior in relation to the challenges of the sector. The purpose of this paper is to map and analyze how individuals within the equine sector in Sweden and Norway define the environmental challenges they are faced with and how these are related to questions about horse welfare. A mixed-methods parallel design was used. The data consist of survey answers and semi-structured interviews. The survey, responded to by 697 Swedish and Norwegian participants, ensured statistical validity and power through a sample size calculation yielding approximately 385 participants. To deepen the understanding, 36 semi structured interviews with Swedish and Norwegian interviewees were conducted. An analysis of convergencies and divergencies between the data sets provided robust insights into the perceptions and behaviors within the equine sector in Sweden and Norway. The findings show that the equine sector has cultivated a stronger environmental commitment over the last 15 years (Svala, 2008). However, many participants express a perceived lack of influence on this transformation. The COM-B model (Michie, Van Stralen & West, 2011; Michie, Atkins & West, 2014) and previous research on ‘thinking structures on climate delay’ (Wormbs & Wolrath, 2023) are used to interpret the data. The analysis indicates that there is an overall capacity for change, and that skills and knowledge exist, but some individuals desire more information and a deeper understanding of the issues at hand. Higher barriers to change were found in the opportunity component, where physical constraints such as location, resources, and time seem challenging for individual actors to influence. Economic factors are also identified as impediments to transformation. Cultural norms related to orderliness within stables, although not directly addressing ecological nor ethical challenges, might serve as a foundation for promoting environmental initiatives that will also improve horse welfare.
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| 8. |
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| 9. |
- 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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| 10. |
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