| 1. |
- Lumbers, R. T., et al.
(författare)
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The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
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Tidskriftsartikel (refereegranskat)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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| 2. |
- Natali, S. M., et al.
(författare)
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Large loss of CO2 in winter observed across the northern permafrost region
- 2019
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Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 9:11, s. 852-857
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Tidskriftsartikel (refereegranskat)abstract
- Recent warming in the Arctic, which has been amplified during the winter(1-3), greatly enhances microbial decomposition of soil organic matter and subsequent release of carbon dioxide (CO2)(4). However, the amount of CO2 released in winter is not known and has not been well represented by ecosystem models or empirically based estimates(5,6). Here we synthesize regional in situ observations of CO2 flux from Arctic and boreal soils to assess current and future winter carbon losses from the northern permafrost domain. We estimate a contemporary loss of 1,662 TgC per year from the permafrost region during the winter season (October-April). This loss is greater than the average growing season carbon uptake for this region estimated from process models (-1,032 TgC per year). Extending model predictions to warmer conditions up to 2100 indicates that winter CO2 emissions will increase 17% under a moderate mitigation scenario-Representative Concentration Pathway 4.5-and 41% under business-as-usual emissions scenario-Representative Concentration Pathway 8.5. Our results provide a baseline for winter CO2 emissions from northern terrestrial regions and indicate that enhanced soil CO2 loss due to winter warming may offset growing season carbon uptake under future climatic conditions.
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| 3. |
- Alamshah, A., et al.
(författare)
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L-arginine promotes gut hormone release and reduces food intake in rodents
- 2016
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902. ; 18:5, s. 508-518
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the anorectic effect of L-arginine (L-Arg) in rodents. Methods: We investigated the effects of L-Arg on food intake, and the role of the anorectic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), the G-protein-coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. Results: Oral gavage of L-Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet-induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L-Arg stimulated GLP-1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP-1 and PYY receptors did not influence the anorectic effect of L-Arg. L-Arg-mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L-Arg suppressed food intake in rats. Conclusions: L-Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L-Arg is unlikely to be mediated by GLP-1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L-Arg suppressed food intake in rats, suggesting that L-Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L-Arg suppresses food intake and its utility in the treatment of obesity.
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| 4. |
- Manzano-Nunez, Ramiro, et al.
(författare)
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Outcomes and management approaches of resuscitative endovascular balloon occlusion of the aorta based on the income of countries
- 2020
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Ingår i: World Journal of Emergency Surgery. - : Springer Science and Business Media LLC. - 1749-7922. ; 15:57
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The Author(s). Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) could provide a survival benefit to severely injured patients as it may improve their initial ability to survive the hemorrhagic shock. Although the evidence supporting the use of REBOA is not conclusive, its use has expanded worldwide. We aim to compare the management approaches and clinical outcomes of trauma patients treated with REBOA according to the countries' income based on the World Bank Country and Lending Groups. Methods: We used data from the AORTA (USA) and the ABOTrauma (multinational) registries. Patients were stratified into two groups: (1) high-income countries (HICs) and (2) low-to-middle income countries (LMICs). Propensity score matching extracted 1:1 matched pairs of subjects who were from an LMIC or a HIC based on age, gender, the presence of pupillary response on admission, impeding hypotension (SBP ≤ 80), trauma mechanism, ISS, the necessity of CPR on arrival, the location of REBOA insertion (emergency room or operating room) and the amount of PRBCs transfused in the first 24 h. Logistic regression (LR) was used to examine the association of LMICs and mortality. Results: A total of 817 trauma patients from 14 countries were included. Blind percutaneous approach and surgical cutdown were the preferred means of femoral cannulation in HICs and LIMCs, respectively. Patients from LMICs had a significantly higher occurrence of MODS and respiratory failure. LR showed no differences in mortality for LMICs when compared to HICs; neither in the non-matched cohort (OR = 0.63; 95% CI: 0.36-1.09; p = 0.1) nor in the matched cohort (OR = 1.45; 95% CI: 0.63-3,33; p = 0.3). Conclusion: There is considerable variation in the management practices of REBOA and the outcomes associated with this intervention between HICs and LMICs. Although we found significant differences in multiorgan and respiratory failure rates, there were no differences in the risk-adjusted odds of mortality between the groups analyzed. Trauma surgeons practicing REBOA around the world should joint efforts to standardize the practice of this endovascular technology worldwide.
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| 5. |
- Clark, K., et al.
(författare)
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Structure-Function Implications of the Ability of Monoclonal Antibodies Against alpha-Galactosylceramide-CD1d Complex to Recognize beta-Mannosylceramide Presentation by CD1d
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- iNKT cells are CD1d-restricted T cells recognizing lipid antigens. The prototypic iNKT cell-agonist alpha-galactosylceramide (alpha-GalCer) alongside compounds with similar structures induces robust proliferation and cytokine production of iNKT cells and protects against cancer in vivo. Monoclonal antibodies (mAbs) that detect CD1d-alpha-GalCer complexes have provided critical information for understanding of antigen presentation of iNKT cell agonists. Although most iNKT cell agonists with antitumor properties are alpha-linked glycosphingolipids that can be detected by anti-CD1d-alpha-GalCer mAbs, beta-ManCer, a glycolipid with a beta-linkage, induces strong antitumor immunity via mechanisms distinct from those of alpha-GalCer. In this study, we unexpectedly discovered that anti-CD1d-alpha-GalCer mAbs directly recognized beta-ManCer-CD1d complexes and could inhibit beta-ManCer stimulation of iNKT cells. The binding of anti-CD1d-alpha-GalCer mAb with beta-ManCer-CD1d complexes was also confirmed by plasmon resonance and could not be explained by alpha-anomer contamination. The binding of anti-CD1d-alpha-GalCer mAb was also observed with CD1d loaded with another beta-linked glycosylceramide, beta-GalCer (C26:0). Detection with anti-CD1d-alpha-GalCer mAbs indicates that the interface of the beta-ManCer-CD1d complex exposed to the iNKT cell TCR can assume a structure like that of CD1d-alpha-GalCer, despite its disparate carbohydrate structure. These results suggest that certain beta-linked monoglycosylceramides can assume a structural display similar to that of CD1d-alpha-GalCer and that the data based on anti-CD1d-alpha-GalCer binding should be interpreted with caution.
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