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| 2. |
- Egerod, Kristoffer L, et al.
(författare)
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A Major Lineage of Enteroendocrine Cells Coexpress CCK, Secretin, GIP, GLP-1, PYY, and Neurotensin but Not Somatostatin.
- 2012
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170.
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Tidskriftsartikel (refereegranskat)abstract
- Enteroendocrine cells such as duodenal cholecystokinin (CCK cells) are generally thought to be confined to certain segments of the gastrointestinal (GI) tract and to store and release peptides derived from only a single peptide precursor. In the current study, however, transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of the CCK promoter demonstrated a distribution pattern of CCK-eGFP positive cells that extended throughout the intestine. Quantitative PCR and liquid chromatography-mass spectrometry proteomic analyses of isolated, FACS-purified CCK-eGFP-positive cells demonstrated expression of not only CCK but also glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide (GIP), peptide YY (PYY), neurotensin, and secretin, but not somatostatin. Immunohistochemistry confirmed this expression pattern. The broad coexpression phenomenon was observed both in crypts and villi as demonstrated by immunohistochemistry and FACS analysis of separated cell populations. Single-cell quantitative PCR indicated that approximately half of the duodenal CCK-eGFP cells express one peptide precursor in addition to CCK, whereas an additional smaller fraction expresses two peptide precursors in addition to CCK. The coexpression pattern was further confirmed through a cell ablation study based on expression of the human diphtheria toxin receptor under the control of the proglucagon promoter, in which activation of the receptor resulted in a marked reduction not only in GLP-1 cells, but also PYY, neurotensin, GIP, CCK, and secretin cells, whereas somatostatin cells were spared. Key elements of the coexpression pattern were confirmed by immunohistochemical double staining in human small intestine. It is concluded that a lineage of mature enteroendocrine cells have the ability to coexpress members of a group of functionally related peptides: CCK, secretin, GIP, GLP-1, PYY, and neurotensin, suggesting a potential therapeutic target for the treatment and prevention of diabetes and obesity.
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| 3. |
- Hodges, Gethin W., et al.
(författare)
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Effect of simvastatin and ezetimibe on suPAR levels and outcomes
- 2018
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Ingår i: Atherosclerosis. - : ELSEVIER IRELAND LTD. - 0021-9150 .- 1879-1484. ; 272, s. 129-136
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown.& para;& para;Methods: We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model. A 1-year Cox analysis, adjusted for established cardiovascular risk factors, allocation to study treatment, peak aortic valve velocity and baseline suPAR, was performed to evaluate relationships between change in suPAR with all-cause mortality and the composite endpoint of major cardiovascular events (MCE) composed of ischemic cardiovascular events (ICE) and aortic valve related events (AVE).& para;& para;Results: After 4.3 years of follow-up, suPAR levels had increased by 9.2% (95% confidence interval [CI]: 7.0%-11.5%) in the placebo group, but only by 4.1% (1.9%-6.2%) in the group with lipid-lowering treatment (p<0.001). In a multivariate 1-year analysis, 1-year suPAR was strongly associated with all-cause mortality, hazard ratio (HR) = 2.05 (1.17-3.61); MCE 1.40 (1.01-1.92); and AVE 1.42 (1.02-1.99) (all p<0.042) for each doubling of suPAR; but was not associated with ICE.& para;& para;Conclusions: Simvastatin and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. Year-1 suPAR was associated with all-cause mortality, MCE, and AVE irrespective of baseline levels (SEAS study: NCT00092677). (C) 2018 Elsevier B.V. All rights reserved.
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| 4. |
- Hodges, Gethin W., et al.
(författare)
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SuPAR Predicts Cardiovascular Events and Mortality in Patients With Asymptomatic Aortic Stenosis
- 2016
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Ingår i: Canadian Journal of Cardiology. - : Elsevier. - 0828-282X .- 1916-7075. ; 32:12, s. 1462-1469
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Tidskriftsartikel (refereegranskat)abstract
- Background: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with subclinical cardiovascular damage and cardiovascular events. Whether suPAR is of prognostic value in asymptomatic patients with aortic stenosis (AS) remains unknown. Methods: Plasma suPAR levels were measured in 1503 patients with a mean age of 68 years who were recruited in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox regression analysis was performed to evaluate associations between suPAR and the composite end points of ischemic cardiovascular events (ICEs), aortic valve events (AVEs), cardiovascular and all-cause mortality after adjusting for traditional cardiovascular risk factors, and allocation to treatment. Results: The multivariate adjusted hazard ratio (HR) (95% confidence interval [CI]) per unit log2 ng/mL increase in suPAR was HR, 1.5; 95% CI, 1.2-1.9; P = 0.002 for ICEs; HR, 1.2; 95% CI, 0.9-1.5; P = 0.071) for AVEs; HR, 2.0; 95% CI, 1.2-3.3; P = 0.007) for cardiovascular mortality, and HR, 2.0; 95% CI, 1.4-2.9; P < 0.001 for all-cause mortality. Conclusions: In patients with mild-moderate AS, suPAR is independently associated with the incidence of ICEs, cardiovascular mortality, and all-cause mortality.
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| 5. |
- Hodges, Gethin W., et al.
(författare)
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SuPAR predicts postoperative complications and mortality in patients with asymptomatic aortic stenosis
- 2018
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Ingår i: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Background We evaluated whether early measurement of soluble urokinase plasminogen activator receptor (suPAR) could predict future risk of postoperative complications in initially asymptomatic patients with mild-moderate aortic stenosis (AS) undergoing aortic valve replacement (AVR) surgery.Methods Baseline plasma suPAR levels were available in 411 patients who underwent AVR surgery during in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox analyses were used to evaluate suPAR in relation to all-cause mortality and the composite endpoint of postoperative complications (all-cause mortality, congestive heart failure, stroke and renal impairment) occurring in the 30-day postoperative period.Results Patients with initially higher levels of suPAR were at increased risk of postoperative mortality with a HR of 3.5 (95% CI 1.4 to 9.0, P=0.008) and postoperative complications with a HR of 2.7 (95% CI 1.5 to 5.1, P=0.002), per doubling in suPAR. After adjusting for the European System for Cardiac Operative Risk Evaluation or Society of Thoracic Surgeons risk score, suPAR remained associated with postoperative mortality with a HR 3.2 (95% CI 1.2 to 8.6, P=0.025) and 2.7 (95% CI 1.0 to 7.8, P=0.061); and postoperative complications with a HR of 2.5 (95% CI 1.3 to 5.0, P=0.007) and 2.4 (95% CI 1.2 to 4.8, P=0.011), respectively.Conclusion Higher baseline suPAR levels are associated with an increased risk for postoperative complications and mortality in patients with mild-moderate, asymptomatic AS undergoing later AVR surgery. Further validation in other subsets of AS individuals are warranted.
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| 6. |
- Jiang, Hui, et al.
(författare)
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Solar forcing of Holocene summer sea-surface temperatures in the northern North Atlantic
- 2015
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Ingår i: Geology. - 0091-7613. ; 43:3, s. 203-206
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Tidskriftsartikel (refereegranskat)abstract
- Mounting evidence from proxy records suggests that variations in solar activity have played a significant role in triggering past climate changes. However, the mechanisms for sun-climate links remain a topic of debate. Here we present a high-resolution summer sea-surface temperature (SST) record covering the past 9300 yr from a site located at the present-day boundary between polar and Atlantic surface-water masses. The record is age constrained via the identification of 15 independently dated tephra markers from terrestrial archives, circumventing marine reservoir age variability problems. Our results indicate a close link between solar activity and SSTs in the northern North Atlantic during the past 4000 yr; they suggest that the climate system in this area is more susceptible to the influence of solar variations during cool periods with less vigorous ocean circulation. Furthermore, the high-resolution SST record indicates that climate in the North Atlantic regions follows solar activity variations on multidecadal to centennial time scales.
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| 7. |
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| 8. |
- Nørgaard, Jesper, et al.
(författare)
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Absence of Large-Scale Ice Masses in Central Northeast Siberia During the Late Pleistocene
- 2023
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 50:10
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Tidskriftsartikel (refereegranskat)abstract
- Ongoing speculation regarding the existence of large Late Pleistocene ice masses in Northeast Eurasia reflects the dearth of age constraints on glaciations across this vast region. Here, we report the first dates from the central part of Northeast Siberia, consisting of 22 cosmogenic 10Be exposure ages from boulders deriving from a sequence of three moraines in the Chersky Range. The dated moraine sequence indicates progressive contraction of maximum glacier extent from Marine Isotope Stage 6 to the Last Glacial Maximum, while the remotely-sensed mapping indicates an older, more expansive glaciation in the region yet undated. Our results show that Late Pleistocene glaciations were limited to the highlands, and Northeast Siberia did not host a large, coalescent ice sheet during the Last Glacial Maximum or Marine Isotope Stage 6.
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| 9. |
- Orlando, Ludovic, et al.
(författare)
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Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 499:7456, s. 74-
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Tidskriftsartikel (refereegranskat)abstract
- The rich fossil record of equids has made them a model for evolutionary processes(1). Here we present a 1.12-times coverage draft genome from a horse bone recovered from permafrost dated to approximately 560-780 thousand years before present (kyr BP)(2,3). Our data represent the oldest full genome sequence determined so far by almost an order of magnitude. For comparison, we sequenced the genome of a Late Pleistocene horse (43 kyr BP), and modern genomes of five domestic horse breeds (Equus ferus caballus), a Przewalski's horse (E. f. prze-walskii) and a donkey (E. asinus). Our analyses suggest that the Equus lineage giving rise to all contemporary horses, zebras and donkeys originated 4.0-4.5 million years before present (Myr BP), twice the conventionally accepted time to the most recent common ancestor of the genus Equus(4,5). We also find that horse population size fluctuated multiple times over the past 2 Myr, particularly during periods of severe climatic changes. We estimate that the Przewalski's and domestic horse populations diverged 38-72 kyr BP, and find no evidence of recent admixture between the domestic horse breeds and the Przewalski's horse investigated. This supports the contention that Przewalski's horses represent the last surviving wild horse population(6). We find similar levels of genetic variation among Przewalski's and domestic populations, indicating that the former are genetically viable and worthy of conservation efforts. We also find evidence for continuous selection on the immune system and olfaction throughout horse evolution. Finally, we identify 29 genomic regions among horse breeds that deviate from neutrality and show low levels of genetic variation compared to the Przewalski's horse. Such regions could correspond to loci selected early during domestication.
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| 10. |
- Ahnfeldt-Mollerup, Peder, et al.
(författare)
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Resource allocation and the burden of co-morbidities among patients diagnosed with chronic obstructive pulmonary disease : an observational cohort study from Danish general practice
- 2016
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic obstructive pulmonary disease is a leading cause of mortality, and associated with increased healthcare utilization and healthcare expenditure. In several countries, morbidity-based systems have changed the way resources are allocated in general practice. In primary care, fee-for-services tariffs are often based on political negotiation rather than costing systems. The potential for comprehensive measures of patient morbidity to explain variation in negotiated expenditures for patients with chronic obstructive pulmonary disease has not previously been examined. The aim of this study is to analyze fee-for-service expenditure of patients diagnosed with chronic obstructive pulmonary disease visiting Danish general practice clinics and further to assess what proportion of fee-for-service expenditure variation was explained by patient morbidity and general practice clinic characteristics, respectively.METHODS: We used patient morbidity characteristics such as diagnostic markers and multi-morbidity adjustment based on adjusted clinical groups (ACGs) and fee-for-service expenditure for a sample of primary care patients for the year 2010. Our sample included 3,973 patients in 59 general practices. We used a multi-level approach.RESULTS: The average annual fee-for-service expenditure of caring for patients diagnosed with chronic obstructive pulmonary disease in general practice was about EUR 400 per patient. Variation in the expenditures was driven by multimorbidity characteristics up to 28 % where as characteristics such as age and gender only explained 5 %. Expenditures increased progressively with the degree of multimorbidity. In addition, expenditures were higher for patients who had diagnostic markers based on ICPC-2 (body systems and/or components such as infections and symptoms). Nevertheless, 9.8-15.4 % of the variation in expenditure was related to the clinic in which the patient was cared for.CONCLUSION: Patient morbidity and general practice clinic characteristics are significant patient-related fee-for-service expenditure drivers in chronic obstructive pulmonary disease care.
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