| 61. |
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| 62. |
- Rawshani, Araz, 1986, et al.
(författare)
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Cardiac arrhythmias and conduction abnormalities in patients with type 2 diabetes
- 2023
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The association between type 2 diabetes (T2D) and the development of cardiac arrhythmias and conduction disturbances has not been extensively studied. Arrhythmia was defined as atrial fibrillation and flutter (AF/AFl), ventricular tachycardia (VT) and ventricular fibrillation (VF), and conduction abnormality as sinus node disease (SND), atrioventricular (AV) block or pacemaker implantation, and intraventricular conduction blocks (IVCB). Incidence rates and Cox regression were used to compare outcomes, and to assess optimal levels for cardiometabolic risk factors and risk associated with multifactorial risk factor control (i.e., HbA1c, LDL-C, systolic blood pressure (SBP), BMI and eGFR), between patients with versus without T2D. The analyses included data from 617,000 patients with T2D and 2,303,391 matched controls. Patients with diabetes and the general population demonstrated a gradual increase in rates for cardiac conduction abnormalities and virtually all age-groups for AF/AFI showed increased incidence during follow-up. For patients with versus without T2D, risks for cardiac arrhythmias were higher, including for AF/AFl (HR 1.17, 95% CI 1.16-1.18), the composite of SND, AV-block or pacemaker implantation (HR 1.40, 95% CI 1.37-1.43), IVCB (HR 1.23, 95% CI 1.18-1.28) and VT/VF (HR 1.08, 95% CI 1.04-1.13). For patients with T2D who had selected cardiometabolic risk factors within target ranges, compared with controls, risk of arrythmia and conduction abnormalities for T2D vs not were: AF/AFl (HR 1.09, 95% CI 1.05-1.14), the composite of SND, AV-block or pacemaker implantation (HR 1.06, 95% CI 0.94-1.18), IVCB (HR 0.80, 95% CI 0.60-0.98), and for VT/VF (HR 0.97, 95% CI 0.80-1.17). Cox models showed a linear risk increase for SBP and BMI, while eGFR showed a U-shaped association. Individuals with T2D had a higher risk of arrhythmias and conduction abnormalities than controls, but excess risk associated with T2D was virtually not evident among patients with T2D with all risk factors within target range. BMI, SBP and eGFR displayed significant associations with outcomes among patients with T2D.
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| 63. |
- Schuur, E. A. G., et al.
(författare)
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Climate change and the permafrost carbon feedback
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 520:7546, s. 171-179
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Forskningsöversikt (refereegranskat)abstract
- Large quantities of organic carbon are stored in frozen soils (permafrost) within Arctic and sub-Arctic regions. Awarming climate can induce environmental changes that accelerate the microbial breakdown of organic carbon and the release of the greenhouse gases carbon dioxide and methane. This feedback can accelerate climate change, but the magnitude and timing of greenhouse gas emission from these regions and their impact on climate change remain uncertain. Here we find that current evidence suggests a gradual and prolonged release of greenhouse gas emissions in a warming climate and present a research strategy with which to target poorly understood aspects of permafrost carbon dynamics.
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| 64. |
- Simonsen, A. H., et al.
(författare)
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A novel panel of cerebrospinal fluid biomarkers for the differential diagnosis of Alzheimer's disease versus normal aging and frontotemporal dementia
- 2007
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 24:6, s. 434-440
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: An early and accurate diagnosis of Alzheimer's disease (AD) is important in order to initiate symptomatic treatment with currently approved drugs and will be of even greater importance with the advent of disease-modifying compounds. METHODS: Protein profiles of human cerebrospinal fluid samples from patients with AD (n = 85), frontotemporal dementia (n = 20), and healthy controls (n = 32) were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to verify previously discovered biomarkers. RESULTS: We verified 15 protein biomarkers that were able to differentiate between AD and controls, and 7 of these 15 markers also differentiated AD from FTD. CONCLUSION: A panel of cerebrospinal fluid protein markers was verified by a proteomics technology which may potentially improve the accuracy of the AD diagnosis.
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| 65. |
- Simonsen, A H, et al.
(författare)
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Amyloid beta1-40 quantification in CSF: comparison between chromatographic and immunochemical methods.
- 2007
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 23:4, s. 246-50
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Amyloid beta (Abeta) is the principal component of senile plaques, one of the hallmarks of Alzheimer's disease (AD). Evidence is accumulating that soluble aggregates (oligomers) of Abeta are important in the pathogenesis of AD. METHODS: We compared three different methods for quantification of the 40 amino acid form of Abeta (Abeta40) in CSF, two based on antibodies [ELISA and surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF) with antibody-coated arrays] and one based on direct binding of proteins to a protein array [SELDI-TOF and immobilized metal affinity [copper] (IMAC30)]. RESULTS: CSF Abeta40 concentration was only found to be significantly elevated in AD (127% of control levels; p=0.0095) using SELDI-TOF with IMAC30 arrays. CONCLUSIONS: These data suggest that the measured Abeta level in CSF may differ depending on whether antibody-based methods are used or not, possibly caused by epitope masking due to Abeta oligomerization or to binding of Abeta to carrier proteins.
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| 66. |
- Simonsen, A H, et al.
(författare)
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Identification of a novel panel of cerebrospinal fluid biomarkers for Alzheimer's disease.
- 2008
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 29:7, s. 961-8
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Tidskriftsartikel (refereegranskat)abstract
- An early and accurate diagnosis of Alzheimer's disease (AD) is required to initiate symptomatic treatment with currently approved drugs and will be of even greater importance if disease modifying compounds in development display a clinical effect. Protein profiles of human cerebrospinal fluid samples from AD patients (n=95) and population-based healthy controls (n=72) were analyzed by SELDI-TOF-MS in order to discover and characterize novel candidate biomarker combinations that differentiate AD patients from normal aging in this explorative study. Thirty candidate biomarkers (ROC AUC>0.7) were discovered that could differentiate patients with AD from healthy controls. Protein sequence determination and positive identification of 15 biomarkers revealed potential associations between the identified markers and AD pathogenesis. A multi-marker combination of five peaks could distinguish AD from healthy control individuals with high sensitivity (97%) and specificity (98%). The panel of five markers was tested on a blinded independent data set of 30 AD samples and 28 controls giving 100% sensitivity and 97% specificity. This novel panel of biomarkers could potentially be used to improve the accuracy of diagnosis of AD.
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| 67. |
- Suh, Alexander, et al.
(författare)
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Ancient horizontal transfers of retrotransposons between birds and ancestors of human pathogenic nematodes
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Parasite host switches may trigger disease emergence, but prehistoric host ranges are often unknowable. Lymphatic filariasis and loiasis are major human diseases caused by the insect-borne filarial nematodes Brugia, Wuchereria and Loa. Here we show that the genomes of these nematodes and seven tropical bird lineages exclusively share a novel retrotransposon, AviRTE, resulting from horizontal transfer (HT). AviRTE subfamilies exhibit 83-99% nucleotide identity between genomes, and their phylogenetic distribution, paleobiogeography and invasion times suggest that HTs involved filarial nematodes. The HTs between bird and nematode genomes took place in two pantropical waves, >25-22 million years ago (Myr ago) involving the Brugia/Wuchereria lineage and >20-17 Myr ago involving the Loa lineage. Contrary to the expectation from the mammal-dominated host range of filarial nematodes, we hypothesize that these major human pathogens may have independently evolved from bird endoparasites that formerly infected the global breadth of avian biodiversity.
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| 68. |
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| 69. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 70. |
- Zetterqvist, Anna, et al.
(författare)
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Nuclear Factor of Activated T Cells Is Activated in the Endothelium of Retinal Microvessels in Diabetic Mice.
- 2015
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Ingår i: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6753 .- 2314-6745. ; 2015
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Tidskriftsartikel (refereegranskat)abstract
- The pathogenesis of diabetic retinopathy (DR) remains unclear but hyperglycemia is an established risk factor. Endothelial dysfunction and changes in Ca(2+) signaling have been shown to precede the onset of DR. We recently demonstrated that high extracellular glucose activates the Ca(2+)/calcineurin-dependent transcription factor NFAT in cerebral arteries and aorta, promoting the expression of inflammatory markers. Here we show, using confocal immunofluorescence, that NFAT is expressed in the endothelium of retinal microvessels and is readily activated by high glucose. This was inhibited by the NFAT blocker A-285222 as well as by the ectonucleotidase apyrase, suggesting a mechanism involving the release of extracellular nucleotides. Acute hyperglycemia induced by an IP-GTT (intraperitoneal glucose tolerance test) resulted in increased NFATc3 nuclear accumulation and NFAT-dependent transcriptional activity in retinal vessels of NFAT-luciferase reporter mice. In both Akita (Ins2(+/-) ) and streptozotocin- (STZ-) induced diabetic mice, NFAT transcriptional activity was elevated in retinal vessels. In vivo inhibition of NFAT with A-285222 decreased the expression of OPN and ICAM-1 mRNA in retinal vessels, prevented a diabetes driven downregulation of anti-inflammatory IL-10 in retina, and abrogated the increased vascular permeability observed in diabetic mice. Results identify NFAT signaling as a putative target for treatment of microvascular complications in diabetes.
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