| 51. |
- Pattaro, Cristian, et al.
(författare)
-
Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
|
|
| 52. |
- Rydén, Lars, et al.
(författare)
-
ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD
- 2013
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:39, s. 3035-3087
-
Tidskriftsartikel (refereegranskat)abstract
- This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.
|
|
| 53. |
- Santesson, Sabina, et al.
(författare)
-
Airborne Single Cell Chemistry
- 2002
-
Ingår i: European Biotechnology News. ; 1:1, s. 39-40
-
Tidskriftsartikel (populärvet., debatt m.m.)
|
|
| 54. |
- Schulz, Christina-Alexandra, et al.
(författare)
-
Plasma kidney injury molecule-1 (p-KIM-1) levels and deterioration of kidney function over 16 years
- 2020
-
Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 35:2, s. 265-273
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The kidney injury molecule-1 (KIM-1) has previously been associated with kidney function in rodents and humans. Yet its role as a predictive marker for future decline in kidney function has remained less clear.Methods: At baseline (1991-1994), fasting plasma KIM-1 (p-KIM-1) was measured in 4739 participants of the population-based Malmö Diet and Cancer Study. Creatinine and cystatin C were used to calculate estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Collaboration 2012 creatinine-cystatin C equation at baseline and follow-up examination (2007-2012). Incident CKD was defined as an eGFR <60 mL/min/1.73 m2 at follow-up.Results: During a mean follow-up time of 16.6 years, high p-KIM-1 levels were associated with a greater decline in eGFR (quartile 1 -1.36 versus quartile 4 -1.54 mL/min/1.73 m2; P < 0.001). In multivariate analyses, the risk for incident CKD at the follow-up examination was higher among participants with baseline p-KIM-1 levels in the highest quartile {odds ratio [OR] 1.45 [95% confidence interval (CI) 1.10-1.92]} compared with those within the lowest quartile. The relative impact of baseline p-KIM-1 on incidence of CKD [OR 1.20 (95% CI 1.08-1.33) per 1 standard deviation (SD) increase in p-KIM-1] was comparable to those of age and systolic blood pressure (SBP) [OR 1.55 (95% CI 1.38-1.74) and OR 1.21 (95% CI 1.09-1.35) per 1 SD increase, respectively]. Adding p-KIM-1 to a conventional risk model resulted in significantly improved C-statistics (P = 0.04) and reclassified 9% of the individuals into the correct risk direction (continuous net reclassification improvement P = 0.02). Furthermore, the risk for hospitalization due to impaired renal function increased with increasing baseline p-KIM-1 [hazard ratio per 1 SD 1.43; (95% CI 1.18-1.74)] during a mean follow-up time of 19.2 years.Conclusion: Our results show that p-KIM-1 predicts the future decline of eGFR and risk of CKD in healthy middle-aged participants. Whether p-KIM-1 can be used to prioritize preventive action that needs to be further investigated.
|
|
| 55. |
- Scuteri, Angelo, et al.
(författare)
-
Aging Population : Challenges and Opportunities in a Life Course Perspective
- 2015
-
Ingår i: Early Vascular Aging (EVA) : New Directions in Cardiovascular Protection - New Directions in Cardiovascular Protection. - 9780128013878 - 9780128016763 ; , s. 17-20
-
Bokkapitel (refereegranskat)abstract
- In most Western countries the mean longevity for both men and women has increased dramatically over the past 100 years. This was first attributable to a reduction in perinatal and child mortality when deliveries became safer and conditions for children more healthy, such as better nutrition. In recent decades another trend is visible, that is, a reduction of the negative impact of chronic disease in midlife and a postponement of life-threatening medical conditions until old age. This is why the mean life expectancy now reaches around 80 years in many developed countries, even if there is still a substantial gap to the shorter life span of many people living in developing countries, but also in the former Soviet Union. To better understand this demographic transition we need to consider the influence of environmental and social factors, as our genetic setup will not change in the shorter time perspective (centuries). On the other hand we also need a deeper understanding of the influence of early life programming on adult health and longevity to fully grasp the shifting demography of human populations, in a life course perspective.
|
|
| 56. |
- Svensson, Thomas, et al.
(författare)
-
Plasma concentration of Caspase-8 is associated with short sleep duration and the risk of incident diabetes mellitus
- 2018
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 103:4, s. 1592-1600
-
Tidskriftsartikel (refereegranskat)abstract
- Context: The biological mechanism for the association between sleep duration and incident diabetes mellitus (DM) is unclear. Sleep duration and Caspase-8, a marker of apoptotic activity, have both been implicated in beta cell function.Objective: To investigate the associations between sleep duration and plasma Caspase-8, and incident DM, respectively.Design: Prospective cohort study.Setting: The Malmö Diet and Cancer (MDC) Study is a population-based, prospective study run in the city of Malmö, Sweden.Participants: 4023 individuals from the MDC Study aged 45-68 years at baseline without a history of prevalent DM, and with information on habitual sleep duration.Main outcomes: Incident DM.Results: Mean follow-up time was 17.8 years. Sleep duration was the only behavioural variable significantly associated with plasma Caspase-8. Plasma Caspase-8 was significantly associated with incident DM per standard deviation of its transformed continuous form (hazard ratio [HR]= 1.24, 95% confidence interval [CI] 1.13-1.36), and when dichotomized into high (quartile 4) (HR=1.44, 95%CI: 1.19-1.74) compared to low (quartiles 1-3) concentrations. Caspase-8 interacted with sleep duration; compared to 7-8 hours of sleep and low plasma Caspase-8, individuals with high plasma Caspase-8 and sleep duration <6 hours (HR=3.54, 95%CI: 2.12-5.90), 6-7 hours (HR=1.81, 95%CI: 1.24-2.65), and 8-9 hours (HR=1.54, 95%CI: 1.09-2.18) were at significantly increased risks of incident DM.Conclusions: Sleep duration is associated with plasma Caspase-8. Caspase-8 independently predicts DM years before disease onset and modifies the effect of sleep duration on incident DM. Future studies should investigate if change of sleep duration modifies plasma concentrations of Caspase-8.
|
|
| 57. |
- Thompson, Paul M., et al.
(författare)
-
The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
-
Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
-
Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
|
|
| 58. |
|
|
| 59. |
- Viberg, Peter, et al.
(författare)
-
Reversed phase continuous full filling CEC-ESI-MS
- 2007
-
Ingår i: Chromatographia. - : Springer Science and Business Media LLC. - 0009-5893 .- 1612-1112. ; 65:5-6, s. 291-297
-
Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles were used as a pseudostationary phase in capillary electrochromatography (CEC) electrospray ionisation-mass spectrometry (ESI-MS) for separation of both neutral analytes by a reversed phase mechanism, as well as for cationic analytes by a cation exchange mechanism. Nanoparticles suspended in electrolyte, were injected as a plug prior to the sample using a partial filling technique (PF), or used as electrolyte in a continuous full filling (CFF) technique. An orthogonal ESI probe was used to hinder the nanoparticles from entering the mass spectrometer and to allow detection of analytes co-eluting with concentrated nanoparticle slurries. Two types of nanoparticles were synthesised and used, both of them having a hydrophobic core and a hydrophilic surface. The hydrophobic core gave the nanoparticles reversed phase properties and the hydrophilic surface promoted the formation of stable slurries of nanoparticles in electrolytes with a low concentration of organic modifier. The surface of one of the nanoparticle types was covered with sulphate groups that, besides from enhancing slurry stability and thus enabling reversed phase CEC, also enabled ion exchange CEC. Both nanoparticle types showed reproducible and interpretable retention properties.
|
|
| 60. |
- Wu, Chuanyan, et al.
(författare)
-
Elevated circulating follistatin associates with an increased risk of type 2 diabetes
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-10
-
Tidskriftsartikel (refereegranskat)abstract
- The hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04-1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09-1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.
|
|
