1. |
- Moss, J, et al.
(författare)
-
Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease
- 2018
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 5068-
-
Tidskriftsartikel (refereegranskat)abstract
- Methylation patterns of circulating cell-free DNA (cfDNA) contain rich information about recent cell death events in the body. Here, we present an approach for unbiased determination of the tissue origins of cfDNA, using a reference methylation atlas of 25 human tissues and cell types. The method is validated using in silico simulations as well as in vitro mixes of DNA from different tissue sources at known proportions. We show that plasma cfDNA of healthy donors originates from white blood cells (55%), erythrocyte progenitors (30%), vascular endothelial cells (10%) and hepatocytes (1%). Deconvolution of cfDNA from patients reveals tissue contributions that agree with clinical findings in sepsis, islet transplantation, cancer of the colon, lung, breast and prostate, and cancer of unknown primary. We propose a procedure which can be easily adapted to study the cellular contributors to cfDNA in many settings, opening a broad window into healthy and pathologic human tissue dynamics.
|
|
2. |
- Quintana, H. K., et al.
(författare)
-
Diabetes, hypertension, overweight and hyperlipidemia and 7-day case-fatality in first myocardial infarction
- 2016
-
Ingår i: International Journal of Cardiology Metabolic & Endocrine. - : ELSEVIER SCI LTD. - 2214-7624. ; 12, s. 30-35
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Out-of-hospital deaths due to a first myocardial infarction (MI) are frequent and a big challenge for prevention. Increased knowledge about factors influencing MI fatality is needed. Metabolic risk factors have been studied in relation to MI fatality in-hospital but studies considering also out-of-hospital deaths are few. Aim: To assess howdiabetes and other metabolic risk factors associate with death within 7 days after first time MI among subjects aged between 45 and 70 identified in Stockholm County 1992-1994. Methods: Data were collected using questionnaires (close relatives of fatal cases were asked to fill the questionnaire), physical examinations, national registers and autopsy reports. Risk ratios (RR) of 7-day MI fatality with 95% confidence intervals (CI) associated with the risk factors under study were calculated using binomial regression with log link. Results: Out of 1905 first time MI cases included, 524 died within 7 days. After adjustments for age, sex, current smoking, education and general comorbidity, diabetes, but not hypertension and hyperlipidemia, was associated with MI fatality (RR 1.68, 95% CI 1.20-2.28). Overweight, as compared to normal BMI, was inversely associated with MI fatality (multiple adjusted RR 0.68, 95% CI 0.49-0.94); obesity results pointed in the samedirection (multiple adjusted RR 0.79, 0.52-1.16). Conclusions: In this population-based inception cohort study, diabetes but not hypertension and hyperlipidemia were associated with MI fatality. This further emphasizes the importance of diabetes as a cardiovascular risk factor and the need for close surveillance of diabetic patients. Overweight was however associated with decreased MI fatality.
|
|
3. |
|
|
4. |
|
|
5. |
|
|
6. |
|
|
7. |
|
|
8. |
|
|
9. |
- Spalding, KL, et al.
(författare)
-
Impact of fat mass and distribution on lipid turnover in human adipose tissue
- 2017
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 15253-
-
Tidskriftsartikel (refereegranskat)abstract
- Differences in white adipose tissue (WAT) lipid turnover between the visceral (vWAT) and subcutaneous (sWAT) depots may cause metabolic complications in obesity. Here we compare triglyceride age and, thereby, triglyceride turnover in vWAT and sWAT biopsies from 346 individuals and find that subcutaneous triglyceride age and storage capacity are increased in overweight or obese individuals. Visceral triglyceride age is only increased in excessively obese individuals and associated with a lower lipid removal capacity. Thus, although triglyceride storage capacity in sWAT is higher than in vWAT, the former plateaus at substantially lower levels of excess WAT mass than vWAT. In individuals with central or visceral obesity, lipid turnover is selectively increased in vWAT. Obese individuals classified as ‘metabolically unhealthy’ (according to ATPIII criteria) who have small subcutaneous adipocytes exhibit reduced triglyceride turnover. We conclude that excess WAT results in depot-specific differences in lipid turnover and increased turnover in vWAT and/or decreased turnover in sWAT may result in metabolic complications of overweight or obesity.
|
|
10. |
- Zilg, B., et al.
(författare)
-
A new model for the estimation of time of death from vitreous potassium levels corrected for age and temperature
- 2015
-
Ingår i: Forensic Science International. - : ELSEVIER IRELAND LTD. - 0379-0738 .- 1872-6283. ; 254, s. 158-166
-
Tidskriftsartikel (refereegranskat)abstract
- Analysis of potassium concentration in the vitreous fluid of the eye is frequently used by forensic pathologists to estimate the postmortem interval (PMI), particularly when other methods commonly used in the early phase of an investigation can no longer be applied. The postmortem rise in vitreous potassium has been recognized for several decades and is readily explained by a diffusion of potassium from surrounding cells into the vitreous fluid. However, there is no consensus regarding the mathematical equation that best describes this increase. The existing models assume a linear increase, but different slopes and starting points have been proposed. In this study, vitreous potassium levels, and a number of factors that may influence these levels, were examined in 462 cases with known postmortem intervals that ranged from 2 h to 17 days. We found that the postmortem rise in potassium followed a non-linear curve and that decedent age and ambient temperature influenced the variability by 16% and 5%, respectively. A long duration of agony and a high alcohol level at the time of death contributed less than 1% variability, and evaluation of additional possible factors revealed no detectable impact on the rise of vitreous potassium. Two equations were subsequently generated, one that represents the best fit of the potassium concentrations alone, and a second that represents potassium concentrations with correction for decedent age and/or ambient temperature. The former was associated with narrow confidence intervals in the early postmortem phase, but the intervals gradually increased with longer PMIs. For the latter equation, the confidence intervals were reduced at all PMIs. Therefore, the model that best describes the observed postmortem rise in vitreous potassium levels includes potassium concentration, decedent age, and ambient temperature. Furthermore, the precision of these equations, particularly for long PMIs, is expected to gradually improve by adjusting the constants as more reference data are added over time. A web application that facilitates this calculation process and allows for such future modifications has been developed. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
|
|