49 research outputs found
Being Born Large for Gestational Age is Associated with Increased Global Placental DNA Methylation
Being born small (SGA) or large for gestational age (LGA) is associated with adverse birth outcomes and
metabolic diseases in later life of the offspring. It is known that aberrations in growth during gestation
are related to altered placental function. Placental function is regulated by epigenetic mechanisms
such as DNA methylation. Several studies in recent years have demonstrated associations between
altered patterns of DNA methylation and adverse birth outcomes. However, larger studies that reliably
investigated global DNA methylation are lacking. The aim of this study was to characterize global
placental DNA methylation in relationship to size for gestational age. Global DNA methylation was
assessed in 1023 placental samples by LC-MS/MS. LGA offspring displayed significantly higher global
placental DNA methylation compared to appropriate for gestational age (AGA; p<0.001). ANCOVA
analyses adjusted for known factors impacting on DNA methylation demonstrated an independent
association between placental global DNA methylation and LGA births (p<0.001). Tertile stratification
according to global placental DNA methylation levels revealed a significantly higher frequency of LGA
births in the third tertile. Furthermore, a multiple logistic regression analysis corrected for known
factors influencing birth weight highlighted an independent positive association between global
placental DNA methylation and the frequency of LGA births (p=0.001)
Ionized calcium measurements during regional citrate anticoagulation in CRRT: we need better blood gas analyzers
Stereotactic radiotherapy in the treatment of brain metastases
This thematic review is part of a larger, comparative dosimetric analysis of the evaluation of treatment plans created by different modulated intensity irradiation, which is delivered by means a linear accelerator for the treatment of multiple metastases in the brain. There is currently no consensus as to which method is dosimetrically better. A further study will be aimed at determining the dosimetric advantages of each irradiation technique to introduce additional certainty into the planning process
DNA methylation of the glucocorticoid receptor gene promoter in the placenta is associated with blood pressure regulation in human pregnancy
BACKGROUND:
Blood pressure (BP) regulation during pregnancy is influenced by hormones of placental origin. It was shown that the glucocorticoid system is altered in hypertensive pregnancy disorders such as preeclampsia. Epigenetic mechanism might influence the activity of genes involved in placental hormone/hormone receptor synthesis/action during pregnancy.
METHOD:
In the current study, we analyzed the association of 5'-C-phosphate-G-3' (CpG) site methylation of different glucocorticoid receptor gene (NR3C1) promoter regions with BP during pregnancy. The study was performed as a nested case-control study (n = 80) out of 1045 mother/child pairs from the Berlin Birth Cohort. Placental DNA was extracted and bisulfite converted. Nested PCR products from six NR3C1 proximal promoter regions [glucocorticoid receptor gene promotor region B (GR-1B), C (GR-1C), D (GR-1D), E (GR-1E), F (GR-1F), and H (GR-1H)] were analyzed by next generation sequencing.
RESULTS:
NR3C1 promoter regions GR-1D and GR-1E had a much higher degree of DNA methylation as compared to GR-1B, GR-1F or GR-1H when analyzing the entire study population. Comparison of placental NR3C1 CpG site methylation among hypotensive, normotensive and hypertensive mothers revealed several differently methylated CpG sites in the GR-1F promoter region only. Both hypertension and hypotension were associated with increased DNA methylation of GR-1F CpG sites. These associations were independent of confounding factors, such as family history of hypertension, smoking status before pregnancy and prepregnancy BMI. Assessment of placental glucocorticoid receptor expression by western blot showed that observed DNA methylation differences were not associated with altered levels of placental glucocorticoid receptor expression. However, correlation matrices of all NR3C1 proximal promoter regions demonstrated different correlation patterns of intraregional and interregional DNA methylation in the three BP groups, putatively indicating altered transcriptional control of glucocorticoid receptor isoforms.
CONCLUSION:
Our study provides evidence of an independent association between placental NR3C1 proximal promoter methylation and maternal BP. Furthermore, we observed different patterns of NR3C1 promoter methylation in normotensive, hypertensive and hypotensive pregnancy
Increased global placental DNA methylation levels are associated with gestational diabetes
BACKGROUND:
Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes. It is known that GDM is associated with an altered placental function and changes in placental gene regulation. More recent studies demonstrated an involvement of epigenetic mechanisms. So far, the focus regarding placental epigenetic changes in GDM was set on gene-specific DNA methylation analyses. Studies that robustly investigated placental global DNA methylation are lacking. However, several studies showed that tissue-specific alterations in global DNA methylation are independently associated with type 2 diabetes. Thus, the aim of this study was to characterize global placental DNA methylation by robustly measuring placental DNA 5-methylcytosine (5mC) content and to examine whether differences in placental global DNA methylation are associated with GDM.
METHODS:
Global DNA methylation was quantified by the current gold standard method, LC-MS/MS. In total, 1030 placental samples were analyzed in this single-center birth cohort study.
RESULTS:
Mothers with GDM displayed a significantly increased global placental DNA methylation (3.22 ± 0.63 vs. 3.00 ± 0.46 %; p = 0.013; ±SD). Bivariate logistic regression showed a highly significant positive correlation between global placental DNA methylation and the presence of GDM (p = 0.0009). Quintile stratification according to placental DNA 5mC levels revealed that the frequency of GDM was evenly distributed in quintiles 1-4 (2.9-5.3 %), whereas the frequency in the fifth quintile was significantly higher (10.7 %; p = 0.003). Bivariate logistic models adjusted for maternal age, BMI, ethnicity, recurrent miscarriages, and familiar diabetes predisposition clearly demonstrated an independent association between global placental DNA hypermethylation and GDM. Furthermore, an ANCOVA model considering known predictors of DNA methylation substantiated an independent association between GDM and placental DNA methylation.
CONCLUSIONS:
This is the first study that employed a robust quantitative assessment of placental global DNA methylation in over a thousand placental samples. The study provides large scale evidence that placental global DNA hypermethylation is associated with GDM, independent of established risk factors
Safety and efficacy of regional citrate anticoagulation in continuous venovenous hemodialysis in the presence of liver failure: the Liver Citrate Anticoagulation Threshold (L-CAT) observational study
New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism
The Science Performance of JWST as Characterized in Commissioning
This paper characterizes the actual science performance of the James Webb
Space Telescope (JWST), as determined from the six month commissioning period.
We summarize the performance of the spacecraft, telescope, science instruments,
and ground system, with an emphasis on differences from pre-launch
expectations. Commissioning has made clear that JWST is fully capable of
achieving the discoveries for which it was built. Moreover, almost across the
board, the science performance of JWST is better than expected; in most cases,
JWST will go deeper faster than expected. The telescope and instrument suite
have demonstrated the sensitivity, stability, image quality, and spectral range
that are necessary to transform our understanding of the cosmos through
observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures;
https://iopscience.iop.org/article/10.1088/1538-3873/acb29
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
TSI ultrasound elastography for the diagnosis of chronic allograft nephropathy in kidney transplanted patients
Purpose: To answer the question whether the TSI (tissue strain imaging) sonoelastography
technique can contribute to the diagnosis of chronic renal allograft damage. Material
and methods: A prospective study of 112 patients between June 2010 and April 2011 was
conducted to compare elastography data with biopsy results and laboratory parameters
in order to determine whether any correlations exist. Elastography parameters were
acquired with a high-end ultrasound system and analyzed using the semiquantitative
strain ratio. For comparison, patients were divided into three groups based on biopsy
findings (Banff classification): group A: biopsy not necessary; group B: Banff grade I;
group C: Banff grades II and III. Correlations were assessed by means of correlation
(Pearson) and regression analysis. Differences between ordinal groups were tested
for statistical significance by the Mann-Whitney U test. Results: Mean patient age was
54.2 ± 15.01 years. Fifty-nine percent of the patients were male. The calculated TSI strain
ratio of groups A and C differed significantly (p = 0.024). Groups B and C (p = 0.056)
and groups A and B (p = 0.88) showed no significant difference. The TSI strain ratio
did not correlate with glomerular filtration rate (r = 0.105) or creatinine (r = 0.092).
Conclusion: The TSI sonoelastography technique can contribute to the differentiation of
different stages of renal graft damage (according to Banff classification). However, significant
results were not observed for all investigated features. The TSI technique should
be further evaluated in future studies including larger numbers of patients.Cel: Celem niniejszej pracy było sprawdzenie, czy sonoelastografia TSI (tissue strain
imaging – obrazowanie odkształcenia tkanek) może pomóc w rozpoznaniu przewlekłego
uszkodzenia nerki przeszczepionej. Materiał i metody: Badanie prospektywne, przeprowadzone
od czerwca 2010 do kwietnia 2011 roku, objęło 112 pacjentów. Porównano dane
uzyskane w badaniu elastograficznym z wynikami biopsji oraz z parametrami laboratoryjnymi
w celu zbadania ewentualnych zależności między nimi. Dane elastograficzne zostały
uzyskane przy użyciu wysokiej klasy sprzętu ultrasonograficznego, a ich analizę przeprowadzono,
wykorzystując półilościowy wskaźnik odkształcenia (semiquantitative strain
ratio). W celach porównawczych pacjenci zostali podzieleni na trzy grupy na podstawie
wyniku biopsji (według klasyfikacji Banff): grupa A: biopsja nie jest konieczna, grupa B:
stopień I w klasyfikacji Banff oraz grupa C: stopnie II i III według klasyfikacji Banff.
Korelacje oceniono za pomocą analizy korelacji (Pearsona) i regresji. Z kolei do oceny
istotności statystycznej różnic między badanymi grupami posłużył test U Manna-Whitneya.
Wyniki: Średnia wieku pacjentów wynosiła 54,2 ± 15,01 roku. Mężczyźni stanowili
59% badanych. Wykazano istotną różnicę między wskaźnikami odkształcenia TSI dla
grup A i C (p = 0,024). Nie wykazano natomiast istotnych różnic między grupami B i C
(p = 0,056) oraz A i B (p = 0,88). Nie wykazano również korelacji pomiędzy wskaźnikiem
odkształcenia TSI a współczynnikiem przesączania kłębuszkowego (r = 0,105) i kreatyniną
(r = 0,092). Wnioski: Sonoelastografia TSI może pomóc w różnicowaniu poszczególnych
stadiów uszkodzenia przeszczepu (na podstawie klasyfikacji Banff). Jednak nie
dla wszystkich badanych cech otrzymane wyniki były istotne statystycznie. Technika TSI
powinna być przedmiotem dalszych badań obejmujących większą liczbę pacjentów