S Dor Research Articles

Sixteen-Year Longitudinal Evaluation of Blood-Based DNA Methylation Biomarkers for Early Prediction of Alzheimer's Disease.

DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, has shown promise for Alzheimer's disease (AD) prediction. Testing long-term predictive ability (>15 years) of existing DNAm-based epigenetic age acceleration (EAA) measures and identifying novel early blood-based DNAm AD-prediction biomarkers. EAA measures calculated from Illumina EPIC data from blood were tested with linear mixed-effects models (LMMs) in a longitudinal case-control sample (50 late-onset AD cases; 51 matched controls) with prospective data up to 16 years before clinical onset, and post-onset follow-up. Novel DNAm biomarkers were generated with epigenome-wide LMMs, and Sparse Partial Least Squares Discriminant Analysis applied at pre- (10-16 years), and post-AD-onset time-points. EAA did not differentiate cases from controls during the follow-up time (p > 0.05). Three new DNA biomarkers showed in-sample predictive ability on average 8 years pre-onset, after adjustment for age, sex, and white blood cell proportions (ps: 0.022-<0.00001). Our longitudinally-derived panel replicated nominally (p = 0.012) in an external cohort (n = 146 cases, 324 controls). However, its effect size and discriminatory accuracy were limited compared to APOEɛ4-carriership (OR = 1.38 per 1 SD DNAm score increase versus OR = 13.58 for ɛ4-allele carriage; AUCs = 77.2% versus 87.0%). Literature review showed low overlap (n = 4) across 3275 AD-associated CpGs from 8 published studies, and no overlap with our identified CpGs.

Nitric Oxide Precursors and Dimethylarginines as Risk Markers for Accelerated Measured GFR Decline in the General Population

Nitric oxide (NO) deficiency is associated with endothelial dysfunction, hypertension, atherosclerosis, and chronic kidney disease (CKD). Reduced NO bioavailability is hypothesized to play a vital role in kidney function impairment and CKD. We investigated the association of serum levels of endogenous inhibitors of NO, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), and precursors of NO, arginine, citrulline, and ornithine, with a decline in glomerular filtration rate (GFR) and new-onset CKD. In a prospective cohort study of 1407 healthy, middle-aged participants of Northern European origin in the Renal Iohexol Clearance Survey (RENIS), GFR was measured repeatedly with iohexol clearance during a median follow-up time of 11 years. GFR decline rates were analyzed using a linear mixed model, new-onset CKD (GFR< 60 ml/min per 1.73 m2) was analyzed with interval-censored Cox regression, and accelerated GFR decline (the 10% with the steepest GFR decline) was analyzed with logistic regression. Higher SDMA was associated with slower annual GFR decline. Higher levels of citrulline and ornithine were associated with accelerated GFR decline (odds ratio [OR], 1.43; 95% confidence interval [CI] 1.16-1.76 per SD higher citrulline and OR 1.23; 95% CI 1.01 to 1.49 per SD higher ornithine). Higher citrulline was associated with new-onset CKD, with a hazard ratio of 1.33 (95% CI 1.07-1.66) per SD higher citrulline. Associations between NO precursors and the outcomes suggest that NO metabolism plays a significant role in the pathogenesis of age-related GFR decline and the development of CKD in middle-aged people.

Clinical applicability of the Polygenic Risk Score for breast cancer risk prediction in familial cases

BackgroundCommon low-risk variants are presently not used to guide clinical management of familial breast cancer (BC). We explored the additive impact of a 313-variant-based Polygenic Risk Score (PRS313) relative to...

Prediction of twin pregnancy preeclampsia based on clinical risk factors, early pregnancy serum markers, and uterine artery pulsatility index.

Objectives:To investigate whether a combination of clinical risk factors, early pregnancy serum markers, and uterine artery pulsatility index (UTPI) can be used to predict twin preeclampsia (PE).Methods:This case control study included women with twin pregnancies who had undergone obstetrics treatments and gave birth at the Huzhou Maternity and Child Health Care Hospital from October 2018 to November 2020. Patients with PE comprised study group, and patients without PE comprised control group based on selection criteria and a 1:1 ratio. Statistical analysis was performed using clinical risk factors, early pregnancy serum markers, and UTPIs, and the area under the receiver operating curve (AUC. Sensitivity, and the specificity of different combinations of these variables were calculated to predict PE in women with twin pregnancy.Results:Logistic regression analysis revealed four independent predictors for the onset of PE during twin pregnancies: first delivery (OR, 7.51; P=0.045), conception method (OR, 7.11; P=0.036), β-HCG level (per SD OR, 2.73; P=0.026), and UTPI (OR, 0.17; P=0.043). First-delivery and IVF pregnancy methods both lead to a 7-fold increase in the PE risk during twin pregnancies. Every one sigma (standard deviation) increase in the β-HCG level led to a 2.73-fold increase in the PE risk. Every UTPI increment by 1.0 reduces the risk of PE by 83%. The prediction efficiencies were based on an AUC of 0.837, a sensitivity of 69%, and a specificity of 92% for the clinical risk factors; an AUC of 0.800, a sensitivity of 81%, and specificity of 78% for the β-HCG level, and an AUC of 0.814, a sensitivity of 88%, and a specificity of 65% for the UTPI. AUC was 0.928, sensitivity 85%, and a specificity 88% after applying the three types of indicators together for prediction.Conclusions:By combining early pregnancy serum markers (β-HCG), and UTPI, the predictive value for PE during twin pregnancy is improved together with its sensitivity and specificity.

Relationship between erythrocyte phospholipid fatty acid composition and obesity in children and adolescents

Observational studies have reported inconsistent results on the association between circulating fatty acids and obesity. The objective of this study was to investigate the relationship between erythrocyte phospholipid fatty acid composition and obesity in children and adolescents. We conducted a case-control study including 1442 obese and 1442 normal-weight children and adolescents. Circulating fatty acid composition between cases and controls were compared both in the present study and literature-based meta-analysis. Individual fatty acids contributing most to discriminating cases and controls were identified by orthogonal partial least squares-discriminant analysis and their associations with obesity were explored by a conditional logistic regression model. Five saturated fatty acids (14:0, 16:0, 17:0, 18:0, 20:0) were higher, 9 polyunsaturated fatty acids (18:3n-3, 20:3n-3, 20:5n-3, 22:5n-3, 22:6n-3, 18:2n-6, 20:2n-6, 20:3n-6, 20:4n-6) were lower in cases than in controls, while pooled results from the comparative meta-analysis were only consistent in 22:5n-3, 22:6n-3 and 18:2n-6. The orthogonal partial least squares-discriminant analysis model indicated that 16:0, 18:0, 20:4n-6, and 22:6n-3 were the fatty acids contributing most to discriminating cases and controls. In the conditional logistic regression model, significant positive associations were found for 16:0 (per 1 SD OR=1.43, 95% CI, 1.35-1.52) and 18:0 (per 1 SD OR=1.12, 95% CI, 1.09-1.16), while significant inverse associations were found for 20:4n-6 (per 1 SD OR=0.63, 95% CI, 0.58-0.69) and 22:6n-3 (per 1 SD OR=0.56, 95% CI, 0.52-0.61). Erythrocyte phospholipid 16:0 and 18:0 were positively and 20:4n-6 and 22:6n-3 were inversely associated with obesity in children and adolescents.

Serum C-peptide, Total and High Molecular Weight Adiponectin, and Pancreatic Cancer: Do Associations Differ by Smoking?

Background: Studies examining associations between circulating concentrations of C-peptide and total adiponectin, two biomarkers related to obesity and insulin secretion and sensitivity and pancreatic ductal adenocarcinoma (PDA) risk have shown inconsistent results and included limited numbers of smokers.Methods: We examined associations of these biomarkers and high molecular weight (HMW) adiponectin with PDA, overall, and by smoking status. We conducted a pooled nested case-control analysis in 3 cohorts (Prostate, Lung, Colorectal, and Ovarian Cancer Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and Cancer Prevention Study-II), with 758 cases (435 current smokers) and 1,052 controls (531 smokers) matched by cohort, age, sex, race, blood draw date and follow-up time. We used conditional logistic regression adjusted for age, smoking, diabetes, and body mass index to calculate ORs and 95% confidence intervals (CI).Results: Circulating C-peptide concentration was not associated with PDA in never or former smokers, but was inversely associated with PDA in current smokers (per SD OR = 0.67; 95% CI, 0.54-0.84; Pinteraction = 0.005). HMW adiponectin was inversely associated with PDA in never smokers (OR = 0.43; 95% CI, 0.23-0.81), not associated in former smokers, and positively associated in smokers (OR = 1.23; 95% CI, 1.04-1.45; Pinteraction = 0.009). Total adiponectin was not associated with PDA in nonsmokers or current smokers.Conclusions: Associations of biomarkers of insulin secretion and sensitivity with PDA differ by smoking status. Smoking-induced pancreatic damage may explain the associations in smokers while mechanisms related to insulin resistance associations in nonsmokers.Impact: Future studies of these biomarkers and PDA should examine results by smoking status. Cancer Epidemiol Biomarkers Prev; 26(6); 914-22. ©2017 AACR.

Impact of maternal and paternal smoking on birth outcomes.

The adverse effects of maternal and paternal smoking on child health have been studied. However, few studies demonstrate the interaction effects of maternal/paternal smoking, and birth outcomes other than birth weight have not been evaluated. The present study examined individual effects of maternal/paternal smoking and their interactions on birth outcomes. A follow-up hospital-based study from pregnancy to delivery was conducted from 1997 to 2010 with parents and newborn infants who delivered at a large hospital in Hamamatsu, Japan. The relationships between smoking and growth were evaluated with logistic regression. The individual effects of maternal smoking are related to low birth weight (LBW), short birth length and small head circumference. The individual effects of paternal smoking are related to short birth length and small head circumference. In the adjusted model, both parents' smoking showed clear associations with LBW (odds ratio [OR] = 1.64, 95% confidence interval [CI] 1.18-2.27) and short birth length (-1 standard deviation [SD] OR = 1.38, 95% CI 1.07-1.79; -2 SD OR = 2.75, 95% CI 1.84-4.10). Maternal smoking was significantly associated with birth weight and length, but paternal smoking was not. However, if both parents smoked, the risk of shorter birth length increased.

Antioxidant status and its association with elevated depressive symptoms among US adults: National Health and Nutrition Examination Surveys 2005–06

We examined the relationship of elevated depressive symptoms with antioxidant status as measured by serum levels of carotenoids, retinol+retinyl esters, vitamin C and vitamin E. Data from the National Health and Nutrition Examination Surveys 2005–06 on US adults aged 20–85 years (n=1,798) were analyzed. Depressive symptoms were measured using the Patient Health Questionnaire with a score cutpoint of 10 to define “elevated depressive symptoms”. An inverse association between total carotenoid level and elevated depressive symptoms was found with a reduction in the odds by 38% overall with each SD increase in exposure, and by 34% among women (p&lt;0.05). A dose‐response relationship was observed when total carotenoids were expressed as quartiles [Q4 vs. Q1: OR=0.42; 95% CI:0.24–0.72, P&lt;0.001; p‐ value for trend=0.042], though no significant associations were found with other antioxidant levels. Among carotenoids, β‐carotene and lutein+zeaxanthins had an independent inverse association with elevated depressive symptoms among US adults (per 1 SD OR=0.62, 95%CI:0.39–1.00 and 0.69, 95% CI: 0.50–0.96, respectively, p&lt;0.05). Total carotenoids (mainly β‐carotene and lutein+zeaxanthins) in plasma were associated with reduced levels of depressive symptoms among community‐dwelling US adults.

Glucose variability does not contribute to the development of peripheral and autonomic neuropathy in type 1 diabetes: data from the DCCT

Glucose variability does not contribute to the development of peripheral and autonomic neuropathy in type 1 diabetes: data from the DCCT

New perceptions on the S Doradus phenomenon and the micro variations of five Luminous Blue Variables (LBVs)

We investigated the photometric histories of the LBVs HR Car in the Galaxy, R 127, R 110 and R 71 in the LMC, and R 40 in the SMC by collecting all available photometry. All these objects have been reasonably well observed over the last few decades and a number of S Dor (SD) phases” (episodes of enhanced light) is well documented. Time-scales lie between 1.4 and 25 y. During the SD cycles two different types of micro-variations (amplitudes ) are present: one near the minima (time-scale from 2 to 6 weeks; colours generally blue in the maxima and red in the minima) and the other one near the maxima (time-scale ; colours generally red in the maxima and blue in the minima). Halfway the ascending and descending branches of the SD cycles the stars switch rather abruptly from one type to the other. We argue that the two types of SD phases are probably caused by different instability mechanisms.

Variations of S Dor and HDE 269006

Variations of S Dor and HDE 269006