A substantial observational literature relating specific fatty acid classes to chronic disease risk may be limited by its reliance on self-reported dietary data.
We aimed to develop biomarkers for ...saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acid densities, and to study their associations with cardiovascular disease (CVD), cancer, and type 2 diabetes (T2D) in Women’s Health Initiative (WHI) cohorts.
Biomarker equations were based primarily on serum and urine metabolomics profiles from an embedded WHI human feeding study (n = 153). Calibration equations were based on biomarker values in a WHI nutritional biomarker study (n = 436). Calibrated intakes were assessed in relation to disease incidence in larger WHI cohorts (n = 81,894). Participants were postmenopausal women, aged 50–79 when enrolled at 40 United States Clinical Centers (1993–1998), with a follow-up period of ∼20 y.
Biomarker equations meeting criteria were developed for SFA, MUFA, and PUFA densities. That for SFA density depended somewhat weakly on metabolite profiles. On the basis of our metabolomics platforms, biomarkers were insensitive to trans fatty acid intake. Calibration equations meeting criteria were developed for SFA and PUFA density, but not for MUFA density. With or without biomarker calibration, SFA density was associated positively with risk of CVD, cancer, and T2D, but with small hazard ratios, and CVD associations were not statistically significant after controlling for other dietary variables, including trans fatty acid and fiber intake. Following this same control, PUFA density was not significantly associated with CVD risk, but there were positive associations for some cancers and T2D, with or without biomarker calibration.
Higher SFA and PUFA diets were associated with null or somewhat higher risk for clinical outcomes considered in this population of postmenopausal United States women. Further research is needed to develop even stronger biomarkers for these fatty acid densities and their major components.
This study is registered with clinicaltrials.gov identifier: NCT00000611.
Several common variants in the intron 1 of FTO (fat mass and associated obesity) gene have been reliably associated with BMI and obesity in European populations. We analyzed two variants (rs9939609 ...and rs8050136) in 4,189 Chinese Han individuals and conducted a meta‐analysis of published studies in Asian population to investigate whether these variants are associated with type 2 diabetes (T2D) and obesity in Asian population. In this study, both the minor allele A of rs9939609 and the minor allele A of rs805136 were associated with increased risk of T2D, independent of measures of BMI; the odds ratios (ORs) per copy of the risk allele were 1.19 for rs9939609 (95% confidence interval (CI), 1.04–1.37; P = 0.01) and 1.22 for rs8050136 (95% CI, 1.07–1.40; P = 0.004) after adjusting for age, sex, and BMI. Our results also showed association with risk of obesity (rs9939609: OR = 1.39 (95% CI 1.04–1.85), P = 0.02; rs8050136: OR = 1.45 (95% CI 1.09–1.93), P = 0.01) but no association with overweight. These results were consistent with the pooled results from our meta‐analysis study (for diabetes, rs8050136, P = 1.3 × 10−3; rs9939609, P = 9.8 × 10−4; for obesity, rs8050136, P = 2.2 × 10−7; rs9939609, P = 9.0 × 10−9). Our findings indicate that the two variants (rs9939609 and rs8050136) in the FTO gene contribute to obesity and T2D in the Asian populations.
Some Shanghai Clinical Center f a role of Niemann-Pick type C1 (
) for obesity traits. However, whether the loss-of-function mutations in
cause adiposity in humans remains unknown. We recruited 25 ...probands with rare autosomal-recessive Niemann-Pick type C (NP-C) disease and their parents in assessment of the effect of heterozygous
mutations on adiposity. We found that male
carriers had a significantly higher BMI than matched control subjects or the whole population-based control subjects. Consistently, male
mice had increased fat storage while eating a high-fat diet. We further conducted an in-depth assessment of rare variants in the
gene in young, severely obese subjects and lean control subjects and identified 17 rare nonsynonymous/frameshift variants in
(minor allele frequency <1%) that were significantly associated with an increased risk of obesity (3.40% vs. 0.73%, respectively, in obese patients and control subjects,
= 0.0008, odds ratio = 4.8, 95% CI 1.7-13.2), indicating that rare
variants were enriched in young, morbidly obese Chinese subjects. Importantly, participants carrying rare variants with severely damaged cholesterol-transporting ability had more fat accumulation than those with mild/no damage rare variants. In summary, rare loss-of-function
mutations were identified as being associated with human adiposity with a high penetrance, providing potential therapeutic interventions for obesity in addition to the role of
in the familial NP-C disease.
In this study, a matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) strategy using cucurbitnuril (CBn) as a host molecule is proposed for the analysis of low molecular weight ...(LMW) compounds in complex samples. As a proof-of-concept, CB6 was selected as the host molecule, and endogenous polyamines in plant tissue were chosen as the target analytes. Due to the molecular recognition and mass shifting properties of CB6, the ionic signals associated with polyamines were moved to the higher mass region (>1000 Da) after specifically binding to CB6, while signal interference derived from the conventional organic matrix and the complex sample matrix remained in the low mass region because of the incompatibility of their molecular size with CB6 cavities. The strategy not only facilitated the analysis of LMW compounds in complex samples by MALDI MS, but also offered high throughput by accomplishing the entire analytical procedure within 10 min. The detection of polyamine concentration showed good linearity in the range of 0.02–10.0 ng/μL with correlation coefficients (R) greater than 0.9915. The limits of detection were 8.8–28.8 pg. The good reproducibility and reliability of the method were demonstrated by excellent intraday and interday precisions with relative standard deviations less than 7.9%, and the recovery ranged from 92.1% to 117.1%. Finally, the good sensitivity of the method allowed for the quantitative analysis of endogenous polyamine concentrations in various micro-tissues of Arabidopsis thaliana (20.0–740.0 μg fresh weight for each sample).
Display omitted
•A cucurbitnuril assisted MALDI MS strategy was presented.•Cucurbit6uril was employed as a selective mass shifting reagent of MALDI MS.•Quantitation of endogenous polyamines was realized in plant micro-tissues (∼μg FW).•High throughput analysis of polyamines in plant was accomplished within 10 min.
Objective
To determine the relationship of the gain‐of‐function variant A750T in leucine‐rich repeat containing G protein‐coupled receptor 4 (LGR4) with central obesity and related metabolic ...phenotypes.
Methods
The LGR4 A750T (c.2248 G > A) variant was detected by Sanger sequencing in a discovery young population and a validation community‐based population with obesity from eastern China. Fat indices determined by anthropometry and computed tomography scans and clinical biochemical measurements were collected for association analysis.
Results
LGR4 A750T was significantly correlated with waist circumference (P = 0.030) and waist‐to‐height ratio (P < 0.001) in the young cohort (N = 594) and with waist‐to‐hip ratio (P = 0.013) in the community population (N = 1067). Combined analysis showed a significant correlation of the variant with waist circumference (P < 0.001) and waist‐to‐hip ratio (P = 0.021). Moreover, the variant had a remarkable correlation with abdominal visceral fat area (P = 0.004) and was associated with 2‐h plasma insulin (P = 0.009) and the Matsuda index (P = 0.027) after an oral glucose tolerance test in young subjects with obesity.
Conclusions
The LGR4 A750T variant may contribute to central obesity characterized by abdominal visceral fat accumulation.
To develop an approach for automatically analyzing bone metastases (BMs) on bone scintigrams based on deep learning technology.
This research included a bone scan classification model, a regional ...segmentation model, an assessment model for tumor burden and a diagnostic report generation model. Two hundred eighty patients with BMs and 341 patients with non-BMs were involved. Eighty percent of cases were randomly extracted from two groups as training set. Remaining cases were as testing set. A deep residual convolutional neural network with different structures was used to determine whether metastatic bone lesions existed, regions of lesions were automatically segmented. Bone scan tumor burden index (BSTBI) was calculated; finally, diagnostic report could be automatically generated. The sensitivity, specificity and accuracy of classification model were compared with three physicians with different clinical experience. The Dice coefficient evaluated the effect of segmentation model and compared to the result of nnU-Net model. The correlation between BSTBI and blood alkaline phosphatase (ALP) level was analyzed to verify the efficiency of BSTBI. The performance of report generation model was evaluated by the accuracy of interpretation of report.
In testing set, the sensitivity, specificity and accuracy of classification model were 92.59%, 85.51% and 88.62%, respectively. The accuracy showed no statistical difference with moderately and experienced physicians and obviously outperformed the inexperienced. The Dice coefficient of BMs area was 0.7387 in segmentation stage. Based on the whole model frame, our segmentation model outperformed the nnU-Net. BSTBI value changed as the BMs changed. There was a positive correlation between BSTBI and ALP level. The accuracy of report generation model was 78.05%.
Deep learning based on automatic analysis frameworks for BMs can accurately identify BMs, preliminarily realize a fully automatic analysis process from raw data to report generation. BSTBI can be used as a quantitative evaluation indicator to assess the effect of therapy on BMs in different patients or in the same patient before and after treatment.
Background
Cardiometabolic abnormalities are a leading cause of death among women, including women with cancer.
Methods
This study examined the association between prediagnosis cardiovascular health ...and total and cause‐specific mortality among 12,076 postmenopausal women who developed local‐ or regional‐stage invasive cancer in the Women's Health Initiative (WHI). Cardiovascular risk factors included waist circumference, hypertension, high cholesterol, and type 2 diabetes. Obesity‐related cancers included breast cancer, colorectal cancer, endometrial cancer, kidney cancer, pancreatic cancer, ovarian cancer, stomach cancer, liver cancer, and non‐Hodgkin lymphoma. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for important predictors of survival.
Results
After a median follow‐up of 10.0 years from the date of the cancer diagnosis, there were 3607 total deaths, with 1546 (43%) due to cancer. Most participants (62.9%) had 1 or 2 cardiometabolic risk factors, and 8.1% had 3 or 4. In adjusted models, women with 3 to 4 risk factors (vs none) had a higher risk of all‐cause mortality (HR, 1.99; 95% CI, 1.73‐2.30), death due to cardiovascular disease (CVD) (HR, 4.01; 95% CI, 2.88‐5.57), cancer‐specific mortality (HR, 1.37; 95% CI, 1.1‐1.72), and other‐cause mortality (HR, 2.14; 95% CI, 1.70‐2.69). A higher waist circumference was associated with greater all‐cause mortality (HR, 1.17; 95% CI, 1.06‐1.30) and cancer‐specific mortality (HR, 1.22; 95% CI, 1.04‐1.42).
Conclusions
Among postmenopausal women diagnosed with cancer in the WHI, cardiometabolic risk factors before the cancer diagnosis were associated with greater all‐cause, CVD, cancer‐specific, and other‐cause mortality. These results raise hypotheses regarding potential clinical intervention strategies targeting cardiometabolic abnormalities that require future prospective studies for confirmation.
Lay Summary
This study uses information from the Women's Health Initiative (WHI) to find out whether cardiac risk factors are related to a greater risk of dying among older women with cancer. The WHI is the largest study of medical problems faced by older women in this country.
The results show that women who have 3 or 4 risk factors are more likely to die of any cause, heart disease, or cancer in comparison with women with no risk factors.
It is concluded that interventions to help to lower the burden of cardiac risk factors can have an important impact on survivorship among women with cancer.
Among postmenopausal women with select early‐stage cancers associated with metabolic syndrome, a higher number of cardiometabolic abnormalities is associated with a significantly higher risk of overall death in addition to a higher risk of death due to cancer, heart disease, and other causes. These findings highlight a major gap in the care of patients with cancer and the need for improved efforts by public health systems to improve cancer survivorship.
Invited for the cover of this issue is the group of Lyle Isaacs and Simin Liu at the University of Maryland and Wuhan University of Science and Technology. The image depicts two packed “sandwiches” ...and one supramolecular “Russian doll” that are assembled by host–guest and charge‐transfer interactions. Read the full text of the article at 10.1002/chem.201604149.
“Besides the simultaneous encapsulation of multiple guests by cucurbit10uril (CB10), the most interesting finding is that tetracationic cyclophane, blue box, can be included inside CB10, and a CB10 protected pseudorotaxane, “Russian doll”, can be assembled by threading a guest through the cavities of both blue box and CB10.” Read more about the story behind the cover in the Cover Profile and about the research itself on page 17612 ff. (DOI: 10.1002/chem.20164149).
To explore the feasibility of morphological and functional evaluation of the lateral pterygoid muscle (LPM) by diffusion tensor imaging (DTI) in vivo.
30 healthy volunteers underwent DTI with the jaw ...in the rest position, opening and clenching. Diffusion parameters of the superior head of the LPM (SHLP) and the inferior head of the LPM (IHLP) at different jaw positions were calculated.
When the jaw was in the rest position, λ
of the SHLP was significantly lower than that of the IHLP; fractional anisotropy (FA) value of the SHLP was significant higher than that of the IHLP. There was no significant difference in λ
, λ
and apparent diffusion coefficient (ADC) value. During jaw opening, there was significant increase of all three eigenvalues and ADC value, and significant decrease of FA value both at the SHLP and IHLP. Clenching caused a significant increase in the ADC and all three eigenvalues, and caused a significant decrease of FA at the SHLP. However, at the IHLP, the variations of all diffusion parameters by clenching in the intercuspal position showed no significance when compared with those at rest.
The morphological and functional changes of LPM fibres caused by jaw movements could be sensitively detected by DTI which may serve as a new and non-invasive method for simultaneously investigating the functional and morphological features of the LPM during jaw movement.
A new application of DTI is proposed for the morphological and functional evaluation of the LPMs. The results show that the significant change of three eigenvalues indicates the activity of the LPM in a specific jaw movement, a finding that shows the potential value of DTI serving as a new and non-invasive method for investigation of the LPM.
Diet quality is a risk factor for chronic disease and mortality. Differential DNA methylation across the epigenome has been associated with chronic disease risk. Whether diet quality is associated ...with differential methylation is unknown. This study assessed whether diet quality was associated with differential DNA methylation measured across 445 548 loci in the Women's Health Initiative (WHI) and the TwinsUK cohort.
The discovery cohort consisted of 4355 women from the WHI. The replication cohort consisted of 571 mono- and dizygotic twins from the TwinsUK cohort. DNA methylation was measured in whole blood using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). A meta-analysis, stratified by study cohort, was performed using generalized linear models that regressed methylation on AHEI-2010, adjusting for cell composition, chip number and location, study characteristics, principal components of genetic relatedness, age, smoking status, race/ethnicity and body mass index (BMI). Statistical significance was defined as a false discovery rate < 0.05. Significant sites were tested for replication in the TwinsUK cohort, with significant replication defined by P < 0.05 and a consistent direction.
Diet quality was significantly associated with differential DNA methylation at 428 cytosine-phosphate-guanine (CpG) sites in the discovery cohort. A total of 24 CpG sites were consistent with replication in the TwinsUK cohort, more than would be expected by chance (P = 2.7x10-4), with one site replicated in both the blood and adipose tissue (cg16379999 located in the body of SEL1L).
Diet quality was associated with methylation at 24 CpG sites, several of which have been associated with adiposity, inflammation and dysglycaemia. These findings may provide insight into pathways through which diet influences chronic disease.
PDF
