Publications by authors named "Simin Liu"

397 Publications

Diffusion Tensor Imaging of the Lateral Pterygoid Muscle in Patients with Temporomandibular Joint Disorders and Healthy Volunteers.

Korean J Radiol 2021 Oct 1. Epub 2021 Oct 1.

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: This study aimed to explore the feasibility of functional evaluation of the lateral pterygoid muscle (LPM) using diffusion tensor imaging (DTI) in patients with temporomandibular joint disorders (TMDs).

Materials And Methods: A total of 119 patients with TMD (23 male and 96 female; mean age ± standard deviation, 41 ± 15 years; 58 bilateral and 61 unilateral involvements for a total of 177 joints) and 20 healthy volunteers (9 male and 11 female; 40 ± 13 years; 40 joints) were included in this prospective study. Based on DTI of the jaw in the resting state, the diffusion parameters, apparent diffusion coefficient (ADC), fractional anisotropy (FA), λ1, λ2, and λ3 of the superior and inferior heads of the LPM (SHLPM and IHLPM) were measured. Patients with TMD with normal disc position (ND), anterior disc displacement with reduction (ADWR), and anterior disc displacement without reduction (ADWOR) were compared.

Results: Patients with TMD overall, and ADWR and ADWOR subgroups had significantly higher ADC, λ1, λ2, and λ3 in both the SHLPM and IHLPM than those in volunteers ( < 0.05 for all), whereas the ND subgroup only had significantly higher ADC and λ1 ( < 0.001). Meanwhile, significant differences in FA in the SHLPM and IHLPM were found between volunteers and ADWOR ( = 0.014 and = 0.037, respectively). Among the three TMD subgroups, except for λ3 and FA in the ADWR subgroup, ADWR and ADWOR subgroups had significantly higher ADC, λ1, λ2, and λ3 and lower FA than those in the ND group ( < 0.050). There was no significant difference in diffusion variables between ADWR and ADWOR. In ADWOR, the osteoarthritis group had significantly higher λ3 and lower FA values in the IHLPM than those in the non-osteoarthritis group.

Conclusion: DTI successfully detected functional changes in the LPM in patients with TMD. The unsynchronized diffusivity changes in the LPM in different subgroups of TMD signified the possibility of using diffusion parameters as indicators to identify the severity of LPM hyperfunction at various stages of TMD.
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http://dx.doi.org/10.3348/kjr.2021.0132DOI Listing
October 2021

Slab boundary artifact correction in multislab imaging using convolutional-neural-network-enabled inversion for slab profile encoding.

Magn Reson Med 2021 Oct 15. Epub 2021 Oct 15.

Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, People's Republic of China.

Purpose: This study aims to propose a novel algorithm for slab boundary artifact correction in both single-band multislab imaging and simultaneous multislab (SMSlab) imaging.

Theory And Methods: In image domain, the formation of slab boundary artifacts can be regarded as modulating the artifact-free images using the slab profiles and introducing aliasing along the slice direction. Slab boundary artifact correction is the inverse problem of this process. An iterative algorithm based on convolutional neural networks (CNNs) is proposed to solve the problem, termed CNN-enabled inversion for slab profile encoding (CPEN). Diffusion-weighted SMSlab images and reference images without slab boundary artifacts were acquired in 7 healthy subjects for training. Images of 5 healthy subjects were acquired for testing, including single-band multislab and SMSlab images with 1.3-mm or 1-mm isotropic resolution. CNN-enabled inversion for slab profile encoding was compared with a previously reported method (i.e., nonlinear inversion for slab profile encoding [NPEN]).

Results: CNN-enabled inversion for slab profile encoding reduces the slab boundary artifacts in both single-band multislab and SMSlab images. It also suppresses the slab boundary artifacts in the diffusion metric maps. Compared with NPEN, CPEN shows fewer residual artifacts in different acquisition protocols and more significant improvements in quantitative assessment, and it also accelerates the computation by more than 35 times.

Conclusion: CNN-enabled inversion for slab profile encoding can reduce the slab boundary artifacts in multislab acquisitions. It shows better slab boundary artifact correction capacity, higher robustness, and computation efficiency when compared with NPEN. It has the potential to improve the accuracy of multislab acquisitions in high-resolution DWI and functional MRI.
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http://dx.doi.org/10.1002/mrm.29047DOI Listing
October 2021

Genetic discovery and risk characterization in type 2 diabetes across diverse populations.

HGG Adv 2021 Apr 9;2(2). Epub 2021 Mar 9.

Division of Statistical Genomics, School of Medicine, Washington University, St. Louis, MO, USA.

Genomic discovery and characterization of risk loci for type 2 diabetes (T2D) have been conducted primarily in individuals of European ancestry. We conducted a multiethnic genome-wide association study of T2D among 53,102 cases and 193,679 control subjects from African, Hispanic, Asian, Native Hawaiian, and European population groups in the Population Architecture Genomics and Epidemiology (PAGE) and Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortia. In individuals of African ancestry, we discovered a risk variant in the gene (rs11466334, risk allele frequency (RAF) = 6.8%, odds ratio [OR] = 1.27, p = 2.06 × 10), which replicated in independent studies of African ancestry (p = 6.26 × 10). We identified a multiethnic risk variant in the gene (rs13052926, RAF = 14.1%, OR = 1.08, p = 5.75 × 10), which also replicated in independent studies (p = 3.45 × 10). We also observed a significant difference in the performance of a multiethnic genetic risk score (GRS) across population groups (p = 3.85 × 10). Comparing individuals in the top GRS risk category (40%-60%), the OR was highest in Asians (OR = 3.08) and European (OR = 2.94) ancestry populations, followed by Hispanic (OR = 2.39), Native Hawaiian (OR = 2.02), and African ancestry (OR = 1.57) populations. These findings underscore the importance of genetic discovery and risk characterization in diverse populations and the urgent need to further increase representation of non-European ancestry individuals in genetics research to improve genetic-based risk prediction across populations.
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http://dx.doi.org/10.1016/j.xhgg.2021.100029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486151PMC
April 2021

Achieving Enhanced Photochromic Properties of Diarylethene through Host-Guest Interaction in Aqueous Solution.

Chemistry 2021 Sep 17. Epub 2021 Sep 17.

The State Key Laboratory of Refractories and Metallurgy, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, 430081, P. R. China.

Diarylethene (DTE) has been widely used in fluorescence probes, molecular logic gates, optical data-storage devices owing to the excellent photochromic property, while constructing high-performance photochromic DTE in aqueous media remains a big challenge. Herein we present several host-guest systems formed between cucurbit[n]uril (CB[n], n=7, 8, 10) and two water-soluble DTE derivatives 1 and 2. It was found that host-guest interactions not only affect the photophysical properties of photochromic guests, but also make great differences on the photoreaction process. Different host-guest binding behaviors also lead to different effects on the photochromic properties of guests. In the presence of CB[n], both 1 and 2 showed enhanced emission and higher fluorescence quenching ratio at photostationary state. Besides, CB[10]⋅1 exhibited faster response rate in cyclization reaction and better photofatigue resistance than free 1 in aqueous solution, while the supramolecular assembly of (CB[8]) ⋅(2) showed slower response rate in both directions of the reversible photoreaction. Besides, the photofatigue resistance of 2 can be greatly improved through binding with CB[7]. Our results suggest that host-guest interactions could be an efficient way to improve photochromic properties of DTE in aqueous solution.
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http://dx.doi.org/10.1002/chem.202102731DOI Listing
September 2021

Biosynthesis of 3'-O-methylisoorientin from luteolin by selecting O-methylation/C-glycosylation motif.

Enzyme Microb Technol 2021 Oct 29;150:109862. Epub 2021 Jun 29.

Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing, China; College of Chemical Engineering, Nanjing Forestry University, Nanjing, China; Jiangsu Key Lab of Biomass-Based Green Fuels and Chemicals, Nanjing, China. Electronic address:

Glycosylation and methylation of flavonoids are the main types of structural modifications and can endow flavonoids with greater stability, bioactivity, and bioavailability. In this study, five types of O-methyltransferases were screened for producing O-methylated luteolin, and the biosynthesis strategy of 3'-O-methylisoorientin from luteolin was determined. To improve the production of 3'-O-methylluteolin, the S-adenosyl-l-methionine synthesis pathway was reconstructed in the recombinant strain by introducing S-adenosyl-l-methionine synthetase genes. After optimizing the conversion conditions, maximal 3'-O-methylluteolin production reached 641 ± 25 mg/L with a corresponding molar conversion of 76.5 %, which was the highest titer of methylated flavonoids reported to date in Escherichia coli. 3'-O-Methylluteolin (127 mg) was prepared from 250 mL of the broth by silica gel column chromatography and preparative HPLC with a yield of 79.4 %. Subsequently, we used the biocatalytic cascade of Gentiana triflora C-glycosyltransferase (Gt6CGT) and Glycine max sucrose synthase (GmSUS) to biosynthesize 3'-O-methylisoorientin from 3'-O-methylluteolin in vitro. By optimizing the coupled reaction conditions and using the fed-batch operation, maximal 3'-O-methylisoorientin production reached 226 ± 8 mg/L with a corresponding molar conversion of 98 %. Therefore, this study provides an efficient method for the production of novel 3'-O-methylisoorientin and the biosynthesis strategy for methylated C-glycosylation flavonoids by selective O-methylation/C-glycosylation motif on flavonoids.
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http://dx.doi.org/10.1016/j.enzmictec.2021.109862DOI Listing
October 2021

Analysis of Genetic Alterations Related to DNA Methylation in Testicular Germ Cell Tumors Based on Data Mining.

Cytogenet Genome Res 2021 25;161(6-7):382-394. Epub 2021 Aug 25.

Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Embryonal carcinoma (EC) and seminoma (SE) are both derived from germ cell neoplasia in situ but show big differences in growth patterns and clinical prognosis. Epigenetic regulation may play an important role in the development of EC and SE. This study investigated the DNA methylation-based genetic alterations between EC and SE by analyzing the datasets of mRNA expression and DNA methylation profiling. The datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified between EC and SE by limma package in R environment. Gene function enrichment analysis of the DEGs was performed on the DAVID tool, the results of which suggested differences in capability of pluripotency and genomic stability between EC and SE. The minfi package and wANNOVAR tool were used to identify differentially methylated genes. A total of 37 genes were discovered with both mRNA expression and the accordant DNA methylation changes. The findings were verified by the sequencing data from The Cancer Genome Atlas database, and Kaplan-Meier survival analysis was performed. Finally, 5 genes (PRDM1, LMO2, FAM53B, HCN4, and FAM124B) were found that showed both low expression and high methylation in EC, and were significantly associated with relapse-free survival. The findings of methylation-based genetic features between EC and SE might be helpful in studying the role of DNA methylation in cancer development.
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http://dx.doi.org/10.1159/000516385DOI Listing
October 2021

Tunable White-Light Emissions of Azapyrene Derivatives with Cucurbit[]uril Hosts in Aqueous Solution.

Org Lett 2021 Sep 19;23(17):6633-6637. Epub 2021 Aug 19.

The State Key Laboratory of Refractories and Metallurgy, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, China.

Cucurbit[]uril (CB[])-mediated assembly of π-conjugated azapyrene derivatives with rigid aromatic rings as bridging units into optically tunable complexes is reported. Due to the hindrance of rotation of diazapyrene moieties and the enhancement of intramolecular charge transfer of chromophore guests within the cavity of the CB[8] host, color tuning including white-light emission was easily achieved by introducing CB[8] into the guest aqueous solution, therefore suggesting a feasible strategy for the creation of tunable white-light emission materials through CB[]-based host-guest interactions.
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http://dx.doi.org/10.1021/acs.orglett.1c02081DOI Listing
September 2021

Genetic insights into biological mechanisms governing human ovarian ageing.

Nature 2021 08 4;596(7872):393-397. Epub 2021 Aug 4.

Genome Integrity and Instability Group, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.

Reproductive longevity is essential for fertility and influences healthy ageing in women, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.
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http://dx.doi.org/10.1038/s41586-021-03779-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611832PMC
August 2021

Relationship Between a Plant-Based Dietary Portfolio and Risk of Cardiovascular Disease: Findings From the Women's Health Initiative Prospective Cohort Study.

J Am Heart Assoc 2021 08 4;10(16):e021515. Epub 2021 Aug 4.

Department of Nutritional Sciences University of Toronto Ontario Canada.

Background The plant-based Dietary Portfolio combines established cholesterol-lowering foods (plant protein, nuts, viscous fiber, and phytosterols), plus monounsaturated fat, and has been shown to improve low-density lipoprotein cholesterol and other cardiovascular disease (CVD) risk factors. No studies have evaluated the relation of the Dietary Portfolio with incident CVD events. Methods and Results We followed 123 330 postmenopausal women initially free of CVD in the Women's Health Initiative from 1993 through 2017. We used Cox proportional-hazard models to estimate adjusted hazard ratios (HRs) and 95% CI of the association of adherence to a Portfolio Diet score with CVD outcomes. Primary outcomes were total CVD, coronary heart disease, and stroke. Secondary outcomes were heart failure and atrial fibrillation. Over a mean follow-up of 15.3 years, 13 365 total CVD, 5640 coronary heart disease, 4440 strokes, 1907 heart failure, and 929 atrial fibrillation events occurred. After multiple adjustments, adherence to the Portfolio Diet score was associated with lower risk of total CVD (HR, 0.89; 95% CI, 0.83-0.94), coronary heart disease (HR, 0.86; 95% CI, 0.78-0.95), and heart failure (HR, 0.83; 95% CI, 0.71-0.99), comparing the highest to lowest quartile of adherence. There was no association with stroke (HR, 0.97; 95% CI, 0.87-1.08) or atrial fibrillation (HR, 1.10; 95% CI, 0.87-1.38). These results remained statistically significant after several sensitivity analyses. Conclusions In this prospective cohort of postmenopausal women in the United States, higher adherence to the Portfolio Diet was associated with a reduction in incident cardiovascular and coronary events, as well as heart failure. These findings warrant further investigation in other populations.
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http://dx.doi.org/10.1161/JAHA.121.021515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475059PMC
August 2021

Pasta meal intake in relation to risks of type 2 diabetes and atherosclerotic cardiovascular disease in postmenopausal women : findings from the Women's Health Initiative.

BMJ Nutr Prev Health 2021 30;4(1):195-205. Epub 2021 Apr 30.

Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island, USA.

Objective: To evaluate the association between pasta meal intake and long-term risk of developing diabetes or atherosclerotic cardiovascular disease (ASCVD, including coronary heart disease (CHD) and stroke) in postmenopausal women.

Design: Prospective cohort study.

Setting: Women's Health Initiative (WHI) in the USA.

Participants: 84 555 postmenopausal women aged 50-79 in 1994, who were free of diabetes, ASCVD and cancer at baseline who were not in the dietary modification trial of the WHI, completed a validated food frequency questionnaire, and were evaluated for incident diabetes and ASCVD outcomes during the follow-up until 2010.

Main Outcome Measure: Diabetes and ASCVD.

Results: Cox proportional hazards models were used to estimate the association (HR) between quartiles of pasta meal consumption (residuals after adjusting for total energy) and the risk of incidence diabetes, CHD, stroke or ASCVD, accounting for potential confounding factors, with testing for linear trend. We then statistically evaluated the effect of substituting white bread or fried potato for pasta meal on disease risk. When comparing the highest to the lowest quartiles of residual pasta meal intake, we observed significantly reduced risk of ASCVD (HR=0.89, 95% CI 0.83 to 0.96, p trend=0.002), stroke (HR=0.84, 95% CI 0.75 to 0.93, p trend=0.001), CHD (HR=0.91, 95% CI 0.83 to 1.00, p trend=0.058) and no significant alteration in diabetes risk (HR=1.02, 95% CI 0.96 to 1.07, p trend=0.328). Replacing white bread or fried potato with pasta meal was statistically associated with decreased risk of stroke and ASCVD.

Conclusions: Pasta meal intake did not have adverse effects on long-term diabetes risk and may be associated with significant reduced risk of stroke and ASCVD. The potential benefit of substituting pasta meal for other commonly consumed starchy foods on cardiometabolic outcomes warrants further investigation in additional high-quality and large prospective studies of diverse populations.
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http://dx.doi.org/10.1136/bmjnph-2020-000198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258098PMC
April 2021

Improving distortion correction for isotropic high-resolution 3D diffusion MRI by optimizing Jacobian modulation.

Magn Reson Med 2021 11 14;86(5):2780-2794. Epub 2021 Jun 14.

Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China.

Purpose: To improve distortion correction for isotropic high-resolution whole-brain 3D diffusion MRI when in a time-saving acquisition scenario.

Theory And Methods: Data were acquired using simultaneous multi-slab (SMSlab) acquisitions, with a b = 0 image pair encoded by reversed polarity gradients (RPG) for phase encoding (PE) and diffusion weighted images encoded by a single PE direction. Eddy current-induced distortions were corrected first. During the following susceptibility distortion correction, image deformation was first corrected by the field map estimated from the b = 0 image pair. Intensity variation was subsequently corrected by Jacobian modulation. Two Jacobian modulation methods were compared. They calculated the Jacobian modulation map from the field map, or from the deformation corrected b = 0 image pair, termed as J and J , respectively. A modified version of the J method, with proper smoothing, was further proposed for improved correction performance, termed as J .

Results: Compared to J modulation, less remaining distortions are observed when using the J and J methods, especially in areas with large B0 field inhomogeneity. The original J method causes signal-to-noise ratio (SNR) deficiency problem, which manifests as degraded SNR of the diffusion weighted images, while the J method maintains the original image SNR. Less estimation errors of diffusion metrics are observed when using the J method.

Conclusion: This study improves the distortion correction for isotropic high-resolution whole-brain 3D diffusion MRI by optimizing Jacobian modulation. The optimized method outperforms the conventional J method regarding intensity variation correction and accuracy of diffusion metrics estimation, and outperforms the original J method regarding SNR performance.
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http://dx.doi.org/10.1002/mrm.28884DOI Listing
November 2021

DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function.

Clin Epigenetics 2021 Jun 2;13(1):121. Epub 2021 Jun 2.

Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Background: The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies.

Results: We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E-03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang's 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (β =  - 0.12, 95% CI = [- 0.16, - 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E-08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (β = 0.12 [0.07, 0.16], p = 2.08E-06). The "first-generation" clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria.

Conclusion: DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease.
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http://dx.doi.org/10.1186/s13148-021-01082-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170969PMC
June 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Sex and Race Differences in the Risk of Ischemic Stroke Associated With Fasting Blood Glucose in REGARDS.

Neurology 2021 08 27;97(7):e684-e694. Epub 2021 May 27.

From the Departments of Emergency Medicine (T.E.M.), Neurology (K.L.F.), Epidemiology (S.L.), Medicine (S.L.), and Surgery (S.L.), and Center for Global Cardiometabolic Health, Brown University School of Public Health (S.L.), Alpert Medical School of Brown University, Providence, RI; Departments of Biostatistics (D.L.L., G.H.) and Epidemiology (A.P.C., V.J.H.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (D.O.K.), University of Michigan Medical School, Ann Arbor; and Department of Medicine, Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital/Harvard Medical School, Boston, MA.

Objective: To investigate sex and race differences in the association between fasting blood glucose (FBG) and risk of ischemic stroke (IS).

Methods: This prospective longitudinal cohort study included adults age ≥45 years at baseline in the Reasons for Geographic And Racial Differences in Stroke Study, followed for a median of 11.4 years. The exposure was baseline FBG (mg/dL); suspected IS events were ascertained by phone every 6 months and were physician-adjudicated. Cox proportional hazards were used to assess the adjusted sex/race-specific associations between FBG (by category and as a restricted cubic spline) and incident IS.

Results: Of 20,338 participants, mean age was 64.5 (SD 9.3) years, 38.7% were Black, 55.4% were women, 16.2% were using diabetes medications, and 954 IS events occurred. Compared to FBG <100, FBG ≥150 was associated with 59% higher hazards of IS (95% confidence interval [CI] 1.21-2.08) and 61% higher hazards of IS among those on diabetes medications (95% CI 1.12-2.31). The association between FBG and IS varied by race/sex (hazard ratio, FBG ≥150 vs FBG <100: White women 2.05 [95% CI 1.23-3.42], Black women 1.71 [95% CI 1.10-2.66], Black men 1.24 [95% CI 0.75-2.06], White men 1.46 [95% CI 0.93-2.28], = 0.004). Analyses using FBG splines suggest that sex was the major contributor to differences by race/sex subgroups.

Conclusions: Sex differences in the strength and shape of the association between FBG and IS are likely driving the significant differences in the association between FBG and IS across race/sex subgroups. These findings should be explored further and may inform tailored stroke prevention guidelines.
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http://dx.doi.org/10.1212/WNL.0000000000012296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377876PMC
August 2021

Flavonoid consumption and cardiometabolic health: Potential benefits due to foods, supplements, or biomarkers?

Am J Clin Nutr 2021 07;114(1):9-11

Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.

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http://dx.doi.org/10.1093/ajcn/nqab147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246617PMC
July 2021

High-resolution whole-brain diffusion MRI at 3T using simultaneous multi-slab (SMSlab) acquisition.

Neuroimage 2021 08 1;237:118099. Epub 2021 May 1.

Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China. Electronic address:

High-resolution diffusion MRI (dMRI) is a crucial tool in neuroscience studies to detect fine fiber structure, depict complex fiber architecture and analyze cortical anisotropy. However, high-resolution dMRI is limited by its intrinsically low SNR due to diffusion attenuation. A series of techniques have been proposed to improve the SNR performance, but most of them are at the cost of long scan time, which in turn sacrifice the SNR efficiency, especially for large FOV imaging, such as whole-brain imaging. Recently, a combination of 3D multi-slab acquisition and simultaneous multi-slice (SMS) excitation, namely simultaneous multi-slab (SMSlab), has been demonstrated to have potential for high-resolution diffusion imaging with high SNR and SNR efficiency. In our previous work, we have proposed a 3D Fourier encoding and reconstruction framework for SMSlab acquisition. In this study, we extend this 3D k-space framework to diffusion imaging, by developing a novel navigator acquisition strategy and exploring a k-space-based phase correction method. In vivo brain data are acquired using the proposed SMSlab method and compared with a series of different acquisitions, including the traditional 3D multi-slab, 2D SMS and 2D single-shot EPI (ss-EPI) acquisitions. The results demonstrate that SMSlab has a better SNR performance compared with 3D multi-slab and 2D SMS. The detection capacity of fine fiber structures is improved using SMSlab, compared with the low-resolution diffusion imaging using conventional 2D ss-EPI.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118099DOI Listing
August 2021

Triple Stack of a Viologen Derivative in a CB[10] Pair.

Org Lett 2021 Jul 14;23(14):5283-5287. Epub 2021 Apr 14.

Aix Marseille Univ, CNRS, ICR, Marseille, France.

A viologen-phenylene-imidazole () conjugate, previously shown to be singly complexed by CB[7] and doubly bound by CB[8], is herein shown to form antiparallel triple stacks in water with cucurbit[10]uril (CB[10]), pairwise complexing the guest trimer. The quinary host:guest 2:3 complex showed features assignable to charge-transfer interactions. Under reductive conditions, CB[10] could solubilize a radical, even though CB[10] and reduced are almost insoluble, thereby illustrating a possible new application for CB[10].
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http://dx.doi.org/10.1021/acs.orglett.1c00773DOI Listing
July 2021

Dietary Patterns of Insulinemia, Inflammation and Glycemia, and Pancreatic Cancer Risk: Findings from the Women's Health Initiative.

Cancer Epidemiol Biomarkers Prev 2021 06 7;30(6):1229-1240. Epub 2021 Apr 7.

Interdisciplinary Ph.D. Program in Nutrition, The Ohio State University, Columbus, Ohio.

Background: Pancreatic cancer risk is increasing in countries with high consumption of Western dietary patterns and rising obesity rates. We examined the hypothesis that specific dietary patterns reflecting hyperinsulinemia (empirical dietary index for hyperinsulinemia; EDIH), systemic inflammation (empirical dietary inflammatory pattern; EDIP), and postprandial glycemia [glycemic index (GI); glycemic load (GL)] are associated with pancreatic cancer risk, including the potential modifying role of type 2 diabetes (T2D) and body mass index (BMI).

Methods: We calculated dietary scores from baseline (1993-1998) food frequency questionnaires among 129,241 women, 50-79 years-old in the Women's Health Initiative. We used multivariable-adjusted Cox regression to estimate HRs and 95% confidence intervals (95% CI) for pancreatic cancer risk.

Results: During a median 19.9 years of follow-up, 850 pancreatic cancer cases were diagnosed. We observed no association between dietary scores and pancreatic cancer risk overall. However, risk was elevated among participants with longstanding T2D (present >3 years before pancreatic cancer diagnosis) for EDIH. For each 1 SD increment in dietary score, the HRs (95% CIs) were: EDIH, 1.33 (1.06-1.66); EDIP, 1.26 (0.98-1.63); GI, 1.26 (0.96-1.67); and GL, 1.23 (0.96-1.57); although interactions were not significant (all >0.05). Separately, we observed inverse associations between GI [0.86 (0.76-0.96), = 0.0068] and GL [0.83 (0.73-0.93), = 0.0075], with pancreatic cancer risk among normal-weight women.

Conclusions: We observed no overall association between the dietary patterns evaluated and pancreatic cancer risk, although women with T2D appeared to have greater cancer risk.

Impact: The elevated risk for hyperinsulinemic diets among women with longstanding T2D and the inverse association among normal-weight women warrant further examination.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172436PMC
June 2021

Biomarkers of phthalates and inflammation: Findings from a subgroup of Women's Health Initiative participants.

Int J Hyg Environ Health 2021 05 1;234:113743. Epub 2021 Apr 1.

Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA, USA. Electronic address:

Background: Recent experimental work has shown that phthalates may increase inflammation. Prior research has not examined the role of exposure to phthalates in relation to inflammatory status among postmenopausal women who are at higher risk of developing inflammation-related chronic disorders.

Objectives: We aimed to examine the associations of urinary phthalate biomarker concentrations with circulating levels of c-reactive protein [CRP] and interleukin-6 [IL-6] among 443 postmenopausal women selected into a breast cancer case-control study nested within the Women's Health Initiative (WHI).

Methods: A total of 13 phthalate metabolites were measured in urine samples provided at WHI enrollment from 1993 to 1998. We also measured baseline levels of CRP and IL-6 in these women's serum or plasma samples. Multivariable linear models were used to investigate the role of each phthalate biomarker in relation to CRP and IL-6, adjusting for potential confounding factors and specifically evaluating the role of BMI.

Results: In adjusted models we observed positive associations of monocarboxynonyl phthalate (MCNP) with CRP (β = 0.092; 95% CI 0.026, 0.158) and IL-6 (β = 0.108; 95% CI 0.013, 0.204). These positive associations were attenuated and non-significant, however, after further adjustment for body mass index (BMI). In contrast, we observed inverse associations of monoethyl phthalate (MEP) (β = -0.019; 95% CI -0.036, -0.001) and monobenzyl phthalate (MBzP) (β = -0.034; 95% CI -0.058, -0.010) with CRP levels only after adjustment for BMI. Other phthalate biomarkers examined were not significantly associated with either CRP or IL-6 levels.

Conclusions: Overall, these results do not suggest an important role for phthalates in promoting an inflammatory response. Future prospective studies are warranted to improve understanding of these associations, particularly in clarifying the role of BMI.
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http://dx.doi.org/10.1016/j.ijheh.2021.113743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096686PMC
May 2021

Remnant cholesterol is prospectively associated with CVD events and all-cause mortality in kidney transplant recipients: the FAVORIT study.

Nephrol Dial Transplant 2021 Mar 24. Epub 2021 Mar 24.

Center for Primary Care, Prevention, Brown University, Providence, RI, USA.

Background: The cholesterol content of circulating triglyceride-rich lipoproteins is characterized as remnant cholesterol, although little is known about its role in the development of CVD outcomes, all-cause mortality, or transplant failure in kidney transplant recipients. Our primary aim was to investigate the prospective association of remnant cholesterol and the risk of CVD events in renal transplant recipients with secondary aims evaluating remnant cholesterol and renal graft failure and all-cause mortality among participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial.

Methods: Among 4,110 enrolled participants, 98 were excluded for missing baseline remnant cholesterol levels and covariates. Non fasting remnant cholesterol levels were calculated based upon lipid profiles in 3,812 FAVORIT trial participants at randomization. Wilcoxon-type test for trend were used to compare baseline characteristics across remnant cholesterol quartiles. Cox proportional hazards regression was used to evaluate the association of baseline remnant cholesterol levels with time to primary and secondary study outcomes.

Results: During a median follow-up of 4.0 years, we documented 548 CVD incident events, 343 transplant failures, 452 All-Cause deaths. When comparing highest quartile 4 to quartile 1, proportional hazards modeling revealed a significant increase in CVD risk (HR, 1.32; 95% CI, 1.04-1.67) and all-cause mortality risk (HR, 1.34; 95% CI, 1.01-1.69). A non-significant increase in transplant failure was seen as well (HR, 1.20; 95% CI, 0.87-1.64).

Conclusion: Remnant cholesterol is associated with CVD and all-cause mortality in long-term kidney transplant recipients KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of remnant cholesterol-lowering therapy on these outcomes may be warranted.
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http://dx.doi.org/10.1093/ndt/gfab068DOI Listing
March 2021

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Am J Hum Genet 2021 04 12;108(4):564-582. Epub 2021 Mar 12.

The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.
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http://dx.doi.org/10.1016/j.ajhg.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059339PMC
April 2021

Deep learning for intelligent diagnosis in thyroid scintigraphy.

J Int Med Res 2021 Jan;49(1):300060520982842

Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Objective: To construct deep learning (DL) models to improve the accuracy and efficiency of thyroid disease diagnosis by thyroid scintigraphy.

Methods: We constructed DL models with AlexNet, VGGNet, and ResNet. The models were trained separately with transfer learning. We measured each model's performance with six indicators: recall, precision, negative predictive value (NPV), specificity, accuracy, and F1-score. We also compared the diagnostic performances of first- and third-year nuclear medicine (NM) residents with assistance from the best-performing DL-based model. The Kappa coefficient and average classification time of each model were compared with those of two NM residents.

Results: The recall, precision, NPV, specificity, accuracy, and F1-score of the three models ranged from 73.33% to 97.00%. The Kappa coefficient of all three models was >0.710. All models performed better than the first-year NM resident but not as well as the third-year NM resident in terms of diagnostic ability. However, the ResNet model provided "diagnostic assistance" to the NM residents. The models provided results at speeds 400 to 600 times faster than the NM residents.

Conclusion: DL-based models perform well in diagnostic assessment by thyroid scintigraphy. These models may serve as tools for NM residents in the diagnosis of Graves' disease and subacute thyroiditis.
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http://dx.doi.org/10.1177/0300060520982842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812409PMC
January 2021

Insulinemic and Inflammatory Dietary Patterns Show Enhanced Predictive Potential for Type 2 Diabetes Risk in Postmenopausal Women.

Diabetes Care 2021 03 8;44(3):707-714. Epub 2021 Jan 8.

Interdisciplinary PhD Program in Nutrition, The Ohio State University, Columbus, OH

Objective: The empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores assess the insulinemic and inflammatory potentials of habitual dietary patterns, irrespective of the macronutrient content, and are based on plasma insulin response or inflammatory biomarkers, respectively. The glycemic index (GI) and glycemic load (GL) assess postprandial glycemic potential based on dietary carbohydrate content. We tested the hypothesis that dietary patterns promoting hyperinsulinemia, chronic inflammation, or hyperglycemia may influence type 2 diabetes risk.

Research Design And Methods: We calculated dietary scores from baseline (1993-1998) food frequency questionnaires among 73,495 postmenopausal women in the Women's Health Initiative, followed through March 2019. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% CIs for type 2 diabetes risk. We also estimated multivariable-adjusted absolute risk of type 2 diabetes.

Results: During a median 13.3 years of follow-up, 11,009 incident cases of type 2 diabetes were diagnosed. Participants consuming the most hyperinsulinemic or proinflammatory dietary patterns experienced greater risk of type 2 diabetes; HRs (95% CI) comparing highest to lowest dietary index quintiles were EDIH 1.49 (1.32-1.68; < 0.0001) and EDIP 1.45 (1.29-1.63; < 0.0001). The absolute excess incidence for the same comparison was 220 (EDIH) and 271 (EDIP) cases per 100,000 person-years. GI and GL were not associated with type 2 diabetes risk: GI 0.99 (0.88-1.12; = 0.46) and GL 1.01 (0.89-1.16; = 0.30).

Conclusions: Our findings in this diverse cohort of postmenopausal women suggest that lowering the insulinemic and inflammatory potentials of the diet may be more effective in preventing type 2 diabetes than focusing on glycemic foods.
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http://dx.doi.org/10.2337/dc20-2216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896263PMC
March 2021

Epigenome-wide association study of diet quality in the Women's Health Initiative and TwinsUK cohort.

Int J Epidemiol 2021 05;50(2):675-684

Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, USA.

Background: 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.

Design: 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.

Results: 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).

Conclusions: 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.
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http://dx.doi.org/10.1093/ije/dyaa215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128469PMC
May 2021

Cardiometabolic Risk Factors and Preclinical Target Organ Damage Among Adults in Ghana: Findings From a National Study.

J Am Heart Assoc 2020 12 7;9(24):e017492. Epub 2020 Dec 7.

Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention Department of Cardiology Guangdong Cardiovascular Institute Guangdong Provincial People's HospitalGuangdong Academy of Medical Sciences Guangzhou China.

Background Although sub-Saharan Africa has a high prevalence of cardiovascular diseases (CVDs), there remains a lack of systematic and comprehensive assessment of risk factors and early CVD outcomes in adults in sub-Saharan Africa. Methods and Results Using a stratified multistage random sampling method, we recruited 1106 men and women, aged >18 years, from the general population in Ghana to participate in a national health survey from 2016 to 2017. In Ghanaian adults, the age-standardized prevalence of known CVD risk factors was 15.1% (95% CI, 12.9%-17.3%) for obesity, 6.8% (95% CI, 5.1%-8.5%) for diabetes mellitus, 26.1% (95% CI, 22.9%-29.4%) for hypertension, and 9.3% (95% CI, 7.1%-11.5%) for hyperuricemia. In addition, 10.1% (95% CI, 7.0%-13.2%) of adults had peripheral artery disease, 8.3% (95% CI, 6.7%-10.0%) had carotid thickening, 4.1% (95% CI, 2.9%-5.2%) had left ventricular hypertrophy, and 2.5% (95% CI, 1.5%-3.4%) had chronic kidney disease. Three CVD risk factors appeared to play prominent roles in the development of target organ damage, including obesity for peripheral artery disease (odds ratio [OR], 2.22; 95% CI, 1.35-3.63), hypertension for carotid thickening (OR, 1.92; 95% CI, 1.22-3.08), and left ventricular hypertrophy (OR, 5.28; 95% CI, 2.55-12.11) and hyperuricemia for chronic kidney disease (OR, 5.49; 95% CI, 2.84-10.65). Conclusions This comprehensive health survey characterized the baseline conditions of a national cohort of adults while confirming the prevalence of CVD risk factors, and early CVD outcomes have reached epidemic proportions in Ghana. The distinct patterns of risk factors in the development of target organ damage present important challenges and opportunities for interventions to improve cardiometabolic health among adults in Ghana.
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http://dx.doi.org/10.1161/JAHA.120.017492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955390PMC
December 2020

Serum folate levels and cognitive performance in the ELSA-Brasil baseline assessment.

Arq Neuropsiquiatr 2020 11;78(11):672-680

Universidade de São Paulo, Hospital Universitário, Centro de Pesquisa Clínica e Epidemiológica, São Paulo SP, Brazil.

Background: Most studies that analyze the association between serum folate levels and cognitive function either restrict their assessments to specific clinical scenarios or do not include middle-aged individuals, to whom strategies for preventing cognitive impairment may be more feasible.

Objective: To examine the association between serum folate levels and cognitive function in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline assessment.

Methods: Data from 4,571 ELSA-Brasil participants who live in the state of São Paulo, aged 35-74 years, were analyzed. The word list learning, delayed recall, word recognition, verbal fluency, and Trail Making Test Part B consisted in the cognitive tests. For each test, age, sex, and education-specific standardized scores and a global cognitive score were calculated. Crude and adjusted linear regression models were used to examine the associations of serum folate levels with cognitive test scores.

Results: In multivariable-adjusted models, serum folate was not associated with global cognitive score (β=-0.043; 95% confidence interval [95%CI] -0.135 to 0.050 for lowest vs. highest quintile group), nor with any cognitive test performance. We did not find associations between serum folate and global cognitive scores in subgroups stratified by age, sex, or use of vitamin supplements either.

Conclusions: We did not find significant associations between serum folate and cognitive performance in this large sample, which is characterized by a context of food fortification policies and a consequent low frequency of folate deficiency. Positive results from previous studies may not apply to the increasingly common contexts in which food fortification is implemented, or to younger individuals.
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http://dx.doi.org/10.1590/0004-282X20200074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917542PMC
November 2020

Gut Microbiota May Play a Significant Role in the Pathogenesis of Graves' Disease.

Thyroid 2021 05 7;31(5):810-820. Epub 2021 Jan 7.

Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Gut microbiota are considered to be intrinsic regulators of thyroid autoimmunity. We designed a cross-sectional study to examine the makeup and metabolic function of microbiota in Graves' disease (GD) patients, with the ultimate aim of offering new perspectives on the diagnosis and treatment of GD. The 16S ribosomal RNA (rRNA) V3-V4 DNA regions of microbiota were obtained from fecal samples collected from 45 GD patients and 59 controls. Microbial differences between the two groups were subsequently analyzed based on high-throughput sequencing. Compared with controls, GD patients had reduced alpha diversity ( < 0.05). At the phylum level, GD patients had a significantly lower proportion of ( = 0.008) and a significantly higher proportion of ( = 0.002) compared with the controls. At the genus level, GD patients had greater numbers of and , although fewer , , , , , , and than controls (all  < 0.05). Subgroup analysis of GD patients revealed that may play a key role in the pathogenesis of autoimmune thyroid diseases. Nine distinct genera showed significant correlations with certain thyroid function tests. Functional prediction revealed that may be an important microbe in certain metabolic pathways that occur in the hyperthyroid state. In addition, linear discriminant analysis (LDA) and effect size (LEfSe) analysis showed that there were significant differences in the levels of 18 genera between GD patients and controls (LDA >3.0, all  < 0.05). A diagnostic model using the top nine genera had an area under the curve of 0.8109 [confidence interval: 0.7274-0.8945]. Intestinal microbiota are different in GD patients. The microbiota we identified offer an alternative noninvasive diagnostic methodology for GD. Microbiota may also play a role in thyroid autoimmunity, and future research is needed to further elucidate the role.
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http://dx.doi.org/10.1089/thy.2020.0193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110022PMC
May 2021

Rotaxanating Metallo-supramolecular Nano-cylinder Helicates to Switch DNA Junction Binding.

J Am Chem Soc 2020 12 20;142(49):20651-20660. Epub 2020 Nov 20.

School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.

A class of rotaxane is created, not by encapsulating a conventional linear thread, but rather by wrapping a large cucurbit[10]uril macrocycle about a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate as the axle. The resulting pseudo-rotaxane is readily converted into a proper interlocked rotaxane by adding branch points to the helicate strands that form the surface of the cylinder (like branches and roots on a tree trunk). The supramolecular cylinder that forms the axle is itself a member of a unique and remarkable class of helicate metallo-drugs that bind Y-shaped DNA junction structures and induce cell death. While pseudo-rotaxanation does not modify the DNA-binding properties, proper, mechanically-interlocked rotaxanation transforms the DNA-binding and biological activity of the cylinder. The ability of the cylinder to de-thread from the rotaxane (and thus to bind DNA junction structures) is controlled by the extent of branching: fully-branched cylinders are locked inside the cucurbit[10]uril macrocycle, while cylinders with incomplete branch points can de-thread from the rotaxane in response to competitor guests. The number of branch points can thus afford kinetic control over the drug de-threading and release.
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http://dx.doi.org/10.1021/jacs.0c07750DOI Listing
December 2020

Association of Premature Menopause With Risk of Abdominal Aortic Aneurysm in the Women's Health Initiative.

Ann Surg 2020 Nov 4. Epub 2020 Nov 4.

Departments of Epidemiology, Surgery, and Medicine, Brown University, Providence, Rhode Island.

Objective: To determine if premature menopause and early menarche are associated with increased risk of AAA, and to explore potential effect modification by smoking history.

Summary Of Background Data: Despite worse outcomes for women with AAA, no studies have prospectively examined sex-specific risk factors, such as premature menopause and early menarche, with risk of AAA in a large, ethnically diverse cohort of women.

Methods: This was a post-hoc analysis of Women's Health Initiative participants who were beneficiaries of Medicare Parts A&B fee-for-service. AAA cases and interventions were identified from claims data. Follow-up period included Medicare coverage until death, end of follow-up or end of coverage inclusive of 2017.

Results: Of 101,119 participants included in the analysis, the mean age was 63 years and median follow-up was 11.3 years. Just under 10,000 (9.4%) women experienced premature menopause and 22,240 (22%) experienced early menarche. Women with premature menopause were more likely to be overweight, Black, have ≥20 pack years of smoking, history of cardiovascular disease, hypertension, and early menarche. During 1,091,840 person-years of follow-up, 1125 women were diagnosed with AAA, 134 had premature menopause (11.9%), 93 underwent surgical intervention and 45 (48%) required intervention for ruptured AAA. Premature menopause was associated with increased risk of AAA [hazard ratio 1.37 (1.14, 1.66)], but the association was no longer significant after multivariable adjustment for demographics and cardiovascular disease risk factors. Amongst women with ≥20 pack year smoking history (n = 19,286), 2148 (11.1%) had premature menopause, which was associated with greater risk of AAA in all models [hazard ratio 1.63 (1.24, 2.23)]. Early menarche was not associated with increased risk of AAA.

Conclusions: This study finds that premature menopause may be an important risk factor for AAA in women with significant smoking history. There was no significant association between premature menopause and risk of AAA amongst women who have never smoked. These results suggest an opportunity to develop strategies for better screening, risk reduction and stratification, and outcome improvement in the comprehensive vascular care of women.
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http://dx.doi.org/10.1097/SLA.0000000000004581DOI Listing
November 2020
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