Publications by authors named "Alexis C Wood"

Importance: Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited.

Objective: To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4).

Design, Setting, And Participants: The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018.

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Introduction: Growing interest centers on the association between circulating ketone bodies (KB) and cognitive function, notably in aging and neurodegenerative diseases.

Methods: Associations of plasma KB with incident dementia and cognitive performances were examined among Multi-Ethnic Study of Atherosclerosis (MESA) participants. KB were measured using plasma samples collected following an overnight fasting at Exam 1 (2000-02) and detailed cognitive testing at Exam 5 (2010-2012,  = 4392), Exam 6 (2016-2018,  = 1838), and in MESA-MIND (2019-2021,  = 2060).

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Objective: This study aimed to investigate serum metabolomic biomarkers associated with incident type 2 diabetes mellitus (T2DM) and evaluate their performance in improving T2DM risk prediction.

Methods: Untargeted proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolomics analyses were conducted in the Multi-Ethnic Study of Atherosclerosis (MESA; n=3460; discovery cohort) and Rotterdam Study (RS; n=1556; replication cohort). Multivariable cause-specific hazards models were used to analyze the associations between 23,571 serum metabolomic spectral variables and incident T2DM.

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Background: Maternal periodontal disease is associated with preterm and low-birthweight deliveries, but randomized trials of likely efficacious treatments (e.g., dental scaling and root planing) during pregnancy have not reduced these adverse outcomes.

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Background: Although some randomized trials have reported beneficial effects of protein intake on cardiometabolic risk factors, evidence from prospective studies have not supported a strong link between protein intake and cardiovascular disease (CVD) risk. It is also unclear whether diversity in protein intake plays a role in CVD risk.

Objective: We investigated prospective associations of (1) protein intake, overall and by food source and (2) diversity of protein sources with risk of CVD, coronary heart disease (CHD), and stroke.

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Background: Inflammation is a feature of coronary heart disease (CHD), but the role of proinflammatory microbial infection in CHD remains understudied.

Methods And Results: CHD was defined in the MESA (Multi-Ethnic Study of Atherosclerosis) as myocardial infarction (251 participants), resuscitated arrest (2 participants), and CHD death (80 participants). We analyzed sequencing reads from 4421 MESA participants in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program using the PathSeq workflow of the Genome Analysis Tool Kit and a 65-gigabase microbial reference.

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Article Synopsis
  • The study investigates the role of dietary flavonoids in reducing atherosclerosis-related cardiovascular diseases by analyzing data from 5,599 participants in the MESA study.
  • Researchers examined the link between flavonoid intake and various subclinical markers of atherosclerosis, considering factors like time, sex, race/ethnicity, and smoking status.
  • Results showed that higher flavonoid intake was associated with significantly lower odds of having poorer ankle-brachial indices and carotid plaques, suggesting the potential protective effects of flavonoids on cardiovascular health.
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  • Circulating metabolite levels are indicators of human health and can be influenced by genetic factors; however, most research has focused on European populations.
  • The study utilized metabolomics data from 25,058 diverse individuals, identifying 1,778 gene loci linked to 667 metabolites and providing methods for data analysis and handling.
  • Notably, the research uncovered new genetic associations, including 108 novel gene-metabolite pairs, and highlighted sex differences in metabolism, enhancing the understanding of genetic influences on human health.
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Background: An increasing body of evidence suggests that neuroinflammation is one of the key drivers of late-onset Alzheimer's disease (LOAD) pathology. Due to the increased permeability of the blood-brain barrier (BBB) in older adults, peripheral plasma proteins can infiltrate the central nervous system (CNS) and drive neuroinflammation through interactions with neurons and glial cells. Because these inflammatory factors are heritable, a greater understanding of their genetic relationship with LOAD could identify new biomarkers that contribute to LOAD pathology or offer protection against it.

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Background And Aims: Calcific aortic valve disease is associated with increased thrombin formation, platelet activation, decreased fibrinolysis, and subclinical brain infarcts. We examined the long-term association of aortic valve calcification (AVC) with newly diagnosed dementia and incident stroke in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: AVC was measured using non-contrast cardiac CT at Visit 1.

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Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. There is ongoing debate about the mechanisms that mediate metformin's effects on energy balance. Here, we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite N-lactoyl-phenylalanine (Lac-Phe) in cells, in mice and two independent human cohorts.

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Article Synopsis
  • Children with congenital anomalies of the kidney and urinary tract (CAKUT) and neurogenic bladder (NGB) are more susceptible to treatment failure for urinary tract infections (UTIs) compared to those with normal anatomy, but research on this is limited.
  • A study analyzed 482 children aged 0 to 17 presenting with UTIs to emergency departments between 2017 and 2018 and found a 6% rate of treatment failure.
  • The duration of antibiotic treatment was similar for both those who experienced treatment failure and those who did not, highlighting the need for more extensive studies to explore the effects of bacteremia on treatment outcomes.
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  • Large-scale studies on gene-environment interactions often simplify outcomes and covariates to improve data consistency, which can hinder the understanding of complex relationships, such as those between physical activity and HDL cholesterol.* -
  • The study refined a previously identified interaction between the rs295849 genotype and physical activity on HDL cholesterol levels, using datasets from the Women's Genome Health Study, UK Biobank, and Multi-Ethnic Study of Atherosclerosis.* -
  • Findings showed that the interaction effect was stronger when looking at medium-sized HDL particles compared to total HDL cholesterol, highlighting variations based on gender and the specific lipid metrics used.*
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Background: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.

Methods: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed.

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Short-chain fatty acids (SCFAs) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched SCFAs (BSCFAs; isobutyrate, isovalerate, and methylbutyrate) is largely unknown. In a cohort of 219 non-Hispanic White participants and 126 African American participants, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, and lipid traits, and other SCFAs.

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Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. The mechanisms that mediate metformin's effects on energy balance remain incompletely defined. Here we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite Lac-Phe in mice as well as in two independent human cohorts.

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Background And Aims: To investigate associations between avocado intake and glycemia in adults with Hispanic/Latino ancestry.

Methods And Results: The associations of avocado intake with measures of insulin and glucose homeostasis were evaluated in a cross-sectional analysis of up to 14,591 Hispanic/Latino adults, using measures of: average glucose levels (hemoglobin A1c; HbA1c), fasting glucose and insulin, glucose and insulin levels after an oral glucose tolerance test (OGTT), and calculated measures of insulin resistance (HOMA-IR, and HOMA-%β), and insulinogenic index. Associations were assessed using multivariable linear regression models, which controlled for sociodemographic factors and health behaviors, and which were stratified by dysglycemia status.

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Background/purpose: Hispanic/Latinos in the US are at increased risk for type 2 diabetes (T2D). Data suggest that avocado intake is associated with better glycemic control, but whether this translates to protection from T2D has not been studied. The goal of the current analyses was to examine whether consuming avocados at baseline is associated with lower incident T2D over a six-year period, compared to not consuming avocados at baseline.

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Background The relationship between alcohol consumption and ectopic fat distribution, both known factors for cardiovascular disease, remains understudied. Therefore, we aimed to examine the association between alcohol consumption and ectopic adiposity in adults at risk for cardiovascular disease. Methods and Results In this cross-sectional analysis, we categorized alcohol intake among participants in MESA (Multi-Ethnic Study of Atherosclerosis) as follows (drinks/day): <1 (light drinking), 1 to 2 (moderate drinking), >2 (heavy drinking), former drinking, and lifetime abstention.

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Background: Whether red meat consumption is associated with higher inflammation or confounded by increased adiposity remains unclear. Plasma metabolites capture the effects of diet after food is processed, digested, and absorbed, and correlate with markers of inflammation, so they can help clarify diet-health relationships.

Objective: To identify whether any metabolites associated with red meat intake are also associated with inflammation.

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Article Synopsis
  • Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are important for human health, and previous studies have identified strong genetic signals related to these fats in a specific gene region called FADS among European Americans.
  • A new genome-wide association study (GWAS) was conducted with Hispanic American and African American participants to explore genetic signals for n-3 and n-6 PUFAs, confirming the FADS association and finding additional signals nearby in the DAGLA and BEST1 genes.
  • Notably, the study discovered unique genetic associations related to arachidonic acid in Hispanic Americans, including a specific genetic variant in the POLD4 gene that is common in this group but absent in others, highlighting the
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Background: Avocado consumption is linked to better glucose homeostasis, but small associations suggest potential population heterogeneity. Metabolomic data capture the effects of food intake after digestion and metabolism, thus accounting for individual differences in these processes.

Objectives: To identify metabolomic biomarkers of avocado intake and to examine their associations with glycemia.

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Inflammation contributes to lung function decline and the development of chronic obstructive pulmonary disease. Omega-3 fatty acids have antiinflammatory properties and may benefit lung health. To investigate associations of omega-3 fatty acids with lung function decline and incident airway obstruction in a diverse sample of adults from general-population cohorts.

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