NIH-supported implementation science and nutrition research: a portfolio review of the past decade.

Objective: This portfolio analysis aims to describe the scope of NIH-funded extramural research grants at the intersection of nutrition research and implementation science (IS) from 2011 to 2022 and to offer insights into future research opportunities relevant to the Strategic Plan for NIH Nutrition Research 2020-2030. Methods: A portfolio analysis of funded grants using NIH reporting systems was conducted to identify nutrition research and IS awarded between fiscal years 2011 and 2022. The authors screened the titles and abstracts for inclusion criteria: research and career development awards involved a nutrition and/or dietary intervention and measured a stated implementation outcome or used an IS theory, model, or framework. Results: In total, 33 NIH-funded awards met the inclusion criteria. Almost half of the awards (48.5%) were investigator-initiated research projects compared to research career awards and cooperative agreements. While studies were predominantly conducted in the United States, 15.2% were conducted in low- and middle-income countries in Africa, Latin America, and Asia. Adults aged 19-64 years and children aged 2-11 years represented most of the study populations (45.5 and 15.2%, respectively). Studies provided nutrition/dietary guidelines and created culturally tailored interventions, which were then adapted in collaboration with community partners in schools, hospitals, and religious settings. The most cited IS outcomes were feasibility, costs, adoption, and acceptability. Sixteen awards (48.5%) used an IS theory, model, or framework to guide their work. Discussion: The findings show the breadth of NIH-funded nutrition and implementation research and highlight potential research opportunities.

Opportunities to advance implementation science and nutrition research: a commentary on the Strategic Plan for NIH Nutrition Research.

Despite population-wide recommendations by the U.S. Dietary Guidelines for Americans and others to encourage health-promoting dietary patterns, the proportion of Americans following dietary recommendations remains low. The gaps in the adoption and integration of evidence-based dietary interventions, practices, programs, and policies (EBIs) into community and clinical settings signal the need to strengthen efforts in implementation science (IS) in nutrition research to understand and alleviate barriers to adopting and sustaining healthy dietary behaviors and practices. Equally important is the translation of this research into practice in a variety of settings and across the diversity of populations. Recognizing this need, the U.S. National Institutes of Health (NIH) 2020-2030 Strategic Plan for NIH Nutrition Research calls for the expansion of IS as a key opportunity to advancing nutrition research. This commentary highlights three scientific opportunities to stimulate IS in nutrition research and provides examples for each opportunity. These include: (a) Advance consideration of implementation and dissemination early in the design of interventions to facilitate opportunities for equitable scale-up and sustainability of EBIs, (b) Develop and test strategies for equitable implementation of nutrition and diet EBIs in health care and community settings, and (c) Build and strengthen the infrastructure, capacity, and expertise needed to increase use of IS in clinical and community nutrition research to swiftly move the research into practice. By advancing the three opportunities identified in this commentary, the scientific community has the potential to advance the field of nutrition research and IS with the ultimate goal of improving public health.

While dietary guidelines have proven effective in clinical studies, most Americans do not follow these tested guidelines. More work is needed to bring research into practice so that all populations can benefit from the research. The U.S. National Institutes of Health recognizes this need and highlights it as a key opportunity in its 2020­2030 Strategic Plan for NIH Nutrition Research. This commentary describes three scientific opportunities that can help to stimulate the research needed to move research into practice, toward the ultimate goal of improving public health.

An evaluation of the National Institutes of Health grants portfolio: identifying opportunities and challenges for multi-omics research that leverage metabolomics data.

BACKGROUND: Through the systematic large-scale profiling of metabolites, metabolomics provides a tool for biomarker discovery and improving disease monitoring, diagnosis, prognosis, and treatment response, as well as for delineating disease mechanisms and etiology. As a downstream product of the genome and epigenome, transcriptome, and proteome activity, the metabolome can be considered as being the most proximal correlate to the phenotype. Integration of metabolomics data with other -omics data in multi-omics analyses has the potential to advance understanding of human disease development and treatment. AIM OF REVIEW: To understand the current funding and potential research opportunities for when metabolomics is used in human multi-omics studies, we cross-sectionally evaluated National Institutes of Health (NIH)-funded grants to examine the use of metabolomics data when collected with at least one other -omics data type. First, we aimed to determine what types of multi-omics studies included metabolomics data collection. Then, we looked at those multi-omics studies to examine how often grants employed an integrative analysis approach using metabolomics data. KEY SCIENTIFIC CONCEPTS OF REVIEW: We observed that the majority of NIH-funded multi-omics studies that include metabolomics data performed integration, but to a limited extent, with integration primarily incorporating only one other -omics data type. Some opportunities to improve data integration may include increasing confidence in metabolite identification, as well as addressing variability between -omics approach requirements and -omics data incompatibility.

Dietary patterns and associations with BMI in low-income, ethnic minority youth in the USA according to baseline data from four randomised controlled trials.

Few studies have derived data-driven dietary patterns in youth in the USA. This study examined data-driven dietary patterns and their associations with BMI measures in predominantly low-income, racial/ethnic minority US youth. Data were from baseline assessments of the four Childhood Obesity Prevention and Treatment Research (COPTR) Consortium trials: NET-Works (534 2-4-year-olds), GROW (610 3-5-year-olds), GOALS (241 7-11-year-olds) and IMPACT (360 10-13-year-olds). Weight and height were measured. Children/adult proxies completed three 24-h dietary recalls. Dietary patterns were derived for each site from twenty-four food/beverage groups using k-means cluster analysis. Multivariable linear regression models examined associations of dietary patterns with BMI and percentage of the 95th BMI percentile. Healthy (produce and whole grains) and Unhealthy (fried food, savoury snacks and desserts) patterns were found in NET-Works and GROW. GROW additionally had a dairy- and sugar-sweetened beverage-based pattern. GOALS had a similar Healthy pattern and a pattern resembling a traditional Mexican diet. Associations between dietary patterns and BMI were only observed in IMPACT. In IMPACT, youth in the Sandwich (cold cuts, refined grains, cheese and miscellaneous) compared with Mixed (whole grains and desserts) cluster had significantly higher BMI (ß = 0·99 (95 % CI 0·01, 1·97)) and percentage of the 95th BMI percentile (ß = 4·17 (95 % CI 0·11, 8·24)). Healthy and Unhealthy patterns were the most common dietary patterns in COPTR youth, but diets may differ according to age, race/ethnicity or geographic location. Public health messages focused on healthy dietary substitutions may help youth mimic a dietary pattern associated with lower BMI.

Funding of Hispanic/Latino Health-Related Research by the National Institutes of Health: An Analysis of the Portfolio of Research Program Grants on Six Health Topic Areas.

Hispanics/Latinos are expected to constitute 25% of the U.S. population by 2060. Differences in the prevalence of health risk factors, chronic diseases, and access to and utilization of health-care services between Hispanics/Latinos and other populations in the U.S. have been documented. This study aimed to describe and analyze the landscape of Research Program Grants (RPGs) funded by the National Institutes of Health (NIH) between 2008 and 2015 involving Hispanic/Latino health research in six health condition areas-asthma, cancer, dementia, diabetes, liver/gallbladder disease, and obesity-and to identify opportunities for continued research in these areas. Using an NIH internal search engine, we identified new and renewal Hispanic/Latino health RPGs searching for specific Hispanic/Latino identifiers in the Title, Abstract, and Specific Aims. We used descriptive statistics to examine the distribution of funded RPGs by NIH disease-based classification codes for the six health condition areas of interest, and other selected characteristics. The most prominent clusters of research subtopics were identified within each health condition area, and performance sites were mapped at the city level. Within the selected time frame, 3,221 Hispanic/Latino health-related unique RPGs were funded (constituting 4.4% of all funded RPGs), and of those 625 RPGs were eligible for review and coding in the present study. Cancer and obesity were the most commonly studied health condition areas (72%), while studies on mechanisms of disease-biological and non-biological-(72.6%), behavioral research (42.1%) and epidemiological studies (38.1%) were the most common types of research. Most of the primary performance sites were in California, Texas, the northeastern U.S., and Illinois. The predominance of mechanistic, behavioral, and epidemiological studies in our analysis poses opportunities to evaluate knowledge gained and their clinical application, explore new research questions, or to update some methods or instruments. The findings of the present study suggest opportunities to expand research in understudied mechanisms of disease that could explain differences in prevalence of conditions like diabetes and cancer among different heritage groups. In addition, our findings suggest that the impact of interventions or policies designed to reduce health disparities, innovative multi-level interventions, implementation and dissemination studies, the role of health information technology on health outcomes, and the intersectionality of individual, sociocultural, geographic, and other factors on health outcomes, among others, are understudied approaches, which could potentially advance research in Hispanic/Latino health and contribute to the achievement of better health outcomes in this diverse population.

Report of the National Heart, Lung, and Blood Institute Working Group on Hypertension: Barriers to Translation.

The National Heart, Lung, and Blood Institute convened a multidisciplinary working group of hypertension researchers on December 6 to 7, 2018, in Bethesda, MD, to share current scientific knowledge in hypertension and to identify barriers to translation of basic into clinical science/trials and implementation of clinical science into clinical care of patients with hypertension. The goals of the working group were (1) to provide an overview of recent discoveries that may be ready for testing in preclinical and clinical studies; (2) to identify gaps in knowledge that impede translation; (3) to highlight the most promising scientific areas in which to pursue translation; (4) to identify key challenges and barriers for moving basic science discoveries into translation, clinical studies, and trials; and (5) to identify roadblocks for effective dissemination and implementation of basic and clinical science in real-world settings. The working group addressed issues that were responsive to many of the objectives of the National Heart, Lung, and Blood Institute Strategic Vision. The working group identified major barriers and opportunities for translating research to improved control of hypertension. This review summarizes the discussion and recommendations of the working group.

Perspective: Dietary Biomarkers of Intake and Exposure-Exploration with Omics Approaches.

While conventional nutrition research has yielded biomarkers such as doubly labeled water for energy metabolism and 24-h urinary nitrogen for protein intake, a critical need exists for additional, equally robust biomarkers that allow for objective assessment of specific food intake and dietary exposure. Recent advances in high-throughput MS combined with improved metabolomics techniques and bioinformatic tools provide new opportunities for dietary biomarker development. In September 2018, the NIH organized a 2-d workshop to engage nutrition and omics researchers and explore the potential of multiomics approaches in nutritional biomarker research. The current Perspective summarizes key gaps and challenges identified, as well as the recommendations from the workshop that could serve as a guide for scientists interested in dietary biomarkers research. Topics addressed included study designs for biomarker development, analytical and bioinformatic considerations, and integration of dietary biomarkers with other omics techniques. Several clear needs were identified, including larger controlled feeding studies, testing a variety of foods and dietary patterns across diverse populations, improved reporting standards to support study replication, more chemical standards covering a broader range of food constituents and human metabolites, standardized approaches for biomarker validation, comprehensive and accessible food composition databases, a common ontology for dietary biomarker literature, and methodologic work on statistical procedures for intake biomarker discovery. Multidisciplinary research teams with appropriate expertise are critical to moving forward the field of dietary biomarkers and producing robust, reproducible biomarkers that can be used in public health and clinical research.

Food insecurity and obesity: research gaps, opportunities, and challenges.

Food insecurity, defined as a lack of consistent access to enough food for an active, healthy life, is a major public health concern with 11.8% of U.S. households (15.0 million) estimated to be affected at some point in 2017 according to the United States Department of Agriculture Economic Research Service. While the link between food insecurity, diet quality, and obesity is well documented in the literature, additional research and policy considerations are needed to better understand underlying mechanisms, associated risks, and effective strategies to mitigate the adverse impact of obesity related food insecurity on health. With its Strategic Plan for NIH Obesity Research, the NIH has invested in a broad spectrum of obesity research over the past 10 years to understand the multifaceted factors that contribute to the disease. The issue of food insecurity, obesity and nutrition is cross-cutting and relates to many activities and research priorities of the institutes and centers within the NIH. Several research gaps exist, including the mechanisms and pathways that underscore the complex relationship between food insecurity, diet, and weight outcomes, the impacts on pregnant and lactating women, children, and other vulnerable populations, its cumulative impact over the life course, and the development of effective multi-level intervention strategies to address this critical social determinant of health. Challenges and barriers such as the episodic nature of food insecurity and the inconsistencies of how food insecurity is measured in different studies also remain. Overall, food insecurity research aligns with the upcoming release of the Strategic Plan for NIH Nutrition Research and will continue to be prioritized in order to enhance health, lengthen life, reduce illness and disability and health disparities.

Snacking characteristics and patterns and their associations with diet quality and BMI in the Childhood Obesity Prevention and Treatment Research Consortium.

OBJECTIVE: To describe snacking characteristics and patterns in children and examine associations with diet quality and BMI. DESIGN: Children's weight and height were measured. Participants/adult proxies completed multiple 24 h dietary recalls. Snack occasions were self-identified. Snack patterns were derived for each sample using exploratory factor analysis. Associations of snacking characteristics and patterns with Healthy Eating Index-2010 (HEI-2010) score and BMI were examined using multivariable linear regression models. SETTING: Childhood Obesity Prevention and Treatment Research (COPTR) Consortium, USA: NET-Works, GROW, GOALS and IMPACT studies. PARTICIPANTS: Predominantly low-income, racial/ethnic minorities: NET-Works (n 534, 2-4-year-olds); GROW (n 610, 3-5-year-olds); GOALS (n 241, 7-11-year-olds); IMPACT (n 360, 10-13-year-olds). RESULTS: Two snack patterns were derived for three studies: a meal-like pattern and a beverage pattern. The IMPACT study had a similar meal-like pattern and a dairy/grains pattern. A positive association was observed between meal-like pattern adherence and HEI-2010 score (P for trend < 0⋅01) and snack occasion frequency and HEI-2010 score (ß coefficient (95 % CI): NET-Works, 0⋅14 (0⋅04, 0⋅23); GROW, 0⋅12 (0⋅02, 0⋅21)) among younger children. A preference for snacking while using a screen was inversely associated with HEI-2010 score in all studies except IMPACT (ß coefficient (95 % CI): NET-Works, -3⋅15 (-5⋅37, -0⋅92); GROW, -2⋅44 (-4⋅27, -0⋅61); GOALS, -5⋅80 (-8⋅74, -2⋅86)). Associations with BMI were almost all null. CONCLUSIONS: Meal-like and beverage patterns described most children's snack intake, although patterns for non-Hispanic Blacks or adolescents may differ. Diets of 2-5-year-olds may benefit from frequent meal-like pattern snack consumption and diets of all children may benefit from decreasing screen use during eating occasions.

Implementing the National Heart, Lung, and Blood Institute's Strategic Vision in the Division of Cardiovascular Sciences.

As we commemorate the 70th Anniversary of the National Heart, Lung, and Blood Institute (NHLBI) and celebrate important milestones that have been achieved by the Division of Cardiovascular Sciences (DCVS), it is imperative that DCVS and the Extramural Research community at-large continue to address critical public health challenges that persist within the area of Cardiovascular Diseases (CVD). The NHLBI's Strategic Vision, developed with extensive input from the extramural research community and published in 2016, included overarching goals and strategic objectives that serve to provide a general blueprint for sustaining the legacy of the Institute by leveraging opportunities in emerging scientific areas (e.g., regenerative medicine, omics technology, data science, precision medicine, and mobile health), finding new ways to address enduring challenges (e.g., social determinants of health, health inequities, prevention, and health promotion), and training the next generation of heart, lung, blood, and sleep researchers. DCVS has developed a strategic vision implementation plan to provide a cardiovascular framing for the pursuit of the Institute's overarching goals and strategic objectives garnered from the input of the broader NHLBI community. This plan highlights six scientific focus areas that demonstrate a cross-cutting and multifaceted approach to addressing cardiovascular sciences, including 1) addressing social determinants of cardiovascular health (CVH) and health inequities, 2) enhancing resilience, 3) promoting CVH and preventing CVD Across the lifespan, 4) eliminating hypertension-related CVD, 5) reducing the burden of heart failure, and 6) preventing vascular dementia. These priorities will guide our efforts in Institute-driven activities in the coming years but will not exclude development of other novel ideas or the support of investigator-initiated grant awards. The DCVS Strategic Vision implementation plan is a living document that will evolve with iterative dialogue with the NHLBI community and adapt as the dynamic scientific landscape changes to seize emerging opportunities.

The Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures Project: Rationale and Approach.

BACKGROUND: Individual variability in response to multiple modalities of obesity treatment is well documented, yet our understanding of why some individuals respond while others do not is limited. The etiology of this variability is multifactorial; however, at present, we lack a comprehensive evidence base to identify which factors or combination of factors influence treatment response. OBJECTIVES: This paper provides an overview and rationale of the Accumulating Data to Optimally Predict obesity Treatment (ADOPT) Core Measures Project, which aims to advance the understanding of individual variability in response to adult obesity treatment. This project provides an integrated model for how factors in the behavioral, biological, environmental, and psychosocial domains may influence obesity treatment responses and identify a core set of measures to be used consistently across adult weight-loss trials. This paper provides the foundation for four companion papers that describe the core measures in detail. SIGNIFICANCE: The accumulation of data on factors across the four ADOPT domains can inform the design and delivery of effective, tailored obesity treatments. ADOPT provides a framework for how obesity researchers can collectively generate this evidence base and is a first step in an ongoing process that can be refined as the science advances.

Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures: Behavioral Domain.

BACKGROUND: The ability to identify and measure behaviors that are related to weight loss and the prevention of weight regain is crucial to understanding the variability in response to obesity treatment and the development of tailored treatments. OBJECTIVES: The overarching goal of the Accumulating Data to Optimally Predict obesity Treatment (ADOPT) Core Measures Project is to provide obesity researchers with guidance on a set of constructs and measures that are related to weight control and that span and integrate obesity-related behavioral, biological, environmental, and psychosocial domains. This article describes how the behavioral domain subgroup identified the initial list of high-priority constructs and measures to be included, and it describes practical considerations for assessing the following four behavioral areas: eating, activity, sleep, and self-monitoring of weight. Challenges and considerations for advancing the science related to weight loss and maintenance behaviors are also discussed. SIGNIFICANCE: Assessing a set of core behavioral measures in combination with those from other ADOPT domains is critical to improve our understanding of individual variability in response to adult obesity treatment. The selection of behavioral measures is based on the current science, although there continues to be much work needed in this field.

A Systematic Review of Obesity Disparities Research.

CONTEXT: A review of interventions addressing obesity disparities could reveal gaps in the literature and provide guidance on future research, particularly for populations with a high prevalence of obesity and obesity-related cardiometabolic risk. EVIDENCE ACQUISITION: A systematic review of clinical trials in obesity disparities research that were published in 2011-2016 in PubMed/MEDLINE resulted in 328 peer-reviewed articles. Articles were excluded if they had no BMI, weight, or body composition measure as primary outcome or were foreign (n=201); were epidemiologic or secondary data analyses of clinical trials (n=12); design or protocol papers (n=54); systematic reviews (n=3); or retracted or duplicates (n=9). Forty-nine published trials were summarized and supplemented with a review of ongoing obesity disparities grants being funded by the National, Heart, Lung and Blood Institute. EVIDENCE SYNTHESIS: Of the 49 peer-reviewed trials, 27 targeted adults and 22 children only or parent-child dyads (5 of 22). Interventions were individually focused; mostly in single settings (e.g., school or community); of short duration (mostly ≤12 months); and primarily used behavioral modification (e.g., self-monitoring) strategies. Many of the trials had small sample sizes and moderate to high attrition rates. A meta-analysis of 13 adult trials obtained a pooled intervention effect of BMI -1.31 (95% CI=-2.11, -0.52, p=0.0012). Institutional review identified 140 ongoing obesity-related health disparities grants, but only 19% (n=27) were clinical trials. CONCLUSIONS: The reviews call for cardiovascular-related obesity disparities research that is long term and includes population research, and multilevel, policy, and environmental, or "whole of community," interventions.

The Productivity of NHLBI-Funded Obesity Research, 1983-2013.

OBJECTIVE: To describe and elucidate the time trends of the academic productivity of NHLBI's obesity-related research funding via bibliometric analysis of 30 years of NHLBI-supported obesity-related publications. METHODS: In total, 3,545 NHLBI-funded obesity-related publications were identified in the Thomson Reuters InCites™ database. Shared references in a community detection algorithm were used to identify publication topics. Characteristics of publications and topical communities were analyzed based on citation count and percentile rank. A percentile rank >90 was considered "highly cited." RESULTS: Obesity-related publications increased more than 10-fold over 30 years, whereas NHLBI-funded publications only increased twofold NHLBI-funded obesity publications were cited a median of 23 times (IQR 8-55, range 0-2,047, mean 52). Thirty percent of these publications were highly cited compared to the expected ten percent. Six topical communities were present in 1983 compared to 16 in 2013. The most highly cited topical areas were sleep (n = 199 publications, 38% highly cited), cardiovascular morbidity and mortality (n = 277, 36%), obesity correlates and consequences (n = 588, 35%), and asthma and inflammation (n = 283, 35%). CONCLUSIONS: NHLBI-funded obesity publications have contributed substantially to the obesity literature, with many highly cited. Publications grew in number and topical diversity over 30 years and grew at a faster rate than total NHLBI publications.

Using 2 Assessment Methods May Better Describe Dietary Supplement Intakes in the United States.

BACKGROUND: One-half of US adults report using a dietary supplement. NHANES has traditionally assessed dietary supplement use via a 30-d questionnaire but in 2007 added a supplement module to the 24-h dietary recall (24HR). OBJECTIVE: We compared these 2 dietary assessment methods, examined potential biases in the methods, and determined the effect that instrument choice had on estimates of prevalence of multivitamin/multimineral dietary supplement (MVMM) use. METHODS: We described prevalence of dietary supplement use by age, sex, and assessment instrument in 12,285 adults in the United States (>19 y of age) from NHANES 2007-2010. RESULTS: When using data from the questionnaire alone, 29.3% ± 1.0% of men and 35.5% ± 1.0% of women were users of MVMMs, whereas data from the 24HR only produced prevalence estimates of 26.3% ± 1.1% for men and 33.2% ± 1.0% for women. When using data from both instruments combined, 32.3% ± 1.2% of men and 39.5% ± 1.1% of women were classified as MVMM users. Prevalence estimates were significantly higher by 2-9% in all age-sex groups when using information from both instruments combined than when using data from either instrument individually. A digit preference bias and flattened slope phenomenon were observed in responses to the dietary supplement questionnaire. A majority (67%) of MVMMs were captured on both instruments, whereas 19% additional MVMMs were captured on the questionnaire and 14% additional on the 24HR. Of those captured only on the 24HR, 26% had missing label information, whereas only 12% and 9% of those captured on the questionnaire or both, respectively, had missing information. CONCLUSIONS: Use of both the dietary supplement questionnaire and the 24HR can provide advantages to researchers over the use of a single instrument and potentially capture a larger fraction of dietary supplement users.

Garlic and onions: their cancer prevention properties.

The Allium genus includes garlic, onions, shallots, leeks, and chives. These vegetables are popular in cuisines worldwide and are valued for their potential medicinal properties. Epidemiologic studies, while limited in their abilities to assess Allium consumption, indicate some associations of Allium vegetable consumption with decreased risk of cancer, particularly cancers of the gastrointestinal tract. Limited intervention studies have been conducted to support these associations. The majority of supportive evidence on Allium vegetables cancer-preventive effects comes from mechanistic studies. These studies highlight potential mechanisms of individual sulfur-containing compounds and of various preparations and extracts of these vegetables, including decreased bioactivation of carcinogens, antimicrobial activities, and redox modification. Allium vegetables and their components have effects at each stage of carcinogenesis and affect many biologic processes that modify cancer risk. This review discusses the cancer-preventive effects of Allium vegetables, particularly garlic and onions, and their bioactive sulfur compounds and highlights research gaps.

Urinary lignans and inflammatory markers in the US National Health and Nutrition Examination Survey (NHANES) 1999-2004 and 2005-2008.

PURPOSE: Chronic inflammation has been implicated in the etiology of various chronic diseases. We previously found that certain urinary isoflavones are associated with markers of inflammation. In the present study, we examined the associations of serum C-reactive protein (CRP) and white blood cell (WBC) count with lignans, which are more frequent in the Western diet than isoflavones. METHODS: Our analysis included 2,028 participants of NHANES 2005-2008 and 2,628 participants of NHANES 1999-2004 aged 18 years and older. The exposures of interest were urinary mammalian lignans (enterodiol and enterolactone). Outcome variables were two inflammatory markers (CRP [≤10 mg/L] and WBC [≥3.0 and ≤11.7 (1,000 cells/µL)]). Log-transformed CRP concentration and WBC count by log-transformed creatinine-standardized concentrations of mammalian lignans were used for linear regression. RESULTS: Statistically significant inverse associations of urinary lignan, enterodiol, and enterolactone concentrations with circulating CRP and WBC counts were observed in the multivariate-adjusted models: In NHANES 2005-2008, per one-percent increase in lignan concentrations in the urine, CRP concentrations and WBC counts decreased by 8.1 % (95 % CI -11.5, -4.5) and 1.9 % (95 % CI -2.7; -1.2), respectively. Per one-percent increase in enterodiol and enterolactone, WBC counts decreased by 2.1 % (95 % CI -2.8, -1.3) and 1.3 % (95 % CI -1.9, -0.6), respectively. In NHANES 1999-2004, analogous results were 3.0 % (95 % CI -5.6, -0.3), 1.2 % (95 % CI -2.0; -0.4), 1.0 % (95 % CI -1.8, -0.2), and 0.8 % (95 % CI -1.4, 0.2). CONCLUSIONS: Mammalian lignans were inversely associated with markers of chronic inflammation. Due to the cross-sectional design, our findings require confirmation in prospective studies.

Preventive effects of NSAIDs, NO-NSAIDs, and NSAIDs plus difluoromethylornithine in a chemically induced urinary bladder cancer model.

Urinary bladder cancer prevention studies were performed with the nonsteroidal anti-inflammatory drugs (NSAID) naproxen (a standard NSAID with a good cardiovascular profile), sulindac, and their nitric oxide (NO) derivatives. In addition, the effects of the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO), alone or combined with a suboptimal dose of naproxen or sulindac was examined. Agents were evaluated at their human equivalent doses (HED), as well as at lower doses. In the hydroxybutyl(butyl)nitrosamine (OH-BBN) model of urinary bladder cancer, naproxen (400 or 75 ppm) and sulindac (400 ppm) reduced the incidence of large bladder cancers by 82%, 68%, and 44%, respectively, when the agents were initially given 3 months after the final dose of the carcinogen; microscopic cancers already existed. NO-naproxen was highly effective, whereas NO-sulindac was inactive. To further compare naproxen and NO-naproxen, we examined their effects on gene expression in rat livers following a 7-day exposure. Limited, but similar, gene expression changes in the liver were induced by both agents, implying that the primary effects of both are mediated by the parent NSAID. When agents were initiated 2 weeks after the last administration of OH-BBN, DFMO at 1,000 ppm had limited activity, a low dose of naproxen (75 ppm) and sulindac (150 ppm) were highly and marginally effective. Combining DFMO with suboptimal doses of naproxen had minimal effects, whereas the combination of DMFO and sulindac was more active than either agent alone. Thus, naproxen and NO-naproxen were highly effective, whereas sulindac was moderately effective in the OH-BBN model at their HEDs.

Navigating the road ahead: addressing challenges for use of metabolomics in epidemiology studies.

Metabolomics platforms allow for the measurement of hundreds to thousands of unique small chemical entities, as well as offer extensive coverage of metabolic markers related to obesity, diet, smoking, and other exposures of high interest to health scientists. Nevertheless, its potential use as a tool in population-based study design has not been fully explored. As the field of metabolomics continues to mature, and in part, accelerate through the National Institutes of Health (NIH) investment of ≤65 million in the Common Fund's Metabolomics Program (https://common fund.nih.gov/metabolomics/index), it is time to consider those challenges most pertinent to epidemiologic studies.

3,3'-diindolylmethane rapidly and selectively inhibits hepatocyte growth factor/c-Met signaling in breast cancer cells.

3,3'-Diindolylmethane (DIM), an indole derivative from vegetables of the Brassica genus, has antiproliferative activity in breast cancer cells. Part of this activity is thought to be due to DIM inhibition of Akt signaling, but an upstream mechanism of DIM-induced Akt inhibition has not been described. The goals of this study were to investigate the kinetics of inhibition of Akt by physiologically relevant concentrations of DIM and to identify an upstream factor that mediates this effect. Here we report that DIM (5-25 µM) inhibited Akt activation from 30 min to 24h in tumorigenic MDA-MB-231 cells but did not inhibit Akt activation in non-tumorigenic preneoplastic MCF10AT cells. DIM inhibited hepatocyte growth factor (HGF)-induced Akt activation by up to 46%, cell migration by 66% and cell proliferation by up to 54%, but did not inhibit induction of Akt by epidermal growth factor or insulin-like growth factor-1. DIM decreased phosphorylation of the HGF receptor, c-Met, at tyrosines 1234 and 1235, indicating decreased activation of the receptor. This decrease was reversed by pretreatment with inhibitors of p38 or calcineurin. Our results demonstrate the important role of HGF and c-Met in DIM's anti-proliferative effect on breast cancer cells and suggest that DIM could have preventive or clinical value as an inhibitor of c-Met signaling.