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The etiology of type 2 diabetes is rooted in a myriad of factors and exposures at individual, community, and societal levels, many of which also affect the control of type 1 and type 2 diabetes. Not only do such factors impact risk and treatment at the time of diagnosis but they also can accumulate biologically from preconception, in utero, and across the life course. These factors include inadequate nutritional quality, poor access to physical activity resources, chronic stress (e.g., adverse childhood experiences, racism, and poverty), and exposures to environmental toxins. The National Clinical Care Commission (NCCC) concluded that the diabetes epidemic cannot be treated solely as a biomedical problem but must also be treated as a societal problem that requires an all-of-government approach. The NCCC determined that it is critical to design, leverage, and coordinate federal policies and programs to foster social and environmental conditions that facilitate the prevention and treatment of diabetes. This article reviews the rationale, scientific evidence base, and content of the NCCC’s population-wide recommendations that address food systems; consumption of water over sugar-sweetened beverages; food and beverage labeling; marketing and advertising; workplace, ambient, and built environments; and research. Recommendations relate to specific federal policies, programs, agencies, and departments, including the U.S. Department of Agriculture, the Food and Drug Administration, the Federal Trade Commission, the Department of Housing and Urban Development, the Environmental Protection Agency, and others. These population-level recommendations are transformative. By recommending health-in-all-policies and an equity-based approach to governance, the NCCC Report to Congress has the potential to contribute to meaningful change across the diabetes continuum and beyond. Adopting these recommendations could significantly reduce diabetes incidence, complications, costs, and inequities. Substantial political resolve will be needed to translate recommendations into policy. Engagement by diverse members of the diabetes stakeholder community will be critical to such efforts.

FoodData Central (FDC) is the center of the USDA-based food-composition information web. It is an integrated data system that presently provides-in 1 place-5 distinct types of data containing information on food and nutrient profiles. Each data type has a unique purpose. Two of the data types-Foundation Foods (FF) and Experimental Foods (EF)-represent "a bridge to the future" in food and nutrient composition. They provide data and metadata that have never previously been available from a database. The other 3 data types are well established and familiar to many users: Standard Reference (SR) Legacy, Food and Nutrient Database for Dietary Studies (FNDDS), and Global Branded Foods Products Database (GBFPD). After100 y of maintaining food-composition data within the USDA, it was clear that change was needed to respond to the rapid increase in the number and variety of foods in the food supply, evolution of analytical approaches, and new agricultural practices and products. FDC is USDA's answer to the challenge of providing reliable, web-based, transparent, and easily accessible information about the nutrients and other components of foods to meet the increasingly diverse needs of many audiences, including public health professionals, agricultural and environmental researchers, policy makers, nutrition professionals, health care providers, product developers, and the public at large.

Carbohydrates are the most abundant biomolecules in nature, and specifically, polysaccharides are present in almost all plants and fungi. Due to their compositional diversity, polysaccharide analysis remains challenging. Compared to other biomolecules, high-throughput analysis for carbohydrates has yet to be developed. To address this gap in analytical science, we have developed a multiplexed, high-throughput, and quantitative approach for polysaccharide analysis in foods. Specifically, polysaccharides were depolymerized using a nonenzymatic chemical digestion process followed by oligosaccharide fingerprinting using high performance liquid chromatography-quadru-pole time-of-flight mass spectrometry (HPLC-QTOF-MS). Both label-free relative quantitation and absolute quantitation were done based on the abundances of oligosaccharides produced. Method validation included evaluating recovery for a range of polysaccharide standards and a breakfast cereal standard reference material. Nine polysaccharides (starch, cellulose, beta-glucan, mannan, galactan, arabinan, xylan, xyloglucan, chitin) were successfully quantitated with sufficient accuracy (5-25% bias) and high reproducibility (2- 15% CV). Additionally, the method was used to identify and quantitate polysaccharides from a diverse sample set of food samples. Absolute concentrations of nine polysaccharides from apples and onions were obtained using an external calibration curve, where varietal differences were observed in some of the samples. The methodology developed in this study will provide complementary polysaccharide-level information to deepen our understanding of the interactions of dietary polysaccharides, gut microbial community, and human health. U.S. Department of Agriculture Agricultural Research Service (USDA-ARS) (NACA) [58-8040-0-014]; National Institutes of Health (NIH) Published version This project is funded by the U.S. Department of Agriculture Agricultural Research Service (USDA-ARS) (NACA #58-8040-0-014). Funding from the National Institutes of Health (NIH) is also acknowledged.

Dietary fiber has long been known to be an essential component of a healthy diet, and recent investigations into the gut microbiome-health paradigm have identified fiber as a prime determinant in this interaction. Further, fiber is now known to impact the gut microbiome in a structure-specific manner, conferring differential bioactivities to these specific structures. However, current analytical methods for food carbohydrate analysis do not capture this important structural information. To address this need, we utilized rapid-throughput LC-MS methods to develop a novel analytical pipeline to determine the structural composition of soluble and insoluble fiber fractions from two AOAC methods (991.43 and 2017.16) at the total monosaccharide, glycosidic linkage, and free saccharide level. Two foods were chosen for this proof-of-concept study: oats and potato starch. For oats, both AOAC methods gave similar results. Insoluble fiber was found to be comprised of linkages corresponding to beta-glucan, arabinoxylan, xyloglucan, and mannan, while soluble fiber was found to be mostly beta-glucan, with small amounts of arabinogalactan. For raw potato starch, each AOAC method gave markedly different results in the soluble fiber fractions. These observed differences are attributable to the resistant starch content of potato starch and the different starch digestion conditions used in each method. Together, these tools are a means to obtain the complex structures present within dietary fiber while retaining "classical" determinations such as soluble and insoluble fiber. These efforts will provide an analytical framework to connect gravimetric fiber determinations with their constituent structures to better inform gut microbiome and clinical nutrition studies. Published version Public domain – authored by a U.S. government employee

Background Climate change presents an increasing challenge for food-nutrition security. Nutrition metrics calculated from quantitative food system projections can help focus policy actions. Objectives To estimate future chronic and hidden hunger disability-adjusted life years (DALYs)—due to protein-energy undernutrition and micronutrient deficiencies, respectively—using food systems projections to evaluate the potential impact of climate change and agricultural sector investment for adaptation. Methods We use a novel combination of a chronic and hidden hunger DALY estimation procedure and food system projections from quantitative foresight modeling to assess DALYs under alternative agricultural sector scenarios to midcentury. Results Total chronic and hidden hunger DALYs are projected to increase globally out to 2050—by over 30 million compared with 2010—even without climate change. Climate change increases total DALY change between 2010 and 2050 by nearly 10% compared with no climate change. Agricultural sector investments show promise for offsetting these impacts. With investments, DALY incidence due to chronic and hidden hunger is projected to decrease globally in 2050 by 0.24 and 0.56 per 1000 capita, respectively. Total global DALYs will still rise because projected population growth will outpace the rate reduction, especially in Africa south of the Sahara. However, projections also show important regional reductions in total DALYs due to chronic (13.9 million in South Asia, 4.3 million in East Asia and the Pacific) and hidden hunger (7.5 million in East Asia and the Pacific) with investments. Conclusions Food system projections to 2050 show a decreasing DALY incidence from both chronic and hidden hunger. Population growth is projected to outpace these improvements and lead to increasing total chronic and hidden hunger DALYs globally, concentrated in Africa south of the Sahara. Climate change increases per-capita chronic and hidden hunger DALY incidence compared with no climate change. Agricultural sector investments show the potential to offset the climate impact on DALYs.

Adipose stem cells (ASCs) are reported to play a role in normal physiology as well as in inflammation and disease. The objective of this work was to elucidate inter-individual differences in growth, gene expression and response to inflammatory stimuli in ASCs from different donors. Human ASC1 (male donor) and ASC2 (female donor) were purchased from Lonza (Walkersville, MD). Cell proliferation was determined by the sulforhodamine B assay. After time-dependent treatment of ASCs with or without bacterial lipopolysaccharide (LPS), marker gene mRNAs for proliferation, steroid hormones, and xenobiotic and immune pathways were determined using RT-PCR, and secreted cytokine levels in media were measured using the Bio-Plex cytokine assay kit. ASCs from both donors expressed androgen receptors but not estrogen receptors. ASC2 had a 2-fold higher proliferation rate and a 6-fold higher level of proliferation marker Ki67 mRNA than ASC1. ASC2 exhibited significantly greater fold induction of TNF-α and CCL2 by LPS compared to ASC1. TNF-α and GM-CSF protein levels were also significantly higher in the LPS-induced ASC2 media, but IL-6 secretion was higher in the LPS-induced ASC1 media. Our findings suggest that inter-individual variability and/or possible sex differences exist in ASCs, which may serve as a key determinant to inflammatory responses of ASCs.

The ASN Board of Directors appointed the Nutrition Research Task Force to develop a report on scientific methods used in nutrition science to advance discovery, interpretation, and application of knowledge in the field. The genesis of this report was growing concern about the tone of discourse among nutrition professionals and the implications of acrimony on the productive study and translation of nutrition science. Too often, honest differences of opinion are cast as conflicts instead of areas of needed collaboration. Recognition of the value (and limitations) of contributions from well-executed nutrition science derived from the various approaches used in the discipline, as well as appreciation of how their layering will yield the strongest evidence base, will provide a basis for greater productivity and impact. Greater collaborative efforts within the field of nutrition science will require an understanding that each method or approach has a place and function that should be valued and used together to create the nutrition evidence base. Precision nutrition was identified as an important emerging nutrition topic by the preponderance of task force members, and this theme was adopted for the report because it lent itself to integration of many approaches in nutrition science. Although the primary audience for this report is nutrition researchers and other nutrition professionals, a secondary aim is to develop a document useful for the various audiences that translate nutrition research, including journalists, clinicians, and policymakers. The intent is to promote accurate, transparent, verifiable evidence-based communication about nutrition science. This will facilitate reasoned interpretation and application of emerging findings and, thereby, improve understanding and trust in nutrition science and appropriate characterization, development, and adoption of recommendations.

BackgroundBovine milk oligosaccharides (BMOs) have several demonstrated and hypothesized benefits including roles in cognitive development and antipathogenic activities, making them promising ingredients for infant formulas and nutraceutical applications. BMO extraction from bovine milk is challenged by low concentrations relative to nonbioactive simple sugars like lactose. BMO abundances are known to vary with a cow's lactation stage, breed, and parity, but these characteristics are difficult to modify in existing dairy herds. In contrast, diet modification is an accessible target, and is already known to influence milk yield, lipid content, protein levels, and monosaccharide compositions.ObjectivesTo determine the impact of a low starch high fiber versus a high starch low fiber diet on overall BMO profiles and individual BMO abundances in Holstein dairy cattle.MethodsMilk samples were collected from 59 midlactation Holsteins in a crossover study featuring dietary modification with either a low starch high fiber or high starch low fiber feed. BMO profiles were evaluated by nano-LC quadrupole time-of-flight tandem MS, and differences in BMO abundances between diets were evaluated using linear mixed effects modeling.ResultsA total of 19 BMOs were identified across the sample set, including 4 large fucosylated compounds. Seven BMOs were found to have significantly more positive percent changes in yield-adjusted abundance from the pre-experiment baseline period for milk samples collected during feeding with the low starch high fiber diet compared with the high starch low fiber diet.ConclusionsConsuming the low starch high fiber diet promoted greater overall BMO production than the high starch low fiber diet in a population of midlactation Holsteins. Additionally, this study afforded the opportunity to investigate the impact of other factors potentially influencing BMO abundances, furthering understanding of how dairy herd management practices can positively impact milk composition and support the potential use of BMOs as functional ingredients.

Training to ensure good documentation practices and adherence to regulatory requirements in human nutrition randomized controlled trials has not been given sufficient attention. Furthermore, it is difficult to find this information conveniently organized or in a form relevant to nutrition protocols. Current gaps in training and research surveillance exist in clinical nutrition research because training modules emphasize drugs and devices, promote reliance on monitoring boards, and lack nutrition expertise on human nutrition research teams. Additionally, because eating is essential, ongoing, and highly individualized, it is difficult to distinguish risks associated with interventions from eating under free-living conditions. Controlled-feeding trials provide an option to gain more experimental control over food consumed, but at a price of less external validity, and may pose human behavior issues that are unrelated to the intervention. This paper covers many of the expected practices for documentation and regulation that may be encountered in planning and conducting nutrition intervention trials with examples and references that should be useful to clinical nutrition researchers, funders of research, and research institutions. Included are definitions and guidance on clinical nutrition research oversight (institutional review boards, data safety and monitoring boards, US FDA); participant safety; standard operating procedures; training of investigators, staff, and students; and local culture and reporting requirements relevant to diet-related clinical research conduct and documentation.

BACKGROUND: Branched-chain fatty acids (BCFAs) are rumen-derived fatty acids comprising ∼2% of bovine-milk fatty acids. BCFAs possess anti-inflammatory properties and enriching the BCFA content of bovine milk may provide human health benefits. OBJECTIVE: We determined whether forage content impacts the BCFA content of milk from Holstein cows and identified fatty acid phenotypes in high vs. low BCFA–containing milks. METHODS: Holstein cows (n = 62), fed for 67 d in a crossover design, consumed a diet with high forage and low concentrate (HF:C) and a diet with low forage and high concentrate (LF:C). Milk samples were collected at the end of each treatment period and fatty acid content determined. Paired t-tests, 1-factor ANOVA, sparse partial least-squares discriminant analysis (sPLSDA), and Pearson's correlation analysis were used to analyze the data. RESULTS: The total milk fatty acid concentration for cows fed the HF:C diet was greater than that of cows fed the LF:C diet (4.2 ± 0.7 g/100 mL vs. 3.9 ± 0.9 g/100 mL). sPLSDA demonstrated separation of the dietary treatments, with BCFAs and odd-chain fatty acids as primary determinants. Total BCFA content in milk fat was elevated by HF:C intake compared with LF:C intake (1.80 vs. 1.68%). Quintile separation of high vs. low BCFA milks resulted in 4 groups: HF:C /low BCFAs, HF:C /high BCFAs; LF:C /low BCFAs, and LF:C /high BCFAs. Milks from the high BCFA quintiles had lower palmitic acid content (29.6% vs. 34.4%) but higher oleic acid content than milks from the low BCFA quintiles (19.7% vs. 17.0%). Some cows were identified as high BCFA producers or low BCFA producers regardless of diet. CONCLUSIONS: BCFA content of milk is diet-sensitive but variation in responses exists. The potential to produce milk with high BCFA content and lower SFA content needs further study.

BackgroundA more sustainable dairy cow diet was designed that minimizes use of feed components digestible by monogastric animals by increasing the quantity of forages.ObjectivesThis study determined if feeding lactating cows the more sustainable, low-starch and high-fiber (LSHF) diet was associated with changes in raw milk microbiota composition and somatic cell count (SCC).MethodsIn a crossover design, 76 lactating Holstein cows were assigned to an LSHF diet or a high-starch and low-fiber (HSLF) diet, similar to common dairy cow diets in the United States, for 10 wk then placed on the opposite diet for 10 wk. The LSHF diet contained greater quantities of forages, beet pulp, and corn distillers' grain, but contained less canola meal and no high-moisture corn compared with the HSLF diet. Raw milk samples were collected from each cow 4-5 d before intervention and 5 wk into each diet treatment. Within 4 d, additional milk samples were collected for measurement of SCC using Fossmatic 7. The microbial community was determined by sequencing the 16S rRNA gene V4-V5 region and analyzing sequences with QIIME2. After quality filtering, 53 cows remained.ResultsRaw milk microbial communities differed by diet and time. Taxa associated with fiber consumption, such as Lachnospiraceae, Lactobacillus, Bacteroides, and Methanobrevibacter, were enriched with the LSHF diet. Meanwhile, taxa associated with mastitis, such as Pseudomonas, Stenotrophomonas, and Enterobacteriaceae, were enriched with the HSLF diet. Relatedly, an interaction of diet and time was found to impact SCC.ConclusionsIn raw milk, consumption of an LSHF diet compared with an HSLF diet was associated with changes in abundance of microbes previously associated with fiber consumption, udder health, and milk spoilage. Further research is needed to determine if an LSHF diet indeed leads to lower rates of mastitis and milk spoilage, which could benefit the dairy industry.

Summary Background Increasing atmospheric concentrations of carbon dioxide (CO2) affect global nutrition via effects on agricultural productivity and nutrient content of food crops. We combined these effects with economic projections to estimate net changes in nutrient availability between 2010 and 2050. Methods In this modelling study, we used the International Model for Policy Analysis of Agricultural Commodities and Trade to project per capita availability of protein, iron, and zinc in 2050. We used estimated changes in productivity of individual agricultural commodities to model effects on production, trade, prices, and consumption under moderate and high greenhouse gas emission scenarios. Two independent sources of data, which used different methodologies to determine the effect of increased atmospheric CO2 on different key crops, were combined with the modelled food supply results to estimate future nutrient availability. Findings Although technological change, market responses, and the effects of CO2 fertilisation on yield are projected to increase global availability of dietary protein, iron, and zinc, these increases are moderated by negative effects of climate change affecting productivity and carbon penalties on nutrient content. The carbon nutrient penalty results in decreases in the global availability of dietary protein of 4·1%, iron of 2·8%, and zinc of 2·5% as calculated using one dataset, and decreases in global availability of dietary protein of 2·9%, iron of 3·9%, and zinc of 3·4% using the other dataset. The combined effects of projected increases in atmospheric CO2 (ie, carbon nutrient penalty, CO2 fertilisation, and climate effects on productivity) will decrease growth in the global availability of nutrients by 19·5% for protein, 14·4% for iron, and 14·6% for zinc relative to expected technology and market gains by 2050. The many countries that currently have high levels of nutrient deficiency would continue to be disproportionately affected. Interpretation This approach is an improvement in estimating future global food security by simultaneously projecting climate change effects on crop productivity and changes in nutrient content under increased concentrations of CO2, which accounts for a much larger effect on nutrient availability than CO2 fertilisation. Regardless of the scenario used to project future consumption patterns, the net effect of increasing concentrations of atmospheric CO2 will slow progress in decreasing global nutrient deficiencies. Funding US Environmental Protection Agency, Consultative Group on International Agricultural Research (CIGAR) Research Program on Policies, Institutions and Markets (PIM), and the CGIAR Research Program on Climate Change and Food Security (CCAFS).

OBJECTIVES: Branched chain fatty acids (BCFA) are rumen-derived fatty acids comprising about 2% of bovine milk fatty acids. BCFA possess anti-inflammatory properties and enriching the BCFA content of bovine milk may provide human health benefits of milk consumption. In this work, we determined whether high vs low forage diets impact the BCFA content of milk from Holstein cows and identified fatty acid phenotypes in high vs low BCFA-containing milks. METHODS: In this study, 62 Holstein cows were fed for 70 days, in a cross-over design fashion, either a high forage: concentrate (HF: C) diet or a low forage: concentrate (LF: C) diet. At the end of the 70-day feeding period, cows were switched to the alternate feeding arm. Milk samples were collected prior to the start of the first feeding period and at the end of each treatment period. Milk fatty acid content was determined by fatty acid methyl ester analysis. Paired t-tests, one-way ANOVA, and sparse partial least squares discriminant analysis (sPLSDA) were used to analyze the data. RESULTS: The total milk fatty acid concentration at the end of HF: C diet period was greater than that of the LF: C diet (4.2 ± 0.9 g/100 mL vs 3.95 ± 0.9 g/100 mL). sPLSDA demonstrated clear separation of the dietary treatments, with BCFA and odd-chain fatty acids as primary determinants. Total BCFA content was elevated by HF: C intake (1.86 ± 0.13%) vs LF: C intake (1.77 ± 0.14%). Quintile separation of high vs low BCFA milks resulted in 4 groups (n = 12) HF: C/low BCFA, HF: C/high BCFA; LF: C/low BCFA, and LF: C/high BCFA. The total BCFA contents of the low BCFA milks were not different regardless of forage content (1.70 ± 0.06% and 1.61 ± 0.04%) and were lower than the high BFCA milks (2.04 ± 0.11% and 1.98 ± 0.11%). Milks from the high BCFA quintiles had lower saturated fatty acid (SFA) content but higher oleic acid content than milks from the low BCFA quintiles. Of the 62 cows, 5 cows were identified as high BCFA producers and 6 cows as low BCFA producers regardless of the LF: C or HF: C diets. CONCLUSIONS: The data demonstrate that the BCFA content of milk is diet-sensitive but variation in cow responses suggest factors such as genotype or rumen microbiome composition may play significant roles. The potential to produce milk with high BCFA content and lower SFA content needs further study. FUNDING SOURCES: USDA-ARS Projects 3062–53000-001–00D, 5090–31000-025–00D, 80–8040-05–01-0000–0000.

Several studies have linked diesel engine exhaust particulate matter (DPM) to adverse health effects. To examine the effects of biodiesel blends on light-duty diesel engine exhaust composition, concentrations of a select number of target compounds were determined in petrodiesel-biodiesel [waste vegetable oil (WVO) and soybean (SOY) feedstocks] fuel blends, lubricating oil, and exhaust particulate matter (PM). Particulate matter was generated from a light-duty diesel engine running on a transient drive cycle and fueled with WVO (B10, B20, B50, and B100 where Bxx refers to volume % biodiesel in fuel blend) and SOY (B20 and B100) biodiesel fuels blended with ultralow sulfur diesel (ULSD) reference fuel (B00). As expected, concentrations of individual n-alkanes (C12–C24) decreased with increasing biodiesel content but were absent from B100 for both WVO and SOY feedstocks. No target PAHs, carbonyls, and quinones were detected in B00 fuel, biodiesel fuel blends (for both WVO and SOY), or lubricating oil. No FAM...

The USDA Agricultural Research Service (ARS) conducts research of value to US agriculture and the food supply. Most research conducted in the past has been reductionist in nature and primarily one- or two-dimensional. However, the colliding challenges of feeding a burgeoning world population, maintaining a food supply that both provides sufficient nutrition without contributing to obesity and other chronic diseases and addresses the impact of agriculture on, as well as by, the environment, have changed the complexity of the task. Today9s challenges have become multidimensional, requiring systems-type approaches across multiple and diverse disciplines. These projects cut across traditional boundaries and seek to optimize agricultural productivity within the context of reducing environmental impact and maintaining or increasing nutritional value that ultimately impacts public health. In short, new projects must take a systems approach, and the synergy gained from this approach is only made possible by simultaneous modeling of disparate data sets, demanding a new approach to data.

Machine learning and classical statistics were used to unravel the complex data set generated by the analysis of 77 fatty acids in milk from 76 cows fed 3 forages. Multivariate analysis of variance – principal components analysis (mANOVA-PCA) was used to deconvolute the data and determine the variance contributed by the main experimental factors: forage, the arbitrary cow groups, cow-to-cow variability, and milking day. All four factors contributed significantly to the data variance at the 99% confidence level as did the cross-factor variances. Cow-to-cow variance constituted 51% of the total variance of the data set and had to be removed before the significance of the other factors could be determined. The 3 forages were then found to generate milk fatty acid profiles that were significantly different. The PCA loadings showed that the major contributors to separate clustering of the forages were the less concentrated branched chain fatty acids. Fatty acids with even numbers of carbons were more concentrated, contributed high signal levels, and high noise, but were not significant in discriminating between forages. Classical paired analysis also removed the cow-to-cow variance and allowed discrimination between forages. The results showed that forages can significantly impact the fatty acid composition of milk.

It is well established that particulate matter (PM) continues to be a major air pollutant challenge for human health globally, and vehicle exhaust PM emissions have been linked to many adverse health effects. However, the relative toxicity of biodiesel emissions compared to petroleum diesel remains unclear. Given the legislated mandates to increase biodiesel fuel use in response to energy security and climate concerns, in this study we examined the relationships between biodiesel fuel blend, exhaust particle oxidative potential (OP), and PM composition. Mechanistically, there is a growing consensus that the formation of reactive oxygen species (ROS) due to PM exposure leads to subsequent oxidative stress and inflammation at the cellular level. Here, dithiothreitol (DTT) assays were performed on impinger samples of PM obtained from light-duty diesel engine transient cycle emission tests with two biodiesel feedstocks, soybean (SOY) and waste vegetable oil (WVO), blended with ultralow sulfur petrodiesel at f...

Bioactive food components or functional foods have recently received significant attention because of their widely touted positive effects on health beyond basic nutrition. However, a question continues to lurk: are these claims for 'super foods' backed by sound science or simply an exaggerated portrayal of very small 'benefits'? Efforts to establish health benefits by scientific means pose a real challenge in regards to defining what those benefits are, as well as how effective the foods are in justifying any health claim. This review discusses the pitfalls associated with the execution, interpretation, extrapolation of the results to humans and the challenges encountered in the dietary research arena from a basic scientist's perspective.

SUMMARY This chapter briefly introduces basic biochemistry of protein and amino acids (AAs) and their chemical structures, followed by the discussion on the dynamic process of protein and amino digestion, absorption, and their turnover in whole body and specific tissues in vivo as the biochemical and physiological basis in assessing protein requirements. The latter part of the chapter provided an in-depth discussion of the latest knowledge of the indicators used to assess protein requirements and AA requirements. The chapter finishes with a discussion of the current recommended intakes for protein and AAs, along with aspects of their use in nutritional assessment and issues in developing recommendations of protein/AAs for health maintenance throughout the life cycle.

While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a September,2018transdisciplinaryworkshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research.

Many terms for plant-derived food components are commonly used in the literature, but there is a notable lack of standardization and definition of nomenclature. The use of terms is often field-specific, leading to misunderstanding and problems with literature searches and systematic reviews, and results in isolated and divided research; this impacts not only publication quality but also innovation, regulatory compliance, and enforcement. To begin to address this issue, this narrative review describes the current use and definition of terms. The terms are either chemical and/or origin-based, such as phytochemical (chemicals from plants), or function-based, such as phytonutrient, bioactive, or nutraceutical. The ultimate goal is to establish a common harmonized, evidence-based understanding for when to use each term, thereby providing clarity and a specific scientific basis for such nomenclature. Neither the quality nor the quantity of evidence needed to allow the use of functional terms such as phytonutrient or nutraceutical is specifically discussed here; rather, it is simply noted that evidence is needed to apply these terms. The next step would be to define the evidence necessary for a compound to have a functional descriptor. The aim in this article is to establish scientific criteria for definitions that could be applied to clearly define and differentiate commonly used terms and thus ensure their consistent application in the scientific literature.

Rice, a staple food for more than half of the world's population, is grown in >100 countries with 90% of the total global production from Asia. Although there are more than 110,000 cultivated varieties of rice that vary in quality and nutritional content, after post-harvest processing, rice can be categorized as either white or brown. Regional and cultural preferences as well as need for stability during storage and transport are the final determinants of market availability and final consumption. In addition to calories, rice is a good source of magnesium, phosphorus, manganese, selenium, iron, folic acid, thiamin and niacin; but it is low in fiber and fat. Although brown rice is promoted as being "healthier" because of bioactive compounds, including minerals and vitamins not present in white rice after polishing, white rice is more widely consumed than brown. This is for several reasons, including cooking ease, palatability, and shelf life. Polished rice has a higher glycemic load and may impact glucose homeostasis but when combined with other foods, it can be considered part of a "healthy" plate. With the projected increase in the global population, rice will remain a staple. However, it will be important to encourage intake of the whole grain (brown rice) and to identify ways to harness the phytonutrients that are lost during milling. Furthermore, as the world faces environmental challenges, changing demographics and consumer demands, farmers, healthcare providers, food manufacturers and nutritionists must work collaboratively to assure adequate supply, nutritional integrity and sustainability of rice production systems globally.

While great interest in health effects of natural product (NP) foods and dietary supplements persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs,especially Phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a September, 2018 transdisciplinary workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for: NPcharacterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. NPCTsprioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research.

OBJECTIVES: To discuss good practices and criteria for optimal design and interpretation of pre-clinical and clinical natural product (NP) research in order to increase benefit from our investment in NP clinical trials (CT). Background: Large, randomized, controlled CT often fail to reject the null hypothesis or show rigorous evidence of benefit. This includes recent large, NIH-supported CT of nutrients such as vitamin D and selenium, and of botanical dietary supplements. Negative and positive outcomes may be equally important for public health, but because large CT cost at least $20 M each, plus opportunity costs, it is important that CT designs maximize the yield of actionable information regardless of outcome. METHODS: Experts and stakeholders from academia, government and the private sector collaboratively developed a broadly attended workshop in which good practices to enhance rigor, reproducibility and translational relevance were discussed. RESULTS: N/A. CONCLUSIONS: Critical issues in CT design include product identity, reproducibility and pharmacology (where feasible), power to test a primary outcome significant to consumers, and placebo controls. When basing a CT on traditional use or prior in vitro or in vivo studies, similarity of product (e.g., source identity, methods of preparation, form and intake), health outcome and population (e.g., age, sex, genetics, diet and environment), require careful consideration. Appropriate controls for known types of in vitro assay interference (e.g., aggregation, membrane disruption, protein denaturation) are imperative. Compounds with limited bioavailability, or activity only at concentrations above those achievable by ingestion, are likely poor candidates for dietary CT. Translational validity of model systems should be carefully assessed. Appropriate analyses (e.g., p-curve and meta-regression methods) should be used to obtain bias-corrected effect size estimates, and to identify research areas where the evidence base may be weaker than published findings suggest. Finally, CT prioritization should consider expected impact on public health, and whether known NP causal mechanisms of action are such that useful information, e.g., on product bioavailability or biological activity, are generated even if the completed CT fails to reject the null hypothesis. FUNDING SOURCES: NIH, FDA, USDA.

The goal of this work was to evaluate changes in dietary fiber measured by the traditional enzymatic-gravimetric method (AOAC 991.43) and the more recently accepted modified enzymatic-gravimetric method (AOAC 2011.25), mono- and disaccharides, and starch as a function of assessed ripeness in a controlled study of a single lot of bananas and in bananas at the same assessed stages of ripeness from bananas purchased in retail stores, from different suppliers. Sugars, starch, and dietary fiber were analyzed in bananas from a single lot, at different stages of ripeness, and in retail samples at the same assessed stages of ripeness. Mean fiber measured by the traditional enzymatic-gravimetric method (EG) was similar to 2 g/100g and not affected by ripeness. Mean fiber assessed with the recently modified method (mEG) was similar to 18 g/100g in unripe fruit and decreased to 4-5 g/100g in ripe and similar to 2 g/100g in overripe bananas. Slightly ripe and ripe bananas differed by similar to 1.1 g/100g in the controlled single-lot study but not among retail samples. There was a large increase in fructose, glucose and total sugar going from unripe to ripe with no differences between ripe and overripe. Aside from stage of ripeness, the carbohydrate composition in retail bananas is likely affected by differences in cultivar and post-harvest handling. Results from this study demonstrate the importance of measuring dietary fiber using the mEG approach, developing more comprehensive and sensitive carbohydrate analytical protocols and food composition data, and recognizing the impact of different stages of maturity and ripeness on carbohydrate intake estimated from food composition data. National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [60-8040-0-005]; United States Department of Agriculture (USDA) Agricultural Research Service (ARS)United States Department of Agriculture (USDA)USDA Agricultural Research Service [58-8040-9-013]; USDA ARSUnited States Department of Agriculture (USDA)USDA Agricultural Research Service [58-8040-8-020]; Virginia Tech [58-8040-8-020] Published version This work was supported by the National Cancer Institute under intra-agency cooperative agreement 60-8040-0-005 with United States Department of Agriculture (USDA) Agricultural Research Service (ARS) via cooperative agreement 58-8040-9-013 between USDA and Virginia Tech and cooperative agreement 58-8040-8-020 between USDA ARS and Virginia Tech.

OBJECTIVES: A dynamic US food supply and need for assessment of diet on health demands transparent, easily accessible information on foods and food components and related data on production and variability for researchers, health and nutrition policymakers and professionals, and food manufacturers. USDA is to develop an integrated food data system to address these needs and provide capacity for higher resolution compositional data analysis and an increase in available food metadata. METHODS: Create an integrated database system with five unique types of data: 1) Foundation Foods - nutrient values and extensive underlying metadata on commercially available foods that are highly consumed either as a whole food or food ingredient 2) SR Legacy (2018), the final release of Standard Reference 3) The Food and Nutrient Database for Dietary Studies - nutrient values for foods and beverages reported in What We Eat in America, National Health and Nutrition Examination Survey; 4) the USDA Global Branded Food Products Database, industry-provided label data for over 350,000 foods from a public-private partnership; and 5) Experimental Foods that will include information from multiple sources about foods produced under experimental conditions. RESULTS: FoodData Central was first launched in April 2019 and receives major updates every 6 months. Increased resolution of metadata, such as agricultural data, allows users to investigate many factors, including geographical and agricultural practices that affect the nutritional profiles of foods and dietary intake estimates. Continually added data, foods, and sample information provide research insights on attributes that influence the variability of classic nutrients and emerging bioactive compounds of public health importance. CONCLUSIONS: FoodData Central (https://fdc.nal.usda.gov/) is an integrated data system that provides expanded nutrient profile data and links to related agricultural and experimental research. The system's evolution includes exploring and implementing new database technologies and advanced knowledge systems to enhance searching, retrieval, and research capabilities. FUNDING SOURCES: United States Department of Agriculture, Agricultural Research Service.

Rising CO2 levels may induce nutritional deficits (protein, minerals, and vitamins) in the highest rice-consuming countries., Declines of protein and minerals essential for humans, including iron and zinc, have been reported for crops in response to rising atmospheric carbon dioxide concentration, [CO2]. For the current century, estimates of the potential human health impact of these declines range from 138 million to 1.4 billion, depending on the nutrient. However, changes in plant-based vitamin content in response to [CO2] have not been elucidated. Inclusion of vitamin information would substantially improve estimates of health risks. Among crop species, rice is the primary food source for more than 2 billion people. We used multiyear, multilocation in situ FACE (free-air CO2 enrichment) experiments for 18 genetically diverse rice lines, including Japonica, Indica, and hybrids currently grown throughout Asia. We report for the first time the integrated nutritional impact of those changes (protein, micronutrients, and vitamins) for the 10 countries that consume the most rice as part of their daily caloric supply. Whereas our results confirm the declines in protein, iron, and zinc, we also find consistent declines in vitamins B1, B2, B5, and B9 and, conversely, an increase in vitamin E. A strong correlation between the impacts of elevated [CO2] on vitamin content based on the molecular fraction of nitrogen within the vitamin was observed. Finally, potential health risks associated with anticipated CO2-induced deficits of protein, minerals, and vitamins in rice were correlated to the lowest overall gross domestic product per capita for the highest rice-consuming countries, suggesting potential consequences for a global population of approximately 600 million.

Diesel engine emissions are an important source of ultrafine particulate matter (PM) in both ambient air and many occupational settings. Biodiesel is a popular, ‘green’ alternative to petroleum diesel fuel, but little is known about the impact of ‘real world’ biodiesel combustion on workplace PM concentrations and particle characteristics including size, morphology, and composition; or on biological responses. The objectives of the present work were to characterize PM workplace concentrations and tailpipe emissions produced by the combustion of commercially purchased low sulfur petrodiesel and a waste grease B20 blend (20% biodiesel/80% petrodiesel by volume) in heavy duty diesel (HDD) nonroad equipment operating in a ‘real world’ rural recycling center. Furthermore, we assessed the in vitro responses of cell lines representing human lung epithelial cells (BEAS-2B) and macrophages (THP-1) after 24 h of exposure to these real-world particles. Compared to petroleum diesel, use of B20 in HDD equipment resulted in lower mass concentrations of PM2.5, PM

We recently reported that lowering the high, habitual palmitic acid (PA) intake in ovulating women improved insulin sensitivity and both inflammatory and oxidative stress. In vitro studies indicate that PA can activate both cell membrane toll-like receptor-4 and the intracellular nucleotide oligomerization domain-like receptor protein (NLRP3). To gain further insight into the relevance to human metabolic disease of dietary PA, we studied healthy, lean and obese adults enrolled in a randomized, crossover trial comparing 3-week, high-PA (HPA) and low-PA/high-oleic-acid (HOA) diets. After each diet, both hepatic and peripheral insulin sensitivities were measured, and we assessed cytokine concentrations in plasma and in supernatants derived from lipopolysaccharide-stimulated peripheral blood mononuclear cells (PBMCs) as well as proinflammatory gene expression in skeletal muscle. Insulin sensitivity was unaffected by diet. Plasma concentration of tumor necrosis factor-α was higher during the HPA diet. Lowering the habitually high PA intake by feeding the HOA diet resulted in lower secretion of interleukin (IL)-1β, IL-18, IL-10, and tumor necrosis factor-α by PBMCs, as well as lower relative mRNA expression of cJun and NLRP3 in muscle. Principal components analysis of 156 total variables coupled to analysis of covariance indicated that the mechanistic pathway for the differential dietary effects on PBMCs involved changes in the PA/OA ratio of tissue lipids. Our results indicate that lowering the dietary and tissue lipid PA/OA ratio resulted in lower leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes, but the relevance to diabetes risk is uncertain.

Background. Increases in atmospheric concentrations of carbon dioxide (eCO2) affect global nutrition through impacts on agricultural productivity and nutrient content of food crops. Methods. We used a global economic model of the agricultural sector to project per capita availability of protein, iron, and zinc in 2050. Estimated changes in productivity of individual agricultural commodities were used to model effects on production, trade, prices, and consumption. The resulting food supply was combined with two sources of data on eCO2 effects on nutrient content. Findings. While technological change, market responses, and the productivity effects of CO2 yield fertilization are projected to increase global availability of dietary protein, iron, and zinc, these increases are dampened by negative effects of climate change impacts on productivity and eCO2 impacts on nutrient content. Both datasets show projected eCO2 decreases global availability of nutrients in crops by enacting a 2·4% to 4·3% penalty on expected gains by mid-century. The penalty on nutrient content of wheat is ~3 times larger. Many countries currently experiencing high levels of nutrient deficiency would continue to be disproportionately affected. Interpretation. This approach represents an improvement in estimating future impacts on global food security by simultaneously projecting climate change impacts on crop productivity and changes in nutrient content under eCO2, which accounts for a much larger effect on nutrient availability than CO2 fertilization. Regardless of the scenario used to project future consumption patterns, the net effect of rising atmospheric CO2 concentrations will slow progress in achieving reductions in global nutrient deficiencies. Funding: This research was funded by the U.S. Environmental Protection Agency under contract EPBPA16H0002. Support was also provided through the CGIAR Research Programs on Policies, Institutions, and Markets (PIM) and Climate Change, Agriculture and Food Security (CCAFS). The views expressed in this document are those of the authors and do not necessarily reflect those of their affiliated institutions including the U.S. Environmental Protection Agency or the U.S. Department of Agriculture. Declaration of Interest: The authors declare no competing interests.

Relative to diets enriched in palmitic acid (PA), diets rich in oleic acid (OA) are associated with reduced risk of type 2 diabetes. To gain insight into mechanisms underlying these observations, we applied comprehensive lipidomic profiling to specimens collected from healthy adults enrolled in a randomized, crossover trial comparing a high-PA diet to a low-PA/high-OA (HOA) diet. Effects on insulin sensitivity (SI) and disposition index (DI) were assessed by intravenous glucose tolerance testing. In women, but not men, SI and DI were higher during HOA. The effect of HOA on SI correlated positively with physical fitness upon enrollment. Principal components analysis of either fasted or fed-state metabolites identified one factor affected by diet and heavily weighted by the PA/OA ratio of serum and muscle lipids. In women, this factor correlated inversely with SI in the fasted and fed states. Medium-chain acylcarnitines emerged as strong negative correlates of SI, and the HOA diet was accompanied by lower serum and muscle ceramide concentrations and reductions in molecular biomarkers of inflammatory and oxidative stress. This study provides evidence that the dietary PA/OA ratio impacts diabetes risk in women.

Epidemiological studies have shown that advancing age is associated with an increased prevalence of cardiovascular disease (CVD). Vascular smooth muscle cells (VSMC) comprise the major arterial cell population, and changes in VSMC behavior, function, and redox status with age contribute to alterations in vascular remodeling and cell signaling. Over two decades of work on aged animal models provide support for age-related changes in VSMC and/or arterial tissues. Enhanced production of reactive oxygen species (ROS) and insufficient removal by scavenging systems are hallmarks of vascular aging. VSMC proliferation and migration are core processes in vascular remodeling and influenced by growth factors and signaling networks. The intrinsic link between gene regulation and aging often relates directly to transcription factors and their regulatory actions. Modulation of growth factor signaling leads to up- or downregulation of transcription factors that control expression of genes associated with VSMC proliferation, inflammation, and ROS production. Four major signaling pathways related to the transcription factors, AP-1, NF-κB, FoxO, and Nrf2, will be reviewed. Knowledge of age-related changes in signaling pathways in VSMC that lead to alterations in cell behavior and function consistent with disease progression may help in efforts to attenuate age-related CVD, such as atherosclerosis. Antioxid. Redox Signal. 12, 641–655.

With the advent of nanotechnology, concerns about the potential adverse health effects of nanomaterials have been expressed, especially to workers and users [1, 2]. For these reasons, screening assays are needed to assess a myriad of chemically and physically diverse nanomaterials. Because of the expense of in vivo experiments and public and governmental urging to develop alternatives to animal testing, in vitro models may be more attractive for preliminary testing of nanomaterials to assess their potential toxicologic effects and ability to elicit disease. Human health concerns for nanomaterials are predicated historically by epidemiologic and clinical studies on naturally occurring fibers and particles such as asbestos and silica, respectively. Whereas inhalation of asbestos fibers is associated with the development of nonmalignant (pleural and pulmonary fibrosis or asbestosis) and malignant diseases (lung cancers and mesotheliomas) [3, 4], silica is associated primarily with the development of silicosis, an occupationally-linked pulmonary fibrosis [5]. After decades of research, the complex mechanisms of disease by these minerals are still incompletely understood, but several properties appear important in the long-term health effects of asbestos fibers. These include: 1) respirability or ability to enter the lung; 2) durability, due to intrinsic lack of solubility and/or inability to be cleared by macrophages in the lung, pleura or peritoneum; 3) fibrous geometry; 4) length to width ratio, i.e., longer (> 5 μm) and thinner fibers are more carcinogenic and fibrogenic; and 5) surface properties which play a role in the generation of reactive oxygen or nitrogen species (ROS/RNS) [6]. In addition, both ROS and RNS have been linked to the generation and augmentation of the inflammatory responses to asbestos and silica, and inflammation is thought to be key to the development of fibrosis and many cancers [7]. We recently have shown that stimulation of the inflammasome of human macrophages via NADPH oxidase acts as a sensor for the production of proinflammatory cytokines such as interleukin-1β by asbestos, suggesting that inflammation mediates responses of target cells of lung disease [8]. These studies underscore the importance of effective screening strategies for nanomaterials using multiple cell types, especially since nano-sized particles and fibers may be similar to ultrafine (UF) particles that can penetrate the endothelium of the lung and be transported to distal organs such as the heart and brain [1, 2]. For testing of the pathogenic effects of asbestos and asbestos-like fibers, most in vitro assays have been designed using target cells of the lung and pleura with endpoints such as cytotoxicity, proliferation, and genotoxicity. These phenomena are related to the multiple stages of cancer development which may involve genotoxic (changes to DNA) as well as proliferative events that can lead to the selective expansion of an asbestos-mutated cell population. In this chapter, we review in vitro assays for cytotoxicity, proliferation, genotoxicity, and more robust toxicogenomic approaches that can be used to screen nanomaterials for their potential pathogenic effects. Since the majority of these assays have been standardized in our laboratory using a variety of pathogenic minerals (asbestos, silica) and nonpathogenic particles (fine titanium dioxide [TiO2] or glass beads), we will frequently supplement our discussion of nanomaterials with mention of other mineral/particle types to demonstrate each assay's utility in predicting toxicity. Although cell-free in vitro assays to predict dissolution of nanomaterials in the body are not discussed in detail, they are recommended to predict nanomaterial durability over time, especially since it has been shown that diseases resulting from exposure to other pathogenic materials, such as asbestos, require decades to develop [3, 4].

The antioxidant response element (ARE) is an essential component of upstream regulatory sequences present on genes for most phase II detoxification enzymes, including the glutamate cysteine ligase catalytic subunit (GCLC). NF-E2-related factor 2 (Nrf2) is a principal transcription factor that binds to the ARE and plays a key role in cellular responses to stress via the Keap1-Nrf2-ARE pathway. However, the ARE that mediates human GCLC gene expression has not been found in the rat. Thus, how the ARE-mediated Keap1-Nrf2-ARE pathway regulates glutathione homeostasis in the rat remains a puzzle. We have identified a putative ARE sequence approximately 4 kb upstream in the rat GCLC. We further defined the rat GCLC-ARE in the category with the most ARE characters, that is, this rat GCLC-ARE is a sequence-specific site that significantly enhances promoter activity in reporter genes. The rat GCLC-ARE is an Nrf2-mediated element to which binding has been demonstrated in nuclear extracts and induced by tert-butylhydroquinone. Given the central role that rat models play in toxicology and pathology, this first discovery of the rat GCLC-ARE enhancer similar to that found in the human gene has broad implications for the study of antioxidant defenses and their regulation in a number of different fields.

Background Associations between air pollution and morbidity/mortality from cardiovascular disease are recognized in epidemiologic and clinical studies, but the mechanisms by which inhaled fibers or particles mediate the exacerbation of atherosclerosis are unclear. Objective and methods To determine whether lung inflammation after inhalation of a well-characterized pathogenic particulate, chrysotile asbestos, is directly linked to exacerbation of atherosclerosis and the mechanisms involved, we exposed apolipoprotein E–deficient (ApoE−/−) mice and ApoE−/− mice crossed with CD4−/− mice to ambient air, NIEHS (National Institute of Environmental Health Sciences) reference sample of chrysotile asbestos, or fine titanium dioxide (TiO2), a nonpathogenic control particle, for 3, 9, or 30 days. Results ApoE−/− mice exposed to inhaled asbestos fibers had approximately 3-fold larger atherosclerotic lesions than did TiO2-exposed ApoE−/− mice or asbestos-exposed ApoE−/−/CD4−/− double-knockout (DKO) mice. Lung inflammation and the magnitude of lung fibrosis assessed histologically were similar in asbestos-exposed ApoE−/− and DKO mice. Monocyte chemoattractant protein-1 (MCP-1) levels were increased in bronchoalveolar lavage fluid and plasma, and plasma concentrations correlated with lesion size (p < 0.04) in asbestos-exposed ApoE−/− mice. At 9 days, activator protein-1 (AP-1) and nuclear factor-κB (NF-κB), transcription factors linked to inflammation and found in the promoter region of the MCP-1 gene, were increased in aortas of asbestos-exposed ApoE−/− but not DKO mice. Conclusion Our findings show that the degree of lung inflammation and fibrosis does not correlate directly with cardiovascular effects of inhaled asbestos fibers and support a critical role of CD4+ T cells in linking fiber-induced pulmonary signaling to consequent activation of AP-1– and NF-κB–regulated genes in atherogenesis.

Happy New Year! With 2015 now open like a chapter’s worth of blank pages, a quick look back at 2014 keeps us apprised of Nutrition Reviews ’ unfolding story. Some of the more notable events include: Nutrition Reviews ’ increased impact factor (5.541) and ranking (5 of 78 journals in the Nutrition & Dietetics category); changes to the editorial team; modifications of the journal’s author guidelines and procedures; and a new publishing partnership with Oxford University Press (new journal homepage: http://nutritionreviews.oxfordjournals.org/). For the first, deep and sincere thanks are extended to all of our authors, reviewers, and readers! While a journal’s impact factor is not the only measure of its success, it is inextricably interwoven with the efforts of many dedicated and hardworking individuals whom we are honored to work with and to serve. In 2015, we look forward to building on the relationships already established and to developing …

Epidemiological studies report that exposure of expectant mothers to outdoor air pollution correlates with an increased risk of obesity, insulin resistance (IR) and earlier onset of type 2 diabetes mellitus in her offspring. To test the hypothesis that prenatal exposure to PM from PD combustion will lead to alterations in weight (WT) gain and insulin sensitivity, pregnant C57BL/6J mice were exposed daily to

Manganese-superoxide dismutase (MnSOD) is one of the major cellular antioxidant defense systems. To study the effect of age on the regulation of MnSOD in the vasculature, we compared MnSOD expression and its transcriptional regulation in explanted vascular smooth muscle cells (VSMC) isolated from old (24 months old) versus young (6 months old) rats and grown in a normal (5 mM) or high (12.5 and 25 mM) glucose or tumor necrosis factor alpha (5 ng/ml) environment to induce oxidative stress. Both MnSOD protein and activity were reduced in VSMC from old compared with young animals. FOXO3a, a member of the family of Forkhead transcription factors, interacted with the promoter of the rat MnSOD gene at a specific binding site. Inhibition of FOXO3a transcription with small interfering RNA led to a reduction in MnSOD gene expression. VSMC from old rats had increased phosphorylated FOXO3a at Ser(253), which paralleled the reduction of MnSOD protein. Treatment of VSMC with 5 nm insulin-like growth factor-1 induced phosphorylation of Akt and FOXO3a over time, repressing FOXO3a DNA binding and consequently MnSOD gene expression. Furthermore, Akt activity was selectively increased in VSMC from the old, supporting the hypothesis that increased age-related Akt activity might be responsible for the phosphorylation and inactivation of FOXO3a, which in turn down-regulates MnSOD transcription.