bluuebunny/crossref_metadata_2025 huggingface dataset:
Contemporary Approaches to Risk Stratification and Treatment
Authors: Flack John M.
Published: June 2021

Diagnosing individuals with “hypertension” can be accomplished several ways. One approach is simply using an extreme outlier cut‐point (≥ 140/90 mm Hg) above which all individuals are considered hypertensive. A modification of this approach is to lower the level of the extreme cut‐point (≥130/80 mm Hg) in groups with known higher absolute cardiovascular‐renal risk (chronic kidney disease, diabetes mellitus). Prospective clinical trial data are not available for all high‐risk groups for which treatment decisions must be made today. Moreover, randomized, hard end‐point clinical trials though extremely important do not ask all of the important questions and are not the only source of data that merits consideration. Risk stratification, treatment, and authoritative guidelines, if practical and useful, remain an artful elixir of epidemiological data, clinical trials examining BP response and hard endpoint data, basic science and physiological investigations, genetics – and reasonable extrapolations to various population subgroups for which there may be limited clinical data. This talk will cover contemporary approaches to risk stratification, new therapeutic targets, and other practical considerations in the identification and management of the patient with hypertension.
What makes a grant application competitive
Authors: Carman George M
Published: June 2021

The key step in preparing a competitive grant application begins with an idea. The idea doesn't have to be complicated; it just has to be sound. Your idea must be conveyed in a manner that is easy to understand, and sufficient information must be presented (e.g., background and preliminary data) to give confidence that new and useful information will be forthcoming. Follow instructions, use good grammar, and organize the application in a logical manner. Don't assume that the reader will understand what you mean; spell it out. Emphasize the importance of your idea.
How to Work WITH Your Program Director
Authors: Chitnis Parag R
Published: June 2021

Providing advice to potential and current principal investigators is one of the responsibilities of the program directors at federal funding agencies. They can be a rich source of helpful advice about preparing the original proposal as well as about revising your proposal for resubmission. This presentation will provide information about how to approach the staff at federal funding agencies, what type of questions to ask (and not to ask), and how to make best of the information obtained from the program directors to prepare a competitive grant proposal.
Middle schoolers want more than games for health education on the internet
Authors: Muzaffar Henna , Castelli Darla , Goss David , Scherer Jane , Chapman‐Novakofski Karen
Published: June 2021

A diabetes awareness website (the HOT project: Healthy Outcomes for Teens) with content (diet and exercise) specific for 14–17 year olds with type 2 diabetes or at risk for type 2 diabetes was developed. The content focused on skills/knowledge assessment, overview of diabetes/food, food groups/diabetes, physical activity/weight management, and eating for target blood glucose levels in 5 modules. Our objective was to elicit information from those participants relative to the appeal of the website after the intervention to enhance its sustainability/usability. Subjects (n=42) were recruited from 3 school districts in central Illinois and had participated in the HOT project intervention (12 focus groups, n=2–5 each). The interview sessions took an average of 60–90 minutes, were audio taped and then transcribed verbatim. Content analysis was used to identify 3 themes: kid appeal, healthy living, and living with and without diabetes. Within kid appeal, three sub themes were found: social, entertainment and information. The most significant finding of this study was that while participants wanted more games, they also wanted more information and more social interaction. Sleeping, friendship, and studying along with website content were mentioned concerning healthy living. About half had relatives with diabetes and were more familiar with diabetes terminology and concepts. Funding: ADAF, NSRL, ISA.

Grant Funding Source: Funded by ADAF, NSRL and ISA
Intake of fish and omega‐3 (n‐3) fatty acids: effect on bone during actual and simulated weightlessness
Authors: Smith Scott M. , Pierson Duane L. , Mehta Satish K. , Zwart Sara R.
Published: June 2021

Space flight has many negative effects on human physiology, including bone and muscle loss. These are some of the systems on which intakes of fish and n‐3 fatty acids have positive effects. These effects are likely to occur through inhibition of inflammatory cytokines (such as TNFα) and thus inhibition of downstream NF‐κB activation. We documented this effect in a 3D cell culture model, where NF‐κB activation in osteoclasts was inhibited by eicosapentaenoic acid, an n‐3 fatty acid. We have extended these studies and report here (a) NF‐κB expression in peripheral blood mononuclear cells of Space Shuttle crews on 2‐wk missions, (b) the effects of n‐3 fatty acid intake after 60 d of bed rest (a weightlessness analog), and (c) the effects of fish intake in astronauts after 4 to 6 mo on the International Space Station. After Shuttle flights of ~2 wk, NF‐κB p65 expression at landing was increased (P <0.001). After 60 d of bed rest, higher intake of n‐3 fatty acids was associated with less N‐telopeptide excretion (Pearson r = −0.62, P < 0.05). Higher consumption of fish during flight was associated with higher bone mineral density (Pearson r = −0.46, P < 0.05). Together with our earlier findings, these data provide mechanistic cellular and preliminary human evidence of the potential for n‐3 fatty acids to counteract bone loss associated with spaceflight. This study was supported by the NASA Human Research Program.
Stearidonic acid‐enriched soybean oil: A source of cardioprotective omega‐3 fatty acids
Authors: Krul Elaine Susan , Lemke Shawna L , Mukherjea Ratna , Goldstein Daniel A , Su Hong , Nemeth Margaret A , Harris William S
Published: June 2021

Stearidonic acid (SDA) is the product of the rate‐limiting enzyme (delta‐6 desaturase) in the conversion of alpha‐linolenic acid (ALA) to eicosapentaenoic acid (EPA). Through biotechnology, SDA has been produced at levels of 20%–30% of total fatty acids in soybean oil (SDA SBO). The objective was to assess the effects of SDA SBO compared to EPA or commodity SBO on red blood cell (RBC) EPA+DHA levels (the omega‐3 index) and other markers. Volunteers were randomized to SDA SBO (15 g/day providing 4.1 g SDA) plus 1 g/day SBO oil in gelcaps (SDA group) or to 15 g/day commodity SBO with either EPA ethyl esters (1 g/d; EPA group) or 1 g/day SBO oil in gelcaps (control group) for 12 weeks (N=157 completed). The overall mean (±SD) omega‐3 index at baseline was 4.3±1.1% and was unchanged at 12 weeks in the control group but increased by 17.7% and 19.7% in the SDA and EPA groups, respectively (ANCOVA, both p<0.001). Older subjects and those with higher baseline %EPA had greater absolute %EPA in their RBCs after treatment (P=0.037 and P=0.005, respectively). Fasting triglycerides (TG) were reduced 26–30% by SDA or EPA treatment vs. control (p=0.029) for a subset population with baseline TG levels >150 mg/dL, when assessed by a post hoc repeated measures analysis. In conclusion, SDA SBO significantly raised the omega‐3 index to an extent associated with a reduced risk for cardiac events based on epidemiologic and published clinical studies.
Effects of α‐Linolenic Acid (ALA) Versus Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Mood Status in Healthy Adults
Authors: Mazhar Wajeeha , Wien Michelle , Sabaté Joan
Published: June 2021

Study Objective

There is mounting evidence associating intake of n‐3 essential fatty acids ALA, EPA and DHA with mood states. This study aims to compare the effects of flaxseed oil, a terrestrial source of the n‐3 ALA versus algae oil, a marine source of EPA/DHA (V‐Pure) on mood status in healthy adults.

Methods

We performed a randomized cross‐over feeding study (three 8‐week dietary study periods) in 24 healthy adults. Subjects consumed three eucaloric diets Control, flaxseed oil (6–7g of ALA/2400 kcal/d) and algae (0.20/0.72g EPA/DHA per 2400 kcal/d). Mood state was assessed by two self‐rating questionnaires: Profile of Mood States (POMS) and Depression Anxiety and Stress Scale (DASS) administered at the end of each study period.

Results

Compared with control, the flaxseed diet exhibited a tendency to decrease POMS and DASS depression scores by 14% and 39% respectively. Algae diet tended to raise depression scores by 31% and 33% respectively (all p>0.05). Similar trends were observed for stress scores while scores for vigor were reversed for the diets.

Conclusions

Longer studies are needed to test the effects of diet enriched with ALA and/or EPA/DHA on mood states which may clarify the tendencies observed during our short term study.
Effects of polyunsaturated n‐3 fatty acids in the prevention of metabolic syndrome in golden syrian hamster fed with high fat diet
Authors: Fatima Kasbi Chadli , Kadiatou Soumah , Thierry Magot , Patrick Nguyen , Ouguerram Khadija
Published: June 2021

High fat diets are among majors factor for the predisposition to metabolic syndrome including obesity, insulin resistance, dyslipidemia, and cardiovascular diseases. Previous studies have demonstrated the effects of ω3 polyunsaturated fatty acids (PUFA) on dyslipidemia. In our study we investigated the preventive effect of this fatty acid in western diet (45% of total energy intake) enriched (HFDω3) or not (HFD) in ω3 PUFA (EPA and DHA) at ω6/ω3=3 ratio on different parameters: the lipids status (plasma TG, total cholesterol, and HDL cholesterol), the insulin sensitivity, and the body composition. The results indicate that PUFA ω3 had no effect on food consumption but tended to lower body fat percentage (HFD:17.6±4 %; HFDω3: 13.9±6; p=0.09), prevented weight gain (HFD:124±7g; HFDω3:111±6g; p=0.02), and limited hypertriglyceridemia (HFD: 2.03±0.3g/L; HFDω3: 1.41±0.2g/L; p=0.01) and postprandial TG (HFD: 2.65±0.7g/L; HFDω3: 1.58±0.5g/L; p=0.04) This reduction resulted from lower that was reduced by 60% 4 hours after injection of triton (HFD: 7.93 ± 1.61g/L; HFDω3: 4.19 ± 0.88g/L; p=0.01). HFD enriched on ω3 PUFA have also positive effect on insulin sensitivity (HOMA Matthews p=0.04). We conclude that ω3 PUFA have protective effect against obesity and dyslipidemia in golden Syrian hamster fed with high fat diet.
Improved diet quality, nutrient intake, and health associated with out‐of‐hand tree nut consumption in U.S. Adults: NHANES 1999–2004
Authors: Fulgoni Victor L , O'Neil Carol E , Keast Debra R , Nicklas Theresa A
Published: June 2021

NHANES (1999–2004), data were used to examine the association of out‐of‐hand tree nut consumption (almonds, Brazil nuts, cashews, filberts, macadamias, pecans, pine nuts, pistachios, and walnuts) with diet quality, nutrient intakes, and health risks in adults 19+ yrs (n=13,292). Using 24 hour recall data, tree nut consumption was defined as intake of ≥¼ ounce/d tree nuts eaten out‐of‐hand excluding tree nuts contained in cereals and other foods. Means, prevalence rates, and standard errors, were determined via ANOVA (adjusted for covariates). Consumers (n=514) had improved diet quality, measured using Healthy Eating Index‐2005, (60.0 ± 0.6 vs. 49.6 ± 0.3, p<0.01) and significantly higher (p<0.01) intakes of adult shortfall nutrients (difference between groups): fiber (4.5 g/d), vitamin E (3.9 mg AT/d), magnesium (102 mg/d), and potassium (278 mg/d) with lower sodium intake (−283 mg/d). BMI (−0.9 kg/m2, p<0.01), waist circumference (−2.0 cm, p<0.01) and the prevalence (%) of hypertension (29.2 ± 2.1 vs. 33.8 ± 0.7, p<0.05), low HDL‐C (27.8 ± 2.2 vs. 34.0 ± 0.7, p<0.01), and metabolic syndrome (17.7 ± 2.5 vs. 26.3 ± 0.7, p<0.01) were lower in consumers as compared to non‐consumers. Tree nut consumption was associated with a higher overall diet quality score, improved nutrient intakes, and lower prevalence of health risks. (Supported by International Tree Nut Council Nutrition Research & Education Foundation)
Food sources of calcium, phosphorus, vitamin D, and potassium in the U.S.
Authors: Fulgoni Victor L , Keast Debra R , Quann Erin E , Auestad Nancy
Published: June 2021

Dietary food patterns recommended for children and adults include two/three daily servings of dairy foods to provide important bone building nutrients, namely calcium (Ca), phosphorus (P), and vitamin D and contribute to potassium (K) intakes. The aim of this study was to determine dietary sources of Ca, P, vitamin D, and K in the U.S. using NHANES, 2003–2006 data. Intakes were determined for subjects, 2+ yrs (n=16,822) with a reliable 24‐hr recall interview on the first day. With food mixtures/mixed dishes classified by their main ingredient, the top five food categories as sources (%) of Ca were dairy (38.6), grains (28.8), beverages (7.2), sweets and desserts (7.2), and meat, poultry and fish (4.5); of P were grains (28.6), dairy (22.0), meat, poultry and fish (21.0), sweets and desserts (6.7), and eggs, legumes and nuts (6.4); of vitamin D were dairy (52.3), meat, poultry and fish (19.3), grains (11.3), eggs, legumes and nuts (4.9), and fruit/fruit juice (3.4); and of K were grains (20.3), meat, poultry and fish (16.2), dairy (13.9), vegetables (13.7), and fruit/fruit juice (11.1). Fluid milk was the number one single food source of Ca, P, vitamin D, and K providing 21.5, 12.3, 42.6, and 9.9%, respectively, of the total dietary intake of these nutrients. In conclusion, these data continue to support that dairy products and fluid milk, in particular, are the major sources of important nutrients from food in the U.S. diet. (Supported by the National Dairy Council)
Contributions of food intake to serum 25 OH vitamin D levels in healthy African American and Caucasian Los Angelinos
Authors: Arab Lenore , Nelson Casey , Cambou Mary Catherine , Kim Heeyoung , Horst Ronald , Wessling‐Perry Katherine , Jardack Patricia
Published: June 2021

To determine the impact of diet on circulating levels of vitamin D we studied healthy, weight constant African Americans and Caucasians in Los Angeles. We examined the relative contributions of dietary intakes from fish, dairy and multivitamin supplements from 6 24‐hour recalls. Distinct racial differences were noted, with a median of 21.2 ng/ml for African Americans, and 34.4 for Caucasians. Multiple linear regression models, adjusted for age and gender were run to examine the relationship between serum vitamin D levels and dietary consumption of vitamin D‐rich foods. Across the total population, dairy consumption was strongly related to 25 OH vitamin D levels, with the contributions from full fat and non‐fat milk demonstrating statistically significant regression coefficients of 1.45 and 1.78, respectively. The elevation in vitamin D seen per 100 g full fat milk consumption was also almost twice as great among the African American subjects (2.0 vs 1.1 ng/ml elevation per 100 g). Fish consumption was not significantly related to circulating levels in this population. Use of a multivitamin had almost twice the impact among the African Americans (11.6 vs 6.3 ng/ml elevation per tablet). The lack of association with fish and the differential effects of diet in African Americans deserves further attention. Supported by NIH R01CA105048.
All‐trans retinoic acid increases matrix metalloproteinase‐9 expression in murine myeloid dendritic cells through retinoic acid receptor‐α interaction with and histone acetylation of the promoter
Authors: Lackey Denise E. , Hoag Kathleen A.
Published: June 2021

Myeloid dendritic cells (DC) are antigen presenting cells that migrate to secondary lymphoid tissues following activation. We have previously shown that treatment of mouse DC with all‐trans retinoic acid (atRA) decreases adherence through production and activity of matrix metalloproteinase (MMP)‐9. The Mmp‐9 promoter does not, however, contain a traditional retinoic acid response element for atRA to transduce its signal for gene regulation. To identify the mechanism by which atRA increases MMP‐9 production in DC, we performed electrophoretic mobility shift assays for the consensus Sp1, AP‐1 and NFκB binding sites located in the Mmp‐9 promoter. We found no consistent change in nuclear protein binding to Sp1 or AP‐1 consensus sequences in response to atRA, while binding to NFκB decreased compared to retinoic acid receptor (RAR)‐alpha antagonist treatment. We next performed chromatin immunoprecipitation assays to assess the effect of atRA on Mmp‐9 promoter activity. We found that atRA increased recruitment of RARα (38%) and histone acetyltransferase p300 (24%) to the Mmp‐9 promoter and increased histone H3 acetylation in the promoter by 29%. We conclude that atRA increases transcription of Mmp‐9 directly by enhancing RARα promoter binding, recruitment of p300, and subsequent acetylation of histone H3. Supported by the Department of Food Science and Human Nutrition, Michigan State University.

Grant Funding Source: Department of Food Science and Human Nutrition, Michigan State University
Vitamin A is Required for Maintenance of Plasmacytoid Dendritic Cells in Mouse Peyer's Patches
Authors: Duriancik David M , Hoag Kathleen A
Published: June 2021

In the mouse, myeloid dendritic cells (DCs) and lymphoid DCs are responsible for stimulating T helper (Th) 2 and Th1 responses, respectively. Plasmacytoid (pDCs) secrete large amounts of type 1 interferons (IFN‐α/β) in response to virus infection. Vitamin A up‐regulates CCR9 on numerous cell populations for homing to the small intestine. In addition, pDCs express high amounts of CCR9. The objective of our study was to determine the effects of vitamin A deficiency on the DC populations of Peyer's patches. We hypothesized that pDCs would be decreased in the Peyer's patches of vitamin A‐deficient mice. In house bred, specific pathogen‐free, C57BL/6J mice were depleted of vitamin A through diet and sacrificed at 8, 10, and 12 weeks of age. Flow cytometry was used to identify the DC subpopulations of Peyer's patches and High Performance Liquid Chromatography was used to assess liver retinol activity equivalents. Precursor DCs and pDCs decreased as severity of vitamin A deficiency increased. Plasmacytoid DCs of the Peyer's patches are more tolerogenic than pDCs of the spleen. In addition, vitamin A plays a critical role in maintaining the balance of T regulatory and T helper 17 cell populations. Therefore, vitamin A deficiency decreases pDCs of the Peyer's patches, likely contributing to impaired tolerance and increased Th17 cells in the mucosa.

Grant Funding Source: Intramural Funds
Cranberry phytochemicals modify human immune function and appear to reduce the severity of cold and flu symptoms
Authors: Nantz Meri P. , Rowe Cheryl A. , Muller Catherine E. , Creasy Rebecca , Chapkin Chelsea , Pasqualini Sofia , Lozada Jillian , Khoo Christina , Percival Susan S.
Published: June 2021

Proanthocyanidins (PACs) are complex molecules that have been suggested to have health benefits, most recently in relation to immune function. Cranberries are an excellent source of PACs, possessing both the A‐ and B‐type linkages, and in addition, contain other polyphenols. We hypothesized that the PAC contained in cranberries could modify specific human immune cells in vivo, particularly the γδ T cell which is known to recognize and respond to PACs in vitro. This effect is thought to be related to non‐microbial priming of the immune cells by the phytochemicals. In a randomized, double‐blind, placebo‐controlled human study, 10 weeks of consumption of a beverage containing a powder derived from cranberries resulted in a fivefold increase in proliferation of γδ T cells ex vivo, a 30% increase in NK cell proliferation and a 20% reduction in IL‐17 secretion. Subjects consuming the beverage made with cranberry powder had fewer cold and flu symptoms (p=0.010) when compared to those consuming the placebo. The incidence of illnesses, total missed work days, and decrease in activities tended to be lower, however actual values were not significantly different from placebo. Consumption of cranberry phytochemicals was shown to modify certain aspects of immune function, suggesting that consuming cranberries may help support immune health. Supported by Ocean Spray Cranberries, Inc and FAES
Pro‐atherogenic effects of probucol may be mediated through alterations in the coagulation system in apo E‐KO mice
Authors: Moghadasian Mohammed H. , Xu Zuyuan , Othman Rgia A. , Azordegan Nazila , Shen Garry
Published: June 2021

We have previously shown that probucol paradoxically increases atherogenesis in apo E‐KO mice, while dietary phytosterol significantly reduce the disease in this animal model. Male apo E‐KO mice were fed with an atherogenic diet containing 9% (w/w) fat and 0.2% (w/w) cholesterol in the presence of either 2% (w/w) dietary phytosterol mixture (phytosterol‐treated group, n=8), or 1% (w/w) probucol (probucol‐treated group, n=8) or nothing (control group, n=8) for 18 weeks. Plasma total cholesterol levels were significantly decreased in both treated groups as compared to controls. Aortic atherosclerotic lesion size was significantly lower in the phytosterol‐treated and significantly higher in the probucol‐treated mice as compared to controls. Plasma and aortic PAI‐1 levels were significantly higher in the probucol‐treated animals as compared to controls, while these values were comparable between the phytosterol‐treated and control mice. Both DNA microarray and RT‐PCR tests showed a significant increase in the expression of F13a1 in the liver of probucol treated mice as compared to controls. These observations suggest that pro‐atherogenic effects of probucol maybe mediated through alterations in the coagulation system in this animal model.
Zinc supplementation, small intestinal morphology and disaccharidases activity
Authors: Tran Cuong D , Cool Jo , Xian Cory J
Published: June 2021

The present study examined the effect of increasing dietary zinc (Zn) concentrations in the weaning mouse diet and the lack of metallothionein (MT) expression on intestinal morphology and disaccharidases activity. MT‐I&II null (MT−/−) and wild‐type (MT−/−) female mice at 3.5 weeks of age were randomly allocated to be fed with 2 (2Zn), 15 (15Zn) and 50 (50Zn) mg Zn/kg diet for 5 weeks. Duodenal, jejunal and ileal segments were collected and either fixed in 10% formalin for histological analysis or snap frozen in liquid nitrogen for analysis of sucrase, lactase and maltase activities. No differences in body weight gained were observed between genotypes or dietary groups. Villus height and crypt depth were increased by 15% in MT+/+ mice compared to MT−/− mice. Duodenal disaccharidase activities were significantly higher in MT+/+ mice compared to MT−/− mice particularly those fed the 2Zn diet. At the 50Zn diet, jejunal sucrase and lactase activities were significantly higher in MT−/− (13313±2314 μmol glucose/well/min/g tissue; 4107±364; mean ±SEM) compared to MT+/+ mice (7054±608; 1818±174). Similarly, ileal lactase activities were higher in MT−/− (1480±192) compared to MT+/+ (629±353) mice particularly those fed the 2Zn diet. Increasing dietary Zn in the weaning diet did not affect disaccharidases expression in wild type mice. The presence of MT enhances the morphological and functional development of the gut.
The “muscle‐full” effect after oral protein: time‐dependent concordance/discordance between muscle protein synthesis (MPS) and mammalian target of rapamycin (mTOR)‐associated signaling
Authors: Atherton Philip James , Etheridge Timothy , Watt Peter William , Wilkinson Daniel , Selby Anna Louise , Rankin Debbie , Smith Kenneth , Rennie Michael John
Published: June 2021

How the brief rise‐and‐fall of MPS occurs after raising blood amino acids (AA) by IV infusion is unknown. We predicted that mTOR‐associated signaling responses would prefigure those of MPS after oral protein. 8 men (~21 y, BMI 22–24 kg.m−2) received [1,2‐13C2]leucine (1mg.kg.h−1) over 8.5 h, the first 2.5 of which preceded drinking 48 g whey suspension; muscle was intermittently biopsied throughout. MPS was measured as capture of [1,2‐13C2]leucine and signaling markers by immunoblotting. MPS rate trebled 45–90 min after whey (i.e. myofibrillar 0.03±0.01 vs. 0.1±0.01%.h−1; means±SE, P<0.001) thereafter falling to baseline, despite raised plasma (+105%; P<0.01) and muscle [leucine] (+54%; P<0.01) at 180 min. Increases in kinase activity of protein kinase B (PKB) and of eukaryotic initiation‐factor 4GSer1108 phosphorylation preceded the MPS rise, whereas increases in phosphorylation of p70S6 kinaseTh389 (+112%; P<0.01) and eIF4E‐binding protein‐1Thr37/46 (+155%; P<0.01) were superimposable with the MPS profile for 90 min. However, whereas MPS fell thereafter, all signals (except PKB, which mirrored insulin responses) remained elevated, echoing declining plasma [AA]. We confirm that MPS responses to [AA] are brief but large; however, as mTOR signaling outlasts them, the latter probably reflects [AA] only and unknown elements signal “muscle full”, thereby inhibiting MPS. Support: RCUK, BBSRC, EXGENESIS

Grant Funding Source: Physiology (APS)
Nutrient sensing anabolic pathway is increased in the elderly following chronic dietary leucine supplementation
Authors: Casperson Shanon , Sheffield‐Moore Melinda , Paddon‐Joones Douglas
Published: June 2021

Leucine has been shown to act as a key regulator of the nutrient sensing anabolic pathway. Acute administration of leucine affects the phosphorylation status of several proteins involved in translation initiation that are regulated by the mTOR pathway. We conducted a 14 day pilot study in which we supplemented regular daily meals of community dwelling elders (n=8, 63–76 yrs) with a small amount of leucine (4 g per meal; 3 meals per day; days 2–13). On days 1 and 14, muscle biopsies were obtained in the post‐absorptive state to determine leucine‐induced modulation of the mTOR signaling pathway. After 14 days of leucine supplementation, there was a trend toward increased phosphorylation of mTOR (P=0.06). In addition, the phosphorylation of the downstream effectors 4E‐BP1 (P=0.03) and p70S6K (P=0.08) were increased. These data suggest that a provision of leucine supplementation facilitates an adaptive change in components of the mTOR signaling pathway in aging human muscle.

Grant Funding Source: UTMB Claude D. Pepper Older Americans Independence Center # P30 AG024832 (to D. Paddon‐Jones) and NIH/NCI grant 5R01 CA127971 (to M. Sheffield‐Moore).
GCN2 is Essential for Oligodendrocyte Development and Myelination in the Brains of Mice Born Deficient in Branched‐Chain α‐Ketoacid Dehydrogenase Kinase (BDK)
Authors: Anthony Tracy G , Bunpo Piyawan , Cundiff Judy K , Harris Robert A , Wek Ronald C
Published: June 2021

The eukaryotic initiation factor 2 (eIF2) kinase, GCN2, is critical for surviving branched chain amino acid deficiency during early postnatal life. Mice deleted for both BDK and the gene encoding GCN2 are indistinguishable from littermates at birth but beginning at day 7 stop gaining weight, and then become progressively wasted and neurologically unresponsive until expiring by day 15. To understand the cause of the neurological defect, whole brains from GCN2‐BDK double null mice (GB) were compared to wild‐type and heterozygous littermates at days 11–14 postpartum. At d 11–14, GB brains were much lighter than healthy littermates and were extremely fragile and soft upon dissection. Phosphorylation of eIF2 and mRNA expression of Activating Transcription Factor 4 (ATF4) were significantly increased in BDK null brains but not in GB brains. Messenger RNA levels of asparagine synthetase and C/EBP Homologous Protein (CHOP) were also significantly increased in BDK null brains but not in GB brains. Moreover, in brains from GB mice but not BDK null mice, myelin basic protein (MBP) expression and mRNA expression of MBP and Olig2, a marker of pre‐oligodendrocyes, were all reduced greater than 50%. Finally, gene expression of superoxide dismutase 2 (SOD2) in GB was reduced 40%, suggesting a compromised ability to protect against oxidative stress. These data suggest that GCN2 is critically important for oligodendrocyte development and the onset of myelination under conditions of amino acid stress during early postnatal life.
Dietary yeast β‐glucan does not improve the response to influenza vaccination in neonatal piglets
Authors: Cope Shannon C , Hester Shelly N , Comstock Sarah S , Monaco Marcia H , Donovan Sharon M
Published: June 2021

Purified yeast (1,3/1,6)‐β‐D‐glucan (βG) has been shown to enhance immune responsiveness. Herein, the hypothesis that βG would modulate the lung immune development and improve influenza vaccination response was tested. Piglets (n=5–6/group) were fed formula containing 0 (control), 1.8, 18 or 90 mg βG/kg body weight. Half of the piglets in each treatment were vaccinated (FV) by i.m. injection against influenza (Fluzone) on d7 and received a booster on d14. Piglets were euthanized on d7 and d21. Weight gain and formula intake were unaffected by diet or vaccination. Fluzone‐specific serum IgG was measured by ELISA. FV piglets had higher (p<0.001) IgG titer at d14 and 21 than non‐V piglets. This was unaffected by βG. Cytokine (IL −2, −4, −10, −12 and −17) mRNA in lung was unaffected by age or dietary βG. Lung TGFβ‐1 mRNA was greater (p<0.05) in d21 than d7 piglets, and lung TGFβ‐2 mRNA was lower (p<0.001) in all âG diets compared to control. T‐cell phenotypes were examined in mediastinal lymph nodes (MSLN) by flow cytometry. In MSLN, CD4+ T‐cells decreased, while CD8+ T‐cells increased between d7 and d21 (p<0.001), but these developmental patterns were unaffected by dietary βG. Thus, with the exception of reducing TGFâ‐2 mRNA in lung, dietary βG did not affect cytokine expression, T‐cell phenotypes or vaccination response in piglets. (Funded by Abbott Nutrition)
Phytosterols (PS) as immunomodulators of Multiple Sclerosis (MS)
Authors: Valerio Michael , Liu Hongbaio , Heffner Reid , Zivadinov Robert , Ramanathan Murali , Weinstock‐Guttman Bianca , Awad Atif B.
Published: June 2021

MS is a neurological autoimmune disorder affecting millions globally. Experimental Autoimmune Encephalomyelitis (EAE) is a well accepted animal model which is widely used to study MS. MS is characterized by CNS infiltration with immune cells and demyelination. PS are plant sterols which have been shown to have anti‐inflammatory properties. The objective of this project was to examine the effect of PS on EAE clinical score and identify a possible underlying mechanism. Mice were divided into PS and control groups, treated with PS or vehicle by gavage one week before disease induction and continue thereafter while maintained on a low PS diet. Mean clinical disease score (0–5) of PS treated mice was 0.33 versus 2.4 in control mice. Brain histological studies indicated significantly (p=0.007) less lymphocyte infiltration in PS treated mice. Immunohistochemical staining for macrophages/microglia, using F4/80 antibodies, indicated significantly (p=0.029) less infiltration in brains of PS treated mice. Demyelination was significantly (p=0.029) less in PS treated mice compared to controls. Cytokine analysis on brain tissue and splenocyte homogenate showed significant increase in IL‐10 and decrease in MCP‐1 in PS treated animals. It was concluded that PS reduces the clinical signs of the disease and this could be mediated by immune modulation. Supported by grants from NMSS and JFJ.

Grant Funding Source: National Multiple Sclerosis Society and JFJ Foundations
A majority of children in Los Angeles and New York City have elevated urine osmolality associated with not drinking water at the start of the school day
Authors: Stookey Jodi , Brass Bernie , Holliday Ava , Arieff Allen , Constant Florence
Published: June 2021

This study determined the prevalence and dietary correlates of elevated urine osmolality, a possible risk factor for reduced cognitive performance, in children (9–11y) at the start of the school‐day in Los Angeles (LA) and New York City (NYC). Randomly selected children in LA (n=334) and NYC (n=208) recorded morning food and beverage intake and gave a urine sample on a school‐day between 8:30–9:30am. In LA and NYC, 63% and 66% of children had elevated urine osmolality (>800 mOsm/kg). In multivariable‐adjusted logistic regression models, children who did not drink water in the morning were 3 times more likely to have elevated urine osmolality than children who had no food or fluid, food but no drink, or a beverage other than water in the morning. The relative odds of elevated urine osmolality associated with milk or juice was the same as that associated with overnight fluid restriction. Urine osmolality below 800 mOsm/kg was associated with >500ml drinking water. A majority of children in LA and NYC have elevated urine osmolality associated with not drinking water in the morning.

Funding source: Unrestricted grant from Nestle Waters
Barriers to Healthy Nutrition and Food Preparation Practices of Rural Families
Authors: McWhinney Sharon , McKyer Lisako , Outley Corliss , McDonald Andrea
Published: June 2021

The increased incidence of obesity is a major concern and intervention efforts to thwart this trend in low income minority populations continue. Good nutritional habits and behavioral practices are important for healthy weight management and maintenance. This project was conducted to gain insight the personal and contextual factors, and barriers, impacting food preparation and consumption in rural families'. Focus groups were conducted with 100 low income parents from rural communities to collect cultural perspectives and to identify barriers to healthy eating and food preparation practices. Statements were extracted and categorized from the focus group transcripts. Analysis of the data resulted in themes including general food purchases, preparation practices, and barriers to good nutrition. Food preparation was based primarily on family history and tradition; example ‘fired fish Fridays’, and ‘family member preferences’. Advertising and children in charge were discussed by most of the participants as being significant barriers to healthy eating. Surprisingly, many of the families dining out decisions were determined by daily specials offered at local fast food restaurants with little thought given to the nutritional value of meals.

Funding for this project was made possible by 1P20MD0002295 from the National Center on Minority Health and Health Disparities.
Beyond food insecurity: How context can help improve complementary feeding interventions
Authors: Paul Keriann H. , Khalfan Sabra S. , Muti Monica , Humphrey Jean H. , Stoltzfus Rebecca J.
Published: June 2021

Context has not been elaborated in current recommendations for complementary feeding (CF) interventions apart from a categorization of food security. We compared 2 food insecure settings in Africa to explore how context affects CF practices and nutrient intakes and in turn a suitable intervention strategy. We conducted 24‐hr recalls and interviews with mothers of 6–12 mo‐olds in rural Zimbabwe (n=32) and Pemba Island, Tanzania (n=44). In both settings, many infants had suboptimal nutrient intakes, poor dietary diversity, and hygiene. Pemba had poor breastfeeding, and Zimbabwe had low energy density. Contextual determinants were indigenous knowledge, livelihoods, family foods, agriculture, and the ecosystem. Both settings require education targeting indigenous knowledge and family eating behaviors. A home‐based fortificant is enough for Pemba because the island's ecosystem provides sufficient sources of macronutrients. However, Zimbabwe needs a fortified food‐based supplement to overcome the poor agricultural and economic context. Assessing context was essential to intervention design. A framework for formative research is proposed. Supported in part by DFID and NIH grant T32 HD007331.

Grant Funding Source: NIH grant T32 HD007331
Properties of oat β‐glucan influence its LDL cholesterol lowering effect in humans
Authors: Wolever Thomas MS , Tosh Susan M , Gibbs Alison L , Brand‐Miller Jennie , Duncan Alison M , Hart Valerie , Lamarche Benoit , Thomson Barbara , Duss Ruedi , Wood Peter J
Published: June 2021

Consuming 3g oat β‐glucan (OBG) daily is considered sufficient to lower serum LDL cholesterol (LDL). Not all studies show this, possibly because β‐glucan bioactivity is reduced in some food products by low solubility or low molecular‐weight (MW). We tested whether daily consumption of 3g OBG (OatWell®) reduced LDL and whether LDL lowering depended on log(MW×C), where C = dose×solubility. Healthy subjects (n=367) with LDL ≥3.0 and ≤5.0mmol/L were randomly assigned to the following treatments in a double‐blind, parallel design clinical trial: 1.5g high‐MW (3H), 2g medium‐MW (4M), 1.5g medium‐MW (3M) or 2g low‐MW (4L) OBG in cereal or a control wheat fiber cereal (W) twice daily for 4wk. After 4wk on 3H LDL was less than on W by 0.21 mmol/L (95% confidence interval; 0.11, 0.30, P=0.0023). Analysis of covariance showed log(MW×C) was a significant determinant of week 4 LDL (P=0.003). The size of treatment effects was not significantly affected by age, sex, centre or baseline LDL. We conclude that consuming 1.5g high‐MW OBG twice daily reduces LDL by 0.2mmol/L, but efficacy is reduced with OBG of lower MW and/or C. Thus, the physico‐chemical properties of β‐glucan influence oat's LDL‐lowering effect. Funded by the Swedish Governmental Agency for Innovations Systems and CreaNutrition.
Glyceollins, one of the phytoalexins derived from soybeans under fungal stress, enhance insulin sensitivity and exert insulinotropic actions in vitro and in vivo
Authors: Park Sunmin , Ahn Il Sung , Kim JEONG HWAN , Kim JONG SANG
Published: June 2021

Glyceollins are known to anti‐estrogenic phytoalexins but they have not been studied for anti‐diabetic properties. We hypothesized that glyceollins play an important role in glucose homeostasis through regulating glucose utilization in adipocytes and by improving ¥â‐cell function and survival in vitro and in vivo. Glyceollins improved insulin‐stimulated glucose uptake in 3T3‐L1 adipocytes without activating the peroxisome proliferator‐activated receptor‐gamma‐¥ã agonist. In addition, glyceollins slightly improved glucose‐stimulated insulin secretion without palmitate treatment in Min6 cells, and they potentiated insulinotropic actions when 500¥ìM palmitate treatment was used to induce ¥â‐cell dysfunction. This was associated with decreased ¥â‐cell apoptosis due to attenuation of ER stress, determined by mRNA levels of XBP‐1, ATF4, ATF6 and CHOP. The 8‐week oral consumption of the fraction containing glyceollins improved glucose tolerance during oral glucose tolerance test in diabetic mice induced by low‐dose multiple injections of streptozotocin. It also potentiated glucose‐stimulated insulin secretion and prevented ¥â‐cell apoptosis in the mice. In conclusion, glyceollins help normalize glucose homeostasis by potentiating ¥â‐cell function and survival and by improving glucose utilization in adipocytes.
Kimchi lactic acid bacteria and health benefits
Authors: Park Kun‐Young , Kim Boh‐Kyung
Published: June 2021

Kimchi contains a high number of lactic acid bacteria (108~9/ml), organic acids (lactic, acetic, succinic, propionic acids, etc.), vitamin B complex, and modified functional phytochemicals formed during the fermentation process. Vitamin C, carotenoids, chlorophylls, tocopherol, isothiocyanates, indole‐3‐carbinol, flavonoids, β‐sitosterol, dietary fiber, capsaicinoids, unsaturated fatty acids, allyl sulfur compounds, gingerel, organic acid, lactic acid bacteria, se, etc are the nutraceuticals found in kimchi. The representative kimchi lactic acid bacteria (LAB) reported so far are Leu. mesenteroides, Leu. citreum, Leu. gasicomitatum, Leu. kimchii, Leu. inhae, Weissella Koreensis, Weissella cibaria, Lac. plantarum, Lac. sakei, Lac. delbrueckii, Lac. buchneri, Lac. brevis, Lac. fermentum, Ped. acidilactici and Ped. pentosaceus. LAB from kimchi revealed high preventive capability of the mutation induced by 4‐NQO, MeIQ and Trp‐p2 as much as (or higher than) Lac. acidophilus from dairy products, regardless of their viability. The cell wall fraction, rather than in the cytosol fraction was responsible for the antimutagenic activity of the lactic acid bacteria. Kimchi LAB exhibited antitumor, antimutagenic effect, increase immune function, decrease avian influenza virus, decrease atopy, antiallergy, production of GABA, etc. During the administration of kimchi in humans, the cell counts of Lactobacillus and Leuconostoc increased (p<0.05). The enzymes of β‐glucosidase, β‐glucuronidase and nitroreductase in the colon decreased during the kimchi intake (p<0.05). Kimchi LAB fermentation increased anticancer effect in HT‐29 human colon carcinoma cells. Optimally ripened (OpR) kimchi induced apoptosis as determined by DAPI staining and increased Bax, and decreased in the expression of Bcl‐2.
CLINICAL EFFICACY OF PROBIOTIC STRAINS AND THEIR APPLICATION FOR DEVELOPMENT
Authors: Ji Geun Eog
Published: June 2021

Probiotic strains such as B. bifidum BGN4, B. lactis AD011, Lactobacillus acidophilus AD031, and L. casei IBS041 were developed through the series of in vitro and animal experiments. Double‐blind, randomized placebo‐controlled human trials with combinatory probiotic strains including Bifidobacterium and Lactobacillus significantly lowered the prevalence of atopic dermatitis in infants and the pain scores in irritable bowel syndrome patients. Recently, the application of lactic acid bacteria for the transformation of ginsenosides has drawn considerable interests because of their potential to enhance the biological activities of ginseng. Ginsenosides have been regarded as the principal components responsible for pharmacological and biological activities of ginseng. After transformation, major ginsenosides comprised of compound K, Rh1, and Rh2. Fermented ginseng (FG) showed greater effect than unfermented ginseng in the suppression of ovalbumin‐induced allergy. The FG also lowered blood glucose level in the DB/DB mice model. In conclusion, selected probiotic strains were shown to exert clinical efficacies and enhance the biological activities of ginseng.
Diets high in saturated fat increase intestinal inflammation associated with IBD via alterations in the microbiota
Authors: Devkota Suzanne , Wang Yunwei , Antonopoulos Dion , Chang Eugene
Published: June 2021

Clinical evidence suggests the chronic inflammation seen in inflammatory bowel diseases (IBD) results from a combination of environmental/microbial factors on a background of genetic susceptibility. This study evaluates the environmental factor of dietary fat composition on the incidence of IBD via alterations in gut microbiota. Male C57bl/6j mice (6 w/o) were fed a high saturated fat (SF; 47% energy from carbohydrates, 16% energy from protein, 37% energy from fat), high polyunsaturated fat (PF; 47:16:37), or a low fat control diet (C; 70:16:14) for 3 wks (n=10/diet). Cecal contents were collected for microbial pyrosequencing of 16s rDNA and revealed a “bloom” of b.wadsworthia, a cytotoxic proteobacteria, only in the SF diet. Body weight was greater on SF diet than PF and LF despite no significant difference in kcals consumed, suggesting an increased microbial capacity for energy harvest on SF, a contributing factor to local inflammation. Next, male IL‐10−/− mice (4 w/o), a model of spontaneous colitis, were fed LF or SF (n=5/diet) for 12 wks. Only 20% of these mice developed colitis on LF vs. 100% on SF accompanied by a 4‐fold increase in pro‐inflammatory IL‐6 and IL‐12 and a microbial profile like that of the C57bl/6j mice fed SF. These data indicate that SF diets create an environment favorable for the growth of harmful bacteria contributing to incidence to IBD.

Supported by the National Institutes of Health R01 and T32

Grant Funding Source: National Institutes of Health
A Reduced Carbohydrate Diet Results in Loss in Lean Mass in Peripubertal African American Girls
Authors: Casazza Krista
Published: June 2021

Pharmacologic lowering of insulin has been shown to improve insulin dynamics, delay reproductive maturation and result in less body fat accumulation over time in early maturing girls. Modification of the diet may result in comparable outcomes. The main objective of the project was to examine the effectiveness of a diet low in carbohydrate on improving metabolic profile and promoting weight loss in overweight African American (AA) females aged 9–14 years. The study included two phases utilizing a eucaloric (weight‐stable) in the first phase and a hypocaloric diet (weight‐loss; 1000kcal deficit) in the second phase. Twenty‐four girls were randomized to one of two diets, a reduced carbohydrate diet (redCHO;42% CHO, 40% fat) or standard (STAN; 60% CHO, 22% fat). Energy requirements were determined by indirect calorimetry and all meals were provided to the participants. Fasting blood samples were collected for metabolic analysis and body composition was assessed by DXA. During the eucaloric phase, subjects on the redCHO diet had a greater reduction in triglycerides (p<0.05), with no other differences in metabolic profile observed. In addition, participants on the redCHO diet had greater weight loss (p<0.05); however, the weight loss was due to loss of muscle mass, not fat or bone mass. During the hypocaloric phase, there were no differences in weight loss or body composition between the diet groups.

Grant Funding Source: APS
Epigenetic Modifications Cause Transcriptional Repression of p21 Gene in Mammary Gland in the Offspring of Protein‐Restricted Rats
Authors: Zheng Shasha , Pan Yuan‐Xiang
Published: June 2021

Maternal nutrition during pregnancy is an important intrauterine environmental factor resulting in persistent alteration of the offspring epigenome and is associated with developmental susceptibility as well as the health outcome in later life. This study examined the effect of maternal low protein diet on the regulation of p21 gene expression in offspring mammary gland in rat. Timed‐pregnant Sprague‐Dawley rats were fed one of the two isocaloric diets, control (18% casein) or low protein diet (LP, 9% casein) during gestation period. Compared to control, offspring rats from LP group showed 38% decrease in p21 mRNA level in mammary gland. Western blot analysis confirmed the down‐regulation of p21 at protein level. Chromatin immunoprecipitation (ChIP) assay demonstrated that the down‐regulation of p21 transcription in LP offspring was associated with histone code changes within the p21 promoter region, including reduced acetylation of histone H3 and H4. These results supported the hypothesis that maternal protein restriction during pregnancy programs p21 expression and histone code in offspring mammary gland.

Grant Funding Source: NIH