bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of diets based on gene expression data produces foods which improve renal health and ameliorate sarcopenic obesity (246.3)
Authors: Jackson Matthew , Panickar Kiran , Yerramilli Murthy , Jewell Dennis
Published: June 2021

Etiology of aging manifests reduced renal health and sarcopenic obesity with characteristic changes in gene expression. Cats were fed a control food (CD), known to improve indices of age‐related pathology, or one of two diets (ED1 & ED2; n = 27 each diet) that contained ingredients producing expression profiles reflective of a young animal in cell models. The protocol was approved by IACUC. Health was monitored via clinical and physical indices. Results from ED1 & ED2 were the same and were significant with P < 0.05, unless noted. Renal health improved on all diets, as indicated by improved glomerular filtration rate (GFR) and reduced levels of symmetrical dimethylarginine. Analysis of plasma metabolomics showed that creatine, betaine, dimethylarginines, acylcarnitines and cortisol were negatively correlated with GFR, indicating possible value as renal health markers. Body weight was unchanged, but cats fed ED1 & ED2 lost fat mass and retained (ED1) or increased (ED2) lean mass. Metabolomics showed that circulating amino acids, including the felinine analog of glutathione, and glycerophospho‐lipids were positively correlated with lean mass. Thus, design of diets based on gene expression data led to foods capable of improving renal health and ameliorating sarcopenic obesity, while metabolomic profiling of cats consuming these foods identified markers predicting ameliorated age‐related co‐morbidities.
Diet supplemented with anti‐inflammatory and antioxidant nutrients enhance circulating markers of improved health in aging dogs (246.6)
Authors: Panickar Kiran , Jackson Matthew , Gao Xiangming , Yerramilli Murthy , Jewell Dennis
Published: June 2021

Aging is associated with chronic low‐grade inflammation and increased oxidative stress. Such age‐related changes may have adverse effects on general health including associated renal, cardiovascular, neurological and dermatological problems. The effect diet supplemented with ingredients having anti‐inflammatory effects including carrots, spinach, tomato pomace, carnitine, and α‐lipoic acid was tested in older dogs. Animals (n=81) were maintained on control or experimental diet for 6 months. Urine and blood and analysis were conducted prior to administering the diet and at 3 and 6 months. The experimental protocol was reviewed and approved by IACUC. When compared to the control diet there was an increased level of peroxiredoxins and DHA at 6 months but a reduction in prostaglandin E2 was observed in both control and experimental groups. There was a significant reduction in 8‐OH‐DG, a marker of DNA damage, and serum SDMA, a marker of progressive kidney dysfunction, when compared to controls. Markers of muscle and cartilage degradation including 3‐methyl histidine and 4‐hydroxyproline respectively, were lower in the experimental group. Harmful microbial byproducts including p‐cresol sulfate and catechol sulfate were also decreased in the experimental group. These data indicate an important role of diet supplemented with potential antioxidant and anti‐inflammatory nutrients in older animals.
Peripheral blood mononuclear cell (PBMC) gene expression in human infants shifts from innate to adaptive immunity in the first six months of life (247.5)
Authors: Donovan Sharon , Monaco Marcia , Drnevich Jenny , Lönnerdal Bo , Kvistgaard Anne , Peng Yong‐mei
Published: June 2021

The newborn immune system is developmentally naïve, but undergoes rapid maturation upon exposure to environmental antigens. As part of a clinical trial in infants aimed at assessing how diet impacts PBMC transcriptome, genes that were developmentally regulated independent of diet‐ were discovered. Blood samples were obtained from breast‐fed (n=60) and three sets of formula‐fed (n=186 total) infants at 1, 4 and 6 mos of age. PBMC were isolated, RNA extracted and gene expression assessed using the Affymetrix HuGene 2.0ST gene chip. To evaluate patterns of gene expression, Weighted Gene Correlation Network Analysis (WGCNA) was performed on 6,441 probe sets with an overall 4x3 ANOVA FDR p‐value<0.3. Three gene clusters with similar patterns of expression in each diet (1 vs. 4 & 6 mos) encompassing 1085 genes were identified. Functional analysis was performed with MetaCore. Pathways with higher expression at 1‐mo reflected cellular proliferation, innate defense processes (defensins, hydrogen peroxide‐induced killing) and Th17‐derived cytokines. By 4‐ to 6‐mos of age, genes associated with humoral immunoglobulin‐mediated immunity and interferon and IL‐4 signaling predominated. These data illustrate for the first time the developmental ontogeny of gene expression in circulating immune cells of human infants.

Grant Funding Source: Arla Foods and Biostime
Changes in body composition and C‐reactive protein in overweight, lactating women (247.8)
Authors: Shearer Elyse , Wideman Laurie , Lovelady Cheryl
Published: June 2021

Obesity has been linked with elevation of the inflammatory protein, C‐reactive protein (CRP), which increases risk of developing chronic disease. CRP levels less than 1.0 mg/L are associated with a low risk, 1.0 to 3.0 mg/L medium risk, and greater than 3.0 mg/L high risk. Weight loss, specifically loss of abdominal fat, may decrease CRP. Breastfeeding may help reduce CRP. The objective of this study was to determine the effect of weight loss on inflammation in 20 overweight, fully breastfeeding women. Weight, height, waist circumference, and body composition (determined by DXA) were measured at 4 and 20 weeks postpartum. Serum samples were obtained, and concentrations of CRP were measured by ELISA. There was an average (range) loss of weight of ‐4.7 kg (2.8 to ‐11.6 kg), fat mass of ‐4.69 kg (0.45 to ‐13.3 kg), and trunk fat of ‐2.89 kg (0.27 to ‐7.3 kg). There was a non‐significant decrease in CRP from 3.99 to 3.04 mg/L, with 2 participants moving from high to medium risk, and 2 moving from medium to low risk. There was a significant positive association between change in trunk fat and change in CRP (R2=0.20). Also, weight (R2=0.19), fat mass (R2=0.19), and trunk fat (R2=0.24) were significantly positively associated with CRP at endpoint. These results suggest that loss of abdominal fat is associated with a significant reduction of CRP in overweight, fully breastfeeding women and may reduce their risk for chronic disease.
Plasma metabolomic profiles associated with hospital mortality in surgical critical illness (248.2)
Authors: Frediani Jennifer , Park Young‐ja , Hebbar Gautam , May Addison , Wischmeyer Paul , Sax Harry , Kudsk Kenneth , Uppal Karan , Jones Dean , Ziegler Thomas
Published: June 2021

Background: Plasma metabolomic profiling provides an opportunity for discovery‐based studies on human metabolism during illness. We sought to define metabolites that differ between intensive care unit (ICU) patients that did or did not survive hospitalization.

Methods: Subjects matched on demographics and nutrient administration in a RCT on glutamine supplementation in surgical ICU patients were selected based on hospital mortality. Serial plasma was analyzed using high‐resolution LC‐MS methods. False discovery rate (FDR; q=0.05) and hierarchal cluster analysis was used to distinguish accurate mass ions (metabolites) significantly different between groups. The METLIN Metabolite Database was used to match ions to known metabolites.

Results: A total of 22,305 metabolites were detected (54, 5, 33, and 113 were significantly different between the two groups at days 0, 3, 7, and 14, respectively). Survivors and non‐survivors were differentiated at both day 0 and day 14 by 3 metabolite matches (2 unknowns and stearic acid), and by several others at days 7 and 14 (2 unknowns, terpenoids, drug metabolites). Several drug metabolite matches were higher and several endogenous metabolites were lower in non‐survivors, respectively.

Conclusion: High‐resolution LC‐MS can identify plasma metabolomic profiles associated with hospital mortality in adults with surgical critical illness.

Grant Funding Source: Supported by grants from the National Institutes of Health Fogarty grants D43 TW007124
Carbohydrate feeding and impact on global metabolomics in relation to insulin sensitivity in men with metabolic syndrome (248.8)
Authors: Watkins Bruce , Pappan Kirk , Kim Jeffrey , Freidenreich Daniel , Kunces Laura , Volk Brittanie , Saenz Catherine , Volek Jeff
Published: June 2021

Restriction in dietary carbohydrate (CHO) for several weeks results in a metabolic state where fatty acids and ketones become primary fuels, which correlates with improved insulin sensitivity and management of type 2 diabetes. To gain a broader understanding of the metabolic correlates to dietary CHO manipulation in relation to insulin sensitivity we performed serum global metabolomic analysis in men with metabolic syndrome who were fed calorically‐controlled diets for 21 d that incrementally increased CHO and decreased fat. The diets (isocaloric and isonitrogenous) consisted of low (LC), moderate (MC) and high (HC) CHO levels corresponding to 47, 131, and 345 g CHO/d. HOMA insulin resistance decreased by 50% from baseline (BL) to LC (3.0 to 1.5) and increased after MC (1.7) and HC (2.0). Change in HOMA from BL to LC was positively correlated to changes in butyrylcarnitine, gamma‐glutamyltyrosine, threobromine, and tyrosine, and inversely with α‐ketobutyrate and andro steroid monosulfate 2. The change in HOMA from LC to HC was positively correlated to 4‐hydroxyphenylpyruvate, alanine, arabinose, aspartate, gamma‐glutamyltyrosine, N6‐acetyllysine, and palmitoyl sphingomyelin, and inversely correlated with methyl‐β‐glucopyranoside. In summary, several novel metabolic markers were identified that may help explain the variable response in insulin sensitivity to dietary CHO restriction and refeeding.
Pomegranate extract intake reduces CVD and diabetes risk factors, stress hormone levels and improves overall quality of life scores in a double‐blind, placebo‐controlled study (249.2)
Authors: Al‐Dujaili Emad , Stockton Angela
Published: June 2021

Background and Aim: Pomegranates provide a rich and varied source of antioxidant biophenols. We have shown that pomegranate juice consumption may alleviate cardiovascular risk factors by reducing systolic and diastolic BP and exercise‐induced oxidative stress. This study investigates the effect of pomegranate extract (PE) intake on BP, HOMA‐IR, stress hormone and quality of life in human volunteers. Methods: Healthy volunteers (7 males and 22 females) participated in a randomized, double‐blind, placebo‐controlled study (BMI: 25.05±3.91kg/m², age: 34.5±13.7years). All subjects consumed either one PE (Pomanox, Pomegreat) or placebo capsule daily, after a meal, for 4 weeks. Each PE capsule weighed 1.083g and contained 650mg of PE (240mg punicalagins and 350mg total biophenols) plus 433mg maltodextrin. Dietary history and habits were recorded. Salivary cortisol and cortisone levels (AM, noon, PM) were assessed by sensitive ELISAs, and fasting blood was obtained at baseline and after 4 weeks to compare BP, glucose, insulin and insulin resistance. Results: Systolic BP was significantly reduced following PE from 120.3 ±13.3 to 115.6 ±13.1mmHg (P= 0.012). There was a reduction in the HOMA‐IR levels from 2.22 ± 2.6 to 1.61 ± 1.9 (P=0.045), and glucose, insulin and uric acid all decreased from baseline. No significant changes were recorded in volunteers taking the placebo. Salivary cortisol levels (AM; p<0.001 and Noon; p=0.016), and cortisol/cortisone ratio (AM from 1.11±0.51 to 0.55±0.26, p<0.001, Noon 1.57±0.85 to 0.75±0.72, p<0.001 and PM; 1.22±0.9 to 0.74±0.59, p=0.011) were all reduced in the PE group. Physical (p=0.018), social functioning (p=0.021), pain (p=0.003), general health (p=0.008) and overall QoL score (p=0.007) were improved in those taking PE. Conclusions: PE ameliorates cardiovascular risk factors, stress levels and improves quality of life. The decrease in insulin resistance could be of benefit to those who suffer from type2 diabetes, metabolic syndrome or obesity.
TMAO an L‐carnitine metabolite does not affect foam cell formation or cholesterol efflux in J774 mouse macrophage (249.6)
Authors: Bellamine Aouatef , Drazul‐Schrader Denise , Collins Heidi , Owen Kevin , Skoulis Nick , Adelman Steve
Published: June 2021

Trimethylamine N‐oxide (TMAO) is a common metabolite of the L‐carnitine, recently linked to atherosclerosis initiation and progression in mice. TMAO was associated with a modest increase in the RNA levels of known cholesterol transporters and suggested to drive changes in the reverse cholesterol transport (RCT) pathway. To assess the direct effect of TMAO on two components of atherosclerosis: foam cell formation and cholesterol efflux, J774 mouse macrophages were exposed to increasing concentration of TMAO (0, 1, 3, 10, 30 and 100 μM) in presence of 12 and 50 μg/ml acetylated LDL (acLDL) for 24 hours and cholesterol content and cholesterol efflux were measured. No changes in total, free or esterified cholesterol mass in response to acLDL were observed at any TMAO concentration. Furthermore, when apo‐AI was used as cholesterol acceptor, TMAO did not affect ABCA1 cholesterol‐mediated efflux. When using HDL3, an acceptor for cholesterol efflux mediated by SR‐BI, ABCG1 or passive diffusion, TMAO did not affect cholesterol efflux. Together, these results suggest that neither cholesterol efflux via ABCA1, ABCG1 or SR‐BI nor cholesterol loading were affected by TMAO up to 100 μM (about 10‐fold higher than the Cmax in humans). In conclusion, TMAO up to 100 μM showed no effect on foam cell development or inhibition of cholesterol efflux, major pathways in atherosclerotic disease development.
Efficacy and safety of high‐dose cholecalciferol in patients with pulmonary tuberculosis in Tbilisi, Georgia (250.7)
Authors: Ziegler Thomas , Tukvadze Nestan , Kipiani Maia , Sanikidze Eka , Hebbar Gautam , Ramakrishnan Usha , Martorell Reynaldo , Kempker Russell , Tangpricha Vin , Blumberg Henry
Published: June 2021

Background: We tested whether high‐dose oral cholecalciferol (VD3) enhances efficacy of anti‐TB drugs in pulmonary TB infection. Methods: Double blind, randomized, controlled, intent‐to‐treat trial in adults with pulmonary TB in Tbilisi, Georgia. A total of 199 subjects were randomized to VD3 (1,400,000 IU; n=100) or placebo (n=99) over 16 weeks + standard anti‐TB drugs. Sputum TB cultures were obtained at weeks 0, 2, 4, 6, 8, 12 and 16. Cox analysis was used for the primary outcome (time to culture conversion). Results: Of 784 subjects screened, 100 received VD3 and 99 placebo. Most subjects (> 85%) were VD deficient at entry (serum 25OH VD level < 20 ng/mL). 23 subjects (12%) had multidrug‐resistant TB (MDR‐TB) (12 vitamin D, 11 placebo). Entry demographic factors were similar between groups. VD3 was safe, with similar blood calcium levels and adverse events between groups. With VD, serum 25OH VD levels peaked at ≍ 100 ng/mL at 8 weeks and decreased to ≍ 60 ng/mL by week 16. Culture conversion was similar between groups at 8 weeks and over time [HR=0.84 (0.62‐1.15)]. However, the MDR‐TB subset showed enhanced culture conversion with VD3 therapy vs. placebo at 8 weeks (40 vs. 88%) and over time (each p<0.04). Conclusions: High‐dose VD3 was safe and did not improve TB clearance in the overall cohort of TB patients. However, clinical efficacy in patients with MDR‐TB suggests that VD treatment trials focus on this subset of patients.

Grant Funding Source: Supported by NIH/NIDDK K24 DK096574 and Emory Global Health Institute
Food neophobia in Latino preschoolers: correlation with intake and pilot intervention results (252.2)
Authors: Haemer Matthew , Goldberg Shauna , Tong Suhong , Johnson Susan
Published: June 2021

Background: Parent perception of a child’s willingness to try new foods may impact the dietary patterns and has not been well described in low‐income Latino preschool children.

Objectives: 1. To describe relationships between parent perceived neophobia, a child’s willingness to try foods, and intake of healthful foods; and, 2. To describe results of an intervention to decrease perceived neophobia among low‐income Latino parents and increase liking of healthful foods among preschool‐aged children.

Methods: Mothers and their children 3‐7 years participated. Questionnaires assessed maternal‐reported neophobia at baseline. Child's familiarity, willingness‐to‐try, and liking of 10 healthful foods were assessed at baseline. Children completed 10 childcare sessions with activities focused on increasing familiarity with healthful foods. A 1oz portion of each food was offered at each session and consumption was measured. Parents received a report on session content and snacks consumed. Parent and child surveys were repeated following the intervention. Spearman correlation coefficients tested associations and paired t‐tests compared changes in mean responses.

Results: 29 dyads completed baseline and follow‐up assessments. Most foods were unfamiliar to 80% or more of children. Parent‐report neophobia was not significantly correlated with the number of foods a child reported willingness to try r=0.25 (p=0.23), consumed 0.16 (p=0.11), or liked ‐0.05 (p=0.83). On 20 point scales, parent reported neophobia decreased ‐2.2 (‐3.7, ‐0.7) p=0.0073 and child liking of foods increased a 3.4 (0.8, 5.9) p=0.0129 after the intervention. Conclusions: Parents did not predict a child’s stated willingness to try healthful foods, consumption, or liking. Parent‐reported neophobia and child’s liking were modifiable. This pilot should be expanded to a larger population using a controlled design.

Grant Funding Source: Supported by the Colorado Health Foundation
Reliability and validity of mapping the community food environment using direct observation: a case study in urban Guatemala (255.4)
Authors: Kanter Rebecca , Caplan Emily , Chang Fabian , Koeppel Leah , Chomitz Benjamin , Alvey Jeniece , Garcia Rosario , Solomons Noel W.
Published: June 2021

Background: Measures of the community nutrition environment are important to understanding the food environment, which affects individual diet.

Objective: To determine the reliability and validity of direct observation as a low‐cost method in mapping a food environment in Guatemala.

Methods: Two teams of two raters were asked to walk two urban thoroughfares in urban Quetzaltenango, Guatemala. Both teams were instructed to record the address, food outlet type, and the main items sold by each food outlet. Teams walked each thoroughfare on separate days and in opposite directions, respectively. Mirror‐image correspondence analysis was used to determine the inter‐rater reliability between teams. The validity of direct observation in mapping a community food environment in Quetzaltenango was determined based on the face validity of this work by two experts who also walked the same thoroughfares.

Results: The inter‐rater reliability between teams was moderate for both thoroughfares A and B (Percent agreement 65% and 60%), respectively. The face validity of this work was classified as also being moderate.

Conclusions: In Guatemala, where store listings are incomplete and addresses are not well‐marked, we have shown that direct observation is a low‐cost method that has the potential to be both reliable and valid to map the community food environment in a low‐ and middle income country.
The geographic distribution of diabetes by census tract among insured adults in King County, WA (255.7)
Authors: Rehm Colin , Arterburn David , Drewnowski Adam
Published: June 2021

Objective: To evaluate the geographic concentration of adult diabetes by census tract (CT) in King County, WA, in relation to socioeconomic factors.

Methods: Data for 59767 adult men and women enrolled in the Group Health (GH) healthcare system as of July 31, 2006 were used to estimate the prevalence of diagnosed diabetes at the CT level. Diabetes status was identified using laboratory, pharmacy, and diagnosis data from GH’s electronic medical record databases. Measures of socioeconomic status (SES) drawn from the 2000 US Census were median home values, % of residents with a college degree and median household incomes. Spatial regression models were used to assess the relation between socioeconomic variables and diabetes.

Results: Smoothed CT diabetes prevalence, obtained using an Empirical Bayes tool, ranged from 6.9 to 21.2%. The spatial distribution of diabetes was non‐random (Moran’s I=0.46), showing a concentration of high prevalence in south King County and a concentration of low prevalence in north Seattle. In spatial regression models, CT‐level home values and college education were more strongly associated with diabetes than were income. For each additional $100,000 in median home values, diabetes prevalence was 1.4% lower. The three SES factors each explained more of the variance in diabetes than demographic variables. The three SES factors,, population density, race/ethnicity, age and spatial dependence explained 52% of the variance in diabetes, Conclusions: To our knowledge, this is the first report to show major social disparities in adult diabetes prevalence at the CT scale that is based, moreover, on medical diagnosis. Analyses of data at sufficiently fine geographic scale are needed to guide targeted local interventions to prevent and treat chronic disease.

Grant Funding Source: Supported by NIH grants P20 RR020774‐03, R01 DK076608‐04 and R21 DK020774
Prenatal vitamin D supplementation and infant vitamin D status in Bangladesh (256.4)
Authors: Perumal Nandita , Mahmud Abdullah , Baqui Abdullah , Roth Daniel
Published: June 2021

We aimed to determine the effect of prenatal vitamin D supplementation on infant vitamin D status in Dhaka, Bangladesh (23°N), where vitamin D supplementation is not routine. Serum 25‐hydroxyvitamin D (25(OH)D) concentration was measured at <1, 2, 4, and 6 months of age among infants born to women randomized to receive vitamin D3 (VD: 35,000 IU/week) or placebo (PL) during the 3rd trimester of pregnancy. Mean 25(OH)D (n=115) was significantly higher among infants born to VD vs PL mothers at <1 month (80 ± 20 nmol/L vs 22 ± 18 nmol/L; P<0.001) and at 2 months of age (52 ± 19 nmol/L vs 40 ± 23 nmol/L; P=0.04), but the groups were similar at 4 months (P=0.41) and 6 months (P=0.27). Among infants of PL mothers (n=55), mean 25(OH)D increased to 78 ± 29 nmol/L by 6 months of age. Measured environmental (e.g. season) and dietary factors did not substantially explain the increase in 25(OH)D with age. In conclusion, high‐dose prenatal 3rd trimester vitamin D supplementation substantially improved infant vitamin D status during the early postnatal period. The age‐related rise in 25(OH)D from birth to 6 months suggested that routine postnatal infant vitamin D supplements may have a limited role in this setting.

Grant Funding Source: Supported by the Thrasher Fund and the Department of Paediatrics, Hospital for Sick Children
Lipid‐based nutrient supplement for pregnant women improve birth outcomes among primiparous but not multiparous women in Ghana (256.7)
Authors: Adu‐Afarwuah Seth , Lartey Anna , Okronipa Harriet , Peerson Janet , Vosti Stephen , Ashorn Per , Dewey Kathryn
Published: June 2021

Nutrient deficiencies are common among pregnant women in low‐income countries. The iLiNS Project developed a small‐quantity lipid‐based nutrient supplement (LNS, 20 g/d, 118 kcal) for pregnant and lactating women, to enrich local diets with essential fatty acids, high‐quality protein and 22 micronutrients. In a randomized, partially double‐blind, controlled trial in Ghana, pregnant women were randomized to receive daily: a) iron & folic acid (IFA), (b) capsules with 18 micronutrients (MMN) or c) LNS. Newborns were generally measured within 48 h of birth. In the full sample (n=930), groups did not differ significantly in birth outcomes (0.063蠄p蠄0.087 for birth weight and head circumference; otherwise p>0.10). Primiparity was a significant effect modifier: among multiparas (who had a low incidence of low birth weight ≍7.5%), groups did not differ, but among primiparas, infants in the LNS group had greater birth weight (+200 g), z‐scores for birth length (+0.48) and head circumference (+0.40), and lower risk for low birth weight and small‐for‐gestational age (RR (95% CI) = 0.32 (0.12, 0.63) and 0.49 (0.31, 0.72) , respectively) compared to those in the IFA group. Similar differences were observed for LNS vs. MMN but not IFA vs. MMN. We conclude that LNS can improve birth outcomes among sub‐groups at higher risk for fetal growth restriction, which in this sample were the primiparas.

Grant Funding Source: Supported by a grant to the University of California, Davis from the Bill & Melinda Gates Foundation
Adiposity may differently affect bone mass in black, brown and white post‐menopausal women (257.6)
Authors: Chain Amina , Faerstein Eduardo , Bezerra Flavia
Published: June 2021

We evaluated bone mass adequacy and its association with waist and hip circumferences in Brazilian post‐menopausal women stratified by self‐reported skin color. Participants (n=161, mean age 57y) were part of a university staff cohort at Rio de Janeiro (the Pró‐Saúde study). Bone mineral content (BMC) and density (BMD) of total body (TB), lumbar spine (L1‐L4), total hip (TH) and femoral neck (FN) were assessed by DXA. Waist and hip circumferences were measured using standard methods. Differences between skin color groups (black, n=48; brown, n=47 and white, n=66) were evaluated by one‐way ANOVA. Associations between bone parameters and waist or hip circumferences were investigated by Pearson´s and by partial correlation. Prevalence of osteopenia and osteoporosis were 38% and 3%, respectively. TB, TH and FN BMD T‐scores were higher in black compared to white women (P<0.05). Waist and hip circumferences correlated positively with BMC, BMD and BMD T‐score at all bone sites in all skin color groups (r蠅0.29; P<0.05). After adjustment for weight and post‐menopausal period, associations between bone parameters and waist and/or hip circumferences were not significant or, in the case of white women, became negative (r蠄‐0.29; P<0.05) for TB and TH BMC, BMD and BMD T‐scores. Our results indicate higher bone mass in blacks compared to brown and white post‐menopausal women and suggest that waist and hip adiposity may be detrimental to bone mass, especially in white women.

Grant Funding Source: Supported by CAPES, FAPERJ (Brazil)
Systemic arginine depletion: effects on protein synthesis and blood pressure in mice (258.4)
Authors: Marini Juan , Didelija Inka
Published: June 2021

Arginine (Arg) is a semi‐essential amino acid involved in protein synthesis (PS) and blood pressure (BP) regulation. Arg deiminase (ADI) is a bacterial enzyme that hydrolyses Arg imino group to yield citrulline (Cit) and NH3. Pegylated ADI (ADI‐PEG) administration in animals and humans results in the depletion of circulating Arg. To investigate the effect of ADI‐PEG on PS and BP, ADI‐PEG or Saline (Sal) were administered i.m. to male mice. Plasma Arg concentration was negligible (<1; Sal 80 µmol/L), but Cit increased several fold (1100; Sal 80 µmol/L) in ADI‐PEG treated mice. Arg and Cit fluxes were greater in ADI‐PEG mice (Arg 543 vs 910, Cit 126 vs 402 µmol•kg‐1•h‐1, Sal and ADI‐PEG, resp.). The conversion of Arg to Cit, usually used as a proxy for NO production, increased from 4.1 to 496 µmol•kg‐1•h‐1, demonstrating the activity of the deiminase. Phenylalanine and tyrosine fluxes and phenylalanine hydroxylation were not different between the two treatments, indicating no changes in whole body protein kinetics. Protein fractional synthesis rate was not different for most tissues, but it was lower in the brain, thymus and testicles of ADI‐PEG treated mice. 14C Cit incorporation showed an identical pattern. Mean BP was reduced in ADI‐PEG treated mice (105 vs Sal 118 mm Hg, P< 0.008), despite the virtual absence of Arg in blood. These results demonstrate the capacity of many cell types to derive ARG from Cit to meet their needs.

Grant Funding Source: Supported by USDA/ARS Cooperative Agreement No 58‐6250‐6‐001
Differences in extramyocellular lipid and physical function in older adults with sufficient and insufficient vitamin D status (260.2)
Authors: Redzic Maja , Powell David , Lutz Charles , Thomas D.
Published: June 2021

The metabolic role of extramyocellular lipid (EMCL) has yet to be elucidated. An inverse relationship between EMCL and physical function, and EMCL and vitamin D status has been described in vitamin D‐deficiency (25(OH)D < 20 ng/mL). The purpose of this study was to assess differences in muscle lipid and physical function in community dwelling elderly with vitamin D insufficiency (25(OH)D 蠄 30 ng/mL) compared to vitamin D levels that may promote extra‐skeletal health (25(OH)D 蠅 40 ng/mL). 25(OH)D and four square step test (FSST) were assessed in 21 adults aged 65 to 83 years. Gastrocnemius IMCL and EMCL were measured with magnetic resonance spectroscopy and fat ratio segmentation, respectively. Mean body mass index (BMI) was 26.9±0.9 kg/m2. Mean EMCL was 20.2±0.9% with a range of 11.8 to 25.9% and intramyocellular lipid (IMCL) to water ratio was 0.5±0.06. Participants who were vitamin D insufficient (23.9±1.1 ng/mL) had significant higher levels of lateral gastrocnemius EMCL and slower FSST times compared to vitamin D replete (54.7±3 ng/mL) (p<0.05). IMCL, BMI, age, and activity levels were not significantly different between vitamin D groups. These data suggest that vitamin D status 蠄 30 ng/mL may contribute to EMCL accumulation and impaired physical function independent of activity and body mass. A vitamin D status higher than what is normally deemed as sufficient may be needed to measure muscle function.

Grant Funding Source: Partially sponsored by NIH CTSA UL1TR000117.
Supplementation with milk proteins and micronutrients improves bone mineralization and micronutrient intake but is equally effective than nutrition education to reduce body weight of obese children (262.6)
Authors: Oropeza Lorena , García Olga , Ronquillo Dolores , Martínez Guadalupe , Camacho Mariela , Caamaño María , Rosado Jorge
Published: June 2021

In a longitudinal controlled and randomized study the effect of supplementing with milk proteins and multiple micronutrients on anthropometry, body composition, and metabolic syndrome indicators was evaluated. A total of 152 obese children (8.5 ± 1.3y) were assigned to one of two groups: a) Nutrition Education (NE) + two daily doses (237mL each) of a supplement with milk proteins and multiple micronutrients (MPMS), b) NE alone. Both treatments were given for 24 wk. Weight, height, waist circumference, and blood pressure were measured at 0, 12 and 24 wk. Diet was evaluated using three 24 hr‐recalls at 0 and 24 wk. Body composition was evaluated at baseline and after 24 wk. A fasting blood sample was taken at 0 and 24 weeks to determine glucose, insulin and lipids profile. A total of 134 children finished the study. Bone mineral content and bone mineral density were significantly higher in the NE+MPMS group than the NE group at the end of the study (P<0.01). Micronutrient intake was higher in the NE+MPMS group than in the NE group (p<0.05). Both groups significantly reduced BMI for age, waist‐height ratio, total fat percent, abdominal fat percent, and energy intake (p<0.05), but no differences were observed between groups. Also, both groups reduced the indicators of metabolic syndrome but no differences were found between groups. In conclusion, MPMS together with a NE increases bone mineral mass and micronutrient intake. Both treatments are beneficial to reduce obesity in school‐aged children.

Grant Funding Source: Supported by CONACYT
Relation between sugar‐sweetened beverage consumption and incident hypertension: a systematic review and meta‐analysis of prospective cohorts (267.4)
Authors: Jayalath Viranda , de Souza Russell , Ha Vanessa , Kendall Cyril , Jenkins David , Sievenpiper John
Published: June 2021

Background: The role of fructose‐containing sugar‐sweetened beverages (SSBs) in incident hypertension is unclear.

Aims: To quantify the relation between fructose‐containing SSBs and incident hypertension, we conducted a systematic review and meta‐analysis of prospective cohorts.

Methods: MEDLINE, EMBASE, CINAHL, and the Cochrane registry were searched (through August 4, 2013) for relevant prospective cohorts. We pooled risk ratios (RR) of extreme (lowest vs. highest) quantiles of intake using generic inverse variance random effects models. Heterogeneity and cohort quality were assessed.

Results: Five prospective cohorts (n=240,508) with 79,584 cases of hypertension observed over 蠅3‐million person‐years were included. SSB intake ranged from none to 蠅1‐serving (200mL, 8 or 12 oz)/day. Comparing extreme quantiles, SSBs significantly increased the risk of developing hypertension by 11% (RR:1.11 [95%CI: 1.06 to 1.17]), and a positive linear dose‐response was established (β=0.0027, p<0.001). However, significant heterogeneity was observed (I²=64%, p=0.02).

Limitations: Significant unexplained heterogeneity and residual confounding due to important collinearity with a Western dietary pattern.

Conclusions: SSBs are associated with a small risk of developing hypertension in five cohorts. Its contribution to hypertension risk appears to be small relative to other established risk factors.

Grant Funding Source: Supported by Calorie Control Council
Household food insecurity and maternal dietary quality during pregnancy and early postpartum period in rural Bangladesh (268.3)
Authors: Na Muzi , West Keith , Shamim Abu , Shaikh Saijuddin , Mehra Sucheta , Labrique Alain , Ali Hasmot , Wu Lee , Klemm Rolf , Christian Parul
Published: June 2021

Household food insecurity (HFI) is a cause of chronic malnutrition in rural South Asia, although little is known about how measured, long‐term diets of women of reproductive age covary by reported level of food security (FS). This relationship was examined during a micronutrient intervention trial in rural northern Bangladesh. We prospectively assessed diet by a 7‐day food frequency questionnaire among a cohort of 14,377 mothers in the 1st and 3rd trimester of pregnancy, and at 3 mo postpartum, or ~1 yr period. A HFI index was created from a 9‐item standardized tool, asked at 6 mo postpartum. At each time, dietary quality, reflected by the number of major food groups represented in the diet, decreased progressively with poorer FS, driven by reductions in animal source and other nutrient dense foods. On average, the proportion with which women reported any weekly intake of dairy, meat, eggs and fruit decreased from 51 to 19%, 51 to 17%, 56 to 16% and 34 to 10% as the HFI decreased from secure to severely insecure (all p for trend <0.001). Staple grains changed little (~90% to 85%, p<0.001), but edible oil intake was unaffected (at ~100%) by gradient of HFI. Although declining with HFI (p<0.001), 蠅80% of all women reported eating fish the previous week. Antenatal and early postnatal dietary quality is lower in a dose‐response way, while grain and oil intake are least affected by chronic HFI in rural Bangaldesh.

Grant Funding Source: Supported by the Bill and Melinda Gates Foundation (Grant GH614)
Child food insecurity is associated with altered daily activities, school absenteeism, and stunting (268.7)
Authors: Bernal Jennifer , Frongillo Edward , Herrera Hector , Rivera Juan
Published: June 2021

Food insecurity (FI) is detrimental for children in several developmental domains, but there are almost no empirical data explaining why and how this occurs. Alternations in child daily activities may be an important mechanism linking child FI with its developmental consequences. We aimed to investigate the association of child FI with three sets of outcomes: participation in daily activities, schooling, and stunting in children, and to compare the associations of child and mother reports of FI with these outcomes. We collected cross‐sectional data from 131 mother‐child pairs in Miranda State, Venezuela on FI, daily activities, schooling, and anthropometric measurements. FI items reported by mothers and children were used to create one mother and two child scales, each with reliability of 0.74. FI reported by children was significantly associated with higher work activities (i.e., raising food crops, food shopping, doing home passive chores, cooking at home, and taking care of siblings), greater television watching and napping, and higher rates of school absenteeism and stunting. In contrast, FI reported by mothers was not associated with any of the child outcomes. These findings demonstrate that child experiences of and responses to FI alter daily activities in ways that are likely detrimental to their development, interfere with schooling, and place children at nutritional risk as exhibited by stunting.
Influence of dose and intensity of 6 months of aerobic exercise training on body composition and lipid profiles in participants with pre‐diabetes (272.2)
Authors: Starr Kathryn , Bales Connie , Granville Esther , Slentz Cris , Bateman Lori , Willis Leslie , Piner Lucy , Kraus William
Published: June 2021

The Studies Targeting Risk Reduction Intervention through Defined Exercise (STRRIDE) compared exercise of varied dose/intensity to the “gold standard” of diet + exercise as used in the Diabetes Prevention Program (DPP). The findings for body composition and lipid responses to 3 exercise treatments, low dose/moderate intensity (LMEX; n=36), high/moderate (HMEX; n=34), and high/vigorous (HVEX; n=36) relative to weight‐loss diet+ LMEX (D+LMEX; n=41) are reported here. The D+LMEX reached the same weight loss as DPP at 6 mo., namely 6.6% (‐6.1+5.0 kg). Body mass changes were ‐0.9+3.3, ‐2.1+2.5, and ‐1.6+2.5 kg for LMEX, HMEX, and HVEX, respectively. The corresponding reduction in body fat was greatest (p<0.05) for D+LMEX (‐6.1+5.0 kg). Lean mass varied <1 kg and both LDL and total cholesterol were unchanged. HDL cholesterol increased equally (p<0.05) in D+LMEX (+2.3+6.1 mg/dL) and HVEX (+2.2+4.4 mg/dL) and also improved in HMEX (+1.6+4.6 mg/dL). Only D+LMEX (p<0.0001) and HVEX (p<0.05) reduced triglycerides (TG); however, D+LMEX had a greater reduction (p<0.05) compared to HVEX (‐28.3+34.7 vs ‐16.7+45.4 mg/dL). In summary, body weight, fat mass, and TG were most robustly improved by D+LMEX. HDL cholesterol was modestly increased in all groups but LMEX. These findings illustrate the importance of matching exercise prescription to the clinical goal and underscore the unique metabolic benefits of diet‐induced weight loss.

Grant Funding Source: Supported by NIDDK R01‐DK081559 and NIA AG000029
Daily pistachio consumption benefits multiple cardiovascular risk factors in type 2 diabetes (272.3)
Authors: West Sheila , Sauder Katherine , McCrea Cindy , Ulbrecht Jan , Kris‐Etherton Penny
Published: June 2021

Cardiovascular disease is the leading cause of morbidity and mortality in type 2 diabetes, and dietary modification continues to be the first line of therapy recommended for risk management. This study compared the effects of two healthy diets that differed in fat content on multiple cardiovascular risk factors. We enrolled 30 adults with type 2 diabetes in a randomized, crossover, controlled‐feeding study with isocaloric diet periods. After a 2wk run‐in on a typical Western diet (36% total fat, 12% saturated fat), participants consumed a low‐fat control diet (27% total fat, 7% saturated fat) and a moderate fat pistachio diet (33% total fat, 7% saturated fat) for 4wk each. While on the pistachio diet, participants consumed pistachios equivalent to 20% of daily calories (ranging from 2‐5 ounces/day). At the end of each diet period, we assessed blood pressure, systemic hemodynamics, lipids and lipoproteins, glucose control, endothelial function, inflammation, and heart rate variability. Treatment effects were assessed with the mixed models procedure in SAS v9.3. Compared to the low‐fat control diet, the pistachio diet reduced total peripheral resistance (1682 vs 1746 dyne‐sec/cm5), systolic ambulatory blood pressure (113.8 vs 117.3 mmHg), fasting triglycerides (140 vs 164 mg/dl), the total:HDL cholesterol ratio (4.0 vs. 4.3), and fructosamine (228 vs 233 µmol/L); and improved several indices of heart rate variability. There was no difference between treatments in resting blood pressure, endothelial function, fasting glucose, and inflammation. This study provides further evidence that daily pistachio consumption can improve the cardiovascular risk profile in adults with type 2 diabetes.

Grant Funding Source: Supported by American Pistachio Growers
Trigger healthy: healthy samples induce healthy shopping (273.5)
Authors: Tal Aner , Wansink Brian
Published: June 2021

The studies aimed to examine the influence of food samples on subsequent grocery shopping. Participants in three studies received more or less healthy (e.g., apple) or unhealthy (e.g., cookie) samples and subsequently shopped in a virtual (studies 1, 3) or actual (study 2) grocery store. For both different food type samples (studies 1‐2) and different framing of samples (study 3) we found that healthy samples lead to more healthful choices. In study 1, participants imagining eating an apple (vs. a cookie) chose a greater net of healthier items (4.1) than those imagining sampling a cookie (1.3). In study 2, grocery shoppers sampling an apple spent more money on fruits and vegetables ($6.41) than those sampling a cookie ($5.68) or no sample ($5.02). In study 3, participants (N = 118) drinking milk advertised as “healthy” selected a greater net of healthier items (3.55) than those drinking milk advertised as ”indulgent” (1.65), or no sample (.69), p = .02. These findings suggest consumers choose products similar in healthiness to samples even with product choices that are determined by situation rather than independent choice.
CCR2 deficiency fails to protect mice with renal artery stenosis from chronic renal injury (278.7)
Authors: Grande Joseph , Kashyap Sonu , Knudsen Bruce , Warner Gina
Published: June 2021

Recent studies have implicated CCR2 ‐ CCL2 signaling in macrophage influx and development of chronic renal disease in human and experimental renal artery stenosis (RAS). We sought to test the hypothesis that development of chronic renal disease would be abrogated in CCR2 knockout (KO) mice. We established RAS in CCR2 KO and WT mice (n=10) through placement of a cuff on the right renal artery We have shown that the cuff reproducibly reduces blood flow by 65% to the kidney. Sham mice underwent manipulation of the right renal artery without cuff placement. Both CCR2 KO and WT mice developed hypertension, which persisted throughout the 4 week study. There was no difference in renal atrophy between CCR2 KO (53+//‐14.6% cortical surface area) and WT (61.2%+/‐14%) mice. Furthermore, there were no significant differences in F4/80+ macrophage infiltration (12.78+/‐4.9% surface area for CCR2 KO mice and 13.13+/‐ 3.1% for WT mice) or CD3+ T cell infiltration. Infiltrating macrophages were predominantly iNOS+ M1 phenotype; few arginase+ cells were observed in any group. Urine protein excretion was similar in CCR2 KO and WT mice. CCL was induced to a similar extent in CCR2 KO and WT mice. Furthermore, no differences in CCL5, CCL7, CCR5, CCR1, or iNOS expression was observed between CCR2 KO and WT mice. We conclude that macrophage infiltration and chronic renal damage occurs in mice with deletion of CCR2. Future studies will identify signaling pathway(s) responsible for macrophage influx and chronic renal damage in this model.

Grant Funding Source: AI‐100911
Analysis of the repaglinide concentration increase produced by gemfibrozil and itraconazole based on the inhibition of the hepatic uptake transporter and metabolic enzymes (292.2)
Authors: Kudo Toshiyuki , Hisaka Akihiro , Sugiyama Yuchi , Ito Kiyomi
Published: June 2021

The plasma concentration of repaglinide is reported to increase greatly when given after repeated oral administration of itraconazole (ICZ) and gemfibrozil (GEM). The present study analyzed this interaction based on a physiologically based pharmacokinetic (PBPK) model incorporating inhibition of the hepatic uptake transporter and metabolic enzymes involved in repaglinide disposition. Firstly, the plasma concentration profiles of inhibitors (ICZ, GEM and GEM glucuronide (GEM‐glu)) were reproduced by a PBPK model to obtain their pharmacokinetic parameters. The plasma concentration profiles of repaglinide were then analyzed by a PBPK model, together with those of the inhibitors, assuming a competitive inhibition of CYP3A4 by ICZ, mechanism‐based inhibition of CYP2C8 by GEM‐glu, and inhibition of OATP1B1 by GEM and GEM‐glu. The plasma concentration profiles of repaglinide were well reproduced by the PBPK model and the validity of the obtained parameters was confirmed by sensitivity analyses and by reproducing the repaglinide/GEM interaction in the cases of different dosing schedules. The present findings suggested that the reported concentration increase of repaglinide, suggestive of synergistic effects of the co‐administered inhibitors, can be quantitatively explained by the simultaneous inhibition of the multiple clearance pathways of repaglinide.
Genetic contribution to scar outcome (337.3)
Authors: Dunnwald Martine , Smith Brian , Nidey Nichole , Baum Christian , Hamilton Grant , Miller Steven , Wehby George , Moreno Lina
Published: June 2021

Wound healing and scar remodeling are part of the normal tissue repair process occurring after injuries and surgical procedures. No two individuals heal equally, and it is well known that wound healing outcomes vary widely in apparently healthy individuals, suggesting that genetic factors contribute to tissue repair. We took advantage of facial images of cleft scars to develop a novel digital imaging analysis method that provides reproducible, sensitive and unbiased assessments of post‐surgical scarring. It is based on the principle that in every individual, the scar outcome is linked, amongst other factors, to the difference between the color of the scar and the color of the unaffected skin. This method detected a very significant difference in all three colors, and for all patients, between the scarred and the contralateral unaffected upper lip (P ranging from 1.20‐05 to 1.95‐14). Using this model, we identified genetic variants in TGFB3 and ARHGAP29 associated with suboptimal healing outcome. We believe that identification of genetic risk factors for poor wound healing and ultimately genetic testing could provide an important first tool to detect individuals at risk for poor outcome.
The chordate origins of the second heart field and head muscle stem cells (345.2)
Authors: Christiaen Lionel
Published: June 2021

The vertebrate head and cardiac muscles share a common origin in the pharyngeal mesoderm, but the cellular and molecular details of the initial fate choices remain obscured by the complexity of vertebrate embryos. In ascidians, common progenitors of heart and atrial siphon muscle (ASM) undergo stereotyped asymmetric divisions to produce first heart precursors, second heart precursors and ASM precursors. The ASM‐specific transcription factor COE is necessary and sufficient to promote pharyngeal muscle specification and block the heart program. We found that a cross‐antagonism between Tbx1 and NK4/Nkx2‐5 activities acts upstream of COE and GATAa to direct pharyngeal muscle versus heart specification in separate ASM and second heart precursors, respectively.

Using a genomics approach, we showed both the cardiac and pharyngeal muscle programs are primed in cardiopharyngeal progenitors. We show that, following fate restriction, ASM precursors produce the myofibers that differentiate, and Notch‐mediated lateral inhibition suppresses MyoD expression and promote “stemness” in stem‐like progenitors that produce most body wall muscles. Our analyses of the ascidian cardiopharyngeal mesoderm shed new light on the evolutionary and ontogenic origins of the second heart field and head muscle stem cells.